Second EditionSM Raju BSc MBBS MD Professor and Head Department of Biochemistry Sreevalsam Institute of Medical Sciences Edappal, Malappuram, Kerala, India Bindu Raju MD Director Hospitalist Program Metroplex Hospital Killeen, Texas, USA M Sivakumar MD Professor and Head Department of Anatomy Pondicherry Institute of Medical Sciences Kalapet, Puducherry, India
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Anatomy and Physiology for General Nursing & Midwifery (GNM)
First Edition: 2006
Second Edition: 2015
Printed atDedicated to
Our Nursing StudentsPreface to the Second Edition
The content of this book has been revised totally. The figures are provided with multicolor and are redrawn. The book is primarily intended for general nursing students based on the syllabus recommended by the Indian Nursing Council (INC), but it will also provide a good understanding of physiology as required for nursing practice and for those preparing for ‘Commission on Graduates of Foreign Nursing Schools (CGFNS)’ examination.
The book is designed in a comprehensive way to cater the needs of nursing students.
Bindu RajuPreface to the First Edition
The book Anatomy and Physiology for General Nursing is primarily intended for students of general nursing, but will also provide a good understanding of physiology as required for nursing practice and for those preparing for CGFNS examination. The book is prepared based on the syllabus recommended for general nursing by the Indian Nursing Council (INC).
The book is designed in a comprehensive way to cater the needs of nursing students.
It is always a pleasant experience to work with Shri Jitendar P Vij (Group Chairman) of M/s Jaypee Brothers Medical Publishers (P) Ltd, New Delhi. I thank Mr Ankit Vij (Group President), Mr Tarun Duneja (Director–Publishing) and all staff of Bengaluru Branch of M/s Jaypee Brothers Medical Publishers (P) Ltd. I also thank the artists of Jaypee Brothers, Bengaluru branch for the final touches given to the figures in this book. Indeed, the authors are thankful to every staff of the publishing house for his or her sustained efforts in publishing this book.
Finally, I would like to mention the sustained inspiration provided by my wife Smt Hemavathi AM.ANATOMY AND PHYSIOLOGY
Time: 90 Hours
This course is designed to help students gain knowledge of the structure and function of the human body and recognize any deviation from normal health in order to render effective nursing services.
Upon completion of this course, the student will be able to:
Describe in general the structure and functions of the human body.
Describe in detail the structure and functions of the different organs and systems in the human body.
Apply the anatomical and physiological principles in the practice of nursing.
Introduction to Anatomical Terms
Organization of Body Cells, Tissues, Organs, Systems, Membranes and Glands
Note: Whenever possible related clinical application should be included in each unit.
The earliest studies of ‘anatomy and physiology’ were aimed at treating illnesses and injuries. Such studies set the stage for the development of modern medicine with standardized terms.
Anatomy deals with the structure (morphology) of the body and its parts, whereas physiology studies the functions of these parts.
Anatomists rely on observation, while physiologists employ experimentation. The functional role of a part depends on how it is constructed.
HUMAN BODY PLAN
The human body begins to take shape during the embryonic development. While the embryo is a tiny hollow ball of dividing cells, it begins forming the tissues and organs that compose human body. By the end of 3rd week of human embryo, it has bilateral symmetry (a body plane in which the left and right sides are the mirror images of each other) and has developing vertebrate characteristics that will support an upright body:
The human body is a precisely structured container of chemical reactions.
Biology is the study of living things that include the study of the human body.
The study of body structure, which includes size, shape, composition and perhaps even coloration is called ‘anatomy’.
The study of how body functions is called ‘physiology’.
The purpose of this chapter is to enable the nursing students to gain an understanding of ‘anatomy and physiology’ with the emphasis on the normal structure and function.
Levels of Structural Organization (Fig. 1.1)
The chemicals that make up the body may be divided into two major categories. They are inorganic and organic:
Inorganic chemicals are usually simple molecules made of one or more elements other than carbon. For example, water, oxygen, carbon dioxide (an exception) and minerals such as iron, calcium and sodium.
Organic chemicals are often very complex and always contain the elements carbon and hydrogen. Examples are carbohydrates, fats, proteins and nucleic acids.
The smallest living units with a definite structure and function are cells. Cells are the smallest living subunits of a multicellular organism such as a human being. There are many different types of cells; each is made of chemicals and carries out specific chemical reactions.
A tissue is a group of cells with similar structure and function. There are four groups of tissue (Figs 1.2A to D):
Epithelial tissue cover or line body surfaces; some are capable of producing secretions with specific functions. The outer layer of skin and sweat glands are examples of epithelial tissue.
Connective tissue connects and supports parts of the body; also some are involved in transport and storage materials. Examples are blood, bone and adipose tissue (fat).
Muscle tissue is specialized for contraction, which brings about movement. Examples are skeletal muscles, smooth muscles and the heart muscle (cardiac muscle).
Nerve tissue is specialized to generate and transmit electrochemical impulses that regulate body functions. The examples are brain and optic nerves.
An organ is a group of two or more different types of tissues precisely arranged to perform specific functions and usually have recognizable shape. The examples are heart, brain, kidneys, liver and lungs.
System Level (Organ Systems)
An organ system is a group of organs that all contribute to a particular function. Examples are the circulatory, respiratory and digestive systems. Each organ system carries out its own specific function, but for the organism to survive, the organ systems must work together; this is called integration of organ system.
Organism level is the most complex level. All the organ systems of the body that function with one another constitute the total organism (one living individual).
Life Processes or Characteristics of Life
All living organisms carry on certain processes that set them apart from non-living things. The following are several of the more important life processes in humans:
Metabolism is the sum of all chemical reactions that occur in the body. The first phase of metabolism is called catabolism that provides energy needed to sustain life by breaking down energy yielding substances such as food molecules. The other phase is called anabolism that uses the energy from catabolism to make various molecules that form body structures and enable them to function.
Assimilation is the changing of absorbed substances into forms that are chemically different from those that entered the body.
Responsiveness is the ability to detect and respond to changes outside or inside the body. Seeking water to quench thirst is a response to water loss from body tissue.
Movement includes motion of the whole body, individual organs, single cells or even structures inside cells.
Growth refers to an increase in size. It may be due to an increase in: the size of existing cells, the number of cells or the amount of substance surrounding cells. It occurs whenever an organism produces new body materials faster than old ones, which are worn out or replaced.
Differentiation is the process whereby unspecialized cells become specialized cells. Specialized cells differ in structure and function from the cells from which they originated.
Reproduction refers either to the formation of new cells for growth, repair or replacement, or to the making of a new individual.
Respiration: Obtaining oxygen and eliminating carbon dioxide.
Digestion: Breaking down food substances chemically and mechanically.
Absorption: The passage of substances through certain membranes.
Circulation: The movement of substances within the body in body fluids.
Excretion: Removal of wastes that are produced by body.
Maintenance of Life or Survival Needs
The structures and functions of almost all body parts help to maintain the life of organism. The only exception is an organism’s reproductive structure, which ensure that its species will continue into the future. Life requires certain environmental factors, which includes the following:
Water is the most abundant chemical in the body and it is required for many metabolic processes and provides the environment in which most of them take place. Water also transports substances within the organism and is important in regulating body temperature.
Food is the substances that provide the body with necessary chemicals (nutrients) in addition to water. Food is used for energy supply, the raw materials for building new living matter and other help such as to regulate vital chemical reactions.
Oxygen is required to release energy from food substances. This energy in turn drives metabolic processes. Approximately 20% of the air we breathe is oxygen.
Heat (body temperature) is a form of energy; it is the product of metabolic reactions. Normal body temperature is around 37°C or 98°F. Both low and high body temperatures are dangerous to the organism.
Pressure (atmospheric) is necessary for our breathing.
Principal Organ Systems of The Human Body
Integumentary system includes the skin and structures derived from it, such as hair, nails, sweat and sebaceous glands. It protects the body and forms a barrier to pathogens and chemicals. Helps to regulate body temperature, eliminates waste, synthesize vitamin D and receive certain stimuli such as temperature, pressure and pain.
Skeletal system includes all 206 bones of the body, their associated cartilage and the joints of the body. Bones support and protect the body, assist in body movement, store minerals and also house bone marrow that produces blood cells.
Muscular system specifically refers to skeletal muscle tissue and tendons. They participate in bringing about movement, maintaining posture and produces heat.
Circulatory and cardiovascular system includes the heart, blood and blood vessels. It transports oxygen and nutrients to tissues and removes waste.
Lymphatic system is sometimes included with the immune system or circulatory system because it works closely with both systems. The lymph, lymphatic vessels and structures are organs (spleen and lymph nodes) containing lymph tissue. It cleans and returns tissue fluid to the blood and destroys pathogens that enter the body.
Nervous system includes the brain, spinal cord, nerves and sense organs such as the eye and ear. Its function is to interpret sensory information, regulate body functions such as movement by means of electrochemical impulses.
Endocrine system includes all hormone producing glands and cells such as the pituitary gland, thyroid gland and pancreas. Hormones regulate body functions.
Respiratory system includes the lungs and a series of associated passageways such as the pharynx (throat), larynx (voice box), trachea (windpipe) and bronchial tubes leading into and out of them. Its function is to exchange oxygen and carbon dioxide between the air and blood.
Digestive system is a long tube called gastrointestinal (GI) tract and associated organs such as the salivary glands, liver, gallbladder and pancreas. It breaks down and absorbs food for use by cells and eliminates solid and other waste.
Urinary and excretory systems include the kidneys, urinary bladder and urethra that together produce, store and eliminate urine. Removes waste products from the blood, and regulate volume and pH of blood.
Immune system consists of several organs, as well as white blood cells in the blood and lymph. It includes the lymph nodes, spleen, lymph vessels, blood vessels, bone marrow and white blood cells (lymphocytes). They provide protection against infection and disease.
Reproductive system includes organs that produce, store and transport reproductive cells (sperms and eggs). In women, provides a site for the developing embryo (fetus).
All of the above systems function together to help the human body to maintain homeostasis. A person who is in good health is in a state of homeostasis.
Homeostasis reflects the ability of the body to maintain relative stability and to function normally despite constant changes. Changes may be external or internal and the body must respond appropriately.
As we continue to study the human body, keep in mind that the proper functioning of each organ and organ system has a role to perform in maintaining homeostasis.
The human body uses homeostasis mechanisms to maintain its stable internal environment.
Homeostasis mechanism work much like a thermostat (negative feedback) that is sensitive to temperature and maintains a relative constant water temperature in a water boiler.
To communicate effectively with one another, researchers and clinicians have developed a set of terms to describe anatomy that have precise meaning. Use of these terms assumes the body in the anatomical position (Figs 1.3A and B). This means that the body is standing erect, face forward with upper limbs at the sides and with the palms forward.
As a standard point or frame of reference, the human body is described as being in the anatomical position when it is standing erect, facing you, feet together flat on the floor, the arms slightly raised from the sides with the palms facing forward. Here is a list of useful directional terms. Know not only what they mean but also how to correctly use them.
Anatomical Planes (Fig. 1.4)
Sagittal plane divides the body into right and left halves:
Midsagittal divides the body right down the middle into equal halves
Parasagittal divides the body into unequal parts.
Coronal (Frontal) plane divides the body into front and back.
Transverse plane divides the body into superior (top) and inferior (bottom) parts.
Supine is lying on the back.
Prone is lying on the abdomen.
Relative Position (Orientation and Directional Terms)
Terms of relative position describe the location of one body part with respect to another (Fig. 1.5). This includes the following:
Superior means that a body part is above another part or is closer to the head.
Inferior means that a body part is below another body part or towards the feet.
Anterior means towards the front.
Ventral also means towards the front.
Posterior is the opposite of anterior; it means towards the back.
Dorsal also is the opposite of anterior; it means towards the back.
Medial relates to an imaginary midline dividing the body in equal right and left halves, e.g. the nose is medial to the eyes.
Lateral means towards the side with respect to the imaginary midline, e.g. the ears are lateral to the eyes.
Proximal describes a body part that is closer to a point of attachment or closer to the trunk of the body than another part, e.g. the elbow is proximal to the wrist.
Distal is the opposite of proximal. It means that a particular body part is farther from the point of attachment or farther from the trunk of the body than another part, e.g. the fingers are distal to the wrist.
Superficial means situated near the surface.
Peripheral also means outward or near the surface.
Deep describes parts that are more internal.
Cortex the outer layer of an organ.
Medulla the inner portion of an organ.
Terms for Common Movements
Flexion: Bending at a joint to approximate the two connected parts together.
Extension: Straightening out from a position of flexion.
Abduction: Drawing away from the median axis of the body.
Adduction: Bringing toward the median line of the body.
MAIN BODY PARTS
The whole body is built around the bony framework and consists of three main parts:
The head and neck
The trunk that includes chest, abdomen and pelvis
Limbs that includes upper and lower limbs.
The skull consists of cranium that protects brain and eyes, and the mandible that is hinged to the skull. The movement of mandible is essential for chewing and speech.
Thorax is the upper part of the trunk, its wall is made of bony framework that houses the lungs and heart apart from the contents of the mediastinum:
Anteriorly the thorax is bounded by sternum, costal cartilage and front ends of the ribs.
Posteriorly it is bounded by dorsal part of the vertebral column made of 12 thoracic vertebral bones and intervertebral disks.
Laterally it is bounded by 12 ribs and intercostal muscles.
Superiorly it is bounded by the root of the neck with its muscles and blood vessels.
Inferiorly it is bounded by the diaphragm, which separates the thorax from the abdomen. Diaphragm is a dome-shaped muscular structure. The esophagus, aorta and inferior vena cava pass through it.
Contents of Thorax
Central part of the thoracic cavity is occupied by the mediastinum that extends anteriorly from behind the sternum to vertebral column posteriorly. On either side of the sternum lungs are situated.
Heart is situated in the left side of the mediastinum enclosed in a fibrous bag called pericardium.
Trachea enters the thorax through its superior opening from the neck and passes down along the posterior aspect of the mediastinum until it divides into left bronchus and right bronchus that enter the two lungs.
Esophagus as continuation of pharynx enters the thorax through its superior opening from the neck. It lies just in front of and to the left of the vertebral column and behind the trachea. It enters the abdomen through an opening in the diaphragm to join the stomach.
Aorta is the continuation of arch of the aorta; the superior and inferior vena cava, the thoracic duct and the lymph nodes are the other contents of the thorax.
Abdomen is the biggest cavity in the body, which is arbitrarily divided into abdomen proper and pelvis. The pelvis is bounded posteriorly by the sacrum, ischium on either sides, pubic bone in the front and muscles of the pelvic floor inferiorly:
Abdomen is bounded anteriorly by the muscles of the abdominal wall; the rectus, internal and external oblique, and transversus on either side.
It is bounded posteriorly by the lumbar part of the vertebral column, psoas, quadratus lumborum and iliacus muscles.
Superiorly it is bounded by the diaphragm.
Contents of the Abdominal Cavity
Stomach and intestine
Liver, gallbladder and spleen
The pancreas, kidneys, adrenal glands, abdominal aorta and inferior vena cava. All of these structures lie posterior to the peritoneum.
Contents of the Pelvic Cavity
The sigmoid colon, pelvic colon and the rectum
The urinary bladder
Reproductive organs in the female
Some loops of the small intestine.
Many organs and organ systems in the human body are housed in compartments called body cavities (Fig. 1.6).
These cavities protect delicate internal organs from injuries and from the daily wear of walking, jumping or running.
The body cavities also permit organs such as the lungs, the urinary bladder and the stomach to expand and contract, while remaining securely supported.
The body can be divided into an appendicular portion (upper and lower limbs) and an axial portion (head, neck and trunk), which contains a dorsal and a ventral cavity. Organs within these cavities are called viscera:
The dorsal cavity can be divided into the cranial cavity and vertebral canal.
The ventral cavity is made up of a thoracic cavity (mediastinum divides the thorax into right and left halves) and an abdominopelvic cavity (divided into the abdominal cavity and the pelvic cavity) separated by the diaphragm.
Smaller cavities within the head include the oral cavity, nasal cavity, orbital cavities and middle ear cavities.
The cell is a structural, functional and biological unit of all organisms. It is an autonomous self-replicating unit that may exist as functionally independent unit of life. As in the case of unicellular organism or as a subunit in a multicellular organism such as in plants and animals, i.e. specialized to carry out particular function towards the cause of the organism as a whole.
Robert Hooke is credited with the naming of the cell after looking at the cork. Leeuwenhoek studied and described the first living cell and Schleiden stated all plants were made from cells. Similarly Schwann stated all animals were made from cells.
Virchow proposed the cell theory, which states that:
Cell is the smallest unit of life
All living things are made from cells
All cells come from other cells.
Watson and Crick elucidated the structure of deoxyribonucleic acid (DNA) based on crystallographic studies of DNA done by Rosalind Elsie Franklin.
Plasma Membrane/Cell Membrane
Plasma/Cell membrane is the outer limit of the cell that encloses different cellular organelles (Fig. 2.1).
It is a selectively permeable membrane. It allows only certain substances to pass back and forth. Ions such as Na+, K+ cannot pass through the membrane by themselves; they must be helped.
Plasma membrane has proteins embedded inside them, which will help transport mechanisms.
Plasma membrane is a lipid bilayer (a double membrane made from phospholipids and proteins).
A phospholipid has a hydrophilic (water loving) end made from phosphorous group and a hydrophobic (water hating) end made from two fatty acid molecules.
Plasma membrane contains integral proteins and peripheral proteins that are used as ‘markers’.
Each cell in the body has a peripheral protein (a marker) that is unique. This is how the body recognizes the cells, which are self and which are foreign.
Many cells have sugar groups attached to them that are called glycocalyx. This sugar is sticky and helps the cells to stay attached to each other.
Each type of cell in the body uses a different type of glycocalyx. This is how the body recognizes cells apart as which is a stomach cell, a brain cell, etc.
Cells lining the absorptive surface in a tissue possess microscopic finger-like projections called microvilli that increases surface area.
Tight protein molecules adhere the cells together like cement and there is no way to break this junction without tearing cell.
Dermatomes use proteins like threads to sew the cell together, which can be undone.
Gap plasma membrane of two or more cells fuse to form a bridge, which can pass materials back and forth between cells.
Movement Through the Membrane
There are many ways in which materials can pass through the membrane. One such method is simple diffusion, which only occurs for small, non-polar molecules (e.g. CO2 or O2). These molecules are small enough to squeeze between the phosphate heads of the phospholipids. Small polar molecules can also pass through, but usually the non-polar fatty acids in the membrane repel them. The rate at which the small non-polar molecules pass through is based upon the difference in concentration of that molecule on either side of the membrane.
The second method, by which molecules can move through the cell membrane, is by passive transport, which allows highly polar molecules to move through the fatty acid bilayer that would normally not permit them to enter. One form of passive transport utilizes protein channels, whereby protein molecules in the membrane form a tunnel through which polar molecules may diffuse without ever coming in contact with the fatty acids. A second type of passive transport is known as facilitated diffusion. In this process proteins called carrier proteins bond with the molecule on one side of the membrane, move through the membrane and then release it on the other side.
Another type of transport, called active transport, requires an input of energy by the cell. For example, to prevent too much water from entering the cell and causing it to burst, cells have some special structure called contractile vacuoles, which pump the water out.
Movement of a molecule without any type of work being done by cell. Cell will create a natural current (called concentration gradient) that moves things in, out and around.
Diffusion: Movement of molecules from areas of high concentration to areas of low concentration, through a permeable membrane.
Osmosis: It is the movement of water through a semi-permeable membrane, from a solution of low concentration to one of higher concentration.
Isotonic: The percentage is equal on both sides, i.e. in and out of the cell, so net flow is zero.
Hypertonic: There is more dissolved stuff outside the cell than inside, so water leaves the cell and shrinks it.
Hypotonic: There is less dissolved stuff outside the cell than inside, so water rushes into the cells and swells it.
This movement inside and outside of cells creates a pressure gradient that can be measured and this is what our bodies use to filter (blood, lymph).
Facilitated diffusion: It is a carrier-mediated process. This mechanism does not require energy, but the rate of transport is more rapid than diffusion process. It is dependent on concentration gradient.
The cell must use energy in order to move things around, in or out, and goes against the concentration gradients such as:
Exocytosis: Getting stuff out of the cell.
Endocytosis: Getting stuff into the cell.
Pinocytosis: Brings in small stuff and liquids.
Phagocytosis: Brings in large particles.
Cytoplasm: It is the jelly-like gel that fills the cell and holds the organelles in place.
Mitochondria: These are the ‘powerhouse of the cell’:
Have a double membrane and their own DNA (were once bacteria)
Site of cellular respiration, which breaks down sugar to form adenosine triphosphate (ATP) (cellular energy)
Inner membrane is highly folded to form cristae that increase the surface area to make more ATP.
Ribosome: It is the site of protein synthesis:
Ribo means proteins
Free ribosomes float in the cytoplasm and make proteins for the cell’s own use
Attached ribosomes make proteins to be shipped out of the cell.
Endoplasmic reticulum (ER): It is the subway system. It has a system of canals and channels through the cytoplasm.
Rough ER: It has ribosomes attached that helps to move proteins around.
Smooth ER: It produces lipids and carbohydrates.
Golgi apparatus: It is the packaging house of the cell (the Post Office). It is found near the nucleus:
Anything that is to be sent out of the cell is sent to the golgi bodies (GB) to be packaged
Many packages are called vesicles.
Lysosomes: These are known as the suicide sacs:
Structures contain digestive enzymes that breaks down old and decaying cell parts
It split open in order to release the enzymes.
Peroxisomes: When cells break down food, they naturally make hydrogen peroxide (H2O2), which is toxic to the cells:
Peroxisomes break down H2O2 into water and oxygen for the cells use.
Some rods are used to give the cell shape and structure (like our bones)
Some rods are used to hold the organelles in place
Some rods help move organelles around.
Centrosome: It is used in cell division of animal cells:
Make protein fibers that are used in mitosis and meiosis to move structures around.
Nucleus: It is the brain of the cell:
It has a protective double membrane around it called nuclear envelope/membrane contains the cell’s DNA
Contains a smaller organelle called nucleolus.
Nucleolus: It contains the DNA that tells the cell how to make ribosomes for protein synthesis.
Mitosis is the term for cell division that produces two daughter cells identical to the parent cell. In humans, each of these cells will have 46 chromosomes.
The five stages of mitosis are:
Interphase: This is the stage where the cell carries on its normal processes. DNA replicates during this stage.
Prophase: During prophase the main process begins. First the chromatin begins to coil up and condense. Once that happens they are referred to as chromatids. When two chromatids join, the pair is called chromosome. The chromosome is held together by the centromere. Chromosomes first become visible during prophase. The nuclear membrane, as well as the nucleoli disappears and the centrioles move to opposite ends of the cell, while the mitotic spindle forms between them.
Metaphase: During metaphase, the chromosomes all meet up at the middle of the cell. The centromeres of the chromosome align with the spindle fiber.
Anaphase: The chromosome splits at the centromere and each chromatid pulls apart and move towards opposite poles of the cell as the spindle fibers shorten.
Telophase: The most obvious landmark of telophase is the formation of the cleavage furrow, which will divide the cytoplasm and hence the cell, in two. The chromosomes once again become chromatin (long, unwound threads of DNA) and the nuclear membrane reforms. The final result of mitosis has been the formation of two identical daughter cells, each containing 46 chromosomes.
Meiosis is the type of cell division that produces sex cells. Spermatogonia and oogonia are primitive sex cells and have 46 chromosomes (the same number as other cells in our bodies), but for them in order to become mature gametes (sperm and eggs) they must reduce this number to 23. To do this, meiosis has more stages (Fig. 2.2):
Interphase I: The same events take place in this stage as that take place in the interphase stage of mitosis. DNA replicates.
Prophase I: Just like in mitosis, the chromatin begins to coil up and condense, the nuclear membrane disappears and the centrioles begin their migration, while the spindle fiber forms between them. The difference between this stage and what happens in mitosis is that crossing over occurs. This is where pieces of chromosomes exchange with pieces of other chromosomes.
Metaphase I: During metaphase, all the chromosomes meet up at the middle of the cell. The centromeres of the chromosome align with the spindle fibers.
Anaphase I: During anaphase of mitosis, the centromere split and each chromatid moves to opposite pole. This does not happen here. The centromere does not split, and instead whole chromosomes undergo this migration.
Telophase I: Same as in mitosis, the cleavage furrow forms and divides the cell into two daughter cells. Each of these cells contain 23 chromosomes.
Interphase II: There is no interphase II. The DNA has already been replicated.
Prophase II: Same as during prophase of mitosis. Each of the cells has 23 chromosomes (remember that each chromosome is actually chromatids).
Metaphase II: Chromosomes meet at the middle.
Anaphase II: This time, the centromere splits and one chromatid of the chromosome goes to one pole and the other to the opposite pole.
Telophase II: Same as in mitosis except that each cell has 23 chromosomes.
Tissue is a group of cells with similar structure and function. The cells differ in appearance according to particular type of tissue to which they belong and the specialized functions they perform. There are four groups of tissues:
Connective tissue is the most widespread and abundant tissue in the human body. Different types of cells are found in connective tissues and they come in many varieties. One feature of connective tissue is the presence of matrix, which is composed of the ground substance and the fibers.
Fibers Found in Connective Tissue
Collagen: These fibers are white in appearance and are very strong, and are the most abundant fibers.
Elastic: These fibers, as you guess are able to stretch and so they provide flexibility. With branches they appear yellow.
Reticular: The thinnest fibers are also branched. These fibers are made of special cells called fibroblasts.
Loose Connective Tissue
Areolar: Found in the superficial fascia and the lamina propria of mucous membranes. Areolar is the most widespread type of connective tissue. Its matrix is semi-fluid and it contains all three types of fibers. There is much space between all of the fibers and cells (Fig. 2.3A).
Adipose: This tissue has lot of fat cells, which are packed tightly. The nucleus of each fat cell is pushed to the side of the cell. Adipose tissue is found in subcutaneous tissue and serves several functions like protection and insulation (Fig. 2.3B).
Reticular: It has lot of reticular cells accompanied by reticular fibers. This type of connective tissue forms the framework for different organs.
Dense Connective Tissue
Dense fibrous connective tissue can be further classified into regular or irregular. Dense regular has many collagen fibers arranged in parallel rows. Dense irregular contains many collagen fibers as well, but the arrangement has no regular pattern.
Elastic: Contains elastic fibers, which permit stretching.
Special Features of Cartilage
Unlike other forms of connective tissue, cartilage has a poor blood supply. Chondrocytes are the cells found in cavities called lacunae. The lacunae give the appearance of bubbles under the microscope.
Types of Cartilage
Elastic cartilage: Provides support with flexibility. Contains elastic fibers.
Fibrocartilage: Have collagen fibers mostly. Compose the intervertebral disks, where it offers support and cushioning.
Hyaline cartilage: It is found at the articular surfaces. One cannot really see the fibers here and the matrix appears glassy (Fig. 2.4).
Bone: It is a type of connective tissue in which the matrix is very hard. The bone cells, called osteocytes, secrete the matrix. Many collagen fibers are embedded in the matrix.
Blood: It is a type of connective tissue with a fluid matrix.
Mesenchyme: It is found in the embryo. Gives rise to all other types of connective tissue.
Mucoid tissue: It is found in the umbilical cord.
Bone is a type of connective tissue where the matrix is hard and calcified. The matrix contains many collagen fibers. The term for these layers of the matrix is lamellae. The other features are:
Each of these white spots in the Figure 2.6 is an osteocyte within a lacuna.
In the center of each osteon is a passageway called haversian canal (Fig. 2.7). Within this canal, the blood vessels supply nutrients to the osteocytes through the canaliculi. Radiating out from the haversian canal, like spokes on a wheel, are the canaliculi.
Osteocytes are not the only type of cells found in bone. Osteoblasts are the cells that lay down new bone and destroy old bone so that growth can occur. Osteoclasts also begin to destroy bone, when the body is deficient of calcium as well as when bone is not used.
Other Terms to Know
Spongy bone: Spongy bone has no haversian systems. Instead the arrangement is like a web (trabeculae).
Diaphysis: The shaft of a long bone.
Epiphysis: The ends of a long bone.
Periosteum: A covering over the surface of the bone, made of dense connective tissue.
Articular cartilage: Hyaline cartilage, which covers the epiphyseal surface where a bone forms a joint with another bone. Epiphyseal surfaces, which are not part of an articulating surface, are covered by periosteum.
The markings on bones (such as tuberosities, lines, crests and spines) serve as sites of attachment for muscles and/or ligaments.
Openings in bones (such as foramen, fossa, fissures, etc.) serve as passageway for blood vessels and/or nerves.
Projections on bones (like heads and condyles) take part in forming joints.
Types of Bones
Long bones: They are made primarily of compact bone, except at the ends (epiphysis), which has only a thin layer of compact bone covering a great deal of spongy bone. For example, long bones include the humerus and femur. They are bones that are longer than they are wide.
Short bones: They are shaped like the carpals and tarsals and contain mostly spongy bone.
Flat bones: Example of flat bones are those of skull. Contain spongy bone in between surrounding layers of compact bone.
Irregular bones: Example is vertebrae.
Sesamoid bones: Example is patella. Sesamoid bones are enclosed in tendons.
Epithelial tissue always has a free surface. Cells are close together and attached to the basement membrane. Epithelial tissue types are named by their shape and number of layers.
Simple: One layer of cells.
Stratified: More than one layer of cells.
Pseudostratified: One layer of cells that appears to be multilayered.
Squamous: Flat cells.
Cuboidal: Cube-shaped cells.
Types of Epithelial Tissue
Simple squamous: Found in the alveoli of the lungs, lines blood vessels. One layer of flat cells permits filtration and diffusion.
Stratified squamous: Two types—keratinized and non-keratinized. Keratinized is found in dry areas, like the skin and non-keratinized stratified squamous is found in wet areas, like the esophagus and vagina. The many layers of cells offer protection of these areas.
Simple cuboidal: One layer of cube shaped cells. Simple cuboidal lines the kidney tubules. Its functions are secretion and absorption.
Stratified cuboidal: Many layers of cube shaped cells. Stratified cuboidal lines the ducts of mammary glands and salivary glands. Its function is to offer protection of the areas of lines.
Simple columnar: Two types—ciliated and non-ciliated. Non-ciliated can be found in the gastrointestinal tract. One can find goblet cells here also (which secrete mucus). Ciliated simple columnar lines are the fallopian tubes and the cilia beat to move the oocyte through the tube.
Stratified columnar: Like other stratified epithelial types, its function is to protect and also secrete uncommon epithelial type.
Pseudostratified columnar: Lines the upper respiratory tract, where it functions is to produce and move mucus (has cilia and goblet cells).
Transitional: Found in the lining of the urinary bladder. The cells change shapes from a rounder appearance to a flatter one as the bladder fills, so their function is to permit distension of the bladder.
Endocrine glands: Release their products (hormones) directly into the blood. Examples of endocrine glands are thyroid, pituitary and ovary.
Exocrine glands: Release their products (sweat, oil, ear wax, milk, etc.) into a duct.
Types of Multicellular Exocrine Glands
Holocrine: The whole cell and its contents are secreted into duct. For example, sebaceous glands.
Apocrine: Part of the cell pinches off and is secreted into the duct. For example, mammary glands.
Merocrine: Only the products are secreted into the duct. Most of the exocrine glands are of this type.
Types of Muscle
There are three types of muscles (Figs 2.8A to C), namely the skeletal muscle, cardiac muscle and smooth muscle.
Skeletal muscle may be called voluntary muscle (because it can be manipulated by conscious effort) or striated muscle (because it appears to be striped). The muscle cell also called fiber, contains many nuclei. Each muscle fiber is made up of bundles of smaller fibers called myofibrils. Each myofibril is made up of smaller fibers called myofilaments. Some of these myofilaments are thick (made of myosin) and some are thinner (made of actin, tropomyosin and troponin). Each myofilament has several sarcomeres, which are the contractile units of the muscle. Cell structures have different names than those found in other types of cells and the muscle cells even have structures that cannot be found in other types of cells.
Muscle cell structures
Sarcolemma is the cell membrane.
Sarcoplasm is the cytoplasm.
Sarcomere is the contractile unit of the muscle. The sarcomere (Fig. 2.9) extends from one Z line of a myofibril to the next Z line of that myofibril.
Z lines (or Z disk) are found in the middle of each I band.
I band is thinner and has lighter colored striations that alternate with A bands.
A band is thicker and has darker color striations that alternate with I bands.
Myofilaments make up myofibrils; consist of myosin (thicker), actin, tropomyosin and troponin (all thinner).
Myofibrils make up muscle cells (fibers).
Connective tissue covering the fibers are:
Endomysium: Around an individual muscle fiber.
Perimysium: Around a fascicle (bundle of fibers).
Epimysium: Around many fascicles.
Skeletal muscles produce movement by contracting (Fig. 2.10), which pulls the insertion bone towards the origination bone.
Figures 2.8A to C: Three types of muscles. A. Heart muscle cells; B. Skeletal muscle cells;C. Smooth muscle cells
Smooth muscle has no A or I bands, it does not have the striated appearance of skeletal muscle. Smooth muscle is involuntary, meaning that no thought or conscious effort is needed to cause muscle contraction. There are two types of smooth muscle.
Single unit: Located in the viscera such as gastrointestinal tract, uterus, bladder and small arteries.
Multiunit: Located in large arteries, respiratory tract and iris.
Cardiac muscle is located only in the heart. It has a striated appearance and is involuntarily controlled. Cardiac muscle also has a feature that is foreign to the other muscle types, i.e. intercalated disks.
The physiology of muscle contraction is very elaborate and very confusing. Basically, it happens as follows:
The energy for muscle contraction comes from the breaking of two bonds in ATP.
Acetylcholine released by a neuron into the neuromuscular junction binds to receptors on the motor end plate of the muscle cell. The nerve impulse conducts over sarcolemma and triggers the release of calcium ions from sacs in the sarcoplasmic reticulum into the sarcoplasm.
Calcium ions in the sarcoplasm combine with troponin molecules, which allow myosin to interact with actin. The thin myofilaments are pulled towards the center of the sarcomere, which causes the sarcomere and the myofibrils to shorten and contract. Relaxation of the muscle occurs, when calcium and troponin separates, preventing myosin-actin interaction.
All-or-none law: Muscle cells either contract with all possible force, or they do not contract at all (remember that this applies to individual muscle fibers, not entire muscles).
Skeletal muscle is voluntary and only contracts when stimulated. Cardiac and smooth muscle are involuntary.
Muscles move from the point of insertion towards the origination site.
There are two distinct types of cells found in nervous system:
Neurons or nerve cells with their processes called neurites, convey motor or sensory impulses.
Neuroglia, ependyma and Schwann cells are the types of cells that are non-excitable with numerous functions including mechanical support for the neurons.
The size of neurons (Fig. 2.11) varies considerably in size, some being the largest cells in the whole body. The nervous tissue containing the cell bodies of neurons is sometimes called gray matter. Aggregations of nerve cell bodies are known as nuclei or ganglia and they are dark in appearance. A neuron consists of three main parts.
Cell body is the largest part and contains the nucleus and much of the cytoplasm (area between the nucleus and the cell membrane), most of the metabolic activity of the cell including the generation of ATP (compound that stores energy) and synthesis of protein.
Dendrites are short branch extensions spreading out from the cell body. Dendrites receive stimulus (action potentials) and carry impulses from the environment or from other neurons and carry them toward the cell body.
A long fiber that carries impulses away from the cell body. Each neuron has only one axon.
The axon ends in a series of small swellings called axon terminals. Neurons may have dozens or even 100s of dendrites, but usually only one axon. The axons of most neurons are covered with a lipid layer known as the myelin sheath. The myelin sheath both insulates and speeds up transmission of action potentials through the axon.
In the peripheral nervous system, myelin is produced by Schwann cells, which surround the axon.
Gaps (nodes) in the myelin sheath along the length of the axon are known as the nodes of Ranvier.
The skin (Fig. 2.12) is the body’s largest organ and serves many functions: regulation of body temperature, protection from environment, excretion of some wastes and absorption of some chemicals and vitamins, and sensations:
Epidermis has five layers and is made up of stratified squamous epithelial tissue:
Stratum corneum is the outermost layer of the epidermis. The cells here are dead.
Stratum granulosum is found in thicker skin.
Stratum lucidum will be found in between stratum corneum and stratum granulosum. Cells die in the stratum granulosum.
Stratum spinosum is the layer in which cells appear spiny under the microscope.
Stratum basale is the germinating layer, where mitosis takes place and that forms new skin cells. As new cells are formed, the older cells are pushed out, layer by layer, until they die and are eventually sloughed off. Cells containing pigment are found here.
Dermis is thicker than the epidermis and consists of connective tissue (dense irregular fibrous). The dermis has two layers—the papillary layer and the reticular layer.
Papillae form ridges on the skin for increased friction. This is what forms fingerprints.
Arrector pili muscle is attached to hairs. It is smooth muscle. When the muscle contracts, the hair ‘stands up’ (Goose-bumps).
Sebaceous gland produces sebum (oil).
Hair bulb is the root of the hair.
Meissner’s corpuscle sense pain and temperature. Touch receptors.
Sweat gland secretes sweat.
Subcutaneous tissue (superficial fascia) will have areolar connective tissue and adipose tissue.
Homeostasis is derived from the Latin, homeo or constant, and stasis or stable, which means remaining stable or remaining the same.
The human body manages highly complex interactions to maintain functioning within a normal range. These interactions within the body facilitate compensatory changes supportive of physical and psychological functioning. This process is essential for the survival of the person. The liver, the kidneys, brain and endocrine system helps to maintain homeostasis. The liver is responsible for metabolizing toxic substances and maintaining carbohydrate metabolism. The kidneys are responsible for regulating blood water levels, reabsorption of substances into the blood, maintenance of salt and ion levels in the blood, regulation of blood pH and excretion of urea and other wastes.
An inability to maintain homeostasis may lead to death or a disease condition known as ‘homeostatic imbalance’. For instance, heart failure may occur when negative feedback mechanisms become overwhelmed and destructive positive feedback mechanisms takeover. Other diseases, which result from a homeostatic imbalance include diabetes, dehydration, hypoglycemia, hyperglycemia, gout and any disease caused by the presence of a toxin in the bloodstream. Medical intervention can help restore homeostasis and possibly prevent permanent damage to the organs.
Homeostasis is the basic physiological principle of maintaining constant cell composition and function, despite external fluctuations. In other words, it can be explained as stable operating conditions in which the three components such as receptor, integrator and effector interact (Fig. 3.1). Walter Cannon an American physiologist first coined this term in 1932. It comes from two Greek words meaning ‘standing the same’, but this is a misnomer and in fact the more common description is that of ‘dynamic equilibrium’.
A unicellular organism such as an amoeba needs to be able to take in oxygen, food and nutrients, and to excrete waste products. It needs a constant state of hydration and a controlled temperature for a happy life. Man is complex and multicellular, but each cell in our body has the same needs as the amoeba and we have developed complex mechanisms to provide each cell with all that it needs.
Not many human cells are in direct contact with the outside world and they use a ‘middleman’ to supply the chemically stable and thermostatically controlled environment they need. This middleman is the interstitial fluid.
A vast number of mechanisms are involved that are triggered by changes in extracellular fluid.
These mechanisms act by negative feedback to restore or preserve the optimum state by producing a change in the opposite direction—too much produces less and too little produces more. Requirements of a homeostatic mechanism are:
Detectors that monitor internal and external variables, e.g. photoreceptors, chemoreceptors and baroreceptors.
Coordinating mechanisms that relay information. Nerves act quickly; hormones are slower, but last longer.
Integrating center (e.g. hypothalamus and medulla) that receives information interprets and sends appropriate signals to effectors.
Effectors bring about changes that restore the balance, e.g. muscles, heart, glands and kidneys.
Any stimulus that disrupts the ‘steady state’ of homeostasis is a stress and may be psychological (e.g. anxiety) or physiological (external, e.g. heat or internal, e.g. raised blood sugar).
Analogy is often made with heating and cooling systems where a fall in temperature will trigger the thermostat, fire up the boiler and heat up the radiators until the temperature rises and then the thermostat will switch off. A rise in temperature will fire up the air conditioning until the temperature falls to the pre-set level and then the system will switch off.
We have some control over our external temperature (clothes, food and heating), but cells produce heat during metabolism and if it is not utilized proteins and enzymes throughout the body would curdle and become useless.
Skin capillaries dilate to help heat radiated off
Sweat glands activated to help heat evaporate off
The system switches off (negative feedback) once desired temperature is achieved.
Thermoreceptors in hypothalamus activate the following:
Thyroid hormones, which increase metabolic rate
Central nervous system (CNS) shuts down skin capillaries and sweat glands
Food metabolized in liver, to produce heat
In animals, piloerection (fur stands on end) traps heat
If core temperature continues to fall, shivering produces heat from muscle contraction
Blood flow to the skin can range from 250 to 2,500 mL/min as a homeostatic mechanism.
The kidneys maintain acid-base homeostasis by regulating the pH of the blood plasma. Gains and losses of acid and base must be balanced. The study of the acid-base reactions in the body is acid-base physiology.
Blood Gas Levels
Refer Respiratory Physiology section to understand how the peripheral and central chemoreceptors maintain blood oxygen and carbon dioxide levels within very narrow limits using negative feedback mechanisms.
A fall in body fluid reserves (lots of causes can be considered) causes a rise in osmotic pressure of blood, which is detected by osmoreceptors in hypothalamus. In turn, hypothalamus sends message to posterior pituitary to release antidiuretic hormone (ADH), which acts on distal tubules of kidney that reabsorbs water into the blood.
A rise in body fluids stops release of ADH and excess water is passed as urine.
It is not quite as simple as this because the first one triggers other homeostatic mechanisms, but this gives an idea.
Peripheral thermoreceptors in skin (detectors) relay information via nerves (coordinating mechanism) to temperature control center on hypothalamus (integrating center), which also contains central thermoreceptors sensitive to the heat of passing blood. This triggers the sympathetic nervous system, for example, when a person is confident observe the maintenance of blood glucose levels as a homeostatic mechanism and make a flow chart of the many ways that negative feedback works when blood glucose levels are high or low.
Blood Calcium Levels
A rise in blood calcium stimulates thyroid gland to release calcitonin, which arrests calcium release from bone and blood calcium level returns to normal.
A fall in blood calcium stimulates parathyroids to release parathyroid hormone, which stimulates calcium release from the bone and causes calcium reabsorption from kidney. Vitamin D is activated and increases calcium absorption from gut. It also increases calcium release from bone. When the calcium levels return to normal the whole mechanism switches off.
One can work through many other examples and use this general principle in many of the answers.
The study of fluid and electrolyte balance gives an overall understanding of its imbalance in the body and its implications.
Water has a specific gravity of 1.000
In a lean adult, water makes up 60%–70% of body weight
Every liter of surplus water increases body weight by 1 kg
Adipose tissue contains less water, therefore in an obese person water, only accounts for 30% of total body weight
Men have a greater proportion of water than women
In neonates up to 75% of body is of water.
Some Important Definitions
The two solutions of the same concentration, which produce no resultant flow through a semipermeable membrane.
Solution with a higher osmotic pressure, i.e. a more concentrated solution.
Solution with a lower osmotic pressure, i.e. a weaker, more dilute solution.
One that allows osmosis and diffusion to take place.
When a strong solution is separated by a semipermeable membrane from a weak solution, then provided the substance dissolved (i.e. the solute) can pass through the membrane, the solute will pass from the stronger to the weaker solution until both solutions have the same strength. The solute moves down a concentration gradient, this is how gases, nutrients and waste products move.
When a concentrated and a weak solution are separated by a semipermeable membrane, which will not allow the solute to pass, water will pass through the membrane until the solutions are equal in concentration, this is called as osmosis
FLUID AND ELECTROLYTE BALANCE
Total body water (TBW) in an adult is about 40 L:
Intracellular: 25 L
Extracellular: 15 L (has two divisions—interstitial and plasma):
Interstitial: 12 L
Plasma: 3 L.
Normal Blood Volume
The normal blood volume is 5–6 in an adult:
Blood comprises of blood cells and plasma
Packed cell volume of blood (hematocrit) is 45%
Plasma is 55%.
In order to maintain homeostasis, all systems need to function adequately; the amount taken in should equal the amount eliminated out.
The important plasma proteins are albumin (55%), globulins (38%) and fibrinogen (7%). The important functions they perform are as follows:
Exert colloid osmotic pressure (oncotic pressure) to keep fluid in the circulation, rather than leaking out into the tissues as edema
Function as antibodies
Act as clotting factors
Form a protein reserve, which can be used by the body in starvation
Buffer plasma, correcting acid-base balance
Function as enzymes.
Fluid Movement Among Compartments
Osmotic and hydrostatic pressures regulate the continuous exchange and mixing of body fluids. Osmotic pressure is dependent on the ratio of solutes (plasma proteins and sodium) to solvent (water). Hydrostatic pressure equals blood pressure and is therefore dependent on anything that affects blood pressure (BP).
Forces Responsible for Fluid Flow at Capillaries
The direction of fluid movement is dependent upon the differences between two opposing forces. Hydrostatic pressure tends to push fluid out of the capillary and osmotic pressure tends to pull fluid back into the capillary.
At the arterial end hydrostatic pressure is 35 mm Hg and osmotic pressure is 25 mm Hg therefore the net filtration pressure is 10 mm Hg, it means fluid is forced out of the capillary and into the surrounding tissues.
At the venous end the hydrostatic pressure is 17 mm Hg, however osmotic pressure remains at 25 mm Hg, therefore net filtration pressure is –8 mm Hg. A negative value means the fluid is pulled back into the capillary; the small net leakage that remains behind in the interstitial space is picked up by lymphatic vessels and returned to the circulation.
Up to 3 L of intravascular fluid per day is lost to the interstitial space and this would lead to hypovolemia if this fluid were not returned via the lymphatic system.
Lymphatic vessels form a one way system in which lymph flows only to the heart. This transport system begins in blind-ended lymph capillaries, which we have between the tissue cells and blood capillaries in the loose connective tissue of the body.
Lymph capillaries are widespread, but they are absent in bone, bone marrow and the central nervous system. Lymph capillaries drain into lymphatic collecting vessels (similar to veins). These drain into lymphatic trunks, which eventually form two lymphatic ducts (right and left). Each lymphatic duct drains into the venous circulation at the junction of the internal jugular and subclavian veins.
Formation of Edema
Edema is an atypical accumulation of fluid in the interstitial space leading to tissue swelling. Edema may be caused by any event that steps up the flow of fluid out of the intravascular compartment or hinders its return.
Anything that affects the relative balance between hydrostatic and osmotic pressure leads to an increase in net filtration pressure, which results in edema. causes of edema:
Elevated fluid pressure in the capillaries, e.g. in heart failure
Decreased osmotic pressure, e.g. loss of plasma proteins in severe burns
Increased osmotic pressure of interstitial fluid, e.g. in the inflammatory response
Blocked lymphatic channels, e.g. by tumors or surgical removal of lymphatic
Increased capillary permeability, e.g. in anaphylaxis or severe inflammation.
Excess fluid in the interstitial space increases the distance oxygen and nutrients must diffuse from the capillaries to the cells, therefore edema if not corrected can impair cellular function.
Control of Fluid Balance
Fluid balance is controlled by two mechanisms:
Input is regulated by thirst.
Output is regulated by antidiuretic hormone (ADH) and aldosterone.
Thirst is the driving force controlling fluid intake. A decrease in 10% of plasma volume or an increase of 1%–2% of plasma osmolality results in a dry mouth and stimulates the thirst center in the hypothalamus. The dry mouth is the result of a rise in plasma osmotic pressure, which causes less fluid to leave the bloodstream. The salivary glands need fluid from the blood to produce saliva, therefore if there is less fluid and less saliva the mouth feels dry. When the mouth is dry, we feel the need to drink therefore taking in fluid to restore fluid balance. The thirst center contains osmoreceptors, which respond to the increase in plasma osmolality by sending out messages to drink water and therefore increase fluid intake.
Osmoreceptors found in the thirst center in the hypothalamus respond to a rise or fall in the osmotic pressure of the blood and extracellular fluid (ECF).
Osmoreceptors ➔ hypothalamus ➔ posterior pituitary ➔ ADH
Increased tonicity (increased osmolality of plasma) ➔ increased ADH production ➔ fluid retained by kidneys ➔ decreased tonicity (decreased osmolality of plasma and increased fluid volume)
Renin-angiotensin-aldosterone system (RAAS) mechanism is given in Figure 4.1:
Volume receptors in thorax detect decreased volume
Kidney detects fall in BP
Juxtaglomerular apparatus (JGA) detects fall in Na+ concentration in distal tubule (Fig. 4.2).
These three changes lead to renin secretion, which stimulates angiotensin I secretion that is converted to angiotensin II. An elevated level of angiotensin II leads to:
Stimulation of thirst center
Constriction of blood vessels
Increased reabsorption of Na+ by proximal tubule accompanies reabsorption of water that results in increase in plasma volume
Secretion of aldosterone by the adrenal cortex
Reabsorption of Na+ by distal tubule and again water is drawn back with the Na+ increased secretion of K+.
The RAAS also plays a vital role in short-term maintaining of BP by increasing blood volume along with vasoconstriction.
Atrial Natriuretic Peptide Causes Loss of Both Sodium and Water
When the blood volume is too high, as the blood enters the heart the atria are stretched more than normal. The stretching of atria causes release of atrial natriuretic peptide (ANP) from atrial cells.
The ANP inhibits aldosterone, renin and ADH secretion, and increases glomerular filtration rate (GFR) that causes the body to lose both Na+ and water. Thereby the blood volume is restored to normal.
The atoms (Fig. 4.3) are made of a dense, positively charged nucleus comprising protons (P+) and neutrons (n) around which negatively charged electrons (e–) revolve in orbits/shells.
Neutrons carry no charge. It has the same mass as that of proton. Protons and neutrons together constitute the nucleus of atoms. Therefore, the atomic weight of an element will correspond to the total number of protons and neutrons present in the nucleus.
Electron is abbreviated as e– and is negatively charged. The mass of an electron is only 1/2,000 of a proton. The electrons are the fundamental unit of electricity. A stream of electrons produces an electric current.
Theory of Ionization of Atom
The Greek word ion means, ‘moving’. The ionized atoms and particles move in an electric field.
In an atom the number of positive charges (protons) is equal to the number of negative charges (electrons). When an atom loses an electron, it acquires a net positive charge and is called cation. For example:
Na ➔ Na+ + e–, H ➔ H+ + e–
Similarly, when an atom gains an electron, it acquires a net negative charge and is called anion. For example:
Cl + e– ➔ Cl–
Any atom with a net positive or negative charge due to loss or gain of an electron is called ion. The electrons take part in all chemical reactions. The electrons revolve around the nucleus at different energy levels or in shells. The inner most ‘K’ shell has the maximum capacity to accommodate two electrons, the second ‘L’ shell can accommodate eight electrons, the third ‘M’ shell can accommodate eight electrons and so on.
Sodium with an atomic number 11 has 11 electrons; two in K shell, eight in L shell and the remaining one in M shell. The natural tendency for an atom is to completely fill up the shells with electrons. Thus an atom having a single electron in the outermost M shell tends to lose it, so that the K and L shells are completed. Hence, the sodium atom with 11 electrons tends to ionize easily.
Similarly, chloride with an atomic number of 17 has 17 electrons; two in K shell, eight in L shell and seven in M shells, if the sodium atom accepts one more electron, the outer most shell will be completed. Hence, chlorine has the tendency to accept one electron to become ionized. Thus, sodium can donate one electron and chlorine can accept it. This is the basis of the chemical reaction between sodium and chloride. In the above example, the valence of both sodium and chlorine is one, because the exchange is with regard to one electron.
When all the shells are completely saturated with electrons, the atom becomes sluggish in chemical reactions. Helium with two electrons, neon with 10 electrons, and argon with 18 electrons is inert gases, since all the shells are saturated with electrons.
Ions are charged atoms or molecules that can conduct electricity (Table 4.1). Cations (+ve charge) are those that have lost electrons, and anions (–ve charge) are those that have gained electrons. Since ions are charged they conduct electricity. Without ions there can be no nerve impulse or excitability.
The Na+ and K+ are monovalent (one charge) cations, but Ca2+ and Mg2+ are divalent (two charges) cations. They control metabolism, trigger muscle contraction, control secretion of hormones and transmit nerve impulses.
Na+ and K+ are the Major Cations in Biological Fluids
Potassium (K+) concentration is high inside cells and sodium (Na+) concentration is high outside cells. Such ion gradient is maintained by Na+/K+-ATPase pump that utilizes about one third of basal metabolic energy.
The Na+ and K+ gradient across the cell interior and exterior are like electrical energy stored in a battery. Energy stored in the form of Na+ and K+ gradient can be tapped when ions flow. That is how Na+ and K+ produce action potential of excitable cells.
Sodium is the most abundant cation in ECF, which is mainly responsible for the osmotic pressure of ECF and linked closely with water. Sodium concentration affects kidney regulation of water and electrolytes (think about the action of aldosterone).
Sodium is necessary for the transmission of impulses in nerve and muscle fibers. In excess, sodium causes thirst, dry mucous membranes, oliguria, twitching and seizures. Sodium deficit leads to neurological dysfunction manifested as weakness, tremors, irritability, convulsions; it also causes edema and hypotension.
Physiological range of serum sodium ranges from 135 to 145 mEq/L.
Hyponatremia: It is a common electrolyte imbalance that refers to a deficiency of sodium in relation to body water. In hyponatremia the plasma level of sodium is less than 135 mEq/L.
Causes of hyponatremia are GI losses through vomiting, diarrhea and nasogastric suction, renal losses through diuretics, skin losses from wound drainage and burns, and adrenal insufficiency.
Hypernatremia: Refers to excess of sodium in relation to body water. In hypernatremia, plasma level of sodium is more than 145 mEq/L.
Causes of hypernatremia are excessive intake of sodium chloride in food, sodium bicarbonate preparations and sodium containing IV fluids or decreased renal secretion due to renal insufficiency, and use of cortical steroid. It can also result from loss of body water, which leads to an over concentration of sodium, decreased fluid intake or increased fluid loss, diaphoresis, hyperventilation, fever and diarrhea.
Potassium is the dominant intracellular electrolyte. It controls cellular osmotic pressure.
It helps regulate acid-base balance. Potassium activates several enzymatic reactions. It helps maintain neuromuscular excitability. Potassium influences kidney function. In excess it causes weakness, malaise, muscle irritability, bradycardia and arrhythmias. A deficit leads to muscle weakness, arrhythmias, possible cardiac arrest, alkalosis and hypoventilation.
Physiological range of serum potassium ranges from 3.5 to 5.0 mEq/L.
Hypokalemia: Deficiency of potassium in relation to body water is less than 3.5 mEq/L.
Causes of hypokalemia are excessive loss of potassium due to diuretics, vomiting and diarrhea or inadequate replacement of lost potassium.
Hyperkalemia: Excess of potassium in relation to body water is more than 5 mEq/L.
Causes of hyperkalemia are renal failure, cellular damage, insulin deficiency, adrenal deficiency and rapid IV infusion of potassium.
Calcium is needed for blood clotting, cell membrane permeability and to help maintain neuromuscular excitability. About 99% of body’s calcium is found in bones. Calcium deficiency produces tetany and seizures. Calcium in excess leads to lethargy, dehydration, cardiac arrhythmias and coma.
The physiological range of serum calcium is from 8.9 to 10.1 mg/dL.
Hypocalcemia: Serum calcium is less than 8.9 mg/dL.
Causes of hypocalcemia are parathyroid deficiency, vitamin D deficiency, renal disease, cancer, pancreatitis, massive blood transfusions, enema and laxative abuse.
Hypercalcemia: Serum calcium is more than 10.1 mg/dL.
Causes of hypercalcemia are cancer, excessive intake of vitamin D, excessive intake of milk or alkaline antacids, hyperparathyroidism, immobilization and reduced renal function.
Magnesium is the second most abundant intracellular cation. It activates several enzymatic reactions and is essential for myocardial function. It is needed for neurotransmission and neuromuscular activity. Elevated levels of magnesium in serum leads to lethargy, impaired central nervous system (CNS) functioning, coma and respiratory depression. A deficit causes tremors, increased neuromuscular activity and seizures.
Physiological range of serum magnesium is from 1.5 to 2.5 mEq/L.
Hypomagnesemia: The serum magnesium level is less than 1.5 mEq/L.
Causes of hypomagnesemia are impaired intake, impaired intestinal absorption, excessive urinary excretion and secondary to diuretics, and chronic alcoholism.
Hypermagnesemia: The serum magnesium level is more than 2.5 mEq/L.
Causes of hypermagnesemia are renal failure, diabetic ketoacidosis, magnesium sulfate therapy and use of magnesium-based laxatives.
The blood is a transport system, which plays an important role in the homeostasis of the body. It circulates all through the body and is in intimate relationship with various tissues. The functions of blood are as follows:
Oxygen and carbon dioxide
Waste products (metabolic wastes, excessive water and ions)
Regulation of heat (to regulate body temperature).
Acid-base maintenance (by buffering).
Blood loss (hemorrhage) by clotting mechanism
Many disease-causing agents by leukocytes and immunoglobulins. About 5 L of blood is present in an average adult.
Composition of Blood
The blood is composed of:
Red blood cells (erythrocytes)
White blood cells (leukocytes)
Red Blood Cells (Erythrocytes)
Erythrocytes are biconcave disk-like structures.
They lack nucleus and cannot reproduce.
The average lifespan of erythrocytes is about 120 days.
They contain a substance called hemoglobin (each RBC has about 280 million hemoglobin molecules), which is essential for oxygen and carbon dioxide transport.
Contain carbonic anhydrase (critical for transport of carbon dioxide).
Normal erythrocyte count is 4–6 million/mm3 of blood and hematocrit (packed cell volume) value is of about 42% for females and 45% for males.
Hemoglobin (Figs 5.1A and B) is composed of four globin (highly folded polypeptide chains) and four heme groups (protoporphyrin IX with iron). Therefore iron is essential for the formation of hemoglobin.
Each hemoglobin molecule can carry four molecules of oxygen.
When carrying oxygen it is called oxyhemoglobin, and when not carrying oxygen it is called reduced hemoglobin.
It can also combine with carbon dioxide and helps in transport of carbon dioxide from the tissues to the lungs.
Erythropoiesis (Fig. 5.2) is the formation of erythrocytes in the body. Every day human body must produce about 2.5 million new RBCs.
In adults, erythropoiesis occurs mainly in the marrow of the sternum, ribs, vertebral processes, proximal epiphyses of the femur and humerus, and skull bones.
The process begins with a cell called hemocytoblast or stem cell, which have nucleus. Their next stage is normoblast, which are also nucleated. The normoblast loses its nucleus and become reticulocytes that are passed into the circulation as mature erythrocytes and the rate of erythrocyte formation is regulated by oxygen levels:
Hypoxia (lower than normal oxygen levels) is detected by cells in the kidneys
Kidney cells release the hormone erythropoietin into the blood
Erythropoietin stimulates erythropoiesis by the bone marrow.
The process of maturation of proerythroblast into normoblast requires vitamin B12 (erythrocyte-maturing factor, cyanocobalamin) and folic acid. Good dietary sources of vitamin B12 are liver, and good source of folic acid is green leafy vegetable. Lack of cyanocobalamin and folic acid in the diet or malabsorptive diseases causes megaloblastic anemia.
Iron is necessary for the synthesis of hemoglobin that fills the normoblast before they can become mature red corpuscles. Good dietary source of iron are meat and green leafy vegetables. Lack of iron in the diet or chronic bleeding disorders result in iron deficiency anemia.
An average daily diet provides about 10–25 mg of iron, but not all of it is available for absorption. It is mainly absorbed from the duodenum and upper jejunum. Men lose about 1 mg of iron each day in red cells and epithelium cells shed into the gastrointestinal tract (GIT), but a woman loses about 20 mg during each menstrual period.
The requirement for iron increases during pregnancy and lactation. Although most of the iron is used for hemoglobin synthesis, it is also vital for synthesis of myoglobin and many iron containing enzymes.
Iron is transported in the blood bound to a protein called transferrin. The serum transferrin can be measured by its capacity to bind iron that is known as total iron binding capacity (TIBC). The normal range of TIBC is 45–70 mmol/L and normal range of serum iron is 12–26 mmol/L.
The stored form of iron in the body are ferritin and hemosiderin. chronic accumulation in tissues causes hemosiderosis and hemochromatosis, which is a common occurrence in patients with thalassemia who receive repeated blood transfusion.
The normal level of hemoglobin ranges from 13 to 18 g/dL in men, and 11.5 to 16.5 g/dL in women. The normal mean corpuscular hemoglobin (MCH) ranges from 27 to 32 picogram and the mean corpuscular hemoglobin concentration (MCHC) ranges from 31 to 35 g/dL.
Hemoglobin has strong affinity for oxygen. The oxygenated arterial blood has a bright red color, while the deoxygenated (having lost oxygen) blood in the veins has a bluish purple color.
Hemoglobin has much stronger affinity for carbon monoxide, with which it forms carboxyhemoglobin that cannot carry oxygen and the individual exposed to carbon monoxide may die of anorexia.
Carboxyhemoglobin causes the individual to develop a cherry-red hue in contrast to cyanosis of anoxia.
White Blood Cells (Leukocytes)
Have nuclei and do not contain hemoglobin.
Total leukocyte count is 5,000–9,000/mm3.
Granular WBCs include:
Neutrophils (50%–70% of WBCs)
Basophils (less than 1%).
Agranular (or non-granular) WBCs include:
Granular leukocytes contain numerous granules in the cytoplasm and their nuclei are lobed. Agranular WBCs have few or no granules in the cytoplasm and have a large spherical nucleus. Granular WBCs are produced in the bone marrow (Fig. 5.5), while agranular WBCs are produced in lymph tissue, e.g. lymph nodes (lymph nodes are specialized dilations of lymphatic tissue, which are supported within by a meshwork of connective tissue called reticulin fibers and are populated by dense aggregates of lymphocytes and macrophages).
The primary functions of the various WBCs are:
Neutrophils phagocytoze bacteria and cellular debris; very important in inflammation
Eosinophils help break down blood clots and kill parasites
Basophils synthesize and store histamine (a substance released during inflammation) and heparin (an anticoagulant); function(s) remain unclear
Monocytes phagocytoze (typically as macrophages) in tissues of the liver, spleen, lungs and lymph nodes
Lymphocytes; immune response (including production of antibodies).
Some important characteristics of leukocytes (particularly neutrophils) are as follows:
Capable of diapedesis (also called extravasation)
Capable of ameboid movement
Exhibit chemotaxis (attracted to certain chemicals, such as those released by damaged cells).
Platelets are formed from cells called megakaryocytes present in bone marrow. They have no nucleus, but can secrete a variety of substances and can also contract (because they contain actin and myosin).
Normal platelet count in the blood is about 250,000/mm3.
They remain functional for about 7–10 days (after which they are removed from the blood by macrophages in the spleen and liver).
They play an important role in hemostasis (preventing blood loss).
Plasma is composed of water, proteins, inorganic constituents, nutrients, waste products, hormones and dissolved gases. The functions of each of the constituents are as follows:
Water serves as transport medium and carries heat.
Albumin is produced in the liver that is important in maintenance of osmotic pressure. About 60%–80% of plasma proteins are albumins.
Globulins are produced in the liver. There are two globulins designated as alpha and beta. Some are important for transport of materials through the blood (e.g. thyroid hormone and iron) and some are clotting factors.
The gamma globulins are immunoglobulins (antibodies) produced by lymphocytes.
Fibrinogens are produced in the liver and are important in clotting.
Inorganic constituents (1% of plasma), e.g. sodium, chloride, potassium and calcium are required for cellular activities.
Nutrients: Glucose, amino acids, lipids and vitamins are the sources of energy and building blocks of macromolecules.
Waste products, e.g. nitrogenous wastes like urea are on their way for elimination by renal system.
Dissolved gases: Oxygen (required for cellular respiration) and carbon dioxide (product of metabolism).
Hormones are the regulators of cellular metabolism.
Hemostasis is the process by which blood loss is prevented from broken vessel. The various mechanisms involved are as follows:
Vascular spasm is the vasoconstriction of injured vessel due to contraction of smooth muscle in the wall of the vessel. This ‘spasm’ may blood flow and blood loss, but will blood loss.
Formation of a platelet plug (Figs 5.6A to C) is by aggregation of platelets at the point where a vessel ruptures. This occurs because platelets are exposed to collagen; a protein found in the connective tissue located just outside the blood vessel. Upon exposure to collagen, platelets release adenosine diphosphate (ADP) and thromboxane. These substances cause the surfaces of nearby platelets to become sticky and, as ‘sticky’ platelets accumulate, a ‘plug’ forms.
Blood coagulation (clotting): The result of all of this is a clot; formed primarily of fibrin threads (or polymers), but also including blood cells and platelets. Blood clots in the right places prevent the loss of blood from ruptured vessels, but in the wrong place can cause problems such as a stroke (refer below the heading ‘Inappropriate Clotting’) or heart attack.
Clot retraction is the process of ‘tightening’ of clot.Contraction of platelets trapped within clot shrinks fibrin meshwork and pulls the edges of damaged vessel closer together. Over time (with the amount of time depending on the amount of damage), the clot is dissolved and replaced with normal tissue.
Fibrinolysis is dissolution of clot. Plasminogen (a plasma protein) is activated by many factors and becomes plasmin. Plasmin in turn breaks down fibrin meshwork and phagocytic WBCs remove products of clot dissolution.
Coagulation of Blood
The mechanism of blood clotting is a complicated one, but the general principle is simple and important. The essential changes are the conversion of soluble fibrinogen to insoluble fibrin. This forms a mesh of threads that entangles the blood cells and then contracts to express the serum.
The coagulation of blood involves a cascade of reactions resulting in the conversion of prothrombin (factor II) into thrombin and the action of this on fibrinogen (factor I), converting it into fibrin.
The other factors necessary for blood coagulation are tissue thromboplastin, platelet factors, calcium (factor IV), antihemophilic (factor VIII) and Christmas (factor IX) factors. Prothrombin is synthesized in the liver that requires vitamin K. Certain factors hasten clotting, while others retard it. These are often having clinical significance.
Factors Hastening Coagulation of Blood
Injury to the tissues; clean-cut wounds bleed much more freely than crushed wounds
Contact with foreign wounds; surgical dressings speed up clot formation
Temperature; elevated temperatures (packing wounds with swabs soaked in hot saline at 49°C) hasten clotting.
Factors Retarding Blood Coagulation
Sodium or potassium citrate prevents clotting by removing calcium
Oil, paraffin and grease prevent clotting
Local cold delays clotting
Heparin prevents clotting
Adrenaline stops bleeding by vasoconstriction.
Thrombus (clot) can be formed in an intact vessel, possibly due to roughened vessel walls (atherosclerosis) or slow-moving blood (e.g. in varicose veins); small quantities of fibrin form and accumulate, which forms an embolus (‘moving’ clot).
Excessive bleeding can result from deficient or abnormal clotting factors or deficiency of formed elements of blood:
Inability to produce certain factor(s).
Abnormally low platelet count
Immunity is the body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells. It consists of following activities:
Defense against invading pathogens (viruses and bacteria)
Removal of ‘worn-out’ cells (e.g. old RBCs) and tissue debris (e.g. from injury or disease)
Identification and destruction of abnormal or mutant-cells (primary defense against cancer)
Rejection of ‘foreign’ cells (e.g. organ transplant)
Allergies: Response to normally harmless substances
Major Targets of Body Defense System
Bacteria induce tissue damage and produce disease largely by releasing enzymes or toxins that physically injure or functionally disrupt affected cells and organs
Viruses that can only reproduce in host cells and cause cellular damage or death by:
Depleting essential cellular components
Causing cellular production of substances toxic to cell
Transforming normal cells into cancer cells
Inducing destruction of cells because infected cell no longer recognized as ‘normal-self’ cell.
The immune system is comprised of a diverse array of tissues and cells throughout the body that work cooperatively to protect us against pathogens. Immune responses can be classified into two types, the specific and the non-specific. In the specific immune response, the type or species of an individual pathogen is recognized and the immune system launches a response unique to that pathogen. In the non-specific response, the pathogen is merely recognized as foreign to the body and is destroyed by a more generalized response.
Human defenses start with physical barriers (nasal secretions and saliva, respiratory defenses, intact skin, stomach acids and genitourinary tract secretions) that exist both externally and internally. These structures come into close contact with the external environment and are therefore susceptible to attack:
Skin, when intact is impervious to most pathogens.
Nasal passages have microscopic hairs that trap dust particles. Mucus flushes away the detritus, along with many microorganisms.
Eyes produce secretions containing the enzyme lysozyme that is also found in saliva and nasal secretions. Lysozyme is an enzyme that attacks the cell wall of bacteria.
Ears protect themselves by ceruminous glands in the external auditory canal secreting cerumen or ear wax, which traps bacteria. As earwax dries, it flakes off, so removing any trapped microorganisms from the canal.
The mouth constantly produces saliva that contains the antibacterial enzymes lysozyme and lactoferrin. Saliva also washes the mouth and removes food debris.
The respiratory tract needs protection as the air entering the lungs may contain viruses. The mucous membranes that line the respiratory tract secrete mucus that traps any microorganisms that one may have breathed in. On the epithelia of the respiratory system are minute hairs called cilia that are able to waft in an upward direction to remove the mucus and any foreign substances trapped in it from the respiratory tract. The mucus moves to the pharynx where it is usually swallowed.At the end of the respiratory tree, mobile WBCs called macrophages, patrol the alveoli to deal with any pathogens they find there.
The digestive tract is another potential target because of the usual habit of inadvertent swallowing of many microorganisms when one eat and drink. The stomach secretions include hydrochloric acid and pepsin, which help digest proteins. Fortunately, these secretions also digest most bacteria, although if sufficient are consumed at any one time, they can reach the duodenum and ileum where defenses are fewer and cause gastrointestinal infections. Some bacteria such as Helicobacter pylori positively enjoy acidic conditions and can colonize the gastric mucosa of the stomach.
These surface barriers to infection are effective, but can be breached. If this happens, the person need a second line of defense to protect against infection. The internal defenses are both non-specific and specific in nature.
Non-specific Immune Responses
Non-specific immune responses include the following:
Inflammation is the tissue response to injury that serves to defend against foreign invader
Natural killer cells are lymphocyte-like cells that rather non-specifically lyses and destroy virus-infected cells and cancer cells
The complement system inactive plasma proteins that when activated, destroy foreign cells.
Inflammation is a non-specific immune response to tissue damage by trauma, chemical agents and microbial pathogens. The inflammatory response that occurs immediately after tissue damage prevents pathogenic proliferation, minimizes further damage to cells and tissue and finally enhances repair and healing. Inflammation manifests itself by redness, swelling, heat and pain, together with alteration of function. The processes involved in inflammation may be summarized as:
Mobilization of resident macrophages
Increase in vascular permeability
Infiltration of area by leukocytes
Damage repair—clotting process.
The redness and heat observed in inflammation are caused by vasodilation bringing blood to the area of injury. Swelling is edema resulting from increased vascular permeability, allowing plasma into the interstitial area. Swelling may also cause pain by pressing on and stimulating pain neurons. Mechanism as follows:
Bacterial invasion or tissue damage ➔ Release of histamine by mast cells (plus chemotaxins by damaged cells) ➔ Arterial vasodilatation and increased capillary permeability ➔ Increased blood flow to tissue and accumulation of fluid ➔ Increased numbers of phagocytes and more clotting factors into surrounding tissues ➔ Defense against foreign invader plus ‘walling off’ of inflamed area
Interferon is a family of similar proteins, which interfere with replication of the same or unrelated viruses in other host cells. The mechanism of action is as follows:
Virus enters a cell ➔ Cell releases interferon ➔ Interferon binds with receptors on uninvaded cells ➔ Uninvaded cells produce enzymes capable of breaking down viral mRNA ➔ Virus enters previously uninvaded-cell (now with interferon) ➔ Virus-blocking enzymes are activated ➔ Virus unable to multiply in newly invaded cells
Natural Killer Cells
Natural killer cells are lymphocyte-like cells that destroy virus-infected cells and cancer cells by lysing their membranes upon first exposure (Fig. 5.7). The mode of action is similar to cytotoxic T cells (but latter can attack only cells to which they have been previously exposed).
Natural killer cells are an important first line of defense against newly arising malignant-cells and cells infected with viruses, bacteria and protozoa. They form a distinct group of lymphocytes with no immunological memory. They constitute 5%–16% of the total lymphocyte population. Their specific function is to kill infected and cancerous cells.
The complement system (Fig. 5.8) consists of a series of proteins that work to ‘complement’ the work of antibodies in destroying bacteria. Complement proteins circulate in the blood in an inactive form. The so-called ‘complement cascade’ is set off when the first complement molecule, C1, encounters antibody bound to antigen in an antigen-antibody complex. Each of the complement proteins performs its specialized job in turn, acting on the molecule next in line. The end product is a cylinder that punctures the cell membrane and, allows fluids and molecules to flow in and out that destroys the target cell.
Complement system is activated by invading organisms and more often, triggered by antibodies (‘complements’ action of antibodies), which consists of 11 plasma proteins produced by liver. Their functions are as follows:
Membrane-attack complex proteins form a channel in membrane of invading cell. The resulting influx of water causes lysis (or bursting) of the invading cell.
Opsonins (bind with microbes and thereby enhance their phagocytosis) under certain circumstances of infection (bacteria or viruses) may become coated with opsonins (C3b, a complement protein or IgG, an antibody). Such microbes are said to be opsonized (opsonin comes from a Greek word meaning ‘sauce’ or ‘seasoning’; they make the bacterium or virus more palatable and more easily ingested by a phagocyte). Opsonins dramatically increase the rate of adherence and ingestion of a pathogen.
Vasodilation and increased vascular permeability to increase blood flow to invaded area.
Stimulate release of histamine from mast cells (enhances vascular changes characteristic of inflammation).
Activate kinins reinforces vascular changes induced by histamine and act as powerful chemotaxins.
Specific Immune Responses
The specific immune system responds to and retains a memory of specific antigen from specific pathogens, i.e. each species and subspecies of pathogen is recognized such as by the specific immune system. This ability to recognize and memorize specific antigen provides us with one of the most powerful medical tools such as vaccination.
Antigens are the recognition markers found on all cells—human, animal, fungal and bacterial cells and even viral capsules. Antigens are generally glycoproteins expressed on the surface of cells that are recognized by the immune system. Antigens can be divided into two common groups—self and non-self. Self-antigen is the normal protein expressed on our own cells and unless we have an identical twin, it is unique to ourselves. All other antigen is non-self and if recognized by the immune system will provoke an immune response.
Specific immune response is aimed at attacking selected ‘targets’ following prior exposure. It has two classes of responses:
Cell-mediated immunity (activated T lymphocyte) recognize and destroy body cells that have gone awry, including virus-infected cells and cancer cells
Humoral immunity (antibodies produced by B lymphocyte) is most effective against bacteria and their toxins plus a few viruses.
There are various groups of leukocytes involved in the specific immune system. These include the T lymphocytes, the B lymphocytes and the antigen-presenting cells.
Both T lymphocytes and B lymphocytes are produced in the bone marrow and reside mainly in the lymph nodes.
T lymphocytes specialize in destroying virally infected cells or cells that have been infected by intracellular parasites. As the cell dies, so does the pathogen and the chance of the infection spreading to other cells is reduced.
CD4 T cell is also known as a T helper (Th) cell
CD8 T cell is also known as a cytotoxic T (Tc) cell.
There is a difference in the action of the two types of T cell. CD4 cells are activated first; they will then stimulate CD8 T cells, which are responsible for killing the infected cells. They also play a central role in the activation of other immune response in the body.
CD4 T lymphocytes: CD4 T cells respond to the antigen presented by antigen-presenting cells (APC) such as dendritic cells. These cells scavenge the body for viral antigen and transport it through the lymphatic system to the T cells resident in the lymph nodes. The T cells then become activated to the specific antigen that has been presented to it (Fig. 5.9).
Recognition of the viral fragment activates the CD4 T cell: CD4 T cells start to multiply and send signals to other immune cells such as CD8 T cells, B lymphocytes, macrophages and natural killer cells. CD4 T cells activate these cells by releasing cytokines (chemical signals) such as interleukins, interferon and tumor necrosis factor. The effect of this mass mobilization of immune cells is to swamp an infected area with a massive immune response that overwhelms the pathogens and kills infected cells.
CD8 (cytotoxic) T lymphocytes: Also called killer or cytotoxic T cells, these are the only T cells that can directly attack and kill other cells. Once activated, CD8 T cells leave the lymph nodes and travel around the body in the circulatory and lymphatic systems, searching for the antigen that first activated the CD4 T cell. Their main targets are virus infected cells, but they will also attack bacteria, parasites and cancer cells. Once their target is found, they bind to it and release granules of perforin that create pores into the target cell membrane. These pores allow enzymes, also released by the CD8 cells, to enter the target cell and induce a form of cell suicide called apoptosis.
Suppressor T cells: There is another group of regulatory T cells called suppressor T cells that suppress the activity of B cells and other types of T cells after the pathogen has been destroyed. These suppressor T cells are responsible for winding down and switching off the immune response when the cause of infection has been eliminated, but their mechanism of action is poorly understood.
Humoral Immunity is Mediated Through B Cells/B Lymphocytes
Mature B cells are predominantly found in the lymph nodes where they monitor the lymph for signs of foreign antigen. B cells that bind with an antigen will subsequently differentiate into plasma cells and memory cells. Plasma cells begin to produce antibodies (up to 2,000 per second), whereas memory cells remain dormant until a person is again exposed to the same antigen.
The B cell uses its receptor to bind a matching antigen (Fig. 5.10), which it proceeds to engulf and process. Then it combines a fragment of antigen with its special marker, the class II protein. This combination of antigen and marker is recognized and bound by a T cell carrying a matching receptor. The binding activates the T cell, which then releases lymphokines and interleukins that transform the B cell into an antibody-secreting plasma cell.
The antibodies produced by B cells are key weapons in the specific immunity defense system. They have antigen recognition sites on the end of their arms that will bind to antigen on pathogenic organisms and mark them for destruction by other immune cells such as phagocytes:
Antibodies clump bacteria together in a process called agglutination. Bacteria are unable to replicate.
Antibodies bind to viruses and toxins rendering them harmless.
Antibodies bind to the flagella (tail-like structures) of bacteria, which immobilizes them.
Antibodies promote opsonization; they bind to bacteria and stimulate phagocytosis by macrophages.
Antibodies activate the complement system to destroy bacteria.
Antibodies are Y-shaped protein molecules, with two heavy chains and two light chains (Fig. 5.11). Both heavy and light chains have variable regions that bind antigens. Disulfide bonds hold the two heavy and two light chains together. Antibodies are grouped into five subclasses:
IgM is secreted early in an immune response; they act as B cell surface receptors for antigen attachment
IgG is most abundant antibody; produced in large numbers
IgE is mediator for common allergic responses (hay fever, asthma and hives).
The variable regions of immunoglobulin molecule bind antigens, disulfide bonds hold the two heavy and two light chains together. Antibodies are grouped into five subclasses:
IgA is a dimeric (double) form of antibody. They are the major antibody found in secretions; tears, saliva, sweat and mucus. They have an important role in respiratory infections.
IgD function is uncertain and may have a role in modulating the action of B cells.
IgE has a role in the activation of mast cells in the inflammatory response.
IgG is the most abundant antibody found in blood, lymph and cerebrospinal fluid. Around 15% of serum protein comprises IgG antibody. IgG agglutinates and immobilizes bacteria and binds to pathogens, promoting opsonization. It also activates the complement system, binds to and neutralizes viruses and toxins.
IgM is a pentameric (five-form) antibody complexes that are efficient agglutinators and activators of complement. The circulating anti-A and anti-B antibodies are those that characterize the ABO blood group system.
IgA and IgM antibodies
IgA is a doublet found concentrated in body fluids such as tears, saliva and the secretions of the respiratory and GIT. It is thus, in a position to guard the entrances to the body
IgM usually combines in star-shaped clusters. It tends to remain in the bloodstream, where it is very effective in killing bacteria.
Immunoglobulins provide protection by:
Neutralization of antigens; they bind with bacterial toxins to prevent them from harming susceptible cells; may also bind with viruses and prevent them from entering body cells.
Agglutination by formation of antibody antigen complex.
Enhancing activities of other defense systems:
Activation of complement system
Enhancement of phagocytosis
Stimulation of killer cells.
PLASMA CELLS VS MEMORY CELLS
Plasma cells are the prolific producers of customized antibodies (IgG antibodies).
They have lots of rough endoplasmic reticulum (RER) because antibodies are proteins and RER is needed to make proteins (because of the associated ribosomes) and then transport them out of the cell. Formation and subsequent production of antibodies takes several days after exposure to an antigen and peak antibody production may occur a week or two after exposure. This is referred to as the primary response (Fig. 5.12).
Memory cells remain dormant, but respond quickly if exposed to the antigen a second time. These cells are responsible for secondary response, a response so fast and effective that infection is typically prevented. They form the basis for long-term immunity.
ACTIVE IMMUNITY VS PASSIVE IMMUNITY
Active (natural) is the production of antibodies as a result of exposure to an antigen (immunization).
Passive is the direct transfer of antibodies formed by another person (or animal), e.g. transfer of IgG antibodies from mother to fetus across placenta or in colostrum (first milk) or treatment for rabies or poisonous snake venom.
Infants are born with relatively weak immune responses. They have, however, a natural ‘passive’ immunity; they are protected during the 1st month of life by means of antibodies they receive from their mothers. The antibody IgG, which travels across the placenta, makes them immune to the same microbes to which their mothers are immune. Children who are nursed also receive IgA from breast milk; it protects the digestive tract. Passive immunity can also be conveyed by antibody-containing serum obtained from individuals who are immune to a specific infectious agent. Immune serum globulin or ‘gamma globulin’ is sometimes given to protect travelers to countries where hepatitis is widespread. Passive immunity typically lasts only a few weeks.
‘Active’ immunity (mounting an immune response) can be triggered by both infection and vaccination. Vaccines contain microorganisms that have been altered so they will produce an immune response, but will not be able to induce full-blown disease. Some vaccines are made from microbes that have been killed. Others use microbes that have been changed slightly so they can no longer produce infection. They may, for instance, be unable to multiply. Some vaccines are made from a live virus that has been weakened or attenuated, by growing it for many cycles in animals or cell cultures.
Cell-mediated immunity is mediated through lymphocytes, which defend against invaders that ‘hide’ inside cells (where antibodies and complement system cannot reach them). To be effective they must be in direct contact with their targets. They get activated by foreign antigen, only when present on surface of cell that also has ‘self-antigens’ (except whole transplanted foreign cells). The precursors of T cells undergo maturation in thymus, where they are educated in two ways:
They learn to recognize the ‘self’ markers or histocompatibility antigens, which they will encounter in the tissues. These ‘self’ markers, which are at the cell surface, are the antigens, which cause transplant rejection and they are also known as human lymphocyte antigens (HLA) or transplantation antigens. It is the thymus, which teaches the T cells what to recognize as self.The genes controlling the HLA are known collectively as the major histocompatibility complex (MHC). The immune response genes, which control the ability of immunocompetent-cells to respond to antigen, are very closely related to the MHC. The MHC gene is in some way involved in cell cooperation, such as that between T and B lymphocytes.
They acquire the ability to kill cells, which bear foreign antigens (non-self ). In doing this, they become cytotoxic T lymphocytes. They can see the foreign antigens on the cells infected with viruses or fungi and on transplanted cells and proceed to kill them. Because they have been programmed to recognize the self, they do not attack the body’s own normal cells. Under certain circumstances, however, they do attack self and these results in an autoimmune disease, e.g. lupus erythematosus.
T cells are of three types as follows:
Cytotoxic (killer) T cells—destroy host and cells bearing foreign antigen (e.g. host-cells invaded by viruses and cancer cells).
Helper T cells—enhance development of B cells into antibody-secreting cells and enhance activity of cytotoxic and suppressor T cells.
Suppressor T cells—suppress B cell antibody production and cytotoxic and helper T cell activity; effects are primarily the result of chemicals called cytokines (or lymphokines).
Cytotoxic T Cells
Most frequently target the host-cells infected with viruses, by releasing perforin molecules that destroy target T cells; perforin molecules form channels in target cell membrane and allows water to rush in, thereby target-cells are lysed.
Helper T Cells
Activation of helper T cells requires macrophages (macrophage presents foreign antigen in combination with ‘self-antigen’), which secrete cytokines that ‘help’ the immune response.
Suppressor T Cells
These cells limit the responses of other cells (B and T cells), make immune response self-limiting, prevent excessive immune response, which might be detrimental to body and may also prevent immune system from attacking a person’s own cells and tissues. Autoimmunity may arise in several ways:
Reduction in suppressor T-cell activity.
Normal self-antigens modified by drugs, environmental chemicals, viruses or mutations.
Exposure to antigen very similar to self-antigen.
VACCINATION AND THE IMMUNE SYSTEM
Both the B and T cells play an important role in vaccinations that use the body’s own immune system to protect us against potentially dangerous pathogens.
After exposure to antigen, either by infection or vaccination, some B and T cells become memory cells and have long lives, residing in the lymph nodes, waiting to detect the antigen that triggered their original production.
B cell clones that do not become plasma cells become B memory cells. On subsequent exposure to an antigen, B memory cells initiate an immediate response that produces billions of antibodies that destroys the pathogen even faster and more effectively than on its first encounter. Vaccination uses non-infective antigens to prepare the memory cells that respond quickly to any signs of infection. Vaccination utilizes this ability to retain a memory of antigen to confer protection against some of the most deadly diseases that can affect human species.
ABO Blood Groups
When discussed about someone’s blood type, focus is about what kind of antigens they have present on their red blood cell’s surface (Fig. 5.13). Often when discussed about antigens the focus is on something foreign, but in this case the antigen is self. Blood typing is important in preventing transfusion reactions (Table 5.1):
Type A: Has A antigen on the RBC surface and anti-B antibody in the plasma.
Type B: Has B antigen on the RBC surface and anti-A antibody in the plasma.
Type AB: Has both A and B antigens on the RBC surface, and neither of the antibodies in the plasma. Because of the lack of antibodies in the plasma, type AB persons can receive any type of blood as long as the Rh factor is matched.
Type O: Has no antigen on the RBC surface, and both anti-A and anti-B in the plasma. Because the cells do not have an antigen, type O blood can be given to anyone as long as the Rh factor is matched.
Antibodies are produced if antigen is not present. Antigens are produced because common intestinal bacteria have A- and B-like antigens. These antibodies are produced by age of about 6 months.
If anti-A antibodies are mixed with blood cells that have the A antigen or anti-B antibodies are mixed with blood cells that have the B antigen, the results will be agglutination or clumping of RBCs. This reaction can be used to type blood. Take two drops of ‘unknown’ blood and place a drop of anti-A antibody solution on one blood drop and a drop of anti-B antibody solution on the other blood drop. Then, observe for any clumping occurs. If clumping occurs in the drop of blood in which the anti-A antibodies are added, then the A antigen is present and, of course, if there is no clumping, then the A antigen is not present. If clumping occurs in the drop of blood in which the anti-B antibodies are added, then the B antigen is present and, of course, if there is no clumping, then the B antigen is not present. Using this information, the blood type can be determined (Table 5.2).
Type O blood is the most common blood type, followed by type A and type B. The least common blood type is AB.
O+ 37%, O- 6%, A+ 34%, A- 6%
B+ 10%, B- 2%, AB+ 4%, AB- 1%
In the above chart, the blood types are listed with either positive or negative. The positive or negative refers to the presence or absence of the Rh factor.
Individuals with type O are often called universal donor, because they have no antigens, hence no clumping.
Individuals with type AB are often called universal recipient, because they have no antibodies, hence no clumping.
Rh Blood Group
Another important antigen that to be identified is the Rh group.
Figures 5.14A to C: If a baby inherits Rh-positive (Rh+) blood from the father and the mother is Rh-negative (Rh–) problems can develop if the blood cells of mother and baby mix during birth
The blood of an Rh-positive person has the antigen on the RBC surface, while the blood of an Rh-negative person does not. Unlike the ABO blood groups, there is no antibody present in the plasma normally. An antibody will be formed only if an Rh-negative person is exposed to Rh-positive blood.
A good example of this is what happens with hemolytic disease of the newborn. This is only a concern for an Rh-negative mother carrying an Rh-positive baby. If mother and baby’s blood mixes at birth, mother will form antibodies against the Rh antigen. This becomes a problem for the next Rh-positive baby. Mother’s antibodies will attack the second Rh-positive baby’s RBCs causing agglutination (Figs 5.14A to C). This is a life-threatening situation for the newborn. To prevent this from happening, mother will be given a shot (RhoGAM) after the birth of her first Rh-positive baby, and then again after the births of any other Rh-positive babies. Mother will also be given this shot after any procedures that may cause mixing of maternal and fetal blood (like an amniocentesis) or following a miscarriage.
ERYTHROBLASTOSIS FETALIS(RH DISEASE)
Hemolysis of fetal erythrocytes can cause anemia or fetal death. This may occur when an Rh-negative mother and Rh-positive father have an Rh-positive fetus.
RhoGAM is used in the treatment for Rh disease; contains antibodies specific for Rh-positive antigen (a good example of passive immunity), which should be injected to the mother within 72 hours after birth of Rh-positive baby.
Lymphatic system is closely connected with the blood and circulatory system. It is an extensive drainage system that returns water and proteins from various tissues back to the bloodstream. It is comprised of a network of ducts, called lymph vessels or lymphatics that carries lymph; a clear, watery fluid that resembles the plasma of blood. This system is considered as part of the blood and circulatory system because lymph comes from blood and returns to blood and because its vessels are very similar to the veins and capillaries of the blood system. Throughout the body, wherever there are blood vessels, there are lymph vessels and the two systems work together:
As blood circulates throughout the body, fluid from the blood leaks into tissue.
A network of vessels known as the lymphatic system collects the fluid and returns it to the circulatory system (Fig. 6.1).
This fluid is known as lymph. This transparent yellowish fluid that is collected in lymphatic capillaries, move to larger lymph vessels. Similar to veins, lymph vessels contain valves that prevent back flow of lymph. Lymph vessels form a one-way system that returns fluids collected from tissues back to bloodstream.
The lymphatic system has no pump like the heart. Lymph must be moved through vessels by the squeezing of skeletal muscles.
These lymph vessels pass through small bean-shaped enlargements (organs) called lymph nodes, which acts as filters and producers of special white blood cells called lymphocytes that are specialized to fight infection.
The fluid is returned to the circulatory system at an opening in a vein located under the left clavicle, just below the shoulder.
The entire lymphatic system flows toward the bloodstream, returning fluid from body tissues to the blood (Fig. 6.2). If there were no way for excess fluid to return to the blood, the body tissues would become swollen. For example, when a body part swells, it may be because there is too much fluid in the tissues in that area. The lymph vessels collect that excess fluid and carry it to the veins through the lymphatic system.
This process is crucial because water, proteins and other molecules continuously leak out of tiny blood capillaries into the surrounding body tissues. This lymph fluid has to be drained and should returns to the blood via the lymphatic vessels. These vessels also prevent the back flow of lymph fluid into the tissues.
Figure 6.1: Connection between lymphatic capillary and tissue fluid. Lymphatic capillaries are blind-ended tubes in which adjacent endothelial cells overlap each other, forming flap-like minivalves
The lymphatic system also helps to defend the body against invasion by disease causing agents such as viruses, bacteria or fungi. Harmful foreign materials are filtered out by small masses of tissue called lymph nodes (Fig. 6.3) that lie along the network of lymphatic vessels. These nodes help in purifying lymphocytes (WBCs), some of which produce antibodies. They also stop infections from spreading through the body by trapping disease-causing germs and destroying them.
The spleen also plays an important part in the immune system and helps the body to fight infection. Like the lymph nodes, the spleen contains antibody producing lymphocytes. These antibodies weaken or kill bacteria, viruses and other organisms that cause infection. The macrophages in the spleen destroy damaged erythrocytes and clear them from the bloodstream.
The lymphatic system (Fig. 6.4) is a network of very fine vessels or tubes called lymphatics that are found in every part of the body except the central nervous system (CNS). The major parts of the system are the bone marrow, spleen, thymus gland, lymph nodes and tonsils. Other organs, including the heart, lungs, intestines, liver and skin also contain lymphatic tissue.
Lymph nodes are round- or kidney-shaped and range in size from very tiny to 1 inch in diameter. They are usually found in groups in different places throughout the body including the neck, armpit, chest, abdomen, pelvis and groin. About two thirds of all lymph nodes and lymphatic tissue are within or near the gastrointestinal tract (GIT).
Lymphocytes are WBCs in the lymph nodes that help the body to fight with infection by producing antibodies, which destroy foreign matter such as bacteria or viruses. Two types of lymphocytes are T cells and B cells. Some lymphocytes become stimulated and enlarged when they encounter foreign substances these are called immunoblasts.
All the lymph collected from the entire left side of the body, the digestive tract and the right side of the lower part of the body flows into a single major vessel; the thoracic duct. The thoracic duct arises anterior to the second lumbar vertebra as enlarged sac, beginning as the cisterna chyli (Fig. 6.5). This sac like lymphatic mass collects lymph from lower limbs of the body as well as the digestive system (Peyer’s patch). Thoracic duct contains smooth muscle in order to aid lymph flow.
Frequent movement is critical for humans to properly move lymph and prevent lymph fluid buildup in certain areas of the body. The thoracic duct empties about 100 mL of lymph every hour into the left subclavian vein.
The lymph from the right side of the head, neck and chest is collected by the right lymph duct, empties into the right subclavian vein near the right side of the neck.
The spleen is found on the left side of the abdomen. Unlike other lymphoid tissue, red blood cells (RBCs) flow through it. It helps to control the amount of blood and blood cells that circulate through the body, and helps to destroy damaged cells.
In adult mammals, the bone marrow is the site of B cell generation and one of the sites of T cell generation. It also produces erythrocytes, granulocytes, monocytes and platelets. Early on, it was discovered that when the spleen (another major component of the immune system) was irradiated, it was depleted of cells. However, when it was reconstituted with bone marrow cells, it soon began to develop colonies on it. After some time it recovered its appearance and function. This was a strong indication that the bone marrow was responsible for generating the stem cells, which give rise to all the other immune cells. It was found that the bone marrow was the place where the maturation of B lymphocytes occurred. However, an irradiated animal needed to have a thymus for the bone marrow cell therapy to work. It was soon discovered that only immature ‘pre-T’ cells are generated in the bone marrow. Their maturation takes place in the thymus.
The thymus (Fig. 6.6) is a bilobed, grayish organ located in the thoracic cavity just below the neck, the thymus develops from the endoderm. During its development many cells migrate towards it, most of which are lymphocytes. The thymus is divided into two distinct compartments, the outer cortex and inner medulla. Both regions are densely populated with lymphocytes (or thymocytes, while in the thymus). Most of the cortical lymphocytes are immature and unable to carry out immune functions. Mature immunocompetent cells are found in the medulla in greater numbers. The main function of the thymus is to develop immature T cells into immunocompetent T cells. This process begins with the production of pre-T cells in the bone marrow and their subsequent transport to the thymus via the blood. The pre-T cells are then taken into the cortex of the thymus. Here, a series of molecular events take place allowing the cells to recognize certain antigens. Some of the cells recognize self-components and a process of negative selection eliminates them. Those that fail the selection die and those that live proceed to the medulla, and eventually into the bloodstream where they act upon foreign agents in the body.
The spleen (Fig. 6.7) serves two major functions in the body. One function is destruction of old RBCs and the other is the major site for mounting the immune response. The spleen behaves similar to a lymph node, but instead of filtering the lymphatic fluid it filters the blood. Blood entering the spleen travels through progressively smaller arterioles until it is deposited in an area known as the red pulp. This is where the RBCs are processed. Surrounding each of the arterioles is a sheath of lymphoid cells, which make up the periarteriolar lymphoid sheaths (PALS). The interface between the PALS and the blood is a region of intense phagocytic activity and sets the stage for an immune response. The immune reactivity of the spleen is especially effective for dealing with blood-borne antigens such as bacteria that reach the blood.
Lymph drains into open-ended, one-way lymph capillaries. It moves slowly than blood, pushed along mainly by a person’s breathing and contractions of the skeletal muscles. The walls of blood capillaries are very thin and they have many tiny openings to allow gases, water and chemicals to pass through to nourish cells and to take away waste products. Interstitial fluid passes out of these openings to bathe the body tissues.
Lymph vessels recycle the interstitial fluid and return it to the bloodstream in the circulatory system. They collect the fluid and carry it from all of the body’s tissues, and then empty it into large veins in the upper chest, near the neck.
Lymph nodes are made of a mesh-like network of tissue. Lymph enters the lymph node and works its way through passages called sinuses. The nodes contain phagocytes that engulf (phagocytoze) and destroy bacteria, dead tissue and other foreign matter, removing them from the bloodstream. After these substances have been filtered out, the lymph leaves the nodes and returns to the veins where it re-enters the bloodstream.
When a person has an infection germs collect in great number in the lymph nodes. For example if the throat is infected, the lymph nodes of the neck may swell. Sometimes the phagocytes may not be able to destroy all of the germs, which result in local infection of the nodes.
Because the lymphatic system extends to the far reaches of the body, it also plays a role in the spread of cancer. This is why lymph nodes near a cancerous growth are usually removed with the growth.
Disease Conditions, Disorders and Dysfunctions
Because the lymphatic system branches through most of the parts of the body, it may be involved in a wide range of conditions. Diseases may affect the lymph nodes, spleen or the collections of lymphoid tissue that occur in certain areas of the body.
Disorders of the Lymph Nodes
Lymphadenopathy: It is an increase in the size of a lymph node or nodes, most often as the result of a nearby infection (e.g. lymphadenopathy in the neck, might be the result of an infection of the throat). Less commonly (particularly in children), swelling of the lymph nodes can be due to an infiltration of cancerous cells. If lymphadenopathy is generalized (meaning that the swelling is present in several lymph node groups throughout the body), it usually indicates that the person has a systemic disease.
Lymphadenitis or adenitis: It is an inflammation (swelling, tenderness, and sometimes redness and warmth of the overlying skin) of the lymph node due to an infection of the tissue in the node itself. In children, this condition most commonly involves the lymph nodes of the neck.
Lymphomas: These are a group of cancers that arise from the lymph nodes; these diseases result when lymphocytes undergo changes and start to multiply out of control. The involved lymph nodes enlarge and the cancer cells crowd-out healthy cells and may form tumors (solid growths) in other parts of the body.
Splenomegaly: It is the enlargement of spleen. In children, the spleen is usually small enough that it cannot be felt by pressing on the abdomen, but the spleen can enlarge to several times its normal size with certain diseases.
There are many possible reasons for this including various blood diseases and cancers, but the most common cause in children is infection, particularly viral infections. Infectious mononucleosis, a condition usually caused by the Epstein-Barr virus (EBV), is one of many viral infections associated with an enlarged spleen. Individuals with an enlarged spleen should avoid contact sports because they can have a life-threatening loss of blood if their spleen is ruptured.
Tonsillitis: It is an extremely common condition, particularly in children. Tonsillitis occurs when the tonsils (Fig. 6.8) (the collections of lymphoid tissue in the back of the mouth at the top of the throat) are involved in a bacterial or viral infection that causes them to become swollen and inflamed. The tonsils normally help to filter out bacteria and other microorganisms to aid the body in fighting infection. Symptoms include sore throat, high fever, and difficulty in swallowing. The infection may also spread to the throat and surrounding areas, causing pain and inflammation (pharyngitis).
The integumentary system includes the skin and its accessory organs such as hair, nails and a variety of glands, which act as a barrier to protect the body from the outside world. Outer cover of the body is skin that continues with the mucous membrane lining the body orifices. Integumentary system also functions to retain body fluids, protect against disease, eliminate waste products and regulate body temperature.
The word integument comes from a Latin word that means to cover. The skin is the human body’s largest organ, accounting for 12–15% of body weight. It has a large surface area of around 1.8 m2 (adult) and varies in thickness at different parts of the body from less than 0.5 mm on the lips to 4 mm on the soles of the feet.
The most important function of skin is protection of the body. The other functions of the integumentary system include:
Serving as a barrier against infection and injury
Helping to regulate body temperature
Receive information about the external environment
Subcutaneous fat serves as a store for fat and water
Removing waste products from the body
Providing protection against ultraviolet (UV) radiation from the sun
Producing vitamin D (calcitriol).
The skin contains several types of sensory receptors that serve as the gateway through which sensations such as pressure, heat, cold and pain are transmitted to the nervous system. The skin is composed of three layers, the epidermis, dermis and hypodermis (Fig. 7.1).
The epidermis is predominantly made of stratified squamous epithelium, but other cells including melanocytes, keratinocytes, Langerhans cells and Merkel cells are also present. No blood vessels are found in the epidermis so cells obtain their nutrients from capillaries in the dermis. The epidermis is composed of five distinct layers (Fig. 7.2):
Sometime referred to as stratum germinativum, it is made up of a single layer of columnar or cuboidal cells with the lower surface of cells attached to dermis via their basement membrane.
It receives nutrients from the blood via the dermal vessels. This is the layer where mitosis (cell division) takes place that replenishes the cells of skin. New cells are produced in the stratum basale and these cells gradually migrate up through the epidermis until they are sloughed off the stratum corneum. Merkel cells interface with sensory neurons, acting as pressure sensors for touch.
Sometimes called prickle cell layer, it consists of several layers of polyhedral (many-sided) cells. Interlocking spine-like projections help the binding of this layer with the help of desmosomes (cell-cell adhesion structures). This gives the skin much of its strength. Active protein synthesis takes place in the stratum spinosum; the cells start to produce keratin, a tough connective tissue. Some cell division also takes place in the lower stratum of this layer. In the upper strata, the cells become somewhat flattened. Melanin is produced by melanocytes that give skin its color. Langerhans cells have an immunological function, protecting the skin against invading microbes.
Cells of the stratum spinosum gradually migrate outwards and into this (two to four cells thick) layer. The cells become flattened and start to lose their nuclei and other organelles. The granules that give the layer its name contain keratohyalin that is involved in cross-linking keratin fibers. This layer also secretes a lipid-rich fluid that acts as a waterproof barrier against the loss of body fluids and entry of fluids from the outside environment. This is a transition layer between living and dead cells.
Stratum lucidum is a layer composed of flat, translucent and dead cells. The stratum lucidum appears only in the palms of the hands and the soles of the feet.
Stratum Corneum (Horny Layer)
Stratum corneum is a thick layer of dead cells containing soft keratin that keeps skin elastic. Cells below contain a fatty substrate that keeps skin waterproof and prevents cracking of the skin, and allowing bacteria inside. Cells are constantly being sloughed off and replaced by cells from lower layers.
The dermis is a highly elastic, tough and flexible tissue made up of a meshwork of collagenous, reticular and elastic fibers. It is subdivided into two main layers, the upper papillary layer and the reticular layer.
Upper Papillary Layer
The papillary region is the most superficial region of the dermis. It has a large surface area due to nipple-like structures called dermal papillae that extend into the epidermis. Capillary loops from arteries to veins in the dermis provide nutrients and facilitate gas exchange with the lower layers of the epidermis. There are nerve endings for heat, pain, cold and pressure. Encapsulated nerve endings are found in this layer that detect the sensation of touch. In the fingertips, double rows of papillae are found.
Reticular layer is made up of loose connective tissue and has relatively few cells. Pacinian corpuscles are distributed through the dermis and function as pressure receptors. Most of the layer is an elastic network of tough collagen fibers, interwoven with elastin fibers. Collagenous fibers arranged in special pattern and incisions made parallel to these lines during surgery results in faster wound healing. Stretch marks from pregnancy are largely due to breaks in these collagen and elastic fibers. All of the fibers are produced by fibroblasts and include:
Collagenous fibers—tough fibers that provide support for skin
Reticular fibers—thinner collagenous fibers that form a fine mesh that provides support
Elastic fibers—produced by fibroblast cells, and provide flexibility to the skin.
Hair follicles and associated sebaceous glands are found in this layer. These glands secrete sebum; a mixture of lipids and salts that provide protection against bacteria and fungi, and also pheromones that gives the person their individual smell. When the glands become blocked, the sebum oxidizes forming so-called ‘blackheads’.
Hair on the head provide some protection, but apart from the axial regions, most human hair is vestigial, presumably from the time in ancient ancestry when we more closely resembled our simian ancestors. Arrector muscles are attached to hair, allowing the hair to become more erect. At one time this would have raised our hair and helped conserve heat, but in modern humans we just observe ‘goose bumps’.
Sweat glands are of two types—eccrine and apocrine glands.
Eccrine glands are mainly responsible for producing the sweat that cools the skin in thermoregulation. As sweat evaporates, the transition from liquid to vapor uses energy and that energy comes from the surface of the body. This transfer of heat energy from the body to water vapor cools the skin and the blood circulating through it.
Apocrine glands are found predominantly in the axilla and do not start producing sweat until puberty. The sweat produced by these glands is oilier than that produced by the eccrine glands and is partly responsible for the individual’s body odor (hence, the widespread use of underarm deodorants). These glands increase their secretions in times of stress or sexual arousal.
There are relatively few cells in the dermis. Fibroblasts produce the structural fibers mentioned above, macrophages remove damaged cells and mast cells respond to injury by initiating the inflammatory response.
HYPODERMIS (SUBCUTANEOUS LAYER)
Subcutaneous layer is thicker than the dermis and also tends to be thicker in females. Comprised predominantly of adipose tissue containing adipocytes (fat cells), it is an area for the formation and storage of fat. Areolar tissue, a loosely connected network of fibers provides elasticity and connects the skin to underlying structures.
We humans are warm-blooded organisms capable of maintaining a relatively constant central body temperature of about 36.8°C (rectal temperature is about 0.5°C higher) irrespective of the surrounding temperature. The temperature of the skin and subcutaneous tissue is variable depending on the environmental temperature. The normal body temperature is at its peak in the early evening hours and at its lowest in the early morning hours.
The constant level of body temperature is maintained by a balance between the heat generated in the body as a result of metabolic processes and the heat lost by the body to the environment. Failure to maintain a balance results in hyperpyrexia (elevated temperature).
Production of heat in the body is the result of various metabolic processes going on in the body constantly. The maximum heat production is in the liver, endocrine glands and muscle. Muscular activity accounts for about 30% of heat production, which further increases with physical activities. When insufficient heat is produced or body is exposed to cold environment, the body shivers (involuntary contraction of skeletal muscles) to generate required heat. Our body gains heat when exposed to warm environment.
Heat loss from the body is principally through skin by radiation, conduction, convection and evaporation.
Radiation is transfer of body heat to nearby objects that are cooler than the skin surface. The heat from the internal organs to the skin surface is conveyed by the bloodstream. Thereby, radiation of heat from the skin surface to the environment can be greatly increased by dilatation of cutaneous blood vessels. When the environmental temperature is much higher than the body temperature, the heat cannot be dissipated. This is the basis of heat stroke in very hot climate.
Conduction is referred to transfer of heat from skin surface to objects in direct contact with the skin. Heat is rapidly lost from the skin surface to an object, which is good conductor of heat such as metals and cotton clothing. Heat loss is minimized by wearing poor conductors of heat such as woolen or fur clothing.
Convection is loss of heat away from the body by movement of air. The air in contact with body surfaces gets warmed and less dense, which is displaced by cooler air that is denser. Thereby the cooler air takes the heat away from the body surface.
Evaporation is the process of conversion of water into air, which utilizes heat. The insensible perspiration, continuously takes away certain amount of body heat by this mechanism. The process of evaporation cannot be controlled. When the body temperature rises, large amounts of heat is lost by sweating, which is an efficient means of large amounts of heat loss particularly when the environmental temperature is greater than 37°C. When the humidity of the surrounding air is high, sweat cannot evaporate and even an environmental temperature of 27°C becomes uncomfortable.
Control of Temperature Regulation
The temperature regulating center of the thalamus plays an important role in the regulation of body temperature. It has two groups of neurons; one group is sensitive to cold and the other group is sensitive to heat, which receives information from the temperature receptors in the body.
A fall in body temperature makes the temperature regulating centers to conserve heat by increasing impulses to sympathetic nerve impulses, which causes vasoconstriction of cutaneous blood vessels and simultaneously causes shivering that generates heat. These two mechanisms together elevate body temperature.
A rise in body temperature make the temperature regulating centers to inhibit sympathetic nerve impulses that results, in vasodilatation of cutaneous blood vessels with simultaneous stimulation of sweat glands to secrete more sweat to the skin surface. the two mechanism together lower the body temperature.
Disorders Related to Thermoregulation
Hypothermia is the condition when the body temperature falls below 35°C. It results in decreased metabolic activity, decreased blood flow to the tissues and decreased oxygen supply to the tissues. If this condition is left untreated, the individual becomes drowsy and comatose due to cerebral ischemia. Death may occur when the temperature falls below 26°C due to ventricular fibrillation.
Pyrexia is an elevated body temperature higher than the normal. The causes of pyrexia are toxins released from infecting organism and products of protein breakdown. These substances act on the thermoregulating centers as long as they are present in the body. Such substances are called pyrogens.
Hyperpyrexia is an extremely dangerous condition when the body temperature is more than 40.5°C. Such a condition rapidly increases the cellular metabolism and the thermoregulatory system fails to dissipate heat. The rectal temperature exceeding 42°C causes irreversible brain damage.
CONDITIONS/DISORDERS AFFECTING INTEGUMENTARY SYSTEM
Flames, hot water or steam, sunlight, electricity or corrosive chemicals may cause burns of the skin. The severity of burns ranges from minor to fatal and the classification of burns is based on the extent of damage:
First-degree burn: Only the superficial epidermis is burned and is painful, but not blistered. First-degree burn causes death of epidermal cells.
Second-degree burn: Deeper layers of epidermis are affected, could have inflammation, blisters and the burned skin is often painful.
Third-degree burn: The entire epidermis is charred or burned away and the burn may extend into the dermis. Often such a burn is not painful at first, if the receptors in the dermis have been destroyed.
Extensive third-degree burn: Potential life-threatening because of loss of skin. without this natural barrier, living tissue is exposed to the environment and is susceptible to infection and dehydration.
Acne vulgaris (cystic acne or simply acne) is a common human skin disease, characterized by areas of skin with seborrhea (scaly red skin), comedones (blackheads and whiteheads), papules (pinheads), pustules (pimples), nodules (large papules) and possibly scarring. Acne affects mostly that parts of skin which have the densest population of sebaceous follicles; these areas include the face, the upper part of the chest and the back. Severe acne is inflammatory, but acne can also manifest in non-inflammatory forms. The lesions are caused by changes in pilosebaceous units; skin structures consisting of a hair follicle and its associated sebaceous gland changes that require androgen stimulation.
Acne occurs most commonly during adolescence and often continues into adulthood. In adolescence, acne is usually caused by an increase in testosterone, which accrues during puberty and regardless of sex. For most people, acne diminishes over time and tends to disappear or at the very least decreases by age of 25. However, no way to predict how long it will take to disappear entirely and some individuals will carry this condition well into their thirties, forties and beyond.
Some of the large nodules were previously called ‘cysts’ and the term nodulocystic has been used to describe severe cases of inflammatory acne. The ‘cysts’, or boils that accompany cystic acne, can appear on the buttocks, groin and armpit area, and anywhere else where sweat collects in hair follicles and perspiration ducts. Cystic acne affects deeper skin tissue compared to other common acne.
Aside from scarring, its main effects are psychological such as reduced self-esteem and in very extreme cases depression or suicide. Acne usually appears during adolescence, when people already tend to be most socially insecure. Early and aggressive treatment is therefore advocated by some to lessen the overall long-term impact to individuals.
Sunburn is a form of radiation burn that affects living tissue such as skin that results from an overexposure to UV radiation commonly from the sun. Normal symptoms consist of red or reddish skin that is hot to the touch, general fatigue and mild dizziness. An excess of UV radiation can be life-threatening in extreme cases. Exposure of the skin to lesser amounts of UV radiation will often produce a suntan.
Excessive UV radiation is the leading cause of primarily non-malignant skin tumors. Sunscreen is widely agreed to prevent sunburn and some types of skin cancer. Clothing, including hats, is considered the preferred skin protection method. Moderate sun tanning without burning can also prevent subsequent sunburn as it increases the amount of melanin and a skin photoprotectant pigment that is the skin’s natural defense against overexposure. Importantly, both sunburn and the increase in melanin production are triggered by direct DNA damage. When the skin cells’ is damaged by UV radiation, type I cell death is triggered and the skin is replaced. Malignant melanoma may occur as a result of indirect DNA damage, if the damage is not properly repaired. The treatment of sunburn is conservative, although some skin creams can help with the symptoms.
Skin cancers (neoplasms) are named after the type of skin cell from which they arise. Basal cell cancer originates from the lowest layer of the epidermis and is the most common, but least dangerous skin cancer. Squamous cell cancer originates from the middle layer and is less common, but more likely to spread and if untreated, becomes fatal. Melanoma, which originates in the melanocytes (pigment-producing cells), is the least common, but most aggressive fumor, most likely to spread and if untreated, become, fatal. Still, melanoma has one of the higher survival rates among major cancers. Most cases are caused by overexposure to UV rays from the sun or sunbeds.
Albinism (achromia, achromasia or achromatosis) is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of tyrosinase, a copper-containing enzyme involved in the production of melanin. Albinism results from inheritance of recessive gene alleles. Albinism is associated with a number of vision defects such as photophobia, nystagmus and astigmatism. Lack of skin pigmentation makes for more susceptibility to sunburn and skin cancers. In rare cases such as Chédiak-Higashi syndrome, albinism may be associated with deficiencies in the transportation of melanin granules. This also affects essential granules present in immune cells leading to increased susceptibility to infection.
Vitiligo is characterized by the complete or partial absence of pigment in the skin, but unlike albinism it is due to autoantibodies formed against melanocytes.
Psoriasis is an immune-mediated disease that affects the skin. It is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms.
Psoriasis occurs when the immune system mistakes a normal skin cell for a pathogen and send out faulty signals that cause overproduction of new skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of stroke and treating high blood lipid levels may lead to improvement. There are five types of psoriasis namely plaque, guttate, inverse, pustular and erythrodermic. The most common form plaque psoriasis, is commonly seen as red and white hues of scaly patches appearing on the top first layer of the epidermis (skin). Some patients have no dermatological signs or symptoms. The terms psoriasis, roughly means ‘itching condition’.
In plaque psoriasis, skin rapidly accumulates at the affected sites, which gives it a silvery-white appearance. Plaques frequently occur on the skin of the elbows and knees, but can affect any area, including the scalp, palms of hands and soles of feet, and genitals. In contrast to eczema, psoriasis is more likely to be found on the outer side of the joint.
The disorder is a chronic recurring condition that varies in severity from minor localized patches to complete body coverage. Fingernails and toenails are frequently affected (psoriatic nail dystrophy) and can be seen as an isolated sign. Psoriasis can also cause inflammation of the joints, which is known as psoriatic arthritis. Between 10 and 30% of all people with psoriasis also have psoriatic arthritis.
The cause of psoriasis is not fully understood, but is believed to have a genetic component and local psoriatic changes can be triggered by an injury to the skin known as the Koebner’s phenomenon. Various environmental factors have been suggested that aggravate psoriasis including oxidative stress, stress and withdrawal of systemic corticosteroids, as well as other environmental factors, but few have shown statistical significance. There are many treatments available, but because of its chronic recurrent nature, psoriasis is a challenge to treat. Withdrawal of corticosteroids (topical steroid cream) can aggravate the condition due to the ‘rebound effect’ of corticosteroids.
Each hair consists of a shaft that is extending above the skin and a root embedded in the skin. The hair root is enclosed in a follicle whose lower end expands to form a bulb (Fig. 7.3).
The base of the bulb contains blood vessels, nerve endings and melanocytes. Hair is formed by the cells at the hair follicles, which are tube-like pockets of epidermal cells that extend into the dermis. Individual hair are actually large columns of dead cells that are filled with keratin. Hair consists of three layers, an outer cuticle made of flattened horny cells, a cortex of spindle-shaped pigmented cells and the medulla of cells that lose their nuclei and push upwards away from the papilla.
Arrector pilorum are bundles of smooth muscles that are inserted into the wall of individual hair follicles and are innervated by sympathetic nerve fibers. Stimulation of sympathetic nerves will contract arrector pili and make the hair to stand on end.
Rapid cell growth at the base of the hair follicle in the hair root causes hair to grow longer. Hair get its color from melanin. Hair follicles are in close contact with sebaceous glands. The oily secretions of these glands help to maintain the condition of each individual hair. Hair protects and insulates the body. Most individual hairs grow for several years and then fall out.
Nails are hard plates of modified horny cells that form a protective covering on the dorsal surface of the tips of fingers and toes, which have rich capillary bed (Figs 7.4A and B). Nails rest on a bed of tissue filled with blood vessels, giving the nails a pinkish color.
Nail body is firmly attached to nail bed composed of modified epidermal cells. Nail root is embedded in a fold of skin called nail groove, which is flanked by the nail wall. Nails grow from an area of rapidly dividing cells known as the nail root. During cell division, the cells fill with keratin and produce a tough, strong plate-like nail. Nails grow at a rate of 0.5–1.2 mm per day, with fingernails growing faster than toenails.
The adult human body consists of approximately 206 bones, which are organized into an internal framework called skeleton. Because the human skeleton is an internal structure, biologists refer it as an endoskeleton. The variation in size and shape among the bones that make up the skeleton reflects their different roles in the body.
In order to retain their shape and form, living things need some type of support.
In single-celled organisms, this support is provided by the cell membrane.
In multicellular animals, the support is provided by one of the two forms of a skeleton.
There are two types of animal skeletons:
Exoskeleton—an outside skeleton, found in arthropods (spiders, crustaceans, insects and crabs).
Endoskeleton—an inside skeleton, found in vertebrates.
The skeleton of humans is composed of a special connective tissue (tissue that joins other tissues together) called bone.
The human skeletal system consists of 206 bones, the other associated tissues and other structures that make up the joints of the skeleton.
The types of tissue present are bone tissue, cartilage and fibrous connective tissue, which form the ligaments that connect bone to bone.
Functions of the Skeletal System
The bones that make up the skeletal system serve four important functions:
Provides a framework that supports the body. The muscles that are attached to the bones move the skeleton.
Protects some internal organs from mechanical injury. For example, the rib cage protects the heart and lungs or skull around the brain.
Contains and protects the red bone marrow, which is hematopoietic (blood forming) tissue. Some white blood cells (leukocytes) are also produced in bones.
Provides a storage site of inorganic salts, such as calcium. Calcium may be removed from the bone to maintain a normal blood calcium level, which is essential for blood clotting and proper functioning of the muscles, and nerves.
Bones also provide a system of levers (rigid rods that can be moved about a fixed point) on which a group of specialized tissues (muscles) act to produce motion.
STRUCTURE OF BONES
Bones are a solid network of living cells (osteocytes), living tissue and fibers (collagen) that are supported by a matrix (deposits) of calcium salts (Fig. 8.1).
The calcium salts give strength to bones to perform their protective functions.
The function of osteocytes is to regulate the amount of calcium that is deposited in or removed from the bone matrix.
A tough membrane called periosteum surrounds each bone. Periosteum is a fibrous connective tissue membrane, whose collagen fibers merge with those of the tendons and ligaments that are attached to the bone.
The periosteum contains a network of blood vessels, which supply oxygen, nerves and nutrients to the bone.
The joined surfaces of bones are covered with articular cartilage, which provides a smooth surface for movement.
Beneath the periosteum, is a thick layer of compact bone (one of two types of bone tissue).
Compact bone is dense and similar in texture to ivory; it is far from being solid. A thick layer of compact bone called diaphysis enables the shaft of long bones to endure the large amount of stress; it receives upon impact with a solid object.
Compact bone is composed of cylinders or tubes of mineral crystals and protein fibers called lamellae (Fig. 8.2).
In the center of each cylinder, is a narrow channel called Haversian canals that contain blood vessels and nerves.
Blood vessels run through interconnected Haversian canals, creating a network that carries nourishment to the living bone tissue.
The second type of bone tissue is the spongy bone, the inside layer of compact bone.
Spongy bone is not soft and spongy, but actually quite strong (Fig. 8.3). Near the ends of bones (epiphysis) where force is applied, spongy bone is organized into structures that resemble the supporting girders of a bridge.
The structure of spongy bone helps add strength to bone without adding mass. It is arranged along points of pressure or stress, making bones both light and strong.
Embedded in compact and spongy bone are cells known as osteocytes that can either deposit the calcium salts in bone or absorb them again.
Osteocytes are responsible for bone growth and changes in the shape of bones.
The cavities of bone contain a soft tissue called bone marrow.
There are two types of bone marrow found in most bones:
Yellow bone marrow is found in most bones, but primarily fills, the shafts of long bones and is made up of blood vessels, nerve cells, but consists mostly of fat cells (adipose tissue). It serves as an energy reserve. It can also be converted to red bone marrow and produce blood cells when severe blood loss occurs.
Red bone marrow is found in spongy bone, the ends of long bones, ribs, vertebrae, the sternum, and the pelvis. It produces red blood cells (RBCs) and special white blood cells (WBCs) called lymphocytes, and other elements of blood (platelets).
CLASSIFICATION OF BONES
Bones can be classified as one of four types based on their shape (Fig. 8.4):
Long bones are the bones of the arms, legs, hands and feet (but not the wrist or ankles). The shaft of the long bones is the diaphysis and the ends are called epiphysis. The diaphysis is made up of compact bone and is hollow that forms a canal within the shaft. This canal contains yellow bone marrow, which is mostly adipose tissue. The epiphyses are made of spongy bone covered by a thin layer of compact bone.
Short bones are the bones of the wrist and ankles.
Flat bones are the ribs, shoulder blades, hip bones and cranial bones.
Irregular bones are the vertebrae and facial bones.
Short, flat and irregular bones are made of spongy bone covered with a thin layer of compact bone. Within the spongy bone, red bone marrow is found.
DEVELOPMENT OF BONES
Bone growth begins long before birth (Fig. 8.5). The basic shape of a long bone, such as an arm bone is first formed as cartilage.
Cartilage is a tough, but flexible connective tissue. Unlike bone, it does not contain blood vessels.
Cartilage cells must rely on the diffusion of nutrients from tiny blood vessels (capillaries) in surrounding tissue.
The cells that make up cartilage are scattered in a network of fibers, composed of an elastic protein called collagen.
Cartilage is dense and fibrous. It can support weight, but is still extremely flexible.
Many bones in a newborn baby are composed almost entirely of cartilage.
Later, the cartilage cells are replaced by cells that form the bones. The cartilage is replaced during ossification or the process of bone formation.
Ossification begins to take place up to 7 months before birth, as mineral (calcium and phosphorus) deposits are laid down near the center (center of ossification) in each bone.
Bone tissue forms as osteocytes secrete mineral deposits that replace the cartilage or a bone matrix gradually replaces the original cartilage.
The long bones develop and grow throughout childhood at centers of ossification in their epiphysis (ends).
Growth occurs in the epiphyseal disk or plate (growth plates) at the junction of the diaphysis with each epiphysis (at each end of the bone).
An epiphyseal disk is still cartilage and the bone grows in length, as more cartilage is produced on the epiphysis side.
On the diaphysial side, the osteoblasts (cells that produce bone matrix, a blast cell is a ‘producing’ cell and ‘osteo’ means bone) replace the cartilage.
Between the ages of 16 and 25 years, all the cartilage of the epiphyseal disk are replaced by bone. This is called closure of the epiphyseal disk and the bone lengthening process stops.
In adults, cartilage is found in those parts of the body where flexibility is needed.
Such places include the tip of the nose, the external ear, the voice box (larynx) and the ends of bones where joints are formed. Cartilage is also found where the ribs are attached to the breastbone (sternum), thus allowing the rib cage to move during breathing.
Cartilage provides an important combination of strength and flexibility.
All the bones in the body make up the skeleton (Fig. 8.6). There are 206 total bones in the human body. The skeleton supports the body weight, enables it to move and protects many of its internal organs. The human skeleton has two divisions:
The axial skeleton consists of the skull, vertebral column and the rib cage.
The appendicular skeleton consists of the bones of the arms and legs, shoulder, and the pelvic girdle.
Axial Skeleton Bones
The skull consists of eight cranial bones and 13 facial bones.
The ears consist of six bones, and a floating bone in the throat, the hyoid.
The vertebral column (spinal column or backbone) consists of seven cervical (neck) vertebrae, 12 thoracic and five lumbar vertebrae, five vertebrae fuse into one sacrum and four to five small vertebrae fuse into one coccyx (the tail bone).
The rib cage (thoracic cage) consists of the 12 pairs of ribs, a total of 24 bones and the sternum or breastbone.
Appendicular Skeleton Bones
The pectoral girdle consists of four bones and upper limb consists of 60 bones.
The hands and wrist consists of 54 separate bones.
The pelvic girdle consists of two bones and the lower limb consists of 60 bones.
The feet and ankles consist of 52 separate bones.
BONE FRACTURES AND THEIR REPAIR
A fracture means that a bone has been cracked or broken. A bone fracture may be a simple crack or the bone may actually break into two or more pieces. There are different types of fracture classified as to the extent of damage:
Simple (closed): The broken parts are still in normal anatomical position; surrounding tissue damage is minimal (skin is not pierced).
Compound (open): The broken end of a bone has been moved and it pierces the skin; there may be extensive damage to surrounding blood vessels, nerves and muscles.
Greenstick: The bone splits longitudinally (breaks along the long axis of the bone). The bones of children contain more collagen than do adult’s bone and tend to splinter rather than break completely.
Comminuted: Two or more intersecting breaks create several bone fragments.
Impacted: The broken ends of a bone are forced into one another; many bone fragments may be created.
Spontaneous (pathologic): A bone breaks without apparent trauma; may accompany bone disorders such as osteoporosis.
Even simple fracture involves significant bone damage that must be repaired, if the bone is to resume normal function. Fragments of dead or damage bone must first be removed. This is accomplished by osteoclast (a bone-destroying cell), which dissolve and reabsorb the calcium salts of bone matrix (imagine a building that has just collapsed; the ruble must be removed before reconstruction can take place. This is what the osteoclasts do). Then new bone must be produced. The inner layer of the periosteum contains osteoblasts that are activated when bone is damaged. The osteoblasts produce bone matrix to knit the broken ends of bone together. Holding the broken ends close to each other and keeping them completely still speeds the healing of bones. That is why a bone fracture is often treated by encasing the fractured limb in a cast. Since most bone has a good blood supply, the repair process is usually relatively rapid and a simple fracture often heals within 6 weeks. Other factors that influence the repair include age of the person, general state of health and nutrition (a diet with sufficient calcium, phosphorus, vitamin D and protein. If any of these nutrient is lacking, bone repair will be a slower process).
Osteoporosis is a condition wherein the bones are brittle. As bones grow longer, they also grow thicker and denser. In young adults, the density of bone usually remains constant as bone tissue is broken down and replaced at a steady rate. During middle age, bone replacement gradually becomes less efficient and bones may become less dense. The loss of bone density is called osteoporosis, and can cause bones to become light, brittle and easily broken. Although both men and women lose bone as the age advances, women are at a greater risk for osteoporosis for two reasons:
Women’s bones are usually smaller and lighter than men’s bones.
The production of female sex hormones decline rapidly during menopause (sex hormones help to maintain bone density); this decline in hormone production increases the rate of bone loss.
Bone density can only be increased during teens and twenties. Therefore regular exercise and a healthy diet during this age will make bones healthier, and will also pay off later. The stronger the bones are at this age, the less likely an individual is to get affected by osteoporosis later.
Vertebral column is the central part of the skeleton, which supports the head and encloses the spinal cord (Figs 8.7A and B). Its construction provides a great strength with a moderate degree of mobility. These features depend on the spine having a number of separate bones, held together by ligaments, and tough intervertebral disks made of fibrocartilage, which act as shock absorbers. The bones of the spine give origin for many muscles.
There are a total of 24 individual vertebrae in the spinal column plus the fused vertebrae that make up the coccyx and sacrum. The vertebrae are divided into regions and there are a specific number in each region. The cervical region is the most superior and has seven vertebrae. Next are the thoracic region with 12 and finally the lumbar region with five.
Sacrum is formed by fusion of five sacral vertebrae and the coccyx by fusion of four coccygeal vertebrae.
The bones of the vertebral column become increasingly larger as the column descends and reaches a maximum width at the upper border of the sacrum, and then gets reduced in size as it tapers off into the coccyx.
When the spinal column is viewed from the side, four curves are seen:
In the cervical region, forms a convex forward curve.
In the thoracic region, it has a convex backward curve. An excessive curvature is known as kyphosis or hunchback.
In the lumbar region, it forms a convex forward curve. When it is excessively convex, it is termed lordosis. The normal lordosis of the lumbar region in women acts as a support for the contracting uterus.
The sacrum and coccyx form a marked forward concavity.
The point where the last lumbar vertebra joins the sacrum, a pronounced lumbosacral angle is formed.
When the spinal column forms lateral curvatures, it is abnormal and referred to as scoliosis.
The general plan of all the vertebral bones is same with certain variations in different regions of the spinal column. A separate description is required for atlas, axis, sacrum and coccyx.
Typical Vertebrae Structure
A typical vertebra consists (Fig. 8.8) of:
A spinous process on the posterior side of the vertebrae that projects forward and backwards.
The vertebral neural arch formed by two laminae that are more posterior than the pedicle and two pedicles that are more anterior than the lamina.
Two transverse processes on either side.
A body, which is the anterior part of the vertebrae.
Vertebral foramen is the opening through which the spinal cord passes.
Superior articular processes that articulate with the vertebrae above it and face toward the spinous process.
Inferior articular processes that articulate with the vertebrae below it and face away from the spinous process.
Types of Vertebrae
Cervical vertebrae have smaller bodies and shorter, bifid (double ended) spinous processes that stick straight back (Fig. 8.9). The real telltale sign of cervical vertebrae is the presence of transverse foramen in the transverse process for the passage of the vertebral artery, which the thoracic and lumbar vertebrae do not have.
The first two vertebrae (C1 and C2) are named, the atlas and the axis respectively.
The atlas along with axis is adapted to carry the weight of the head and to facilitate its movements (Fig. 8.10). The atlas has no body, instead it consists of a ring of bone that enclosing a very large vertebral canal. On the anterior aspect of which is a small facet for articulation with the dense odontoid process of the axis. The atlas pivots around the dense, when the head is rotated. The upper surface of the atlas bears on each side, a superior articular facet on a thick lateral mass for articulation with the occipital condyles of the skull. The atlanto-occipital joints are so formed facilitates nodding and lateral flexion. The articulation with the skull allows the head to move in a nodding direction (the ‘yes’ movement), while the articulation with the dens of the axis allows the head to move from side to side (the ‘no’ movement). Both atlas and axis have no spinous processes.
The axis is the second cervical vertebra (Fig. 8.11). It is characterized by an odontoid process (tooth-like projection) in the anterior side of the body, which project upwards. This projection actually represents and occupies the position of the missing body of the atlas.
On the anterior surface is a small facet, which articulates with the anterior arch of the atlas that permits the rotation of the head. The spinous process of the axis is large and strong that can take the pull of muscles that extend, retract and rotate the head.
Dislocation and fracture of cervical vertebrae may occur as a result of fall on the head with acute flexion of the neck or as a result of a forward jerk in motorcar accidents. Since their intervertebral facets are relatively horizontal, dislocation of cervical vertebrae can occur without fracture. Whereas, the fractures of thoracic and lumbar vertebrae occurs when they are dislocated forward, since their intervertebral facets are relatively vertical.
Thoracic vertebrae have a body, which is a kind of heart shaped and the spinous process is long, and points backwards and downwards (Figs 8.12A and B). The fourth thoracic vertebra is heart shaped. The bodies of the fifth to eighth thoracic vertebrae are slightly flattened on their left side, owing to the pressure of the descending aorta. An aortic aneurysm in this region will erode the bodies of these four vertebrae. On each side of the body, there are two costal facets; one each for the heads of the rib and one each on the tips of transverse process for the articulation with the tubercles of the ribs.
Lumbar vertebrae are much larger with a bean-shaped body. The spinous process is short and points straight back (Figs 8.13A and B). The transverse process of the fifth lumbar vertebra is massive.
The sacrum is made up of five vertebrae, which fuse in adulthood (Fig. 8.14). It has a wide base, articulating above with the fifth lumbar vertebra to form the lumbosacral angle and a narrow blunted apex inferiorly that articulates with the coccyx. The sides of the sacrum join with the ilium of os coxae to form the sacroiliac joint. The dorsal surface of the coccyx is convex and the pelvic surface is concave, which helps to increase the capacity of true pelvis. Between the body and the lateral parts of the sacrum, are the four anterior sacral foramina for the passage of nerves. The upper margin of the body project forwards and is called promontory of the sacrum. The posterior convex surface has the sacral crest, which is surmounted by three of the four rudimentary spinous tubercles. The neural canal is continued into the sacrum, as the sacral canal and its lower end opens onto the surface of the bone at the sacral hiatus below the third or the fourth spinous tubercle. The sacral canal contains the cauda equina, the filum terminale and the fifth sacral nerve, which emerges at the sacral hiatus.
The female sacrum is typically wider and the ventral concavity is deeper. The pelvic surface faces more downwards in the female.
Coccyx is made of three to five vertebrae fused together. It is triangular in shape and its base articulates above with the sacrum, and tapers off inferiorly as apex. The external anal sphincter originates from the apex of coccyx. Part of the gluteus maximus muscle originates from the dorsal surface of the coccyx and the lower part of the sacrum.
Ligaments of the Vertebral Column
The following ligaments hold the vertebrae of the spinal cord together (Fig. 8.15):
The anterior and posterior longitudinal ligaments, which run the whole length of the spine, join the anterior and posterior aspects of the vertebral bodies.
Ligamentum flava made of elastic tissue, connect the laminae.
Supraspinous ligaments link the spinous processes.
Intervertebral disks made of fibrocartilage, join the bodies of vertebrae. Each disk consists of a gelatinous nucleus pulposus that is surrounded by annulus fibrosus. The rupture of annulus fibrosus posteriorly, as a result of trauma or degeneration will allow the protrusion of nucleus pulposus into the vertebral canal. This condition is known as prolapsed intervertebral disk. The common site of prolapse is fifth lumbar, or between fifth lumbar and first sacral vertebrae. It is one of the causes of sciatica.
The landmark for lumbar puncture is the intervertebral space between the fourth and fifth lumbar vertebra, which can be identified by a line drawn between the highest points of iliac crests passing across the spinal column.
Other Important Vertebral Information
In between each pair of vertebrae is the intervertebral disk made of fibrocartilage. It adds support and absorbs shock.
The opening formed in between two ‘stacked’ vertebrae is the intervertebral foramen. Nerves pass through these openings. The spinal cord passes through the vertebral foramen.
Thoracic vertebrae form the bony framework of thorax posteriorly, anteriorly by the sternum and costal cartilage, and the ribs form the reminder (Fig. 8.16). It is separated below from the abdominal cavity by the diaphragm and communicates above with the root of the neck through thoracic inlet.
The anatomic landmarks of the anterior chest wall, such as various reference lines and angles are commonly used (Fig. 8.17) to identify respiratory findings as follows:
The angle of Louis (also called sternal angle) is a useful place to start counting ribs, which helps to localize a respiratory finding horizontally. If the sternal notch is identified, then move the fingers down the manubrium a few centimeters until a distinct bony ridge is felt. This is the sternal angle. The second rib is continuous with the sternal angle; slide your finger down to localize the second intercostal space. The angle of Louis also marks the site of bifurcation of the trachea into the right and left main bronchi, and corresponds with the upper border of atria of the heart.
Reference lines help pinpoint findings vertically. For example, the major division (‘oblique fissure’) between lobes of lung in the anterior chest crosses the fifth rib in midaxillary line and terminates at the sixth rib in the midclavicular line.
Sternum is a dagger-shaped flat bone, which is slightly convex anteriorly and concave posteriorly. It is highly vascular trabecular bone covered by a layer of compact bone. The spongy interior contains red marrow that can be aspirated through a wide-bore needle for diagnostic evaluation. On each side of the sternum, there are seven indentations for the attachment of costal cartilage. The manubrium, body and xiphoid process are parts of the sternum (superior to inferior respectively). They are fused in the adult skeleton. The xiphoid process is an important landmark for cardiopulmonary resuscitation (CPR).
The manubrium articulates on either side with the clavicle at the sternoclavicular joint, and with the first and second costal cartilage. The adjoining body of the sternum articulates with the part of the second costal cartilage and the cartilage of third, fourth, fifth, and sixth ribs, while the cartilage of seventh rib articulates at the junction of body and xiphoid process.
The xiphoid process is the lower part of the sternum, sometimes remain cartilaginous, but is usually ossified. The fibers of linea alba and rectus abdominis muscles are attached to the xiphoid process. Part of the diaphragm is also attached to its posterior part.
To gain access to the heart during surgery, the sternum is cut mid vertically.
The ribs are arch-shaped bones, which form the greater part of the thorax. They articulate with the spine posteriorly and are directed forward, and downward to articulate with sternum in the front. There are usually 12 pair of ribs that are classified into two groups; the true ribs and false ribs (floating ribs).
The upper seven pairs are true ribs, which attach directly to the sternum by the costal cartilages.
The lower five pairs are false ribs. The first three pairs attach to the sternum indirectly and the last two pairs (the floating ribs) have no attachment to the sternum at all.
The spaces in between the ribs are called ‘intercostal spaces’ and are landmarks used in physical examinations.
The first two and the last three pairs of ribs have special features, but the remaining are similar.
A typical rib has a head, a neck and the remaining portion is called shaft. The head has two facets for articulations with the corresponding vertebra posteriorly and the vertebra above it. The neck lies in front of the transverse process of the corresponding vertebra. It has a facet for articulation with the transverse process and a tubercle at the junction of neck, and shaft of the rib.
The shaft of the rib is long, flat, curved and twisted on itself. The shaft has superior and inferior borders and a smooth internal surface grooved interiorly (costal groove), which is occupied by intercostal vein, artery and nerve. The superior and inferior borders provide attachment for intercostal muscles that pass to the ribs immediately above and below it. The smooth interior surface is lined by the parietal pleura that are firmly attached to the periosteum of the ribs.
The first rib is broad, short and flat. It is curved more than any other rib. Its surface faces upwards and downwards. The inner border of the upper surface has a scalene tubercle to which scalenus anterior muscle is attached. The subclavian vein passes in the groove in front of the tubercle and the subclavian artery passes along with the lower trunk of the brachial plexus in the groove, behind the tubercle.
The second rib is twice as long as the first rib and is much less curved.
In some individuals, the cervical rib is found that articulates with the transverse process of the seventh cervical process. Its anterior end may be free or articulate with the first thoracic rib. If it exerts pressure on the overlying lower trunk of the brachial plexus, it causes paresthesia in the ulnar aspect of the forearm and wasting oof small muscles of the hand. Occasionally, it exerts pressure on the overlying subclavian artery that cause ischemia or gangrene in the upper limb.
The floating ribs (11th and 12th) are short and thin, and have no tubercle. The head has only one facet.
Fractured ribs can sometime pierce through the lungs causing leakage of air and blood into the pleural cavity (hemopneumothorax). Crushing injuries of the thorax can loosen a portion of the thoracic cage (stove-in chest), when the thorax moves paradoxically. With inspiration, the chest moves in and with expiration, the chest moves out. These situations are emergencies when drains need to be inserted into the chest and connected to water seal, and also positive pressure ventilation is to be given through endotracheal or tracheostomy tube.
Costal cartilages are flattened bars of hyaline cartilage that connect the upper seven ribs to the sternum and the eighth, ninth and 10th rib to the cartilage immediately above them. The cartilages of 11th and 12th ribs are tapered and are continuous with the muscles of the abdominal wall. The costal cartilage provides mobility and flexibility to the thoracic cage. In old age they get ossified, which makes them difficult to provide cardiac massage.
Intercostal space is the space in between ribs (Fig. 8.18). It contains three muscles such as external, internal and innermost intercostal muscles, and a neurovascular bundle (intercostal vein, artery and nerve).
Disease of the thoracic spine, such as tuberculosis can cause irritation of the nerve, which causes referred pain in the front of chest where they terminate and the pus from the thoracic vertebrae tend to track along the neurovascular bundle, and erupt as a cold abscess.
The intercostal space is made use for accessing thoracic cage for surgeries by retracting the ribs.
SHOULDER GIRDLE AND BONES OF UPPER LIMB
The humerus of the upper limb is attached to the bones of the trunk by means of shoulder girdle (joint), which consists of the clavicle and scapula (Fig. 8.19). The bones of the upper limb are as follows: humerus, ulna and radius, eight carpal bones, five metacarpals and 14 phalanges.
The clavicle (collar bone) is a long curved bone that forms the anterior part of the shoulder joint. It has a shaft and two ends (Fig. 8.20). The medial end articulates with the sternum and is called sternal end. The lateral end articulates with acromion process of the scapula and is called acromion end.
Clavicle is the most commonly fractured bone caused by violence or fall on the shoulder. The usual site of clavicular fracture is at the middle or the medial third. The patient usually presents with supporting the sagging limb with the opposite arm.
Scapula is a triangular flat bone with anterior (costal surface) and posterior surfaces (dorsal surface), three angles, and three borders (Figs 8.21A to C). It lies on the back of thoracic cage and superficial to the ribs. Scapula forms the posterior aspect of shoulder girdle.
The costal surface (anterior surface) of scapula is called subscapular fossa and is facing the ribs. The dorsal or posterior surface is divided into supraspinous and infraspinous fossa by a prominent bony ridge that passes across it, to end at the lateral superior end as acromion process, which overhangs the shoulder joint.
Humerus is the long bone of the upper limb and is the longest bone. It has a shaft and two ends (Fig. 8.22). The upper end of the humerus has a head, which is one-third sphere. The head articulates with glenoid cavity of the scapula that forms the shoulder joint. The constricted part immediately below the head is called anatomical neck. On the outer side of the upper end, there is a rough prominence just below the anatomical neck, which is called greater tuberosity. Just behind this prominence, there is a smaller prominence called lesser tuberosity. In between these two tuberosities is the bicipital groove (intertubercular sulcus) in which the tendon of the long head of biceps muscle lie. Below the tuberosities, the bone becomes narrower and is liable for fractures; hence this point is called surgical neck.
The shaft is rounded in the upper part, but becomes flattened sideways in the lower part. Just above the midpoint of length of the shaft, on the lateral aspect is a rough tuberosity, where the deltoid muscle is inserted and hence called deltoid tuberosity. On the back of the shaft, a groove runs obliquely from the medial to the lateral aspect that gives passage to the radial nerve and is called radial groove (spiral groove).
The lower end of the humerus is flat. At its lowest end are the articulating surface for ulna and radius. The medial side of the articulating surface is pulley shape for articulation with ulna and is called trochlea. The lateral side of the articulating surface articulates with radius and is called capitulum.
On either side of the articulating surface at the lower end, are two epicondyles. The one on the lateral side is called lateral epicondyle and the one on the medial side is called medial epicondyle.
Fracture of the Humerus
Fracture of the humerus is common. When the shaft is fractured below the deltoid insertion, the radial nerve may be injured. The fracture at the surgical neck is commonly due to impacted injuries, when the axillary nerve may get involved. The fracture of lower end of the shaft involving medial epicondyle may injure ulnar nerve. In children, supracondylar fracture of the humerus is common.
Ulna is long bone, which is situated on the medial side in the forearm (Fig. 8.23). It is slightly longer than the radius and its head is at the lower end.
The upper end of the ulna is strong and thick that enters into the formation of elbow joint. When the arm is straight, the olecranon process that project upwards and backwards at the upper end of the ulna, fits into the olecranon fossa of the humerus. When the arm is bent at elbow, the coronoid process at the upper end of ulna, which is smaller, projects in front and fits into the coronoid fossa of the elbow.
The shaft of the ulna tapers toward its lower end. The anterior surface provides attachment for flexor muscles of the arm and fingers, whereas the posterior surface provides attachment for extensor muscles. The shaft provides attachment for pronator and supinator muscles that act on the forearm and wrist.
The lower end of ulna is small from which two small eminences arise. A smaller rounded eminence on the lateral side is called head, which articulates with the medial side of the lower extremity of the radius to form the radioulnar joint. The other eminence is pointed and is called styloid process. The styloid process projects downward from the back of the lower end.
The long bone that lies laterally in the forearm is called radius. The upper end of the radius is small and is button shaped with a shallow upper surface that articulates with the capitulum of the humerus. The medial side of the head articulates with the radial notch of the ulna. Just below the head is the neck. On the medial side of the lower part of the neck, is the radial tuberosity to which the tendon of biceps muscle is attached.
The shaft of the radius is narrower and more rounded in the upper part. Toward the lower end, it is wider and the shaft is curved outwards. The anterior surface of the shaft provides attachment for deep flexors and pronators, and the posterior aspect provides attachment for deep extensors and supinators. The interosseous ligament in between the ulna and radius separates the muscles on the front from the muscles on the back of the forearm.
The lower end of the radius is square in shape and participates in the formation of two joints. The inferior surface of the lower end of the radius articulates with the scaphoid and lunate bones to form the wrist joint, whereas the inferior surface toward the medial side at the lower end articulates with the ulna to form the inferior radioulnar joint. The lateral aspects of the lower end of the radius extend downwards as styloid process of the radius.
A transverse break of the lower end of the radius, about an inch above the wrist is called Colle’s fracture. This fracture is quite common among the elderly, when they fall onto the outstretched hand. Such an injury can also tear the ligaments and the styloid process of the ulna may be fractured.
There are three groups of bones that go into the formation of wrist and hand (Fig. 8.24):
The first group of eight bones are the short bones called carpus, some of these (scaphoid and lunate) go into the formation of wrist.
The second group of five long bones are the metacarpals that form the skeleton of the palm of hand.
The third group of 14 long bones are the phalanges or bones of the fingers.
The eight carpal bones are arranged in two rows of four bones each. The proximal rows of four bones from lateral to medial are scaphoid (boat shaped), lunate (semilunar), triquetral and pisiform. The distal row of four carpal bones is trapezium, trapezoid, capitate and hamate.
The scaphoid and lunate articulate above with the lower end of radius, to form the wrist joint and below, they articulate with some of the carpal bones of the second row.
Each of the five metacarpal bones has a shaft and two ends. The end that articulates with the carpal bone is called carpal end, which forms carpometacarpal joint. The distal end that articulates with the phalanges is called head. The shaft of the phalanges is prism shaped with their broadest surface directed posteriorly. The interosseous muscles are attached to the sides of the shaft.
The 14 phalanges are also long bones. Each finger has three phalanges with the exception of thumb that has two phalanges. The shaft of phalanges taper toward the distal end.
Most often, the scaphoid bone gets fractured when falling heavily on the hand. The fractures and dislocation of bones of the hand are the result of direct violence.
On the palmar surface of carpal bones, a flexor retinaculum is present that is called carpal tunnel. Beneath which the tendons to the hand and the median nerve passes. Any condition that causes narrowing of this tunnel will create pressure on the median nerve resulting in numbness, tingling and weakness of the muscles supplied by it.
The pelvic girdle connects the trunk to the lower extremities. It is formed by a part of the axial skeleton; the sacrum and coccyx are wedged in between the two innominate bones. The two innominate bones articulate with each other in front with the symphysis pubis (Fig. 8.25).
The pelvis is divided into true pelvis and false pelvis. The true pelvis is the space that lies below the brim of the pelvic girdle and the space that lies above the brim of pelvic bones is the false pelvis. The inlet of the true pelvis is the brim formed by the promontory of the sacrum, the iliopectineal line on either side and the crest of pubic bone. The boundaries of outlet are formed by the coccyx and the ischial tuberosities.
Joints of Pelvis
The sacroiliac joint is formed by the articulation of the articular surface of the ilium and the sides of the sacrum. The ligaments that unite these two bones are strong and only limited movement is possible at this joint. The two pubic bones are connected with each other in the front by a pad of cartilage called symphysis pubis.
BONES OF THE LOWER LIMB
The acetabulum is a cup shaped, deep cavity formed by the union of three bones; the front part is formed by the pubis, the upper part by ilium, and the back part by the ischium. The head of the femur articulates with the acetabulum to form the hip joint (Fig. 8.26). The articulating surface of acetabulum is horseshoe shaped and is interrupted at its lowest point by the acetabular notch, which permits the passage of vessels into the joint. A roughened non-articulating surface at the bottom of acetabulum is the acetabular fossa, which is filled with pad of fat. The lower part of the fossa gives attachment to the ligamentum teres of femoral head.
Femur is a long bone and the longest bone in the body. The upper end has a head that articulates with acetabulum to form the hip joint and the lower end articulates with the tibia to form the knee joint (Fig. 8.27).
The shaft or the body of the femur between these two ends runs obliquely and medially from the hip up to the knee.
The upper end of the femur forms two third of a sphere called head. At the summit, it is a roughened ovoid depression that provides attachment to the ligamentum teres. Below the head is a long-flattened neck that joins the shaft. At the junction of neck and shaft, there are two prominences; the one that lies above and on the lateral side is the greater trochanter, and the one that lies below, behind and on the medial side is the lesser trochanter. The intertrochanteric line is an elevated marking present between the two trochanters in front of the neck. The intertrochanteric crest unites the two trochanters at the back of the neck. At the midpoint of intertrochanteric crest is the quadrate tubercle.
The shaft of the femur curves forward and is smooth, and rounded in the front. On the posterior side of the shaft, is a well-defined ridge called linea aspera to which many muscles including adductors of thigh are attached.
The lower end is wide and has two prominent condyles, an intercondylar notch, a popliteal surface, and a patellar surface.
The two condyles are involved in the formation of knee joint. On the posterior aspect, the two condyles are separated by a condylar notch, which gives attachment to cruciate ligaments of the knee joint. On the anterior aspect, the two condyles are separated by patellar surface that extends over the anterior aspect of both condyles on which the patella rests. The tibial surface of the femoral condyles lies below and rests on the upper articulating surface of the condyles of the tibia. This surface is divided into two areas by the deep intercondylar notch. The popliteal surface of the bone lies above the condyles at the back. It forms the floor of the popliteal space on which the popliteal vessels lie.
The femur articulates with innominate bone, patella and the tibia, but it does not articulate with fibula. The fracture of the neck of the femur is usually the result of trips and falls, which is more common among the elderly. The fracture of the shaft may cause displacement and overriding of the fragments due to spasm of thigh muscles.
Patella is a sesamoid bone, developed within the tendon of the quadriceps femoris muscle. The apex of patella is pointing downwards. The anterior surface of the bone is rough and the posterior surface smooth, which articulates with the patellar surface of the lower end of the femur. It lies in front, but does not enter into the knee joint.
Vigorous contraction of thigh muscles can cause transverse fracture of the patella. Falling heavily on the knee or direct blow on the kneecap can cause stellate fracture.
The main skeleton of the leg is tibia and it lies medial to the fibula (Fig. 8.28). It is a long bone with a shaft and two ends. The upper end is the most expanded portion of the bone, and has the medial and lateral condyles. The upper surface of the condyle is flat and smooth that forms the articulating surface for the femur. The presence of semilunar cartilage on the articulating surface deepens the articulating surface for the reception of femoral condyles.
The inferior part of the lateral condyle on the posterior aspect forms a facet for articulation with the head of the fibula at the superior tibiofibular joint. On the posterior aspect, the popliteal notch separates the two condyles. Just below the condyles on the front, lies the tibial tuberosity, whose upper part gives attachment for the patellar tendon to which the quadriceps extensor muscle is inserted. The lower part of the tuberosity is subcutaneous that receives the weight of the trunk during kneeling.
On cross section, the shaft of tibia is triangular. The anterior border is subcutaneous in its middle part and is prominent, which forms the crest of the tibia. The medial surface of the shaft is subcutaneous in most of its extent; a useful area for taking bone grafts. Soleal ridge is found on the posterior aspect of the shaft, which runs downwards and medially.
The lower end of the tibia is slightly expanded and goes into the formation of ankle joint. The medial sides of the lower end extend downwards as the medial malleolus. The front of the tibia is smooth and the tendons passing to the foot glide over it.
The lateral surface of lower end articulates with the fibula at the tibiofibular joint. The tibia articulates with three bones—the femur, fibula and talus.
The fibula is a long bone with a shaft and two ends. It is the lateral bone of the leg. The upper end is the head, which articulates with the back of the outer condyle of the tibia, but does not enter into the formation of the knee joint.
The shaft is slender and it lies deeply embedded in the muscles of the leg, and provides attachment to numerous muscles.
The lower ends of the fibula extend downwards laterally as lateral malleolus.
Violence can cause fracture of tibia and fibula separately or together. The commonest fracture of the fibula is Pott’s fracture, occurring above the ankle joint. The stress fracture is caused in the shaft of fibula.
BONES OF THE FOOT
Tarsal, metatarsal and phalangeal bones form the skeleton of the bone (Fig. 8.29).
There are seven tarsal bones, all are short bones made up of cancellous bone tissues covered with compact bone. These bones support the body weight when standing.
The largest foot bone is calcaneum. It lies at the back of the foot, forming the heel that transmits the body weight to the ground posteriorly. The large muscles of the calf are attached to calcaneum through tendon of Achilles. Calcaneum articulates with the talus above and cuboid in the front. The central and highest point of the foot is formed by talus, which supports the tibia and articulates with the malleoli at either side. A boat-shaped bone called navicular lies on the medial aspect of the foot between the talus at the back and the three cuneiform bones in front. The cuneiform bones articulate with the three medial metatarsals in the front and the navicular, and cuboid bone posteriorly. Cuboid bone, which articulates with the calcaneum posteriorly, and the two lateral metatarsal bones in the front forms the lateral aspect of the foot.
Metatarsal and Phalangeal Bones
There are five metatarsal bones; all are long bones with a shaft and two ends.
The proximal ends of metatarsal articulate with tarsal bones and the distal ends articulate with proximal phalanges. The first metatarsal is thick and short, but the second metatarsal is the longest.
The phalanges of the foot are similar to those of the fingers, but are much shorter.
Arch of the Foot
The foot has four arches:
The medial arch (internal longitudinal arch) is formed from back to front; the posterior support of the arch is formed by talus, the summit of the arch is formed by the navicular bone and the anterior support of the arch is formed by the navicular, the three cuneiforms, and the heads of the three medial metatarsals.
The lateral arch (outer longitudinal arch) is formed by the calcaneum, the cuboid and the two lateral metatarsal bones (Fig. 8.30).
The transverse tarsal arch is formed by tarsal bones and is posterior to the metatarsal arch.
The transverse metatarsal arch is formed by heads of metatarsal bones. The first and the fifth metatarsal forms the pliers of the arch. When standing the arch is almost flat, but at rest it assumes an arch shape.
The bones of the arches of foot are held together by the ligaments and supported by the muscles. The shape of the arch is maintained by:
The close adaptation of bones
The ligaments of the foot are strong
The action of the muscles attached to the front and back of the tibia.
The fractures of the bones of the feet are more painful, because of weight-bearing function.
The deviation of the great toe, which lies obliquely across the second toe, is called hallux valgus.
Depression of the metatarsal heads that form the transverse arch can lead to painful involvement of digital nerve.
Flat foot may follow injuries to foot and ankle or as a result of disturbances of balance, which may be traumatic or postural as in deformity of the spine, pelvis or lower limbs.
BONES OF THE SKULL
The bony framework of head has two parts; the cranium made of eight bones and the facial skeleton made of 14 bones (Fig. 8.31).
The upper surface of cranium is known as the vault of the skull, which is smooth on its outer surface and has ridges, and depression on its inner surface to accommodate the brain and blood vessels. The lower part of the cranium is known as base of the skull, which has many holes for the passage of blood vessels and nerves.
The cranial bones are one each of occipital, frontal, sphenoid and ethmoid, and two each of parietal and temporal.
The occipital bone occupies the back and lower part of the cranium. It is pierced by the foramen magnum through which the medulla oblongata descends to join the spinal cord (Fig. 8.32). On either side of the foramen magnum are bony masses that form the occipital condyles, which articulate with the atlas (Fig. 8.33).
The roof and the sides of the skull are formed by the two parietal bones. Its outer surface is smooth, but deep furrows that lodge the cranial arteries, mark the inner surface. At about the middle of the bone, on the interior surface is a deep furrow formed by middle meningeal artery. The rupture of this artery causes pressure effects on the underlying soft brain; first on the same side and later on the opposite side as well.
The pressure effect is manifested as alteration in the pupil size, an important nursing observation during the care of patients with head injuries.
The forehead and the upper part of the orbital cavities are formed by the frontal bone. The inner half of supraorbital margin is marked by the supraorbital foramen through which the supraorbital nerves and vessels pass (Fig. 8.34). The inner surface of frontal bone has depressions formed by the convolutions of the brain.
The lower part of the sides of the skull is formed by two temporal bones that consist of number of parts (Fig. 8.35):
The squamous part project upwards to which temporalis muscle is attached. An upward and forward projection of this is the zygomatic process, which joins the zygomatic bone. Behind and below the root of this process, lies the external auditory meatus.
The mastoid part lies behind and continues downward as the mastoid process. The sternomastoid muscle is attached to its outer surface. The interior of mastoid process has spaces known as mastoid air cells; the largest of these that lies in the front is named as tympanic antrum. The tympanic antrum is lined by epithelium that is continuous with the middle ear. The infections of the middle ear can spread into tympanic antrum and cause suppuration.
The petrous part of the temporal bone is wedged in, at the base of the skull and contains the hearing apparatus.
The ethmoid bone is cubicle in shape. It is light, spongy, and is situated at the roof of the nose, wedged in between the orbits (Fig. 8.36). It has two lateral masses known as labyrinths composed of ethmoidal sinuses, which are closed except where they communicate with the nasal cavity. The ethmoid is made of perpendicular plates and cribriform plate. The perpendicular plate forms the upper part of the nasal septum. The cribriform plate fits into a notch on the frontal bone. The olfactory bulbs lie on top of the cribriform plate and the filaments of the olfactory nerves pass through the perforations into the upper part of the nose.
The sphenoid bone has the shape of a bat with spread out wings (Fig. 8.37). It has a body and two greater, and two lesser wings. The body has a depression known as sella turcica (pituitary fossa) in which the pituitary gland lies.
SUTURES OF THE CRANIUM
The bones of the skull are joined together by immovable joints known as sutures. The only exception is the mandible, which articulates with the temporal bone at the mandibular joint. The important sutures are as follows:
The coronal suture is found between the frontal and the two parietal bones.
The sagittal suture is between the two parietal bones that run before backwards along the top of the skull.
The lambdoid suture runs in between the occipital bone and the two parietal bones.
At birth, the skull bones are not completely ossified and the space between the skull bones is filled with membrane.
The membranous spaces between skull bones are known as fontanels. The largest fontanel, called anterior fontanel is found at the junction of the frontal and the two parietal bones, where the coronal sagittal sutures meet (Fig. 8.38). It is diamond shaped and measures about 4 cm from back to front. It forms a soft spot on the head of the infant through which the pulsating brain can be palpated. This fontanel usually closes at the age of 18 months.
Another fontanel that lies posteriorly at the junction of the two parietal and the occipital bones is known as posterior fontanel. It closes soon after birth.
SINUSES OF THE SKULL
Within the bones of the skull, several cavities or chambers filled with air are found, which are known as sinuses (Fig. 8.39). The important sinuses are the frontal, maxillary, ethmoid and sphenoid (paranasal sinuses) that communicate with the nose. These air sinuses make the bones light and provide resonance to the voice.
There are two frontal sinuses in the frontal bone, situated on either side of the root of the nose above the inner angle of the eye.
There are two maxillary sinuses on either side of the nose in the maxillary bones.
Mastoid antrum is the largest of the mastoid cells that lie in the mastoid process.
Infection spreading from the nose into the air sinuses that communicates with is collectively known as sinusitis. Infection of frontal sinus cause severe headache, rise in temperature, and malaise. The close proximity of the frontal sinuses with the frontal lobe of the brain can sometimes cause frontal lobe abscess. Fractures of the base of the skull with meningeal tear can allow cerebrospinal fluid (CSF) to leak into these sinuses.
Skeleton of face is made of 14 bones. All the bones of the face are joined by sutures, except the mandible (Fig. 8.40):
Nasal bones form the nose bridge.
Palatine bones form the roof of the mouth (palate) and the floor of the nose.
Lacrimal bones form the tunnel for the tear ducts and part of the orbit at the inner angle of the eye through which the secretions from the eye is carried to the nasal cavity.
Zygomatic bone is two in number, form the cheek bones. The processes from these bones join with the zygomatic processes of the temporal bones to form zygomatic arch.
Vomer bone forms the lower part of the bony partition in the nose.
Inferior turbinate bones are the larger pair of three projections (nasal conchae) from the lateral wall of the maxilla.
Two maxillae form the upper jaw and contain the upper teeth. The body of the maxillae has maxillary sinus that communicates with the nasal cavity through two small openings.
The mandible forms the lower jaw (Fig. 8.41). Apart from the ossicles of the ear, mandible is the only other movable bone in the skull. Mandible consists of a body, which is the central, horizontal, curved part that contains the teeth and forms the chin. The two upright portions on either side are known as rami, which join the body at the angle of the jaw.
The ramus terminates above in two processes, the process that is in front is the coronoid process and the one behind is condyle of the jaw or sometimes called head. The head articulates with the temporal bone to form temporomandibular joint. The mandible can be depressed, and elevated as in opening and closing the mouth. It can be protruded, retracted and moved slightly from side to side as in mastication.
The bony framework of the nose is composed of two cavities, situated in about the middle of the face. The two cavities are separated from each other by a thin partitions that extend upwards from the palate up to the frontal bone. These cavities communicate with the air sinuses.
Head injuries are quite common in road accidents and need immediate attention. Cerebral concussion may be transient and escape notice. If the patient has an absent swallowing and cough reflex following head injuries, the patient should immediately be put in prone with the head lowered. This prevents the regurgitation of stomach contents and bleeding from the mouth getting inhaled. If the patient is not breathing, keep the airway open and if required, start artificial respiration as first aid. Since scalp is highly vascular, scalp wounds bleed, which should be stopped by applying pressure and sutures. The nurse should be familiar with the knowledge of levels of consciousness, observation and care of the unconscious patients to report the deterioration or progress of the patient.
In cases of fracture of the base of the skull, blood and CSF may be discharged from the nose and ears. The other signs and symptoms of injury to brain include, increased intracranial pressure (edema and intracranial bleeding) that give rise to loss of consciousness, full-bounding pulse and hypertension, and cerebral irritation causing restlessness and disorientation. Cerebral edema can be treated by administration of dehydrating drugs, such as mannitol and urea.
JOINTS OF THE BONES
Joints are places where two bones come together, which allow the bones to move without damaging each other. Joints are responsible for keeping bones far enough apart so they do not rub against each other as they move. At the same time, joints hold the bones in place (Fig. 8.42).
Classification of Joints
Based on the amount of movement possible, the joints are classified as follows.
Synarthrosis is an immovable joint, often called fixed joints and allows no movement between bones.
These joints are interlocked and held together by connective tissue or they are fused together. The places where bones of the skull meet (suture) are the examples of immovable joints (Fig. 8.43).
Amphiarthrosis is a slightly movable joint (semi-movable joints) and permits a small amount of movement. These bones are farther apart from each other than immovable joint bones. The joints between the two bones of the lower leg (tibia and fibula) and the joints of the vertebrae are examples of slightly movable joints.
Diarthrosis is a freely movable joint. Most of the joints in the body are freely movable joints. In freely movable joint, the ends of the bones are covered with a layer of cartilage that provides a smooth surface at the joint.
The synovial joints are surrounded by a fibrous joint capsule that helps to hold the bones together and at the same time, allows for movement. The joint capsule consists of two layers:
One of the layers of the joint capsule may thicken to form strips of tough connective tissue called ligaments. Ligaments are attached to the membranes that surround bones and hold the bones together and in place.
The outer layer of the joint capsule produces synovial fluid, which forms a thin lubricating film over the surface of a joint and protects the ends of bones from friction. This lubricating film enables the cartilage found on the ends of the bones to slip, past each other more smoothly as the joint moves.
In some freely movable joints, small pockets of synovial fluid form bursae. A bursa reduces the friction between the bones of a joint and also acts as a tiny shock absorber.
If a joint is injured, too much fluid moves into the bursa, causing it to swell and become painful. This condition is called bursitis. A more serious disorder that affects the joints is arthritis or inflammation of the joint.
There are two forms of arthritis that affect joints.
Rheumatoid arthritis: This develops when the immune system begins to attack the body. The joints become inflamed, swollen, stiff and deformed.
Osteoarthritis: It is a degenerative joint disease (DJD) in which the cartilage covering the surface of bones, becomes thinner and rougher. As a result, bone surfaces rub against each other causing severe discomfort.
Types of Freely Movable Joints
Freely movable joints are grouped according to the shapes of surfaces of the adjacent bones. There are six types of freely movable joints (refer Fig. 8.43) as given below.
Ball and socket joint: It permits circular movement, the widest range of movement. The shoulder joint enables to move the arm up, down, forward and backward, as well as to rotate in a complete circle.
Hinged joint: It permits a back-and-forth motion. The knee enables the leg to flex and extend. The elbow allows to move the forearm forward and backward.
Pivot joint: It permits rotation of one bone around another. The elbow enables the hand to turn over. It also allows to turn head from side to side.
Gliding joint: It permits a sliding motion of one bone over another. It is found at the ends of the collarbones, between wrist bones and between anklebones.
Saddle joint: It permits movement in two planes. This type of joint is found at the base of the thumb.
Ellipsoid joint: It allows for a hinge type movement in two directions. The joints that connect fingers with the palm and toes with the soles of feet are examples.
Joints of Fingers
The bones in the palm of the hand are called metacarpal bones. One metacarpal connects to each finger and thumb.
The five fingers of the hand are made up of phalanges, small bone shafts that line up to form each finger and thumb (Fig. 8.44).
The main knuckle joint is formed by the connection of the phalanges to the metacarpals. This joint is called metacarpophalangeal joint (MCP). This joint acts like a hinge when fingers and thumb are bent, and straightened.
The three phalanges in each finger are separated by two joints, called interphalangeal (IP) joints. The one closest to the MCP (knuckle) is called proximal IP (PIP) joint. The joint near the end of the finger is called distal IP (DIP) joint. The thumb only has one IP joint between the two thumb bones. The IP joints of the digit also work like hinge joints when the hand is bent and straightended.
The finger and thumb joints are covered on the ends with articular cartilage. This white, shiny material has a rubbery consistency. The function of articular cartilage is to absorb shock and provide an extremely smooth surface to facilitate motion. There is articular cartilage essentially everywhere that two bony surfaces move against one another or articulate.
Sternoclavicular joint is a gliding joint formed between the sternal end of the clavicle and the clavicular facet of the sternum. When a person falls heavily on the shoulder, the sternoclavicular joint may dislocate forward or backward.
Acromioclavicular joint is a gliding joint formed between the acromion end of the clavicle and the acromion process of the scapula. This joint enhances the freedom of movement of the humerus at the shoulder joint. Subluxation of shoulder joint is more common than its dislocation due to dislocation of acromioclavicular joint.
Shoulder joint is the synovial joint of the ball and socket variety (Fig. 8.45). The head of the humerus is one third of a sphere that articulates within the glenoid cavity of the scapula. The glenoid cavity is deepened by the attachment of fibrocartilaginous rim (glenoid labrum). Ligaments that form a loose capsule hold the bones of the joint together. The degree of movement is dependent on the muscles surrounding the joint and the atmospheric pressure. The looseness of the capsular ligament allows the free movement in all directions—abduction, adduction, flexion, extension, medial and lateral rotation, internal and external rotation, and circumduction. The gliding movement of the scapula on the chest wall enhances the movement at the shoulder joint.
Abduction of shoulder joint: It is performed by the action of supraspinatus and the deltoid muscles. This movement is limited to 90 degrees. Further elevation to 180 degrees is brought about by the rotation of the scapula on the chest wall by trapezius.
Adduction at the shoulder joint: It is brought about by the weight of the arm, as well as by the contraction of muscles of the front and behind thorax; pectoralis major and latissimus dorsi.
Flexion: It is the arm, which is carried forwards and across the chest, by the action of pectoralis major and the deltoid.
Muscles attached to the scapula: These are teres major, latissimus dorsi and the posterior fibers of the deltoid bring about extension at shoulder joint.
External and internal rotation of shoulder joint and circumduction: These are possible due to the concerted action of almost all the muscles attached to the shoulder joint.
Dislocation and subluxation of the head of the femur as a result of trauma, is common due to the laxity of capsular ligament. The dislocation is the complete separation of the joint surfaces due to tearing of the capsule. Subluxation is an incomplete separation as a result of stretching of the capsule. Dislocation may complicate fractures of the upper extremity of the humerus.
Elbow joint is a hinge joint formed between the trochlear surface of the humerus, and the trochlear notch of the ulna that forms the humeroulnar joint and the head of the radius articulate with capitulum of the humerus to form humeroradial joint. All the four articulating surfaces lie within the joint capsule (Fig. 8.46). In the movement of the joint, the radius is curved backwards and forwards with the ulna. The movements possible at elbow are flexion and extension.
Carrying angle of the elbow: When the elbow is extended and the forearm, and hand supinated, it forms about 170 degrees with the upper arm (Fig. 8.47). This obliquity of the articulating surface between the humerus and ulna is that when the articles are carried, it is clear of the body.
Dislocation of the elbow joint: It is often complicated by the fractures of the bones forming elbow joint. Fracture of the coronoid process of ulna results in backward dislocation of the elbow.
Other features of elbow joint are:
The action of biceps, brachialis and flexor muscles of the forearm, bring flexion at the elbow joint.
Pronation is brought about by the action of pronators and flexor carpi radialis muscles.
Extension is by the action of triceps and anconeus muscles.
Supination is by the action of biceps, brachioradialis and extensors of the thumb muscles.
Biceps is principally a flexor muscle of elbow, but due to its insertion into tuberosity of radius, it is also able to rotate the forearm into supination position.
Radioulnar joints are formed by superior and inferior radioulnar joints (Fig. 8.48), and the middle radioulnar joint formed by the interosseous membrane, separates the anterior and posterior muscles of the forearm. The movements between the ulna and radius are free. When the head of the radius rotates within the annular ligament at the superior radioulnar joint, the lower end of the radius rotates at the head of the ulna at the inferior radioulnar joint. This movement aids pronation and supination of the forearm. Pronation is the rotation of radius on the ulna, until the hand lies palm downwards.
In supination, the radius and ulna lie parallel to each other, and the palm facing upwards.
Dislocation of the head of the radius with displacement forwards, occur in young people falling forward heavily on the extended forearm. Pulled elbow is the subluxation of the radial head in young children due to sudden jerk on the arm.
Wrist joint is also known as radiocarpal joint (Fig. 8.49). It is a condylar joint, formed by the articulation of the lower end of the radius and the articular disk below the head of the ulna, with the concave surface for the reception of the upper aspects of the scaphoid, lunate, and the triquetral bones. The movements possible at this joint are flexion and extension, and abduction and adduction.
The sprains and strains are quite common due to trauma to the wrist joint. Such a condition requires support to the wrist joint for some time; otherwise there is a tendency to drop things. Falling on the palm of the hand can result in dislocation of one or more carpal bones or the fracture of scaphoid or navicular bone. The fracture of the first metacarpal of the hand results in a part subluxation, called Bennett’s fracture.
Muscles involved in the movement of wrist: These are flexion by the long muscles crossing the front of the wrist, extension by the muscles crossing the back of the wrist joint. Adduction by the carpal extensor and flexor muscles on the ulnar side of the wrist joint. Adduction is by the carpal extensors and flexor on the radial side of the wrist joint.
Muscles involved in the action of the hand: These are the long extensors and the long flexors attached to the fingers, and the small muscles attached to the carpal bones. The thumb is capable of flexion, extension, adduction and abduction, and opposing to the fingers as in grasping.
Hip joint is the ball and socket variety of synovial joint. The acetabulum of the innominate bone, which receives the head of the femur, is deepened by the presence of acetabular labrum in its circumference. The ligaments of the hip joint are the cartilage, which forms a rim and further deepens the acetabulum for the reception of head of the femur.
The capsular ligament of the hip joint is thick and strong, which limits the movement of the hip joint in all direction as well as helps to maintain the erect posture, while standing (Fig. 8.50). The important ligaments of the capsule are iliofemoral ligaments, the bands that lie in front of the joint and the pubofemoral ligament that holds the femur to the pubic bone. The movements at the hip joint are flexion, extension, abduction and medial and lateral rotation. A combination of all these movements is called circumduction.
Muscles at Hip Joint
The muscles that help bring about different movements at the hip joint are as follows:
Flexion is brought about by iliopsoas and rectus femoris
Extension by gluteus maximus and the hamstring
Adduction by a group of adductors at the medial aspect of the thigh
Abduction by gluteus minimus and medius
Lateral rotation by gluteus maximus
Medial rotation by iliopsoas.
Congenital dislocation of hip joint is much more common than any other joints. It is noticed first when the child begins to walk, which produces ungainly gait that cause disablement in later life.
Dislocation of hip joint can occur in any of the direction, but the most common is the backward and medial dislocation. The direction of dislocation is determined by the position of thigh at the time of impact.
The knee joint is a modified hinge joint (Fig. 8.51). It is formed between the condyles of the femur and the superior surface of the articulating condyle of the tibia. The smooth patellar surface of the femur receives patella that glides over it during the movements of the knee joint. The patella is in front of the main articular parts, but does not enter into the formation of knee joint. The ligaments and the muscles surrounding it, particularly quadriceps femoris, stabilize the knee joint.
Structures Within the Knee Joint
The important structures that lie within the knee joint are:
The semilunar cartilage, placed on the articulating surface of the tibia that deepens to receive the condylar surface of the femur.
The cruciate ligaments that pass from the top of the tibial condyles to the rough surfaces on the intercondyloid notch of the femur. It helps to limit the movement of the knee joint and bind the bones firmly together.
Capsular ligaments are the expansion from the muscles and the tendons that surround, and pass over the joint (Fig. 8.52).
The synovial membrane of the knee joint is the largest in the body. It not only lines the knee joint but also extend upwards and downwards beneath the ligaments of the patella to form several bursae around the joint.
Movements at the Knee Joint
The movements at the knee joint are flexion, extension and limited medial rotation:
Extension of the knee joint is brought about by quadriceps femoris muscle
Flexion by hamstring, and gastrocnemius muscles
Medial rotation by popliteus muscle that is deeply placed at the back of the tibia.
Trauma to the knee joint can cause acute synovitis. Since the synovial membrane is extensive, the swelling accompanying inflammation can rise above the patella on each side.
Bursitis: It is the inflammation and swelling of one or more of the bursae around the knee joint. The inflammation of the bursa between the patella and skin is the most common, which affects the people who kneel quite often housemaid’s knee. The diseases of the knee joint often affect the hamstring muscles; contraction of this muscle results in flexional deformity.
The articulating surfaces of the knee joint, though not well-adapted, is one of the strongest and most stable joint because of the ligaments and strong muscles that surround it. Twisting of the joint in flexion is accompanied by pain and often locking the knee joint in flexion, because of a cartilage getting lodged between the condyles that prevents extension at the joint. Due to trauma, one of the semilunar cartilages may be torn, displaced or detached.
An interosseous ligament, similar to found in the arm between radius and ulna, forms tibiofibular joint between the shafts of tibia and fibula.
The ankle joint is formed by the articulation of the lower ends of the tibia and its medial malleolus, and the lateral malleolus of the fibula that together forms a socket to receive the body of the talus. This joint is a hinge joint that is stabilized by the capsule formed by a ligament on the medial aspect, which passes from the medial malleolus to the adjoining tarsal bones. This ligament is often torn in severe sprains of the ankle as in slipping off a kreb or getting the foot into a hole.
Movements at the Ankle Joint
The movements at the ankle joint are dorsiflexion and plantar flexion. The muscles involved in various movements at ankle joint are as follows:
Dorsiflexion is brought about by tibialis anterior muscle and the long extensors of the toes.
Plantar flexion is brought about by gastrocnemius muscle, tibialis posterior and the long flexors of the toes.
Joints of the Foot
Dorsal, plantar and interosseous ligaments hold the tarsal bones together. The joints between tarsal bones are gliding joints. On the undersurface of the talus and the upper surface of the calcaneum, a thick interosseous ligament grooves the joint surface of both the bones (Fig. 8.53).
The joints between the head of the talus and the navicular, and between the cuboid and calcaneum, are called mediotarsal joints. It is at these joints, the movement of inversion and eversion take place.
During eversion, the inner border of the foot is lowered so that the sole is directed outwards. In inversion, the outer border of the foot is lowered so that the sole of the foot is directed inwards. At the talocalcaneal joint, slight abduction and adduction occurs. The tarsometatarsal, the metatarsophalangeal and the interphalangeal joints are similar to those found in the hand.
Muscles Concerned with Arch of the Foot
The muscles concerned with maintaining the arch of the foot are tendons of peroneus longus that passes beneath the sole, tibialis anterior from the front and tibialis posterior from the back of the leg, forming a double sling to support the arches of the foot.
Arthritis: It is the inflammation of a joint that frequently affects the middle aged and the elderly.
Rheumatoid arthritis: It is polyarthritis, which is bilateral and symmetrical in distribution. Most often it affects the small joints, forming osteophytes (Heberden’s nodes) at the interphalangeal joints. This condition is treated by administration of steroids that arrest the spread of the disease.
Osteoarthritis: It is a progressive degenerative disorder of the cartilage of joints that progresses with advancing age. It begins as a monoarthritis, but may spread to other joints. The joints most affected are the knee joint, hip joint and intervertebral joints. Painful stiff joints that limit the movement characterize it. Treated usually by administration of steroids orally or intra-articularly. Weight reduction also helps such individuals.
The use of arthroscopic techniques has been particularly important for injured patients. Arthroscopy is a minimally invasive cartilage surgery and reconstructions of torn ligaments. Arthroscopy help patients to recover from the surgery in a matter of days, rather than weeks to months required by conventional ‘open’ surgery. It is a very popular technique. Knee arthroscopy is one of the most common operations performed by orthopedic surgeons today and is often combined with meniscectomy or chondroplasty. The majority of orthopedic procedures are now performed arthroscopically.
The modern total hip replacement was pioneered in the 1960s. The joint surfaces could be replaced by metal or high-density polyethylene implants cemented to the bone with methyl methacrylate bone cement. There have been continuous improvements in the design and technique of joint replacement (arthroplasty) with many contributors, including uncemented arthroplasty techniques with the bone bonding directly to the implant.
Knee replacements was developed in 1970s, by utilizing a fixed-bearing system and mobile-bearing system with the similar technology used in rheumatoid arthritis patients for osteoarthritis.
Unicompartmental knee replacement: It is an alternative to a total knee replacement in a selected patient population, where only one weight-bearing surface of an arthritic knee is replaced.
Joint replacements are available for other joints on a limited basis, most notably shoulder, elbow, wrist, ankle, spine and fingers.
Surface Replacement of Joints
In recent years, surface replacement of joints, in particular the hip joint has become more popular amongst younger and more active patients. This type of operation delays the need for the more traditional and less bone-conserving total hip replacement, but carries significant risks of early failure from fracture and bone death.
Problems and Solutions with Joint Replacements
One of the main problems with joint replacement is wear of the bearing surfaces of components. This can lead to damage the surrounding bone and contribute to eventual failure of the implant. Use of alternative bearing surfaces, particularly in younger patients, is an attempt to improve the wear characteristics of joint replacement components has increased in recent years. These include ceramics and all metal implants. The plastic (actually ultrahigh-molecular weight polyethylene) can also be altered in ways that may improve wear characteristics.
SURFACE ANATOMY OF HEAD
The position of the longitudinal fissure that separates the two cerebral hemispheres and the position of the superior sagittal sinus of the dura mater is marked by drawing a line from the external occipital protuberance of the occipital bone, forwards over the top of the skull, to a point at the center of the base of the nose.
Central sulcus or fissure of Rolando of brain can be marked on the skull surface by finding the midpoint of the line drawn from the external occipital protuberance of the occipital bone, forwards over the top of the skull, to a point at the center of the base of the nose. A line drawn from about an inch behind this midpoint and the ear gives the direction of the central sulcus.
Mastoid process is the bony elevation behind the ear.
Parotid gland is situated between the mastoid process and the ramus of the mandible, but spreads over the masseter muscle and beneath the zygomatic arch. The parotid duct passes forward and pierces the buccinator muscle to enter the mouth opposite the second upper molar tooth.
Sternocleidomastoid muscle that runs obliquely from the temporal bone to the front of the clavicle divides the region of neck into anterior and posterior triangles (Fig. 9.1). The clavicle separates the neck from the thorax.
Anterior triangle of the neck is further subdivided into the carotid triangle and the digastric triangles. The contents of the carotid triangle are the carotid artery and its divisions into internal and external carotids, the internal jugular vein, numerous other veins, arteries and nerves. The digastric triangle that lies below the jaw contains parts of the submandibular and parotid salivary glands, a branch of the facial nerve and facial artery, and other structures more deeply placed, including some of the carotid vessels.
Posterior triangle of the neck is bounded in front by the sternocleidomastoid muscle, behind by the anterior border of trapezius muscle and the intermediate third of clavicle forms the base (Fig. 9.2). Its contents are portions of the cervical and brachial plexuses of nerves, a chain of lymphatic glands that lie posterior to the sternocleidomastoid, nerves and blood vessels. At the base of this lies the first rib over which the subclavian artery passes. It is here that digital pressure can be applied to the subclavian artery.
Manubrium sterni is a valuable landmark, since a part of the arch of the aorta and the innominate veins lie behind it. The trachea commences immediately below the cricoid cartilage and passes into the thoracic cavity to terminate by dividing into right and left bronchus at the level of the sternal angle (angle of Louis).
Esophagus also begins at the lower border of the cricoid cartilage and runs downward behind the trachea.
Thymus gland lies behind the manubrium and the upper part of the body of the sternum in a child, and in some cases it may extend upwards into the neck.
RELATIONSHIP BETWEEN STERNUM AND VERTEBRAL COLUMN
In relation to the vertebral column, the top of the sternum lies opposite the joint between the second and third thoracic vertebrae.
The angle of Louis lies between the fourth and fifth thoracic vertebrae.
The articulation between the body of the sternum and the xiphi sternum lies about the level of the disk between the ninth and tenth thoracic vertebrae.
The sternal angle or angle of Louis can be felt through the skin; it is the level of attachment of the second rib.
At the other end of the sternum is the infrasternal angle or xiphoid, where a shallow depression can be seen and felt. By running the finger from this angle outwards along the lower borders of the ribs, the costal margin, which is formed by the cartilages of the seventh, eighth, ninth and the tenth ribs can be felt, and seen in thin subjects.
The apex beat of the heart can be felt and sometimes can be seen in the fifth left intercostal space, 9 cm away from midline.
Abdomen is divided into nine regions by four imaginary lines (two vertical and two horizontal) drawn on the abdominal surface (Fig. 9.3).
The subject should lie supine on an examination couch or other suitable flat surface with the abdomen fully exposed.
Mark (using skin pencils) the following on the anterior abdominal wall:
Subcostal plane (the approximate upper limit of the abdominal cavity (diaphragm muscle) by a slightly oblique line (right side 1–2 cm higher than the left side) drawn across the front of the chest at the level of the xiphisternal joint).
Intertubercular plane (horizontal line joining the tubercles of the iliac crests).
Right and left midclavicular lines (vertical line joining the midclavicular and midinguinal points).
It enters the abdomen in front of T12 vertebra and descends on the bodies of L1–L4 vertebrae. It is about 2 cm wide and tends to incline approximately 1 cm to the left at its lower (inferior) end, where it terminates in the supracristal plane by bifurcating into the common iliac arteries. Palpate its pulsation in the infrasternal angle.
Inferior Vena Cava
Inferior vena cava (IVC) lies immediately to the right of the abdominal aorta. It is about 3 cm wide and extends vertically from the transtubercular plane to the level of the xiphisternal joint.
Kidneys and Ureters
Kidneys lie adjacent to the T12 to L3 vertebral bodies. The transpyloric plane bisects the left kidney. The right kidney is approximately 1–2 cm lower. The lateral lines bisect each kidney vertically. The hilum of each kidney is 5 cm from the midline and the upper poles are a little nearer to the midline than the lower poles. Each kidney is approximately 11 cm by 5 cm. Each ureter leaves the hilus and descends vertically. The right ureter is lateral to the IVC.
Suprarenal gland rests on the upper pole of its respective kidney. The right is triangular (dunce cap-shaped) and extends partly behind the IVC. The left is crescent-shaped and extends down the medial border of the kidney to the renal hilus.
Duodenum marks the pyloric orifice as a vertical ellipse 3 cm in height and 2 cm to the right of the midline, in the transpyloric plane. The first (superior) part runs to the right and slightly superiorly, and is foreshortened in perspective to 3 cm in length. The second (descending) part lies to the right of L1–L3 vertebrae anterior to the medial border of the right kidney and to the IVC. The third (horizontal) part runs transversely to the left for about 8 cm (in perspective) across the midline in front of the L3 vertebral body. The fourth (ascending) part passes superiorly for 3 cm, on the left of L2, lateral to the aorta and medial to the left kidney and ureter.
The superior margin rises from the upper pole of the left kidney to the fifth intercostal space in the left lateral line. It then curves inferiorly (convex laterally) to meet the lateral contour of the left kidney in the transpyloric plane. Complete the outline by curving the line over the upper pole of the kidney.
The head of the pancreas occupies the C-shaped concavity of the duodenum. The body extends slightly upwards and to the left across the front of the lower end of the left suprarenal gland and the left kidney, and the tail rests on the lower part of the visceral surface of the spleen.
It begins in the transtubercular plane just lateral to the right lateral line. Mark it by a pair of vertical, scalloped lines, about 5 cm apart, drawn upwards towards the transpyloric plane but not quite reaching it.
Note: The ascending colon terminates anterior to the lower part of the right kidney.
Mark this as you did the ascending colon, from the lower pole of the spleen, descending across the lateral part of the left kidney and continuing downwards lateral to the lateral line, as far as the anterior superior iliac spine in the left iliac fossa. End by curving medially to the pelvic brim in the left lateral line.
Mark the cardiac orifice (cardioesophageal junction) as a vertical ellipse 3 cm high and 3 cm to the left of the midline, midway between the xiphisternal joint and the transpyloric plane. Mark the lesser curvature descending vertically from the lower edge of the cardiac orifice to the transpyloric plane, then turning sharply to the right (incisura angularis) to join the upper edge of the pyloric orifice. Mark the greater curvature from the upper edge of the cardiac orifice as a dome extending up to the fifth rib in the left lateral line, then descending along the superior margin of the spleen to the lower part of the left kidney. It then turns upwards and to the right to join the lower edge of the pylorus.
It occupies parts of the right hypochondriac and epigastric regions, extending transversely into the left hypochondriac region and occupying a part of the lumbar region also.
Mark the fundus as a pouch projecting downwards and laterally into the angle between the right costal margin and the lateral edge of the rectus abdominis muscle (about the size of an egg). The gallbladder overlies the superior part of the duodenum and the transverse colon.
It forms a depression running down the middle line of the abdomen from the xiphoid process to the symphysis pubis. On each side of this line the rectus abdominis can be felt.
McBurney’s point is at the junction of the middle and outer thirds of a line drawn from the umbilicus to the aanterior uperior iliac spine on the right side. It is the site of maximum tenderness in appendicitis.
On the posterior aspect of the trunk the vertebral spines can be palpated; the spine of the seventh cervical vertebra is prominent. The vertebral prominence of the spine and lower angle of the scapula can be felt and seen in thin subjects. The scapula lies in relation to the vertebral column opposite the distance between the spines of the second to the seventh dorsal vertebrae.
The position of the posterior superior iliac spine (on each side) can be distinguished by a dimple. The crest of the ilium can be palpated in its entire length and at its highest point it lies on a level with the interval between the third and fourth lumbar vertebrae. By marking this line with a skin pencil, the position below which it is safe to perform lumbar puncture is indicated. The spinal cord ends at the level of junction between the first and second lumbar vertebrae.
The suprasternal notch, the sternal angle (of Louis), the xiphoid and the anterior superior iliac spine can be felt.
Nélaton’s line is an imaginary line drawn from the anterior superior iliac spine, backwards to the tuberosity of the ischium. It cuts through the center of the hip joint and across the top of the greater trochanter of the femur. It is useful in assessing the position of the femoral head in dislocation of the hip joint or if the neck of the femur is fractured.
When applying a splint or plaster, it is important to remember, to keep the wrist extended, so that it does not impinge on the metacarpophalangeal joints, but terminates below them to ensure that the patient can flex fingers, over the splint, to right angles with the palm of the hand.
The body must get rid of the waste products of cellular activity. The process of removing metabolic waste is called excretion. The metabolic wastes include excess water and salts, carbon dioxide from cellular respiration, nitrogenous compounds from the breakdown of proteins and urea. It is vital to maintain the body’s internal environment. The skin, lungs and kidneys along with their associated organs make up the excretory system.
The urinary system not only excretes waste products such as nitrogenous wastes and dissolved wastes but also help maintain homeostasis by returning the content of water, bicarbonate and other physiologically important substances in the blood.
The urinary system consists of (Fig. 10.1):
The kidneys, which secrete urine
The ureters that convey the urine from kidney to bladder
The bladder that acts as a reservoir
The urethra for discharge of urine from the bladder.
The kidneys are essentially regulatory organs, which maintain the volume and composition of body fluid by filtration of blood and selective reabsorption and secretion of filtered solutes. Human body has two kidneys, one on each side of the vertebral column near the lower back; the left kidney is behind the stomach and the right kidney is behind the liver. Together they regulate the chemical composition of blood.
The kidneys are retroperitoneal organs (i.e. located behind the peritoneum) situated on the posterior wall of the abdomen on each side of the vertebral column, at about the level of the 12th rib. Each kidney is surrounded by renal adipose capsule (fatty tissue). The left kidney is slightly higher in the abdomen than the right, whereas the right kidney is at a lower level due to the presence of the liver that pushes the right kidney down.
The kidneys are bean shaped, deep purple colored organs, each measuring 10–13 cm (4–5 inch) in length, 6 cm (2½ inch) in breadth and 2.5–4 cm (1½ inch) in thickness. An adult kidney weighs about 140 g. They lie obliquely behind the peritoneum of the posterior abdominal wall with their upper poles nearer the midline than their upper poles. A thin capsule of fibrous tissue surrounds each kidney. The inner border or hilum is directed towards the vertebral column, which contains the renal blood vessels, nerves and the renal pelvis (the funnel-shaped upper end of the ureter). The center of the hilum is opposite the lower border of the spine of first lumbar vertebra, about 5 cm from the median plane. The outer border is convex. The vessels of the kidneys enter and leave at the hilum. Each kidney is surmounted by an adrenal gland. The right kidney is shorter and thicker than the left.
The kidneys take their blood supply directly from the aorta via the renal arteries; blood is returned to the inferior vena cava via the renal veins (Fig. 10.2). Urine (the filtered product containing waste materials and water) excreted from the kidneys passes down the fibromuscular ureters and collects in the bladder. The bladder muscle (the detrusor muscle) is capable of distending to accept urine without increasing the pressure inside; this means that large volumes of urine can be collected (700–1,000 mL) without high pressure damage to the renal system.
When urine is passed, the urethral sphincter at the base of the bladder relaxes, the detrusor contracts and urine is voided via the urethra.
Ureters extend from the renal pelvis as a dilatation to open obliquely into the posterior wall of the bladder. Each ureter is the thickness of goose-quill and 35–40 cm (14–16 inch) in length that runs behind the peritoneum. It consists of:
An outer fibrous covering (adventitia)
Inner mucosa consists of transitional epithelium
Middle muscularis consists of circular and longitudinal muscle layer.
Urinary bladder is a pear-shaped organ situated in the pelvis in front of the other contents and behind the symphysis pubis. The lowest part is fixed and is called base, the upper part or fundus raises the bladder when filled with urine. The apex lies forward beneath and behind the symphysis pubis. The interior of bladder is lined by mucosa made of transitional epithelium and the wall is made of detrusor (muscularis), which has 3 layers of smooth muscle. The two ureters open as ureteral orifice into the inferior triangular area of the bladder, which is called trigone. In the females, the bladder lies between the symphysis pubis and the uterus, and vagina. It is separated from the uterus by a fold of peritoneal pouch called uterovesical pouch.
Urethra voids urine from urinary bladder to outside the body. Urethral wall is composed of mucosa (has a variety of epithelia) and muscularis layers. Female urethra is about 4 cm long and transports only urine. Male urethra is about 20 cm long and transports urine and semen. The male urethra has three regions—prostatic (in prostate), membranous and spongy (in penis).
Micturition is another word for urination and in most animals it happens automatically. The act of micturition occurs when 170–230 mL of urine have accumulated in the bladder. Micturition is a reflex act, which can be controlled and inhibited by the contraction of the muscular coat of the bladder and relaxation of the sphincter muscles (Fig. 10.3).
As the bladder fills with urine, stretch receptors in the wall of the bladder send signals to the parasympathetic nerves to relax the band of smooth muscle that forms the internal urethral sphincter. As the muscle relaxes, the urethra opens and urine is voided to the outside environment.
A second sphincter, the external urethral sphincter is skeletal muscle controlled by motor neurons. These neurons are under conscious control and this means we are able to exercise control over when and where we urinate. This control is a learned response that is absent in the newborn infant.
STRUCTURE/FUNCTIONS OF KIDNEY
When the kidney is cut lengthwise through its medial and lateral borders, it is seen to consist of a pale outer region the cortex and a darker inner region the medulla (Fig. 10.4). The medulla is divided into 8–18 conical regions, called renal pyramids; the base of each pyramid starts at the corticomedullary border and the apex ends in the renal papilla, which merges to form the renal pelvis and then further to form the ureter. In humans, the renal pelvis is divided into two or three divisions, the major calyces, which in turn divide into further minor calyces. The walls of the calyces, pelvis and ureters are lined with smooth muscle that can contract to force urine towards the bladder by peristalsis.
The cortex and the medulla are made up of nephrons; these are the functional units of the kidney and each kidney contains about 1.3 million of them.
The nephron is the functional unit of the kidney, responsible for the actual purification and filtration of the blood (Fig. 10.5). About one million nephrons are in the cortex of each kidney and each one consists of a renal corpuscle and a renal tubule, which carry out the functions of the nephron. The renal tubule consists of the convoluted tubule and the loop of Henle.
The nephron is part of the homeostatic mechanism of our body. This system helps regulate the amount of water, salts, glucose, urea, creatinine and other minerals in the body. The nephron is a filtration system located in the kidney that is responsible for the reabsorption of water and salts. This is where glucose eventually is absorbed in the body. Diabetics have trouble reabsorbing the glucose in their body and hence a lot of it comes out in the urine hence the name ‘diabetic’ or ‘sweet urine’.
Loop of Henle
Loop of Henle is the part of the nephron that contains the basic pathway for the filtrate. The filtrate begins at the Bowman’s capsule and then flows through the proximal convoluted tubule. It is here that sodium, water, amino acids and glucose get reabsorbed. The filtrate, then flows down the descending limb and then back up. On the way it passes a major bend called loop of Henle. This is located in the medulla of the kidney. As it approaches the top again, hydrogen ions flow into the tube and down the collecting duct.
So essentially, nutrients flow in through the left and exit through the right. Along the way, salts, carbohydrates and water pass through, and are reabsorbed.
The glomerulus is the main filter of the nephron and is located within the Bowman’s capsule. The glomerulus resembles a twisted mass of tiny tubes through which the blood passes. The glomerulus is semipermeable, allowing water and soluble wastes to pass through and be excreted out into the Bowman’s capsule as urine. The filtered blood passes out of the glomerulus into the efferent arteriole to be returned through the medullary plexus to the interlobular vein.
The Bowman’s capsule contains the primary filtering device of the nephron, the glomerulus. Blood is transported into the Bowman’s capsule from the afferent arteriole (branching off of the interlobular artery). Within the capsule, the blood is filtered through the glomerulus and then passes out via the efferent arteriole. Meanwhile, the filtered water and aqueous wastes are passed out of the Bowman’s capsule into the proximal convoluted tubule.
In addition to the uriniferous tubules the kidney contains blood vessels. The renal artery brings blood from the abdominal aorta to the kidneys.
Branches of this ramify in the kidney and break up into the afferent arterioles, each forming a knot of capillaries in one of the malpighian body (tuft of capillary loops within and surrounded by Bowman’s capsule that together form the beginning of a nephron). The efferent vessels then emerge as a small efferent arteriole, which breaks up to form a second capillary network (peritubular capillaries) around the uriniferous tubules. These capillaries eventually reunite to form the renal vein, which conveys the blood from the kidney to the inferior vena cava. The blood circulating through the kidney has therefore a double set of capillary vessels. the primary objective is to retain the blood in the vicinity of the uriniferous tubules upon which the function of kidney depends.
Homeostasis of water, solutes and electrolytes:
Regulates fluid volume
Regulates inorganic ions (i.e. calcium, sodium)
Regulates organic compounds (glucose)
Excretion of metabolic waste:
Creatinine and urea (ammonia is toxic nitrogenous waste from catabolism of proteins and nucleic acid)
Liver converts ammonia to urea
Kidney excretes urea.
Involves three processes:
Everyday kidneys filter about 180 L of plasma, but only 1–1.8 L of urine is produced per day, which means 99% of filtrate is reabsorbed.
Glomerular filtration is non-selective that means the body has no control over what is filtered. The glomerulus is like a sieve and any molecule small enough will pass through. Filtration is passive and needs no energy.
Glomerular Rate of Filtration is Dependent on a Pressure Gradient
The blood in the glomerulus is under a relatively high pressure due to the difference in the diameters of the afferent and efferent arterioles. The difference between the hydrostatic pressure and the colloid osmotic pressure determines the filtration rate. Think about what will happen if blood pressure falls. What happens if there is backpressure in the Bowman’s capsule due to damage to the renal tubules? What if the patient is very dehydrated?
About 20% of plasma flowing through glomerulus is filtered, which amounts to a glomerular filtrate of 120 mL/min.
Regulation of Glomerular Filtration Rate
Glomerular hydrostatic pressure and glomerular filtration rate (GFR) are constant over a range of systolic pressure of BP: 80–180 mm Hg. Kidney has internal mechanisms (autoregulation) for maintaining GFR by altering the diameters of afferent and efferent arterioles.
Tubular reabsorption is concerned with conservation of solutes and water from the glomerular filtrate. Tubular reabsorption can be passive or active. Surface area of tubule is increased by microvilli (brush border).
Proximal Convoluted Tubule
Proximal convoluted tubule (PCT) is involved in passive reabsorption of urea and water. It also exchanges the following anions for H+—bicarbonate, chloride, phosphate and sulfate.
The following are actively reabsorbed at the proximal tubule, which means they require carriers and energy (ATP)—glucose, amino acids, sodium, potassium, calcium, vitamin C and uric acid. About two-third of filtrate reabsorbed by the PCT is independent of the body’s needs; the PCT cannot make adjustments in what is reabsorbed.
Loop of Henle and Descending Limb
Loop of Henle and descending limb is involved in passive reabsorption of water (Fig. 10.6) into the medulla. Sodium and chloride are also reabsorbed into the medulla.
Ascending limb reabsorbs chloride actively, but sodium and bicarbonate are passively reabsorbed. By the time the glomerular filtrate reaches ascending loop of Henle, 85% of water and 90% of sodium and chloride have been reabsorbed, and majority of reabsorption is not influenced by the body’s needs. Ascending limb of loop of Henle is impermeable to water.
The volume of filtrate decreases by 20% in the loop of Henle; therefore water is conserved.
Distal Convoluted Tubule
Distal convoluted tubule is involved in active reabsorption of sodium (dependent on aldosterone) and potassium. Water is passively reabsorbed under the control of antidiuretic hormone (ADH).
Collecting ducts are involved in active reabsorption of chloride. Active reabsorption of sodium (dependent on aldosterone) and potassium, and passive reabsorption of water also take place.
The distal part of the nephron is impermeable to water in the absence of ADH. Therefore this is where the ‘fine tuning’ occurs depending on the body’s needs.
Tubular Secretion is Reverse of Reabsorption
Solutes move from the peritubular capillaries into the lumen of the nephron by active and passive transfer.
Proximal convoluted tubule actively secretes some drugs, thiamine, choline, creatinine and histamine into the tubular lumen.
Distal convoluted tubule actively secretes ions such as potassium, H+ and bicarbonate ions.
NORMAL CONSTITUENTS OF URINE
Urea: Quantity of urea excreted is proportional to protein intake in the diet and catabolism of tissue protein. In liver diseases such as acute yellow dystrophy of liver and cirrhosis, production of urea is greatly reduced, since ammonia derived from amino acid metabolism is not converted to urea. In nephritis, excretion of urea in urine may be decreased because the ability of the kidney to excrete urea is severely impaired.
Ammonia: Ordinarily there is very little ammonia in freshly voided urine. In severe nephritis, urinary ammonia is greatly decreased because capacity of kidney to form ammonia is impaired. In cystitis (infection of bladder) urinary ammonia is greatly increased because bacteria in the bladder hydrolyze urea.
Uric acid: It is the end product of purine metabolism. It is derived from dietary nucleoprotein and tissue nucleoprotein metabolism. Uric acid excretion in urine is elevated in gout and leukemia.
Creatinine: It is the product of creatine breakdown. Excretion of creatinine in urine is constant in the subject with creatine free diet.
Creatine coefficient: It is defined as the ratio between the amounts of creatine excreted in 24 hours and the body weight in kilogram. It is commonly 20–26 mg/Kg/24 hours in normal man.
Chlorides: Over a period of 24 hours, normally 6–9 g of chloride is excreted as 10–15 g of sodium chloride. Sodium excretion is greatly reduced in diarrhea, vomiting certain stages of nephritis and excessive perspiration.
Potassium: It is increased in urine in the presence of excessive tissue catabolism.
Sodium: Excretion is increased in hypofunction of adrenal cortex (Addison’s disease).
KIDNEY FUNCTION TESTS (RENAL FUNCTION TESTS)
Control of Kidney Function
The main purpose of our kidneys is to maintain the chemical composition of our blood.
The kidneys are the master chemist of the blood supply.
Two important things controlled by the kidneys are: Concentration of water in blood; and the level of salt in our blood.
Drink too much liquid and the kidneys will decrease the rate of reabsorption, excess water is sent to the urinary bladder to be excreted.
Eat salty foods and the kidneys will respond by returning less salt to the blood by reabsorption. The excess is excreted in our urine.
These are the tests performed to assess renal functions:
Urine examination: Volume, specific gravity, urinary reaction, chemical examination and microscopic examination.
Chemical examination of blood:
Excretion of waste products such as urea, creatinine and uric acid.
Water and electrolyte balance, serum potassium concentration.
Acid-base balance abnormalities.
Concentrating power of the kidney and urinary dilution tests.
Radiological and imaging investigations of the kidney, such as plain X-ray, intravenous pyelography and ultrasonography.
Clearance tests are aimed at assessing the following:
Glomerular filtration rate (inulin clearance, 125 mL/min)
Blood flow through kidney (P-aminohippuric acid (PAHA) clearance, 650 mL/min)
Overall renal efficiency (urea clearance 75 mL/min, creatinine clearance 140 mL/min).
The popular tests for assessment of renal function are the renal clearance tests.
The renal clearance test can be defined as the volume (mL) of plasma (blood), which has been cleared of a substance in question via urine over a period of unit time (1 minute). This can be calculated by the formula:
Clearance of X (mL/min) = UXV/PX
X is a substance in question:
The clearance value of X is the volume of plasma completely cleared of X.
UX is concentration of X in 1 mL of urine;
PX is concentration of X in 1 mL of plasma;
V is volume (mL) of urine formed per minute.
Inulin Clearance Test
Inulin clearance test is performed to estimate glomerular filtration rate (GFR). In renal failure GFR is reduced. Inulin is a low molecular weight polysaccharide that can pass through the renal filtering membrane with absolute ease. Further, inulin is neither secreted nor reabsorbed by the renal tubules. Hence, it is presumed that the entire quantity of inulin present in the urine after an intravenous injection of inulin solution must have come from the glomerular filtration.
The normal value of inulin clearance in a man of 1.73 m2 surface area is about 125 mL/min. It is usually reported in terms of inulin clearance in mL/sqm (70 mL/min/m2) of body surface/min.
Inulin clearance is the flux of inulin filtered through the glomerular barrier per minute is (GFR × Cp/0.94). All inulin molecules remains in the filtrate and is excreted in the urine.
Thus, the amount excreted is equal to the amount filtered:
GFR × Cp/0.94 = (Cu × V°u) mmol/min
About 10 g of inulin, dissolved in 100 mL of normal saline, is administered intravenously at the rate of 10 mL per minute. At the end of IV infusion ask the patient to empty the bladder completely and discard the urine. Exactly 30 minutes later ask the patient to completely empty the bladder to give urine for analysis. At the same time take a specimen of blood for analysis.
The volume of urine measured in mL is formed over 30 minutes time. Calculate the urine formed in mL/min.
Estimate the amount of inulin present in 1 mL of urine and 1 mL of serum samples collected.
Calculate the clearance applying the above formula.
Equations to Assess Renal Function
The law of mass balance (Fick’s principle) states that the delivery of pulmonary arterial hypertension (PAH) (at low plasma concentration) to the kidney is equal to its excretion rate at steady state. At low plasma concentration of PAH, almost all of it is cleared (90%) from the blood during one transit through the kidney. Thus the renal plasma clearance is equal to the effective renal plasma flow (ERPF):
ERPF = Jexcr/Cp; RPF = ERPF/EPAH
The effective renal blood flow (ERBF) is calculated by the help of total body hematocrit (normally 0.45). If ERPF is measured to be 600 mL plasma per min, we can calculate ERBF: 600/(1–0.45) = 1,090 mL whole blood per min at rest. This is 20%–25% of cardiac output. The true RBF is 10% higher than the measured ERBF (i.e. 1,200 compared to 1,090 mL whole blood).
Plasma clearance is defined as the volume of arterial plasma that contains the same amount of substance as contained in the urine flow per minute:
Cu is the concentration of the substance expressed as mg/mL in urine;
Cp is the concentration of the substance expressed as mg/mL in plasma and V°u is the volume of urine flow expressed as mL/min.
Excretion fraction (EF) for a substance is the fraction of its glomerular filtration flux, which passes to and is excreted in the urine.
EF = Jexcr/Jfiltr
Jexcr = (Cu × V°u)
Jfiltr =(GFR × Cfiltr) it follows that:
EF = (Cu × V°u)/(GFR × Cfiltr)
Cfiltr is the concentration of the substance in the ultra filtrate. The excretion fraction for inulin is one (1). Substances with an EF above one are subject to net secretion. Substances with an EF below one are subject to net reabsorption.
Extraction fraction (E) for a substance is the fraction extracted by glomerular filtration from the total substance delivery to the kidney via renal blood plasma.
E = Jfiltr/Jtotal = (Ca–Cvr)/Ca
Substances with an E of one are cleared totally from the plasma during their first passage of the kidneys. Inulin has an extraction fraction of 1/5. Extraction fraction of PAH is 0.9.
Other Kidney Functions
Creatinine clearance provides a fair clinical estimate of the renal filtration capacity.
The renal control of body fluid osmolality maintains the normal cell volume intracellular volume (ICV) by changes of renal water excretion.
Normally, we excrete 1,500 mL (range: 1,200–1,800) of water and 2–5 g of Na+ (equivalent of 5–12 g NaCl) every day.
Nitrogen derived from amino acid metabolism is excreted as 30 g or half a mol of urea per day. Daily renal excretion of uric acid, creatinine, hormone metabolites and hemoglobin derivatives approximates their daily production.
The daily renal excretion of metabolic intermediates and foreign molecules (drugs, toxins, chemicals and pesticides) matches their intake or production.
Kidneys are also involved in hormone production. The important hormones synthesized and secreted by kidneys are erythropoietin, renin, kinins, prostaglandins and 1, 25-dihydroxycholecalciferol.
Alterations in hemodynamic or toxic substances cause acute tubular necrosis. Cardiogenic and hypovolemic shock causes renal vasoconstriction ➔ renal ischemia ➔ hypoxic damage (in particular damage of the renal medulla) ➔ acute renal failures. Ischemic tubular damage further reduces GFR, because of reflex spasms of the afferent arterioles and due to tubular blockage with accumulation of filtrate in the early part of the proximal tubules.
Interstitial inflammation of the kidney is more often caused by a hypersensitivity reaction to drugs [antibiotics, phenacetin and non-steroidal anti-inflammatory drugs (NSAIDs)], but can also be caused by bacterial pyelonephritis.
Diabetic nephropathy is characterized by hypertension, albuminuria and low GFR with glomerulosclerosis (thickening of the basement membrane and damage of the glomerular filter by disruption of the protein cross-linkages). The earliest evidence is usually microalbuminuria, which may be followed by intermittent albuminuria and persistent albuminuria.
Nephroblastoma (Wilms´ tumor) is the most frequent intra-abdominal tumor in both girls and boys. It is a large abdominal mass found sometimes with signs of intestinal obstruction. It is a rapidly growing tumor that spread to lungs. The diagnosis is confirmed with excretion urography and arteriography.
Renal cell carcinoma (hypernephroma) is the most common of all malignant renal tumors in adults with a positive history of tobacco smoking. It is strongly associated with a rare autosomal dominant inherited disease (genetic locus is on chromosome 3p) called von Hippel-Lindau syndrome (hemangioblastomas in the cerebellum and the retina).
Anuria or oliguria (< 500 mL daily) indicates the presence of hypotension or renal disease (Table 10.1).
Polyuria (> 2,500 mL of urine daily) is the sign of diabetes (both diabetes mellitus and diabetes insipidus).
Microalbuminuria (i.e. 50–150 mg/L) indicates glomerular barrier disorder, such as diabetic glomerular disease.
Glucosuria with hyperglycemia is the sign of diabetes mellitus.
Glucosuria without hyperglycemia is a sign of a proximal reabsorption defect.
Elevated urea excretion is seen in uremia.
Elevated creatinine excretion indicates a large muscle mass in a healthy person.
Table 10.1 Daily renal output and its composition in various renal disease conditionsComponentConcentrationDaily renal excretionFinding/DiseaseWater500–2,500 mL< 500 mL/Nephropathy, shock> 2,500 mL/DiabetesPotassium60–70 mmol90 mmol daily< 20 mmol daily/Low diet> 150 mmol daily/Rich dietSodium50–120 mmol150 mmol dailyProtein20 mg/L30–150 mg dailyMicroalbuminuria/DiabetesProteinuria/NephropathyGlucoseZeroNegligibleGlucosuria/Diabetes mellitusGlucosuria/Proximal defectUrea200–400 mmol500 mmol dailyHigh excretion/UremiaCreatinine0.11,500–2,000 mg dailyHigh excretion/Large massLow excretion/Muscular atrophyOsmolality> 600 m0smol/kgAcceptable concentration capacity
Low creatinine excretion is the sign of muscular atrophy or aging.
DISEASES OF RENAL SYSTEM
Acute tubular necrosis
Urinary tract infection
Urinary tract obstruction
Tumors of the kidney.
The severity and cause of kidney disease is evaluated by measurement of the GFR.
Glomerulonephritis is an immunologically mediated injury of renal glomeruli of both kidneys. Most patients suffer from postinfectious glomerulonephritis or immune complex nephritis. In this disorder, the circulating antigen-antibody complexes are deposited in the glomeruli or free antigen is bound to antibodies trapped in the capillary network. In majority of cases the antigen is derived from b-hemolytic streptococci/Lancefield group A, but also other bacteria, viruses, parasites (malaria) or drugs (antibiotics, phenacetin and NSAIDs). A few patients produce antibodies against their own antigens [e.g. host DNA in systemic lupus erythematosus, malignant tumor antigen, or antiglomerular basement membrane (anti-GBM)].
The insoluble antigen-antibody complex precipitates in the basement membrane of the glomerular capillaries, which causes proliferation of cells of the glomeruli. The two together reduce glomerular filtration rate (GFR) and to some extent the renal blood flow (RBF) measured as PAH clearance. Thus the infection depresses the glomerular filtration fraction (GFF = GFR/RBF).
The acute postinfectious glomerulonephritis occurs typically in a child, who has suffered from streptococcal tonsillitis a few weeks before. Acute nephritis is characterized by hematuria, proteinuria and oliguria with salt-water retention causing edema and hypertension, pulmonary edema, and life-threatening hypertensive encephalopathy with fits. Recording of blood pressure and fluid balance with weighing is important in order to prevent hypertension and pulmonary edema to develop into a life-threatening condition.
Uremia is a clinical syndrome dominated by retention of non-protein nitrogen (e.g. urea, uric acid, NH4+ creatinine and creatine). Uremic patients generally exhibit hyperkalemia [plasma (K+) above 5.5 mmol] and metabolic acidosis (pH below 7.35 and a negative base excess). This is due to the inadequate secretion of K+, NH4+ and H+. In complete renal shutdown, the patient dies within 1–2 weeks without dialysis. Dialysis is mandatory with severe uremia. When serum creatinine rises above 0.7 mmol, renal insufficiency is usually terminal.
Renal Insufficiency (Failure)
Renal insufficiency is a clinical condition, where the number of filtrating nephrons falls below 1/3 of normal and the GFR is below 40 mL/min, which is inadequate to clear the blood of non-protein nitrogen substances such as urea, uric acid, creatinine and creatine. The retention of non-protein nitrogen in plasma is called azotemia and the clinical syndrome is called uremia (Table 10.2).
The prerenal causes are hypovolemia with hypotension or impaired cardiac pump function or the combination. Extremely severe states of circulatory shock (prerenal cause) results in acute renal insufficiency.
A large group of renal conditions cause renal insufficiency. All postrenal causes are due to an obstruction to urine flow along the urinary tract.
Acute renal insufficiency is a serious disorder, which leads to progressive uremia and chronic renal insufficiency. In addition, the other complications of chronic renal insufficiency are renal osteodystrophy and normochromic, normocytic anemia:
In severe renal failure, kidneys fail to produce sufficient 1, 25-dihydroxycholecalciferol (calcitriol). Calcitriol is required to stimulate Ca2+ transport across the cell and mitochondrial membranes. Lack of calcitriol causes poor absorption of dietary Ca2+ from gastrointestinal (GI) tract and results in low plasma (Ca2+). Since the normal inhibitory effect of calcitriol is lost, the parathyroid hormone (PTH) release is stimulated. After some time a secondary hyperparathyroidism develops with increased resorption of calcium from bone and increased proximal tubular reabsorption of calcium in an attempt to correct the low serum calcium. The calcium resorption from bone results in osteomalacia (soft bones) and in osteoporosis (thin bones).
When normal kidneys are perfused with hypoxemic blood, the peritubular interstitial cells produce large amounts of the glycoprotein hormone, erythropoietin, with strong effect on erythrogenesis. Chronic renal failure leads to erythropoietin deficiency, and thus to anemia, which is of the normochromic, normocytic type.
Hemodialysis: The aim of hemodialysis in patients with renal failure is to eliminate nitrogenous wastes and maintain normal electrolyte concentrations, serum glucose and normal extracellular volume (ECV).
Hemodialysis is performed using a hemodialyzer or artificial kidney, which is a container with series of semipermeable membranes separating the blood from dialysate. It mimics the normal renal excretion of waste. The patient is often connected to the dialyzer by an arteriovenous shunt made by plastic cannulae between the radial artery and an adjacent vein. The arterial blood flows at a rate of 200–300 mL/min into the artificial kidney and after dialysis the blood is returned to the venous system. Dialysate is pumped through the container at a rate of 500 mL/min. Dialysate is a mixture of purified water with salts and glucose in a composition comparable to normal fasting plasma, but without proteins. Bicarbonate or acetate buffer is present at a concentration of about 35 mmol. A plastic shunt connects the two cannulae on the forearm between dialysis sessions and the large arterial blood flow is sufficient to avoid coagulation in the plastic shunt. Dual-lumen venous catheters placed centrally are also in use. An adult patient with acute renal failure requires 4–5 hours dialysis three times a week. If the sodium concentration of the dialysate is too high, the patient complains of thirst and the arterial pressure starts to rise. Low dialysate calcium may result eventually in secondary hyperparathyroidism, whereas a high dialysate calcium concentration causes hypercalcemia.
Renal Transplantation: Suitable patients with chronic renal failure are offered renal transplantation. Rejection of the transplant is due to complement-fixing antibodies in the blood or later caused by cellular or humoral immunity. Rejections that occur years after the transplantation are frequently caused by ischemic damages of the kidney.
Donation of a kidney leaves the donor with only one kidney. Immediately following the kidney removal, the GFR of donor falls to half its original value, because half the functioning nephrons have been removed. Most donors will increase their GFR soon, toward normal values by compensatory work hypertrophy of the remaining kidney. Each remaining nephron must filter and excrete more osmotically active particles than before.
Acute Tubular Necrosis
Acute tubular necrosis results from hemodynamic or toxic causes. Cardiogenic and hypovolemic shock cause acute renal failure similar to renal vasoconstriction. Renal ischemia leads to hypoxic damage of the renal medulla, because of the normally relatively poor oxygenation. Ischemic tubular damage causes tubular blockage with accumulation of filtrate in the early part of the proximal tubules and hypoxic damage of the proximal tubular reabsorption capacity. These together lead to reflex spasms of afferent arterioles and reduced GFR.
This condition is characterized by loss of appetite and energy, nausea and vomiting, nocturia and polyuria. Oliguria is seen only when the GFR is severely depressed. Even a GFR of only 1 mL/min, in contrast to normal 125 mL/min, may result in a daily urine flow of 1,440 mL (if there is a total loss of tubular reabsorption and no luminal obstruction). This urine flow appears normal, but unfortunately there is an almost total loss of glomerular and tubular function. Sufficient regeneration of the tubular epithelium allows clinical recovery.
Sometimes renal cortex also is necrotic and the following healing process and scarring results in glomerulosclerosis. This is also found following radiation nephritis.
One third of all insulin-dependent diabetics develop nephropathy. It is characterized by hypertension, persistent albuminuria and a decline in GFR. The earliest evidence of glomerular damage may occur 5–15 years following microalbuminuria. This is followed by intermittent albuminuria and persistent albuminuria. The mortality rate is high.
In diabetic nephropathy there is glomerulosclerosis and thickening of the basement membrane, as result of disruption of protein cross-linkages of the glomerular filter, which results in glomerular hyperfiltration. Excess nitric oxide (NO) production dilates the afferent arterioles and reduces the arteriolar resistance and increases the glomerular capillary pressure. The interstitial lesions cause ascending infections and patients typically show hypertrophy and hyalinization of afferent and efferent arterioles. Obstruction of the renal blood flow (ischemia) leads to hypoxic damage of the renal tissue.
The relative oversecretion of angiotensin may be involved in the pathogenesis of diabetic nephropathy. This is suggested by the effectiveness of ACE inhibitors therapy, which reduces urinary albumin excretion. The prophylactic therapy postpones the development of diabetic nephropathy and hypertension with persistent microalbuminuria.
The nephrotic syndrome refers to a serious increase in the permeability of the glomerular barrier to albumin, resulting in a marked loss of albumin in the urine. The albuminuria (more than 3 g/day) causes hypoalbuminemia and generalized edema.
The number and size of pores in the glomerular barrier increase due to disruption of protein-linkages. Negatively charged glycoproteins in the glomerular barrier repel negatively charged proteins. The amount of negatively charged glycoproteins is reduced in glomerular disease. Edema is visible in the face—especially around the eyes.
A serious, but rare complication may develop when a large volume of fluid accumulates in the abdominal cavity as ascites.
Urinary Tract Infection
Urination (micturition) is controlled by the micturition reflex. Stretch or contraction of the smooth muscles in the bladder wall is sensed by mechanoreceptors and signaled via the pelvic nerve to the sacral spinal cord. Increased parasympathetic tone (via pelvic nerves and muscarinic receptors) cause sustained bladder contraction. Normally, contraction of the bladder muscles by micturition almost completely empties the bladder.
Recurrent infections of the urinary tract are frequent among females. Fecal bacteria are transferred to the periurethral region and finally to the bladder via the short female urethra. Bladder urine is normally sterile owing to bladder mucosal factors and other local defense mechanisms. Bacteria adhere to the bladder epithelium and multiply, when defense mechanisms function insufficiently. Prolonged bladder catheterization predisposes to bladder infection and even a few days can be critical.
The diagnosis of bladder infection is based on more than 100, 000 bacteria per mL of clean-catch midstream urine. Quite a few patients with significant bacteriuria do not develop nitrite enough to be shown by dipstick tests.
Typical symptoms are frequent micturition (polyuria), painful voiding (dysuria), suprapubic pain and smelly urine perhaps with hematuria.
Escherichia coli (E. coli) and other coliform bacteria cause the majority of urinary tract infections; these infections are treated successfully with antibiotics (amoxicillin, trimethoprim, etc.) either as a single shot or for longer periods.
Bacterial pyelonephritis typically causes interstitial inflammation of the kidneys, but the interstitial inflammation is more often caused by a hypersensitivity reaction to drugs (antibiotics, phenacetin and NSAIDs).
Pyelonephritis begins in the renal pelvis and then progresses into the renal medullary tissue. The essential function of the medulla is to concentrate the urine during water depletion. Therefore, in patients with pyelonephritis, the ability to concentrate the urine is abolished/decreased (isosthenuria/hyposthenuria). The ability to dilute the urine deteriorates also. Thus, in isosthenuria the urine is always isotonic with the plasma.
The patient with acute nephritis has fever, skin rashes and acute renal failure with eosinophiluria and eosinophilia. First of all the offending drug must be withdrawn and the renal failure may require dialysis.
Chronic tubulointerstitial nephritis is caused by pyelonephritis, NSAIDs, diabetes mellitus, hyperuricemia, irradiation damage, etc. The major problem is that long lasting consumption of large amounts of analgesics leads to terminal renal failure. Nephrotoxic analgesics must be abandoned.
The patient presents with uremia, albuminuria, polyuria, hematuria, anemia and most often a history of analgesic abuse. Papillary necrosis can be present with papillary tissue passed in the urine or obstructing the ureter or urethra. In patients with tubular damage of the renal medulla, the ability to concentrate the urine is abolished together with the ability to dilute the urine. Thus, the urine is always isotonic with the plasma (isosthenuria). The result is polyuria and salt wasting. As the inflammation progresses to the cortex the glomerular filtration deteriorates with accumulation of non-protein nitrogen in the plasma water (azotemia) and the clinical syndrome uremia.
An isolated damage of the Na+ reabsorption (salt-losing nephritis) is a condition in which the disease processes are mainly due to dysfunction in the renal medulla. There is a marked loss of Na+ in the urine and seriously low extracellular volume (ECV) and blood volume (hypovolemia with threat of imminent shock). Thus the patient must have a high salt intake to prevent shock and other complications.
Acute hyperuremic nephropathy occurs in patients, where the condition leads to rapid destruction of cell nuclei (at the start of treatment for malignant disorders or obesity). Large quantities of nucleoproteins are released and the production of uric acid is increased. The urate concentration increases in the ECV. Above a critical concentration of 420 mmol, the urate precipitates in the form of uric acid crystals, provided the fluid is acid. This concentration threshold defines hyperuricemia.
Precipitation in the joints with pain is termed gout (arthritis urica) and precipitation of uric acid crystals also occurs in the tubules, the collecting ducts and the urinary tract. Normally, urate ions are actively reabsorbed in the proximal tubules by a Na+ cotransport. Urate ions can also be actively secreted from the blood to the tubular fluid.
Allopurinol is prescribed during radiotherapy or cytotoxic therapy. Acute cases are also treated with allopurinol and forced alkaline diuresis.
Uric acid stones are found in patients with hyperuricemia and in patients secreting sufficient urate without hyperuricemia. Calcium stones may be formed around a nucleus of uric acid crystals.
Bilateral renal disease such as chronic glomerulonephritis is a frequent cause of hypertension, whereas unilateral renal disease, such as renal artery stenosis, is a fairly seldom cause of hypertension. Stenosis (narrowing of the lumen) of one renal artery, leads to renal hypotension with excess renin production and systemic (secondary) hypertension.
Exposure to fluid loss, reduced glomerular propulsion pressure and increased sympathetic activity releases renin from the juxtaglomerular cells in the afferent glomerular arteriole, so the renin-angiotensin-aldosterone cascade is triggered (Fig. 10.7).
Angiotensin II stimulates the aldosterone liberation from zona glomerulosa of the adrenal cortex, and thus stimulates Na+ reabsorption and K+ secretion in the distal tubules.
The result is salt and water retention with increase in blood volume and blood pressure. Angiotensin II also constricts arterioles, with an especially strong effect on the efferent renal arteriole. This reduces the renal blood flow further and also the proximal reabsorption. The development of hypertension in high renin states is mainly due to salt-retention and systemic vasoconstriction.
Stenosis of one renal artery does not always lead to increased erythrogenesis. Stenosis of the renal artery implies less renal blood flow, less glomerular filtration and less NaCl reabsorption with related small oxygen consumption on the affected side. As long as the renal oxygenation is sufficient, the erythropoietin production is normal.
Severe renal artery stenosis implies renal ischemia and hypoxia, which is probably always consequential with complications. A hypoxic kidney has a low creatinine and PAH clearance.
A long-term increase in sodium intake results in changes of the kidney function. Surprisingly, the changes are similar in hypertensive and normotensive humans. Most people increase their ECV and GFR without changing the absolute reabsorption rate of Na+ and water in the proximal tubules. Therefore, the rise in filtration rate of Na+ and water will reach the loop of Henle and the distal tubule. The arterial blood pressure and heart rate is unaffected by the amount of sodium in the diet. The plasma concentrations of active renin angiotensin II and aldosterone decrease with increasing Na+ intake, but atrial natriuretic factor (ANF) and cyclic guanosine monophosphate (GMP) increase. Arginine vasopressin [antidiuretic hormone (ADH)] in plasma does not change.
The reason why this increase in NaCl load to the loop of Henle is not counterbalanced by the tumor growth factor (TGF) system is due to resetting of the TGF mechanism, so a contraction is avoided in spite of the increased salt load. These homeostatic reactions are all appropriate physiological responses in both healthy and hypertensive humans.
A rare cause of renal hypertension is Liddle’s syndrome. This is an autosomal dominant defect characterized by severe hypertension, hypokalemia and metabolic alkalosis. The syndrome is similar to primary hyperaldosteronism, but the renin-aldosterone concentration in plasma is not increased. Liddle’s syndrome is caused by mutation of the gene for the amiloride-sensitive Na+ channel, whereby the channel is wide open. The Na+ entry depolarizes the membrane and favors secretion of K+ and H+.
Urinary Tract Obstruction
Obstruction of the urinary tract may occur at any location and cause dilatation of the above structures. The obstruction is localized within the lumen (stone, sloughed papilla or tumor), within the wall (neuromuscular dysfunction, stricture, congenital urethral valve or pin hole meatus), or pressure from the outside obstruct the tract (e.g. tumors, diverticulitis, aortic aneurysm, prostatic obstruction, retrocaval ureter).
Stretching of the renal calyces as they collect urine promotes their pacemaker activity and initiates peristaltic contraction along the smooth muscle syncytium of the urinary tract.
Obstruction of the urinary tract for weeks may lead to irreversible damage of the renal function in particular when combined with infection. Obstruction of the upper urinary tract with backpressure damage of the kidney is especially dangerous.
Kidney stone disease (nephrolithiasis) attacks only a few percent of the Western population at anytime. Most stones in male patients are composed of calcium complexed with oxalate and phosphate, whereas magnesium, ammonium, phosphate/acetate stones are more common in females. Only a few percent of all renal stones are composed of uric acid crystals or cysteine (mainly in children). Calcium containing and cysteine stones are radiopaque, whereas stones of pure uric acid are radiolucent.
In the presence of infection with urea-splitting bacteria, urea is hydrolyzed to form the strong base ammonium hydroxide:
CO(NH2)2 + H2O ➔ 2NH3 + CO2
NH3 + H2O ➔ NH4+ + OH–
Alkaline urine favors stone formation by crystallization in the supersaturated fluid. Magnesium ammonium phosphate stones are also termed mixed infection stones.
Obstruction or spasm of the ureter causes reflex constriction around the stone with ureteric or renal colic pain. The pain is an excruciating flank pain, with radiation to the iliac fossa and the genitals. The wall of the ureter is innervated with sensory nerve fibers running in the pelvic nerves. Renal colic is considered to be one of the most severe pain experience known. Excretion urography and plain X-ray examination are important in the diagnosis of renal stone disease.
Percutaneous nephrolithotomy, pyelolithotomy or ureterolithotomy can avoid many cutting operations. Also shock-wave disintegration is in use (lithotripsy).
Nephrocalcinosis refers to diffuse renal calcification that is detectable on a plain abdominal X-ray. Patients with hypercalcemia (e.g. primary hyperparathyroidism, hypervitaminosis D and sarcoidosis) or with hyperoxaluria precipitate calcium oxalate and calcium phosphate in the renal parenchyma. In patients with renal tubular acidosis urine fails to get acidified, which favor precipitation of calcium oxalate and phosphate.
A plain X-ray can identify calcification at any site including the renal system.
An organic iodine-containing contrast substance is injected slowly. Serial X-rays are taken, while compression bands are applied to the abdomen in order to obstruct ureteral emptying. Hereby, the upper renal tract is distended by the excreted contrast medium. Following removal of the compression bands, the rate of excretion of contrast is studied with films before and after voiding.
Tumors of the Kidney
Benign and malignant tumors occur in the kidney.
Benign renal fibroma, cortical adenomas or simple cysts seldom cause symptoms and signs. Those of no clinical importance are found incidentally at autopsy. Juxtaglomerular cell tumors are seldom. They produce large amounts of renin, which causes hypertension.
Hemangioma may bleed following trauma and cause fatal blood loss.
Malignant renal tumors are nephroblastoma and renal cell carcinoma.
Nephroblastoma (Wilms´ tumor) is the most frequent intra-abdominal tumor in both girls and boys. It usually presents within the first 3 years of life. A large abdominal mass is found sometimes with signs of intestinal obstruction. The tumor grows rapidly and spread to the lungs. The diagnosis is confirmed with excretion urography, arteriography or scanning.
Radiotherapy and chemotherapy, combined with nephrectomy have improved the long-term survival rate.
Renal cell carcinoma (hypernephroma) accounts for more than 90% of all the malignant renal tumors in adults—in particular smokers. There is a strong association with a rare autosomal dominant inherited disease called von Hippel-Lindau syndrome (hemangioblastomas in the cerebellum and the retina). The genetic locus is on chromosome 3p. The tumor arises from proximal tubular epithelium and lies within the kidney, but the prognosis is worse, if the tumor penetrates the renal capsule. The tumor is often protruding and the neoplastic cells have an unusually clear cytoplasm.
Renal cell carcinoma is a likely source of ectopic hormone production. Increased production of erythropoietin leads to erythrocytosis and polycythemia. Release of parathyroid hormone-like substance leads to hyperparathyroidism and hypercalcemia. Release of abnormal quantities of renin triggers the renin-angiotensin-aldosterone cascade and leads to systemic hypertension. Metastasis to distant regions are frequently found in the lungs and in the bones (osteolytic metastasis). Solitary tumors are treated by partial or total nephrectomy or with interferon.
The nervous and endocrine systems are the main control systems of the body. The nervous system controls processes requiring fast responses such as muscle movement. The endocrine system exerts its influence on processes generally requiring long-term control such as growth and reproduction.
The endocrine system produces chemical messengers called hormones in special glandular tissue. The hormones are released and travel in the blood to target cells and tissues, where they exert their effects.
The endocrine system consists of endocrine glands (ductless glands), which secrete hormones directly into the bloodstream. Hormones are the chemicals that circulate in the bloodstream and affect many types of body cells.
A gland is an organ that consists of cells, which secretes materials into other regions of the body. The human body has two types of glands called exocrine and endocrine glands (Fig. 11.1):
Exocrine glands secrete non-hormonal chemicals into ducts, which are transported to a specific location inside and outside the body. The examples are sweat glands, mucous glands, salivary glands and other digestive glands.
Endocrine glands are ductless glands that are located throughout the body. They secrete hormones into the bloodstream through the fluid that surrounds them.
Hormone is defined as a chemical signal, which regulates the body’s activities. Its site of action is different from the site of synthesis. Hormones are secreted in small amounts into the bloodstream and they influence the activity of distant cells.
Some organs, which are not considered as endocrine glands, also produce hormones. The brain and kidney are two such organs that produce hormones.
Hormones secreted into blood travel to a specific tissue or organ called target cells, where they elicit a specific response.
Hormones are essential for maintaining homeostasis.
The endocrine system works hand-in-hand with the nervous system to:
Maintain the body’s internal steady state-homeostasis (nutrition, metabolism, excretion, water and electrolyte balances)
React to stimuli from outside the body
Regulate growth, development and reproduction
Produce, use and store energy.
The endocrine and nervous systems are so closely linked that they are often considered a single system—the neuroendocrine system.
Both nerve impulses and hormones elicit a response, but they differ in the following ways:
Nerve impulses prompt a nearly instantaneous response to a change in the environment
Hormones on the other hand are released more slowly than nerve impulses, but their effects usually last longer
Effects of some hormones can last 10–20 minutes. Some hormones can last for several hours.
TYPES OF HORMONES
Hormones fall under two general categories:
Steroid hormones that are synthesized from cholesterol.
Steroid hormones are produced by adrenal cortex, ovaries and testes. They do not bind with the plasma membrane receptors of the target cells (Fig. 11.2). They can freely enter the cell and the cell nucleus. Once in the cytoplasm, a steroid hormone binds with a receptor protein to form hormone-receptor complex that enter the cell nucleus and bind to deoxyribonucleic acid (DNA), where it will trigger changes in the chromosomes to produce specific proteins. The classical examples are male sex hormone (testosterone) and the female sex hormones (estrogen and progesterone).
Peptide hormones (amino acid-based hormones) are polar molecules (possess both positive and negative ends), hence cannot pass (diffuse) through the plasma membrane of their target cells and must send their message from outside the target cell. Most of these hormones require a two-messenger system for the action (Fig. 11.3).
Peptide hormones are the first messengers that attach to receptors on the plasma membrane. In the second step the message is passed on to another molecule inside the cytoplasm to generate a second messenger. In many cases, the hormone-receptor complex indirectly activates an enzyme that converts molecules of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) inside the target cell. The cAMP acts as a second messenger by indirectly activating other enzymes and proteins in the target cell. Thus, cAMP initiates a chain of biochemical events that leads to functional changes within the target cell. Binding of a single molecule of hormone to a receptor on the cell membrane can generate the formation of many second messenger molecules.
Prostaglandins are a group of hormone-like lipid molecules that are also involved in regulation of cell activities. Features are the following:
Unlike hormones, prostaglandins are not produced by specific endocrine glands, but are produced in small quantities by many cells throughout the body
Rather than being transported through the blood to distant regions of the body, prostaglandins act locally
Their effects include relaxation of smooth muscles that line the air passageways and blood vessels, regulation of blood pressure, contraction of the intestinal walls and the uterus, and stimulation of the body’s inflammatory response to infection.
MECHANISM OF HORMONAL ACTION
Why is it that only certain cells and tissues respond to the stimulation of specific hormones? For example, why does antidiuretic hormone (ADH) cause the tubules of the nephron to reabsorb water, but appears to have no influence on the digestive system?
Hormones communicate with cells by binding to receptors on the cell membrane or inside the cell. Certain cells express specific receptors. For example, the tubules of the nephron express receptors to ADH, which is why ADH has an effect on those particular cells. Cells of the digestive system do not express ADH receptors and so are unaffected by the hormone.
The mechanisms of hormonal action depends on the following:
A hormone does not seek out a particular organ, but the organ is awaiting the arrival of the hormone.
Cells that can react to a hormone have specific receptor proteins on their plasma membrane or in their cytoplasm that combine with the hormone in a ‘lock-and-key’ manner; the specific shape of the hormone must match the specific shape of the receptor protein.
Receptors are proteins that are located both inside the cytoplasm and on the surface of a target cell.
Fitting the hormone molecule into the receptor changes the receptor’s shape, which causes the cell’s activities to change.
The main effect of a hormone on a cell is to change the activity or amounts of enzymes (speed up chemical reactions) present in that cell.
The endocrine system responds and adjusts to changes that occur in and outside the body by feedback mechanism. In a feedback mechanism, the last step in a series of events controls the first step.
Homeostasis is defined as a stable internal environment. The endocrine system plays an important role in the maintenance of homeostasis because it affects the activities of cells, tissues and organs throughout the body.
To maintain homeostasis, hormone secretions must be tightly regulated. Most hormones are controlled by feedback mechanisms:
Some hormone systems use negative feedback in which release of an initial hormone stimulates release or production of other hormones or substances that subsequently inhibit further release of the initial hormone.
Some other hormone systems use positive feedback in which release of an initial hormone stimulates release or production of other hormones or substances that stimulates further release of the initial hormone.
Negative feedback mechanisms (regulating hormone release)
The body produces more than 30 hormones; therefore it must be able to regulate the release of these hormones. This is achieved by negative feedback mechanisms; a process by which a change in an environment causes a response that returns conditions to their original state, which helps maintain hormone concentration at a certain level. This process involves interactions of the nervous, endocrine and circulatory systems by which the final step in a series of events inhibits the initial signal in the series. The examples of negative feedback mechanism are the hypothalamus, the anterior pituitary and the endocrine glands controlled by it, which are all involved in a self-regulating negative feedback mechanism. Most endocrine glands help the body to maintain homeostasis, in a way similar to a thermostat maintains temperature.
Antagonistic hormones have an opposite effect on the body. A good example is insulin and glucagon, which function opposite to each other, and help maintain blood glucose levels within normal range.
Endocrine glands are located throughout the body and regulate many of its vital processes. This section discusses the hormones that each endocrine gland produces, their effects on the body (Table 11.1) and the relationship between the hypothalamus and the pituitary gland.
The hypothalamus is the part of the brain and nervous system that regulates body temperature, breathing, hunger and thirst. Located beneath the thalamus in the brain, it regulates our body’s internal environment.
The hypothalamus can also be considered the master switchboard for the endocrine system. The hypothalamus regulates the two lobes of pituitary gland by releasing or releasing-inhibiting hormones.
The hypothalamus links the nervous system to the endocrine system.
Neurosecretory cells of the hypothalamus produce hormones that either are stored in the pituitary gland or regulate the pituitary’s activity.
The hypothalamus is continuously checking (monitoring) conditions inside our body.
If our internal environment (homeostasis) starts to get out of balance, the hypothalamus has several ways to set things right again by sending out a nerve signal to another part of the brain—the medulla to speed up or slow down our heart rate or send out commands in the form of hormones, thus acting like an endocrine gland.
Table 11.1 Endocrine glands and their functionsHormoneTargetFunctionsAdrenal glandCortexAldosteroneCortisolMaintains salt and electrolyte balanceRegulate carbohydrate and protein metabolismMedullaEpinephrine and norepinephrineInitiate body’s response to stress and the ‘flight or fight’ response to dangerOvariesEstrogen and progesteroneRegulates female secondary sex characteristics, maintains growth of uterine liningPancreas (islets of Langerhans)GlucagonInsulinStimulates release of glucoseStimulates absorption of glucoseParathyroid glandsMelatoninRegulates sleep patternPituitary glandTestesAndrogens (testosterone)Regulates male secondary characteristicsThymus glandThymosinStimulates T cell formationThyroid glandThyroxine and triiodothyronineIncreases cellular metabolic rates
The hypothalamus and the pituitary gland are the primary regulators of the endocrine system.
Pituitary gland (hypophysis cerebri) is a small gland, is about 1 cm in diameter is connected to the hypothalamus by a stalk-like structure (Fig. 11.4). The gland is situated at the base of the brain in a saddle-shaped depression in the sphenoid bone known as sella turcica. The small stalk of pituitary is placed just behind the optic chiasma, where the optic nerves from each eye meet.
The pituitary has two portions called posterior and the anterior lobe; each has developed from different tissues and has different functions. Both the lobes are under the control of hypothalamus, but by different mechanisms. a neural mechanism between the hypothalamus and pituitary controls the secretions from the posterior lobe. The secretions of the anterior lobe is controlled by stimulatory and inhibitory hormones secreted by the hypothalamus, which are secreted into the portal venous system that runs in the pituitary stalk and carried into the anterior pituitary lobe.
Posterior Pituitary Lobe
The posterior pituitary stores two hormones (Table 11.2), vasopressin or ADH and oxytocin, both of which are produced by and released from the hypothalamus along the neural pathways.
Antidiuretic hormone or vasopressin causes the kidneys to form more concentrated urine, conserving water. Thus, the kidneys produce small quantity of urine with high solute concentration. The main function of vasopressin is to maintain normal plasma osmolality in the range of 270–290 mOsm/L and plasma volume. Its release is regulated by osmoreceptors in the hypothalamus and stretch receptors in the walls of the atria and great veins. Low plasma volume and high plasma osmolality stimulates the release of vasopressin, which conserves water. Vasopressin release is inhibited by emotional stress, pain and alcohol consumption.
Oxytocin stimulates contractions of the smooth muscles of the uterus during labor and also causes the contraction of smooth muscles of the breast to release milk from the breast of a nursing mother.
Oxytocin is used to induce labor. Vasopressin is used in the treatment of diabetes insipidus.
Anterior Pituitary Lobe
The anterior lobe of pituitary gland is sometimes called master gland because it controls the secretion of other endocrine glands. The anterior lobe of pituitary secretes at least seven hormones (Table 11.3), which have an effect on other endocrine glands. Their formation and releases are under the control of releasing factors (hormones) that are produced and secreted by neurosecretory cells in the hypothalamus. The other hypothalamic cells produce release-inhibiting hormones, which inhibit production and secretion of the anterior pituitary hormones.
The releasing hormones and release-inhibiting hormones are produced in response to various stimuli that are processed by the nervous system. There is at least one releasing hormone for each anterior pituitary hormone.
Growth hormone (GH) or somatotropin stimulates the liver to synthesise somatomedins, which promote cell division, protein synthesis, and bone and muscle growth. It antagonizes the action of insulin on carbohydrate metabolism. A release of GH is inhibited by somatostatins synthesized in the hypothalamus and pancreatic islets.
Oversecretion of GH during childhood will result in gigantism; excessive growth in the length of bones. Hypersecretion of GH in adults lead to acromegaly; enlargement of bones and soft tissues.
Undersecretion during childhood results in stunted growth, which can be treated by administration of GH before the closure of epiphyseal fusion.
Prolactin (PRL) causes mammary gland in breast to develop and produce milk. It also plays a role in carbohydrate and fat metabolism. Serum prolactin levels are normally elevated during lactation. A pathologically elevated PRL level is one of the causes of infertility in women.
Melanocyte-stimulating hormone stimulates the melanocytes of the skin, increasing their production of the dark pigment melanin.
Thyroid-stimulating hormone (TSH) regulates the thyroid to produce and release thyroxine and triiodothyronine.
Adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex, and causes it to produce and release cortisol and aldosterone. There is a diurnal variation in the secretion of ACTH, resulting in plasma cortisol levels being at their peak at about 6 AM and at their lowest at about midnight. This fact forms the basis of a screening test for Cushing’s disease in which there is hypersecretion of cortisol and the diurnal variation is lost.
Gonadotropic hormones include follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which stimulate the gonads; the testes in males and the ovaries in females. It causes the gonads to secrete sex hormones and stimulate gamete (sperm and ovum) production.
Thyroid gland is located at the base of the neck just below the larynx (Fig. 11.5). It has two lobes one on each side of the trachea, joined together by isthmus, which passes in front of the trachea just below the cricoid cartilage. The lobes are conical in shape with upper and lower poles. The upper pole extends up to the side of the thyroid cartilage. It receives blood supply from the superior and inferior thyroid arteries, which are the branches of external carotid and subclavian arteries, respectively. The recurrent laryngeal nerve lies in close relationship to the thyroid gland in the groove between the trachea and esophagus on each side of the neck. The recurrent laryngeal nerve may be damaged during surgery or carcinoma of thyroid that results in hoarse voice.
The thyroid contains two types of cells, the follicular cells that produce thyroid hormones (T3 and T4), and the C cells that produce calcitonin. The shape of the follicular cells depends on whether they are stimulated or not by TSH, released from the pituitary gland. Thyroid glands can store large quantities of thyroid hormones in an inactive form called colloid that contain thyroglobulin within follicles that are lined by follicular cells. These cells convert thyroglobulin to T4 and T3, which are released into the bloodstream. Thyroxine is the main hormone released from the thyroid gland, but by itself is relatively inactive. The active form is T3, which exerts its action on the cells and regulate the basal metabolic rate, normal heart rate, blood pressure, body temperature, growth and maturation, particularly that of nervous tissue.
Calcitonin (C cells or Parafollicular Cells)
Calcitonin inhibits release of calcium from bones or regulates the level of calcium in the blood. Its secretion is solely regulated by the blood calcium levels.
In order to produce T3 and T4, the thyroid gland requires iodine. TSH released from anterior pituitary gland stimulates follicular cells to trap iodine for the synthesis of thyroid hormones. In turn the release of TSH is stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. The feedback mechanisms regulate the releases of TSH and TRH (Fig. 11.6).
Goiter is the swelling of the thyroid gland as a result of iodine deficiency, which can be treated by providing iodized salt. Decreased levels of T4 causes a decrease in the cellular respiration rate, cells produce less energy and become less active.
Hyperthyroidism is the overactivity of thyroid gland that produces too much thyroxine, which results in thyrotoxicosis; nervousness, hot moist hands, elevated body temperature, increased heart and metabolic rates, increased blood pressure, weight loss and in some cases it may cause exophthalmia (protrusion of eyeballs). Hyperthyroidism can be treated with medication or by surgical removal of part of the thyroid gland.
Hypothyroidism is caused by the underactivity of thyroid glands (not enough thyroxine). It causes cretinism in children and myxedema in adults. Decreased hormone production results in lower metabolic rates (lethargy), lower body temperature, lack of energy, dry and thick skin, and gain of body weight. In some cases it is associated with goiter or enlargement of the thyroid gland. Hypothyroidism can be treated with supplementary thyroxine.
Hypothyroidism in infants: It affects normal development of the skeleton, muscular and nervous systems and results in a condition called cretinism. Cretinism is characterized by dwarfism and mental retardation.
Parathyroid glands are four in number. These are small ovoid glands (smaller than pea) that lie on the posterior surface of the thyroid gland (refer Fig. 11.5). They are usually in two pairs called superior and the inferior pairs, attached to or embedded in the posterior surface of the thyroid gland, two in each lobe. Characteristics of parathyroid gland are as follows:
The chief cells of the parathyroid glands produce parathyroid hormone (PTH)/parathormone, which regulates the calcium levels in the blood by increasing the reabsorption of calcium in the kidneys and by increasing the uptake of calcium from the digestive system.
Parathyroid hormone is important in promoting proper nerve and muscle function as well as maintaining bone structure.
Loss of parathyroid causes a drop in the level of calcium in the blood, which may result in violent muscular spasms known as tetany.
Tetany can be relieved by the administration of large amounts of PTH and injections of calcium.
Adrenal Glands (Cortex and Medulla)
There are two adrenal (suprarenal) glands, which are flat, small yellowish bodies situated on top of the upper lobe of each kidney (Figs 11.7A and B). Each gland measures about 5 cm in height, 3 cm wide and 1 cm thick. The adrenal glands require a large supply of blood and release hormones directly into the bloodstream. The adrenal glands are among the most extensively vascularized organs in the body. Three sources of arteries maintain blood supply to the adrenal glands. The superior suprarenal arteries are multiple small branches from the inferior phrenic artery, whereas the middle suprarenal artery is a direct branch from the abdominal aorta. An inferior suprarenal artery, sometimes multiple, arises from the renal artery on each side. After the adrenal glands have been supplied with blood from these arteries, the blood drains through the suprarenal vein to the left renal vein or directly to the inferior vena cava on the right side. The dark interior (medulla) of the gland is composed of sympathetic nerves arising from celiac plexus. The outer part (cortex) of the gland is yellowish (rich in lipids) and has entirely different functions other than the medulla (refer Figs 11.7A and B).
The outer portion makes up 80% of the mass of the gland. Adrenal cortex secretes more than two dozen hormones that are derived from cholesterol and belong to the class of steroid hormones called corticosteroids. These hormones fall into three main groups depending on their main effect. They are aldosterone, cortisol and sex hormones.
The adrenal cortex produces corticosteroids in response to ACTH, which is secreted by the anterior pituitary gland.
Aldosterone (mineralocorticoid) acts on the collecting tubules of the kidney and regulates the reabsorption of sodium and the excretion of potassium. This affects water and salt balance in the body.
Cortisol (glucocorticoid) affects carbohydrate, protein and fat metabolism. It also helps people to cope with stress. The main effects of cortisol are as follows:
Increased output of glucose from liver into the blood
Increased breakdown of proteins
Liberation of fatty acids from the adipose tissue and its redistribution
Suppression of growth hormone release and activity
Decreases eosinophils from the circulation
Immunosuppression and suppression of inflammatory reaction
Enhancement of water diuresis.
Sex hormones (androgens and estrogens) are produced in small quantities, which influence the sexual development and growth. In females adrenal cortex is the source of androgens that are required by both sexes for normal pubertal and skeletal development.
Addison’s disease (hypoadrenalism) is the hypoactivity or decreased activity of the adrenal cortex. It is characterized by weight loss, low blood pressure, general weakness, brown pigmentation of skin and mucous membrane, excessive loss of sodium from the body leading to hyponatremia and dehydration. Death may occur because of heart failure. Administering regular doses of adrenal cortical hormones treats people with Addison’s disease.
Cushing’s syndrome (hyperadrenalism) is the increased activity of the adrenal cortex. It is characterized by obesity with a lemon on toothpicks distribution and a buffalo hump, rounding of the face (moon faced), increase blood sugar levels, high blood pressure and weakening of bones. Treatment involves decreasing the secretion of hyperactive hormone, if possible.
Medulla or the inner portion of adrenal gland is a specialized part of the sympathetic nervous system. It secretes two amino acid based hormones called catecholamines (neurohormones); adrenaline (epinephrine) and noradrenaline (norepinephrine), whose secretion is controlled by sympathetic nervous system in response to fight or flight mechanism.
Adrenaline is more powerful in its actions and makes up 80% of the total secretion. It increases heart rate, causes constriction of arterioles in the body resulting in a rise in blood pressure and blood supply to skeletal muscles, increases the conversion of glycogen to glucose and stimulates the rate of metabolism. They also relax involuntary muscles of the bronchi. These hormones are poured into the bloodstream during fear or anger and they are responsible for many of the changes that accompany emotions.
Noradrenaline stimulates the heart muscle, increases rate and strength of heartbeat, which helps better circulation and supply of fuel to both muscles and brain.
Pheochromocytoma is a tumor of the adrenal medulla, which is rare, but an important cause of hypertension. This condition is treated by surgical removal of the tumor.
The ovaries in females and the testes in males are gamete producing organs that also produce a group of steroid sex hormones. Sex hormones regulate body changes that begin with puberty. Puberty is the adolescent stage during which the sex organs mature and secondary sex characteristics such as facial hair appear. The secretion of LH and FSH by the anterior pituitary gland stimulates the secretion of sex hormones from the gonads.
The ovaries produce ova and sex hormones that affect cells throughout the body. The female sex hormones include estrogens and progesterone.
Estrogens are required for the development of ova and for the formation of the physical characteristics (secondary sex characteristics) associated with the female. These characteristics include the development of the female reproductive system, beginning of the menstrual cycle, widening of the hips and development of the breast. The earliest sign of pubertal change is the growth of hair in the axilla.
Progesterone prepares the uterus for the arrival of a developing embryo and controls the menstrual cycle.
The testes produce sperm and sex hormones that affect cells throughout the body. Testes produce androgens or the male sex hormone. Testosterone is an androgen that regulates male secondary sex characteristics.
Androgens are required for normal sperm production and the development of physical characteristics (secondary sex characteristics) associated with the male. The earliest sign of pubertal change is the growth of hair in the axilla. These characteristics include the growth of facial hair, increase in body size and deepening of the voice.
Pancreas is located just behind the stomach. It is both an exocrine (ducts) and endocrine gland. The hormone producing portion of the pancreas consists of clusters of cells that resemble islands, called islets of Langerhans (Fig. 11.8). Each islet is composed of β-cells that secrete insulin, α-cells that secrete glucagon and δ-cells that produce somatostatin.
Insulin and glucagon regulate the metabolism of blood glucose (sugar) and because of their opposite effects they are, therefore called antagonistic hormones (Fig. 11.9).
Insulin stimulates its target cells by acting on cell membrane receptors and enhances the entry of glucose into most cells (exception hepatic cells), thereby lowering blood glucose levels.
Within the cells insulin enhances the conversion of glucose to glycogen, promotes protein synthesis and inhibits breakdown of fats. Insulin deficiency leads to breakdown of glycogen, proteins and fats, which leads to hyperglycemia and ketoacidosis. Ketone bodies are acetoacetic acid, β-hydroxybutyric acid and acetone, which are derived from the breakdown of fatty acids. Hence, insulin is involved in ‘use or store’ of energy yielding macromolecules. When there is an under secretion of insulin, due to diseases of islets of Langerhans, a condition called diabetes mellitus occurs.
Glucagon stimulates its cells to breakdown stored glycogen and lipolysis, thereby increases the glucose level in the blood.
Normally the blood glucose level remains within a range of 60–100 mg/dL. Any excess of glucose is stored as glycogen in the liver and some extent in muscles. If the blood glucose level increases above its normal or the renal threshold (180 mg/dL) it is excreted in the urine (glycosuria). However, some individuals have low renal threshold and excrete glucose in urine, this condition is called renal glycosuria or physiological glycosuria.
Type I or juvenile onset diabetes mellitus ocurs before the age of 25 years. It is characterised by little or no insulin production and requires a strict diet and daily infections of insulin.
Type II or adult onset; diabetes mellitus occurs after the age of 40 years. Normal amount of insulin one produced in this condition but the cells are unable to respond properly because of lack of insulin receptors. It can be controlled by diet.
Hypoglycemia caused by excess (high) insulin or low blood sugar, a disorder in which glucose is stored rather than being properly delivered to the cells of the body—causing cells from starvation to death. This leads to a lower blood glucose concentration and subsequent release of glucagon and epinephrine (adrenaline). Symptoms of hypoglycemia include lethargy, dizziness, nervousness, overactivity and in extreme cases, unconsciousness (ketoacidosis or diabetic coma) and death. To assist someone with this problem, provide him/her some sugar, such as glucose.
Hyperglycemia caused by low insulin or high blood sugar can cause nausea and rapid breathing, possibly leading to oxygen deficiency, circulatory and nervous system failure, diabetic coma or even death.
The thymus gland is located beneath the sternum (breastbone) and between the lungs. It consists mostly of T cells and plays a role in the development of the immune system. The thymus gland secretes thymosin, an amino acid based hormone that stimulates the formation of T cells, which helps in defending the individual from pathogens.
The pineal gland (Fig. 11.10) is located near the base of the brain. The pineal gland secretes the hormone melatonin. Serum concentration of melatonin increase sharply at night and decrease dramatically during the day (diurnal variation). This cyclic release of melatonin indicates that it helps regulate sleep.
Endocrine cells within the walls of some digestive organs also secrete a variety of peptide hormones that help to digest food. When food is eaten, endocrine cells in the stomach lining secrete gastrin, a hormone that stimulates other stomach cells to release digestive enzymes and hydrochloric acid. Endocrine cells of the small intestine release secretin, a hormone that stimulates the release of various digestive fluids from the pancreas and bile from the liver.
Some of them are present in both gastrointestinal tract (GIT) and within nervous system, where they appear to function as neurotransmitter, hence they are known as brain gut hormones. Examples are enkephalins, somatostatin and vasoactive intestinal peptide (VIP).
The circulatory system is a transport system that comprises of blood, heart and an extensive network of vascular system (blood vessels).
The blood is the vehicle to transport:
Nutrients, oxygen and hormones to various tissues
Carbon dioxide to the lung
Other waste products to the kidney
Toxic substances to the liver for metabolism.
The heart is a muscular pump that has two pumps:
The right side of the heart pumps deoxygenated (venous) to the lungs for elimination of carbon dioxide with simultaneous oxygenation. The left side of the heart pumps the oxygenated (arterial) blood to all organs and tissue of the body.
Venous return of the blood to the heart is by gravity, skeletal muscle activity that squeezes the veins and the inspiratory phase of breathing that sucks the blood toward the thorax.
The vascular system is made up of arteries and their terminal branches the arterioles, veins and their tributaries the venules. Functions are as follows:
Arteries and arterioles distribute blood throughout the body.
Venules and veins collect blood from all over the body.
A network of capillaries between the arterioles and venules provide an environment for exchange of materials. For example, capillary network means organs like the lungs and intestines adds materials to the blood and organs like the lungs and kidneys remove materials from the blood and deposit them back into the external environment.
The oxygenated blood pumped from the left ventricle under high pressure into the aorta is distributed by arteries to all parts of the body, which branches out to narrow arterioles. They in turn branch out to narrow capillaries, whose diameter is approximately that of an erythrocyte. The walls of capillaries are made of only one layer of cells with small spaces between them through which leukocytes can escape by their ameboid movement. It is only through capillaries that the nutrients, water, oxygen, carbon dioxide and metabolic wastes equilibrate between the blood and interstitial fluid.
The capillaries are continuous with venules, which unite to form veins that form superior and inferior vena cava. The deoxygenated blood carried from throughout the body is drained into the right atrium by superior and inferior vena cavae.
The deoxygenated blood is pumped from the right ventricle into the lungs, where the carbon dioxide carried by the blood is exchanged for atmospheric oxygen. This gaseous exchange may be severely affected in lung diseases such as pulmonary edema and fibrosis. Such individuals show signs of cyanosis (blueness of nail beds and mucous membrane). The capillaries in the lungs are continuous with venules and veins to form pulmonary veins that drain oxygenated blood to the left atrium. It should be remembered that in contrast to systemic circulation, the pulmonary veins carry oxygenated blood and the pulmonary artery carries deoxygenated blood.
Deoxygenated blood from the body enters the right atrium.
It flows through the tricuspid valve into the right ventricle. The term tricuspid refers to the three flaps of tissue that make up the valve.
Contraction of the ventricle then closes the tricuspid valve and forces open the pulmonary valve.
Blood flows into the pulmonary artery.
Pulmonary arteries branches immediately carrying blood to the right and left lungs.
Pulmonary artery branches out to arteries, arterioles and capillaries to reach the alveoli of the lungs.
It is here in the alveolar-capillary membrane that the blood gives up carbon dioxide and takes on a fresh supply of oxygen.
The capillary beds of the lungs are drained by venules that are the tributaries of the pulmonary veins.
The heart is the central organ of the cardiovascular system. The heart is a hollow, muscular organ that contracts at regular intervals, forcing blood through the circulatory system (Fig. 12.1). It is cone shaped, about the size of a fist and weighing about 250–300 g.
It is located in the thoracic cavity between the lungs and immediately above the diaphragm. It is directly behind the sternum (breastbone), adjoining costal cartilage and ribs, two-third of it is lying to the left of the median plane. The heart is tilted so that the apex (the pointed end) is oriented to the left and is normally within the left midclavicular line; a line drawn on the chest wall from the midclavicular point on the left clavicle and running parallel with the median plane or midline of the sternum. In cardiac enlargement and lung diseases, the apex may be shifted more to the left. In dextrocardia, the apex of the heart is located on the right side of the chest.
The heart has four chambers; two atria that act as receiving chambers and two ventricles that act as pumping chambers. The atria are thin walled and ventricles are thick walled. The left ventricle has thicker wall and contracts more forcefully. The left ventricle contracts slightly in advance of the right ventricle and its ejection phase is shorter. Therefore, the heart sounds are double.
The walls of the heart are made up of three layers of tissue. The outer and inner layers are epithelial tissue. The middle layer (the walls of the four chambers of the heart) is cardiac muscle tissue called myocardium. Cardiac muscles are not under conscious control of the nervous system. Cardiac muscles have a rich supply of blood, which ensures that they get plenty of oxygen.
The cardiac muscle fibers are aligned in a spiral around the heart that is due to the complex twisting, which takes place during embryological development. This arrangement means that contraction of the heart is in a ‘wringing’ motion, which ensures that blood is emptied from the heart with the maximum efficiency. Unlike smooth and striated skeletal muscles, the cardiac muscle cells are branched with the ends of the branches joined to adjacent cells by structures called intercalated disks. These contain desmosomes, which anchor the cells together securely during muscular contraction. Also found within the intercalated disks are gap junctions, a sort of synapse, which allows action potentials (nervous impulses) to pass from cell-to-cell.
As might be expected in a muscle mass, which may beat continuously for over 70 years, energy supply is of prime importance. The cells contain many adenosine triphosphate (ATP) producing mitochondria fueled by fatty acids; triacylglycerols being the hearts preferred fuel. The heart muscle also has a good supply of myoglobin, which can store a small amount of oxygen and aid the transfer of oxygen from hemoglobin to the mitochondria. Our hearts contract or beat about once in every second of every day of our lives. The heart beats more than 2.5 million times in an average lifespan. The only time the heart gets a rest is between beats.
When the heart sounds are auscultated with a stethoscope we hear two sounds; each having two sounds in it. The sounds are like ‘lurr-ubb durr-up’. The first heart sound is caused by closure of the mitral valve (left side) and tricuspid valve (right side); mitral valve closes before the tricuspid valve. The second sound is due to closure of aortic and pulmonary valves; aortic valve closes before the pulmonary valve.
The two atria are separated from each other by an interatrial septum. A fairly common congenital defect can leave a hole in the interatrial septum, which shunts the arterial blood from the left atrium to the right atrium (because of high pressure), if the blood is shunted in the opposite direction (right to left) it results in central cyanosis.
Two large veins superior and inferior vena cavae enter the right atrium; the superior vena cava drains deoxygenated blood from head and neck and the upper limbs. The inferior vena cava drains deoxygenated blood from the rest of the body. Another small vein called coronary sinus drains blood from the heart muscle.
The venous blood from the right atrium enters the right ventricle through tricuspid valve, which is anchored by chorda tendinae to the papillary muscles arising from the walls of the right ventricle.
The venous blood from the right ventricle is pumped into the pulmonary artery through pulmonary valve made of three semilunar cusps. The pulmonary artery then branches into right and left pulmonary arteries and their branches enter the two lungs, where the blood is oxygenated. The oxygenated blood from the lungs is returned to the left atrium through four large pulmonary veins, two from each lung.
The left atrium empties the oxygenated blood into the left ventricle through mitral valve made of two cusps, which are anchored to the walls of the left ventricle through chorda tendinea and papillary muscles. A sudden rupture of chorda tendinae results in severe incompetence of mitral wall and the blood regurgitates from the left ventricle into the left atrium, the condition is called acute mitral regurgitation.
The left ventricle pumps the oxygenated blood into the large aorta, which is about 2.5 cm in diameter through an opening called aortic valve, made of three semilunar cusps that are stouter than the pulmonary valves. Just above the attached margins of each cusp, there is a dilatation of the wall of the aorta called aortic sinus. The first branches from the aorta are the two coronary arteries that arise from the two aortic sinuses, the third aortic sinus is called non-coronary sinus from which no artery arises. The coronary arteries supply the arterial blood to the cardiac muscle.
Arterial Blood Supply to the Heart
The right coronary artery that arises from the anterior aortic sinus passes forwards between the pulmonary artery and the right atrium to the front of the heart into the groove, between the right atrium and right ventricle (Fig. 12.2). It curves around the right margin of the heart and continues posteriorly, where it branches out and anastomoses with terminal branches of the circumflex branch of the left coronary artery. Before it anastomoses with the left coronary artery, it gives out the descending artery, which descends posteriorly between the interventricular grooves towards, the apex of the heart. The right coronary artery supplies blood to the right atrium, right ventricle, the posterior parts of the interventricular septum and left side of the heart.
The left coronary artery is larger than the right coronary artery; it arises from the left posterior aortic sinus and passes first behind and then to the left of the pulmonary artery to reach the atrioventricular (AV) groove on the left side of the heart. There it divides into an anterior interventricular (descending) artery and a circumflex artery. The descending artery descends in the anterior interventricular groove to the apex and usually turns around the apex into the posterior groove for a few centimeters to anastomose with the posterior interventricular branch of the right coronary artery. The circumflex artery lies in the AV groove anteriorly and turns around the left border of the heart into the posterior part of the groove. The branches of the left coronary artery supplies blood to most of the ventricle, left atrium and interventricular septum and a narrow strip of right ventricle.
Coronary anastomoses occurs between the named branches of the coronary circulation and between small vessels within the myocardium. The axis of the heart is usually offset to the right anteriorly and to the left posteriorly. That is, the left coronary artery supplies part of the right ventricle anteriorly, together with most of the interventricular septum and left ventricle while the right coronary artery supplies the left ventricle posteriorly, the posterior interventricular septum and most of the right ventricle. Anastomoses between large vessels occur at the apex and the ‘crux’, of the heart.
The anterior and posterior interventricular arteries anastomose around the apex. The right coronary and circumflex arteries anastomose posteriorly at the ‘crux’ the point where the interventricular sulcus crosses the line formed by the interatrial and interventricular septae. Further anastomoses occur within the myocardium around the margins of the territory of each artery. In young people, the extent of this anastomosis is limited. With age, as the larger vessels succumb to atherosclerosis, more and more collaterals open up between adjacent territories. However, the extent of anastomoses is usually not sufficient to allow the myocardium to survive obstruction of a major vessel. The blood supply to the myocardium is delivered from the epicardial to the endocardial surface. The endocardial surface is therefore at greatest risk of ischemia.
Control of myocardial vessel caliber is different from that found in the systemic circulation. Local metabolic factors play a large part, with the level of control varying from epicardium to endocardium.
The coronary arteries arise at the point of maximum blood pressure (BP) in the circulatory system. Over the course of time, the arterial walls are apt to lose elasticity, which limits the amount of blood that can surge through them and hence limits the supply of oxygen to the heart. This condition is known as arteriosclerosis.
Fatty deposits called plaque may accumulate on the interior surface of the coronary arteries. This is particularly common in people, who have high levels of cholesterol in their blood. Plaque deposits reduce the lumen of the coronary arteries and thus the amount of blood they can carry.
Atherosclerosis usually along with arteriosclerosis may limit the blood supply to the heart, particularly during times of stress. This deprives the oxygen supply to the heart muscle, which causes anginal pain. The decreased blood supply to the cardiac muscle triggers the formation of a clot causing coronary thrombosis. This stops the flow of blood through the vessel and the capillary network it supplies, causing a heart attack (myocardial infarction). The portion of the heart muscle deprived of oxygen dies quickly of oxygen starvation. If the area is not too large, the undamaged part of the heart can, in time, compensate for the damage. Coronary bypass surgery uses segments of leg veins to bypass the clogged portions of the coronary arteries.
Venous Drainage of Heart
Blood drains back into the heart through the coronary sinus, through the anterior cardiac veins and through the venae cordis minimae draining directly into the chambers. The coronary sinus lies in the posterior AV sulcus. The great cardiac vein accompanies the anterior interventricular artery, draining its territory back toward the AV sulcus and passing to the left and backwards to join the coronary sinus. The great cardiac vein receives tributaries from the left atrium and both ventricles. The middle cardiac vein drains the territory of the posterior interventricular artery into the coronary sinus. The small cardiac vein drains the right side of the right ventricle into the coronary sinus. The anterior cardiac veins drain the anterior part of the right ventricle directly into the right atrium. The venae cordis minimae drain blood from the myocardium directly into all chambers. This route of drainage represents only a very small percentage of venous drainage.
A fibroserous sac that encloses the heart is called pericardium. The outer layer of the sac is fibrous, which is continuous with the external coats of the great vessels and the pretracheal fascia above and it is fused with the central tendon of the diaphragm below. in addition it is attached to the posterior surface of the sternum. The fibrous pericardial layer anchors the heart within the thorax, as well as prevents the over distension of the heart.
Within the fibrous sac is a double-layered serous pericardium. The parietal layer lines the fibrous sac and is reflected around the roots of the great vessels and continues as visceral layer (epicardium) to cover the surface of the heart. In between these two layers is a thin film of fluid that lubricates the two layers to glide over each other with each heartbeat. When abnormal quantity of fluid collects between the two layers of serous pericardium as a result of inflammation or myxedema, the condition is called pericardial effusion.
The atrial walls are comparatively thinner, because atria have to just pass on the blood to ventricles through wide AV openings. The right ventricle has walls thicker than the atria, because it has to pump blood through the lungs. The left ventricle has the thickest wall, because it has to pump blood to all parts of the body.
The atria and ventricles are separated by connective tissue, except at a central point, where the specialized fibers of the AV bundle of His pass through.
The innermost lining of the heart called endocardium is made of a single layer of flattened epithelial cells, resting on fine supportive layer of fine areolar connective tissue rich in elastic fibers. The endothelial layer lining the cavities of the heart is continuous with the blood vessels leaving and entering the heart, as well the cusps of the valves of the heart.
The heart receives only autonomic innervation from the sympathetic chain and the vagus nerve.
Sympathetic Innervation of the Heart
Sympathetic preganglionic nerve fibers originate in the T1–T4 spinal cord segments. Fibers pass to the upper thoracic and cervical sympathetic ganglia. Postganglionic fibers pass down into the thorax from the superior middle and inferior cervical ganglia and the upper four thoracic ganglia. The fibers reach the posterior surface of the heart, where they form the cardiac plexus around the great vessels and bifurcation of the trachea. The cardiac plexus innervates the nodes, vessels and myocardium.
The vagus gives off cardiac branches in the neck, which travel into the thorax to form the cardiac plexus. These preganglionic fibers then synapse with ganglia of the cardiac plexus on the heart.
Visceral Afferent Fibers
While the heart is insensitive to touch visceral afferent fibers conveying other sensory modalities travel in both the vagus and sympathetic nerves. In particular, there are sensory receptors sensitive to pressure located in association with the great vessels. Pain from angina or myocardial infarction is associated with visceral afferent fibers, which travel together with sympathetic efferents. These fibers enter spinal cord segments from T1 to T4 on the left side. This arrangement is the basis for the referred pain experienced during an angina attack or myocardial infarction. Pain is referred to the somatic territories (surface anatomy dermatomes) supplied by these spinal cord segments.
Functioning of Heart
The cardiac cycle consists of the atria beating in unison followed by the contraction of both ventricles, and then the entire heart relaxes for a brief moment. At rest, the heart beats at a rate of 72/min. It has two phases:
One is systole during which the muscles of ventricles contract to push the blood into the pulmonary artery and aorta.
The other is diastole, its duration is twice as long as that of systole during which the ventricular muscles relax, ventricle passively get filled with blood received from the atria during which period the pulmonary and aortic valves are closed. Passive filling of ventricles takes place to an extent of 75% the remaining is by the active contraction of atria.
Towards the end of ventricular diastole, there occurs atrial systole, which is followed by closure of AV valves. Loss of coordinated atrial contraction due to heart block or atrial fibrillation precipitates cardiac failure in a patient with diseased heart, because of reduced time available for ventricular filling and recovery of its muscles.
During the cardiac cycle, pressure within the heart chambers rises and falls with the contraction and relaxation of atria and ventricles. When the atria are filled, pressure in the atria is greater than that of the ventricles, which forces the AV valves to open. Pressure inside atria rises further as they contract, forcing the remaining blood into the ventricles. When ventricles contract, pressure inside them increases sharply, causing AV valves to close and the aortic and pulmonary valves to open. As the ventricles contract, papillary muscles contract, pulling on chorda tendinae and preventing the backflow of blood through the AV valves.
The volume of blood ejected during a single heartbeat is called stroke volume (SV). The total volume of blood ejected over a period of 1 minute is called cardiac output (CO). Therefore the product of heart rate (HR) and stroke volume is the CO:
HR × SV = CO
The normal range of CO is 4–8 L/min.
The normal HR is about 72/min (it is much lower in athletes).
Heartbeat (Cardiac Cycle)
The cardiac cycle is the sequence of events in one heartbeat. In its simplest form, the cardiac cycle is the simultaneous contraction of the two atria, followed a fraction of a second latter by the simultaneous contraction of the two ventricles.
The heart consists of muscle cells that contract in waves. When the first group is stimulated, they in turn stimulate neighboring cells. Those cells stimulate more cells. This chain reaction continues until all cells contract. The wave of activity spreads in such a way that the atria and the ventricles contract in a steady rhythm.
A heartbeat has two phases:
Phase 1-systole is the term for contraction. It occurs when the ventricles contract, closing the AV valves and opening the aortic and pulmonary valves to pump blood into two major vessels leaving the heart.
Phase 2-diastole is the term for relaxation. It occur when the ventricles relax, allowing the backpressure of the blood to closed aortic and pulmonary valves and opening AV valves.
The cardiac cycle also creates the heart sounds each heartbeat produces two sounds, often called lubb-dup that can be heard with a stethoscope.
The first sound, the loudest and longest, is caused by the ventricular systole (contraction) during closure of the AV valves.
If any of the valves do not close properly, an extra sound called heart murmur may be heard.
Although the heart is a single muscle, it does not contract in a single motion. The contraction spreads over the heart like a wave.
The wave begins in a small bundle of specialized heart muscle cells called sinoatrial (SA) node embedded in the right atrium (Figs 12.3A and B).
The SA node is the natural pacemaker of the heart. It initiates each heartbeat and sets the pace for the heart rate.
The impulse spreads from the pacemaker through the cardiac muscle cells in the right and left atrium, causing both atria to contract almost simultaneously.
When the impulse initiated by the SA node reaches another special area of the heart known as the AV node. The AV node is located in the septum between the right and left ventricles. The AV node relays the electrical impulse to the muscle cells that make up the ventricles. The ventricles contract almost simultaneously within a fraction of a second after the atria, completing one full heartbeat.
These contractions cause the chambers to squeeze the blood, pushing it in the proper direction along its path.
The heart initiates its own stimulation from the SA node and AV node, and does not require stimulation from the nervous system.
The autonomic nervous system does influence heart rate. The sympathetic nervous system increases heart rate and the parasympathetic nervous system decreases it.
For most of us, at rest our heart beats between 60 and 80 beats per minute. During exercise, heartbeats can increase to as many as 200 beats per minute.
Cardiac Conduction System
Specialized cardiac muscle tissue conducts impulses throughout the myocardium and comprises the cardiac conduction system (refer Figs 12.3A and B). A self-exciting mass of specialized cardiac muscle called SA node or pacemaker, located on the posterior right atrium and generates the impulses for the heartbeat. Impulses spread next to the atrial syncytium, it contracts, and impulses travel to the junctional fibers leading to the AV node located in the septum. Junctional fibers are small, allowing the atria to contract before the impulse spreads rapidly over the ventricles. Branches of the AV bundle give rise to Purkinje fibers leading to papillary muscles; these fibers stimulate contraction of the papillary muscles at the same time the ventricles contract.
Regulation of the Cardiac Cycle
The amount of blood pumped at any one time must adjust to the current needs of the body (more is needed during strenuous exercise). Branches of the sympathetic and parasympathetic divisions innervate the SA node, so the central nervous system (CNS) controls heart rate. Sympathetic impulses speed up and parasympathetic impulses slow down heart rate.
The cardiac control center of the medulla oblongata maintains a balance between the sympathetic and parasympathetic divisions of the nervous system. Impulses from cerebrum or hypothalamus may also influence heart rate, body temperature and the concentrations of certain ions.
An electrocardiogram (ECG) is a recording of the electrical changes that occur during a cardiac cycle (Fig. 12.4). Electrodes placed at the surface of the body can detect the electrical activity of the heart.
The first wave, the P wave, corresponds to the depolarization of the atria. The QRS complex corresponds to the depolarization of ventricles and hides the repolarization of atria. The T waves end the ECG pattern and correspond to ventricular repolarization.
Analysis of an ECG aids in determining the extent of damage following a heart attack. This is because death of a portion of the heart muscle blocks electrical transmission through that area and alters the appearance of the ECG.
The ventricles can maintain a beat even without a functioning AV node, although the beat is slower. There is however, a danger that impulses arising in the ventricles may become disorganized and random. If this happens, they begin to twitch spasmodically, a condition called ventricular fibrillation. Blood flow ceases and unless the heart rhythm is restarted, death follows swiftly. In fact, ventricular fibrillation is the immediate cause of as much as 25% of all deaths.
Hospital emergency rooms and ambulances are routinely equipped with defibrillators, which, by giving the heart a jolt of direct current, may restore its natural rhythm and save the victim’s life.
Artificial pacemakers are devices that generate rhythmic impulses that are transmitted to the heart by fine wires. Thanks to miniaturization and long-lived batteries, pacemakers can be implanted just under the skin and can be reached through a small incision when maintenance is needed.
Auxiliary Control of the Heart
Although the AV node sets the basic rhythm of the heart, the rate and strength of its beating can be modified by two auxiliary control centers located in the medulla oblongata of the brain. The one sends nerve impulses to down accelerator nerves and the other sends nerve impulses to down a pair of vagus nerves.
The accelerator nerves are part of the sympathetic branch of the ANS, and like all postganglionic sympathetic neurons they release noradrenaline at their endings on the heart. They increase the rate and strength of the heartbeat and thus increase the flow of blood. Their activation usually arises from some stress such as fear or violent exertion. The heartbeat may increase to 180 beats per minute.
The strength of contraction increases as well so the amount of blood pumped may increase to as much as 25–30 L/min.
Vigorous exercise accelerates heartbeat in two ways:
As cellular respiration increases, so does the carbon dioxide level in the blood. This stimulates receptors in the carotid arteries and aorta and these transmit impulses to the medulla for relay by the accelerator nerves to the heart.
As muscular activity increases, the muscle pump drives more blood back to the right atrium. The atrium becomes distended with blood, thus stimulating stretch receptors in its wall. These send impulses to the medulla for relay to the heart [distention of the wall of the right atrium also triggers the release of atrial natriuretic peptide (ANP), which initiates a set of responses leading to a lowering of BP].
The vagus nerve is a part of the parasympathetic branch of the ANS. It runs from the medulla oblongata to the heart. Its activity slows the heartbeat.
Pressure receptors in the aorta and carotid arteries send impulses to the medulla, which relays these by the way of the vagus nerves to the heart. Heartbeat and BP diminish.
Echocardiography is the examination of heart by ultrasound directed through the heart from a transducer placed on the skin, which is echoed back by the structures that it encounters. By this, one can view the four chambers of the heart, valves and their movement, thickness of cardiac walls, pericardial effusion, septal defects, tumors and thrombi inside the heart.
Blood Vessels (Arteries, Veins and Capillaries)
The circulatory system is known as a closed system because the blood is contained within the heart or the blood vessels all the time. The blood vessels that are part of the closed circulatory system of humans form a vast network to help and keep the blood flowing in one direction. After the blood leaves the heart, it is pumped through a network of blood vessels to different parts of the body. The blood vessels that form this network and are part of the circulatory system are the arteries, capillaries and veins. With the exception of capillaries and tiny veins, blood vessels have walls made of three layers of tissue that provides for a combination of strength and elasticity. The arteries and the veins for that matter, are made up of three coats (Fig. 12.5):
Tunica externa is the outermost coat that supports and protects the vessel. This coat is composed of areolar or fibrous connective tissue.
Tunica media is made of smooth muscle and elastic tissue. This layer is thicker in arteries than in veins, which allows for more arterial expansion. The smooth muscle of this coat is innervated by autonomic fibers, which allows control over blood vessel diameter.
Tunica intima is the innermost layer and is made of single layer of simple squamous epithelium.
Arteries and Arterioles (Small Arteries)
Arteries carry blood from the heart to capillaries and the rest of the body. The walls of arteries are generally thicker than those of veins. The smooth muscle cells and elastic fibers that make up the walls help make arteries tough and flexible. This enables arteries to withstand the high pressure of blood as it is pumped from the heart. The force that blood exerts on the walls of blood vessels is known as BP. Except for the pulmonary arteries, all arteries carry oxygen-rich blood. The artery that carries oxygen-rich blood from the left ventricle to all parts of the body, except the lungs, is the aorta. The aorta with a diameter of 2.5 cm is the largest artery in the body. As the aorta travels away from the heart, it branches into smaller arteries, so that all parts of the body are supplied with oxygenated blood. The smallest arteries are called arterioles.
Arterioles branch into networks of very small blood vessels called capillaries (Fig. 12.6). It is thin walled (one cell in thickness) that the real work of circulatory system is done.
Capillary walls consist of only one layer of cells, making it easy for oxygen and nutrients to diffuse from the blood into the tissue. Forces of diffusion drive CO2 and waste products from the tissue into the capillaries. Capillaries are extremely narrow; blood cells moving through them must pass in single file.
The flow of blood moves from capillaries into the veins, which form a system that collects blood from every part of the body and carries it back to the heart (Fig. 12.7). The smallest veins are called venules. Like arteries, veins are lined with smooth muscle. Vein walls are thinner and less elastic than arteries. Veins are more flexible and are able to stretch out readily. This flexibility reduces the resistance to the flow of blood that is encountered on its way back to the heart. Large veins contain valves that maintain the one direction flow of blood. This is important where blood must flow against the force of gravity. The flow of blood in veins is helped by contractions of skeletal muscles, especially those in the legs and arms. When muscles contract they squeeze against veins and help to force blood toward the heart.
The circulatory system is adapted to meet the following requirements:
A constant supply of blood is maintained to brain and vital centers all the time. For example, a temporary interruption of the blood supply to the brain causes fainting whilst prolonged lack of oxygen causes permanent brain damage or death.
Blood flow to organs is adjusted based on their specific needs. For example, blood flow to the skeletal muscle is increased during increased physical activities, blood supply to gastrointestinal (GI) tract is increased immediately after food consumption to aid digestion and absorption of food and blood supply to the surface of body is increased to regulate body temperature.
Right Side of the Heart
Oxygen-poor blood from the body enters the right side of the heart through two large blood vessels called venae cavae. The superior vena cava collects deoxygenated blood from the upper part of the body and the inferior vena cava collects deoxygenated blood from the lower part of the body to the heart (Fig. 12.8).
Both venae cavae empty into the right atrium. When the heart relaxes (between beats), pressure in the circulatory system causes the atrium to fill with blood.
When the heart contracts, blood is squeezed from the right atrium into the right ventricle through flaps of tissue called AV valve that prevents blood from flowing back into the right atrium.
The valve that separates the right atrium and ventricle is called tricuspid valve.
The general purpose of all valves in the circulatory system is to prevent the backflow of blood. They also ensure that blood flows in only one direction.
The specific purpose of the tricuspid valve is to prevent backflow of blood from the right ventricle to the right atrium when the right ventricle contracts.
When the heart contracts second time, blood in the right ventricle is sent through the semilunar (SL) valve known as the pulmonary valve into the pulmonary arteries to the lungs. These are the only arteries to carry oxygen-poor blood. Pulmonary valves at the base of pulmonary arteries prevent blood from traveling back into the right ventricle.
Left Side of the Heart (from Lungs to Body, Oxygenated Blood)
Oxygen-rich blood leaves the lungs and returns to the heart by way of blood vessels called pulmonary veins. These are the only veins to carry oxygen-rich blood.
Returning blood enters the left atrium; it passes through flaps of tissue called AV valve to the left ventricle.
The valve that separates the left atrium and ventricle is called mitral valve or bicuspid valve.
From the left ventricle, blood is pumped through a SL valve called aortic valve into the aorta that carries it to every part of the body except the lungs.
At the base of the aorta is a valve (aortic valve) that prevents blood from flowing back into the left ventricle.
Arteries, veins and capillaries are three main types of blood vessels in the human body; the walls of these vessels are well constructed for the passage of blood throughout the body.
Arteries deliver blood from the heart under high pressure.
Interior walls of arteries have more smooth muscles than those of veins. This enables arteries to change diameters as blood volume and pressure change when the heart beats.
The walls of arteries are thicker than those of veins in order to handle the higher pressure of blood travelling away from the pumping heart.
Arterioles are small arteries that deliver blood to capillaries.
Capillary walls have only one layer of cells, providing an ideal surface for gas exchange to occur.
Venules are small veins connected to capillaries.
Folds in the innermost layer of veins form valves that prevent the backflow of blood.
The greater size and lower proportion of smooth muscle in veins allows them to stretch as much as eight times more than arteries under their lower pressure.
Veins return blood to the heart under lower pressure.
The middle layer of veins and arteries are made of connective tissue and smooth muscle cells.
The aorta is the largest vessel in the body that supplies the oxygenated blood required for all the tissues in the body. It arises from the left ventricle and passes through the thorax and into the abdomen, where it terminates opposite the lower border of the fourth lumbar vertebra. The aorta can be studied in three parts—the ascending part of the aorta, the arch of the aorta and the descending part of the aorta.
The ascending part of the aorta that arises from the left ventricle passes upwards, forwards and to the right for about 5 cm till it reaches the level of the upper border of the second right costal cartilage. from here onwards it continues as arch of the aorta behind the manubrium sterni and runs in a curved course backwards and to the left. finally, it passes downwards to the left side of the body of the fourth thoracic vertebra, from where it descends and is called thoracic aorta. It continues downwards in front of the thoracic vertebrae to enter the abdomen through a hole in the diaphragm at the level of the lower border of 12th thoracic vertebra. From here onwards the aorta is called abdominal aorta. The abdominal aorta descends further down in front of the lumbar vertebrae, to divide at the level of fourth lumbar vertebra into the right and left common iliac arteries.
The point of branching of abdominal aorta can be marked on the surface of the body, represented by a point just below and to the left of the umbilicus and is approximately at the level of a line joining the highest points of the iliac crest.
Sometimes as a result of some diseases process the wall of the aorta can get weakened to form a large bulge to form an aneurysm. This can rupture causing fatal hemorrhage. Sometimes a tear in the tunica intima can allow the blood to pass in between intima and media that allows stripping of intima and media layers, this condition is called dissecting aneurysm.
Some of the branches arising from the aorta are in pairs that pass to each side of the body, while others that arise from the front of the aorta are single.
The first branches of aorta are the left and right coronary arteries that arise from the aortic sinuses, and run in the grooves between the atrium and ventricle to give branches to the heart muscle.
Brachiocephalic or Innominate Artery
Brachiocephalic arises from the convex part of the aortic arch and is the largest branch. It passes upward, backward and to the right, behind the manubrium sterni. After running for about 5 cm from its origin, it divides into the right subclavian and right common carotid arteries.
Common Carotid Artery
While the right common carotid artery arises from the brachiocephalic artery, the left common carotid artery originates directly from the arch of the aorta. Thereafter the course of the two common carotid arteries and their distribution are similar. The common carotid artery passes upward in the carotid sheath along the jugular vein and vagus nerve. It divides into internal and external carotid arteries at the level of the upper border of the thyroid cartilage.
Internal Carotid Artery
Internal carotid artery passes upwards deeply amidst neck muscles and enters the skull through carotid canal in the petrous part of temporal bone to reach the middle cranial fossa of the skull. In the middle cranial fossa it divides into three branches; the anterior and middle cerebral arteries that supply the brain and the ophthalmic artery that supplies the eye.
At the base of the brain, the anterior and middle cerebral arteries communicate with the basilar artery, a continuation of vertebral artery to form circle of Willis that ensures an even distribution of blood to the brain (Fig. 12.9).
External Carotid Artery
External carotid artery has four branches that supply the outer surface of head and neck (Fig. 12.10):
Facial artery passes upwards along the outer surface of the mandible just in front of the angle and supplies the lower part of the face. The pulse of facial artery can be felt as it crosses the lower jaw.
Occipital artery passes behind the ear to supply the occipital part of the scalp.
Superficial temporal artery passes upwards in front of the ear to supply the frontal, temporal and parietal portion of the scalp. The pulse of temporal artery can be felt in front of the external acoustic meatus.
Maxillary artery supplies the structures around the jaws, as well gives off a branch the middle meningeal artery that enters the interior of the skull.
The right subclavian artery is the branch of the brachiocephalic artery, whereas the left subclavian artery arises directly from the arch of the aorta just beyond the origin of left common carotid artery (refer Fig. 12.10). Both the subclavian arteries pass over the corresponding first rib, which then groove and enter the axilla behind the clavicle, where they continue as the axillary arteries. Subclavian artery is the main artery that supplies upper arm, apart from that it gives away three major branches that supply areas other than the upper arm, they are the vertebral artery that passes upwards through the foramina in the transverse processes of cervical vertebrae and enter the skull through foramen magnum, where it branches out to supply the posterior part of the brain cerebellum and thyrocervical trunk.
Axillary artery is the continuation of subclavian artery that runs up to the lower boundary of the axilla.
Brachial artery is the continuation of axillary artery beginning from the lower border of the axilla and extending up to about 1 cm below the elbow joint. It lies close to the humerus and medial to biceps muscle.
Radial and Ulnar Artery
Radial and ulnar arteries arise from the brachial artery about 1 cm below the elbow joint. The ulnar artery runs down the medial side of the forearm and ends at ulna, where it forms the part of palmar arch. The radial artery runs down lateral to radius covered by muscles of the forearm. Just above the wrist it passes to the front of radius, where its pulse can be felt (Fig. 12.11).
Palmar arches are two in number the one is superficial and the other is deep. The ends of radial and ulnar artery pass to front of the wrist and enter the palm of the hand, where they join to form two arches, which run transversely. These arches give out branches that supply the fingers.
Branches of Abdominal Aorta
Abdominal aorta extends from the lower border of 12th thoracic vertebra up to the lower border of the fourth lumbar vertebra, where it branches into left and right common iliac arteries (Fig. 12.12). During this course it gives away many important branches that supply the abdominal viscera and gonads.
The first branch that arises from the abdominal aorta is celiac trunk or axis. It is a short wide trunk that arises from the front of the abdominal aorta immediately after it passes through the diaphragm.
Celiac trunk divides into three branches namely:
Left gastric artery that supplies the stomach
Hepatic artery that supplies stomach, liver, gallbladder and the pancreas
Splenic artery that supplies spleen passes to the left behind the stomach and along the upper border of the pancreas before it reaches the spleen.
Superior mesenteric artery
Superior mesenteric artery arises from the front of the aorta just below the celiac axis, then passes forward to reach the fold of the peritoneum (mesentery) and descends between its layers to supply the entire length of small intestine and a small beginning portion of large intestine.
Renal arteries are two in numbers that arises just below the superior mesenteric artery from either sides of the abdominal aorta at the level of the second lumbar vertebra. The left and right renal arteries supply the corresponding kidneys. The right renal artery passes behind the inferior vena cava to reach the left kidney.
Inferior mesenteric artery
Inferior mesenteric artery arise from the front of the abdominal aorta, much below the origin of renal arteries and gives away branches that supply the distal parts of the large intestine (colon) and rectum.
Common iliac arteries
The abdominal aorta divides into right and left common iliac arteries in front of the lower border of the fourth lumbar vertebra. Each passes downwards and laterally for 4–5 cm and then divides into internal and external iliac arteries.
Internal iliac arteryInternal iliac artery descends into the pelvic cavity and supplies the organs present there. In females it gives rise to uterine artery that supplies uterus.
External iliac arteryExternal iliac artery runs downwards along the brim of the pelvis and passes under the inguinal (Poupart’s) ligament to continue as femoral artery, which is the main artery of the lower limb.
Femoral artery is the continuation of external iliac artery, which commences behind the inguinal ligament and end at a point above the medial condyle of the femur (adductor tubercle). It runs from a point midway between the anterior superior spine of the ileum and the symphysis pubis to the opening in the adductor magnus muscle. The upper half of the artery is quite superficial that lies in the femoral triangle (Scarpa’s triangle). The half of the artery is placed more deeply among the muscles in a special tunnel called Hunter’s canal (adductor canal). The end of the femoral artery runs backwards and behind the femur to enter the popliteal fossa to become popliteal artery. The femoral artery during its course gives branches to muscles around it and the knee joint.
Popliteal artery is the continuation of femoral artery in the popliteal fossa. At the lower end of the fossa it gives out a branch that is called anterior tibial artery, which passes forwards between the tibia and fibula to supply the front of the leg and descends downward on to the dorsum of the foot as dorsalis pedis. The direct downward continuation of popliteal artery to the back of the leg is called posterior tibial artery. Popliteal artery passes behind and below the medial malleolus and lies deeply among the muscle. It is here it divides into the medial and lateral plantar arteries in the sole of the foot. The lateral plantar artery anastomoses with the dorsalis pedis artery to form plantar arch from which digital branches pass to the toes.
Pressure points are the points where the arteries are superficial and can be compressed against some firm underlying structures. These points help in feeling the arterial pulse as well arresting the bleeding distal to these points in case of injury. Examples of pressure points are as follows:
Facial: Against the lower jaw.
Temporal: In front of external acoustic meatus.
Occipital: Against the occipital bone about 2½ inches behind the ear.
Common carotid: Against the cervical vertebrae at the side of the larynx.
Subclavian: Against the first rib in the hollow above the clavicle.
Brachial: Against the medial aspect of the humerus in the middle of the arm.
Radial: At the lower end of the radius just above the wrist on its anterior surface.
Ulnar: Against the anterior surface of the ulna.
Femoral: Against the pubic bone under the inguinal ligament.
Posterior tibial: Against the posterior surface of the medial malleolus.
Dorsalis pedis: Against the upper surface of the navicular bone.
The venous system begins as venules, where the capillaries terminate. The venules join together to form veins that unite to form larger and larger veins until the two great trunks superior and inferior venae cavae are formed. The superior vena cava drains the deoxygenated blood from head, neck and upper limbs. The inferior vena cava drains the blood from the rest of the body and the abdominal viscera. Both the superior and inferior venae cavae empty the blood they carry into the right atrium. The thoracic pump, skeletal muscle pump and the heartbeat aid the draining of venous blood into the heart.
The veins in the body are divided into two groups. The superficial veins are located just under the skin some of which can easily be seen. The deep veins are located deeply among other tissues and accompany the main arteries.
Veins of the Lower Limb
The two long veins of the lower limb are the long saphenous vein and the short saphenous vein (Fig. 12.13). The long saphenous vein begins on the medial side of the dorsum of foot and ascends upwards in front of the medial malleolus, and up the medial side of the leg behind the medial aspect of the knee. Just below the medial end of the inguinal ligament, it passes deeper by piercing through the saphenous opening formed by the deep fascia of the limb. Then it ends in femoral vein. The short saphenous vein commences on the lateral side of the foot and ascends along the center of the back of the calf and pierces the deep fascia of the limb over the popliteal fossa at the back of the knee joint to end in popliteal vein.
The two deep veins of the lower limb are popliteal vein and the femoral vein. The anterior and posterior popliteal veins that accompany the corresponding arteries join to form the popliteal vein. This vein ascends along with the corresponding artery and enters the Hunter’s canal as the femoral vein. It lies within the femoral sheath along with the femoral artery in the femoral triangle (Scarpa’s triangle). It is in this triangle it receives the long saphenous vein, which ascends under the inguinal ligament to become the external iliac vein.
Veins of the Abdomen
The external iliac vein joins the internal iliac vein on the posterior abdominal wall to form the left and right common iliac veins. The two common iliac veins join together just below the bifurcation of the abdominal aorta to form the inferior vena cava. It ascends upwards in front of the bodies of the lumbar vertebrae and lie to the right of the abdominal aorta. During its course in the abdomen it receives the right and left renal veins, from the corresponding kidneys and just before it pierces the diaphragm to enter the thorax it receives a group (2 or 3) of hepatic veins. In the upper part of the abdomen, the inferior vena cava lies on the posterior aspect of liver by forming a groove. Immediately after reaching the thorax, it enters the right atrium.
The hepatic portal system is composed of hepatic vein, and portal vein and their tributaries (Fig. 12.14). The veins draining the stomach, spleen and intestine join to form one large vein, the portal vein. It is formed just behind the neck of the pancreas by the union of superior mesenteric vein and splenic vein. It ascends upward behind the duodenum to reach the portal fissure of the liver, where it enters the liver. Within the liver it branches out into the substance of liver and again unites to form three hepatic veins that leave the liver to join inferior vena cava.
Remember it is only portal vein that begins and ends as capillaries. The physiological importance of portal system is to carry all the absorbed nutrients from the alimentary tract to the liver for further metabolism. Also remember that the hepatic artery has no role in the formation of portal circulation.
Obstruction to portal vein or its branches as a result of thrombosis or hepatic cirrhosis can raise the BP in the portal venous system, what is referred to as portal hypertension. It results in enlargement of the spleen, esophageal varices, hemorrhoids and ascites.
Superior Vena Cava
The superficial and deep veins of the upper limb and the veins from the head and neck join to form the superior vena cava that drains into the right atrium (Fig. 12.15).
Veins of the Upper Limb
The superficial veins of the upper limb begin on the back of the hand, which converge on to the anterior cubital space in front of the elbow joint as cephalic vein. At the bend of the elbow this gives off the median cubital vein that passes on to the medial side to join the basilic vein. The basilic vein ascends along the medial side of the arm, whereas the cephalic vein continues upwards along the lateral side of the arm. The cephalic and basilic veins pass upwards and pierce the deep fascia to accompany the axillary artery as axillary vein.
The deep veins of the upper limb begins as digital veins and accompany the radial, ulnar and brachial arteries as corresponding veins and terminate as axillary vein. The axillary vein continues as subclavian vein, which is joined by the external and internal jugular veins coming from the head and neck to become brachiocephalic veins. Both the brachiocephalic veins join together to become the superior vena cava that drains the blood into the right atrium.
Veins of Head and Neck
The external jugular vein is formed just behind the angle of the jaw by convergence of superficial veins of the scalp (Fig. 12.16). This descends directly, superficial to the sternocleidomastoid muscle and later crosses obliquely to enter the subclavian vein. The facial vein begins as angular vein close to the medial angle of the eye with, which most of the other veins of the face converge to form the facial vein that crosses the lower jaw in front of the angle of the mandible and then passes deep into the neck to join the internal jugular vein. The angular vein communicates with the veins inside the skull, which passes through the orbit of the eye. It is because of such communication between the veins of the skull and the face; the infections of the face can easily spread into the skull.
The veins draining the brain and the venous sinuses that lie between the layers of the dura mater pour their blood into the internal jugular vein.
The superior sagittal sinuses commence in the frontal region of the skull and runs directly backwards in the midline of the occipital region, enclosed in a fold of dura mater, called falx cerebri that separates the right and left cerebral hemispheres.
Before the age of 18 months, when the bones of the skull are not completely fused, there is a diamond-shaped opening between the frontal bone and the two parietal bones, which is only covered by membranes. This opening is called anterior fontanel. The superior sagittal sinus runs directly beneath this opening in the midline and blood can be drawn from this sinus.
A catheter can be passed into the pulmonary artery through basilic vein and hence onwards into the superior vena cava and right atrium and into right ventricle. Its exact position can be located by X-ray imaging. The pressure in the right side of the heart can be measured and blood samples can be collected for estimation of their oxygen content. Catheterization through the vein is called right heart catheterization.
Thrombus formed sometimes due to various causes can get dislodged and enter the pulmonary artery, and the lung result in pulmonary infarct and could be fatal.
Changes in Blood Pressures During the Cardiac Cycle
Cardiac cycle can be descriptively divided into four sequential stages, starting with the general diastolic or period of relaxation. The various stages are as follows (Fig. 12.17).
Stage 1: The heart is in diastole, it is relaxed and the AV valves are open and both the atria and ventricles are filling with blood returning from the venous division. In the aorta, the pressure is still high after ventricular systole, but begins to fall steadily as blood moves through the capillaries. At this point the SL valves are closed, so arterial BP is isolated from ventricular BP.
Stage 2: The heart’s pacemaker SA node generates a nervous impulse that sweeps in a wave across the atria causing them to contract and force their remaining blood into the ventricles, which causes ventricular pressure to increase slightly. In the aorta, the SL valve is still closed, so the steady fall in BP continues.
Stage 3: Ventricular systole starts and the increase in pressure in the ventricle causes the AV valves to close. The pressure in the ventricles increases rapidly causing the SL valves to open with a corresponding increase in aortic pressure. The atria, which are isolated from the ventricles by the closed AV valves continue to receive blood from the venous division.
Stage 4: Ventricular systole finishes and the pressure in the ventricles falls to the point, where the SL valves close causing a small increase in arterial pressure due to the elastic recoil of the arteries forcing blood back towards the valves. This small increase can be seen as a blip on the graph called dicrotic notch. As ventricular pressure falls below atrial pressure, the pressure of blood in the atria open the AV valves and blood flows into the ventricles. The heart is now in general diastole and the cycle of pressure changes starts again.
Nature of Arterial Blood Pressure
Arterial pressure is pulsatile in nature and fluctuates between a high and a low as the heart contracts and relaxes. The maximum pressure of blood on the arterial walls is the systolic pressure and the lowest pressure is the diastolic pressure (Fig. 12.18). The average pressure in the arteries is the mean arterial pressure (MAP). The pulse that can be monitored in certain arteries is the expansion of those arteries during systole.
As the heart contracts, blood is forced from the ventricles into the arteries. The pressure in the arteries is thus increased to their maximum systolic pressure. When the heart goes into its diastolic phase and relaxes, the pressure in the arteries is locked in by the closure of the SL valves. During this phase, pressure in the arteries falls steadily as the blood percolates its way through the tiny arterioles and capillaries. It is important to note that pressures in the heart fluctuate much more than pressures in the arteries. There is always a minimum pressure of 70–80 mm Hg in the arteries, whereas in the heart, the pressure drops to near zero during ventricular diastole. Thus, the arteries act as pressure reservoirs during the heart’s diastolic period, their elastic walls recoiling to ensure an uninterrupted flow of blood through the capillaries (Fig. 12.19).
Pressures differ between blood vessels, being highest in the arteries and falling as the blood progresses through the smaller arterioles and into the capillaries (refer Fig. 12.19). BP is lowest in the veins. Note that blood flow in the capillaries (and veins) is non-pulsatile.
Control of Blood Pressure
Arterial pressure must be maintained at a sufficiently high level to drive the blood through millions of capillaries, which provide nutrients and gas exchange to the cells of the body’s tissues, as well as removes waste from the peripheral tissues. However, pressure should not be so high that it ruptures the small blood vessels or places undue strain on the heart.
Blood pressure is maintained in the short term by the complex interaction of systemic vascular resistance (SVR) and CO. Longer-term regulation calls for adjustment to blood volume.
Cardiac output is the amount of blood pumped by the heart each minute. Systemic vascular resistance is the resistance to blood flow, determined by blood vessel diameter, blood viscosity and total length of blood vessels. The body has short-term control over blood vessel diameter via sympathetic nerves that cause contraction of smooth muscle surrounding the arterioles (Fig. 12.20). The smaller the diameter of the lumen, the greater is the resistance.
The relationship of BP, CO and SVR can be best expressed by a simple formula:
Figure 12.20: Effect of sympathetic stimulation of arterioles on vascular resistance (SVR, systemic vascular resistance)
BP = CO × SVR
(Blood pressure = Cardiac output × Systemic vascular resistance)
If either CO or SVR increases, then BP will increase. If either CO or SVR decreases, then BP decreases.
Cardiac output is expressed by another simple formula:
CO = HR × SV
(Cardiac output = Heart rate × Stroke volume)
If either HR or SV increase, then CO will increase (and so BP increases). If either HR or SV decrease, then CO will decrease (and so BP decreases).
Stroke volume is the amount of blood ejected from the left ventricle during each cardiac cycle (around 70 mL at rest).
Arterial BP is monitored by pressure sensors in the circulatory system called baroreceptors the most important of which are found on the aortic arch and the carotid sinus. These stretch receptors monitor changes in BP and send neural signals to the cardiovascular control center in the medulla. The medulla via the autonomic nervous system regulates the BP by adjustments to the CO of the heart and the peripheral resistance of the arterioles. This process is called baroreceptor reflex. We will now examine the response of the baroreceptor reflex to decrease and increase in BP.
A decrease in BP can be caused by hemorrhage, dehydration, heart attack and even just standing up too quickly. The drop in BP is detected by the baroreceptors as a reduction in arterial stretch, which reduces the rate of signals sent to the control center in the medulla via the afferent neurons. The medulla then increases the sympathetic activity and decreases the parasympathetic activity of the circulatory system. This has the effect of increasing both the SV and HR, which increases the CO. The arterioles are subject to sympathetic vasoconstriction, which increases the SVR. All of these contribute to an increase in BP (Fig. 12.21).
Short-term increase in BP is normally the result of exercise. Obviously, reduced CO would be undesirable, as it would limit our ability to exercise. Fortunately, complex mechanisms in the CNS suppress the baroreceptor response and selective vasodilation occurs that redistributes blood to the exercising muscles. This lowers SVR so that BP only increases moderately, even though CO may have doubled.
Long-term adjustment to BP involves the regulation of sodium ion (Na+) levels in the blood and this is done by the kidney. The level of Na+ in the blood will determine its osmolarity and thus the amount of water it will carry. The regulation of Na+ is via the hormone aldosterone produced by the adrenal glands, which controls the amount of Na+ lost in the urine. The regulation of aldosterone itself is quite complicated. Receptors in the kidney respond to a fall in BP and Na+ levels by triggering the renin-angiotensin-aldosterone cascade, a complex of hormones and plasma proteins, which increases plasma Na+ levels and induces vasoconstriction so increasing BP.
Heart’s Response to Exercise
When we exercise the heart needs to increase its output in order to transport more oxygenated blood to the muscles, so that they can make more energy. This involves an increase in HR and SV.
Remember the formula:
CO = HR × SV
(Cardiac output = Heart rate × Stroke volume)
Figure 12.21: Control of short-term blood pressure fluctuations is through baroreceptor reflex (BP, blood pressure)
Normally, HR is around 70 beats per minute (BPM) and SV is around 70 mL, so average CO is around 5 L/min.
During exercise in a healthy individual, the HR may rise to 150 BPM and SV to 100 mL giving a CO of 15 L/min, a threefold increase. In trained athletes, CO can exceed 20 L/min.
During exercise, sympathetic stimulation of the SA node increases the HR and stimulation of the myocardium increases contractility and so SV. An increase in the volume of blood returning to the heart via the venous system causes the heart to contract more forcefully via a mechanism called Starling’s forces. This reinforces the increase in SV and CO.
An increase in HR and SV results in an increase in CO and logically this should increase BP if we recall the formula:
BP = CO × SVR
(Blood pressure = Cardiac output × Systemic vascular resistance)
Although, CO can treble during vigorous exercise, a corresponding increase in BP could result in damage to tissue and small blood vessels. Fortunately, vasodilation of blood vessels in exercising muscles reduces overall vascular resistance and so keeps systemic BP within acceptable levels. This vasodilation increases the flow of blood to exercising muscles, thus, supplying more oxygen to meet increasing energy demands.
Summary of Blood Pressure
Blood moves through our circulatory system because it is under pressure.
This pressure is caused by the contraction of the heart and by muscles that surround blood vessels.
A measure of force that blood exerts against a vessel wall is called BP.
Blood pressure is always highest in the two main arteries that leave the heart.
Blood pressure is maintained by two ways:
The nervous system, which can speed up or slow down the HR.
The kidneys, which regulate BP by the amount of fluid in our blood.
When blood pressure is too high, kidneys remove water from blood, lowering the total amount of fluid in the circulatory system.
Blood pressure is usually measured in the artery supplying the upper arm.
How to Measure Blood Pressure?
A cuff is inflated around a person’s arm stopping the flow of blood through the artery (Fig. 12.22).
Air pressure in the cuff is slowly released, the first sounds of blood passing through the artery means that the ventricles have pumped with enough force to overcome the pressure exerted by the cuff.
This measurement is known as the systolic pressure or the pressure of the blood when it leaves the ventricles. Normal pressure is about 120 mm Hg for males and 110 mm Hg for females.
Continue to release the air pressure-listening for the disappearance of sound, which indicates a steady flow of blood. This is known as the diastolic pressure or the pressure of the blood is sufficient to keep arteries open constantly even with the ventricles relaxed. Normal pressure according to World Health Organization (WHO) guidelines in a normotensive individual should have a systolic BP of less than 140 and a diastolic pressure of less than 90 mm Hg at rest. Repeated readings of above 160/95 mm Hg may indicate hypertension and intermediate readings are described as borderline.
Blood pressure is given as the systolic number over the diastolic number.
Hypotension occurs acutely in cases of shock due to blood loss, septicemia, myocardial infarction and other causes.
A systolic pressure of less than 80 mm Hg can affect renal perfusion that lead to renal failure.
Chronic hypotension is also seen in individuals with Addison’s disease.
The difference between the systolic and diastolic pressure is called pulse pressure.
Muscles make up the bulk of the body and account for about one-third of its weight. Their ability to contract not only enables the body to move but also provides the force that pushes substances, such as blood and food through the body. Without the muscular system, none of the other organ systems would be able to function.
The skeleton and its joints support, protect and provide flexibility for the body, but the skeleton cannot move by itself.
The muscle tissue that makes up the muscular system performs that job.
A muscle tissue is the tissue that can contract in a co-ordinated fashion, and includes muscles tissue, blood vessels, nerves and connective tissue.
Approximately, 40%–50% of the mass of the human body is composed of muscle tissue.
The muscular system is composed of muscle tissue (muscle fiber) that is highly specialized to contract or to produce movement when stimulated.
The word muscle is derived from the Latin word ‘mus’, meaning ‘mouse’.
Muscle tissue is found everywhere within the body, not only beneath the skin but also deep within the body, surrounding many internal organs and blood vessels.
The size and location of muscle tissue help to determine the shape of the body and the way of movement.
TYPES OF MUSCLE TISSUE
There are three types of muscle tissue or muscles such as skeletal, smooth and cardiac (Fig. 13.1). Each type has a different structure and plays a different role in the body (Table 13.1).
Skeletal muscle is responsible for moving parts of the body, such as the limbs, trunk and face.
Skeletal muscles are generally attached to bones and are at work every time during movement.
Skeletal muscles are responsible for voluntary (conscious) movement.
A skeletal muscle is made up of elongated cells called muscle fibers. Varying movements require contraction of variable number of muscle fibers in a muscle.
Skeletal muscle fibers are grouped into dense bundles called fascicles. A group of fascicles are bound together by connective tissue to form a muscle.
When viewed under a microscope, skeletal muscles appear to have striations (bands or stripes). This gives skeleton muscle the name ‘striated’ muscle.
Most skeletal muscles are consciously controlled by the central nervous system (CNS).
Table 13.1 Types of muscle tissues, their mode of contraction, location and mode of controlType of muscleContractsFound inControlSmoothSlowlyViscera, blood vesselsInvoluntarySkeletalRapidlyTrunk, extremities, head and neckVoluntaryCardiacRapidlyHeartInvoluntary
Skeletal muscle cells are large and have more than one nucleus. They vary in length from 1 mm to 30–60 cm.
Because they are so long and slender, they are often called muscle fibers rather than muscle cells.
Muscle fiber together with the connective tissue, blood vessels and nerves form a skeletal muscle.
Smooth muscles are usually not under voluntary control.
Smooth muscle cells are spindle-shaped and have a single nucleus, are not striated and interlace to form sheets of smooth muscle tissue.
Smooth muscles are found in many internal organs, stomach, intestines and in the walls of blood vessels.
Smooth muscle fibers are surrounded by connective tissue, but the connective tissue does not unite to form tendons, as it does in skeletal muscles.
Most smooth muscle cells can contract without nervous stimulation. Because most of its movements cannot be consciously controlled, smooth muscle is referred to as involuntary muscle.
The contractions of smooth muscles move food through the digestive tract, control the blood flow through the circulatory system and dilate the pupils of the eyes in dim light.
The only place in the body, where cardiac muscle is found is in the heart.
Cardiac cells are striated, but they are not under voluntary control.
Cardiac muscle contract without direct stimulation by the nervous system. A bundle of specialized muscle cells in the upper part of the heart send electrical signals through cardiac muscle tissue, causing the heart to rhythmically contract and pump blood through the body.
The cardiac muscle cell contains one nucleus located near the center; adjacent cells form branching fibers that allow nerve impulses to pass from cell to cell.
A muscle fiber (Fig. 13.2) is a single, multinucleated muscle cell.
A muscle is made up of hundreds or even thousands of muscle fibers, depending on the muscle size.
Although muscle fiber makes up most of the muscle tissue, a large amount of connective tissue and blood vessels, and nerves are also present.
Connective tissue covers and supports each muscle fiber and reinforces the muscle as a whole.
The health of muscle depends on a sufficient nerve and blood supply. Each skeletal muscle has a nerve ending that controls its activity.
Active muscles use a lot of energy and require a continuous supply of oxygen and nutrients, which are supplied by arteries; muscles produce large amounts of metabolic waste that must be removed by veins.
Muscle fibers consist of bundles of thread-like structures called myofibrils.
Each myofibril is made up of two types of protein filaments—thick ones and thin ones.
The thick filaments are made up of a protein called myosin.
The thin filaments are made up of a protein called actin.
Myosin and actin filaments are arranged to form overlapping patterns, which are responsible for the light and dark bands that can be seen in skeletal (striated appearance) muscle.
The region from one Z-line to the next is called sarcomere, the functional unit of muscle contractions.
Mechanism of Muscle Contraction
The sarcomere is the functional unit of muscle contractions.
When muscle cells contract, the light and dark bands contained in muscle cells get closer together.
This happens because when a muscle contracts, myosin filaments and actin filaments interact to shorten the length of a sarcomere.
When myosin filaments and actin filaments come near each other, many knob (heads)-like projections in each myosin filament form cross-bridges with an actin filament.
When the muscle is stimulated to contract, the cross-bridges move, pulling the two filaments pass each other.
After each cross-bridge has moved as far as it can, it releases the actin filament and returns to its original position. The cross-bridge then attaches to the actin filament at another place and the cycle is repeated. This action shortens the length of the sarcomere.
The synchronized shortening of sarcomeres along with the full length of a muscle fiber cause the whole fiber and hence the muscle to contract.
When thousands of actin and myosin filaments interact in this way, the entire muscle cell shortens and this concept is the sliding filament theory (Figs 13.3A to D).
Muscle contractions require energy, which is supplied by adenosine triphosphate (ATP). This energy is used to detach the myosin II heads from the actin filaments (Fig. 13.4).
Because of myosin heads must attach and detach a number of times during a single muscle contraction, muscle cells must have a continuous supply of ATP.
Without, ATP the myosin heads would stay attached to the actin filaments, keeping muscles permanently contracted.
A muscle contraction like a nerve impulse is an all-or-none response either fibers contract or they remain relaxed.
The number of muscle fibers that are stimulated determines the force of muscle contraction; as more fibers are activated, the force of the contraction increases.
Some muscles, such as the muscles that hold the body in an upright position and maintain posture are nearly always at least partially contracted.
Control of Muscle Contraction
Muscles are useful only when they contract in a controlled fashion.
Motor neurons connect the CNS to skeletal muscle cells (effectors); impulses (action potentials) from motor neurons control the contraction of skeletal muscle cells.
The point of contact between a motor neuron and a muscle cell is called neuromuscular junction (Fig. 13.5).
Vesicles or pockets in the axon terminals of the motor neuron release molecules of the neurotransmitter acetylcholine.
These molecules diffuse across the synapse, producing an impulse in the cell membrane of the muscle cell.
The impulse causes the release of calcium ions within the cell. The calcium ions affect regulatory proteins that allow actin and myosin filaments to interact and form cross-bridges.
A muscle cell will remain in a state of contraction until the production of acetylcholine stops.
An enzyme called acetylcholinesterase also produced at the neuromuscular junction destroys acetylcholine and permits the reabsorption of calcium ions into the muscle cell, and terminates the contraction.
Depending on the activity, a person trying to accomplish, the muscle contractions can be weak or strong. The brain (frontal lobes of the cerebrum) decides what and how many muscle cells need to contract? Blinking the eye would be a weak contraction, but for lifting heavy weights the brain would signal most muscle cells to contract.
Muscle sense is the brain’s ability to know where the muscles are and what they are doing? This permits to perform everyday activities without having to concentrate on muscle position.
HOW MUSCLES AND BONES INTERACT?
Skeletal muscles generate force and produce movement only by contracting or by pulling on body parts.
Individual muscles can only pull; they cannot push.
Skeletal muscles are joined to bone by tough connective tissue called tendons.
Tendons attach muscle to bone; the origin is the more stationary bone and the insertion is the more movable bone.
The joint functions as a fulcrum (the fixed point around which the lever moves) and the muscles provide the force to move the lever.
Usually there are several muscles surrounding each joint that pull in different directions.
Most skeletal muscles work in pairs.
When one muscle or set of muscles contracts, the other relaxes.
The muscles of the upper arm are a good example of this dual action—antagonistic muscles.
Flexor is a muscle that bends a joint. Extensor is a muscle that straightens a joint.
When the biceps muscle (on the front of the upper arm, flexor) contracts, it bends or flexes the elbow joint.
When the triceps muscle (on the back of the upper arm, extensor) contracts, it opens or extends the elbow joint.
A controlled movement requires contraction by both muscles.
Antagonistic muscles are opponents, muscles that have opposing or opposite functions. A muscle pulls when it contracts, but exerts no force when it relaxes and cannot push. When one muscle pulls a bone in one direction, another muscle is needed to pull the bone in the other direction (Fig. 13.6).
Synergistic muscles are those with the same function or those that work together to perform a particular function. They also stabilize a joint to make a more precise movement possible.
A normal characteristic of all skeletal muscles is that they remain in a state of partial contraction.
At any given time, some muscles are being stimulated, while others are not. This causes a tightened or firmed, muscle and is known as muscle tone.
Muscle tone is responsible for keeping the back and legs straight, and the head upright even when you are relaxed.
Exercise is the key to maintain good muscle tone within the body.
Muscles that are exercised regularly stay firm and increase in size by adding more materials to the inside of muscle fibers.
Tendons are white, glistening, inelastic fibrous bands that bind the muscles to bones, e.g. Achilles tendon.
Aponeurosis are fibrous tissues that are flattened sheets, which serve as coverings for groups of muscles. Sometimes it connects the muscle to a part it moves.
Fascia is a mixture of areolar and fibrous tissue that wraps and binds soft structure of the body. There are two types of fascia:
Superficial fascia is found beneath the skin and contains fat.
Deep fascia is dense and more fibrous. It forms sheaths that separate groups of muscles. In palm and foot, it is thick and strong:
Palmar fascia is the deep fascia of palm, which is thick and spread out over the palm and binds down the deep structures
Plantar fascia found in the palm is similar to palmar fascia that binds down the deep structures
The important superficial muscles on the anterior and lateral view of human body are shown in Figures 13.7 and 13.8.
It is a physiological inability of a muscle to contract. Muscle fatigue is a result of a relative depletion of ATP. When ATP is absent, a state of continuous contraction occurs. This causes severe muscle cramps.
It is a temporary lack of oxygen. When this occurs muscles will switch from the normal aerobic respiration to a form of anaerobic respiration called lactic acid fermentation. As the oxygen becomes depleted, the muscle cells begin to switch. Oxygen debt leads to the accumulation of metabolic waste (lactic acid) in the muscle fibers, resulting in muscle fatigue, pain and even cramps. Eventually, the lactic acid diffuses into the blood and is transported to the liver. So, if ever soreness experienced after prolong exercise, it may have been caused by oxygen debt—the body could not provide the oxygen to the muscles, they needed to function properly.
MUSCLES OF THE HEAD AND NECK
The muscles of facial expression are supplied by VII cranial nerve. The circular muscle surrounding the eye is orbicularis oculi, which helps in closing the eye. The circular muscle around the mouth situated in the lips is orbicularis oris that helps in closing the mouth. The principle muscle that forms the lateral wall of the mouth is buccinator that helps in chewing and sucking.
The muscles of mastication are temporalis and masseter muscles, which are supplied by branches of V cranial nerve. They help for the movement of jaw for mastication. The temporalis muscle arises from the temporal fossa of the skull and the fibers converge to form a tendon that is inserted to the coronoid process of the mandible.
The masseter muscle is quadrilateral in shape, it arises from of the zygomatic arch and is inserted to the outer surface of the lower jaw at a point anterior to the angle of the mandible.
Superficial Muscles of Neck
Platysma extends from the lower jaw as a thin flat sheet to the deep fascia in front of the neck and up to the chest.
Sternocleidomastoid muscle extends from the manubrium sterni and the medial end of clavicle, and gets inserted to the mastoid processes of the temporal bone on either side behind the ear. Acting singly, each muscle rotates the head toward the opposite side. While acting together, the muscle helps in rotation of the head.
Trapezius is a large triangular muscle extending from the occipital bone, spines of cervical and thoracic area, and gets inserted into the lateral third of the clavicle and acromion process of scapula. This muscle helps in the upward movement of the shoulder girdle.
There are several muscles in the front of neck extending from the lower jaw to the hyoid bone, and from the hyoid bone and thyroid cartilage to the sternum, which are closely related to the trachea and thyroid gland (Fig. 13.9).
One of the important deep muscles of the neck is scalene muscle, which extend from the cervical vertebrae to the first and second ribs.
The muscles of the pharynx are constrictor muscles, which take part in act of swallowing along with muscles of the tongue and floor of the mouth.
The muscles of larynx are external muscles, which along with internal muscles take part in movement of larynx and voice production.
MUSCLES OF SHOULDER GIRDLE AND UPPER LIMB
Muscles that attach scapula to the trunk are the two superficial muscles, the serratus anterior and trapezius and the deep muscle, the rhomboids are shown in Figure 13.10.
Muscles that attach humerus to scapula are supraspinatus, infraspinatus, subscapularis and deltoid.
The deltoid muscle is located on the outside of the shoulder and is recognized by its triangular shape. The deltoid muscle is constructed with three main sets of fibers: anterior, middle, and posterior. These fibers are connected by a very thick tendon and are anchored into a V-shaped channel housed in the shaft of the humerus bone in the arm. The deltoid muscle is responsible for the brunt of all arm rotation and allows a person to carry objects at a safer distance from the body. It is also tasked with stopping dislocation and injury to the humerous when carrying heavy loads. One of the most common injuries to the deltoid muscle is deltoid strain. Deltoid strain is characterized by sudden and sharp pain where injured, intense soreness and pain when lifting the arm out from the side of the body, and/or tenderness and swelling caused by (and located at) the deltoid muscle.
The muscles that attach to chest wall are pectoralis major and minor and latisssimus dorsi.
Muscles of the upper arm are biceps and brachialis, which are in front of the upper arm that helps flexion of elbow joint and the triceps in the back of upper arm that helps the extension at elbow joint.
The biceps muscle has two heads, the short and the long head both originate from the scapula. The long head arises from the top of the glenoid cavity; the short head arises from the tip of the coracoid process and both the heads get inserted to the top of the bicipital tubercle below the head of the radius. Since this muscle passes over the two joints, it can cause the movement at both the joints. The main actions of biceps muscle are supination of the forearm and flexion at elbow joint, also helps the forward movement of the shoulder joint.
The brachialis muscle arises from the front of the shaft of the humerus and gets inserted to the ulna.
The triceps muscle has three heads, the long head arises from the scapula, the lateral and medial heads arise from humerus, and passes from behind to get inserted to the posterior surface of olecranon process at elbow joint. This muscle helps to support the shoulder joint and draw the arm backwards.
Muscles of Forearm
Muscles of the forearm are divided into two groups.
Front of Forearm
Those on the front of forearm are divided into four groups:
Flexor carpi radialis and flexor carpi ulnaris are the muscles involved in flexion of the elbow and wrist joints. These two muscles arise from the humerus and get inserted to the wrist bones.
Flexor digitorum superficialis flexes the fingers, elbow and wrist. It arises from the medial epicondyle of the humerus and gets inserted to the base of middle phalanx of fingers.
Flexor digitorum profundus flexes the wrist and fingers. It arises from the ulna and gets inserted to the distal phalanx of fingers.
Pronator quadratus, pronator teres and brachio-radialis (supinator longus) are the muscles involved in pronation and supination of the arm.
Back of Forearm
Those on the back of forearm are divided into:
Extensor digitorum communis arises from the lateral epicondyle of the humerus, and gets inserted to the wrist bones and finger bones on the posterior surface. It extends the wrist, fingers and also the elbow joint.
Extensor carpi radialis and extensor carpi ulnaris muscles extend the wrist.
Muscles of the Hands and Fingers
The tendons of the flexor muscles in front and extensor muscles in the back of the forearm are inserted to the base of terminal phalanges of the fingers. The thumb has separate flexor and extensor muscles situated in the thenar eminence at the base of the thumb. Similarly, the muscles situated in the hypothenar eminence at the base of the little finger are responsible for the movements of thumb and little fingers. In addition, there are small muscles involved in the movement of fingers. They are lumbrical and interosseous muscles.
Muscles of the Thorax
The pectoralis major is a large fan-shaped muscle that covers the upper anterior part of the chest and anterior part of the axilla. The pectoralis minor is a small triangular muscle that lies deep to pectoralis major. Both these muscles arise from the anterior aspect of the sternum, ribs and costal cartilage. Pectoralis major gets inserted to upper end of the humerus and pectoralis minor gets inserted to coracoid process of the scapula.
The serratus anterior that arise from the ribs passes backwards to the vertebral border of scapula. All the three above-mentioned muscles are involved in adduction of the upper arm.
The internal and external intercostals muscles found in between the ribs are involved in the movement of the rib cage.
The diaphragm is the dome-shaped musculotendinous structure that separates the thoracic cavity from the abdominal cavity. It arises from the lumbar vertebrae as two pillars from the posterior surface of the xiphoid process and from the inner surfaces of the lower six pairs of ribs, to converge as a central tendinous portion (Fig. 13.11).
It aids in respiration; flattens during inspiration that allows lung expansion and rises during expiration that helps lungs to expel air. In addition, when it descends the abdominal viscera are compressed that helps in micturition, defecation and in parturition.
There are three openings in the diaphragm that allows passage of esophagus from the thorax into the abdomen, aorta from the thorax and inferior vena cava from abdomen into the thorax.
The upper surface of the diaphragm is in contact with the apex of the heart with its pericardium and the base of the lungs with their pleura.
The under surface of diaphragm is in contact with the liver, stomach, spleen, kidney and suprarenal glands.
Nerve supply to diaphragm is by phrenic and intercostals nerves.
Muscles of the Abdomen
Muscles of the abdomen are present in layers (Fig. 13.12).
The important muscles are the rectus abdominis, transverse abdominis, and internal and external oblique. The two rectus muscles are the straight muscles of the anterior abdominal wall, which are separated in the midline by a line of tendon (linea alba). The two muscles arise from the pubic bone and get inserted into the xiphoid process and adjacent coastal cartilages. It is enclosed in a dense fibrous sheath formed by the aponeuroses of the two oblique muscles called rectus sheath. Three bands of fibrous tissue called tendinous intersections, interrupt the fibers of the rectus muscle.
Two oblique muscles called external and internal oblique muscles form the sides and the anterior part of the abdominal cavity. The external oblique muscle arises from the lower eighth ribs and pass downwards and forwards to get inserted into the rectus sheath, the iliac crest and the pubic bone. The internal oblique muscle arises from the iliac crest and the inguinal ligament; pass upwards and medially across the external oblique to get inserted to rectus sheath and the lower ribs.
The lower border of the external oblique muscle of the abdomen forms the inguinal ligament (Poupart’s ligament). It extends from the anterior superior iliac spine to the pubic tubercle. The femoral artery, vein and nerve pass under Poupart’s ligament into the thigh.
Inguinal canal lies above the inguinal ligament. It is directed obliquely, downwards and forwards. The length of the canal is about 4 cm with internal and external rings. In males it contains spermatic cord and in females, the round ligament of uterus. Protrusion of intestine or omentum through the internal (deep) to the external (superficial) ring is called inguinal hernia. Similarly, protrusion of abdominal viscera with omentum through umbilicus due to lax abdominal wall is called umbilical hernia. Protrusion of abdominal viscera along with omentum into the thigh through femoral canal is called femoral hernia, which is much more common in women than in men.
Muscles of the Posterior Abdominal Wall
The psoas muscle arising from the lumbar vertebrae and the iliacus muscle arising from the inner surface of the ilium are inserted together into the lesser trochanter of the femur. The quadratus lumborum muscle extends from the iliac crest to the 12th rib. The posterior aspect of the kidney is in close contact with quadratus and psoas muscles.
Quadratus lumborum, iliacus and psoas muscles support the posterior part of the lower abdominal wall. The lumbar plexus lies in the substance of psoas muscle. The structures that lie in front of psoas are abdominal aorta, inferior vena cava, the receptaculum chyli and the lymphatic glands. On either side of iliac bone lies the iliacus muscle. In front of the right iliacus muscle lies the cecum and in front of the left iliacus muscle lies the descending colon (Fig. 13.13).
Muscles of the Back
There are several groups of muscles on either side of the spine that extend for varying distances between the occiput above and the sacrum below. These muscles help to keep the neck in extended position and straighten the spine, which maintain the body in upright posture. The important muscles among these are the erector spinae and the lumbar fascia.
Muscles of the Pelvic Floor
The muscles that extend across the pelvic outlet form the pelvic floor.
Figure 13.13: Muscles of posterior abdominal wall (L1–L5, lumbar vertebra; T12, 12th thoracic vertebra)
The three important muscles that go into formation of floor of the pelvis are levator ani, piriformis and coccygeus. The levator ani aids in defecation. The floor has three openings, one for the urethra and the other for the rectum; in women vagina also passes through the pelvic floor (Fig. 13.14).
MUSCLES OF THE LOWER LIMB
The muscles of the buttock is formed by three muscles namely, gluteus maximus, minimus and medius, respectively (Figs 13.15A and B). The gluteus maximus is the most superficial and the largest. It arises from the ilium and inserted into gluteal tuberosity of femur. The other two muscles arise from ilium and are inserted to the greater trochanter of the femur. All the three muscles are involved in the adduction of thigh.
Muscles of the Thigh
Muscles of the thigh fall under three groups:
Anterior group of muscle are sartorius and quadriceps extensor, which is made of rectus femoris, vastus medialis respectively, vastus lateralis and vastus intermedius. These four muscles terminate as a single tendon, the ligamentum patellae, which gets inserted to the tuberosity of the tibia. Its function is extension at the knee joint (Fig. 13.16).
Posterior group of muscles are also called hamstring muscles. The group includes biceps femoris, semitendinosus and semimembranosus. All the muscles arise from the ischial tuberosity and inserted to the upper end of tibia and fibula.These muscles are capable of extending the hip and flexing the knee.
The medial group of muscles includes adductor longus, brevis and magnus. All of them arise from pubic bone and are inserted into the linea aspera of the femur. These muscles are responsible for adduction of the lower limb.
Muscles of the Leg
Muscles of the leg (Fig. 13.17) are capable of moving the foot and are studied under three groups:
Anterior group of muscles lie in front of interosseous membrane. Tibialis anterior pass from tibia to get inserted to tarsal, which causes dorsiflexion at the ankle. Extensor digitorum longus pass from tibia and gets inserted to toes that bring about extension of toes.
Posterior group of muscles include superficial and deep layers:
The superficial muscles are the gastrocnemius and soleus that form the back of the calf. Gastrocnemius arises from the condyle of femur and the soleus arises from posterior aspect of fibula and tibia. Both the muscles are inserted to calcaneum as Achilles tendon. Their action is plantar flexion of the ankle joint.
The deep muscles are tibialis posterior arising from tibia and fibula, and inserted to tarsal bones. Its action is to plantar flex the ankle. The other muscle is flexor digitorum longus, which flexes the toes.
Fibular group of muscles are called peroneal muscles. They arise from lateral surface of fibula and are inserted into tarsal and metatarsal bone of foot. They act to evert the foot outwards.
Dermatomyositis and Polymyositis
Dermatomyositis and polymyositis cause inflammation of the muscles. Dermatomyositis affect women more than men. Although the peak age of onset is in the fifth decade, the disorders can occur at any age.
Signs and Symptoms
Patients complain of muscle weakness that usually worsens over several months, though in some cases symptoms come on suddenly. The affected muscles are close to the trunk, involving, for example, the hip, shoulder or neck muscles. Muscles on both sides of the body are equally affected. In some cases, muscles are sore or tender. Some patients have involvement of the muscles of the pharynx (throat) or the esophagus, causing problems with swallowing. In some cases, this leads to food being misdirected from the esophagus to the lungs, causing severe pneumonia.
In dermatomyositis, there is a rash, though sometimes the rash resolves before muscle problems occur. A number of different types of rash can occur, including rashes on the fingers, the chest and shoulders or on the upper eyelids. In rare cases, the rash of dermatomyositis appears, but myopathy never develops.
Other problems sometimes associated with these diseases include fever, weight loss, arthritis, cold-induced color changes in the fingers or toes (Raynaud’s phenomenon) and heart or lung problems.
The majority of muscle atrophy in the general population results from disuse. People with sedentary jobs and elderly people with decreased activity can lose muscle tone and develop significant atrophy. This type of atrophy is reversible with vigorous exercise. Bedridden people can undergo significant muscle wasting. Astronauts, free of the gravitational pull of earth, can develop decreased muscle tone and loss of calcium from their bones following just a few days of weightlessness.
Muscle atrophy resulting from disease rather than disuse is generally of two types: the one resulting from damage to the nerves that supply the muscles and the disease of the muscle itself. Examples of diseases affecting the nerves that control muscles would be poliomyelitis, amyotrophic lateral sclerosis (Lou Gehrig’s disease) and Guillain-Barré syndrome. Examples of diseases affecting primarily the muscles would include muscular dystrophy (MD), myotonia congenita and myotonic dystrophy as well as other congenital, inflammatory or metabolic myopathies.
Even minor muscle atrophy usually results in some loss of mobility or power.
Some atrophy that occurs normally with ageing
Cerebrovascular accident (stroke)
Spinal cord injury
Peripheral nerve injury (peripheral neuropathy)
Prolonged corticosteroid therapy
Diabetes (diabetic neuropathy)
Amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease
Muscular dystrophy is a group of rare inherited muscle diseases in which muscle fibers are unusually susceptible to damage. Muscles, primarily voluntary muscles, become progressively weaker. In the late stages of muscular dystrophy, muscle fibers are often replaced by fat and connective tissue. In some types of MD, heart muscles, other involuntary muscles and other organs are affected.
The most common types of MD appear to be due to a genetic deficiency of the muscle protein, dystrophin. There is no cure for MD, but medications and therapy can slow the course of the disease.
Muscular Disorders Caused by Bacteria
Normally, a nerve impulse initiates contraction of a muscle. At the same time, an opposing muscle receives the signal to relax so as not to oppose the contraction. Tetanus toxin blocks the relaxation, so both sets of muscle contract. The usual cause of tetany is lack of calcium, but excess of phosphate (high phosphate-to-calcium ratio) can also trigger the spasms.
Infant botulism (floppy baby syndrome) is the most common form of botulism.
If ingested, the toxin is absorbed in the intestine, goes to the blood and on to the nervous system. It acts on the peripheral nervous system by blocking the impulse that is normally passes along to the nervous system. The muscle contraction can be released, resulting in paralysis by blocking the impulse that is normally passed along the motor end plates.
The function of the respiratory system is to get oxygen (O2)into the body and waste gases out of the body. The function of the respiratory system is to transport gases to and from the circulatory system.
Respiration is a vital function of all living organisms that occurs at two different levels:
At the level of the cell: It is the exchange of gases between the blood and the cells of the body. The mitochondria of eukaryotic cells, requires oxygen for aerobic breakdown of glucose to produces large amounts of ATP. During this process carbon dioxide (CO2) is released, which need to be expelled out. This level of respiration is called internal respiration or cellular respiration.
At the level of the organism: An organism must get oxygen into its cells and CO2 out of cells. This level of respiration is called external respiration because the exchange of gases takes place with the external environment. The exchange of O2 and CO2 occurs between air and blood.
External respiration involves the respiratory system. It is a group of organs working together to bring about the exchange of O2 and CO2 with the environment. It is essential to have a respiratory system to ensure the effective exchange of gases with the atmosphere quickly and efficiently to survive. This occurs every time we take a breath.
The atmosphere is approximately 78% nitrogen (N) and 21% O2. The remaining 1% is made up of CO2, water vapor and other trace gases. The respiratory system has adapted to these concentrations of gases in the atmosphere. If the amount of O2 falls much below 15% the respiratory system will be unable to provide enough O2 to support cellular respiration.
HUMAN RESPIRATORY SYSTEM
The human respiratory system consists of the nose, nasal cavity, pharynx, larynx, trachea, smaller conducting passages (bronchi and bronchioles) and the lungs (Fig. 14.1). The respiratory system may be divided into the upper respiratory tract and the lower respiratory tract:
The upper respiratory tract consists of the parts outside the thoracic (chest) cavity, these are the air passages of the nose, nasal cavities, pharynx (windpipe), larynx (voice box) and upper trachea.
The lower respiratory tract consists of the parts found in the thoracic (chest) cavity such as the lower trachea and the lungs themselves.
Air enters the respiratory system through the mouth or nose. The columnar and ciliated epithelial cells line the mucous membrane of the nasal cavity. Air passing over these cells is moistened, warmed and filtered.
The pharynx is a muscular tube that extends from the base of skull to its junction with the esophagus at the level of the cricoid cartilage. It serves as a passage for both air and food. It lies behind the nose (nasopharynx), behind the mouth (oropharynx) and behind the larynx (laryngeal pharynx). The throat is located where passages from the nose and mouth come together. When food is swallowed, a flap of cartilage called epiglottis presses down and covers the opening to the air passage. From the pharynx, the air moves through the larynx, the upper end of the trachea and into the trachea (windpipe), this leads directly to the lungs.
Epiglottis is attached to the top of the thyroid cartilage of larynx. It is a flap of elastic tissue that forms a lid over the opening to the trachea.
Nose provide a direct connection between the outside air and some of the most delicate tissue in the body. They must filter out dust, dirt, smoke, bacteria and a variety of other contaminants found in air. The first filtering is done in the nose.
The nose will do three things to the air inhaled:
Filter the air
Warm the air
Provide moisture (water vapor or humidity) to the air.
As air passes through the nasal cavities it is warmed and humidified, so that air that reaches the lungs is warmed and moist. The nasal airways are lined with cilia and kept moist by mucus secretions. The combination of cilia and mucus helps to filter out solid particles from the air, warm and moisten it. This prevents damage to the delicate tissues that form the respiratory system. The moisture in the nose helps to heat and humidify the air. This helps to keep the air entering the nose from drying out the lungs and other parts of the respiratory system.
When air enters the respiratory system through the mouth, much less filtering is done. It is generally better to breathe in air through the nose.
The larynx (Adam’s apple or voice box) is located between the pharynx and the trachea (at the top of the trachea). It extends from the pharynx up to the level of sixth cervical vertebra. It is composed of cartilages, ligaments and membranes (Fig. 14.2). The largest of these cartilages is thyroid cartilage, which forms the prominence in front of the neck.
The cricoid cartilage lies just below the thyroid cartilage. Inside and stretched across the larynx are two highly elastic folds of tissue (ligaments) called vocal cords. Air rushing through the voice box causes the vocal cords to vibrate producing sound waves. The warmed, filtered and moistened air passes from the larynx downward into the thoracic cavity through the trachea.
The trachea (Fig. 14.3) is about 10 cm in length that extends from the larynx to about the level of fifth thoracic vertebra. The walls of the trachea are made up of C-shaped rings of tough flexible cartilage. These rings of cartilage protect the trachea, make it flexible and keep it from collapsing or over expanding. The cells that line the trachea produce mucus; the mucus helps to capture dust and still present in the air microorganisms and is swept out of the air passage by tiny cilia into the digestive system.
Within the thoracic cavity, at the level of the fifth thoracic vertebra the trachea divides into two branches, the right and left bronchi. Each bronchus enters the lung on its respective side. The lungs are the site of gas exchange between the atmosphere and the blood. The right lung has three divisions or lobes and is slightly larger than the two-lobed left lung. The lungs are inside the thoracic cavity, bounded by the rib cage and diaphragm. The pleural membrane encases the lungs and lines the entire thoracic cavity. In between the two layers of the pleural membrane mucus is secreted, which decreases friction from the movement of the lungs during breathing.
The further branching of the bronchial tubes is often called bronchial tree. The trachea resembles the trunk of an upside down tree with extensive branches that become smaller and smaller; these smaller branches are the bronchioles. Both bronchi and bronchioles contain smooth muscle tissue in their walls. This muscle tissue controls the size of the air passage. The bronchioles continue to subdivide until they finally end in clusters of tiny hollow air sacs called alveoli.
The lungs are encased in a double-layered serous membrane called pleura. The pleural layer that is in contact with the lung surface pass into the fissures in between the lobes of the lungs, and reflect back at the root of the lung and continues as parietal pleura that covers the interior of chest wall. In between these two layers of pleura is the slight exudates (pleural fluid), which lubricates the surfaces. The pleural fluid prevents the friction between the lungs and chest wall during respiratory movements. Excessive accumulation of fluid in the pleural cavity is called pleural effusion, and air getting into pleural cavity (due to injury) is called pneumothorax.
Groups of alveoli appear as bunches of grapes. Alveoli are the sites of gas exchange in the lungs (Figs 14.4A and B). The alveoli consist of thin, flexible membranes that contain an extensive network of capillaries. The membranes separate gas from liquid. The gas is the air taken in through the respiratory system and the liquid is blood. The functional unit of the lungs is the alveoli; it is here that the circulatory and respiratory systems come together, for the purpose of gas exchange. All exchange of gases in the lungs occurs in the alveoli. Each lung contains nearly 300 million alveoli and has a total surface area about 40 times the surface area of the skin.
The lungs are two in number. They fill the chest cavity, one on each side separated in the middle by the heart, its great vessels and other structures embedded in the mediastinum. The lungs are cone shaped with the apex above that rises a little above the clavicle into the root of the neck. The base of the lungs rests on the floor of thoracic cavity on the diaphragm. The outer surface of the lungs is in contact with the ribs, the inner surface facing the mediastinum is the root of the lung, the posterior border of the inner surface is in contact with the vertebral column and the anterior border of the inner surface overlaps the heart (Fig. 14.5).
The fissures divide the lungs into lobes. The right lung has three lobes and the left lung has two lobes. Each lobe has a number of lobules with a bronchiole. As the bronchiole divides and subdivides, its wall gets thinner and thinner, which finally ends in small dilated sacs called alveoli.
The pulmonary artery that carries deoxygenated blood from the right ventricle to the lungs and its branches lie in contact with the bronchial tubes. These branches of the arteries divide and subdivide to end up into a network of capillaries, which lie in contact with the walls of the alveoli. It is here the exchange of gases take place between the air in the alveoli and the erythrocytes circulating in the capillaries in contact with the alveoli.
The capillaries unite again to form pulmonary veins that leave each lung carrying the oxygenated blood to the left atrium of the heart. The heart in turn supplies the oxygenated blood to the rest of the body.
The root of the lung is formed by pulmonary artery and vein, bronchi, bronchial arteries and veins, lymphatic veins, nerves and lymphatic glands.
MECHANISM OF BREATHING
Breathing is the entrance and exit of air into and out of the lungs. Ventilation is the term for the movement of air in to and out of the alveoli.
Inhalation and Exhalation
Every single time you take a breath or move air in and out of the lungs, two major actions take place (Figs 14.6A and B):
During inspiration (inhalation) the ribs are elevated by the action of external intercostal muscles. This increases intrathoracic volume, thereby the intrathoracic pressure falls and therefore air flows into airway down its pressure gradient.
During expiration (exhalation), ribs are lowered by the action of internal intercostal muscles.This decreases intrathoracic volume, thereby the intrathoracic pressure falls and the air flows out of airway down its pressure gradient.
These two actions deliver O2 to the alveoli, and remove CO2. The continuous cycles of inhalation and exhalation are known as breathing. Most of us breathe 10–15 times per minute.
The lungs are not directly attached to any muscle, so they cannot be expanded or contracted. Inhalation and exhalation are actually produced by movements of the large flat muscle called diaphragm and the intercostal muscles.
The diaphragm is located along the bottom of the rib cage and separates the thoracic cavity from the abdominal cavity. Before inhalation the diaphragm is curved upward into the chest. During inhalation, the diaphragm contracts and moves down, causing the volume of the thoracic cavity to increase. When the diaphragm moves down, the volume of the thoracic cavity increases and the air pressure inside it decreases. The air outside is still at atmospheric pressure (around 760 mm Hg), to equalize the pressure inside and out, the air rushes through the trachea into the lungs (inhaled).
When the diaphragm relaxes, it returns to its curved position. This action causes the volume of air in the thoracic cavity to decrease. As the volume decreases, the pressure in the thoracic cavity outside the lungs increases. This increases the air pressure and causes the lungs to decrease in size. The air inside the lungs is pushed out or exhaled.
At rest breathing is done with the help of diaphragm and intercostal muscles; under extreme conditions of activity other muscles in thoracic cavity can be used to breathe.
Since the breathing is based on atmospheric pressure, the lungs can only work properly, if the space around them is sealed. When the diaphragm contracts, the expanded volume in the thoracic cavity quickly fills as air rushes into the lungs. If there is a small hole in the thoracic cavity, the respiratory system will not work. Air will rush into the cavity through the hole, upset the pressure relationship and possibly cause the collapse of a lung.
Hemoglobin and Gas Exchange
Three important things happen to the air inhaled:
Oxygen is extracted.
Carbon dioxide is added.
Water vapor is added.
This occurs in the alveoli of the lungs; the lungs consist of nearly 300 million alveoli where gas exchange occurs (the exchange of CO2 and O2). Blood flowing from the heart enters capillaries surrounding each alveolus and spreads around the alveolus. This blood contains a large amount of CO2 and very little O2. The concentration of the gases in the blood and the alveolus are not equal (concentration gradient). This causes the diffusion of CO2 from the blood to the alveolus and the diffusion of O2 from the alveolus into the blood. The blood leaving the alveolus has nearly tripled the total amount of oxygen, it originally carried.
Two special molecules help this process of gas exchange to work effectively:
Soap-like macromolecules consisting of phospholipid and protein, which coat the inner surface of the alveolus and keep them open.
Hemoglobin (Hb), an oxygen carrying molecule is a component of blood, which is a red-colored protein found in red blood cells. Each Hb molecule has four sites to which O2 atoms can bind. Thus, one Hb molecule can carry up to four molecules of oxygen.
Inspiration is an active process and expiration is largely a passive process. Inspiration is the result of two processes, the upward movement of the ribs and the downward movement of the diaphragm.
Regulation of Breathing
Breathing is such an important function that the nervous system will not let to have complete control of it. The mechanism of respiration is controlled and regulated by the nervous and chemical control.
Breathing is an involuntary action under control of the medulla oblongata in the lower part of the brain. Sensory neurons in this region control motor neurons in the spinal cord. The efferent impulses pass to the muscles of respiration; impulses to diaphragm are conveyed through phrenic nerves (via vagus), and to intercostal muscles through intercostal nerves. Although breathing can be consciously controlled to a limited extent such as holding the breath, it cannot be consciously suppressed. The need to supply O2 to the cells and remove CO2 is a powerful one. One can only hold the breath until consciousness is lost, and then the brain takes control and normal breathing resumes.
Carbon dioxide and hydrogen ions (blood acidity) are the primary stimuli that cause to breathe. The nervous system must have a way to determine whether enough O2 is getting into the blood. Two special sets of sensory neurons constantly check the levels of gases in the blood. These special sensory receptors are sensitive to the levels of gases in the blood, especially the level of CO2. One set is located in the carotid arteries in the neck, which carry blood to the brain, and the other set is located near the aorta. When CO2 dissolves in the blood, it forms carbonic acid (H2CO3), which is unstable and immediately breaks down into hydrogen ion (H+) and bicarbonate ion (HCO3–):
CO2 + H2O ➔ H2CO3
H2CO3 ➔ H+ + HCO3–
That means most of the CO2 travels in the blood as HCO3–. When the blood reaches the lungs, the series of reactions is reversed. The HCO3– combine with a H+ to form H2CO3, which in turn forms CO2 and water. The CO2 diffuses out of the capillaries into the alveoli and is exhaled into the atmosphere. The change in hydrogen ion concentration following these reactions, change the acidity (pH) of the blood and it is this change in acidity to which the special sensory cells respond to.
The normal volume moved in or out of the lungs during quiet breathing is called tidal volume. In a relaxed state, only a small amount, about 500 mL of air is brought in and out. The amount of air inhaled and exhaled, can be increased by breathing deeply. Breathing in very deeply is inspiratory reserve volume and can increase lung volume by 2,900 mL, which is quite a bit more than the tidal volume of 500 mL. Expiration can also be increased by contracting the thoracic and abdominal muscles. This is called expiratory reserve volume and is about 1,400 mL of air. Vital capacity is the total of resting tidal volume, inspiratory reserve and expiratory reserve volumes; it is called vital capacity because it is vital for life, and the more air you can move, the better off you are. There are a number of illnesses that will decrease vital capacity. Vital capacity can vary a little depending on how much inspiration can be increased by expanding the chest and lungs. During breathing some air never even reaches the lungs; instead it fills the nasal cavities, trachea, bronchi and bronchioles. These passages are not used in gas exchange so they are considered to be dead air space. To make sure that the inhaled air gets to the lungs, we need to breathe slowly and deeply. Even when we exhale deeply some air (about 1,000 mL) is still in the lungs and is called residual volume. This air is not useful for gas exchange. There are certain types of diseases of the lung where residual volume builds up because the person cannot fully empty the lungs. This means that the vital capacity is also reduced because their lungs are filled with useless air. Lung capacity is shown in Figure 14.7.
Stimulation of Breathing
There are two pathways of motor neuron stimulation of the respiratory muscles. The first is the control of voluntary breathing by the cerebral cortex. The second is involuntary breathing controlled by the medulla oblongata.
There are chemoreceptors in the aorta, the carotid body of carotid arteries and in the medulla oblongata of the brainstem that are sensitive to pH. As CO2 levels increase there is a buildup of H2CO3, which releases hydrogen ions and lowers pH. Thus, the chemoreceptors do not respond to changes in O2 levels, but to pH, which is dependent upon plasma CO2 levels.
In other words, CO2 is the driving force for breathing. The receptors in the aorta and the carotid sinus initiate a reflex that immediately stimulates breathing rate and the receptors in the medulla stimulate a sustained increase in breathing until blood pH returns to normal.
This response can be experienced by running 100 meter dash. During this exertion the muscle cells must metabolize ATP at a much faster rate than usual and thus will produce much higher quantities of CO2. The blood pH drops as CO2 levels increase and this will involuntarily increase breathing rate very soon after beginning the sprint. An individual continues to breathe heavily after the race, thus expelling more CO2, until pH has returned to normal. Metabolic acidosis therefore is acutely corrected by respiratory compensation (hyperventilation).
PROBLEMS ASSOCIATED WITH THE RESPIRATORY TRACT AND BREATHING
The environment of the lung is very moist, which makes it a hospitable environment for bacteria. Many respiratory illnesses are the result of bacterial or viral infection of the lungs. Because of constantly being exposed to harmful bacteria and viruses in the environment, the respiratory health can be adversely affected. There are a number of illnesses and diseases that can cause problems with breathing. Some are simple infections and others are disorders that can be quite serious.
Carbon Monoxide Poisoning
Carbon monoxide (CO) poisoning is caused when CO binds to Hb in place of O2. CO binds much stronger to Hb without releasing, which causes unavailability of Hb for O2 binding. The result can be fatal in a very short amount of time.
Mild symptoms: Flu-like symptoms, dizziness, fatigue, headache, nausea and irregular breathing.
Moderate symptoms: Chest pain, rapid heartbeat, difficulty in thinking, blurred vision, shortness of breath and unsteadiness.
Severe symptoms: Seizures, palpitations, disorientation, irregular heartbeat, low blood pressure, coma and death.
Pulmonary embolism is the blockage of the pulmonary artery (or one of its branches) by a blood clot, fat and air or clumped tumor cells. By far the most common form of pulmonary embolism is a thromboembolism, which occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes to the arterial blood supply for one of the lungs. Symptoms may include difficulty in breathing, pain during breathing, and more rarely circulatory instability and death. Treatment, usually, is with anticoagulant medication.
Upper Respiratory Tract Infections
Upper respiratory tract (URT) infections can spread from the nasal cavities to the sinuses, ears and larynx. Sometimes a viral infection can lead to what is called secondary bacterial infection. ‘Strep throat’ is a primary bacterial infection and can lead to an upper respiratory infection that can be generalized or even systemic (affects the body as a whole). Antibiotics are not used to treat viral infections, but are successful in treating most bacterial infections, including strep throat. The symptoms of strep throat can be high fever, severe sore throat, white patches on a dark red throat and stomach ache.
An infection of the cranial sinuses is called sinusitis. Only 1–3% of upper respiratory tract infections are accompanied by sinusitis. This ‘sinus infection’ develops when nasal congestion blocks off the tiny openings that lead to the sinuses. Symptoms include postnasal discharge, facial pain that worsens when bending forward and sometimes even tooth pain can be a symptom. Successful treatment depends on restoring the proper drainage of the sinuses. Taking a hot shower or sleeping upright can be very helpful. Otherwise, using a spray decongestant or sometimes a prescribed antibiotic will be necessary.
Otitis media in an infection of the middle ear. Even though the middle ear is not part of the respiratory tract, it is often a complication seen in children who have a nasal infection. The infection can spread by the auditory (eustachian) tube that leads from the nasopharynx to the middle ear. The main symptom is usually pain. Sometimes, vertigo, hearing loss and dizziness may be present. Antibiotics can be prescribed and tubes are placed in the eardrum to prevent the building up of pressure in the middle ear and the possibility of hearing loss.
Tonsillitis occurs when the tonsils become swollen and inflamed. The tonsils located in the posterior wall of the nasopharynx are often referred to as adenoids. If a patient is suffering from tonsillitis frequently and breathing becomes difficult, they can be removed surgically by a procedure called tonsillectomy.
An infection of the larynx is called laryngitis. It is accompanied by hoarseness and not being able to speak in an audible voice. Usually, laryngitis disappears with treatment of the upper respiratory tract infection. Persistent hoarseness without a upper respiratory tract infection is a warning sign of cancer and should be checked by physician.
Lower Respiratory Tract Disorders
Lower respiratory tract disorders include infections, restrictive pulmonary disorders, obstructive pulmonary disorders and lung cancer.
Lower Respiratory Infections
Acute bronchitis: An infection that is located in the primary and secondary bronchi is called bronchitis. Most of the time, it is preceded by a viral URT infection that led to a secondary bacterial infection. Usually, a non-productive cough turns into a deep cough that will expectorate mucus and sometimes pus.
Pneumonia: It is a bacterial or viral infection in the lungs, where the bronchi and the alveoli fill with a thick fluid. Usually, it is preceded by influenza. Symptoms of pneumonia include high fever and chills with headache and chest pain. Pneumonia can be located in several lobules of the lung and obviously, the more lobules involved, the more serious is the infection. It can be caused by bacteria that are usually held in check, but due to stress or reduced immunity has gained the upper hand.
Restrictive Pulmonary Disorders
Pulmonary fibrosis: Vital capacity is reduced in these types of disorders because the lungs have lost their elasticity. Inhaling particles such as sand, asbestos, coal dust or fiberglass and certain anticancer drugs can lead to pulmonary fibrosis, a condition where fibrous tissue builds up in the lungs. This means lungs cannot inflate properly and are always tending toward deflation.
Asthma: This is a respiratory disease of the bronchi and bronchioles. The symptoms include wheezing, shortness of breath and sometimes a cough that expels mucus. The airways are very sensitive to irritants, which can include pollen, dust, animal dander and tobacco. Even being out in cold air can be an irritant. When exposed to an irritant, the smooth muscle in the bronchioles undergoes spasms. Most asthma patients have at least some degree of bronchial inflammation that reduces the diameter of the airways and contributes to the seriousness of the attack. While asthma is not curable, it is treatable.
Asthma is a lifelong disease, meaning that one is born with it. A little known fact about asthma is that it can remain dormant until a certain age or a strong enough trigger brings it out of dormancy. Asthma is brought out of dormancy by triggers like pollen, smoke and animal dander, not stress. Stress is commonly thought to be a trigger of asthma, which is far away from the truth. while stress can increase the intensity of an attack, it cannot initiate an attack.
Respiratory Distress Syndrome
At birth the pressure needed to expand the lungs requires high inspiratory pressure. In the presence of normal surfactant levels the lungs retain as much as 40% of the residual volume after the first breath and thereafter will only require far lower inspiratory pressures. In case of surfactant deficiency, the lungs will collapse between breaths, this makes the infant work hard and each breath is as hard as the first breath. If this goes on, the pulmonary capillary membranes become more permeable, letting in fibrin rich fluids between the alveolar spaces and in turn form a hyaline membrane. The hyaline membrane is a barrier to gas exchange. this hyaline membrane then causes hypoxemia and CO2 retention that in turn will further impair surfactant production.
Type two alveolar cells produce surfactant and do not develop until the 25th to 28th weeks of gestation. Therefore, respiratory distress syndrome is one of the most common diseases in premature infants. Surfactant synthesis is influenced by hormones such as insulin and cortisol. Insulin inhibits surfactant production, explaining why infants of mothers with diabetes type I are at risk of development of respiratory distress syndrome. Cortisol can speed up maturation of type II cells and therefore production of surfactant. If the baby is delivered by cesarean section, they are at greater risk of developing respiratory distress syndrome because of the reduction in cortisol production due to lack of stress that happens during vaginal delivery. Hence, cortisol increase in high stress helps in the maturation of type II cells of the alveoli that produce surfactant.
Treatment is initiated post birth and in infants who are at high risk for respiratory distress syndrome. The treatment is by administration of synthetic surfactants suspended in a saline solution through the airways by an endotracheal tube.
Sleep apnea is a sleep disorder characterized by pauses in breathing during sleep. These episodes called apneas, last long enough so that one or more breaths are missed and occur repeatedly throughout sleep. The standard definition of any apneic event includes minimum 10 seconds interval between breaths with either a neurological arousal or a blood oxygen desaturation of 3%–4% or greater, or both arousal and desaturation. Sleep apnea is diagnosed with an overnight sleep test called polysomnogram. One method of treating central sleep apnea is with a special kind of continuous positive airway pressure (CPAP) machine with spontaneous time (ST) feature. This machine forces the wearer to breathe a constant number of breaths per minute.
Continuous positive airway pressure in which a controlled air compressor generates an airstream at a constant pressure. This pressure is prescribed by the patient’s physician based on an overnight test or titration.
Cystic fibrosis is most common in Caucasians and will occur to 1 in every 2,500 people. It is most known for its effects on the respiratory tract although it does affects other system as well. The respiratory passages become clogged with thick mucus that is difficult to expel even with vigorous coughing. Breathing becomes difficult and affected individuals run the risk of choking to death with their lungs own secretions unless strenuous effort is made to clear the lungs multiple times every day. Victims frequently will die in the 20s because of pneumonia. In cystic fibrosis, the mucus is thicker and difficult to clear from the passageways. Cystic fibrosis is caused by defect in a type of chloride protein found in apical membranes of epithelial cells in the respiratory system and elsewhere. This defect directly impedes the chlorine ions transport, which then indirectly affects the transport of potassium ions. This causes the epithelium, to not create its osmotic gradient necessary for water secretion. It has been known for a long time that cystic fibrosis is caused by a single abnormal gene. This gene codes for a portion of the chloride channel protein.
NUTRITION FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS
Nutrition is particularly important for ventilator-dependent patient. When metabolizing macronutrients, CO2 and water are produced. The respiratory quotient (RQ) is a ratio of CO2 produced to amount of O2 consumed. Carbohydrates metabolism produces the most amount of CO2, so they have the highest RQ. Fats produce the least amount of CO2. Protein have a slightly higher RQ ratio than fats. It is recommended that chronic obstructive pulmonary disease patients do not exceed a 1.0 RQ. Lowering carbohydrates and supplementing fat or protein in the diet might not result in maintaining the desired outcome because, excess amounts of fat or protein may also result in a RQ higher than 1.0.
The food we consume contains nutrients (chemical substances) or molecules that provide energy and material for growth, repair and maintenance. All the different foods contain at least one of the six kinds of nutrients such as carbohydrates, proteins, lipids (fats), vitamins, minerals and water.
Four of these nutrients—carbohydrates, proteins, fats, and vitamins are organic compounds, because they contain the elements carbon, hydrogen and oxygen. The remaining two nutrients—minerals and water are inorganic compounds.
Nutrition is the science or study of how our bodies obtain energy, build tissue and control body functions using materials supplied in the food we eat. Like any machine that does work, our bodies need fuel, which come in the form of food. It supplies us with energy not only to do work but also to generate the heat that maintains our body temperature.
The amount of energy that can be obtained from food is measured as a calorie. It is the amount of energy needed to raise the temperature of 1 g of water by 1°C.
The energy content of food is expressed in terms of the kilocalorie or kcal, which is 1,000 calories or cal.
Basal Metabolic Rate
The basic energy need of an average-sized adult human is about 1,500 calories/day. Energy needs vary depending on the kind of work we do, how active we are, our gender and our age. Men generally have higher energy needs than women. If we measure our body’s metabolism (the sum of all the chemical processes that take place within an organism) the results would be expressed as basal metabolic rate (BMR), which is equal to the number of kilocalories we must use in a set amount of time just to maintain life. The BMR for females is 1,300–1,500 kcal/day. A male has a BMR of 1,600–1,800 kcal/day.
Food supplies, building materials, the substances required by the cells in our body for proper growth and development. Tissue throughout the body must be repaired and replaced. Proteins and nucleic acids cannot be synthesised unless key compounds are supplied by a complete diet.
A balanced diet includes foods from the four basic food groups or food pyramid (Fig. 15.1), which are:
Vegetables and fruits, 5–9 servings
Grain products, such as bread and cereals, 6–11 servings
Dairy products, 2–3 servings
Protein-rich foods such as meat, fish and beans, 2–3 servings.
According to the food pyramid, a healthy diet consists of many more servings of breads, fruits and vegetables each day than meats and dairy foods.
The six essential nutrients are carbohydrates, proteins, lipids (fats), vitamins, minerals and water.
Carbohydrates meet most of the energy need of our body. These are compounds made of carbon, hydrogen and oxygen in approximately 1:2:1 ratio (C6H12O6). The examples are sugars and starches. Before our body can use energy contained in carbohydrates, it must first be broken down. The digestive system is capable of breaking down most of the carbohydrates into glucose that provides most of the energy used by cells.
If we eat more carbohydrates than our body needs for energy, the excess is changed to glycogen and is stored in the liver and the muscles. When the glycogen stores are full, the body then converts the excess into fat for longterm storage.
According to complexity in the structure, carbohydrates are grouped as monosaccharides, disaccharides and polysaccharides.
Monosaccharides: These are single sugars such as glucose and fructose, a sugar found in fruits.
Disaccharides or double sugars: It consists of two single sugars linked together. Common disaccharides include sucrose (table sugar), lactose (milk sugar) and maltose (sugar contained in cereal grains).
Polysaccharide: This is a carbohydrate made of long chains of sugars. The prefix poly means ‘many’. Starches, such as those in rice, bread, pasta and potatoes are polysaccharides.
The digestive system must breakdown starches into disaccharides; disaccharides are then broken apart to yield simple sugars such as glucose. Starches take longer time than most sugars to breakdown in the digestive system. Starches provide the body with energy over a longer period of time than sugars.
Cellulose is a polysaccharide present in the cell walls of plants, vegetables, fruits, whole grain breads and cereals. Our body cannot breakdown cellulose, so it has no value as a nutrient, but provides fiber (bulk, roughage) an important part of the diet. Fiber aids in digestion and offers some protection against heart disease and certain types of cancer.
Carbohydrates and fats provide the energy, but do not provide many of the materials the body needs for growth and repair. Growth and repair require the materials contained in proteins. Proteins are the construction materials for the body parts such as muscles, skin, blood and other proteins such as enzymes.
Our bodies contain thousands of different proteins, which are made of smaller units called amino acids. All these proteins are made from about 20 different amino acids. Most amino acids are made in the body (12), which are designated as non-essential amino acids. The other eight amino acids, which can only be obtained in the foods we eat, are designated as essential amino acids.
The proteins that contain all eight essential amino acids are called complete proteins. They are of animal origin, such as meat, eggs and dairy products. These proteins are often referred to as class A proteins. The examples of class A proteins are albumin, myosin, caseinogen, globulin and vitellin. Most plant products lack some of the essential amino acids and are called incomplete proteins.
Before our bodies can use the proteins in foods, the proteins must be broken down into their component amino acids. Cells then use the amino acids to synthesize new proteins.
Lipids or Fats
Although too much fat is not healthy, our body does need some fat. They are important for several reasons:
They are a concentrated source of energy.
Fats store other nutrients such as vitamin A.
Fats protect vital organs.
They help keep our skin from drying out.
Lipids, a kind of fat, are important part of the cell membrane.
Fats help to insulate the body against changes in environmental temperature.
Fat is made of three fatty acids joined to a glycerol molecule. Fatty acids are chains of carbon and hydrogen compounds with a weak acid group attached to one end. When we eat foods containing fats, the body must first breakdown the fats into their basic components of glycerol and fatty acids. From these raw materials, other lipids can be made. The body uses lipids to make cell membranes, hormones, and the oils on our skin and hair.
Fatty acids are classified as either saturated or unsaturated. The classification depends on the presence or absence of double bonds in the fatty acid chain. Fats with double bonds are called unsaturated fats. Most unsaturated fats are liquid at room temperature, come from plants and are usually referred to as oils. However, some vegetable oils, such as palm oil and coconut oil, are composed primarily of saturated fats. Fats with many double bonds are called polyunsaturated fats. Saturated fats are usually solid at room temperature and most come from animal products. A fat with only one double bond is called monounsaturated fat.
Fats provide twice as many calories per gram as carbohydrates. Fats are an excellent way to store energy for future use. When a person eats more food than is needed, the body stores extra energy by producing fat. It is deposited in a layer just under the skin.
A healthy diet should contain more of unsaturated fats whenever possible. The good sources of unsaturated fatty acids are the vegetable oils and fish. They offer protection against atherosclerosis.
Water is the most important and the simplest of the essential nutrients. Animals will die from lack of water much before they starve from lack of food. Most of the weight of our bodies is water, which accounts for at least half of our total body mass. Blood plasma (the liquid part of blood) is more than 90% water. The important functions of water are as follows:
Water is an excellent solvent in which food and enzymes are dissolved in the digestive system.
Water dissolves the waste materials that are eliminated in urine.
Water also helps to regulate body temperature. It absorbs the heat released in cellular respiration and distributes the heat throughout the body. When the body needs to cool, the water in the body evaporates as perspiration from the skin, which draws heat from the body. Sweat glands also remove water from tissues to cool the body. Each time we take a breath we lose water.
Water is constantly being lost from the body, so a steady supply of this liquid is required. Every day our body loses about 3–5 L of water through sweat, urine and exhaled air. Most of the water is replaced by drinking liquids, but we can also obtain small quantities of water from the foods we eat and as byproducts of cellular respiration.
If we lose more than 12% of our body water, it results in a serious condition referred to as dehydration, which can cause death if untreated.
Minerals are inorganic substances required for the normal functioning of the body. The examples are calcium, iron, potassium, sodium and magnesium to function properly. Many bodily functions rely on minerals (Table 15.1).
We obtain minerals from the food we eat. The body cannot digest the minerals it takes in; it does lose many of them in sweat, urine and other waste products.
Most of the minerals cannot be stored in the body; hence they must be included regularly in the diet. Some minerals come from foods of plant products; the other minerals can be obtained by eating animal products or other foods. A balanced diet usually provides all the minerals the body needs.
Vitamins are complex organic molecules that are needed by the body in very small amounts that serve as coenzymes. Vitamins do not provide energy, but most of them are enzyme helpers and play a role in cellular reactions (Table 15.2). With the exception of vitamin D, vitamins are not made by the body and must be obtained from food. Vitamin D can be synthesized in the skin under direct sunlight. This synthesis involves the conversion of cholesterol to vitamin D enzymes and sunlight.
The vitamins are classified based on their solubility properties (refer Table 15.2).
Water-soluble vitamins: They cannot be stored in the body and should be included in a balanced diet every day and include vitamins B and C.
Fat-soluble vitamins: They can be stored in the fatty tissue of our bodies and include vitamins A, D, E and K.
Like other essential nutrients, most vitamins can be obtained naturally by eating a balanced diet that includes fresh fruits, vegetables and meats. When the body does not receive a sufficient supply of vitamins, it can develop vitamin deficiency diseases that are as follows:
Deficiency of vitamin C causes scurvy
Deficiency of vitamin A causes night blindness and xerophthalmia
Deficiency of vitamin D can cause osteoporosis
Deficiency of vitamin B1 can cause beriberi
Deficiency of vitamin B2 can cause dermatitis and cracked fissures around the mouth and nose
Deficiency of vitamin B3 (niacin) can cause pellagra
Deficiency of vitamin B12 and folic acid causes anemia.
The principle task of the digestive system is to transfer the nutrients from the food we eat into our body where those nutrients will be used for processes such as providing energy, protein production and general tissue maintenance.
The nutrients must first be broken down physically and chemically. This process of breaking down food into simple molecules that the body can use is called digestion.
The digestive system is a long, hollow tube called gastrointestinal tract (GI tract) or digestive tract. It begins with the mouth and winds through the body to end up as the anus. The GI tract includes the mouth, pharynx, esophagus, stomach, small intestine and large intestine (Fig. 16.1). Digestion is aided by several organs (exocrine glands), along the digestive tract, which includes the salivary glands, the pancreas and the liver, which add their secretions into the digestive system, but are not part of the GI tract (Table 16.1).
The digestive process involves four activities:
Mechanical digestion (breaking down food into fine pulp) is the first task of the digestive system. This increases the surface area of food molecules for the enzymes (digestive chemicals) to act. The process of mechanical digestion is to break food into tiny pieces without changing its chemical structure.
Chemical digestion of food is the second task of the digestive system. In this phase enzymes act on food, to break it down further into much smaller particles, which are chemically simple enough to be absorbed into the bloodstream. For example, starch is broken down to simple sugars, lipids to fatty acids and proteins to amino acids.
Absorption of small molecules into the bloodstream and lymph vessels for distribution to the rest of the body is the last step.
Defecation is the excretion of food substances that cannot be digested (e.g. cellulose) or absorbed.
Both mechanical and chemical digestion begins in the mouth (Fig. 16.2). Chewing is the first step in mechanical digestion.
During chewing, three sets of salivary glands (Fig. 16.3) located near the mouth produce saliva; a mixture of water, mucus and a digestive enzyme called salivary amylase, which is mixed with the chewed food.
Enzymes in the saliva kill bacteria and begin the process of chemical digestion by breaking down starch into disaccharide (maltose). The mucus in the saliva softens and lubricates food, and helps to hold the food together.
Human teeth are well-adapted for chewing many kinds of food. The 32 teeth of the normal adult have three basic shapes (Fig. 16.4A), each with a different function:
Incisors are sharp front teeth used for biting into and tearing pieces of food.
Canines are pointed teeth next to incisors, used to tear or shred food.
Premolars and molars are at the back of the mouth, have large flat surfaces that crush and grind food.
Every tooth has two main parts (Fig. 16.4B), the crown and the root. A tooth is made of four layers of tissue namely enamel, dentin, cementum and pulp.
The crown is covered by enamel, a calcium-containing material that is the hardest substance in the body.
Dentin is a bone like tissue that makes up most of the inside of a tooth.
Cementum is a thin layer covering the dentin of the root.
Pulp is the center of the structure, which contains connective tissue cells, blood vessels and nerve.
The tongue helps to keep the food between the chewing surfaces of the upper and lower teeth by manipulating it against the hard palate (the bony membrane-covered roof of the mouth). This structure is different from the soft palate, an area located just behind the hard palate.
Once the teeth and salivary glands have completed the initial processing, the food is ready to be swallowed. Gathering the food together in a ball called bolus; the tongue pushes it to the back of the mouth and into the pharynx. The pharynx is at the back of the throat that connects the nose and mouth to the digestive, and respiratory tracts. In the pharynx, the GI tract and the respiratory system cross each other. As the tongue moves food into the pharynx, it presses down on a small flap of cartilage called epiglottis. When the epiglottis is depressed, it closes the entrance to the respiratory tract and guides the food down the GI tract.
The bolus moves from the pharynx into the esophagus, a 25 cm long muscular tube that connects the pharynx with the stomach. Once the bolus is in the esophagus, muscles of the esophagus wall move it toward the stomach by peristaltic movement (waves of muscular contractions called peristalsis move food through the digestive tract). The esophagus has two muscle layers: a circular layer that wraps around the esophagus and a longitudinal layer that runs the length of the tube. Contractions of the muscles move the bolus to the cardiac sphincter valve where the esophagus joins the stomach. The sphincter allows food to pass into the stomach, but usually not letting it move back up into the esophagus.
The stomach is a J-shaped muscular sac (Fig. 16.5) located in the upper left side of the abdominal cavity, just below the diaphragm. The stomach is involved in both mechanical and chemical digestion. It has thick expandable walls made of layers of muscles that contract in opposite direction. Mechanical digestion occurs by mixing and churning the food when the stomach walls contract strongly.
These contractions are responsible for the ‘growling’ noises our stomach makes that are the loudest when we have an empty stomach.
Chemical digestion of food in the stomach begins with the actions of hydrochloric acid and an enzyme called pepsin. Gastric glands in the stomach secrete both the substances. This fluid that carry out chemical digestion in the stomach is known as gastric fluid. Pepsin breaks down proteins into shorter chains of amino acids called peptides; pepsin works best at an acidic pH, which is provided by the HCl. The pH at different parts of GI tract is given in table 16.2.
Another fluid secreted by glands in the stomach is mucus, which lubricates food so that it can travel through the digestive tract more easily. It also coats the walls of the stomach and protects the muscle tissue from being broken down by other digestive fluids.
The inner lining of the stomach is a thick, wrinkled mucosal membrane composed of epithelial cells. This membrane is dotted with small openings called gastric pits; they are the open ends of gastric glands that release secretions into the stomach (refer Fig. 16.5). Some of these glands secrete mucus, some secrete digestive enzymes and still others secrete HCl. The mixture of these fluids forms the acidic digestive fluid. The life of cells lining the stomach wall is short and is replaced about every 3 days. The food stays in stomach for about 3–4 hours during which the mechanical and chemical treatment reduces the food to a soft pulp called chyme. chyme is a thick liquid, made up of partially digested proteins, starches vitamins, minerals, and acids, and undigested sugars and fats. Now, the pyloric sphincter valve between the stomach and small intestine opens to allow chyme to pass into the small intestine. By the time chyme leaves the stomach, most proteins have been broken down into smaller polypeptides. Sugars and fats have not yet been chemically altered. Some starch molecules have been broken down into disaccharides.
The pancreas is an organ located behind the stomach (Fig. 16.6). It measures about 7 inches long and extends from the duodenum to the spleen. It has three parts—a head, a neck and a body.
The head lies to the right of the abdominal cavity and within the concavity of the duodenum. The body lies behind the stomach and in front of the first lumbar vertebra. The tail is a narrow part that extends to the left and touches the spleen.
Pancreas is a compound racemose gland composed of lobes and lobules with tiny ducts. The ducts join together to form the main pancreatic duct that joins the common bile duct and drain its secretions into the duodenum through an ampulla. The pancreatic fluid contains enzymes that digest proteins, fats and carbohydrates. It also contains sodium bicarbonate, which neutralizes the HCl in chyme and protects the small intestine.
The liver is a large brownish organ that lies in the uppermost part of the abdominal cavity on the right side, beneath the diaphragm and above the stomach. It is divided into right and left lobes. The upper surface is convex and the lower surface is irregular with the transverse fissure, which is broken by the passage of the vessels that leave the liver. On the under surface the two lobes are separated by the longitudinal fissure and the upper surface is separated by falciform ligament. The liver is further divided into lobes and lobules. The liver is supplied by portal vein and hepatic artery.
One of the functions of the liver is to secrete a yellow-brown liquid called bile, which is stored in a small sac called gallbladder. The entrance of food into the small intestines stimulates the release of bile into the small intestine through a duct called common bile duct.
One of the main functions of bile is to dissolve fat and cholesterol. Fats in the small intestine are broken down into smaller droplets by bile. Bile is a salt containing detergent and if the amount of salt in the bile is insufficient, it can precipitate to form gallstones.
Vessels of the Liver
The hepatic artery that arises from the aorta supplies the oxygenated blood to the liver.
Portal vein, formed by the joining of splenic and superior mesenteric vein, supplies nutrients to the liver, which are absorbed by the intestine.
The hepatic vein returns the blood from the liver to the inferior vena cava.
Bile ducts formed by the joining of the bile capillaries, collect the bile from the liver cells.
Gallbladder is a pear-shaped sac, situated in a fossa on the under surface of liver. It measures 3–4 inches in length and has a volume about 30–50 mL. It has an outer serous peritoneal coat, a middle non-striated muscular tissue and an inner mucous membrane that is continuous with the bile duct. The mucous membrane made of columnar epithelial cells absorbs water and electrolytes from the bile and secretes mucin. The cystic duct measuring 1½ inch in length connects the neck of the gallbladder and the hepatic duct, to form the common bile duct that drains the bile into the duodenum.
The small intestine performs three major functions on chyme that enters from the stomach:
In the small intestine carbohydrates and fats are digested.
Digestion of proteins is completed.
Digested nutrients are absorbed.
Small intestine is long (6 m), but its diameter (2.5 cm) is smaller than that of the large intestines. Small intestine consists of three parts (refer Fig. 16.1):
The duodenum is the first section that measures about 25 cm.
The jejunum is the middle section that measures about 2.5 m.
Ileum makes up the remaining portion.
Some of the digestive fluids and enzymes, which come from glands located in the small intestine, digest proteins and carbohydrates. The sources and substrates of various digestive enzymes are summarized in Table 16.3.
Most nutrients from the digested foods are absorbed into the circulatory system through the cells that line the small intestine. The internal surface of the intestine is lined with finger-like projections called villi (Fig. 16.7). The cells covering the villi, in turn have extensions on their cell membranes called microvilli. Villi increase the surface area (Table 16.4) of the lining of the small intestine, making absorption more efficient.
Nutrients are absorbed through capillaries and tiny lymph vessels called lacteals in the villi (refer Fig. 16.7). Capillaries absorb the carbohydrates (monosaccharides) and proteins (amino acids), and are carried to the liver. The liver neutralizes many toxic substances in the blood and removes excess glucose, converting it to glycogen or fat for storage. The filtered blood then carries the nutrients to all the parts of the body. The tiny lymph vessels called lacteals absorb glycerol and fatty acids, which are carried through the lymph vessels and eventually to the bloodstream through lymphatic vessels near the heart. Most of the nutrients used by the body are absorbed through the lining of the small intestine.
The undigested material leaves the small intestine through a valve and enters the large intestine or colon. It is the final organ of digestion and consists of four major parts: ascending colon, transverse colon, descending colon, and sigmoid colon (refer Fig. 16.1). Near the junction of the small and large intestine is a finger-shaped pouch, which does not serve any known function, and is called appendix. If the appendix becomes infected with bacteria, it results in appendicitis, and must be removed by surgery.
The large intestine is also called colon, it is about 6 cm wide and 1.5 m long. The main function of large intestine includes:
Absorption of water from undigested materials remaining in the digestive tract
Absorption of water-soluble vitamins along with water
Absorption of vitamin K.
When most of the water has been removed from the undigested material, a solid waste matter, called feces is formed.
The feces are propelled through the large intestine by peristaltic movements into the last few inches of the large intestine called rectum (Fig. 16.8). The feces are collected in the rectum and are eliminated through the anus.
Sometimes, a disease or disorder prevents the large intestine from absorbing enough water that result is diarrhea or watery feces. Severe diarrhea can result in a loss of water or dehydration that can be fatal.
The act of defecation is a matter of habit. The rectum is normally empty until just before defecation. This is brought about by the gastrocolic reflexes, which usually functions after breakfast. When the meal reaches the stomach digestion begun, peristalsis is stimulated in the intestine and spreads to the colon. The food residue that has reached the caecum begins to move. The contents of the pelvic colon enter the rectum.
Simultaneously, strong peristalsis occurs in the colon and perineal sensation is experienced. Intra-abdominal pressure is increased by closure of glottis and contraction of the diaphragm, and the abdominal muscles. The anal sphincters relax and the act of defecation is completed.
MECHANISM OF DIGESTION
Digestions of Dietary Carbohydrates
Digestions of dietary carbohydrates from which humans derive energy, are in complex forms such as sucrose, starch (amylose and amylopectin) and glycogen. Cellulose is also consumed, but not digested. The first step in the metabolism of digestible carbohydrate is the conversion of higher polymers to simpler, soluble forms that can be transported across the intestinal wall and delivered to the tissues for immediate use or storage. The hydrolytic breakdown of polymeric sugars begins in the mouth. Saliva has a slightly acidic pH of 6.8 and contains lingual amylase that begins the digestion of carbohydrates. The action of lingual amylase is limited to the area of the mouth and the esophagus; it is virtually inactivated by the much stronger acidic pH of the stomach. The mixture of gastric secretions, saliva, and food, collectively known as chyme, moves to the small intestine.
Pancreatic α-amylase is the main enzyme that digests polymeric carbohydrates in the small intestine. This enzyme has the same activity as salivary amylase, producing oligo- and disaccharides (maltose, maltotriose and α-limit dextrin), which are converted to monosaccharides by intestinal saccharidases such as maltases that hydrolyze di- and trisaccharides, and the more specific disaccharidases such as sucrase, lactase, and trehalase will split sucrose, lactose and trehalose, respectively to their constituent monomeric units. The net result is the almost complete conversion of digestible carbohydrate to its constituent monosaccharides (glucose, fructose and galactose).
The resultant monosaccharides are transported across the intestinal wall to the hepatic portal vein and then to liver parenchymal cells and peripheral tissues. There they enter various metabolic pathways of cells and converted into fatty acids, amino acids and glycogen.
In the absence of lactase, lactose cannot be degraded and is therefore not absorbed. Deficiency of the enzyme results in diarrhea, because the non-absorbed lactose in the intestine osmotically pulls the water into the intestinal lumen and lactose can be converted into toxic substances by the intestinal bacteria.
Lipid Digestion and Intestinal Uptake
Following the ingestion of dietary lipids, which are essentially insoluble in the aqueous environment of the intestine, they get emulsified with the help of bile salts, which are synthesized from cholesterol in the liver and then stored in the gallbladder. Bile salts are secreted into the duodenum following the ingestion of fat.
Emulsification of dietary fats makes them accessible to pancreatic lipases (primarily lipase and phospholipase A2), secreted into the intestine from the pancreas. The action of these enzymes on dietary triacylglycerol generates free fatty acids and mixtures of mono- and diacylglycerols. Pancreatic lipase degrades triacylglycerols at C3 and C1 positions sequentially to generate 1,2-diacylglycerols and 2-acylglycerols. Phospholipids are degraded at the C2 positions by pancreatic phospholipase A2, releasing a free fatty acid and the lysophospholipid. The products of lipid digestion by pancreatic lipases then diffuse into the intestinal epithelial cells, where triacylglycerols are resynthesized.
Dietary triacylglycerols and cholesterol, as well as triacylglycerols and cholesterol synthesized by the liver, are made soluble in the form of lipid-protein complexes called lipoproteins. These complexes contain triacylglycerol and cholesteryl esters surrounded by the polar phospholipids and apolipoproteins. These lipid protein complexes vary in their content of lipid and protein.
These lipid-protein complexes are classified based upon their density [high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL)]. As lipid is less dense than protein, the lower the density of lipoprotein, the less protein will be content present. They are also classified as α-lipoprotein, pre-β-lipoprotein, β-lipoproteins and chylomicrons based on the net charge they carry and their separation by electrophoresis.
Non-specific lipases are found in human milk (not in cow’s milk), thus providing the infant with the enzyme necessary for breaking down the milk fat. Since, this enzyme is not a heat-stable enzyme, pasteurization considerably reduces the digestibility of milk fat of human milk in premature infants.
Lipoprotein lipase (LPL) of the capillary endothelium of many organs splits fatty acids from the triacylglycerols of the chylomicrons and the VLDL. The insulin released following a meal activates the LPL and thus contribute to the rapid breakdown of the absorbed dietary triglycerides.
Protein digestion begins in the stomach, where the three pepsinogens produced by the chief cells of the gastric mucosa are activated to about eight different pepsins by gastric HCl. At pH values between 2 and 5 (HCl), pepsin split proteins at the sites where tyrosine or phenylalanine are present in the molecule. These pepsins are partly inactivated when bicarbonate (HCO3) from the bile and pancreas neutralizes the gastric acid to pH of about 6.5. Proteins are then digested further by the action of trypsin and chymotrypsin, which are capable of splitting both polypeptides and proteins down to peptides. Trypsin is produced in the duodenum from the pancreatic trypsinogen by the action of duodenal enterokinase (peptidase). Trypsin then activates pancreatic chymotrypsinogen to chymotrypsin. Pancreatic carboxypeptidases and aminopeptidases produced by the intestinal mucosa splits, amino acids from the free ends of the peptide chains. The final breakdown of the peptides into individual amino acids is accomplished by the dipeptidases localized on the brush border membrane of the mucosa of the small intestine.
Specific Na+ cotransport system is responsible for secondary active transport of the amino acids from the intestinal lumen into the mucosal cells, after which they enter the blood of the portal vein.
In a number of congenital disorders, the absorption of certain amino acid groups is defective, often accompanied by similar defects in the renal tubules (renal amino aciduria) such as in cystinuria.
PERITONEUM AND PERITONEAL REFLECTIONS
The best way to try to visualize the peritoneum and its reflections is to examine sagittal section through the abdomen. The peritoneum is a double-layered serous membrane (Fig. 16.9). It consists of two main parts, the parietal peritoneum that lines the walls of the abdominal cavity and the visceral peritoneum that is reflected over the visceral organs of the abdominal cavity. The space between these two membranes is called peritoneal space or cavity. In the males it is a closed sac, but in females the uterine tubes open into the peritoneal cavity.
The peritoneum is thrown into many folds; a large fold called greater omentum is hanging down from the greater curvature of the stomach. The other fold called lesser omentum is hanging down from the porta hepatis after enclosing the liver, to the lesser curvature of the stomach where it splits to encircle the stomach. The transverse colon is also enclosed by the peritoneum, which then passes upwards and backwards as the mesocolon to the posterior abdominal wall. Part of this peritoneum forms the mesentery of the small intestine.
The greater and lesser omentum, the mesentery and the mesocolon carry the vessels and the lymphatics from the organs they enclose.
The functions of the peritoneum are as follows:
It covers most of the organs in the abdominal cavity, thus allowing their movement upon each other without friction.
It holds the organs together and keeps them in position.
The lymph nodes and the vessels that supply the organs held by peritoneum protect them from infection.
Types of Jaundice
Jaundice can be distinguished into three types. The normal bilirubin content in the plasma is 0.3–1.0 mg/dL. At concentration of bilirubin above 1.8 mg/dL, jaundice (icterus) develops. Yellow discoloration develops first, in the sclera and later in the skin.
Intrahepatic jaundice: Arises from:
Damage to liver cells by poisons or inflammation (hepatitis) in which transport and conjugation of bilirubin is impaired.
Total absence (Crigler-Najjar syndrome) or deficiency (Gilbert’s syndrome) of glucuronyl transferase, or immaturity of the glucuronidation system at birth, which is aggravated by the possible high rate of hemolysis in the newborn.
An inborn defect (Dubin-Johnson syndrome) to excrete conjugated bilirubin into the canaliculi, or inhibition (by drugs and steroids) to secrete conjugated bilirubin into the canaliculi in which plasma levels of conjugated bilirubin is elevated.
Posthepatic jaundice: Obstruction of the bile ducts by stones or tumor causes reflux (regurgitation) of conjugated bilirubin (direct-reacting) into the bloodstream. Alkaline phosphatase, in this condition is abnormally elevated in the blood, which is an important diagnostic aid.
Diagnostic Findings in Various Types of Jaundice
In jaundice of type 2a, c and 3, the amount of water-soluble bilirubin (conjugated) in the urine is elevated.
In type 3, the stool is clay-colored, because no bilirubin enters the intestine to serve as a source for urobilinogen and stercobilinogen formation.
In prehepatic jaundice, the unconjugated bilirubin not bound to albumin can enter the brain where it gets deposited and exerts a toxic effect (kernicterus). The severity of kernicterus is enhanced in the newborn, whose albumin levels are low, or by medication with substances such as anions and sulfonamides that compete for the available albumin.
LIVER FUNCTION TESTS
The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) can give an indication of liver disease being due to alcohol or not:
If AST/ALT < 1, it indicates a likely non-alcoholic cause
If AST/ALT > 2, this is strongly suspicious of an alcoholic cause
AST and ALT are not prognostic indicators of liver disease. But, partial thromboplastin time (PTT) and globulin are.
Special Considerations in Interpreting Liver Function Tests
A number of pitfalls can be encountered in the interpretation of common liver function tests (LFT):
These tests can be normal in patients with chronic hepatitis or cirrhosis.
The normal range for aminotransferase levels is slightly higher in males, nonwhites and obese persons.
Severe alcoholic hepatitis is sometimes confused with cholecystitis or cholangitis.
Conversely, patients who present soon after passing common bile duct stones can be misdiagnosed with acute hepatitis because aminotransferase levels often rise immediately, but alkaline phosphatase (AP) and gamma-glutamyltransferase (GGT) levels do not become elevated for several days.
Asymptomatic patients with isolated, mild elevation of either the unconjugated bilirubin or the GGT value usually do not have liver disease and generally do not require extensive evaluation.
Overall hepatic function can be assessed by applying the values for albumin, bilirubin and prothrombin time in the modified Child-Turcotte grading system.
The commonly used LFTs primarily assess liver injury rather than hepatic function. Indeed, these blood tests may reflect problems arising outside the liver, such as hemolysis (elevated bilirubin level) or bone disease (elevated alkaline phosphatase level).
Abnormal LFTs often, but not always, indicate that something is wrong with the liver and they can provide clues to the nature of the problem. However, normal LFTs do not always mean that the liver is normal.
Patients with cirrhosis and bleeding esophageal varices can have normal LFTs. Of the routine LFTs, only serum albumin, bilirubin and prothrombin time provide useful information on how well the liver is functioning.
Markers of Hepatocellular Injury
The most commonly used markers of hepatocyte injury are AST [formerly serum glutamic-oxaloacetic transaminase (SGOT)] and ALT [formerly serum glutamate-pyruvate transaminase (SGPT)]. While, ALT is cytosolic, and AST has both cytosolic and mitochondrial forms.
Hepatocyte necrosis in acute hepatitis, toxic injury or ischemic injury results in the leakage of enzymes into the circulation. However, in chronic liver diseases such as hepatitis C and cirrhosis, the serum ALT level correlates only moderately well with liver inflammation. In hepatitis C, liver cell death occurs by apoptosis (programmed cell death) as well as by necrosis. Hepatocytes dying by apoptosis presumably synthesize less AST and ALT as they wither away. This probably explains why at least one third of patients infected with hepatitis C virus have persistently normal serum ALT levels, despite the presence of inflammation on liver biopsy. Patients with cirrhosis often have normal or only slightly elevated serum AST and ALT levels. Thus, AST and ALT lack some sensitivity in detecting chronic liver injury. Of course, AST and ALT levels tend to be higher in cirrhotic patients with continuing inflammation or necrosis than in those without continuing liver injury.
Causes of elevated ALT and AST values in asymptomatic patients (Box 16.1) are:
The AST and ALT values are higher in obese patients, probably because these persons commonly have fatty livers. The ALT levels have been noted to decline with weight loss.
Various liver diseases are associated with typical ranges of AST and ALT levels. ALT levels often rise to several 1,000 U/L in patients with acute viral hepatitis.
The highest ALT levels—often more than 10,000 U/L are usually found in patients with acute toxic injury subsequent to, for example, acetaminophen overdose or acute ischemic insult to the liver. AST and ALT levels usually fall rapidly after an acute insult.
Lactate dehydrogenase (LDH) is less specific than AST and ALT as a marker of hepatocyte injury. However, it is worth noting that LDH is disproportionately elevated after an ischemic liver injury.
The elevated AST to ALT ratio in alcoholic liver disease results in part from the depletion of vitamin B6 (pyridoxine) in chronic alcoholics. The ALT and AST both use pyridoxine as a coenzyme. Alcohol also causes mitochondrial injury, which releases the mitochondrial isoenzyme of AST.
Markers of Cholestasis
Cholestasis (lack of bile flow) results from the blockage of bile ducts or from a disease that impairs bile formation in the liver itself. The AP and GGT levels typically rise to several times the normal level after several days of bile duct obstruction or intrahepatic cholestasis. The highest liver AP elevations, often greater than 1,000 U/L, or more than six times the normal value are found in diffuse infiltrative diseases of the liver such as infiltrating tumors and fungal infections.
Diagnostic confusion can occur when a patient presents within a few hours after acute bile duct obstruction from a gallstone. In this situation, AST and ALT levels often reach 500 U/L or more in the 1st hours and then decline, whereas AP and GGT levels can take several days to rise.
Both AP and GGT levels are elevated in about 90% of patients with cholestasis. The elevation of GGT alone, with no other LFT abnormalities, often results from enzyme induction by alcohol or aromatic medications in the absence of liver disease. The GGT level is often elevated in persons who take three or more alcoholic drinks (45 g of ethanol or more) per day. Thus, GGT is a useful marker for immoderate alcohol intake. Phenobarbital, phenytoin (Dilantin) and other aromatic drugs typically cause GGT elevations twice the normal. A mildly elevated GGT level is a typical finding in patients taking anticonvulsants and by itself does not necessarily indicate liver disease.
Serum AP originates mostly from liver and bone, which produce slightly different forms of the enzyme. The serum AP level rises during the third trimester of pregnancy because of a form of the enzyme produced in the placenta. When serum AP originates from bone, clues to bone disease are often present, such as recent fracture, bone pain or Paget’s disease of the bone (often found in the elderly). Like the GGT value, the AP level can become mildly elevated in patients who are taking phenytoin.
If the origin of an elevated serum AP level is in doubt, the isoenzymes of AP can be separated by electrophoresis. However, this process is expensive and usually unnecessary because an elevated liver AP value is usually accompanied by an elevated GGT level, an elevated 5´-nucleotidase level and other LFT abnormalities. Persistently elevated liver AP values in asymptomatic patients, especially women, can be caused by primary biliary cirrhosis, which is a chronic inflammatory disorder of the small bile ducts. Serum antimitochondrial antibody is positive in almost all of these patients.
The GGT level is often elevated in persons who have three or more alcoholic drinks per day; thus, it is a useful marker for immoderate alcohol intake.
Patients with cirrhosis often have normal or only slightly elevated serum AST or ALT values.
Indicators of How Well the Liver Functions
Bilirubin results from the enzymatic breakdown of heme. Unconjugated bilirubin is conjugated with glucuronic acid in hepatocytes to increase its water solubility and is then rapidly transported into bile. The serum conjugated bilirubin level does not become elevated until the liver has lost at least one half of its excretory capacity. Thus, a patient could have obstruction of either the left or right hepatic duct without a rise in the bilirubin level.
Because the secretion of conjugated bilirubin into bile is very rapid in comparison with the conjugation step, healthy persons have almost no detectable conjugated bilirubin in their blood. Liver disease mainly impairs the secretion of conjugated bilirubin into bile. As a result, conjugated bilirubin is rapidly filtered into the urine, where it can be detected by a dipstick test. The finding of bilirubin in urine is a particularly sensitive indicator of the presence of an increased serum conjugated bilirubin level.
In many healthy persons, the serum unconjugated bilirubin is mildly elevated to a concentration of 2–3 mg per dL (34–51 μmol/L) or slightly higher, especially after a 24-hour fast. If this is the only LFT abnormality and the conjugated bilirubin level and complete blood count are normal, the diagnosis is usually assumed to be Gilbert’s syndrome and no further evaluation is required. Gilbert’s syndrome was recently shown to be related to a variety of partial defects in uridine diphosphate glucuronosyl transferase, the enzyme that conjugates bilirubin.
Mild hemolysis, such as that caused by hereditary spherocytosis and other disorders, can also result in elevated unconjugated bilirubin values, but hemolysis is not usually present if the hematocrit and blood smear are normal. The presence of hemolysis can be confirmed by testing other markers, such as haptoglobin, or by measuring the reticulocyte count.
Severe defects in bilirubin transport and conjugation can lead to markedly elevated unconjugated bilirubin levels, which can cause serious neurologic damage (kernicterus) in infants. However, no serious form of liver disease in adults causes elevation of unconjugated bilirubin levels in the blood without also causing elevation of conjugated bilirubin values.
When a patient has prolonged, severe biliary obstruction followed by the restoration of bile flow, the serum bilirubin level often declines rapidly for several days and then slowly returns to normal over a period of weeks. The slow phase of bilirubin clearance results from the presence of delta (δ)-bilirubin, a form of bilirubin chemically attached to serum albumin. Because albumin has a half-life of 3 weeks, δ-bilirubin clears much more slowly than bilirubin-glucuronide. Clinical laboratories can measure δ-bilirubin concentrations, but such measurements are usually unnecessary if the physician is aware of the δ-bilirubin phenomenon.
Although, the serum albumin level can serve as an index of liver synthetic capacity, several factors make albumin concentrations difficult to interpret. The liver can synthesize albumin at twice the healthy basal rate and thus partially compensate for decreased synthetic capacity or increased albumin losses. Albumin has a plasma half-life of 3 weeks; therefore, serum albumin concentrations change slowly in response to alterations in synthesis. Furthermore, because two-thirds of the amount of body albumin is located in the extravascular, extracellular space, changes in distribution can alter the serum concentration.
In practice, patients with low serum albumin concentrations and no other LFT abnormalities are likely to have a non-hepatic cause for low albumin, such as proteinuria or an acute or chronic inflammatory state. Albumin synthesis is immediately and severely depressed in inflammatory states such as burns, trauma and sepsis, and it is commonly depressed in patients with active rheumatic disorders or severe end-stage malnutrition. In addition, normal albumin values are lower in pregnancy.
Patients with low serum albumin levels and no other liver function test abnormalities are likely to have a non-hepatic cause for low albumin, such as proteinuria.
The liver synthesizes blood clotting factors II, V, VII, IX and X. The prothrombin time (PT) does not become abnormal until more than 80% of liver synthetic capacity is lost. This makes PT a relatively insensitive marker of liver dysfunction. However, abnormal PT prolongation may be a sign of serious liver dysfunction. Because factor VII has a short half-life of only about 6 hours, it is sensitive to rapid changes in liver synthetic function. Thus, PT is very useful for following liver function in patients with acute liver failure.
An elevated PT can result from a vitamin K deficiency. This deficiency usually occurs in patients with chronic cholestasis or fat malabsorption from disease of the pancreas or small bowel. A trial of vitamin K injections (e.g. 5 mg per day administered subcutaneously for 3 day) is the most practical way to exclude vitamin K deficiency in such patients. The PT should improve within a few days.
Measurement of the blood ammonia concentration is not always useful in patients with known or suspected hepatic encephalopathy. Ammonia contributes to hepatic encephalopathy; however, ammonia concentrations are much higher in the brain than in the blood, therefore, do not correlate well. Furthermore, ammonia is not the only waste product responsible for encephalopathy. Thus, blood ammonia concentrations show only a mediocre correlation with the level of mental status in patients with liver disease. It is not unusual for the blood ammonia cconcentration o be normal in a patient who is in a coma from hepatic encephalopathy.
Blood ammonia levels are best measured in arterial blood because venous concentrations can be elevated as a result of metabolism of amino acids in muscles. Blood ammonia concentrations are most useful in evaluating patients with stupor or coma of unknown origin. It is not necessary to evaluate blood ammonia levels routinely in patients with known chronic liver disease who are responding to therapy as expected.
GRADING LIVER FUNCTION BY CHILD-TURCOTTE CLASSIFICATION
Many physicians use the Child-Turcotte classification as modified by Pugh, often termed the ‘Child class’, to convey information about overall liver function and prognosis (Table 16.5). This grading system can be used to predict overall life expectancy and surgical mortality in patients with cirrhosis and other liver diseases.
‘Child class’ (modified by Pugh), is calculated by adding the points as determined by the patient’s laboratory results: class A = 0 to 1; class B = 2 to 4; class C = 5 and higher. The classes indicate severity of liver dysfunction—class A is associated with a good prognosis, and class C is associated with limited life expectancy. Ascites and encephalopathy are graded as ‘none’, ‘controlled with routine medical therapy’ or ‘refractory to medical therapy’.
For elective general abdominal surgery, perioperative mortality is in the neighborhood of several percent for patients who fall into the Child class A, 10–20% for those in class B and approximately 50% for those in class C. These percentages must be balanced by prognostic considerations when transplantation becomes an option. The presence of cirrhosis by itself is not an indication for liver transplantation and transplantation is rarely performed in patients who fall into Child class A. For example, the 10-year survival rate is as high as 80% in patients with hepatitis C and cirrhosis who have Child class A liver function and no variceal bleeding. However, once patients with any type of liver disease fall into the Child-Turcotte class B or class C category, survival is significantly reduced and transplantation should be considered.
MALE REPRODUCTIVE SYSTEM
The primary function of testes is to produce and store sperms. However, it also functions as endocrine gland. Other organs in the male reproductive system (Fig. 17.1)prepare sperm for the possible fertilization of an egg.
Male Reproductive Anatomy
The testes are held in the scrotum (muscular sac) outside the pelvic cavity, therefore testes are at a temperature lower than the body temperature.
Spermatogenesis and spermiogenesis take place in the seminiferous tubules, which are protected from the surroundings by the blood-testes barrier, i.e. the Sertoli cells. Testosterone required for the development of sperms in the testes and epididymis can cross this barrier. Epididymis receives sperms from testis where they mature.
Ductus (vas) deferens transports sperm from epididymis into pelvic cavity where they are stored in seminal vesicles.
Prostate gland and bulbourethral (Cowper’s) gland provide secretion to form seminal fluid.
Penis is a specialized erectile tissue that deposits semen into the vagina. It is composed of spongy tissue and is expanded to form glans penis, where the urethra opens. The skin covering the glans penis is called prepuce or foreskin, which normally retracts. When it does not retract, the condition is called paraphimosis. Surgical removal of prepuce in part or entirely is called circumcision.
In males, urethra is the passageway for both sperm and urine.
Reproduction involves special structures that make up the reproductive system. The reproductive system unlike other systems is not essential to the survival of an individual. Organisms can survive and lead healthy lives without reproducing. However, the reproductive system is important for the survival of the species. Reproduction is absolutely essential for the continuation of the species.
In humans, the reproductive system produces, stores, nourishes and releases specialized sex cells known as gametes. The ways in which the gametes are released makes the fusion of sperm (male gametes) and egg (female gametes) possible in the process of fertilization. From a fertilized egg or zygote, all the cells in a human body are derived.
During the first 6 weeks of development, human male and female embryos are identical in appearance. Major changes occur during the 7th week of development:
The testes, which are the primary reproductive organs of a male, begin to produce steroid hormones (sex) known as androgens. The tissue of the embryo responds to these hormones by developing into the male reproductive organs (Fig. 17.2).
The ovaries or the primary reproductive organs of a female embryo produce steroid hormones (sex) known as estrogens. The tissue of the embryo responds to these hormones by developing into the female reproductive organs.
The male and female reproductive organs develop from exactly the same tissues in the embryo. After birth, the testes and the ovaries continue to produce small amounts of sex hormones. These sex hormones continue to influence the development of the reproductive organs.
Neither testes nor ovaries are capable of producing active reproductive cells (gametes) until puberty. Puberty is a period of rapid growth and sexual maturation during which the reproductive system becomes fully functional. At the completion of puberty, the male and female gonads and reproductive organs are fully developed. The onset of puberty varies among individuals. It may occur anytime from the age of 9 to 15 years. Generally, puberty begins about a year earlier in females than in males. The first sign of pubertal change is the growth of hair in the axilla.
The pubertal changes begin with the release of gonadotropin-releasing hormone (GNRH) by the hypothalamus; the part of the brain that regulates the secretions of the pituitary gland. The pituitary gland in turn produces increased levels of two hormones that affect the gonads:
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH).
Males begin to produce sperm during puberty. The adolescent stage of development is when changes in the body make reproduction possible. At this time, the concentration of the hormone testosterone is high enough to stimulate sperm production. Testosterone is the main androgen (male sex hormone) produced by the testes.
Testes, the primary male reproductive organ develop within the abdominal cavity. Just before birth, the testes descend through a canal into an external sac called scrotum. During the rest of life, the testes (two egg-shaped structures) remain in the scrotum, outside the body where the temperature is about 3°C cooler than the body internal temperature (37°C). The sperm development in the testes requires lower temperature. The testes are composed of clusters of hundreds of tiny tubules called seminiferous tubules. The specialized lining of this extensive network of tubules form the sperms through meiosis.
The FSH and LH released from pituitary gland stimulate the testes to make the principal male sex hormone testosterone. Cells that respond to testosterone are found all over the body, which produces a number of secondary sex characteristics that appear in males at puberty such as deepening of voice, growth of beard and body hair. FSH and testosterone hormones stimulate the development of sperms. When large numbers of sperm have been produced in the testes, the development process of puberty is completed and the reproductive system is now functional.
Sperms are derived from special cells within the testes that go through the process of meiosis to form haploid nuclei found in mature sperm. The chromosome number drops from 46 to 23, four sperm cells result from each cell that begins meiosis. A mature sperm consists of three regions (Fig. 17.3):
Head contains the nucleus (23 chromosomes) and enzymes that help the sperm to penetrate the protective layers that surround the egg cell.
Middle piece is packed with energy releasing mitochondria (energy source) that is required for sperm to reach an egg.
Tail consists of a single, powerful flagellum that propels the sperm.
The developed sperm travel from the seminiferous tubules into the epididymis. Within each epididymis, a sperm matures and gains the ability to swim as its flagellum develops completely. Although most sperm remain stored in each epididymis, some leave the epididymis and pass into the vas deferens, a duct that extends from the epididymis. Each vas deferens enters the abdominal cavity, where it loops around the urinary bladder and merges with the urethra. In a male, both urine and sperm exit the body through the urethra.
In the urethra, sperm mix with fluids secreted by three exocrine glands; the seminal vesicles, bulbourethral glands and the prostate gland to produce seminal fluid, which protects and nourishes the sperm.
The combination of sperm and seminal fluid is known as semen. Semen has a high concentration of fructose, which is the source of energy for sperms. Semen also contains alkaline fluids that help to neutralize the acidic environment of the female’s vagina. The prostaglandins present in the semen stimulate contractions of smooth muscles that line the female reproductive tract, which help sperm to move through the female reproductive system. Between 100 and 200 million sperm are present in 1 milliliter of semen or about 5 million sperm per drop.
The vas deferens merges with the urethra, the tube that leads to the outside of the body through the penis. When the male is sexually excited, the autonomic nervous system make the penis to erect that enables the male to deliver sperm into the vagina. Semen is ejected from the penis by contractions of smooth muscles lining the vas deferens. This process of ejaculation is regulated by the autonomic nervous system and is not completely voluntary. During the process of ejaculation about 300–400 million sperm are released into the reproductive tract of a female; thus the chances of a single sperm fertilizing an ovum (egg), are quite good. The acidic environment of the female reproductive tract kills most sperm. Only a few sperm reach the site of fertilization. Sperm make up only 10% of semen, 90% is the fluid secreted by the three glands.
The most common reproductive problem for older men is prostatic hypertrophy, enlargement of the prostate gland. This causes the urethra to compress and urination becomes difficult. Residual urine in the bladder increases the chance of urinary tract infections. Prostate hypertrophy is usually benign, but cancer of the prostate is one of the more common cancers in elderly men.
Erectile dysfunction (ED) is another common problem seen in ageing males. Any disorder that impairs blood flow in the penis or causes injury to the nerves has the potential to cause ED. It is treatable at any age and awareness of this fact has been growing. More men have been seeking help and returning to normal sexual activity because of improved and successful treatments for ED.
DISEASES THAT AFFECT MALE REPRODUCTIVE SYSTEM
Men may sometimes experience reproductive system problems. Some examples of disorders that affect male reproductive system are disorders of the scrotum, testicles or epididymis.
Disorders of Scrotal Contents
Conditions affecting the scrotal contents may involve the testicles, epididymis or the scrotum itself.
Even a mild injury to the testicles can cause severe pain, bruising or swelling. Most testicular injuries occur when the testicles are struck, hit, kicked or crushed, usually during sports or due to other trauma. Testicular torsion, when one of the testicles twists around, cutting off the blood supply is also a problem that some teen males experience—although it is not common. Surgery is needed to untwist the cord and save the testicle.
This is a varicose vein (an abnormally swollen vein) in the network of veins that run from the testicles. Varicocele commonly develops while a boy is going through puberty. A varicocele is usually not harmful, although in some people it may damage the testicle or decrease sperm production, so it helps for the parents to take their child to see the doctor if the boy is concerned about changes in his testicles.
This is one of the most common cancers in men younger than 40. It occurs when cells in the testicle divide abnormally and form a tumor. Testicular cancer can spread to other parts of the body, but if it is detected early, the cure rate is excellent. Teen boys should be encouraged to learn to perform testicular self-examinations.
It is the inflammation of the epididymis, the coiled tubes that connect the testes with the vas deferens. It is usually caused by an infection such as the sexually transmitted disease chlamydia and results in pain and swelling in the epididymis.
A hydrocele occurs when fluid collects in the membranes surrounding the testes. Hydrocele may cause swelling of the testicle, but are generally painless. In some cases, surgery may be needed to correct the condition.
When a portion of the intestines pushes through an abnormal opening or weakening of the abdominal wall and into the groin or scrotum, it is known as an inguinal hernia. The hernia may look like a bulge or swelling in the groin area. It can be corrected with surgery.
Disorders of Penis
Inflammation of the penis
The symptoms include redness, itching, swelling and pain. Balanitis occurs when the glans (the head of the penis) becomes inflamed. Posthitis is foreskin inflammation, which is usually due to a fungal or bacterial infection.
It is a disorder in which the urethra opens on the bottom of the penis, not at the tip.
It is a tightness of the foreskin of the penis and is common in newborns and young children. It usually resolves itself without treatment. If it interferes with urination, circumcision (removal of the foreskin) may be recommended.
It may develop when a boy’s uncircumcised penis is retracted, but does not return to the unretracted position. As a result, blood flow to the penis may be impaired and the child may experience pain and swelling. A doctor may try to use lubricant to make a small incision, so the foreskin can be pulled forward. If that does not work, circumcision may be recommended.
It occurs when a child is born with genitals that are not clearly male or female. In most boys born with this disorder, the penis may be very small or non-existent, but testicular tissue is present. In a small number of cases, the child may have both testicular and ovarian tissue.
It is a disorder in which the penis although normally formed is well below the average size as determined by standard measurements.
Sexually transmitted diseases (STDs)
They include human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), human papillomavirus (HPV or genital warts), syphilis, chlamydia, gonorrhea, genital herpes and hepatitis B. They are spread from one person to another mainly through sexual intercourse.
It is the inability to get or keep an erection firm enough for sexual intercourse. This can also be called impotence. The word ‘impotence’ may also be used to describe other problems that can interfere with sexual intercourse and reproduction such as problems with ejaculation or orgasm and lack of sexual desire. Using the term ED clarifies that those other problems are not involved.
CONTRACEPTION FOR MEN
Vasectomy is a procedure in which the vas deferens of each testes is cut and tied off to prevent the passage of sperm. Sperm is still produced and stored in crypt sites causing inflammation. Because of this inflammatory response, the immune system acts on them, destroying and then having antisperm antibodies. This causes a lower possibility if the vasectomy is reversed to become fertile again.
Condom usually made of latex or more recently polyurethane are used during sexual intercourse. It is put on a man’s penis and physically blocks ejaculated semen from entering the body of a sexual partner. Condoms are used to prevent pregnancy, transmission of sexually transmitted diseases such as gonorrhea, syphilis and HIV or both.
FEMALE REPRODUCTIVE SYSTEM
Similar to the testes in males, the ovaries in females produce gametes and female sex hormones. The female reproductive system prepares the eggs for possible fertilization. It also contains structures that enable fertilization to occur and that house and nourish a developing baby (Fig. 17.4).
Female Reproductive Anatomy
Female reproductive organs are present within the wide and shallow pelvis, which also supports and allows childbearing. Female reproductive system comprises of:
Ovaries (follicles, corpus luteum) produce ova and hormones
Oviducts (fallopian tubes) deliver ova to uterus
Uterus (womb) has muscular wall (myometrium) lined inside by endometrium
Vagina receives penis during intercourse and is the birth canal for childbearing
Vulva (lips of vagina) includes labia majora and minora
Clitoris is homologous to penis.
The external female organs (Fig. 17.5) are collectively called vulva. It comprises the following parts:
Mons pubis (mons veneris) is a pad of fat that lie in front of the symphysis pubis and is covered with hair at puberty.
Labia majora are two thick folds measuring 3 inches long that form the sides of vulva.
Labia minora are two small folds of skin situated between the upper part of the labia majora and it contains erectile tissue.
Clitoris is a small erectile body that corresponds with the penis of the male. It is situated anterior to the vestibule. Vestibule is limited on either side by the folds of labia and leads to the vagina. The urethra opens into the vestibule in between the vagina and clitoris.
The ducts of vestibular (Bartholin’s) glands that secrete mucus open into the vestibule between hymen and labia minora.
The hymen is a membranous diaphragm, which is perforated in the center to allow menstrual discharge to drain away. This membrane separates the internal and external genitals. Rarely the hymen may be imperforate, which is not noticed till the girl menstruates, when the menstrual secretion collects in the vagina and dilates it. The condition requires surgical incision of the hymen.
Vagina is a muscular tube that extends from the vestibule up to the uterus. It is lined by stratified epithelium and well supplied by blood vessels and nerves. Normally, the vaginal walls are in contact and surround the lower part of the cervix of the uterus. It rises higher behind than in the front. The small recess in front and on the sides of the cervix is called anterior and lateral fornices and the one behind the cervix is called posterior fornix of the vagina.
The anterior surface of the vagina is in relation to the base of the bladder and the urethra, and the posterior aspect of vagina is in relation with the rectum and the rectovaginal pouch (pouch of Douglas). The lower one fourth of the vagina is in contact with perineal body.
Uterus is a pear-shaped, thick muscular organ situated in the pelvis in between the urinary bladder in front and the rectum behind. It measures 2–3 inches long and weighs about 30–60 g. Most of its surface is covered by the peritoneum. The interior of the uterus is the mucous membrane and is called endometrium. The muscular wall is called myometrium. The body of the uterus is flexed forward at the cervix so that the fundus is towards the bladder. The uterus communicates below with the vagina and above with the uterine tubes that opens into it. The two folds of the peritoneum form the round ligament that holds the uterus in place. The ovaries and the fallopian tubes lie on either side of the uterus.
Uterus has three parts (Fig. 17.6) the fundus, the body and the cervix. The fundus is the convex part of the uterus that is above the openings of the uterine tubes. The body extends from the fundus to the cervix from which an isthmus separates it. The part below the isthmus is the cervix. The lumen of the cervix communicates above with the uterine cavity via the internal os and below with the vagina via the external os.
The endometrium retains the fertilized ovum, facilitates the growth of fetus by providing all the required nutrients and expels the baby and the placenta by rhythmic contractions when the fetus is matured.
Ligaments of the Uterus
There are two bundles of connective and muscular tissue, one on each side of the uterus measuring 4–5 inches long called round ligaments.
Each ligament contains blood vessels and is covered by peritoneum. It passes from the upper angle of the uterus, forwards and outwards into the inguinal canal.
The peritoneum covering the midline of the body extends laterally on each side, up to the sides of the pelvis that forms the broad ligament. The fallopian tubes (uterine tubes) are in the free edge of this broad ligament and the ovaries are attached to the posterior layer of the broad ligament. It contains the blood vessels and the lymph vessels of the uterus, fallopian tube and that of the ovaries.
The primary reproductive organs of the female are the ovaries (Fig. 17.7). The two ovaries are located in the lower abdominal cavity; the ovaries usually produce only one egg or ovum per month. In addition to producing ova, the female reproductive system has another important job to perform; each time an egg is released, the body must be prepared to nourish a developing embryo.
Puberty in females start with changes in the hypothalamus that causes the release of FSH and LH from the pituitary gland. The FSH stimulates cells within the ovaries to produce the hormone estrogen, which causes the reproductive system to complete its development and also produce secondary sex characteristics such as enlargement of breast and reproductive organs, widening of the hips and growth of hair in the axilla and pubic regions. It also heralds the beginning of menstrual cycle.
Menopause or climacteric is the cessation of menstruation.
It occurs around the age of 45–50 years, but in some women it can occur earlier or later. Menopause is often accompanied by vasomotor changes with flushing and sweating (hot flush). The breast tissue often shrinks, but may be replaced by fat. Senile changes of ovaries cause the cessation of other internal secretions.
The ovaries are two in number. They are almond-shaped glands situated one on each side of the uterus below the fallopian tubes attached to the broad ligament. The production of ova and the production of estrogens and progesterone that control menstruation are the functions of ovary.
Each ovary (refer Fig. 17.6) contains about 400,000 primary follicles, which are clusters of cells surrounding a single ovum (egg). During the lifetime, fewer than 500 ova (eggs) will actually be released on an average one ova is released about every 28 days from each ovary. The function of a follicle is to prepare a single ovum for release into the part of reproductive system where it can be fertilized. Ova mature within their follicles. The maturing eggs become large, highly complex cells, growing nearly 75,000 times larger than sperm.
When a follicle has completely matured, the ovum (egg) is released. This process is called ovulation. If two eggs mature, fraternal or non-identical twins may result. Ovulation begins at puberty and usually continues until a female is in her late 40s, when menopause occurs. After which follicle development no longer occurs and a female is no longer capable of bearing children (biological clock). Without follicles, the ovaries cannot secrete enough estrogen and progesterone to continue the menstrual cycle and menstruation ceases.
The mature vesicular follicle literally ruptures and the ovum is swept away from the ovary into one of the two fallopian tubes. The fallopian tubes provide a way for an egg to travel from ovary to uterus. The ovum is moved through the fluid filled fallopian tubes by cilia attached to the cells that line the walls of tube. It is during its journey through the fallopian tube that an egg can be fertilized. An egg must be fertilized within 48 hours of its release after that the egg begins to break down. Unfertilized eggs dissolve in the uterus.
After a few days, the ovum passes from the fallopian tube into the uterus whose lining is specially designed to receive a fertilized ovum. The lower entrance to the uterus is called cervix. A sphincter muscle in the cervix controls the opening to the uterus.
In females, the reproductive system and the endocrine system interact to bring about a complex series of periodic events called menstrual cycle (Fig. 17.8). The cycle on an average is about 28 days. Each month, the uterus undergoes a series of changes and prepares to receive and nourish an embryo. The menstrual cycle regulated by the hormones of the endocrine system has four stages: the follicular phase, ovulation, the luteal phase and menstruation.
During the first stage, i.e. the follicular phase of the menstrual cycle, the egg matures and the lining of the uterus grows thicker, many tiny blood vessels grow into the thickened lining in preparation for receiving a fertilized egg. The development of an egg in this stage of the cycle takes about 14 days.
The second stage is ovulation, which is the shortest phase in the cycle (3–4 days), is the release of an egg from a ruptured follicle. Following ovulation, an egg is swept into a fallopian tube where it travels towards the uterus awaiting fertilization. The ovum has enough stored nutrients to survive for about 48 hours.
The third stage is luteal phase that lasts about 14 days. The cells of the ruptured follicle grow larger and fill the cavity forming a new structure called corpus luteum. The corpus luteum begins to secrete large amounts of progesterone and estrogen, which cause the pituitary gland to stop secreting LH and FSH. Progesterone causes the lining of the uterus to become even thicker and is prepared to receive the embryo 4 or 5 days after the egg is released from the ovary. As the embryo settles into the lining of the uterus, the corpus luteum continues to release hormones that cause the uterus to maintain its thickened lining.
Menstruation is the fourth stage. Most of the time if no embryo arrives then the corpus luteum begins to produce least estrogen and progesterone. The decrease in levels of estrogen and progesterone causes the blood vessels in the uterine lining to begin closing and then break. The cells of the uterine lining do not receive adequate blood supply and become loose from the inside of the uterus. The mixture of blood and the cells that made up the lining of the uterus is called menstrual fluid. The passage of this fluid through the vagina and out of the body is called menstruation or the menstrual period, the last stage. It usually lasts from 3 to 7 days. At the end of the period, a new cycle begins—the follicular phase.
The average menstrual cycle is 28 days. Almost all women start their menstrual period 14 days after ovulation occurs. The length of the first stage of the cycle, the period when the follicle is growing differs from women to women.
FERTILIZATION AND DEVELOPMENT
Stages of Fertilization to Implantation
During Sexual Intercourse Large Number of Sperms are Deposited in the Vagina
An average ejaculate contains about 300,000,000 sperms, about 20% of them are non-functional. The alkaline semen neutralizes the acidic solutions of the vagina. Residence of sperms in female genital causes surface reactions (capacitation) in head portion of sperm, which give it the ability to penetrate an egg (Fig. 17.9).
Sperm Undergoes a Long, Hazardous Journey to Fertilize an Egg
Successful fertilization of an egg occurs in the fimbria of the fallopian tube close to the ovary.
Sperm take several hours to travel this distance and in the attempt most of them die or are lost. At the entrance to the fallopian tube only 300,000 sperm are left and only 100 or so make it to the upper end of this tube. The sperm must then fight its way through the layers of cells surrounding the egg, using enzymes from its acrosomal tip. Only a single sperm will be successful.
Fertilization Causes Rapid Changes Leading to Zygote Formation
When one sperm penetrates an egg, reactions take place on the surface of the egg that blocks penetration by other sperm; this is necessary because polyspermy is lethal. The egg cell nucleus is triggered into finishing meiotic division, finally producing a haploid nucleus. The sperm loses its tail and its nucleus swells. The two haploid nuclei from the sperm and egg fuse to form a single nucleus.
As the Zygote Moves Down the Fallopian Tube its Cells Divide to Form a Blastocyst
The new zygote starts to divide by mitosis (about once every 20 hours) and move along the tube in the direction of uterine cavity caused by cilium, which sweeps the zygote along.
Single cell → Morula (mulberry shaped) → Blastocyst (hollow sphere)
Implantation Occurs About 7 Days After Fertilization
For the first 7 days, the embryo has been using food materials originally stored in the egg. Now it embeds itself into the uterine lining so that it can be nourished by the mother. Elaborate connections are made between embryonic and maternal tissue forming the placenta. The important functions of placenta are:
Supplies maternal food and oxygen to embryo
Remove embryonic waste products and deliver it to mother
Become an endocrine organ to produce many hormones required for the well-being of mother and fetus.
Placenta Takes Over Some of the Hormone Secretion Required for Pregnancy
At about 7 days, blastocyst cells produce human chorionic gonadotropin (hCG), which replaces LH and stimulate the corpus luteum to continue producing progesterone. hCG is the basis of the pregnancy test.
Later, in fetal development the placenta takes over the production of progesterone and also produces estrogen and several other hormones that promote growth.
Stages of Fetal Development
Zygotes undergo mitosis, 1 day after fertilization.
Mass of cells become a blastocyst, 5 days after fertilization.
Implantation of blastocyst, about 7 days after fertilization.
Formation of the placenta (cells from embryo and mother).
Blastocyst produces hCG, which stimulates corpus luteum to produce estrogen and progesterone.
The blastocyst grows, differentiates and undergoes morphogenesis to form the fetus.
During the first 7 weeks period, the blastocyst is transformed to an embryo. Later, it is transformed into fetus with some working parts (e.g. kidneys), bone deposition, blood formation and development of external sex organs.
It is characterised by significant increase in size of embryo, beginning of some reflexes and movements such as thumb sucking and gripping.
Growth accelerates during this phase and baby becomes matured, prepared for living independently.
Labor is initiated by increasing concentrations of estrogen and decreasing amounts of progesterone towards the end of pregnancy. During labor, oxytocin is released from posterior pituitary. These hormonal changes cause powerful, rhythmic contractions of uterus and expel the mature infant. This process is called birth or parturition.
Lactation is the secretion of milk and its discharge from the breasts during suckling of the breast. Estrogen and progesterone prepare the breasts for lactation. Prolactin (PRL) stimulates maturity of the breasts and milk production. PRL levels increase after parturition and oxytocin is released by tactile stimulation (suckling) of the breasts by the infant nursing on it.
The mammary glands are accessory to the female reproductive organs whose function is to secrete milk. The breast is situated on either side of the sternum on the chest wall in the superficial fascia on the pectoral area between the sternum and axilla. It extends from the second or third rib, to the sixth or seventh rib. The size and weight of breast is variable.
The breasts are convex anteriorly with a prominence in the middle called nipple. It consists of skin and erectile tissue, and is encircled by a pigmented area called areola. It is pink to dark brown in color. Sebaceous glands are situated near the base of the nipple called Montgomery’s glands that secrete a fatty substance to keep the nipple soft. The nipple is perforated by 15–20 orifices, which are the milk ducts. At puberty the breast develops under the influence of the hypothalamus, anterior pituitary and ovaries, and also requires insulin and thyroid hormone:
During each menstrual cycle 3–4 days before menses, increasing levels of estrogen and progesterone cause cell proliferation and water retention. After menstruation cellular proliferation regresses and water is lost.
During pregnancy cellular proliferation occurs under the influence of estrogen and progesterone plus placental lactogen, prolactin and chorionic gonadotropin.It starts from the 16th week of pregnancy. At delivery, there is a loss of estrogen and progesterone and milk production occurs under the influence of prolactin. During the first 2–3 days after delivery, a thin fluid called colostrum that is rich in protein is secreted. The maintenance of milk secretion is controlled by the hormones from the anterior pituitary (oxytocin) and the thyroid glands.
At menopause involution of the breast occurs because of the progressive loss of glandular tissue.
Structure of Breast
Breast consists of alveolar tissue arranged in lobes separated by fibrous, connective and fat tissue. Each lobe has clusters of alveoli opening into tubules (lactiferous ducts), which unite with other ducts to form larger ducts that terminate as excretory ducts (Fig. 17.10). The ducts enlarge near the nipples that act as reservoirs for the milk; these are called lactiferous sinuses. The sinuses narrow down to pass through the nipple and open on to its surface. The blood supply to the breast is from the branches of axillary, intercostal and the internal mammary arteries. The breast has a rich network of lymphatics. The nerve supply to the breast is from the cutaneous nerves of the chest.
Breast examination should be done 7–10 days after beginning of menses in the following ways:
Inspection: Look for dimpling and nipple deformity.
Axilla: One to two percent of breast cancers initially present as enlarged axillary lymph nodes.
Patienties with supine position with hand behind her head.
Examine from across the table, i.e. right breast from the left side of the table.
Distinguish glandular tissue from breast fat. The breast consists of a mixture of firm glandular tissue and soft fatty tissue. There is a deficit of glandular tissue under the nipple-areolar complex. A typical distribution of glandular tissue is shown as the darkly-shaded area in the following illustration.
Check for loss of pliability as well as for masses.
The fetus leads a parasitic existence during development and before birth (Fig. 17.11). It is dependent on its mother for nutrients, oxygen and the elimination of wastes. The placenta is the life support system of the fetus. The blood vessels of placenta lie very close to the uterine blood vessels, but there are no direct connections. This allows the efficient exchange of nutrients and wastes between the fetal and maternal bloodstreams. Blood vessels in the umbilical cord carry blood between the fetus and the placenta.
The non-functional fetal lungs and the life support functions being accomplished via the umbilical cord require some modifications in the way that the blood is distributed in the body. Two of these modifications, the foramen ovale and the ductus arteriosus are in or near the heart. They are functional only before birth. At or soon after birth, they normally close and become non-functional.
The ductus arteriosus connects the pulmonary artery and aorta. It allows most of the blood pumped out through the pulmonary artery to move into the aorta, bypassing the non-functional lungs.
The foramen ovale connects the right and left atria. It allows some of the blood returning from the systemic circulation to move into the left side of the heart, bypassing the non-functional lungs.
Circulatory Changes that Take Place at Birth
The left umbilical vein constricts and becomes the ligamentum teres in the adult, which extends from umbilicus to liver (right umbilical vein has already disappeared).
Ductus venosus constricts to become ligamentum venosum in the adult that is superficially embedded in the wall of the liver.
Foramen ovale closes by valve-like septum primum as blood pressure in right atrium decreases and pressure in left atrium increases. In the adult, the valve fuses along the margin of foramen ovale and is marked by a depression called fossa ovalis.
Ductus arteriosus constricts to become ligamentum arteriosum that extends from the left pulmonary artery to the aorta.
Umbilical arteries constrict, the distal portion becomes the medial umbilical ligament and the proximal portion functions as superior vesical arteries.
Infertility is the inability to naturally conceive a child or the inability to carry a pregnancy to term. There are many reasons why a couple may not be able to conceive without medical assistance. Infertility affects approximately 15% of couples. Roughly 40% of cases involve a male contribution or factor, 40% involve a female factor and the remaining 20% involve both sexes. Healthy couples in their mid-20s having regular sex have a one-in-four chance of getting pregnant in any given month. This is called ‘fecundity’.
Primary Versus Secondary Infertility
Infertility affects about 10% of the reproductive age population. Female infertility accounts for one-third of infertility cases, male infertility for another third, combined male and female infertility for another 15% and the remainder of cases are unexplained.
Secondary infertility is difficulty conceiving after already having conceived and carried a normal pregnancy. Apart from various medical conditions (e.g. hormonal), this may come as a result of age and stress felt to provide a sibling for their first child. Technically, secondary infertility is not present if there has been a change of partners.
Factors of Infertility
Factors relating to female infertility are:
General factors: Diabetes mellitus, thyroid disorders, adrenal disease, significant liver, kidney disease and psychological factors.
Hypothalamic-pituitary factors: Kallmann’s syndrome, hypothalamic dysfunction, hyperprolactinemia and hypopituitarism.
Ovarian factors: Polycystic ovary syndrome, anovulation, diminished ovarian reserve, luteal dysfunction, premature menopause, gonadal dysgenesis (Turner syndrome) and ovarian neoplasm.
Tubal/peritoneal factors: Endometriosis, pelvic adhesions, pelvic inflammatory disease (PID usually due to Chlamydia) and tubal occlusion.
Cervical factors: Cervical stenosis, antisperm antibodies and insufficient cervical mucus (for the travel and survival of sperm).
Vaginal factors: Vaginismus and vaginal obstruction.
Genetic factors: Various intersexuality/intersexed conditions such as androgen insensitivity syndrome.
In some cases, both the man and woman may be infertile or subfertile and the couple’s infertility arises from the combination of these factors. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile, but the couple cannot conceive together without assistance.
In about 15% of cases of infertility, investigations will show no abnormalities. In these cases, abnormalities are likely to be present, but not detected by current methods. Possible problems could be:
The egg is not released at the optimum time for fertilization
It may not enter the fallopian tube
Sperm may not be able to reach the egg
Fertilization may fail to occur
Transport of the zygote may be disturbed or implantation fails. It is increasingly recognized that egg quality is of critical importance.
Diagnosis of Infertility
Diagnosis of infertility begins with a medical history and physical examination. The healthcare provider may order tests including the following:
An endometrial biopsy, which tests the lining of the uterus
Hormone testing to measure levels of female hormones
Laparoscopy, which allows the provider to see the pelvic organs
Ovulation testing, which detects the release of an egg from the ovary
Pap smear to check for signs of infection
Pelvic examination, to look for abnormalities or infection
A postcoital test, which is done after sex to check for problems with secretions
Special X-ray tests.
Fertility medication, which stimulates the ovaries to ‘ripen’ and release eggs (e.g. clomifene citrate, which stimulates ovulation).
Surgery to restore potency of obstructed fallopian tubes (tuboplasty).
Donor insemination, which involves the woman being artificially inseminated with donor sperm.
In vitro fertilization (IVF) in which eggs are removed from the woman, fertilized and then placed in the woman’s uterus, bypassing the fallopian tubes. Variations on IVF include:
Use of donor eggs and/or sperm in IVF happens when a couple’s eggs and/or sperm are unusable or to avoid passing on a genetic disease.
Intracytoplasmic sperm injection (ICSI) in which a single sperm is injected directly into an egg; the fertilized egg is then placed in the woman’s uterus as in IVF.
Zygote intrafallopian transfer (ZIFT) in which eggs are removed from the woman, fertilized and then placed in the woman’s fallopian tubes rather than the uterus.
Gamete intrafallopian transfer (GIFT) in which eggs are removed from the woman and placed in one of the fallopian tubes along with the man’s sperm. This allows fertilization to take place inside the woman’s body.
Other assisted reproductive technology (ART):
Freezing (cryopreservation) of sperm, eggs, and reproductive tissue.
Frozen embryo transfer (FET).
Alternative and complementary treatments:
Acupuncture: Recent controlled trials published in fertility and sterility has shown acupuncture to increase the success rate of IVF by as much as 60%. Acupuncture was also reported to be effective in the treatment of female anovular infertility (World Health Organization, acupuncture: review and analysis of reports on controlled trials, 2002).
Diet and supplements.
Birth control is a regimen of one or more actions, devices or medications followed in order to deliberately prevent or reduce the likelihood of a woman becoming pregnant. Methods and intentions typically termed birth control may be considered a pivotal ingredient to family planning. Mechanisms, which are intended to reduce the likelihood of the fertilization of an ovum by a sperm may more specifically be referred to as contraception. Contraception differs from abortion in that the former prevents fertilization while the latter terminates an already established pregnancy. Methods of birth control, which may prevent the implantation of an embryo if fertilization occurs are medically considered to be contraception. It is advised to talk with a doctor before choosing a contraceptive. If you have genetic problems or blood conditions such as factor V Leiden, certain contraceptives can be deadly.
The term contraception includes all measures temporary or permanent, designed to prevent pregnancy due to the coital act. An ideal contraceptive method should fulfill the following criteria; it should be widely acceptable, inexpensive, simple to use, safe, highly effective and require minimal motivation, maintenance and supervision.
Various contraceptions are available, but no single universally acceptable method has yet been discovered:
Abstinence (no sex), 100% effective.
Coitus interruptus (pulling out penis from vagina before ejaculation) 77% effective.
Rhythm method, intercourse before ovulation or during menstruation, 60% effective.
Vaginal tampons: Structures used by ancient and medieval civilizations may be accompanied by vinegar, hemlock, opium, honey that were used as spermicides, percent effectiveness unknown.
Diaphragm: Cervical cap, 81% effective with spermicide.
Condom (latex sheath placed over the penis), 90% effective.
IUD probably acts as an irritant to prevent implantation, 95% effective.
Ligation or cutting off of fallopian tubes (tubectomy) in female is about 85% effective. Ligation or cutting off of vas deferens (vasectomy) in males is about 99.6% effective.
Douche-spermicides, 40% effective.
Oral contraception: The pill, suppresses ovulation by releasing estrogen and progesterone derivatives, 98% effective.
Implants: Similar to pill, but it is an implant under the skin, which gradually releases progesterone derivatives, percent effectiveness—need more data.
RU486 (morning after pill) is taken orally, the morning after unprotected sex. It competes for progesterone receptors, disrupts communication between embryo (secretes hCG) and corpus luteum.
SEXUALLY TRANSMITTED DISEASES
Communicable diseases that are transmitted through sexually are called STDs. The commonly encountered STDs are:
Herpes simplex II: Virus causes two types of lesions: oral and genital.
Trichomonas: Protozoan that causes burning and vaginal discharge.
Chlamydia: Bacterium that causes painful urination. It can lead to arthritis, heart disease and other symptoms in men.
Syphilis: Bacterium, 3 stages (sores followed by rash followed by invasion of the organ systems).
Gonorrhea: Caused by bacterial infection and characterized by inflammation of reproductive tract and pelvis (PID). It can spread to other parts of the body (heart, joints).
AIDS: For details refer Chapter 5 under heading ‘Immune System’.
Human experience is affected by both internal and external stimuli. Humans are able to distinguish among many different types of stimuli by means of a highly developed system of sense organs. Sensory systems represent an integration of the functions of peripheral nervous system and central nervous system (CNS). The sensory division of the peripheral nervous system gathers information about the body’s internal conditions and external environment. Sensory systems translate light, sound, temperature, and other aspects of the environment to electrical signals and transmit these signals in the form of action potentials to the CNS, where they are interpreted as touch, taste, sight, smell and sound.
There are millions of neurons in the body that do not receive impulses from other neurons. Instead, the neurons, which are called sensory receptors, react directly to stimulation from the environment. Many receptors that enable the body to receive information from the environment are located in highly specialized organs called sense organs. For example, stimulation include light, sound, motion, chemicals pressure, pain or changes in the temperature.
Once these sensory receptors are stimulated, they transform one form of energy from the environment (light, sound) into another form of energy (action potential) that can be transmitted to other neurons. These action potentials (impulses) reach the CNS.
A sensory receptor is a neuron that is specialized to detect a specific stimulus. There are many kinds of sensory receptors, which can be categorized on the basis of the type of stimuli, they respond to:
Mechanoreceptors respond to movement, pressure, and tension
Photoreceptors (rods and cones) respond to variations in light
Chemoreceptors respond to chemicals
Thermoreceptors respond to changes in temperature
Pain receptors respond to tissue damage.
Specific sensory receptors are contained in specific sense organs. Each of the five senses (sight, hearing, smell, taste and touch) has a specific sense organ associated with it. The most familiar sense organs are the eyes, ears, nose, skin and taste buds. These organs have receptors that can respond to stimuli by producing nerve impulses in a sensory neuron. The receptors convert the energy of a stimulus into electrical energy that can travel in the nervous system.
Receptors inside the body inform the CNS about the conditions of the body. For example, the temperature receptors throughout the body detect changes in temperature. This information travels to the hypothalamus, which helps to control body temperature.
Specialized cells (receptors) within each sense organ enable it to respond to particular stimuli. Messages from sense organs to the CNS are all in the form of nerve impulses. How does our brain know, whether incoming impulse is sound or light? This information is built into the ‘wiring’ in the pathways of neurons that synapse with each other and into the location in the brain where the information arrives. The brain knows, if the information received is from a sensory neuron that comes from light receptors cells, when it gets the message.
TONGUE AND TASTE
The tongue is generally considered as a special sense organ for taste and lies in the floor of the mouth. The blood vessels and nerves pass in and out of the tongue at its root. The margins and the tip of the tongue are in contact with the lower teeth, and its dorsum is arched on the upper surface. The posterior part of the undersurface of tongue is attached to the floor of the mouth by a ligamentous structure that is called frenulum linguae. The anterior part of the tongue is free and appears pointed when protruded, but is rounded when lying in the floor of the mouth.
The tongue is composed of two groups of muscles. Intrinsic muscles perform all the delicate movements of the tongue and the extrinsic muscles attach the tongue to the surrounding parts and perform the larger movements that help mastication and swallowing. The mucous membrane is moist and pink in color. The upper surface is velvety and covered by papillae.
The sense of taste is a chemical sense and the organ that detects taste is the taste bud, not the tongue. The cells that are stimulated by the chemicals are called chemoreceptors. There are more than 10,000 taste buds, which are embedded between bumps on the tongue that are called papillae, but can also be found on the roof of the mouth, on the lips and in the throat.
There are four types of papillae on the human tongue (Fig. 18.1). Only the circumvallate, foliate and fungiform papillae bear taste buds. The tongue detects five flavors—sweet, salt, sour, bitter and umami. Umami is described as ‘savoriness’. Receptors for umami have been recently found. Each taste bud shows a particular sensitivity to one of these tastes:
Circumvallate papillae are 8–12 in number and are the largest. They are arranged in a V-shape at the back of the tongue and each one is surrounded by a little moat-like depression.
Fungiform papillae are fungoid in shape and are distributed over the tip of the tongue.
Filiform papillae are found over the whole surface of the tongue and are the most abundant.
Foliate papillae are distributed on the sides of the tongue on its posterior one-third portion.
During chewing, chemicals from food called tastants, enter the taste pores of the taste buds, where they interact with molecules on finger-like processes called microvilli on the surfaces of specialized taste cells. The interactions trigger electrochemical changes in the taste cells that cause them to transmit signals to the brain by two nerves—the facial nerve and glossopharyngeal nerves. Many of the sensations associated with taste are actually smell sensations; we depend on both senses to detect flavors in food. That is why, when we have a cold and our smell receptors are blocked, food seems to have little or no taste.
The impulses are interpreted together with smell and other sensory input as flavors. Salt can hide bitter flavors. The heat of chili peppers is actually not a flavor, but a response of pain receptors on the tongue. As we age, we lose taste buds and our sensitivity to food decreases. Food tastes bland to older people, so spice it up for them.
Nerve Supply of Tongue
The hypoglossal nerve (XII cranial nerve) innervates the muscles of the tongue.
The general sensations (tactile sense, discrimination of size, shape and texture, and temperature) from the anterior part of the tongue travel along the lingual nerve (branch of V cranial nerve, i.e. trigeminal nerve).
The impulses from taste buds in the anterior part of the tongue travel in the chorda tympani, which joins facial nerve (VII cranial nerve).
The general sensations and impulses from the taste buds in the posterior one third of the tongue are carried by glossopharyngeal nerve (IX cranial nerve).
The examination of tongue includes, observing whether it is dry or moist, the color, texture of the surface, the size and tonicity. Chronic indigestion and deficiency of vitamins, and poor dental hygiene can cause glossitis. In chronic smokers, thick white patches (leukoplakia) may be found on the buccal mucosa and gums.
NOSE AND SMELL
Our sense of smell is one of our two chemical senses, the other being the sense of taste. Both allow us to be aware of substances in our environment and rely on our ability to detect these substances by the chemical nature of their molecules.
The olfactory nerve (I cranial nerve) supplies the end organs of smell. The filaments of this nerve arise in the upper part of the mucous membrane of the nasal cavities that are known as olfactory portion of the nose. The fibrils that originate from the receptors found in the cells of this mucous membrane arborize and makes contact with the fibers from the olfactory bulb. The olfactory bulb is the outlying portion of the brain that forms the olfactory tract (Figs 18.2A and B). The olfactory bulb rests on the cribriform plate of the ethmoid bone. The sensation from the olfactory bulb is passed along the olfactory tract through several relay stations to the olfactory center, which is situated in the cortex of temporal lobe of cerebrum where it is interpreted.
Only gaseous molecules stimulate the sense of smell. These may come directly from the air we breathe or may come from volatile substances released in our mouth, from the food we are eating. The molecules we perceive as smells are called odorants.
Odorant molecules stimulate sensory nerve cells at the top of the nasal cavity and these respond by sending impulses to the brain. The sensory nerve cells involved are called receptor cells, their surfaces have regions on them called receptor sites. These detect the odorant molecules and the process triggers a sequence of changes in the cell that eventually generates an electrical signal.
Olfactory information travels not only to the limbic system, which refers to the primitive brain structures that governs emotions, behavior and memory storage but also to the brain’s cortex or outer layer, where conscious thought occurs. In addition, it combines with taste information in the brain to create the sensation of flavor. Thus, odors have a profound effect on our thoughts, emotions and behavior.
Odor molecules entering the nose are recognized by receptors found in cilia of olfactory neurons. Neurons with specific receptors are arranged randomly within zones in the olfactory lining of the nasal cavity. Signals from neurons with the same receptors converge on structures called glomeruli in the olfactory bulb. The pattern of activity in these glomeruli creates a pattern or code that the brain may interpret as different odors. The information is carried by nerve fibers to many brain regions, where it affects thoughts, emotions and behavior.
Smells are detected in the nose by the specialized receptor cells of the olfactory epithelium. These are called olfactory receptor neurons. In the roof of each nostril is a region called nasal mucosa. This region contains the sensory epithelium—the olfactory epithelium, which is covered by mucus. The epithelium contains the sensory cells, and Bowman’s glands producing the secretion that bathes the surface of the receptors. This is an aqueous secretion containing mucopolysaccharides, immunoglobulins, proteins (e.g. lysozyme) and various enzymes (e.g. peptidases). Also found in the nasal mucosa, is a pigmented-type of epithelial cell—the depth of color is often correlated with olfactory sensitivity, it is light yellow in humans. Pigment may play a part in olfaction, perhaps by absorbing some kind of radiation, like infrared. Finally, the nasal epithelium contains the receptor cells—some 10 million in humans. They possess a terminal enlargement (a ‘knob’) that projects above the epithelial surface from which there extend about 8–20 olfactory cilia. These cilia do not beat (being nonmotile), but they contain the smell receptors.
EAR AND HEARING
The ear is really two sense organs in one. It not only detects sound waves but also senses the position of the head, whether it is still moving in a straight line or rotating. The sound is nothing more than vibrations in the air around us. Deep, low-pitched sounds result from slow vibrations. High-pitched sounds are caused from faster vibrations. In addition to pitch, sounds differ by their loudness or volume.
Vibrations in matter (gas, liquids and solids) produce sound. For example, vocal cords vibrate and push the air through the larynx, which causes the air to vibrate. Remember that sound cannot travel through vacuum. Velocity of sound varies with the media through which it has to travel. In air, velocity of sound is 344 m/s (770 mile/hour), in water 1,500 m/s (3,360 mile/hour) and in solids about 5,000 m/s (11,200 mile/hour).
Pitch is determined by the frequency of vibration (Fig. 18.3). Fast vibrations are perceived as high pitches and slow vibrations as low pitches. When we are young, we can hear vibrations from about 20 Hz to about 20,000 Hz (a Hz is cycle/second).
Sound intensities are measured in decibels; the stronger the vibration/amplitude (higher sound pressure), louder is the noise and vice versa (refer Fig. 18.3). The scale used for sound intensity is logarithmic, because of the wide range of sound intensities that we encounter.
Sound intensities are given in decibels (dB).
Decibel = 20 × log P/Po
P = sound pressure
Po = reference sound
Pressure = pressure at threshold of hearing for 4,000 hertz tone.
The human ear can respond to a range of sound intensities of about a million to one. For intensity of a million times Po, the number of decibels is:
Decibel = 20 × log (1,000,000/1) = 120
Sounds louder than this will be painful and damage the ear.
A few examples of sound intensities are:
Threshold of hearing (4,000 Hz) = 0 dB
Soft whisper = 20 dB
Conversation = 60 dB
Busy traffic = 70 dB
Rock band = 120 dB
Pain threshold = 130 dB.
Parts of Ear
The ear has three essential parts (Fig. 18.4). They are as follows:
The outer ear that collects and amplifies sound.
The middle ear has transducer to convert sound vibrations into action potentials.
Cochlea and the auditory nerves to convert sound vibrations to action potentials signals, and to deliver to the brain for interpretation.
The external ear consists of the visible fleshy part, which helps to collect sounds and funnel them into the auditory canal. The auditory canal connects the external ear with the tympanic membrane, also called eardrum. The auditory canal contains small hairs and wax producing glands that prevent foreign objects from entering the ear. The auditory canal extends into the bone of the head, but stops at the eardrum or tympanic membrane.
The middle ear begins at the eardrum. The sound waves are amplified by bones/ossicles (malleus, incus and stapes) of the middle ear (Fig. 18.5).
The eardrum is attached to the malleus (hammer), which is in attachment to the incus anvil) and in turn is attached to the stapes (stirrup). The starpes transfers the vibrations to a thin membrane covering an opening called oval window.
Because of the way the bones are attached together, the vibrations in the oval window are 20 times larger than those in the eardrum (amplification). If the sound is too loud, small muscles attached to the ear bones contract and dampen the vibrations.
The tympanic membrane transmits the vibrations to the cochlea, which is beginning of the inner ear (refer Fig. 18.5). The cochlea is snail-shaped organ, consisting of three fluid-filled chambers that are separated by membranes. The middle chamber contains the organ of Corti, which is the organ of hearing. When the fluid vibrates, tiny hair cells lining the cochlea are pushed back and forth, providing stimulation that is turned into nerve impulses. These nerve impulses are carried to the brain by the auditory or acoustic nerve.
The ears also contain structures for detecting stimuli that make us aware of our movements and allow us to maintain our balance. These structures are called vestibular apparatus (Fig. 18.6). They are located within the inner ear, just above the cochlea. These are three tiny canals that lie at right angles to each other and are called semicircular canals because each makes half a circle.
Cochlea converts sound vibrations to action potentials in the auditory nerve. Vibration of the oval window causes cochlear fluid (perilymph and endolymph) to vibrate. The fluid vibrations in turn cause the basilar membrane to vibrate, producing traveling waves. The basilar membrane vibrations cause hair cells to bend and evoke generator potential. If generator potentials are large enough, they will stimulate fibers of the auditory nerve to produce action potentials.
Different parts of the cochlea detect different pitches:
High pitches produce waves traveling at the base of the cochlea (near the oval window)
Low pitches produce waves traveling at the apex.
The ear is most sensitive to tones in the range of 500–4,000 Hz (the range of normal speech). An audiogram measures the hearing threshold at different frequencies—the threshold is lowest at middle frequencies (Fig. 18.7).
At about 120 dB, we start to feel the sound as a tickling sensation. The ear is useful in the decibel range between the hearing threshold and the feeling threshold.
At about 130–140 dB, sound starts to produce pain. As we age, we lose our ability to hear high-pitched sounds (hearing loss). Loss in the speech range occurs later.
The auditory nerve delivers the action potential signals to the temporal cortex. After synapsing in the thalamus, different tones of auditory impulses are sent to different parts of the temporal cortex. If the sounds have special meaning (speech, music), other parts of the cortex are activated. Auditory reflexes are controlled by inferior colliculus.
Deafness is of three types—conduction, sensorineural and central.
Conduction deafness: It is the mechanical problem in conducting sound waves to oval window. It is often caused by problems with ear bones (middle ear infections).
Sensorineural deafness: It is due to cochlear or auditory nerve damage. It is often caused by loss of hair cells.
Central deafness: It is due to damage, to auditory pathways or centers in the CNS. It is sometimes caused by strokes.
SENSE OF BALANCE
The organ of balance is vestibular apparatus, which lies near the cochlea in the inner ear (refer Fig. 18.6). Its membranous labyrinth consists of the semicircular canals, the saccule and the utricle. Each of the three semicircular canals widens to form an ampulla containing a crista, which is the receptor organ.
The crista is crowned by a gelatinous cupula, which moves like a swinging door toward one or the other side of its canal through which the cilia of the sensory cells project. The semicircular canals are filled with endolymph that is surrounded by perilymph.
When the head is rotated, the endolymph is displaced in opposite direction and flow within the semicircular canals. This causes the cupula to swing, bending its cilia and causing excitation of the nerve fibers of sensory cells. The fact that each of the semicircular canals is perpendicular to the other two, makes possible the registration of rotatory accelerations in all spatial planes.
The vestibular organ possesses two other sensory epithelia, the saccule and the utricle; each of which contains an otolithic organ, the macula in which statoliths (calcium carbonate crystals) are embedded. When the head is moved, these statoliths displace the membrane with the cilia and stimulate the hair cells. The macula registers linear acceleration and deviations of the head from the vertical position.
EYE AND VISION
The sense organ we use to sense light is the eye and the sensory nerve of sight is optic nerve (II cranial nerve). The eyeball is contained in the bony orbit and protected by appendages such as the eyelids, eyebrows, conjunctiva and the lacrimal apparatus.
The eye has three essential parts (Fig. 18.8):
Optical apparatus that collects and focuses light onto the retina. It also controls and adjusts amount of light entering the eye.
Detector system, which is sensitive to light (for light, dark and color).
Nerve pathways that route signals to the brain for interpretation.
Layers of Eye
The eyeball is oval in shape and is about an inch in diameter. It is composed of three layers (refer Fig. 18.8):
The outer layer consists of the sclera and cornea.
The middle layer contains the choroid, ciliary body and iris.
The inner layer consists of the retina.
The sclera (white of the eye) consists of tough white connective tissue. It helps to maintain the shape of eye and also provides a means of attachment for the muscles that move the eye.
The cornea is the transparent part of the sclera that is in front of the eye. It is the part of the eye through which light enters.
Anterior chamber is present between the cornea and the iris, which is filled with fluid known as the aqueous humor. At the back of this chamber, the pigmented choroid, which contains the blood vessels of the eye, becomes a disk-like structure called iris.
Iris is responsible to provide color to eye. The iris controls the amount of light entering the eye by altering the diameter of the pupil. In the middle of the iris is a small opening called pupil, through which light enters the eye.
The pupil appears as a small black disk in the center of the eye. Tiny muscles in the iris regulate the size of the pupil, controlling the amount of light to enter the eye. In dim light, the pupil opens to increase the amount of light; in bright light, the pupil closes to decrease the amount of light entering the eye.
The lens is situated behind the iris. Light is focused by the lens, which changes shape when pulled by muscles around its edges. The cells that form the lens, contain a special protein called crystalline, which is almost transparent and allows light to pass through. Small muscles attached to the lens cause it to bend; this enables the eye to focus on close and distant objects.
Vitreous chamber lies behind the lens, filled with a transparent jelly-like fluid called vitreous humor.
The retina is present at the back of the eye, which has the layer of special light-sensitive receptor cells or photoreceptors. The photoreceptors convert light energy into impulses that are carried to the CNS.
There are two types of photoreceptors namely rods and cones. We have around 125 million rods and 7 million cones on a single retina. Photoreceptors contain a pigment called rhodopsin that can respond to most wavelengths of light. Rods are extremely sensitive to all colors of light, but do not distinguish different colors. Cones are less sensitive than rods, but they do respond differently to light of different colors, producing color vision. Humans have three kinds of cones. Each type of cone contains a pigment that absorbs different wavelengths of light. When the signals from these three kinds of cone are integrated, a person is able to see all the colors in the visible spectrum. In dim light, when only rods are activated, one may see objects clearly, but not their colors. As the amount of light increase, the cones are stimulated and the colors become clear.
The impulses leave the eye by way of the optic nerve and carried to the part of brain known as the cortex of optic lobe or occipital lobe. Here the brain interprets the visual images and provides information about the external world.
The nerves arising from the ganglion cells in the retina, converge to form the optic nerves (II cranial nerve). This nerve passes backwards and medially, and run through the optic canal to enter the cranial cavity and then to the optic chiasma. The optic nerve has three coverings, i.e. the outer covering is tough and fibrous that blends with the sclera; the middle covering is like arachnoid mater and the inner covering is vascular.
At the optic chiasma (Fig. 18.9), half of the fibers of optic nerve crossover to the opposite side of the optic tract. This kind of arrangement of fibers relates the optic nerve to both sides of the brain. The fibers arising from the medial half of the retina, ends up at the superior colliculus and those arising from the lateral half of the retina, reach the visual cortex after passing through the lateral geniculate body.
Muscles of the Eye
There are six muscles (Fig. 18.10) that coordinate the movement of eyeball—four are straight and the other two are oblique. These muscles lie within the orbit and pass from the bony walls of the orbit, to be attached to the sclerotic coat of the eyeball behind the cornea.
The superior, inferior, lateral and medial recti are the straight muscles of the eye. These muscles move the eyeball upwards, downwards, outwards and inwards respectively.
The superior and inferior oblique muscles move the eyeball obliquely downwards and outwards, and obliquely upwards and outwards respectively. The movements of the two eyeballs are combined. All these muscles are supplied by cranial nerve III, except lateral rectus muscle, which is supplied by cranial nerve VI and superior oblique supplied by cranial nerve IV.
The axes of both the eyes converge simultaneously on the same point. The paralysis of one or more muscles of the eye may result in strabismus (squint). When glasses or reeducation cannot correct the abnormality, it is usually corrected by surgery and reeducation.
Appendages of Eye
The appendages of eye (Fig. 18.11) are described below.
Eyebrows are two thick arches of skin on the superior aspect of the orbit from which hairs grow. They serve to protect the eyes from light.
The eyelids are two tarsal plates composed of dense fibrous tissue, covered by skin and lined with conjunctiva. The upper eyelid is larger than the lower. The upper eyelid is raised by levator palpebrae muscle and closed by orbicularis oculi muscles. At the free margins of the lids, eyelashes are attached that protect the eyes from dust and light.
Conjunctiva is the mucous membrane that lines the eyelids and the front of the sclera. The mucous lining is continuous with the lacrimal ducts, lacrimal sac and with the nasolacrimal ducts.
Lacrimal apparatus is composed of lacrimal gland, lacrimal ducts, lacrimal sac and the nasolacrimal duct. The lacrimal duct is situated at the upper, outer corner of the orbit, and secretes the tears, which spreads across the eyeball and keeps it moist. The excess secretions are drained into the nose through the lacrimal ducts.
SKIN, TOUCH AND RELATED SENSES
All regions of our bodies are sensitive to touch and the largest sense organ is the skin (Fig. 18.12). The mechanoreceptors located throughout the skin, make it possible to sense touch, pressure and tension. The receptors for touch are concentrated in the face, tongue and fingertips.
Body hair also plays an important role in the ability to sense touch. Large numbers of mechanoreceptors are found in the skin at the base of hair follicles.
The skin has several different types of sensory receptors that are just below the surface of the skin. Two types respond to heat or cold—thermoreceptors; two others respond to touch—mechanoreceptors; one type responds to tissue damage, which causes pain—pain receptors.
Sensory receptors for hot or cold are scattered directly below the surface of the skin. There are three to four warm receptors for every cold receptor. The most touch-sensitive areas are the fingers, toes and lips. Pain receptors are located throughout the skin. The sensation of pain can be experienced as either prickling pain (fast pain) or burning and aching pain (slow pain). Pain receptors are stimulated by mechanical, thermal, electrical or chemical energy.
The nervous system and endocrine system are the two systems that monitor the internal and external environments, and regulate metabolic and homeostatic processes. The nervous system is unique to animals, giving them mobility via the coordination of muscle contraction.
Generally, the nervous system is responsible for rapid responses. The slower and more prolonged processes are controlled by the endocrine system. Often the two systems work in tandem, one reinforcing the action of the other.
The nervous system is mainly composed of nerve cells called neurons. Neurons can transmit information along their length very quickly. In the central nervous system (CNS), billions of neurons make up the neuronal networks that perform such complex functions as thought, memory and the control of voluntary and involuntary movements.
The human nervous system is undoubtedly one of the most complex parts of the human body. The brain and spinal cord are at the center of this system and together make up the CNS. The CNS receives information from other parts of the body via the peripheral nervous system (PNS). The CNS processes that information and then sends out instructions to organs, glands and muscles via the PNS.
Before we understand how the nervous system works, we first need to look at the components of the nervous system.
The nervous system is mainly composed of nerve cells called neurons. Neurons can transmit information along their length very quickly. In the CNS, billions of neurons make up the neuronal networks that perform such complex functions as thought, memory and the control of voluntary and involuntary movements.
NEURONS AND NERVOUS SYSTEM
Neurons exist in a variety of shapes and forms, but they all have some common features (Fig. 19.1). The dendrites receive stimulation and transmit nerve impulses along the axon to the axon terminals.
Central Nervous System
The central nervous system is surrounded by the protective bones of the skull and vertebral column. The CNS is the command center of the nervous system, interpreting sensory information and initiating responses. The neurons that make up this loop of information are divided into three classes as given below:
Afferent neurons that transmit information into the CNS
Efferent neurons that transmit information out of the CNS
Interneurons that communicate within the CNS.
The brain itself is incredibly complex and there is no space here to explore it in any detail. An important point to note is that each part of the brain is responsible for a particular function (although there is much interlinking and task sharing). A few important regions in the brain are shown in Figure 19.2. The functions of these are as follows:
Frontal lobes: Thinking, decision-making, personality expressions.
Somatosensory cortex: Processing of sensory information from receptors in the body
Temporal lobes: Processing of speech and sounds
Primary auditory area: Interprets basic characteristics of sounds
Broca’s area: Speaking and understanding speech
Wernicke’s area: Interprets the meaning of speech, converts words into thoughts
Occipital lobe: Processing of visual material
Cerebellum: Coordinates complex movements
Brainstem: Relay station for neural pathways and centers that control basic functions such as breathing and the cardiovascular system.
Peripheral Nervous System
All nerves that are outside the CNS are called peripheral nerves and all the peripheral nerves collectively make up the peripheral nervous system (PNS). The PNS has two functional subdivisions, the sensory and the motor division (Fig. 19.3).
Sensory division consists of nerves that carry information from sensory receptors into the CNS, constantly updating the CNS with events in the internal and external environment.
Motor division transmits impulses from the CNS to organs, muscles and glands. The motor division has two parts, the somatic and autonomic divisions:
Somatic nervous system: It conducts impulses from the CNS to skeletal muscle. This allows to contract muscles and control movements.
Autonomic nervous system (ANS): Most internal organs, tissues and glands are under the control of nerves. This control maintains the internal environment in a steady state called homeostasis. Functions controlled by the ANS include blood pressure and digestion.
The ANS is composed of two parts—the parasympathetic and sympathetic nervous systems, and they have clear anatomical and functional differences. Most internal organs and glands have a nerve supply from both the parasympathetic and sympathetic systems. Generally, these systems work in opposite manner—one stimulating and the other, inhibiting the activities. Together they maintain the internal activity of the body (Table 19.1).
Parasympathetic nervous system: This system maintains body functions to conserve energy and is dominant when the body is at rest.
Sympathetic nervous system: Like the parasympathetic system, this system regulates function and maintains homeostasis. However, it also has the ability to prepare the body to cope with emergencies, stress and increased activity. This is called ‘fight or flight’ response and is an instinctive response to stress.
When a nerve impulse arrives at the axon terminal, an additional process is required to allow continuation of the nerve impulse in the next neuron. Nerve impulses cannot simply jump from neuron to neuron, because at the junction between neurons, there is a small gap. The junction between the neurons is called synapse. It is a very useful area because many of the common drugs such as beta-blockers and Prozac are targeted at the synapse.
Communication between the neurons across the synaptic gap is in the form of chemical messengers called neurotransmitters. The arrival of a nervous impulse at the presynaptic axon terminal triggers the release of the neurotransmitter into the synaptic cleft. Once in the synaptic cleft, the neurotransmitter diffuses toward the postsynaptic membrane and binds to receptors embedded in the membrane. This will either stimulate or inhibit the postsynaptic membrane. Whether messages sent via the neurotransmitter excite or inhibit the postsynaptic neuron, depends on the type of neurotransmitter and the class of receptor.
There are many different types of neurotransmitters including Ach and noradrenaline (norepinephrine) in the PNS, and dopamine and serotonin in the CNS.
Motor impulses are generated in the pyramidal cells situated in the motor area of brain cortex. The impulses travel along the axon, down the spinal cord. The ends of axons branches out and makes close contact with the dendrites of the motor cells in the anterior horn of the spinal cord. The impulses are then passed onto the axons of these cells that form the motor fibers of the anterior root of a spinal cord (Fig. 19.4) and are conveyed to muscle fibers in which they terminate.
Sensory impulses are received by the nerve endings in the periphery (skin), which travel along the nerve fibers to the sensory cells in the posterior root ganglion. Then the impulses pass along the axons of these cells to the spinal cord and ascend to a nucleus in the medulla, and relayed further to the brain. The nerve fibers traveling to and from different parts of the brain, are grouped into definite tracts in the spinal cord.
The cerebrospinal nerves form four types of nerve trunks as follows:
Motor nerves (efferent) carry impulses from the brain to the periphery.
Sensory nerves (afferent) carry impulses from the periphery to the brain.
Mixed nerve trunks contain both motor and sensory fibers. Most of the nerves are of mixed type.
Commissural or associated nerve fibers link up different nerve centers in the brain and spinal cord.
The brain and spinal cord are protected by a bony skull, and are also wrapped in three layers of connective tissue known as the meninges (Fig. 19.5).
The pia mater is the innermost layer, which covers and is bound to the surface of the brain. It is a fibrous layer made up of many blood vessels, which carry nutrients and oxygen to the brain.
The arachnoid is the thin, elastic, web-like layer that separates dura mater and pia mater. It is closely applied to dura mater and is separated from the pia mater by a subarachnoid space that contains cerebrospinal fluid (CSF). The subarachnoid space is enlarged into cisterna magna, between the undersurface of the cerebellum and the medulla oblongata. The CSF can be withdrawn from this space by inserting a needle between the occiput and atlas vertebrae. Great care must be taken while performing this procedure. Inserting the needle too far can damage the medulla oblongata with fatal consequences.
CSF separates the middle and inner meninges and fills four interconnected ventricles or cavities in the brain. Within the ventricles, CSF acts as a transport medium for substances that are important to brain function. The CSF is a clear liquid that protects the brain from mechanical injury by acting as a shock absorber.
Dura mater lines the interior of the cranium and vertebral column, and actually forms the periosteum. At two places it separates into two layers, where the inner layer dips into the brain and support the brain to maintain its position:
The falx cerebri is a sickle-shaped fold of the inner layer of dura mater that dips vertically in the midline, to separate the left and right cerebral hemisphere.
The tentorium cerebelli is a crescentic, arched sheet of the inner layer of the dura mater, which lies horizontally and forms a tent-like roof over the posterior cranial fossa, and separates the cerebrum above and the cerebellum below.
The venous sinuses (sagittal, transverse and cavernous) are contained between the two layers of the dura mater.
The pia mater is closely attached to the brain and spinal cord, and carries small blood vessels to the surface of brain and spinal cord. This membrane dips into all the fissures between the convolutions. It invaginates into the ventricles of the brain to form the tela choroidea and choroid plexuses of the third and fourth ventricles, and the choroid plexuses of the lateral ventricle. The choroid plexuses secrete the CSF. The spinal cord ends at the level of lower border of first lumbar vertebra, but the pia mater continues downward at the lower end of the spinal cord as the filum terminale that gets attached to the dorsum of the coccyx. The subarachnoid space around the filum terminale is a capacious space, which is the preferred site (between third and fourth lumbar vertebrae) for lumbar puncture for the withdrawal of CSF.
CSF is clear alkaline fluid resembling plasma. It acts as a mechanical buffer that protects brain and spinal cord, and provides nourishment to the tissues of the CNS.
VENTRICULAR SYSTEM OF THE BRAIN
Ventricular system of the brain consists of several cavities within the brain that are interconnected (Fig. 19.6). The choroid plexuses is formed by a network of minute capillary blood vessels and covered by pia mater, which project into ventricles and secrete CSF.
There are two lateral ventricles, one in each cerebral hemisphere, and are connected with the third ventricle that lie in the midline between the thalami. The third ventricle is connected with the fourth ventricle through a narrow opening called the cerebral aqueduct that lies between the cerebellum pons and medulla.
CSF from the fourth ventricle passes into the subarachnoid space and central canal of the spinal cord, through openings in the roof of the fourth ventricle.
The CSF is returned to the venous circulation by the arachnoid granulations in the superior sagittal sinus.