Introduction of the CellUNIT I

The science of mammalian physiology involves the study of dynamic inter-relationships that exist among cells, tissues, and organs, and reaches ultimately to the level of the organism as a whole. The cell is the smallest functional unit and it is itself composed of organelles. In this chapter, we shall focus on the structure and function of these organelles.

The cell membrane is a permeability barrier. If a cell is placed in hypotonic solution and if it contains molecules, which cannot penetrate its outer membrane, it will swell; conversely, it will shrink if placed in a hypertonic medium. In both instances water moves down its concentration gradient. Thus, the cell behaves as an osmometer. Nonpolar molecules (gases, lipids) move freely across the membrane; polar molecules penetrate the membrane much less readily and indeed it is the selective permeability of the plasma membrane to certain ions, which determines the excitability characteristics of nerve and muscle cells.

Although the general chemical nature of the membrane found at the cell boundary was predicted on the basis of physiological data, the detailed molecular structure is not yet known. Models 3of cell membranes prepared by combining their lipid and protein constituents (partly known from chemical analysis of purified cell membrane preparations) exhibit some physiological characteristics similar to those of natural membranes. The role of lipid: lipid interactions in membrane structure have been at the center of attention because such interactions can explain much of the presently known phenomena of membrane transport. Quantitative studies of isolated cell membranes revealed that enough lipid is present to be arranged as a bilayer coating the cell. Artificial mixtures of extracted cellular polar lipids (lecithin, phospholipid, and steroids) under appropriate conditions will form a bimolecular layer spontaneously. Presumably the polar (hydrophilic) ends of the lipids form the two outer borders, making them available for interaction with other polar molecules such as proteins. On a weight basis, membranes contain a significantly larger amount of protein than lipid (ratio up to 4:1); however, due to the high molecular weight of proteins, this relationship is reversed on a molar basis (protein to lipid ratio ranging from 1:100 to 10:100). Some proteins are associated peripherally with one of the polar surfaces of the lipid bilayer. Other proteins, the integral membrane proteins, are not restricted to the surfaces of the plasma membranes but extend into the bimolecular lipid layer.

A pattern generally found in almost all cellular membranes prepared for microscopy by conventional techniques consists of three layers, i.e. two electron dense layers on either side of a single electron lucent layer. This has been termed a unit membrane, or a three layered membrane. Electron microscopic examination of osmium tetroxide fixed sectioned tissue shows the cell membrane to be 7-10 nm wide. The electron lucent line in the unit membrane is thought to represent the lipid layer. Hydrophobic bonding in the lipid bilayer region may make it inaccessible to osmium deposition. Thus, the two electron dense lines would result from deposition of osmium at the surfaces of this bilayer. There is much physiological evidence to suggest that the lipid bilayer is interrupted by proteins which, as hydrophilic molecules, connect the two outer surfaces of the membrane and provide transmembrane channels for transfer of water molecules and ions. The protein components of the plasma membrane are either tightly associated with it or more readily dissociated from it.

Membrane components are subject to continual turnover. In certain cell types, portions of the membrane invaginate into the cell and pinch off to form the boundary of an intracellular vesicle, vacuole, or tubule. External material is carried into the cell by this process, referred to asEndocytosis. This material and its enclosing membrane may fuse with lysosomes, or after delivering endocytosed material to an intracellular endosome, 6the specialized endocytic vesicle membrane may return to the plasma membrane. The fusion to the plasma membrane with membranes of intracellular origin is termedExocytosis. When secretary granules exocytose at the cell membranes they release their internal material to the outside of the cell but their membrane are retrieved as endocytic vesicles. These vesicles may, in fact, return to their intracellular origin, the Golgi area. As a result there is a flow of membrane and of material enclosed in membrane-delimited spaces between the surface and intracellular compartments. Similar exchanges seem to occur between certain intracellular organelles, notably the endoplasmic reticulum and the Golgi apparatus. In the various processes involving formation of vesicles (e.g. pinocytic endocytosis) there is often a “bristle” coating, presumably clathrin or a related protein, on the cytoplasmic side of the vesicle membrane. Exocytosis and incorporation into the surface of intracellular membrane containing transport units (e.g. channels or transporters) may be the structural basis for rapid changes of cell permeability by increasing the numbers of cell membrane transporters in response to hormonal stimulation.

Stable imaginations and invaginations of the cell membrane are important elements in providing a dramatic increase in surface areas contact between cell and environment. Microvilli, finger-like envaginations, are generally associated with cell surfaces involved in absorption processes, such as in the intestine and kidney. Conversely, in striated muscle, one finds and invagination of the cell membrane, the transverse tubule, associated with each sarcomere. Since the transverse tubules are continuous with the surface membrane they provide a direct route for the communication of alterations at the cell surface to the contractile system deep within the muscle fiber.7

The nucleus has two principal functions: replication of deoxyribonucleic acid (DNA) and synthesis of ribosomal, messenger, and transfer ribonucleic acids (RNAs). Because it is best understood, we shall discuss in some detail ribosomal RNA synthesis, which occurs in the nucleolus.

The interphase nucleus is readily seen in the light microscope as a spheroidal body with a “suggestion” of internal organization. The DNA-containing material can be specifically stained. The nuclear chromatin can be resolved into two types: euchromatin (loosely coiled) and heterochromatin (Compact). It seems likely that the euchromatic regions are more active in the transcription process than the heterochromatic regions, i.e. there is little demonstrable RNA synthesis in chromosomes that are largely or entirely composed of heterochromatin, as in the case of sperm cells, polymorphonuclear leukocytes, and the Barr body (one of the X chromosomes of female cells). The association of euchromatin with active transcription may account for some of the selective genetic expression associated with characteristic chromosomal uncoiling patterns found in different tissues within the same organism or at different developmental stages in the same tissue.

The boundary of the nucleus, the nuclear envelope, is a double membrane complex. Each membrane is approximately 7-8 nm thick. The envelope, a flattened sac with an enclosed perinuclear space, resembles the rough endoplasmic reticulum (ER): (1) the cytoplasmic surface of the outer (cytoplasmic) nuclear membrane has granules which appear to be ribosomes; (2) direct continuities are seen between the cytoplasmic portion of the nuclear membrane and the ER; and (3) the presence of certain enzymes can be demonstrated cytochemically in both the perinuclear space and the cisternae of the ER.

Often an integrated biochemical and ultra-structural investigation (involving cell disruption, isolation, and analysis of a homogeneous organelle population) leads to the clearest understanding of organelle functionin situ. From such studies, in a variety of cell types, a fraction of membrane – delimited vesicles, referred to as microsomes, is recovered. The 11microsomes perform several functions, including the provision of a base for the attachment of ribosomes, the biosynthesis of lipids, and in the case of striated muscle, the accumulation and release of calcium. In the intact cell, microsomal vesicles are not found as such; rather, one observes a tubular network known as the ER. It is assumed that the majority of microsomal vesicles represent a reproducible, preparative artifact arising during cell disruption by the shearing into fragments and closing up of the tubules and sacs of the ER.

As noted above, the ER (and/or the microsomes derived from the ER) can provide a base for the attachment of ribosomes. Such ribosome carrying ER is referred to as rough ER. Microsomal vesicles derived from this rough ER were found to be capable of protein synthesis, the newly synthesized protein appearing in the vesicle lumen. In the rough ERin situ the nascent protein likewise can be demonstrated within the reticulum lumen. This unidirectional passage into the lumen is thought to result from the folding of the original 0.5 to 1.0 nm wide protein into a three-dimensional structure which is large enough to be retained. The rough ER seems to grow by synthesizing more of itself. The newly made rough ER may lose its ribosomes and thus become converted to smooth ER. The relative proportions of rough and smooth ER vary within different cells; for example, the rough ER is extensive in cells which specialize in synthesizing protein for export, while the smooth ER is extensive in steroid secreting cells.

As noted above, the ER, which lacks ribosomes, is referred to as the smooth ER. The membrane of the ER carries enzymes, which are important in several biosynthetic pathways. For example, the enzymes required for the synthesis of steroid are 12found in microsomal fractions of steroid secreting cells. Enzymes involved in triglyceride synthesis as well as phospholipid synthesis are also found in this fraction the phospholipid sometimes appearing in the ER as small fat droplets. In liver cells, important drug degrading enzymes are associated with the smooth ER. Also, in the hepatocytes, the close spatial relationship of the smooth ER with glycogen, the major storage form of glucose, suggests that the smooth ER may function in glycogen metabolism. In muscle, the smooth ER (sarcoplasmic reticulum) controls the local concentration of calcium ions near the contractile machinery and thereby influences the contraction and relaxation process.

The Golgi apparatus is believed to be a site for the concentration of protein and polysaccharide. It is also a site for completion of the synthesis of the carbohydrate moiety of glycoprotein, e.g. the synthesis of the carbohydrate moieties of thyroglobulin and immunoglobulin begins in the ER, but the terminal sugars are added in the Golgi apparatus. In the case of synthesis of polysaccharides destined for secretion, the precursors are first seen in the Golgi apparatus. Therefore, the apparatus is believed to be the site of synthesis and packaging of polysaccharides for secretion. These products are usually packaged as “granules” within Golgi derived vacuoles or vesicles, which then migrate away from the Golgi apparatus. The enzymes involved in the polymerization of polysaccharide or addition of carbohydrate to protein, glycosyl transferases, have recently been used as marker enzymes for the biochemical isolation of the Golgi apparatus.

Lysosomes have been found in virtually all-animal cells, which have been studied. As organelles they are best defined by biochemical and cytochemical criteria: a lysosome is a membrane-delimited body containing demonstrable acid hydrolase activity and an intervesicular pH of 5-6. Over 30 acid hydrolases are known to occur in the lysosomes; these enzymes can digest essentially all macromolecules. Material to be digested becomes enclosed within lysosomal membranes permitting isolated, controlled degradation. A proton-translocating ATPase maintains the low intervesicular pH. There are numerous findings suggesting that release of hydrolases from the lysosome into the cell may be important in various pathological states. In silicosis (miner,s disease) it is believed that macrophages of the lung take up silica into phagocytic vacuoles which, upon fusion with lysosomes, make the lysosomal membranes leaky. In some inflammations, hydrolases may be released at the surface of the phagocytic cells and affect the adjacent tissues. In many cases these findings are yet to be fully evaluated.

The peroxisomes constitute another group of membrane –delimited bodies. They are often associated with the ER. They are concerned with the metabolism of peroxide: peroxisomes contain enzymes (such as catalase), which destroy hydrogen peroxide and other enzymes, which produce hydrogen peroxide (such as D-amino acid oxidase and, in some species). Peroxisomes have, thus far, been found in essentially all cell types, of which liver and kidney are among the best-established examples. The function of peroxisomes is currently under active investigation, and there is evidence that, in some species, they are involved in carbohydrate synthesis from fat and in the degradation of purines and fats, as well as in the detoxification 15of hydrogen peroxide. New peroxisomes are apparently formed by division of pre-existing peroxisomes.

The early cytologists noted that mitochondria were closely associated with motile processes and were situated in regions of intense metabolic activity such as sites of active transport. Biochemists have since shown that two major metabolic pathways, the tricarboxylic acid cycle and the electron transport chain, are situated with in the mitochondrion; thus, this organelle is involved in the metabolism of lipids, amino acids, and carbohydrates.

The asymmetry observed in certain cell types is sharply at variance with the picture of an idealized cell in which all the organelles surround a central nucleus symmetrically. A nerve cell in which the axon runs several feet as an extension of the perikaryon an elongated muscle cell and a squamous (or columnar) epithelial cell all exemplify such asymmetry. Likewise, the nonrandom (asymmetric) movement of subcellular elements is exemplified by transport of neurosecretory products (axonal flow), sliding myofilaments in muscle contraction, and chromosomal movement in cell division. Electron microscopy of aldehyde-fixed tissue has revealed a morphological basis for asymmetric structure and movement in the form of entities referred to as microtubules and microfilaments; these structures are not membrane – delimited.18

In cross-section microtubules are 20-30 nm in diameter and may be followed for several microns in longitudinal sections. They are found in many regions in which phase contrast and polarizing microscopy had previously demonstrated the presence of formed oriented, elongated elements. Microtubules are often associated with oriented movement, e.g. axonal transport of neurotransmitter from the nerve cell body (where synthesis occurs) to the synaptic terminal where transmitter is released. In nerve cells microtubule subunits are also synthesized in the cell body but assembled in the axon.

Microtubule-like structures may also be organized into organelles. Cilia and flagella are rapidly beating cell processes, which extend 10-200 nm from the cell and are surrounded by a membrane, which is continuous with the plasma membrane. The intracellular basal bodies of cilia and flagella are also composed of microtubular structures arranged in the pattern of nine basic units (often referred to as “9+0”); they are widely assumed to be an alternate form of the centrioles.

Microfilaments are heterogeneous classes of long, thin and non-tubular structures. Thin microfilaments, 5-7 nm in diameter, are made of actin. Among the most commonly seen microfilaments are those, which appear to serve as the structural core of microvilli. Also frequently encountered are tonofilaments on the intracellular side of desmosomes. The best example of association of microfilaments with motion is the extensively developed myofilament system, which forms the basis of muscle contraction. The myofilament proteins, actin and myosin, have now been localized in many other cell types as result of improved techniques for the cellular localization of specific proteins. Results of the application of antibody to actin have implicated some of these protein as a constant component 20of thin (5 nm diameter) microfilaments. Likewise a myosin like protein associated with transiently formed thick microfilaments (10 nm), is found in virtually all cells.

We have thus far limited our view of the cell to those entities circumscribed by and including its boundary, the plasma membrane. Cells rarely are continuous with one another; usually a space of 10-20 nm separates them. Cells are associated in tissues by various means; the best described is the junctional complex in epithelial cell. In this complex then plasma membranes of two adjacent cells contribute to specialized attachment sites: at tight junction (zonual occludens), a desmosome (macula adherens), and between these two usually a less well-defined zonual adherens where the two membranes are separated by a constant 20 nm space. The desmosome may contain organized extra cellular material between the two cell membranes, which may be seen as an additional dense line in parallel with the membranes.

Cell, is the basic unit of all living tissue. Cells are made of nucleus, cytoplasm, and organelles held together by a plasma membrane. The nucleus is the control center of the cell. Most cells have a single nucleus. Without a membrane penetrated by fairly large pores. Within the nucleus are the nucleolus (containing RNA) and chromatin granules (containing protein and DNA) that grow into chromosomes, which determine hereditary traits. Organelles in the cytoplasm include the endoplasmic reticulum, ribosomes, the Golgi complex, mitochondria, lysosomes, and the centrosome. It is the basic structural and functional unit of life. Cells vary widely in both shape and size. The plasma membrane encloses cell contents, mediates exchanges with the extra-cellular environment, and plays a role in cellular communication.

The cell is considered the smallest unit. The tissues are aggregates of these small cells and organs are aggregates these tissues. The processes of health, disease, adaptation, and maladaptation occur at the cellular level. The cell may be described as existing on a continuum of function and structure, ranging from the normal cell, to the adapted cell, to the injured cell, to the dead cell.

Injury is defined as disorder in a steady state regulation. Any stressor that alters the ability of the cell to maintain optimal balance of its adjustment processes will lead to injury. When cells are injured, the extent of the damage depends on the nature, of differentiation or metabolic activity of the cells.

Hypoxia (inadequate tissue oxygenation) is a leading cause of cell injury and death. Hypoxia can arise secondary to (1) vascular disease or injury, which impedes blood flow to tissues, or (2) insufficient oxygenation of blood causes by conditions such as carbon monoxide poisoning. Depending on the severity of the hypoxic state, cells will compensate and recover or be killed. For example, if the femoral artery becomes stenotic, the skeletal muscles of the legs will eventually atrophy as a result 23of the inadequate blood flow and the consequent reduced oxygen supply. Severe or chronic hypoxia will result in cell injury or death. The most common cause of hypoxia is ischemia, or reduced blood supply. When ischemic injury is caused by gradual narrowing of arteries (arteriosclerosis or thrombus) the progressive hypoxia is better tolerated than sudden anoxia (MI, Stroke) caused by an obstruction in the blood supply.

External heat will damage cells by coagulating cytoplasmic protein. Even mild heat results in permanent cellular damage, if it is applied over a prolonged period to individuals with impaired circulation, as seen in peripheral vascular disease. Heart in these cases increases the metabolic needs of cells and tissues and leads to insufficient oxygen levels which, coupled with a reduced capacity to dispose greater-than-normal amounts of waste products, will accelerate the damage to the affected tissue.

There is an increase in metabolic activity and as heat increases, protein is coagulated, and enzyme systems are destroyed, and in extreme charring or carbonization occur. Burns of the epithelium are classified as partial thickness burns if epithelializing elements remain to support healing. Full thickness lacks such elements and must be grafted for healing.

Exposure to radiation causes mutations, inactivates enzymes, and interrupts cell division. The fact that radiation stops mitosis makes radiation therapy important in the treatment of cancer – a disease involving pathologic cell reproduction. Radiation affects virtually all cells, but certain cells are more susceptible than others. Reproductive cells, in the lymph nodes and gastrointestinal tract, and bone marrow are highly sensitive to damage by radiation exposure, whereas cells of cartilage, muscle, brain, and endocrine glands are relatively insensitive. Individuals who work with radioactive materials or nuclear fission reactors, or who are giving or receiving radiotherapy, are most susceptible to cellular trauma from radiation.

Electrical energy generates heat when it passes through the body and may thus produce burns. It also interferes with neural conduction pathways and often causes death from cardiac dysrhythmia. The extent of damage from electrical energy depends on its voltage and amperage, tissue resistance, and the pathways of the current as it passes through the body. Users of electrical equipment should be aware that exposure to 100 mA can be lethal to humans.

Chemicals harm cells by destroying or altering their structure and by disrupting their metabolism. The capacity of a chemical to injure a cell depends on the strength and toxicity of the chemical, as well as the susceptibility of the cell. There are numerous chemicals that can cause cellular injury. Highly toxic substances are called poisons. Minute amounts of poisonous substances such as cyanide and arsenic cause death. Some of the most toxic substances known are bacterial exotoxins, such as diphtheria toxin and botulinum toxin. Environmental 25chemicals, such as herbicides, pesticides, and air pollutants, are potential causes of cellular injury. Children often eat lead-based paint, which tastes sweet. Lead based paint on walls and window binds, comes off in dust particles and if inhaled. Dangerous amounts of lead are also found in water pipes in older homes and are present in the drinking water. The ingested or inhaled lead destroys cells in the nervous system (which may lead to mental retardation in young children), affects blood cell production, and damages the kidneys. Workers around machinery and home owners with gas appliances must guard against carbon monoxide poisoning. Carbon monoxide binds tightly to hemoglobin and prevents normal exchange of oxygen and carbon dioxide.

Microorganisms such as bacteria injure host cells by direct attack or by means of the toxins they produce. Bacterial toxins are classified as being either endotoxins or exotoxins. An endotoxin is a structural component of the outer envelope of gram-negative bacteria and consists of lipopolysaccharide. The toxic mostly released only when the bacteria dies and the cell undergoes lysis. Endotoxins may act directly with macrophages and T lymphocytes causing the release of cytokines. Endotoxins acting on macrophages stimulate the production of interlukin-1 (IL-1) and tumor necrosis factor (TNF) (two cytokines), which in large quantities cause bacterial septic shock, a condition that, is often fatal. Endotoxins may also activate the complement cascade, producing disseminated intravascular coagulation (DIC), another potentially fatal condition. Intervention in endotoxemia is difficult and often impossible to achieve.

Viruses have been described as consisting of mobile genetic elements protected by outer layer of protein and lipoprotein. Viruses attach to specific receptors on host cell surfaces and are taken up by endocytosis. The nucleic acid core of the virus then passes through the vesicular membrane into the interior of the host cell. The viral genome then subverts the host cell metabolic machinery and begins to make vital components. While inside the host cell the virus is protected from reactive cells and solutes of the host. The assembled virions may than exit the cell by either lysing the cell remnant or permitting the cell to remain viable while continuously secreting virions across the cell membrane. Viruses damage host cells by killing, nutrient deprivation, or causing the cell to transform into a tumor state.

Cells can be damaged by physical impact or irritation. Examples of these types of injury include blisters from tight shoes, abrasions, lacerations, and contusions (bruises). The cell can be injured in other ways as well. Light can damage cells of the cornea. Noise can damage the eardrum (tympanic membrane), the ossicle in the middle ear, and the organ of Corti in the inner ear. Prolonged contact with vibrating objects can alter muscle and bone structure, as well as nerve conduction. Clients at risk of these injuries are those who work with hand tools and pneumatic drills.27

Inadequate protein intake decreases the function of the intestinal mucosa and pancreas, which in turn reduces nutrient absorption. Plasma proteins, especially albumin, help retain fluid in blood vessels. When levels of plasma proteins decline, fluid tends to move into interstitial spaces, causing edema. antibiotics or immunoglobulin are proteins therefore; the lack of proteins adversely affects immune system function and so increases the risk of infection. Inadequate carbohydrate intake forces the body to use fats for energy. The liver becomes overwhelmed and ketone bodies are formed that accumulate in the blood, a condition known as ketosis. Ketosis develops because of the rapid breakdown of fatty acids stored in adipose tissue. Fatty acids are used for energy when the intake of carbohydrates is less than 50 grams. Clients at high-risk for ketosis include diabetics, persons on starvation diets and persons on low carbohydrates diet. Increased fat intake often causes fat deposition in heart, liver and muscle and may led to obesity, CHD, stroke or breast and colon cancer. Growth factors include amino acids, purines and pyrimidines and vitamins. These nutrients are required but cannot be synthesized. Insufficient quantities of these substances will seriously impair the ability of the cell to take up and metabolize nutrients, to synthesize macromolecules for structural building and reproduction.

Cells die as a result of being traumatized, through alteration by disease, from failure due to genetic alterations, or through a programmed process called apoptosis. Necrotic processes in the tissues following the death of injured or altered cells have three patterns. (1) Coagulative necrosis results from the slowing or blocking of normal blood supplies to tissues. In this form of necrosis, the membrane of the cell is preserved but the nucleus 28is lost. The necrotic cell is removed by phagocytosis. (2) Caseous necrosis is usually associated with TB, but may be seen in other disorders. The cell membrane is destroyed and the body walls off the damaged area. The central portion of the walled off area looks cheesy and crumbly. (3) Liquificative is seen in the brain tissue. Death of the neuron releases lysosomes into the surrounding area. The lysosomes liquefy the area and leave pockets of liquid and cellular debris. Cells undergoing death byapoptosis usually will not disturb the steady state of the tissue and thus give no sign of its occurrence.

Cells can adapt to environmental stress by structural and functional changes. Some of these adaptations include: hypertrophy, atrophy, hyperplasia, and metaplasia.

It leads to changes in the size of the cells and hence the size of the organs they form. Compensatory hypertrophy resulting in an enlarged muscle mass commonly occurs in the skeletal and cardiac muscle under engages in body building is one example.29

It is shrinkage in cell size leading to decrease in organ size. The decrease in cell size is due to: use blood supply, nutrition, hormonal stimulation and innervations. It is mostly associated with aging. It mostly affects skeletal muscles, secondary sex organs, the heart and the brain.

It is an increase in the number of the new cells in an organ or tissue, as cells multiply volume also increases. It is a mitotic response, but it is reversible when the stimulus is removed. This distinguishes it from neoplasia or malignant growth, which continues after the stimulus is removed. Hyperplasia may be hormonally induced. Examples are breast changes of a girl in puberty or of a pregnant woman, regeneration of the liver cells, new RBCs in blood loss.

It is a cell transformation in which a highly specialized cell changes to a less specialized cell. This serves as a protective function, because the less specialized cell is more resistant to the stress that stimulates the change. In smokers, the ciliated columnar epithelium lining the bronchi is replaced by the squamous epithelium. The squamous cells can survive, however, loss of the cilia and protective mucous can have damaging consequences.

It is a deranged cellular growth or a form of hyperplasia. It occurs form persistent severe injury or irritation.

Cells of the body get injured due to the above said reasons. When this happens there is a naturally occurring response in the healthy tissues adjacent to the site of the injury and this is called inflammatory response. It is a defensive reaction the intent of which is to neutralize, control and eliminate the offending agent and to prepare the site for repair. It is a nonspecific response meant to serve a protective function. For example, inflammation may be observed at the site of a bee sting, in a sore throat, in a surgical incision and in a burn.

Inflammation is categorized primarily by its duration and the type of exudates produced. It is of three types:

It is characterized by local vascular and exudative changes described above and usually lasts for less than two weeks. It is an immediate response and it serves a protective function. When the injurious agent is removed, the inflammation subsides and healing takes place with the return of normal or near normal structure and function.

It develops when the injurious agent persists and the acute response is perpetuated. Symptoms may appear for many months or years. It does not serve a beneficial and protective function but on the contrary is debilitating and may produce long lasting effects. The nature of the exudates becomes proliferative. There is a continuous cycle of cellular infiltration, necrosis and fibrosis (repair and breakdown occur simultaneously). Considerable scarring may occur, resulting in permanent tissue damage.

It falls between acute and chronic inflammation. There are elements of active exudative phase of the acute response and simultaneously there is some repair occurring as in the chronic response.32

The reparative process begins at the time of injury and is interwoven with inflammation. Healing proceeds after the inflammatory debris are removed. It takes place by two processes:

The ability of cells to regenerate depends upon whether they are labile, permanent or stable. There is gradual repair of the defect by proliferation of cells of the same type as those destroyed. Labile cells include those that multiply constantly to replace cells worn out by normal physiological processes. These include epithelial cells of the skin and those lining the GI tract. Permanent cells include neurons – the nerve cells, not their axons. Destruction of a neuron is a permanent loss, but axons may regenerate. If normal activity is to return, tissue regeneration must occur in a functional pattern especially in the growth of several axons. Stable cells have a latent ability to regenerate. Under normal physiological damaged or destroyed, they are able to regenerate, e.g. cells of kidney, liver, pancreas and other organs of the body.

This includes the following: