Solved Question Papers of Pathology and Genetics for BSc Nursing Shamim Akhtar
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LAQs and SAQs for PATHOLOGY (General and Systemic)1

2Cell Injury and Cllular Adaption
3Q. Define necrosis. Mention the types, explain the causes and pathology of each type of necrosis.
A. Definition: Necrosis is defined as the focal death along with the degradation of tissue by hydrolytic enzymes liberated by cells.
Morphologically five distinct types are seen.
  1. Coagulative necrosis
  2. Liquefaction necrosis
  3. Caseous necrosis
  4. Fat necrosis
  5. Fibrinoid necrosis.
The changes which occur in necrosis are cell digestion by lytic enzymes and denaturation of proteins.
The characteristic cytoplasmic change is that it appears homogenous and intensely eosinophilic.
The nuclear changes are condensation of nuclear chromatin which may undergo dissolution or fragmentation into granular clumps.
1. Coagulative Necrosis
Definition: This is the most common type of necrosis usually seen in heart, kidney and spleen.
  • Ischemia (sudden cessation of blood flow): Most common
  • Bacterial agents
  • Chemical agents.
Gross Examination
In early stage the necrotic foci appear pale, firm and slightly swollen with progression they become more yellowish, softer and shrunken.
Microscopic Examination
The hallmark of the coagulative necrosis is the conversion of the normal cell into their tombstones, i.e. normal outline of the cell is retained but their cytoplasmic and nuclear details are lost. However, the cell type can still be identified because of retained shape.
The necrosed cells are swollen and appear more eosinophilic than the normal.
These changes are brought about be denaturation of cellular proteins and enzymatic digestion of the cell.
Eventually the necrosed focus is infiltrated by inflammatory cells and the dead cells are phagocytosed leaving granular debris and fragments of cells.
2. Liquefaction Necrosis
Definition: The liquefaction or colliquative necrosis occurs in brain infarcts and abscess cavity.
  • Ischemia
  • Bacterial or fungal infection.
Gross Examination
The effected area is soft with liquefied center containing necrotic debris. Later, a cyst wall is formed.
Microscopic Examination
The cystic space contains necrotic cell debris and macrophage filled with phagocytosed material.
The liquefaction is brought about by degeneration of the tissue by the action of powerful hydrolytic enzymes.
5 Later a cyst wall is formed by proliferation of capillaries, inflammatory cells and glial cells in case of brain and fibroblasts in case of abscess cavity.
3. Caseous Necrosis
Definition: The caseous necrosis shows combines features of both coagulative and liquefactive necrosis and is found in the center of foci of tuberculous infection.
  • Tuberculosis
  • Chronic granulomatous diseases.
Gross Examination
The foci appear as dry cheese and are soft, granular and yellowish.
Microscopic Examination
The necrosed foci are structureless, eosinophilic and contain granular debris.
The surrounding tissue shows characteristic granulomatous inflammatory reaction consisting of epithelioid cells with interspersed giant cells of Langhan's or foreign body type and peripheral rim of lymphocytes.
4. Fat Necrosis
Definition: The special type of cell death occurring in pancreas and breast differ in their causes and pathology but are similar in morphology of the lesion.
  • Breast, the cause of the necrosis is trauma.
  • Pancreas, the cause of the necrosis is inflammation injury leading to release of pancreatic lipase from the inflamed or injured tissue causing necrosis of the pancreas as well as the fat depot throughout the peritoneal cavity.
  • They also affect the extra-abdominal viscera too.
6In both the cases, there is hydrolysis of neutral fat present in the adipose tissue into glycerol and fatty acids. Then the glycerol leaks out and forms calcium soaps with calcium leaving behind the fatty acid which gives the damaged adipose tissue clouded appearance.
Gross Examination
Fat necrosis appears as yellowish white and firm deposits.
They appear firmer and chalky white after formation of calcium soaps.
Microscopic Examination
The necrosed adipose cell appears cloudy and is surrounded by an inflammatory reaction.
The calcium soaps are identified as amorphous, granular and basophilic material in tissue sections.
5. Fibrinoid necrosis
Definition: The fibrinoid necrosis characterized by deposition of fibrin like material.
  • Immunological tissue injury
  • Hypertension
  • Peptic ulcer.
Gross Examination
The foci shows staining properties of the fibrin.
Microscopic Examination
They appear brightly eosinophilic, hyaline like deposition in the vessel wall or on the luminal surface of the peptic ulcer. A local hemorrhages are also seen.7
Q. Apoptosis.
A. Definition: Apoptosis is a form of coordinated and internally programmed cell death which of significance in a variety of physiological and pathologic conditions.
Morphological Changes
  1. Shrinkage of cell with dense cytoplasm and almost normal organelles.
  2. Convolutions of cell membrane with formation of membrane bound near spherical bodies called apoptotic bodies containing compacted organelles.
  3. Chromatin condensation around the periphery of nucleus. Characteristically, there is no acute inflammatory reaction.
  4. Phagocytosis of apoptotic bodies by macrophages takes place at varying speed. There may be swift phagocytosis or loosely floating apoptotic cells after losing contact with each other and basement membrane.
  5. The H and E staining, apoptotic cell appear round to oval, shrunken masses of intensely eosinophilic cytoplasm containing condensed or fragmented nuclear chromatin and characteristically inflammation is absent.
Biochemical Changes
  1. Proteolysis of cytoskeletal proteins.
  2. Protein-protein crosslinking.
  3. Fragmentation of nuclear chromatin by activation of nucleases.
  4. Appearance of phosphatidylserine on the surface of cell membrane.
  5. Appearance of an adhesive glycoprotein thromboplastin on the outer surface of apoptotic bodies in some forms of apoptosis.
  6. Appearance of phosphatidylserine and thrombospondin on the outer surface of apoptotic cell facilitates early recognition by macrophages for phagocytosis prior to appearance of inflammatory cells.8
Identification of Apoptotic Cells
  1. Staining of chromatin condensation.
  2. Flow cytometry to visualize rapid cell shrinkage.
  3. DNA changes detected by in situ techniques or by gel electrophoresis.
  4. Annexin V as marker for apoptotic cell membrane having phosphatidylserine on the cell exterior.
Molecular Mechanism of Apoptosis
a. Intitiators of apoptosis
  1. Absence of stimuli required for normal cell survival like absence of certain hormones, growth factors or cytokines.
  2. Activation of programmed cell death.
  3. Intercellular stimuli like heat, radiation, hypoxia, etc.
b. Regulators of apoptosis: After apoptosis has been intiated certain proteins convert death signal to the final programmed cell death and thus determine to outcome.
  1. Bcl-2
    • It is a protein located in the outer mitochondrial membrane.
    • It regulates apoptotic process by binding to some other related.
    • Proteins like bax and bad for promoting apoptosis and Bcl-XL for inhibiting apoptosis.
    • Proapoptotic protease activating factor (apaf-1) is another important Bcl-2 binding protein in the cytosol.
  2. Other apoptotic regulator proteins
    • p53, protein, caspases, bax and certain viruses like adenovirus, papillomavirus, hepatitis B virus.
c. Programmed cell death: It occurs by any of the following pathways:
  1. Fas receptor activation: Fas receptor (Cd95) present on the cytotoxic cd8+T cells is activated on coming in contact 9with the target cell which leads to activation of caspases and subsequent proteolysis.
  2. Ceramide generation: Ceramide generated due to hydrolysis of phospholipid sphingomyelin of plasma membrane causes further mitochondrial injury.
  3. DNA damage: DNA damage by ionizing radiation, chemotherapeutic agents, activated oxygen species lead to apoptosis.
DNA damage affects nuclear protein p53 which inducess synthesis of bax, a cell death promoting protein.
d. Phagocytosis: Phagocytes identify the dead apoptotic cells and their fragments due to the cell surface receptors and phagocytose them.
Apoptosis in Biological Process
a. Physiological process
  1. Organized cell destruction in sculpting of tissues during development of embryo.
  2. Physiologic involution of cells in hormone dependent tissues like endometrial shedding regression of lactating breast.
  3. Normal cell destruction followed by replacement proliferation as in intestinal epithelium.
  4. Involution of thymus in early age.
b. Pathological processes
  1. Cell death in tumors exposed to chemotherapeutic agents.
  2. Cell death by cytotoxic T cells in immune mechanisms such as in graft versus host disease and rejection reaction.
  3. Cell death in viral infections.
  4. Pathological atrophy of organs and tissues on withdrawal of stimuli, e.g prostatic atrophy, orchidectomy.
  5. Progressive depletion of Cd4+ T cells is AIDS.
  6. Cell death in response to injurious agents like radiation, hypoxia.
  7. In CNS degenerative diseases like Alzheimer's disease, Parkinson's disease.
10Q. Define gangrene and mention the difference between dry and wet gangrene.
Q. Gangrene.
Q. Define gangrene. Give the difference between dry and wet gangrene. (MUHS May/June 08)
A. Definition: The gangrene is defined as a form of necrosis of tissue with superadded putrefaction.
Difference: The following are the difference given below.
Points of difference
Dry gangrene
Wet gangrene
Commonly limbs
More common in bowel
Arterial occlusion
More commonly venous obstruction less often arterial occlusion
Organ is dry, shrunken and black
Part is moist, soft, swollen, rottenand dark
Limited due to very little blood supply
Marked due to stuffing of organ with blood
Line of demarcation
Present at the junction between healthy and gangrenous part
No clear line of demarcation
Bacteria fail to survive
Numerous present
Generally better due to little septicemia
Generally poor due to profound toxemia
Q. Pathological calcification.
A. Definition: Pathological calcification or heterotopic calci-fication is the deposition of calcium salts in tissues other than osteoid or enamel.
  1. Dystrophic calcification
  2. Metastatic calcification.
I. Dystrophic Calcification
Dystrophic calcification is a type of pathological calcification or deposition of the calcium salts in tissues other than osteoid enamel which dead or degenerate but have normal calcium metabolism and normal serum calcium level.11
Dystrophic calcification may occur due to:
  1. Calcification in dead tissues
    1. Caseous necrosis in tuberculosis is most common site
    2. Liquefaction necrosis in chronic abscesses
    3. Fat necrosis
    4. Infarcts
    5. Thrombi especially in veins
    6. Hematomas in the vicinity of bones
    7. Dead parasites like in hydatid cyst, schistosoma eggs cysticercosis
    8. Calcification in breast cancer
    9. Congenital toxoplasmosis.
  2. Calcification in degenerated tissues
    1. Dense old scars
    2. Atheromas
    3. Monckenberg's sclerosis
    4. Stroma of tumors such as uterine fibroids, breast cancer, thyroid adenoma, etc.
    5. Cysts
    6. Calcinosis cutis
    7. Senile degenerative changes in cartilages, brain, pineal gland.
The process is linked to the formation of normal hydroxyapatite in the bone involving two phases.
  1. Initiation phase: In this phase, the calcium and phosphates begin to accumulate intracellularly in the mitochondria or extracellularly in membrane bound vesicles.
  2. Propagation phase: Here the minerals deposited in the initiation phase are propagated to form mineral crystals.
However, local alteration of pH in the necrotic tissue and release of enzymes form the necrotic or degenerated tissue are also implicated in the pathogenesis.12
Microscopic examination: Routine hematoxylin and eosin stained section shows calcium salts as deeply basophilic irregular and granular clumps. The deposits may be intracellular, extracellular or at both locations. Occasionally heterotopic bone formation of ossification may occur. The calcium salts are confirmed by special stains like silver impregnation method of von Kossa producing black color and alizarin red producing red staining. They also give positive Prussian blue reaction due to diffuse or granular deposits of iron accompanying the pathological calcification.
II. Metastatic Calcification
Metastatic calcification is a type of pathological calcification or deposition of calcium salts in tissues other than osteoid or enamel which are apparently normal but are associated with deranged calcium metabolism and hypercalcemia.
Metastatic calcification occurs in any of the following cases:
  1. Excessive mobilization of calcium from bone (most common)
    1. Hyperparathyroidism: It may be primary due to para-thyroid adenoma or secondary due to parathyroid hyperplasia, chronic renal failure, etc.
    2. Bony destructive lesions: Multiple myeloma, metastatic carcinoma.
    3. Prolonged immobilization: It results in disuse atrophy of bones and hypercalcemia.
  2. Excessive absorption of calcium from the intestines
    1. Hypervitaminosis D
    2. Milk alkali syndrome: It is caused by excessive oral intake of calcium in from of milk and administration of calcium carbonate in the treatment of peptic ulcer.
    3. Hypercalcemia of infancy.13
Metastatic calcification is favored by relatively high pH or alkaline environment at certain sites like lungs, stomach, blood vessels and cornea.
The common sites are the basement mem- brane of tubular epithelium and tubular lamina causing nephrocalcinosis
In the alveolar walls
On the acid secreting fundal glands
Blood vessels
Especially on the internal elastic lamina.
Microscopic examination: Routine hematoxylin and eosin stained sections shows calcium salts as deeply basophilic irregular and granular clumps. The deposits may be intracellular, extracellular or at both locations. Occasionally hetrotropic bone formation or ossification may occur. The calcium deposits can be confirmed by special stains like silver impregnation method of von Kossa producing black color and alizarin red S, that produces red staining. They also give positive Prussian blue reaction due to diffuse or granular iron deposits accompanying the pathological calcification.
Q. What is hyperplasia? Describe differentiating features of atrophy/hypertrophy/hyperplasia.
Q. Hyperplasia
Definition: The hyperplasia is increased in the number of parenchymal cells resulting in enlargement of the organ or tissue. Hyperplasia occurs due to increase recruitment of cells from G0 (resting) phase of the cell cycle to undergo mitosis when stimulated. All cells do not possess hyperplastic growth potential.
Labile cells (epithelial cells of the skin and mucous membranes, cells of the bone marrow and lymph nodes) and stable cells (parenchymal cells of the liver, pancreas, kidney, adrenal and thyroid) can undergo hyperplasia. Permanent cells (neurons, cardiac and skeletal muscles) have little or no capacity for regenerative hyperplastic growth.14
Causes (Types)
According to the cause it is divided into two main categories.
Physiological Hyperplasia
  1. Hormonal hyperplasia: Hyperplasia occurring under influence of hormonal stimulation:
    1. Hyperplasia of female breast at puberty, during pregnancy and lactation.
    2. Hyperplasia of pregnant uterus.
    3. Proliferative activity of normal endometrium after a normal menstrual cycle.
    4. Prostatic hyperplasia in old age.
  2. Compensatory hyperplasia: Hyperplasia occurring following removal of part of an organ or a contralateral organ in paired:
    1. Regeneration of liver following partial hepatectomy.
    2. Regeneration of epidermis after skin abrasion.
    3. Following nephrectomy on one side, there is hyperplasia of nephrons of the other kidney.
Pathologic Hyperplasia
  1. Endometrial hyperplasia following estrogen excess.
  2. In wound healing, there is formation of granulation tissue due to proliferation of fibroblasts and endothelial cells.
  3. Formation of skin warts (hyperplasia of epidermis) due to human papilloma virus infection.
  4. Pseudocarcinoma hyperplasia of the skin.
There is enlargement of the affected organ or tissue and increase in the number of cells.
This is due increased rate of DNA synthesis and hence increased mitoses of the cells.
Differences: The main differentiating features are given in the table on next page.15
Points of difference
Reduction of the number and size of parenchymal cells of an organ or its part which was once normal is called atrophy.
Increase in the size of of the parenchymal cells resulting in enlargement of the organ or tissue without any change in the number of cells is called hypertrophy.
Increase in the number of parenchymal cells resulting in enlargement of the organ or tissue is called hyperplasia.
Number of cells
No change
Cell size
No change
Cell organelles
No change
Rate of cell division
DNA and RNA synthesis
Protein synthesis
Size of affected organ
Small and shrunken
Enlarged and heavy
16Q. Metaplasia
Definition: The metaplasia defined as a reversible change of one type of epithelial or mesenchymal adult cells to another type of adult epithelial or mesenchymal cells usually in response to abnormal stimuli and often reverts back to normal on removal of stimulus.
The types of metaplasia are as follow.
Epithelial Metaplasia
More common and may be patchy or diffuse. Results in replacement by stronger but less specialized epithelium. Metaplastic epithelium is less well-specialized resulting in deprivation of protective mucus secretion and hence more prone to infection.
  1. Squamous metaplasia: It occurs due to chronic irritation that may be mechanical, chemical or infective in origin.
    1. In bronchus in chronic smokers.
    2. In uterine endocervix in prolapse of uterus and in old age.
    3. In gallbladder in chronic cholecystitis with cholelithiasis.
    4. In prostate in chronic prostatitis and estrogen therapy.
    5. In renal pelvis and urinary bladder in chronic infection and stones.
    6. In vitamin A deficiency squamous metaplasia in nose, bronchi, urinary tract, lacrimal and salivary glands.
  2. Columnar metaplasia
    1. Intestinal metaplasia in healed chronic gastric ulcer.
    2. In chronic bronchitis and bronchiectasis conversion of pseudostratified columnar into columnar type.
    3. In cervical erosion.
Mesenchymal Metaplasia
a. Osseous metaplasia: Formation of bone in fibrous tissue, cartilage and myxoid tissue.
  1. In arterial wall in old age.17
  2. In soft tissues in myositis ossifications.
  3. In cartilage of larynx and bronchi in elderly people.
  4. In scar of chronic inflammation of prolonged duration.
  5. In fibrous stroma of tumor.
b. Cartilaginous metaplasia: In healing of fractures cartilaginous metaplasia may occur where there is undue mobility.
Q. Dysplasia
Defination: The dysplasia means disordered cellular development. It is often accompanied with metaplasia and hyperplasia. Therefore, it is also referred to as atypical hyperplasia. It most often occurs in epithelial cells.
Epithelial dysplasia is characterized by following cellular proliferation and cytologic changes.
  1. Hyperplasia of epithelial layers
  2. Disorderly arrangement of cells from basal layer to the surface layer
  3. Cellular and nuclear pleomorphism
  4. Increased nucleocytoplasmic ratio
  5. Nuclear hyperchromatism.
  6. Increased mitotic activity.
Dysplastic changes often occur due to chronic irritation or prolonged inflammation. The dysplastic changes may disappear on removal of the inciting stimulus. However, in a proportion of cases, it progresses to carcinoma in situ or invasive carcinoma.
  1. Uterine cervix
  2. Respiratory tract.
Q. Describe difference between hypertrophy and hyperplasia?
A. The most classical features which differentiate both the conditions are as follows:18
Points of difference
Increased in the size of the parenchymal cells resulting in enlargement of the organ or tissue without any change in the number of cells is called hypertrophy.
Increase in the number of parenchymal cells resulting in enlargement of the organ or tissue is called hyperplasia.
Number of cells
No change
Cell size
No change
Cell organelles
No change
Rate of cell division
Protein synthesis
Size of affected organ
Enlarged and heavy
Q. What is metaplasia?
Q. Define metaplasia. Describe its types with examples.
(MUHS May/Jun 08)
Q. Define metaplasia. Describe its typeswith the examples?
Definition: The metaplasia is defined as a reversible change of one type of epithelial or mesenchymal adult cells to another type of adult epithelial or mesenchymal cells usually in response to abnormal stimuli and often reverts back to normal on removal of stimulus.
The metaplasia is classified in to the following types:
Epithelial Metaplasia
More common and may be patchy or diffuse. Results in replacement by stronger but less specialized epithelium. Metaplastic epithelium is less well-specialized resulting in deprivation of protective mucus secretion and hence more prone to infection.
  1. Squamous metaplasia: It occurs due to chronic irritation that may be mechanical, chemical or infective in origin.
    1. In bronchus in chronic smokers.
    2. In uterine endocervix in prolapse of uterus and in old age.
    3. In gallbladder in chronic cholecystitis with cholelithiasis.
    4. In prostate in chronic prostatitis and estrogen therapy.
    5. In renal pelvis and urinary bladder in chronic infection and stones.
    6. In vitamin A deficiency squamous metaplasia in nose, bronchi, urinary tract, lacrimal and salivary glands.
  2. Columnar metaplasia
    1. Intestinal metaplasia in healed chronic gastric ulcer.
    2. In chronic bronchitis and bronchiectasis conversion of pseudostratified columnar into columnar type.
    3. In cervical erosion.
Mesenchymal Metaplasia
a. Osseous metaplasia: Formation of bone in fibrous tissue, cartilage and myxoid tissue.
  1. In arterial wall in old age.
  2. In soft tissues in myositis ossifications.
  3. In cartilage of larynx and bronchi in elderly people.
  4. In scar of chronic inflammation of prolonged duration.
  5. In fibrous stroma of tumor.
b. Cartilaginous metaplasia: In healing of fractures cartilaginous metaplasia may occur where there is undue mobility.20
Hemodynamic and Electrolyte Imbalance
Q. What is the definition, pathogenesis and fate of the thrombus?
Q. Define thrombosis. Discuss the fate of thrombosis.
(MUH Nov/Dec 08)
A. Definition: Thrombosis is the process of formation of solid mass called thrombus in circulation from the constituents of flowing blood.
Thrombogenesis is initiated by blood vessel injury which initiates hemostatic repair mechanisms.
Three primary events predisposing to thrombus formation are Virchow's triad, i.e.
  1. Endothelial injury
  2. Alteration in flow of blood
  3. Hypercoagulability of blood.
1. Endothelial Injury
  1. Role of blood vessel wall: An intact endothelium by virtue of its functions maintains normal blood flow. An intact endothelium protects the flowing blood from the thrombogenic influence of subendothelium
Elaborates a few antithrombotic factors like:
  • Heparin-like substances which accelerates the action of antithrombin III and inactivates some other clotting factors.21
  • Thrombomodulin an anticoagulant converting thrombin into activator of protein C.
  • Inhibitors of platelet aggregation such as Adpase, PGI2 or Prostacyclin.
  • Tissue plasminogen activator which accelerates the fibrinolytic activity.
Release prothrombotic factors having procoagulant properties like:
  • Thromboplastin or tissue factor
  • von Willebrand factor that causes adherence of platelets to subendothelium.
  • Platelet activating factor, an activator and aggregator of platelets.
  • Inhibitor of plasminogen activator that suppresses fibrinolysis.
Vascular injury exposes the subendothelial connective tissue like collagen, elastin, fibronectin, laminin and glycosaminoglycans which are thrombogenic.
These subendothelial tissues play an important role in initiating hemostasis and thrombosis.
Injury to vessel wall also causes vasoconstriction of small blood vessels so as to reduce blood loss.
Endothelial injury is of major significance in the formation of arterial thrombi and thrombi of the heart.
Conditions and factors which cause endothelial injury and predispose to thrombogenesis are: Endocardial injury in MI, myocarditis, cardiac surgery, prosthetic valves
  • Ulcerated plaques in advanced atherosclerosis
  • Hemodynamic stress in hypertension
  • Arterial diseases
  • Diabetes mellitus
  • Endogenous chemical agents such as hypercholesterolemia, endotoxin
  • Exogenous chemical agents such as cigarette smoke.
ii. Role of platelets: Following endothelial cell injury platelets play a central role in thrombosis as follows:22
Platelet Adhesion
Platelets in circulation adhere to exposed subendothelial collagen with help of von Willebrand's factor.
The canalicular system gets dilated with formation of pseudopods and the cytoplasmic organelles shift the center of the cell.
Platelet Release Reaction
  • Activated platelets undergo release reaction, releasing the platelet granules to the exterior.
  • There is two types of granules released.
Alpha granules
  • It contains fibrinogen, fibronectin; platelet derived growth factor, platelet factor 4 and cationic proteins.
Dense bodies
  • It contains ADP, ionic calcium, serotonin, histamine and epinephrine. Phospholipid complex-platelet factor three gets activated as sequel to platelet activation and release reaction and plays an important role the intrinsic pathway of coagulation. Platelet aggregation ADP, following its release brings about aggregation of additional platelets thus forms a temporary hemostatic plug. This plug is stabilized by fibrin, thrombin and thromboxane A2.
iii. Role of coagulation system
  • Coagulation systems are involved in thrombus formation by converting plasma fibrinogen into solid mass of fibrin. Coagulation mechanism is brought about by an intrinsic and an extrinsic pathway. These mechanisms are regulated to keep the blood in fluid state by protease inhibitors like antithrombin III, protein C, C1 inactivator, α-D1 antitrypsin and α-2 macroglobulin. These act on coagulation factors to oppose the formation of thrombin.
  • Fibrinolytic system it consists of two plasminogen activators.
  • Tissue type derived from endothelial cells and leukocytes.
  • Urokinase like present in plasma.
  • 23These plasminogen activators, converts plasminogen present in plasma, a potent fibrinolytic enzyme.
  • Plasmin so formed acts on fibrin to destroy the clot and produce fibrin split products.
2. Hypercoagulability of Blood
  • Hypercoagulability of blood brings about following changes in the blood composition.
    Increase in coagulation factors like fibrinogen, prothrombin, factor VIIa, VIIIa and Xa.
    Increase in platelet count and their adhesiveness.
    Decreased levels of coagulation inhibitors like antithrombin III, fibrin split products.
  • Conditions where the hypercoagulability of blood is increased are:
    • Nephrotic syndrome
    • Advanced cancers
    • Extensive trauma
    • Burns
    • During puerperium.
  • Factors favoring effect of hypercoagulability on thrombosis are:
    • Advancing age
    • Smoking
    • Use of oral contraceptives
    • Obesity.
3. Alteration of Blood Flow
  • Axial flow of the blood is normal where the most rapidly moving central stream consists of leukocytes and red cells slow moving adjacent stream contain platelets and the most slow moving cell free plasma is close to endothelial layer.
  • Turbulence in the blood flow facilitates formation of atrial and cardiac thrombi.
  • Stasis of blood flow initiates venous thrombi even in absence of endothelial injury.
  • This is because, in turbulence and stasis, the normal axial flow of blood is disturbed causing platelets to come in contact with the endothelium.
  • 24Moreover, turbulence may actually injure the endothelium resulting in deposition of platelets and fibrin.
Even the inhibitors of coagulation fail to reach the site of thrombus resulting in enlargement of thrombus size.
Gross Examination
  • Trombi varies in size, shape and composition depending upon their site of origin.
  • Arterial thrombi are white and mural while venous thrombi are red and occlusive.
  • Mixed thrombi are also common and consist of alternate white and red layers called as lines of Zahn. Arterial thrombi are soft, red and gelatinous whereas white thrombi are firm and pale.
Microscopic Examination
  • The rate of blood flow determines the composition of the thrombi.
  • The lines of Zahn are formed by alternate layers of light staining aggregated platelets admixed with fibrin meshwork and dark staining layers of red cells.
  • Venous thrombi have abundant red cells, leukocytes and platelets entrapped in fibrin meshwork.
Fate of Thrombus
  1. Resolution
    • Thrombus activates the fibrinolytic system with consequent release of plasmin which dissolves the thrombus completely resulting in resolution. Small venous thrombi are completely lysed but not large thrombi.
    • This process can be accentuated by administration of thrombolytic substances like urokinase, streptokinase especially in the early stage when fibrin is in monomeric form.
  2. 25Organization If a thrombus is not removed it undergoes organization as follows:
    • Phagocytic cells like neutrophils and macrophages begin to phagocytose fibrin and cell debris.
    • Leukocytes and endothelial cells liberate proteolytic enzymes which start digesting coagulum.
    • Capillaries grow into the thrombus. Thus fibrovascular granulation tissue is formed which subsequently becomes dense and less vascular and is covered over by endothelial cells.
    • This way thrombus is excluded from vascular lumen and is made part of vessel wall.
    • The new vascular channels in it may reestablish the blood flow by recanalization.
    • This fibrosed thrombus may also undergo hyalinization and calcification.
  3. Propagation
    • The thrombus may enlarge in size due to more and more deposition from the constituents of flowing blood.
    • This may ultimately cause obstruction of vessels.
  4. Thromboembolism
    • Thrombi in early stage and infected thrombi are quite friable and may get detached from the vessel wall.
    • These are released in part or completely in bloodstream as emboli which produces effects according to the site of lodgment.
Q. What is embolism? Describe types and cosequences of fat of embolism.
A. Definition: Embolism is the process of partial or complete obstruction of some part of the cardiovascular system by any mass carried in the circulation.
The transported intravascular mass detached from its site of origin is called an emolus.26
  1. Depending upon the matter in the emboli
    1. Solid: Detached thrombi, atheromatous material, tumor cells clumps.
    2. Liquid: Fat globules, amniotic fluid, bone marrow.
    3. Gaseous: Air.
  2. Depending upon the source of emboli
    1. Bland when sterile
    2. Septic when infected.
  3. Depending upon whether infected or not
    1. Cardiac emboli from left side of heart: Vegetations of endocarditis.
    2. Arterial emboli: From systemic arteries in the brain, spleen, kidney, intestine.
    3. Venous emboli: From plumonary arteries.
    4. Lymphatic emboli.
  4. Depending upon the flow of blood
    1. Paradoxical embolus or crossed embolus: An embolus carried from venous side of circulation to arterial side or vice versa through AV fistula, patent foramen ovale, and septal defect of the heart.
    2. Retrograde embolus: An embolus traveling against the flow of blood.
Fat Embolism
Definition: Embolism is the process of partial or complete obstruction of some part of the cardiovascular system by any mass carried in the circulation.
“Fat embolism is the obstruction to the arterioles and capillaries by the fat globule.”
a. Traumatic causes
  1. Trauma to bones: It is the most common cause of fat embolism.
  2. Trauma to soft tissue: The trauma to soft tissue27
  • Ex. laceration of adipose tissue
  • In puerperium injury to pelvic fatty tissue.
b. Nontraumatic causes
  1. Extensive burns
  2. Diabetes mellitus
  3. Fatty liver
  4. Pancreatitis
  5. Sickle cell anemia
  6. Decompression sickness
  7. Inflammation of bones and soft tissues
  8. Extrinsic fat or oil introduced into the body.
Following theories have been put forward to explain the formation of fat embolism.
a. Mechanical theory
  • Following trauma to bones and soft tissues, the fat globules are released into the venous circulation.
  • The most of the fat gets arrested in small capillaries of the lungs but some of the fat globules pass further into systemic circulation to lodge into other oragans.
b. Emulsion instability theory
  • According to this theory, fat emboli are formed by the aggregation of plasma lipids like chylomicrons and fatty acids due to disturbance in natural emulsification of fat.
  • This theory explains pathogenesis of fat emboli in non-traumatic cases.
c. Intravascular coagulation theory
  • In stress, some factors may activate disseminated intravascular coagulation (DIC) and aggregation of fat emboli.
d. Toxic injury theory
  • According to this theory, high plasma levels of free fatty acids chemically injure the small vessels in lungs increasing their vascular permeability resulting in consequent pulmonary edema.
  • All these mechanisms or theory may act single or in combination.28
Consequences of Fat Embolism
  • The outcome or consequence of fat embolism depends upon the size and quantity of the fat globules and whether the emboli can pass through the lungs into systemic circulation or not.
a. Pulmonary Fat Embolism
  • Small fat globules are not likely to appreciably obstruct the vast pulmonary vascular bed but widespread obstruction of the pulmonary circulation by fat embolism can result in sudden death.
  • Microscopically the lungs after fat embolism shows hyperemia, edema, petechial hemorrhages and changes of adult respiratory distress syndrome (ARDS).
  • Due to small size of fat globule, infarction is not a feature of pulmonary embolism.
  • These fat globules appear as vacuoles in pulmonary arteries, capillaries and alveolar spaces on
    Routine staining and they are confirmed by fat stains such as Sudan dyes, oil red O and osmic acid.
b. Systemic fat embolism
  • Though most of the fat globules get lodged in the pulmonary circulation, some may get into the systemic circulation via patent foramen ovale, arteriovenous shunts in the lungs and vertebral venous plexuses.
  • Then these globules get lodged in the capillaries of brain, kidney, skin, etc.
  • Fat embolism in brain shows petechial hemorrhages on leptomeninges and minute hemorrhages in the parenchyma. It can produce manifestations such as delirium, convulsion, stupor, coma and even sudden death. Microscopically, it shows microinfarct, edema and hemorrhages.
  • Renal fat embolism in the glomerular capillaries causes decreased GFR tubular damage and renal insufficiency.
  • Other organs involvement can be manifested as petechiae in the skin conjunctive and serosal surface appearance of fat globules in urine and sputum, etc29.
Q. Heart failure cells.
A. Definition: Heart failure cells are the hemosiderin laden macrophages seen in the alveoli of lungs in chronic venous congestion or brown induration of lungs due to high altitude of left heart failure.
  • In the chronic venous congestion of lungs, there is rupture of already congested and dilated capillaries causing minute intra-alveolar hemorrhages.
  • The breakdown of the erythrocytes liberates hemosiderin pigment which is taken up by the alveolar macrophages converting them into so called heart failure cells.
Q. What are the differences between transudates and exudates?
Q. Give the difference between transudates and exudates.
(MUHS May/Jun 08)
Q. Write different causes and features to differentiate transudates and exudates. (MUHS Nov/Dec 09)
Points of difference
flamed tissue associated with increased vascular permeability.
Filtrate of blood plasma without changes in endothelial permeability
Inflammatory edema
Noninflammatory edema
Protein content
High (>3 mg/dl) readily coagulate due to high content of fibrinogen and other coagulation factor
Low (>3 mg/dl) mainly albumin, low fibrinogen, has no tendency to coagulate
Low in neoplasms and infections
Same as in blood
Specific gravity
High (>1.018)
Low (<1.015)
Effusion LDH/ serum LDH ratio
Many cells (inflammatory as well as parenchymal)
Few cells, mainly mesothelial cells and cellular debris
Purulent exudate such as pus
Edema in congestive cardiac failure
30Q. Describe the difference between thrombus and postmortem clot.
A. The differences between both the conditions are as follow:
Antemortem thrombi
Postmortem clots
1. Gross
Dry, granular, firm and friabley
•Gelatinous, soft and rubbery
2. Relation
Adherent to vessel wall
•Weakly attached to the vessel wall
3. Shape
May or may not fit their vascular counters
•Take the shape of the vessel or its bifurcation
4. Microscopy
Surface contains apparent lines of Zahn.
•Surface is 'chicken fat' yellow covering the underlying red current jelly
Inflammation and Healing
Q. Define inflammation. Mention the types, sequential vascular changes in acute inflammation.
Q. Define inflammation. Describe in brief vascular and cellular events of acute inflammation. (MUH May/June 08)
A. Definition:
  • Inflammation is defined as the local response of living mammalian tissues to injury due to any agent.
  • It is a body defense reaction in order to eliminate or limit the spread of injurious agent as well as to remove the consequent necrosed cells tissues.
Depending upon the defense capacity of the host and duration of response, inflammation can be of two types.
Acute Inflammation
It is of short duration and represents the early body reaction and repair usually follows.
Chromic Inflammation
It is longer duration and occurs either after the causative agent persists for a longer time or the stimulus itself induces chronic inflammation.32
Vascular Changes in Acute Inflammation
Sequential vascular changes in acute inflammation can be explained under two headings:
  1. Hemodynamic changes
  2. Changes in vascular permeability.
Hemodynamic Changes
Transient vasoconstriction of arterioles for about 3 to 5 seconds in mild form of injury and up to 5 minutes in severe injury.
Next follows persistent progressive vasodilatation of mainly arterioles and to lesser extent venules and capillaries.
It results in increased blood volume in microvascular bed which is responsible for redness and warmth at the inflammatory site.
Progressive vasodilatation elevates the local hydrostatic pressure resulting in transudation of fluid into the extracellular space. This is responsible for swelling of the inflammatory site.
Slowing or stasis of microcirculation occurs next due to increased RBCs concentration or raised blood viscosity as results of increased vascular permeability.
Leukocyte margination along the vascular endothelium occurs next. Leukocytes, mainly neutrophils stick briefly to the vascular endothelium and then move and migrate through the gaps between the endothelial cells into the extravascular space. This process is known emigration.
Altered Vascular Permeability
Pathogenesis: In and around the inflamed tissue, there is accumulation of edema fluid in the interestitial space derived from blood plasma by its escape through the endothelial wall of peripheral vascular bed.
In initial stage, the escape of fluid is due to vasodilatation and consequent elevation in hydrostatic pressure and subsequently due to increased vascular permeability.
The nature of fluid in initial stages is transudate which subsequently becomes characteristic inflammatory exudate.33
Mehanisms of increased vascular permeability
i. Contraction of endothelial cells
  • This is the most common mechanism affecting venules exclusively.
  • The endothelial cells develop temporary gap between them due to their contraction resulting in vascular leakiness.
  • The response begins immediately after injury and lasts for short duration and is usually reversible.
  • The chemical mediators responsible this mechanism are histamine and bradykinin.
ii. Retraction of endothelial cells
  • In this mechanism, there is a reversible retraction at the intercellular junction due to structural reorganization in the cytoskeleton of the cells of the venules.
  • The response is brought about by interleukin-1 and tumor necrosis factor.
  • The response begins after about 4 to 6 hours and lasts for 2 to 4 hours or more.
iii. Direct injury to endothelial cells
  • A direct injury to endothelial cells leads to cell necrosis and consequently there appears a physical gap in the endothelial lining of the microvasculature.
  • The response may appear immediately or after a delay of 2 to 12 hours and lasts for several hours or days.
iv. Endothelial injury mediated by leukocytes
  • Adherence of leukocytes to the endothelium of the inflammatory site causes their activation and results in release of proteolytic enzymes and toxic oxygen radicals.
  • This causes endothelial injury and increased vascular leakiness.
v. Other mechanisms
  • In addition the newly formed capillaries during the process of repair are excessively leaky vesicles and vacules within the cytoplasm of endothelial cells of blood vessels in tumors account for fluid leakage across the cytoplasm.34
Q. Define inflammation? Describe the cellular changes in acute inflammation?
Q. Define inflammation? Describe in brief vascular and cellular events in acute inflammation?
(MUHS May/June 08)
A. Definition:
  • Inflammation is defined as the local response of living mammalian tissues to injury due to any agent.
  • It is a body defense reaction in order to eliminate or limit the spread of injurious agent as well as to remove the consequent necrosed cells tissues.
Cellular Events in Acute Inflammation
Cellular events in acute inflammation can be studied under two headings.
  • Exudation of leukocytes
  • Phagocytosis.
Exudation of Leukocytes
It is the escape of the leukocytes from the lumen of the microvasculature to the interstitial tissue and is the most important feature of acute inflammation. The first line of defense in acute inflammation is polymorphonuclear-neutrophils followed by monocytes and macrophages.
Changes in the Formed Elements of the Blood
Blood flow rate is increased due to vasodilatation in acute inflammation but subsequently there is slowing or stasis of bloodstream. This stasis changes the normal axial flow of blood which consists of central cell stream of leukocytes and RBSs and peripheral cells free plasma layer of close the vessel wall. The central stream cell widens and peripheral plasma zone narrows due to loss of plasma by exudation due to slowing and stasis. This phenomenon is known as margination. Thus the neutrophils of the central stream come to lie close to the vessel wall. This phenomenon is known as pavementing.35
Adhesion or Rolling
The peripherally marginated and pavemented neutrophils stick briefly to the endothelial cells lining the vessel wall or roll over it. This adhesion is produced due to neutralization of the normal negative change on leukocytes and endothelial cells because of injury. This adhesion is felicitated by four distinct adhesion molecules. Selectins such as P-selectin (preformed and stored in endothelial cells and platelets), E selectin (synthesized by cytokine-activated endothelial cells) and L-selectin (Le 4-8 antigenase expressed on surface of lymphocytes and neutrophils) partake in rolling of polymorphoneutrophils over endothelial surface.
Addressins expressed on the surface of leukocytes and endothelium and regulate the localization of subpopulation of leukocytes. Integrins (B and B2 molecules) bring about adhesion between leukocytes and endothelium. Immunoglobulin super family adhesion molecule such as intercellular adhesion molecule such as intercellular adhesion molecule (ICAM-1, 2) help in localizing leukocytes to the site of tissue injury and thus help in transmigration of polymorphoneutrophils.
After sticking of neutrophils to endothelium they move along the endothelium till a suitable site between the endothelial cells is found where the neutrophils throw out cytoplasmic pseudopods.
Then by secreating collagenases, the neutrophils damage the basement membrane locally and escape out into the extravascular space. This phenomenon is known as emigration.
Along with emigration, there is simultaneous diapedesis, i.e. red cells are forced out through the gap between the endothelial cells either by raised hydrostatic pressure or may escape through the endothelial defects left after emigration of leukocytes. Diapedesis is responsible for hemorrhagic appearance to the inflammatory exudate. The damaged basement membrane is repaired almost immediately. The 36dominant cells in the exudate are neutrophils in first 24 hours and are short lived (24–48 hours) but next 24–48 hours monocytes and macrophages appear and they survive much longer.
Chemotaxis is the transmigration of leukocytes across several barriers of endothelium, basement membrane, perivascular myofibroblasts and matrix to reach the interstitial tissue mediated by chemotactic factors.
The concept of chemotaxis cab is illustrated by Boyden's chamber experiment.
Here a millipore filter separates the leukocyte suspension from the test solution containing chemotactic agent in a tissue culture chamber. It is observed that the leukocytes migrate through the pores of filter towards the chemotatic agent. These chemotactic agents are also called as chemokines and they carry specific receptors.
Some of the potent chemokines are:
  • Leukotriene b4
  • Platelet factor 4
  • Components of complement system
  • Cytokines, particularly IL-8
  • Soluble bacterial products
  • Monocyte chemoattractant protein
  • Chemotactic factor for Cd4+ T cells
  • Eotaxin chemotactic for eosinophills.
Phagocytosis is the process of engulfment of solid particulate matter by the cells called as phagocytes.
The two main types of phagocytic cells are
  1. Polymorphonuclear neutrophils: Also called as mcrophages, they appear early in an acute inflammatory response.
  2. Macrophages: These are circulating monocytes and fixed tissue mononuclear pha gocytes.
37 Both these types share a common process of phagocytosis involving four steps:
  • Attachment stage
  • Engulfment stage
  • Secretion stage
  • Degradation stage.
  1. Attachment stage or opsonization: The microorganism to be phagocytosed and the phagocytic cell repel each other due to both having a negatively charged surface. To overcome this repulsion, the microorganisms gets coated with a naturally occurring factor in serum called opsonins. The two main opsonins in the serum and their corresponding receptors on the cell surface are IgG opsonin and corresponding receptor is Fc fragment of immunoglobulin on the surface of polymorphs and monocytes. C3b opsonins fragment of complement and corresponding receptor for C3b on the phagocytic cell surface.
  2. Engulfment stage: The opsonied particle bound to the phagocyte surface is engulfed by formation of cytoplasmic pseudopods around it and enveloping it in phagocytic vacuole. Eventually the membrane of phagocytic vacuole breaks from the cell surface so that membrane lined phagocytic vacuole lies free in the cytoplasm. This is converted into phagolysosome or phagosome on its fusion with the lysosomes of the cell.
  3. Secretion or degranulation stage: The preformed granules stored in the polymorphonuclear neutrophils are discharged into the phagosome and the extracellular environment. The specific secondary granules are discharged while the azurophilic granules are fused with the phagosomes. The polymorphonuclear neutrophils synthesize and secrete numerous other products in addition to granules like:
  • Enzymes: Interleukin 2 and 6, TNF
  • Arachidonic acid metabolites: Prostaglandins, leukotrienes, platelet activating factor
  • Oxygen metabolites: Superoxide oxygen, hydrogen peroxide, hypochlorous acid.
38 iv. Killing or degradation stage: In this final stage, the microorganisms are killed by the antibacterial substances and digested or degraded by hydrolytic enzymes. The antibacterial substances act in any of the following ways.
a. Oxygen dependent bactericidal mechanism: It is an important mechanism carried out by production of (H2O2), hydroxyradical (OH), hypochlorous acid (HOCl), etc. The mechanism of production of these oxygen metabolites is brought out by NADPH oxidase present in the cell membrane of phagosomes. The hydrogenperoxide thus produced has bactericidal property being carried out in presence of an enzyme myeloperoxidase (MPO) present in granules of neutrophils or monocytes or independent of it.
  • MPO dependent killing (H2O2 - MPO halide system): Here H2O2 is converted into hypochlorous acid, a more potent bactericidal in presence of halides by the enzyme MPO.
  • MPO inddependent killing: Here mature macrophages lack the enzyme MPO and they carry out the bactericidal activity by producing OH or O2 from by either by Haber-Weiss reaction (in presence of O2), Fenton reaction (in presence of Fe2+). These reactive oxygen metabolites are particularly useful against the microbes that grow within the phagocytes, e.g. M. tuberculosis.
b. Oxygen independent bactericidal mechanism: Some agent like lysosomal hydrolase, permeability increasing factors, and cationic proteins (defensins) released from phagocytic cell granules do not require oxygen for bactericidal activity.
c. Nitric acid mechanism: Nitricoxide produced by the endothelial cells and activated macrophages seem to have fungicidal and antiparasitic action in animals.
39 Q. What is granuloma? Describe morphology and fate of tuberculous primary complex.
Q. Write the pathology of tuberculosis and precaution to be taken by a nurse. (MUHS Nov/Dec 09)
A. Definition: Granuloma is defined as a circumscribed, tiny lesion, about 1 mm in diameter, composed predominantly of collection of modified macrophages called epithelioid cells and rimmed at the periphery by lymphoid cells.
A. Bacterial
  • Tuberculosis
  • Leprosy
  • Syphilis
  • Granuloma inguinale
  • Brucellosis
  • Cat scratch disease
  • Tularemia
  • Glanders.
B. Fungal
  • Actinomycosis
  • Blastomycosis
  • Cryptococcosis
  • Coccidioidomycosis.
C. Parasitic
  • Schistosomiasis
D. Miscellaneous
  • Sarcoidosis
  • Crohn's disease
  • Silicosis
  • Berylliosis
  • Foreign body granuloma.
Tuberculosis is a chronic granulomatous inflammation characterized by presence of granulomas called the tubercle.40
Evolution of Tubercle
When the tubercle bacilli are intravenously injected into the guinea pig, the bacilli are lodged in pulmonary capillaries evoking an initial response of neutrophils. After about 12 hours; there is progressive infiltration by macrophages. The macrophages dominate the picture henceforth in evolution of tubercle; however they are dominant in the picture from the beginning in cases inhalation of bacilli into the alveoli.
The macrophages start phagocytosing the tubercle bacilli. As a result of immune mechanism the macrophages undergo structural changes in 2–3 days time. Their cytoplasm becomes pale and eosinophilic and their nuclei become elongated and vesicular. These modified macrophages are called epithelioid cells.
The macrophages continue to enter the tissue from circulating monocytes or local proliferation and undergo modification to from more epithelioid cells. These epithelioid cells aggregate into light clusters or granulomas.
Release cytokines in response to sensitized Cd4+ cells and some constituents of mycobacterial cell wall play a role in formation of granuloma.
Some adjacent macrophages fuse to form multinucleated giant cells. The giant cells may be Langerhans type having peripherally arranged nuclei in horseshoe or ring form or clustered at the two poles or may be of foreign body type having centrally placed nuclei.
Around the mass of epithelioid cells and giant cells is a zone of lymphocytes, plasma cells and fibroblasts. At this stage, the lesion is called hard tubercle. Within 10-14 days; the center of the cellular mass begins to undergo caseation necrosis. This stage is called as soft tubercle with center having cheesy appearance and high lipid content. The soft tubercle is a fully-developed granuloma with caseous center. It does not favor rapid proliferation of tubercle bacilli.
The soft tubercle is the hallmark of tuberculous lesions.
41 It consists of a central zone of granular caseation necrosis.
This is surrounded by epithelioid cells and occasional Langerhans’ cells and peripheral, rim of lymphocytes bounded by fibroblasts.
Microscopically caseation necrosis is structureless, eosinophilic and granular material with nuclear debris.
Fate of Tuberculous Granuloma
The caseous material may undergo liquefaction and extend into surrounding soft tissues discharging the contents on the surface. This is called cold abscess.
In tuberculosis of tissues like bones, joints, lymph nodes are lined by tuberculous granulation tissue.
The adjacent granulomas may coalesce together enlarging the lesion which is surrounded by progressive fibrosis.
In the granuloma enclosed by fibrous tissue, calcium salts may get deposited in the caseous material leading to dystrophic calcification and sometimes the lesion may even get ossified over the years.
Q. What is “healing”, “regeneration”and “repair”. Describe the steps in healing by “first intention”.
Q. What is healing by “first intention”? (MUHS May/Jun 09)
A. The descriptive definitions of individual terms are given below.
Healing is the body response to injury in an attempt to restore normal structure and function.
Regeneration is a form of healing where healing takes place by proliferation of parenchymal cells and usually results in complete restoration of the original tissues.42
Repair is also a form of healing where healing takes place by proliferation of connective tissue elements resulting in fibrosis and scarring.
Healing by First Intention
Healing by first intention or primary union is defined as healing of a wound which has the following characteristics:
  1. Clean and uninfected
  2. Surgically incised
  3. Without much loss of cells and tissue
  4. Edges of wound are approximated by surgical sutures.
Steps in Healing by “First Intention”
  1. Initial hemorrhage: Immediately after injury, the space between the approximated surfaces of incised wound is filled with blood which then clots and seals the wound against dehydration and infection.
  2. Acute inflammatory response: Within 24 hours of injury, the polymorphs appear from the margins of incision which are replaced by macrophages by 3rd day.
  3. Epithelial changes: The basal cells of epidermis from both the cut margins start proliferating and migrating towards incisional space in the form of epithelial spurs. A wellapproximated wound is covered by a layer of epithelium in 48 hours. These migrated epidermal cells separate the underlying viable dermis from the overlying necrotic material and clot forming scab which is cast off. The basal cells from the margins continue to divide. A multilayered new epidermis is formed by 5th day and is differentiated into superficial and deeper layers.
  4. Organization: By 3rd day the wound area is invaded by fibroblasts. By 5th day new collagen fibrils start forming which dominate till healing is completed. In 4 weeks, the scar tissue with scanty cellular and vascular elements, a few inflammatory cells and epithelialized surface is formed.
  5. 43 Suture tracks: Each suture track is a separate wound and incites the same phenomenon of primary union. When suture are removed around 7th day, much of epithelialized suture track is avulsed and the remaining epithelial tissue in track is absorbed.
Thus, scar formed in a sutured wound is neat due to close apposition of the margins of wound.
Q. Describe the cardinal signs of acute inflammation, describe bone healing of fracture bone.
Q. Discuss the healing of fractured bone and mentions its complications.
Q. Discuss healing of bone fracture in detail.
(MUHS May/June 08)
Q. Write in detail on “fracture healing”.
(MUHS Nov/Dec 09)
A. Definition: The inflammation is the local response of living mammalian tissues to injury due to any agent.
The response is manifested as the cardinal signs of inflammation which are:
The four cardinal signs of inflammation were named by the Roman writer celsus in 1st century AD. But the very important which is later added to these Virchow's fifth sign.
Functio laesa:
Loss of function.
Healing of Fracture Bone
Bone healing of fracture of long bone healing of fractured bone is similar to healing seen in the skin, i.e. primary and secondary union.
Primary Union of Fracture
It is seen in few special cases when the ends of fracture are approximated by compression clamps. Here, the bony union takes place with formation of medullary callus without periosteal callus formation.44
Secondary Union of Fracture
It is more common process of fracture healing. Which is a continuous process and can be described under three headings.
a. Procallus formations
  1. Hematoma: A hematoma is formed due to bleeding from the torn blood vessels. It fills the area surrounding the fracture forming a loose meshwork of blood and fibrin clots which act as a framework for subsequent granulation tissue formation.
  2. Local inflammatory response: It occurs at the site of injury with exudation of fibrin, polymorphs and macrophages. The macrophages clear away the fibrin RBCs, inflammatory exudate and debris.
    Fragment of necrosed bone are scavenged by macrophages and osteoclasts.
  3. Granulation tissue: It starts growing inward with neovascularization and proliferation of mesenchymal cells fom periosteum and endosteum. The soft tissue thus formed is called callus which joins the ends of the factured bone without much strength.
  4. Callus formation: Within first few days the callus composed of woven bone and cartilage starts. The osteogenic potential bearing cells of inner layer of the perisoteum starts laying down collagen and osteoid matrix in the granulation tissue. The osteoid undergoes calcification and is called woven bone callus.
Woven bone callus covers much wider zone over the cortex on either side of fractured end and bridges the gap between them giving spindle-shaped or fusiform appearance to the union.
This stage is called provisional callus or procallus formation and is arbitrarily divided into external, internal and intermediate procallus.
b. Osseous callus formation
Procallus acts as scaffolding on which osseous callus composed of lamellar bone is formed.
45Woven bone is cleared away by incoming osteoclasts and calcified cartilage disintegrates.
In their place, newly formed blood vessels and osteoblasts invade, laying down osteoid which is calcified and lamellar bone is formed by developing haversian system concentrically around the blood vessels.
c. Remodeling
During the formation of lamellar bone, osteoblastic laying and osteoclastic removal are taking place remodelling the united bone ends. The external callus is cleared away, compact bone or cortex is formed in place of intermediate callus and the bone marrow cavity develops in internal callus.
Complications of Fracture Healing
  1. Fibrous union: It may result instead of osseous union if the immobilization of fractured bone is not done. Occasionally, a false joint may develop at the fracture site (pseudoarthrosis).
  2. Nonunion: It may result if some soft tissue is interposed between the fractured ends.
  3. Delayed union: It may occur due to infection, inadequate blood supply, poor nutrition, movement and old age.
Q. Giant cells.
Q. Define giant cells. What is the various types and condition with which they are associated?
Definition: Giant cells are modified macrophages. When these macrophages fail to deal with particles to be removed the fuse together and form multinucleated giant cells.
Type of Giant Cells
The giant cells are described in detail with their types, morphology and examples in the following table.46
Foreign body giant cell
•These contain numerous nuclei (up to 100) which are uniform in size and shape and resembles the nuclei of macrophages
•These nuclei are scattered throughout the cytoplasm.
•Chronic infective granuloma
Langhan's giant cells
•There nuclei are like the nuclei of Macrophages sand epitheloid cells.
•Nuclei are arranged either around the peripherry in the form of horseshoe or ring or are clustered at the two poles of the giant cells.
Touton's giant cells
•These multinucleated cells have vacuolated cytoplasm due to lipid content.
Tumour giant cells
•These are larger, have numerous nuclei which are hyperchromatic and vary in size and shape
•These giant cells are not derived from macrophages but are formed from dividing nuclei of the neoplastic cells.
•Carcinoma of liver
•Various soft tissue sarcomas
Miscellaneous types
•These include presence of numerous nuclei in mesodermal cells.
•Aschoff cells in rheumaric nodule
•Reed-Sternberg cells of Hodgkin's disease.
Q. Cardinal signsof inflammation
A. The inflammation is the local response of living mammalian tissues to injury due to any agent. This response is mani-fested as the cardinal signs of inflammation which are as follow:
1. Rubor
2. Tumor
3. Calor
4. Dolor
The four cardinal signs of inflammation were named by the roman writer celsus in 1st century AD. To these Virchow'slater added the fifth sign loss of function.
5. Functio laesa: Loss of function.
Q. Primary complex (Gohn's complex).
Q. Describe Ghon's complex.
(MUHS May/Jun 08)
Q. Ghon's lesion.
Q. Describe Ghon's complex.
(MUHS Nov/Dec 09)
A. Definition: Primary complex also known as Ghon's complex is the tuberculous lesion produced at the portal of entry with foci in the draining lymphatic vessels and lymph nodes.
The most common sites for primary complex are lungs and hilar lymph nodes.
  • The other sites are tonsils and cervical lymph nodes.
  • In case if the Mycobacterium is ingested, the primary complex can be found in small intestine and mesenteric lymph nodes.
Components of Gohn's Focus
The primary complex in lungs consists of three components:
  1. Pulmonary component
    • Lesion in the lung is the primary focus or Ghon's focus.
    • It is a 1–2 cm solitary area of tuberculous pneumonia.
    • It is usually located under the pleura in the lower part of the upper lobe.
    • Microscopically the pulmonary component consists of tuberculous granuloma with caseation necrosis.
  2. Lymphatic vessel component
    • The lymphatics draining the pulmonary lesion contain phagocytes containing bacilli and may develop beaded miliary tubercles along the path of the hilar lymph nodes.
  3. Lymph node component
    • This consists of enlarged hilar and tracheobronchial lymph nodes in the area drained.
    • The affected lymph nodes are matted and show caseation necrosis.
    • Microscopically, these lesions are characterized by extensive caseation, tuberculous granulomas and fibrosis.
    • 48These nodal lesions are potential source of reinfection later.
    • In case of primary tuberculosis of alimentary tract due to ingestion of tubercle bacilli, the primary complex is small seen in intestine with enlarged mesenteric lymph nodes producing tabes mesenterica.
Q. Difference between tuberculoid and lepromatous leprosy
A. The main classical differentiating features are mentioned under the tabulated form.
Differentiating features
Tubeculoid leprosy
Lepromatous leprosy
Skin lesions
Asymmetrical, single or a few lesions, hypopigmented and erythematous macular
Symmetrical, multiple, hypopigmented, erythematous, maculopapular or nodular (leonine facies)
Nerve involvement
Present with distinct sensory disturbance
Present but sensory disturbance is less severe
Hard tubercle similar to granulomatous lesions, eroding the basal layer of epidermis, no clear zone
Collection of foamy macrophages or lepra cells in the dermis separated from epidermis by clear zone
Few lepra bacilli, seen in destroyed nerves as granular or beaded forms
Highly positive for lepra bacilli seen as globi or cigarettes in a pack appearance
Good immune response
Lepromin test
Q. Tuberculoma
A. Definition: Tuberculoma is an intracranial mass occurring either solitary or multiple.
It occurs secondary to dissemination of tuberculosis elsewhere in the body.
Gross Examination
A tuberculoma has a central area of caseation necrosis surrounded by fibrous capsule.49
Microscopic Examination
  • The central area of caseous necrosis is surrounded by the typical tuberculous granulomatous reaction.
  • The tuberculoma is surrounded by a zone of gliosis.
  • Advanced cases may show areas of calcification.
Q. Fate of primary tuberculosis
A. Primary tuberculosis may not progress but instead healed by fibrosis and intime undergo calcification and even ossification.
In some cases, it may continue to grow and the caseous material is disseminated through bronchi to the other parts of the same lung or the opposite lung. This is called progressive primary tuberculosis.
At times, bacilli may enter the circulation through erosion in a blood vessel and spread to various tissues and organs. This is called primary miliary tuberculosis and the lesions are seen in organs like liver, spleen, kidney, brain and bone marrow.
In cases of lowered resistance and increased hypersensitivity of the host, the healed lesions of primary tuberculosis may get reactivated causing progressive secondary tuberculosis.50
Infectious and Parasitic Diseases
Q. Parasites causes anemia.
Q. Parasitic infection. (MUHS May/June10, Nov/Dec 08)
A. The following are the parasitic infection of the human body which causes anemia too.
  • Plasmodium falciparum
  • Plasmodium vivax
  • Plasmodium ovale
  • Plasmodium malariae
  • Leishmania donovani
  • Ancylostoma duodenale
  • Diphyllobothrium latum
  • Necator americanus
  • Taenia solium.
Parasitic infection is contamination of one organism with another living organism that then begins to feed off or reside in the initial organism. In humans this generally means infections with very large parasites that can be seen, such as tapeworms or with tiny ones like ameba that take intensive laboratory study to find. When most humans have a parasitic infection they become ill, because their bodies are not supposed to play host to other large or small organisms of certain types, and these other organisms can cause destruction to the body including death if they are not somehow removed.
The greatest chance of getting parasitic infections tends to occur in underdeveloped countries, where methods of keeping 51the water supply free from amoeba or large parasites may not be as advanced. Certain parts of the world run much greater risk for people getting parasitic infections than do others, and these include parts of Asia, Africa and South America. In other parts of Asia, much of Western Europe and most of North America, the likelihood of getting a parasitic infection is much lower, though it still exists.
It's fairly easy to get a parasitic infection from drinking untreated water for instance, and there are plenty of people who might do so on a camping trip and end up with conditions like Giardia. Other ways in which parasites can be passed to a host are through the consumption of undercooked meats or through raw fruit or veggies contaminated by them, bites from certain insects, directly from another person with a parasitic infection, or by direct contact with parasites, such as by playing in the dirt where there might be animal droppings.
Often, a parasitic infection affects the gastrointestinal tract, and people's response especially to amebic infection may be what seems like never-ending stomach flu. People have diarrhea and vomiting for long periods of time. Other large parasites like tapeworm may not result in stomach flu symptoms but these parasites survive by taking away and consuming part of the food humans consume, and this can lead to severe malnutrition. Complications from tapeworm may also arise as new worms are born and move into other areas of the body.
In order to appropriately treat a parasitic infection it must be diagnosed first, and best treatment must be considered for the specific parasite. Diagnosis may be made through a number of means. Many times, doctors evaluate stool samples to look for evidence of parasites, but they may also find parasites through X-ray or other scanning methods, and through skin swabs of certain areas of the body. Next, most people will go on a course of antiparasitic medicine, which can last for several months. People are usually retested at this time to make sure the medicine has worked effectively, and they may be tested again some months later to make certain that another infection has not occurred.
52As with many types of infections, a parasitic infection tends to be most dangerous to people who are vulnerable medically. This can include people with autoimmune diseases like HIV, and those who are very young and very old. However, anyone can get parasitic infections, and when diagnosis is missed, this can result in extreme illness.53
Neoplasm and Cellular Growth
Q. Define neoplasia. Describe the characters of malignant tumors.
Q. Features of malignant tumor. (MUHS May/June 09)
A. Definition: Neoplasia is the abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists in same excessive manner after cesssation of stimuli which provoked the growth.
Characteristic Features of Malignant Tumor
Macroscopic Features
Malignant tumors are usually irregular in shape, poorlycircumscribed and into the adjacent tissues.
Secondary changes like hemorrhage, infarction and ulceration are more often.
Sarcomas have fish flesh-like consistency while carcinomas are firm.
Microscopic Features
i. Microscopic pattern
Malignant tumor differs greatly from the arrangement in normal tissue of origin of the tumor.
There is also loss of basal polarity altered alignment of tumor cells to each other and stromal invasion by tumor cells.
ii. Tumor cytomorphology
Malignant tumors show pleomorphism, i.e. show variation in size and shape of cells.
54Nuclei of malignant tumor cells are enlarged disproportionate to the cell size so that the nucleocytoplasmic ratio is increased from normal 1:5 to 1:1.
Nuclear chromatin is increased and coarsely clumped (hyperchromatism).
The cells show large number of mitoses because of increased number normal mitoses a malignant tumor shows abnormal and atypical mitotic figures such as tripolar, quadripolar and multipolar spindles.
Malignant tumors also show multinucleate tumor giant cells or giant cells containing a single, large and bizarre nucleus.
The cytoplasmic constituents are reduced or lost.
Genetic abnormalities: Malignant tumor cells have abnormal genetic composition in form of aneuploidy often in the form of an increase in the number of chromosome.
Functional changes: Function of the malignant tumor may be lost or retained or may become abnormal.
iii. Angiogenesis and tumor stroma
New blood vessels are formed under stimulation by tumor angiogenesis factors like vascular endothelial growth factor secreted by the tumor cells to provide nutrition to the growing tumor.
iv. Inflammatory reaction
Some cancers may show inflammatory reaction whether acute or chronic.
Growth Rate
Malignant tumor cells grow rapidly.
Local Invasion
Malignant tumors enlarge by expansion by invasion, infiltration and destruction of the surrounding tissue besides distant metastasis.
Tumors invade via the route of least-resistance and often extend through tissue spaces, permeate lymphatics.55
Metastasis is spread of tumor by invasion in such a way that discontinuous secondary tumor mass/asses formed at the site of lodgement. All malignant tumors with few exception like gliomas of CNS and basal cell carcinoma of skin metastasis.
Q. Detection cancer early.
(LAQ) MUHS Nov/Dec 08, May/June 10)
A. Why is it important to find cancer early?
Some common cancers are easier to treat and cure if they are found early. There are many different types of cancer, but most cancers begin when abnormal cells grow out of control and form a lump (called a tumor). The tumor can continue to grow until the cancer begins to spread to other parts of the body. If the tumor is found when it is still small and has not yet spread, curing the cancer can be easy. However, the longer the tumor goes unnoticed, the greater the chance that the cancer has spread. This usually makes treatment more difficult.
How do I know if I am at risk for cancer?
Talk to your doctor. He or she can help you understand your risk for cancer, especially if other members of your family have a history of cancer. Your doctor can also help you understand how your risk for cancer is affected by the following:
  • Using or having used tobacco products, such as cigarettes or chewing tobacco
  • Drinking alcohol
  • Having eaten a diet high in fat for most of your life
  • Being exposed to chemicals that can cause cancer
  • Being at risk for skin cancer.
Depending on your age and your risk factors, your doctor may begin screening you for certain types of cancer. Screening means looking for cancer before it causes symptoms. Some doctors recommend that people who are at high-risk or have a family history of cancer be screened regularly. The recommendations vary for different cancers.56
What screening tests should women have?
To help find breast cancer early, your doctor will probably perform a clinical breast examination (where he or she checks your breasts for lumps) once every 3 years until you're 40 years old. All women age 40 and older should have a mammogram (an X-ray of your breasts) every 1–2 years with or without a clinical breast examination. If you are at highrisk for breast cancer, such as a history of breast cancer in your family, your doctor may want you to have mammograms more often or start having them sooner.
To help find cervical cancer early, have Pap smears at least every three years. During a Pap smear, your doctor takes a sample of cells from your cervix to be tested. Your doctor may also collect cells from your cervix during a Pap test to be tested for the human papillomavirus, or HPV. There are 13 types of HPV that have been linked to cervical cancer and this test can detect abnormal cells before cancer forms.
You should have your first Pap smear when you start having sex or by age 18. You should have a Pap smear at least once every 3 years, unless your doctor suggests that you need one more often. Keep having Pap smears throughout your life, even after menopause.
What screening tests should men have?
To help find prostate cancer early, first talk to your doctor about your risk. Factors such as family history, age and race play a part in the risk of prostate cancer.
The National Cancer Institute, the American Cancer Society, the US. Preventive Services Task Force and the American Academy of Family Physicians recommend that men talk to their doctors about the pros and cons of screening.
If you decide to have screening, your doctor may examine your prostate by putting a gloved, lubricated finger a few inches into your rectum to feel your prostate gland. This is called a digital rectal exam. A normal prostate feels firm and rubbery. If there are hard spots on the prostate, your doctor may suggest additional testing to check for prostate cancer.
57 Another way to screen for prostate cancer is with a blood test called the PSA test. PSA is short for prostate-specific antigen. Men who have prostate cancer may have a higher level of PSA in their blood. However, the PSA level can also be high because of less serious causes, such as infection.
What about colorectal cancer?
Most colorectal cancers begin as a polyp (say “pahl-ip”). At first, a polyp is a small, harmless growth in the wall of the colon. However, as a polyp gets larger, it can develop into a cancer that grows and spreads. See your doctor if you have any of the following warning signs:
  • Bleeding from your rectum
  • Blood in your stool or in the toilet after you have a bowel movement
  • A prolonged change in the consistency of your stool (such as diarrhea) or constipation last several weeks
  • Cramping or pain in your lower stomach
  • A feeling of discomfort or an urge to have a bowel movement when there is no need to have one
  • Unintended weight loss.
Tests used to screen for colorectal cancer include the following:
  • Fecal occult blood test, in which your stool is checked for blood that you cannot see
  • Flexible sigmoidoscopy, in which a tiny camera is inserted into your colon, allowing your doctor to look at the rectum and the lower part of your colon
  • Double contrast barium enema, for which you take an enema and have an X-ray to find abnormal spots
  • Colonoscopy, which is similar to a flexible sigmoidoscopy, except the entire colon is examined.
Colorectal cancer is more common in older people, so doctors usually begin screening people at age of 50. Some people have risk factors that make them more likely to get colorectal cancer at a young age. Screening should begin earlier in these people.
Talk to your family doctor to decide which screening tests you should have and how often you should be screened.
58 What about skin cancer?
The best way to find skin cancer early is to keep an eye on your skin, especially moles. The ABCDE rule (see below) can help you remember what to look for when you are checking any moles on your skin. If you notice any of these signs, talk to your doctor right away.
Signs of skin cancer:The ABCDE rule.
"A" for asymmetry
A mole that, when divided in half, does not look the same on both sides.
"B" for border
A mole with edges that is blurry or jagged.
"C" for color
Changes in the color of the mole, including darkening, spread of color, loss of color, or the appearance of multiple colors such as blue, red, white, pink, purple or gray.
"D" for diameter
A mole larger than th inch in diameter.
"E" for elevation
A mole that is rased above the skin and has an uneven surface.
Q. Define neoplasia. Describe the differences between benign and malignant tumors. Mention spread of malignant tumor.
Q. Give difference between benign and malignant tumor.
(MUHS)(May/Jun 08)
A. Definition: Neoplasia defined as an abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of normal tissue and persists in some excessive manner after cessation of stimuli which provoked the growth. Differentiation of the tumor: The two different conditions are shown in the tabulated form which is as follow:59
Points of difference
Benign tumor
Malignant tumor
A. Macroscopic features
a. Boundaries
Encapsulated or wellcircumscribed
Poorly circumscribed and irregular
b. Surrounding tissue
Often compressed
Usually invaded
c. Size
Usually small
Often large
d. Secondary changes
Occurs less often
Occurs more often
B. Microscopic features
a. Pattern
Usually resembles the tissue of origin closely
Often poor resemblance to tissue of origin
b. Basal polarity
Often lost
c. Pleomorphism
Usually not present
Often present
d. Nucleocytoplasmic ratio
e. Anisonucleosis
Generally present
f. Mitosis
May be present but are always typical mitosis
Mitotic figures increased and are generally atypical and abnormal
g. Tumor giant cells
May be present but without nuclear atypia
Present with nuclear atypia
h. Cytoplasm
May show normal constituents
Normal cytoplasmic elements are reduced or lost
i. Function
Usually well-maintained
May be retained, lost or becomes abormal
C. Growth rate
Usually slow
Usually rapid
D. Local invasion
Often compresses the surrounding tissue without invading or infiltrating them
Usually infiltrates and invades the adjacent tissues
E. Metastasis
Frequently present
Q. Spread of malignant tumor
A. Spread of malignant tumor is follows:
Local Invasion (Direct Spread)
  • Malignant tumors enlarge by expansion but they cause invasion, infiltration and destruction of the surrounding tissue.
  • They invade via the route of least resistance like tissue spaces or permeate lymphatics, blood vessels, perineural spaces or may penetrate a bone by growing through nutrient foramina.
  • They usually invade thin-walled capillaries and veins than thick-walled arteries.60
Metastasis (Distant Spread)
Metastasis is the spread of tumor by invasion in such a way that discontinuous secondary tumors mass or masses are formed at the site of lodgement or in simple words tumor implants which are discontinuous with the primary tumors. All malignant tumors metastasis barring exception of gliomas of CNS, basal cell carcinoma of the skin. Larger more aggressive and rapidly growing tumors are more likely to metastasis.
Routes of Metastasis
a. Lymphatic spread
In general, carcinoma metastasis by lymphatic route while sarcomas by hematogenous route.
Walls of lymphatics are invaded by cancer cells and may form a continuous growth in the lymphatic channel called lymphatic permeation or may detach to form tumor emboli is to the draining. The tumor emboli are carried by the lymph into the next draining lymph node where it enters at its convex surface and are lodged in the subcapsular sinus. Later the whole lymph node is enlarged.
Generally, regional lymph nodes draining the tumor are invariably involved but sometimes lymphatic metastasis do not develop in the first lymph node because of venous lymphatic anastomoses or skip metastasis obliteration of the lymph vessels due to inflammation or radiation.
Retrograde metastasis due to obstruction of lymphatics by tumor cells is seen in unusual site like metastasis of carcinoma of prostate to supraclavicular lymph nodes.
The first lymph node acts as initial barrier filter and destroy tumor cells while the next lymph nodes provide fertile soil for tumor cell growth.
b. Hematogenuos route
It is the common route for sarcomas but certain carcinomas like those of lungs, breast, thyroid, and kidney and prostate frequently metastasis by this route. Liver, lungs, kidney, brain and bones provide good soil for growth of good seeds and 61are common sites of blood-borne metastasis, wheareas the unfavorable sites are spleen and muscle.
Cancer cell readily invade the thin walls of capillaries and veins than arteries which are thick-walled and contain invasion resistant elastic tissue.
The tumor embolus may occlude a small vessel in the microcirculation, extend through the vessel wall and then establish a metastasis at new site of lodgement. Cancers of organ draining into portal vein establish metastasis in liver and those of draining into systemic circulation in the lungs.
Retrograde meastasis may also occur after venous occlusion like in case of cancers of thyroid and prostate metastasing in vertebral bodies.
Pathology of secondaries (blood-borne)
Gross examination: Multiple rounded nodules of varying size, scattered throughout the organ. Sometimes may be bigger than primary tumor. Also capable of further dissemination.
Microscopic examination: Generally reproduce structure of primary tumor.
c. Other routes
i. Transcelomic spread
Certain cancer invade through the serosal wall of the celomic cavity so that the tumor fragments or clusters of tumor cells break off to be carried in the celomic fluid and are implanted elsewhere. Peritoneal cavity more often affected than pleural and pericardial cavity.
Examples: Stomach and ovary for peritoneal cavity and bronchus and breast for pleural and pericardial cavity.
ii. Along epithelium lined surfaces
Intact epithelium and mucus coat are quite resistant to tumor cell penetration thus this route of spread is unsual.
Exceptionally some malignant tumors may spread through
  • Fallopian tube from the endometrium to ovaries or vice versa.
  • Bronchus into alveoli.
  • Ureters from the kidneys into lower urinary tract.
62iii. Cerebrospinal fluid
Malignant tumors of the ependyma and leptomenings spread by releasing tumors fragments and cells into CSF and produce metastasis at other sites in CNF.
iv. Implantation
Rarely, tumor cells may be implanted to a distant site by surgeon's scalpel, needles, and sutures or may be implanted by direct contact such as transfer of carcinoma of lower lips to the apposing upper lip.
Mechanism of spread
Mechanism of spread of malignant tumor: Number of malignant cells is released into circulation but in this population of monoclonal tumors cells, a subpopulation of clonal tumor cells have the right biological characteristics to establish the metastasis (tumor heterogenicity). These right biological monoclonal malignant tumor cells establish metastasis as follows.
a. Invasion of the basement membrane
The epithelial tumor cells overlying the basement membrane is called carcinoma in situ but once they breach the underlying basement membrane they are termed invasive. The factors preventing the breach in the basement membrane are the adhesion molecules helping epithelial cells to adhere to each other and to other components.
  • Epithelial (E) cadherins (cell-cell adhesion molecule) and cantenins (E cadherins cytoskeleton interaction)
    • Expression of these is reduced or lost in most carcinomas allowing individual malignant cells to loosen up and leave primary tumor.
  • Integrins
    • These are transmembrane receptors causing adhesive interactions between individual tumor cells and in tumor cell components of extracellular matrix interactions.
  • Immunoglobulin Supergene Family
    • It includes intercellular adhesion molecule 1 (ICAM-1), MUC 18, CD 44 and vascular cell adhesion molecule (VCAM-1).
    • 63Expression of ICAM-1, MUC-18 and CD 44 is directly correlated with invasion and metastatic potential of tumours while VCAM-1 is down regulated.
b. Passage through the extracellular matrix
After attaching to the basement membrane tumor cell migrate through it by:
  • Autocrine motility factor (AMF): It is a type of tumor cell cytokine which stimulates receptor mediated motility of tumor cell, increases adehesion of tumor cell to the matrix and release lysosomal enzymes.
  • Proteolytic enzymes: Malignant cells elaborate certain proteolytic enzymes like urokinase type plasminogen activator and matrix metalloproteins (MMP) which degrade component of basement membrane like collagen type IV, laminin and proteoglycans.
c. Invasion of lymphatic and vascular channels
Tumor cells penetrate the lymphatic and vascular channels to reach the systemic circulation but only less 0.1% of malignant cells survive to develop metastasis.
d. Extravasation of tumor cells
Tumor cells in the circulation mechanically block capillaries, venules, lymphatics and attach to the vascular endothelium.
Here again the sequence of invading the basement membrane is repeated to expose the basement membrane.
e. Survival and growth of metastatic deposit
Once in the right environment, extravasated malignant cells grow further under the influence of growth factors produced by the host tissue tumor cells and products developed by the cleavage of the matrix. These are PDGF, FGF and TGF-b (brings about angiogenesis).
Q. Differences between carcinoma and sarcoma.
A. The major differences of both the conditions are as follow:64
Malignant epithelial tumors are called as carcinoma
Malignant mesenchymal tumors are called sarcoma (sarcos = fleshy)
Cells of orgin
Microscopic pattern
Consists of acini's, sheets, column or cord of epithelial cells that may be arranged in solid or papillary pattern
Tumor cell lying separated from each other usually by the intercellular substance such as cartilaginous matrix, osteoid, retculin network, etc.
Common route of
Metastasis Examples
Breast carcinoma, carcinoma of colon, carcinoma of pancreas, etc.
Chondroma, osteosarcoma, soft tissue sarcoma, etc.
Q. Anaplasia
A. Definition: Anaplasia is used to describe the lack of differentiation in the neoplastic cells from the corresponding normal cell in terms of morphological and functional resemblance.
Characters of Anaplasia
Anaplasia is a characteristic feature of most malignant tumors.
The noticeable morphological and functional alternations in an anaplastic cell are as follows:
It means variation in size and shape of the tumor cell. Usually the tumor cells bigger than the normal the degree of the pleomorphism correlates with the degree of anaplasia.
Nucleocytoplasmic Changes
Increased nucleocytoplasmic ratio from 1:5 to 1:1 due to disproportionate increases the size of the nuclei of malignant cell. Nuclei of tumor cell shows variation in size (anisonucleosis) and shape.
65Tumor cell shows hypechromatism, i.e. the nuclei shows large amount of coarsely clumped nuclear chromatin due to increase in the amount of nucleoprotein. This causes dark staining of the nuclei. Even a prominent nucleous is seen in the nuclei. The nuclear shape may vary and nuclear chromatin is clumped along the nuclear membrane.
Large number of mitosis are seen in the neoplastic cells more in the poorly differentiated tumors compared to benign and well-differentiated malignant tumors cells.
Multinucleate tumor giant cell containing a single large and bizarre nucleus possessing nuclear characters of the adjacent tumor cells are another important feature of anaplasia in malignant tumors.
The cytoplasm of tumor cell shows the normal constituents in better differentiated and benign neoplasia but not so in more anaplastic tumors cells.
Genetic Abnormalities
The first tumor cell is perhaps produced by mutation in the original normal cell resulting in abnormal gene. This is transmitted to the progeny during the cell division. The other possible cause of genetic abnormality is activation of a normally suppressed oncogen present in the cell or addition of a new genetic material to the cell by a virus.
The chromosomal abnormalities are more marked in more malignant tumors which often show aneuploidy in form of an increase in the number of chromosomes. This is reflected morphologically by increased size of the nucleus.
The most important example of consistent genetic abnormality associated the neoplasm is 95% chronic myeloid leukemia patients, showing presence of Philadelphia chromosome [translocation of long arm of chromosome 9 to part of long arm of chromosome 22 {t (9; 22)}].
Functional Changes
Structural anaplasia is often accompanied by the functional anaplasia. The functional abnormality can be quantitative or qualitative or both. Generally benign tumors and better 66differentiated malignant tumors continue to function well qualitatively but there may be quantitative abnormality.
In more anaplastic tumors there is usually quantitative abnormally or both qualitative and quantitative abnormality.
Q. Routes of metastasis
A. The routes of metastasis are as follows:
a. Lymphatic spread
In general, carcinoma metastasis by lymphatic route while sarcomas by hematogenous route.
Walls of lymphatics are invaded by cancer cells and may form a continuous growth in the lymphatic channel called lymphatic permeation or may detch to form tumor emboli is the draining. The tumor emboli are carried by the lymph into the next draining lymph node where it enters at its convex surface and are lodged in the subcapsular sinus. Later the whole lymph node is enlarged.
Generally, regional lymph nodes draining the tumor are invariably involved but sometimes lymphatic metastasis do not develop in the first lymph node because of venous lymphatic anastomoses or skip metastasis obliteration of the lymphatics by tumor cells is seen at unusual sites like metastasis of carcinoma prostate to supraclavicular lymph nodes. The first lymph nodes acts as initial barrier filter and destroy tumor cells while the next lymph nodes provide fertile soil for tumor cell growth.
b. Hematogenous route
It is the common route for sarcomas but certain carcinomas like those of lungs, breast, thyroid and kidney and prostate frequently metastasis by this route. Liver, lungs, kidney, brain and bones provide good soil for growth of good seeds and are common sites of blood-borne metastasis, whereas the unfavorable sites are spleen and muscles.
Cancer cell readily invade the thin walls of capillaries and veins than arteries which are thick walled and contain invasion resistant elastic tissue.
The tumor embolus may occlude a small vessel in the microcirculation, extend through the vessel wall and then 67establish a metastasis at the new site of lodgement. Cancers of organ draining into portal vein establish metastasis in liver and those of draining into systemic circulation in the lungs.
Retrograde metastasis may also occur after venous occlusion like in case of cancers of thyroid and prostate metastasing in vertebral bodies.
Pathology of secondaries (blood-borne)
General appearance: Multiple rounded nodules of varying size scattered throughout the organ. Sometimes may be bigger than primary tumor. Also capable of further dissemination.
Microscopic examination: Generally reproduce structure of primary tumor.
c. Other routes
i. Transcoelomic spread
Certain cancers invade through the serosal wall of the celomic cavity so that the tumor fragments or clusters of tumor cells break off to be carried in the coelomic fluid and are implanted elsewhere. Peritoneal cavity more often affected than pleural and pericardial cavity.
Example: Stomach and ovary for peritoneal cavity and bronchus and breast for pleural and pericardial cavity.
ii. Along epithelium lined surfaces
Intact epithelium and mucus coat are quite resistant to tumor cell penetration thus this route of spread is unusual. Exceptionally some malignant tumors may spread through:
  • Fallopian tube from the endometrium to ovaries or vice versa.
  • Bronchus into alveoli.
  • Ureters from the kidneys into lower urinary tract.
iii. Cerebrospinal fluid
Malignant tumors of the ependyma and leptomenings spread by releasing tumors fragments and cells into CSF and produce metastasis at other sites in CNS.
iv. Implantation
Rarely, tumor cells may be implanted to distant site by surgeon's scalpel, needles and sutures or may be implanted 68by direct contact such as transfer of carcinoma of lower lips to the apposing upper lip.
Mechanism of Spread of Malignant Tumor
Number of malignant cells are released into the circulation but in this population of monoclonal tumor cells, a subpopulation of clonal tumor cells have the right biological characteristics to establish the metastasis (tumor heterogenicity). These right biological monoclonal malignant tumor cells establish metastasis as follow:
a. Invasion of the basement membrane
The epithelial tumor cells overlying the basement membrane is called carcinoma in situ but once they breach the underlying basement membrane they are termed invasive. The factors preventing the breach in the basement membrane are the adhesion molecules helping epithelial cells to adhere to each other and to other components.
  • Epithelial (E) cadherins (cell-cell adhesion molecule) and cantenins (E cadherins cytoskeleton interaction)
    • Expression of these is reduced or lost in most carcinomas allowing individual malignant cells to loosen up and leave primary tumor.
  • Integrins
    • These are transmembrane receptors causing adhesive interactions between individual tumor cells and in tumor cell components of extracellular matrix interactions.
    • Immunoglobulin supergene family
    • It includes intercellular adhesion molecule 1 (ICAM-1), MUC 18, CD 44 and vascular cell adhesion molecule (VCAM-1).
    • Expression of ICAM-1, MUC-18 and CD 44 is directly correlated with invasion and metastatic potential of tumours while VCAM-1 is down regulated.
b. Passage through the extracellular matrix
After attaching to the basement membrane tumor cell migrate through it by.69
  • Autocrine motility factor (AMF): It is a type of tumor cell cytokine which stimulates receptor mediated motility of tumor cell, increases adehesion of tumor cell to the matrix and release lysosomal enzymes.
  • Proteolytic enzymes: Malignant cells elaborate certain proteolytic enzymes like urokinase type plasminogen activator and matrix metalloproteins (MMP) which degrade component of basement membrane like collagen type IV, laminin and proteoglycans.
c. Invasion of lymphatic and vascular channels
Tumor cells penetrate the lymphatic and vascular channels to reach the systemic circulation but only less 0.1% of malignant cells survive to develop metastasis.
d. Extravasation of tumor cells
Tumor cells in the circulation mechanically block capillaries, venules, lymphatics and attach to the vascular endothelium.
Here again the sequence of invading the basement membrane is repeated to expose the basement membrane.
e. Survival and growth of metastatic deposit
Once in the right environment, extravasated malignant cells grow further under the influence of growth factors produced by the host tissue tumor cells and products developed by the cleavage of the matrix. These are PDGF, FGF and TGF-b (brings about angiogenesis).
Q. Routes of spread of malignant tumors with examples.
(MUHS Nov/Dec 09)
The routes of spread of malignant tumor (See page no. 59 to 63).
Q. Grading and staging of cancer
A. Importance: Grading and staging are two systems to determine the prognosis and choice of treatment of a malignant cancer.
Grading is defined as the macroscopic and microscopic degree of differentiation of the tumor.
70 A cancer can be graded grossly and microscopically. Gross features like exophytic and fungating appearance are indicative of less malignant growth than diffusely infiltrating tumor. Grading is largely based on two important histological features, the degree of anaplasia and the rate of growth. According to it, broders described a grading system for squamous cell carcinoma but it is applicable to other malignant tumors also.
Broder's grading is as follows:
Grade I Well-differentiated (< 25% anaplastic cells)
Grade II Moderately-differentiated (25–50% anaplastic cells)
Grade III Moderately-differentiated (50–75% anaplastic cells)
Grade IV Poorly-differentiated or anaplastic (>75% anaplastic cells).
However, grading of tumor is subjective and degree of differentiation varies from tumor to tumor. Thus, it is common to grade the tumours as well-differentiated, undifferentiated, keratinizing, nonkeratinizing, etc.
Staging means extent of spread of tumor within the patient. It can be assessed by clinical examination, investigation and histopathologic examination. The important systems of staging are TNM staging and AJC staging. The both systems take into account three criteria for staging any neoplasm is primary tumor, nodal involvement and metastasis.
TNM Staging
It was developed by Union International Center Cancer, Geneva (UICC).
It indicates the three components of staging
T: Primary tumor
N: Regional nodal involvement
M: Distant metastases for each of the components, numbers are added to indicate the extent of involvement.
To to T4: In situ to largest and most extensive primary tumor
No to N3: No nodal involvement to widespread lymph node involvement71
Mo to M2: No metastasis to disseminated hematogenous metastases
AJC Staging
It was devised by American Joint Committee and it also takes into account the three components. It divides all cancers into stage 0 to 4.
Q. Carcinoma in situ.
A. Definition: When the cytological features of malignancy are present but the malignant cells are confined to epithelium without invasion across the basement membrane, it is called the carcinoma in situ or intraepithelial neoplasia (CIN). It is a premalignant lesion requiring urgent detection to prevent subsequent invasive cancer.
Characteristic Features
It is characterized by morphological changes in the cells such as increased nuclear cytoplasmic ratio, pleomorphism of cells and nuclei, increased mitotic activity, poor differentiation and sometimes is accompanied by chronic inflammatory cells.
The involved area may be single and small or multifocal. It may return to normal or develop into invasive cancer. It is formed by a sequential transformation from squamous metaplasia to epithelial dysplasia to carcinoma in situ.
  • Uterine cervix at the junction of ecto and endocervix
  • Bowen's disease of the skin
  • Actinic or solar keratosis
  • Oral leukoplakia
  • Interlobular and intraductal carcinoma of the breast.
Q. Laboratory diagnosis of cancer.
Q. Detection of early cancer (MUHS Nov/Dec 08, May /Jun 10)
A. Laboratory diagnosis of cancer plays an important role in prognosis of cancer as early detection of cancer can have better prognosis. The various methods of detection of cancer are as follows:72
Histological Methods
It is the most reliable and certain method of defection of cancer. It is based on microscopic examination of properly fixed tissue. The tissue can be open and excised tumor mass or needle biopsy from the tumor mass. The diagnosis of cancer is made with support of complete clinical and investigation data. This method has stood test of time in arriving at the correct diagnosis.
Cytological Methods
It is the study of cell morphology of tumor cells. It is of two types.
  1. Exfoliative cytology: The cells are derived for the body cavities into which tumor may shed its cells.
  2. Fine neelde aspiration cytology (FNAC): Here the cells are derived by introducing a needle in the lesion under vacuum.
Histochemistry and Cytochemistry
These are additional diagnostic tools which by use of special stains help to detect the chemical composition and constituents of the cell and their products.
It is an immunological method of recognizing a tumor cell by one or more of its specific components called antigens in the cytoplasm, cell membrane or nucleus. These antigens combine with the specific antibodies produced commercially by monoclonal antibody production leading to formation of immune complexes. These immune complexes of antigen antibody are detected by either fluorescent dyes (fluorochromes) or by enzyme system (chromogens) under light microscope. One special group of such monoclonal antibodies is directed against various classes of intermediatory filaments.
These antibodies are usefull in detection and classification of poorly differentiated epithelial or mesenchymal tumors.
73The common intermediatory filaments and the cancers they help to diagnose are:
Carcinomas, mesotheliomas, germ cell
Sarcomas, melanomas, lymphomas
Myogenic tumors
Neural tumors
Glial fibrillary acidic protein (GFAP)
Glial tumors
Biochemical Assay (Tumor Markers)
Another recent advance in cancer detection is the biochemical assay of tumor markers or the products elaborated by the tumor cells in the blood or other body fluids. These tumor markers are normall secreted by the normal cells also but any persistent rise in the concentration of these is indicative of cancer. The tumor markers can be cell surface antigens, cytoplasmic proteins, enzymes, hormones and cancer antigens.
The commonly detected tumor markers are:
i. Oncofetal antigen
  • Alpha fetoprotein
  • Carcinoembryonic antigen.
ii. Cytoplasmic proteins
  • Immunoglobulins
  • Prostate specific antigen.
iii. Enzymes
  • Prostate acid phosphatase
  • Neuron specific enolase.
iv. Hormones
  • Human chorionic gonadotropin
  • Calcitonin
  • Catecholamines and Vanillyl mandelic acid(VMA).
  • Ectopic hormone production.
v. Secreted cancer antigens
  • Ca - 125
  • Ca - 15-3
Modern Technology
These are as follow:
  1. Flow cytometry
  2. In situ hybridization
  3. Molecular diagnostic techniques.
Q. Tumor markers
A. The another recent advance in cancer detection is the biochemical assay of tumor markers or the products elaborated by the tumor cells in the blood or other body fluids. These tumor markers are normally secreted by the normal cells also but any persistent rise in the concentration of these is indicative of cancer. The tumor markers can be cell surface antigens, cytoplasmic proteins, enzymes, hormones and cancer antigens examples are as follows:
S. No.
Tumor marker
Associated tumor
Oncofetal antigens
i. Alphafetoprotein
Hepatocellular carcinoma, nonseminomatous germ cell tumor of testis
ii. Carcinoembryonic antigen
Cancer of bowel, pancreas and breast
Cytoplasmic proteins
i. Immunoglobulins
Multiple myeloma, other gammapathies
ii. Prostate specific antigen
Prostate cancer
i. Prostate acid phosphatase
Prostate cancer
ii. Neuron specific enolase
Neuroblastoma, oat cell carcinoma of lung
i. Human chorionic gonadotropin
Trophoblastic tumors, nonseminomatous germ cell tumors of testis
ii. Calcitonin
Medullary carcinoma of thyroid
iii. Catecholamines and Vanillyl mandelic acid
Neuroblastoma, pheochromocytoma
iv. Ectopic hormone production
Paraneoplastic syndrome
Secreted cancer antigens
i. Ca–125
ii. Ca-15–3
Tumor markers can be used as an adjunct to the pathological diagnosis. It can be used for prognosis and therapeutic purposes.
Q. Morphology of malignant cells.
The morphology of malignant cell on microscopic examination shows variation in size and shape, i.e. they are usually bigger in size. Nuclei is enlarged, disproportionate the cell size and nucleocytoplasmic ratio is increased from 1:5 to 1:1. Nuclei also show variation in size and shape. Nuclear chromatin is increased and coarsely clumped. Mitotic figures are increased and are generally atypical and abnormal. Normal cytoplasmic elements are reduced or lost.
Q. Virchow's node
A. Definition: Virchow's node is an enlarged, hard, left supraclavicular lymph node which can contain metastasis of visceral malignancy. It is named after Rudolf Virchow (1821–1902), the German pathologist who first described the association. It is also called as signal node or jugular gland malignancies of the internal organs can reach an advanced stage before giving symptoms and of the first visible spots where these tumor metastatize is the left supraclavicular lymph node. The left supraclavicular node is the classical Virchow's node because it is on the left side of the neck that the lymphatic drainage of most of the body enters the venous circulation into the left subclavian vein. Differential diagnosis of an enlarged Virchow's node includes lymphoma and infection.76
Blood Vessels and Lymphatic System
Q. Aneurysms
A. Definition:An aneurysm is a permanent abnormal dilatation of a blood vessels occurring due to congenital or acquired weakening or destruction of vessel wall.
  1. Congenital
  2. Acquired
    1. Infective causes: Syphilis, mycotic
    2. Noninfective causes: Atherosclerosis, cystic medial necrosis, polyarteritis nodosa
    3. Trauma.
a. Depending upon the composition of wall
  1. True aneurysm: All the layers of a normal vessel wall are involved
  2. False aneurysm: Has fibrous wall and occurs following trauma to the vessel.
b. Depending upon the shape
  1. Saccular: Large spherical outpouching
  2. Fusiform: Show spindle-shaped dilatation
  3. Cylindrical: Continuous parallel dilatation
  4. Serpentine or varicose: Tortuous dilatation
  5. Berry: Small dilatation especially affecting circle of Willis.77
c. Based on pathogenic mechanism
  1. Atherosclerotic (most common)
  2. Syphilitic
  3. Dissecting
  4. Mycotic.
Atherosclerotic Aneurysm
It is most common type of aneurysm. Common in males after 50 years of age. Commonly affected vessels are abdominal aorta (most common), ascending aorta, arch of aorta, thoracic aorta, iliac arteries and other large systemic arteries.
Pathogenesis: Severe atherosclerotic lesions cause thinning and destruction of medial elastic tissue resulting in atrophy and weakening of the wall. Medial degeneration is the other additional factor.
Gross Examination
Commonly located below renal arteries above the bifurcation of abdominal aorta but may extend to iliac arteries. Mostly fusiform in shape with mural thrombus in lumen variable in size but often than 5–6 cm in diameter.
Microscopic Examination
Predominance of fibrous tissue in media and adventitia. Mild chronic inflammatory reaction in media and adventitia remnants of atheromatous plaques and mural thrombus in intima and inner part of media.
Clinical Effects
i. Rupture
Most serious and fatal complication. Risk depends upon the size and duration of the aneurysm and blood pressure. Rupture may occur in peritoneum or retroperitoneal resulting in sudden and massive bleeding occasionally, there may be a small leak causing slow, progressive blood loss ruptured aneurysms are more likely to get infected.78
ii. Compression
Aneurysm may compress adjacent structures like ureter or erode vertebral bodies.
iii. Arterial occlusion
Inferior mesenteric artery may get occluded due to aneurysm or there may be development of occlusive thrombosis, however collaterals develop slowly thus ischemia of bowel is uncommon. Thromboembolism is common in abdominal aneurysms.
Syphilitic Aneurysm
Occurs as a complication of syphilitic arteritis in tertiary stage of syphilis. Common in males after 50 years of age. Commonly involved vessels are thoracic aorta especially ascending part and arch of aorta. May extend proximally involving aortic valve causing aortic incompetence and syphilitic heart disease and less often extends distally to abdominal aorta.
Syphilitic arteritis causes inflammatory infiltrate around the vasa vasorum of adventitia followed by endarteritis obliterans. This result in ischemic injury to media causing destruction of smooth muscle and elastic tissue of media and scarring. This results in aneurysm formation.
Gross Examination
Commonly located in ascending part and arch of aorta. Mostly saccular in shape and less often fusiform or cylindrical. Usually 3–5 cm in diameter intimal surface wrinkled and shows tree bark appearance. Aortic valve if involved show stretching and rolling of valve leaflets causing valvular incompetence and left ventricular hypertrophy due to volume overload. Such massively enlarged heart due to volume overload is called cor bovinum.79
Microscopic Examination
Features of healed syphilitic aortitis seen. Fibrous thickening of endarteritis obliterans of vasa vasorum in adventitia, the fibrous scar of which may extend to media and intima. Demonstration of spirochetes is rare. Mural thrombus are often found.
Clinical Effects
i. Rupture
Rupture may occur in pleural or pericardial sac, trachea and esophagus causing massive and fatal hemorrhage.
ii. Compression
Compression of adjacent structures like trachea, esophagus, recurrent laryngeal nerve causing dyspnea, dysphagia or hoarseness of voice respectively or may erode vertebrae, ribs, sternum.
iii. Cardiac dysfunction
Involvement of aortic valve causes aortic incompetence and cardiac failure. Cardiac diseases are further aggravated by narrowing of coronary ostia.
Dissecting Aneurysm
Here the blood enters the dissected vessel wall and spreads for varying distance longitudinally.
Commonly involved vessel is aorta. Commonly involved vessel is aorta. Common in males in the age group of 50–70 years. In women it may occur during pregnancy.
The underlying mechanism is weakening of aortic media which may occur due to:
  1. Hypertension (90%)
  2. Nonhypertensive causes (local or systemic connective tissue disorder).
Marfan's syndrome (genetic defect in fibrillin, a connective tissue protein required for elastic tissue formation), cystic 80medial necrosis of Erdheim, iatrogenic trauma during cardic catheterization or coronary bypass surgery, pregnancy. After development of medical necrosis, hemodynamic factors especially hypertension causes tear in the intima and initiate the dissecting aneurysms splitting the media at its weakest point by the inflowing blood. Medial hemorrhage from the vasa vasorum causing intimal tear followed by entry of blood into the media through intimal tear is another possible mechanism.
Gross Examination
No significant dilatation hence also referred as dissecting hematoma. Classically begins in the arch of aorta. 95% cases show sharply incised, transverse or oblique intimal tear, 3–4 cm long, most often located in the ascending part of the aorta. Dissection is most characteristically located between the outer and middle third of the aortic media such that the blood column is located between intima and inner 2/3rd of the media on one side and outer 1/3rd of media and adventitia on the other side.
The extension of dissection proximally involves the aortic valve ring and distally, the abdominal aorta.
Occasionally, the dissection may extend into the branches of the aorta like arteries of neck, coronaries, renal, mesenteric and iliac. Sometimes the entire circumference of the aorta is involved. 10% cases show, a second false intima tear at the distal end of the dissection from where the blood in false lumen reenters the true lumen, and such cases are termed double barrel aorta.
Group A dissection
Type I (75%): Begins in ascending aorta and extends distally for some distance.
Type II (5%): Limited to ascending aorta. 81
Group B dissection
Type III (20%): Begins in the ascending thoracic aorta near the origin of subclavian artery.
Microscopic Examination
Focal separation of fibromuscular and elastic tissue of the media. Numerous cystic spaces in the media containing basophilic ground substance. Fragmentation of the elastic tissue increased fibrosis of the media.
Clinical Effects
i. Rupture: Causes fatal hemorrhage into the pericardium.
ii. Cardiac disease
  • Aortic incompetence due to involvement of aortic valve
  • Fatal myocardial infarction due to obstruction of coronaries
  • Extension of dissection into the cardiac chambers (rare).
iii. Ischemia
Ischemia of tissues especially. Kidney, brain, spinal cord due to obstruction to the branches of the aorta.
Cardiovascular System
Q. What is rheumatic fever? Describe the etiopathogenesis and pathology of rheumatic heart disease.
A. Definition: Rheumatic heart disease is the major cardiac sequelae involving all the three layers of the heart in the chronic stage of rheumatic fever.
  • It is common in children of age group 5-15 years.
  • Both sexes are affected equally.
  • Seen more commonly in poor socioeconomic strata.
  • Rheumatic fever is seen after throat infection by B hemolytic streptococci of group A.
  • The underlying mechanism is induction of hypersensitivity or autoimmunity.
  • The two components of etiopathogenesis are infective component and autoimmune component.
Infective Component
There is often history of infection of pharynx and upper respiratory tract with the B hemolytic streptococci of Lancefield group A 2–3 weeks prior to attack of rheumatic fever. The 2–3 weeks is the latent period for sensitization to bacteria.
  • Subsequent attacks of streptococci exacerbate the rheumatic fever.
  • 83Outbreaks and epidemics of streptococci infection lead to increased incidence of rheumatic fever.
  • Antibiotics lower the incidence and severity of rheumatic fever and its recurrences.
  • Induction of infection in animals produce similar cardiac lesion.
  • There is elevated titer of antibodies to beta hemolytic streptococci group. A such as anti-streptolycin O, antistreptokinase, anti-streptohyaluronidase and anti-DNAase B.
  • Socioeconomic factors like poverty, poor nutrition, population density, etc. increase the spread of infection and thus increase incidence of rheumatic fever.
  • Population in developing countries develops recurrent throat infections and have higher incidence of rheumatic fever.
  • Incidence of rheumatic fever is higher is subtropical and tropical regions where climatic condition favor spread of infection.
  • There is also individual susceptibility and familial incidences.
  • There is also theory suggesting that infection with a concomitant virus enhances the effect of streptococci.
Autoimmune Component
  • Microorganisms from the active rheumatic lesions have failed to grow.
  • Antigenic products of streptococci in throat are absorbed through the blood vessels and lymphatics and are then distributed to different tissues.
These streptococcal antigens incite autogenously tissues to form autoantibodies which react with specific tissues components to produce lesions.
Evidences in favor of this theory are:
  • Antiheart antibodies detectable in patients of rheumatic fever.
  • Experimental induction in rat's by injecting mixture of killed streptococci and emulsions of target tissues.
Rheumatic fever affects all the three layers of the heart (Rheumatic pancarditis) but intensity of their involvement varies.
Rheumatic Endocarditis
Endocardial lesion may involve valvular endocardium (Rheumatic valvulitis) or mural endocardium (Rheumatic mural endocarditis).
Rheumatic Valvulitis
Gross Examination
Acute rheumatic fever
  • The valves in acute rheumatic fever show thickening and loss of translucency of the valves cusps the leaflets.
  • This is followed by the formation of characteristic, small (1-3 mm in diameter) multiple, warty vegetations or verrucae chiefly along the line of closure of leaflets and cusps.
  • These tiny vegetations are almost continuous so that the free margins of the cusps or leaflets appear as a rough and irregular ridge.
  • The vegetations are gray-brown translucent and are firmly attached so the chances of their detachment to form emboli.
  • The frequency of affection of valves is follows in decreasing order of frequency mitral valve alone, mitral valve and aortic valve combined. The tricuspid and pulmonary valves usually show infrequent and slight involvement.
  • The incidence of vegetation is more on the left side of heart due to greater mechanical stress.
Chronic rheumatic fever
It is characterized by permanent deformity of one or more valves especially mitral and aortic.
The frequency of affection of valves is as follows:
  • Mitral valve alone (65–70%), mitral and aortic combined (25%) and rarely tricuspid and pulmonary.
  • 85The chronic healed valves have characteristic fish mouth or button hole stenosis.
  • It is due to diffuse fibrocollagenous thickening and calcification of the valve cusps or leaflets which cause adhesion between the lateral portions especially in the region of commissures.
  • Thickening shortening and fusion of the chrodae tendineae further contribute to chronic valvular lesion.
Microscopic Examination
  • The inflammatory change begin in the region where valves leaflets are attached to fibrous annulus and then extend throughout the entire leaflet whereas vegetations are usually located on the free margin of the leaflets and cusps.
Acute stage
  • There is the edema of the valve leaflets increased number of capillaries infiltration of lymphocytes, plasma cells, histiocytes with many anitschkow cells and a few polymorphs.
  • Occasionally Aschoff bodies with central foci of fibrinoid necrosis and surrounded by palisade of cardiac histiocytes are seen.
  • Vegetations on the free margins of cusps appear as eosinophilic tiny structures mainly consisting of fibrin with superimposed platelet thrombi and do not contain bacteria.
Chronic stage
  • The vegetations undergo organization.
  • Valves show diffuse thickening as a result of fibrous tissue with hyalinization and often calcification.
  • Vascularization is evident in form of thick-walled blood vessels with narrowed lumen.
  • Typical Aschoff's bodies are rare.
Rheumatic Mural Endocarditic
Gross Examination
  • Most common lesion is MacCallum's patch which is the region of endocardial surface in the posterior wall of the 86left atrium just above the posterior leaflet of the mitral valve.
  • It appears as a map like area of thickened roughened and wrinkled part of endocardium.
Microscopic Examination
  • Affected area shows edema, fibrinoid change in the collagen and cellular infiltrate of lymphocytes, plasma cells and macrophages with many Anitschkow cells.
  • Typical Aschoff bodies may sometimes be found.
Rheumatic Myocarditis
Gross Examination
  • In the early stage, the myocardium especially of the left ventricle is soft and flabby.
  • In the intermediate stage, the interstitial tissue of the myocardium shows small foci of necrosis.
  • Later tiny pale foci of the Aschoff bodies may be visible throughout the myocardium.
Microscopic Examination
  • Presence distinctive of Aschoff bodies is the most characteristic feature of rheumatic myocarditis.
  • They are scattered throughout the interstitial tissue of the myocardium and are most frequent in the interventricular septum, left ventricle and left atrium.
  • Thus there may be derangement of the conductive system.
  • Aschoff bodies are identified in the intermediate stage when they appear as granulomas with central fibrinoid necrosis and are surrounded by palisade of Anitschkow cells and multinucleate Aschoff cells.
  • There is infiltration by lymphocytes plasma cells and some neutrophils.
  • In the late stage the Aschoff bodies are gradually replaced by small fibrous scar in the vicinity of the blood vessels and the inflammatory infiltrate subsides.
Rheumatic Pericarditis
Gross Examination
  • Fibrinous pericarditis the usual finding where normal shiny pericardial surface is lost due to deposition of fibrin on its surface and accumulation of slight amount of fibrinous exudates in the pericardial sac.
  • The appearance is like bread and butter appearance, i.e. resembling the buttered surfaces of two slices in a sandwich if the parietal pericardium is pulled off from the visceral pericardium.
  • If fibrous pericarditis fails to resolve and instead undergoes organization the two layers of the pericardium from fibrous adhesions resulting in chronic adhesive pericarditis.
Microscopic Examination
  • Fibrin can be identified on the surface.
  • Subserosal connective tissue is infiltrated by lymphocytes, plasma cells, histiocytes and a few neutrophils.
  • Characteristic Aschoff bodies may be seen which later undergo organization and fibrosis.
  • Organization of exudate causes fibrous adhesions between the visceral and parietal surfaces of the pericardial sac and obliterates the pericardial cavity.
  • Reactivation and recurrences
  • Myocarditis
  • Arrhythmias due to involvement of conduction system
  • Chronic valvular deformities especially mitral stenosis
  • Cardiac failure
  • Bacterial endocarditis
  • Embolism from mural thrombi in left atrium and its appendages.
Q. Fallot's tetralogy
A. Fallot's tetralogy is the most common cyanotic congenital heart disease.
  • It accounts for 10% of congenital heart disease.
Four features of tetralogy are:
  • Ventricular septal defect (VSD) (shunt)
  • Overriding of the aorta
  • Pulmonary stenosis (obstruction)
  • Right ventricular hypertrophy.
Clinical features(Complications of tetralogy of Fallot's)
  • Of these four features extent of ventricular septal defect and pulmonary stenosis determine the severity of the clinical manifestations.
  • Accordingly there are two forms of tetralogy.
i. Cyanotic tetralogy
Here pulmonary stenosis is greater and the VSD is mild so that there is more resistance to the outflow from the right ventricle resulting in right to left shunt at ventricular level and cyanosis.
The effects are:
  • Pressure hypertrophy of the right atrium and ventricle
  • Small and abnormal tricuspid valve
  • Smaller left atrium and ventricles
  • Enlarged aortic orifice.
ii. Acyanotic tetralogy
Here VSD is larger and pulmonary stenosis is mild so that there is mainly left to right shunt with increased pulmonary flow and increased volume in the left heart but no cyanosis.
The effects are:
  • Pressure hypertrophy of the right ventricles and right atrium
  • Volume hypertrophy of the left atrium and ventricle
  • Enlargement of mitral and aortic orifices.89
Q. Aschoff bodies. (Aschoff nodule)
Q. What is rheumatic fever?Describe Aschoff body in detail.
(MUHS May/June 09)
A. Rheumatic fevers are as follows:
Rheumatic Fever
Rheumatic fever (RF) is a systemic, post-streptococcal, nonsuppurative inflammatory disease, principally affecting the heart, joints, central nervous system, skin and subcutaneous tissue. The chronic stage of RF involves all the three layers of the heart (pancarditis) causing major cardiac sequelae referred to as rheumatic heart disease(RHD).
It is common in children of age group 5–15 years.
  • Both sexes are affected equally.
  • Seen more commonly in poor socioeconomic strata.
Aschoff Body
Aschoff body or aschoff nodule is spheroidal or fusiform structures, pathognomonic feature of pancarditis in rheumatic fever.
They are especially found in the interstitium of heart in the vicinity of small blood vessels in the myocardium and endocardium and occasionally in the pericardium and the adventitia of the proximal part of the aorta.
a. Early (exudative or degenerative) stage
  • By about 4th week of illness, the earliest sign of injury becomes apparent.
  • Initially there is edema of the connective tissue and increase in acid mucopolysaccharide in the ground substance.
  • 90This result in separation of collagen fibers by accumulating ground substance.
  • Eventually, the collagen fibers are fragmented and disintergrated and the affected focus takes the appearance and staining characteristic of fibrin.
  • This is known as fibrinoid degeneration.
b. Intermediate(proliferative or granulomatous) stage
  • This stage is apparent in 4th to 13th week of illness and is pathognomonic of rheumatic condition.
  • There is proliferation of cell resulting in formation of lymphocytes, plasma cells, a few neutrophils and the characteristic cardiac histiocytes or Anitschkow cells at the margin of the lesion.
  • Anitschkow cells are large mononuclear cells having central round nuclei and contain moderate amount of amophilic cytoplasm. The nuclei are vesicular and contain prominent central chromatin mass which appear serrated or caterpillar like on longitudinal section and as a small rounded body in the center of the vesicular nucleus like and owl's eye on cross-section.
  • Modified cardiac histiocytes which contain 1-4 nuclei are called Aschoff cells.
c. Late (healing or fibrous) stage
  • It occurs in about 12–16 weeks after illness.
  • The nodules become oval or fusiform in shape 200 m, wide and 600 mm long.
  • Anitschkow cells become spindle shaped with diminished cytoplasm and the nuclei stain solidly and are arranged in palisaded manner.
  • With passage of time, Aschoff bodies becomes less cellular and the collagenous tissue is increased.
  • Eventually it is replace by a small fibrocollagenous scar with little cellularity frequently located perivascularly.
Q. What are the modified Jone's criteria?
A. Modified Jone's criteria are the criteria devised for the diagnosis of rheumatic fever are as follow:
Jones criteria is divided into major and minor.
a. Major criteria
  1. Carditis
  2. Polyarthritis
  3. Chorea (Sydenham's chorea)
  4. Erythema marginatum
  5. Subcutaneous nodules.
Minor criteria
  1. Clinical findings like elevated ESR, raised C-reactive protein, leukocytosis.
  2. Laboratory findings like elevated ESR, raised C-reactive protein, leukocytosis.
  3. Supportive evidence of preceding group a streptococcal infection like positive throat culture raised streptococcal antibody titer.
    • In a case with antecedent avidence of streptococcal throat infections, presence of any two of the major criteria or occurrence of one major criteria favor the diagnosis of rheumatic fever.
Q. Define cor pulmonale? Describe causes (at least three).
A. Cor pulmonale
Definition: Cor pulmonale or pulmonary heart disease is the disease of the right side of the heart resulting from the disorders of the lungs.
  • Pulmonary embolism
  • Chronic bronchitis
  • Pulmonary tuberculosis
  • 92Pneumoconiosis
  • Cystic fibrosis
  • Hyperventilation in marked obesity (pickwickian syndrome)
  • Multiple organized pulmonary emboli.
Q. MacCallum plaque
A. Definition: Most common lesion in rheumatic mural endocarditis is MacCallum's patch which is the region of endocardial surface in the posterior wall of the left atrium just above the posterior leaflet of the mitral valve. It appears as a map-like area of thickened, roughened and wrinkled part of endocardium.
Microscopic Examination
  • Affected area shows edema, fibrinoid change in the collagen and cellular infiltrate of lymphocytes, plasma cells and macrophages with many anitschkow cells.
  • Typical Aschoff bodies may sometimes be found.
Hematopoietic and Reticuloendothelial System
Q. What is anemia? Describe the etiological classification of anemias.
Mention the findings of the peripheral blood smear, laboratory investigations in megaloblastic anemia.
Q. Causes of anemia   (MUHS Nov/Dec 08, May /June 10)
A. Anemia
Definition: Anemia is defined as a hemoglobin concentration in blood below the lower limit of the normal range for the age and sex of the individual.
  • In an adult, the lower extreme of the normal hemoglobin for males is taken as 13 g/dl and for females as 11.5 g/dl.
Classification of Anemia
  • The two sidely accepted classifications are based on the pathophysiology and morphology. Pathophysiological classification (based on pathophysiological mechanism).
A. Anemia due to increased blood loss
  1. Acute posthemorrhagic anemia
  2. Chronic blood loss.
B. Anemia due to impaired red cell production
  1. Cytoplasmic maturation defects
    1. Deficient hem synthesis: Iron deficiency anemia
    2. Deficient globin synthesis: Thalassemic syndromes.
  2. Nuclear maturation defects
    1. Vitamin B12and folic acid deficiency: Megaloblastic anemia.
  3. 94Defect in stem cell proliferation and differentiation
    1. Aplastic anemia
    2. Pure red cell aplasia.
  4. Anemia of chronic disorders
  5. Bone marrow infiltration
  6. Congenital anemia.
C. Anemia due to increased red cell destruction (hemolytic anemia)
  1. Extrinsic (extracorpuscular) red cell abnormalities
  2. Intrinsic (intracorpuscular) red cell abnormalities.
Morphological Classification
Based on the red cell size, hemoglobin content and red cell indices:
  1. Microcytic, hypochromic anemia
  2. Normocytic, normochromic anemia
  3. Macrocytic, normochromic anemia.
Megaloblastic Anemia
  • Megaloblastic anemia is a disorder caused due to impaired DNA synthesis.
  • It is characterized by distinctively abnormal hemopoietic precursors in the bone marrow in which the maturation of the nucleus is delayed relative to that of the cytoplasm.
Laboratory Diagnosis
Laboratory diagnosis of the megaloblastic anemia can be discussed under two headings:
  1. General laboratory investigations of anemia
  2. Special tests to establish the deficient nutrient either vitamin B12 or folic acid.
A. General laboratory findings
  1. Blood picture and red cell indices95
    Hemoglobin values are below normal.
    Red cells
    Blood picture shows characteristic macrocytosis.
    Basophilic stippling and occasional normoblast may be seen.
    Reticulocyte count
    The reticulocyte count is generally low to normal in untreated cases.
    Absolute values
    Red cell indices show MCV—elevated (above 120 fl) MCH—elevated (above 50 pg) MCHC—normal or reduced.
    Blood film may show characteristic hypersegmented neutrophils.
    Platelet count may be moderately reduced and bizarre forms of platelets may also be seen.
  2. Bone marrow findings
    Marrow cellularity
    The marrow is hypercellular with a decreased myeloid-erythroid ratio.
    The erythroid hyperplasia is due to characteristic megaloblastic erythropoiesis. Megaloblasts are abnormal large, nucleated erythroid precursors, having nuclear cyto-plasmic asynchrony, i.e. the development of cytoplasm exceeds the development of the nucleus or nuclear maturation lags behind that of cytoplasm.
    Other cells
    Giant forms of metamyelo-cytes and band cells may be present.
    Marrow iron
    Erythroid precursors show increase in size and number of iron granules on Prussian blue staining.
  3. 96Biochemical findings
    1. There is rise in serum unconjugated bilirubin and LDH due to marrow cell breakdown.
    2. The serum iron and ferritin may be normal or elevated.
B. Special tests for causes of specific deficiency
The test defects the deficiency of either vitamin B12 or folic acid.
a. Tests for vitamin B12
  • Normal serum level of vitamin B12 is 200–900 pg/ml.
  • Values less than 100 pg/ml indicates clinically deficient stage.
  • The vitamin B12 deficiency can be established by
    1. Microbiological assay
      • The serum sample to be assayed is added to a medium containing all other essential growth factors required for a vitamin B12 dependent microorganism like Euglena gracilis, Lactobacillus leichmannii or Escherichia coli.
      • The medium is incubated and the growth is compared with the growth produced by a known amount of vitamin B12.
    2. Radioassay
      • Assays of serum B12 by radioisotope dilution (PID) and radioimmunoassay (RIA) are more sensitive, simple and more rapid than microbiological assay.
b. Schilling test (radioisotope absorption test)
  • Schilling test defects the deficiency of vitamin B12 and also detects and distinguishes lack of intrinsic factor and malabsorption.
  • The test is performed in three stages
i. Stage I (without intrinsic factor):
  • Oral dose of 0.5–2 mg of radioactively labeled vitamin B12 (hot B12) is administered. A large dose of 4 mg of unlabelled vitamin B12 (cold B12) is administered parenterally after 2 hours to saturate the serum and the tissue binding sites.
Normally more than 7% of 1 mg or oral dose of hot B12 is excreted in 24 hours urine sample.
  • A lower quantity of hot B12 is excreted in case of deficiency of intrinsic factor.
ii. Stage II (with intrinsic factor)
  • In the previous stage if the urinary excretion of hot B12 is low, the test is repeated as in stage I with a high dose of intrinsic factor orally.
  • If the 24 hours urine excretion of B12 is normal then it is interpreted that the cause is deficiency of intrinsic factor.
  • If the excretion of hot B12 is still less than it is a case of pernicious anemia.
iii. Stage III (Test for malabsorption of Vitamin B12
  • Here the protein bound excretion confirm vitamin B12 is used and the urinary excretion hot B12 is checked.
  • A normal urinary excretion confirms the cause as the malabsorption.
C. Tests of folate deficiency
  • The normal range of serum folate is 6–12 mg/ml.
  • Values less than 4 mg/ml are considered diagnostic of folate deficiency.
  • It can be detected by
i. Urinary excretion of formiminoglutamic acid (FIGLU)
  • On oral administration of histidine, urinary excretion of FIGLU is increased in case of folate deficiency, as folic acid is required for conversion of FIGLU to gultamic acid in catabolism of histidine.
ii. Serum folate assay
  • Microbiological assay
    • The test is based on the principle that the folic acid co-enzyme, 5-methyl-tetrahydrofolate is required for growth of Lactobacillus casei.
  • 98Radioassay
    • It is done by radioisotope dilution and is similar to serum B12 assay.
iii. Red cell folate assay
  • Red cells contain 20–50 times more folate than serum and assay by microbiological and radioassay are more reliable indicator of tissue stores of folate than serum folate assay.
Respiratory System
Q. Lobar pneumonia.
Q. Define pneumonia. Describe sequential morphologic changes in lobar pneumonia. (MUHS May/June 08)
Q. What is lobar pneumonia? Describe etiology, stages and gross morphology.
A. Definition: Lobar pneumonia is an acute bacterial infection of a part of lobe, the entire lobe or even two lobes of one or both lungs.
  • Pneumococcal pneumonia
    • Infection by Streptococcus pneumoniae account for more than 90% of cases.
  • Staphylococcal pneumonia (Staphylococcus aureus).
  • Streptococcal pneumonia (β-hemolytic streptococci).
    • In children after measles or influenzae, severely debilitated elderly patients and diabetics.
  • Pneumonia by gram-negative aerobic bacteria.
    • Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas, Proteus, Escherichia coli.
  • Microorganisms gain entry into the lungs by—
    • Inhalation of microbes present in the air.
    • Aspiration of organism from nasopharynx or oropharynx.
    • Hematogenous spread from an adjoining site of infection.
    • Direct spread from an adjoining site of infection.
100Predisposing Factors
  • Altered consciousness
    • In unconscious state, the oropharyngeal content may be aspirated.
  • Depressed cough and glottis reflexes
    • Depression of effective cough many allow aspiration of gastric contents.
  • Impaired mucociliary transport
    • Conditions such as cigarette smoking, viral respiratory infections, immotile cilia syndrome, inhalation of hot or corrosive gases and old age impair the normal protection offered by mucus covered ciliated epithelium in the airways from larynx to the terminal bronchioles.
  • Impaired alveolar macrophage function.
    • Pneumonia may occur when alveolar macrophage function is impaired, e.g. cigarette smoke, hypoxia and starvation pulmonary edema viral respiratory infections.
  • Endobronchial obstruction
    • Endobronchial obstruction by tumor, foreign body, cystic fibrosis and chronic bronchitis interfere with effective clearance mechanism.
  • Leukocyte dysfunction
    • Leukocytic disorders including congenital and acquired immunodeficiencies predispose in pneumonia.
  • Lobar pneumonia involves part of a lobe, a whole lobe or two lobes.
  • Lower lobes are affected most commonly.
  • Laennec's divided pathological process of lobar pneumonia in four sequential phases
  1. Stage of congestion
  2. Red hepatization
  3. Gray hepatization
  4. Resolution.
101a. Stage of congestion (initial phase)
  • This stage lasts for 1–2 days.
  • Represents the early acute inflammatory response to bacterial infection.
Gross examination
  • Affected lobe is enlarged heavy, darkred and congested.
  • Cut surface exudes blood-stained frothy fluid.
Microscopic examination
  • Dilatation and congestion of the capillaries in the alveolar walls.
  • Pale eosinophilic edema fluid in the air spaces.
  • A few red cells and neutrophils in the intra-alveolar fluid.
  • Numerous bacteria in alveolar fluid demonstrated by Gram staining.
b. Red hepatization (early consolidation)
  • This phase lasts for 2–4 days.
Gross examination
Affected lobe is red, firm and consolidated
  • Cut section is airless red pink, dry granular and shows liver like consistency.
  • There is accompanied serofibrinous pleurisy.
Microscopic examination
  • Edema fluid of the initial phase is replaced by strands of fibrin.
  • Marked cellular exudate of neutrophils and extravasation of red cells.
  • Many neutrophils showing ingested bacteria.
  • Less prominent alveolar septa due to cellular exhudation.
c. Gray hepatization (late consolidation)
  • This phase lasts 4–8 days.
Gross examination
  • Affected lobe is firm and heavy.
  • Cut surface is dry granular and gray with liver like consistency.
  • The color change from red to gray is centripetal.
  • Fibrinous pleurisy is prominent.
102Microscopic examination
  • Dense and numerous fibrin strands.
  • Cellular exudates of neutrophils are reduced due to disintegration of many inflammatory cells.
  • Red cells are fewer.
  • Macrophages begin to appear in exhudate.
  • Thin clear space separates cellular exhudate from the septal walls.
  • Organisms are less numerous and appear as degenerated form.
d. Resolution
  • This stage starts by 8th to 9th day and is completed in 1–3 weeks if no treatment is administered.
  • If treatment is administered resolution begins on about 3rd day and proceed in a progressive manner.
Gross examination
  • Solid fibrinous constituent is liquefied by enzymatic action, eventually restoring the normal aeration in the affected lobe.
  • This softening process begins centrally and spreads to the periphery.
  • Cut surface is gray-red or dirty brown and frothy yellow creamy fluid can be expressed on pressing.
  • Pleural reaction undergoes organization leading to fibrous obliteration of pleural cavity.
Microscopic appearance
  • Neutrophils diminish and macrophages predominate.
  • Macrophages contain engulfed neutrophils and debris.
  • Granular and fragmented strands of fibrin are seen in alveolar spaces due to progressive enzymatic digestion.
  • Engorged alveolar capillaries.
  • Progressive removal of fluid content as well as cellular exhudate from air spaces partly by expectoration but mainly by lymphatics resulting in restoration of normal lung parenchyma with aeration.
i. Organization
  • Seen in about 3% cases.
  • Exhudate is organized by ingrowth of fibroblasts from the alveolar septa resulting in fibrosed tough, airless leathery lung tissue.
  • This postpneumotic fibrosis is called carnification.
ii. Pleural effusion
  • Seen in about 5% cases.
  • It is due to inflammation of the pleura.
  • It may resolve or undergo organization with fibrous adhesions between visceral and parietal pleura.
iii. Empyema
  • Seen in less than 1% cases.
  • It is encystment of pus in the pleural cavity.
iv. Lung abscess
  • A rare complication due to secondary infection by other organisms.
v. Metastatic infection
  • Extension of infection into pericardium and heart causing purulent pericarditis, bacterial endocarditis and myocarditis.
  • Otitis media, mastoiditis, meningitis, brain abscesses and purulent arthritis are other metastatic infections.
Q. Bronchopneumonia
A. Definition: Bronchopneumonia or lobular pneumonia is infection of the terminal bronchioles that extend into the surrounding alveoli resulting in patchy consolidation of the lungs.
Gross Examination
  • The patchy areas of red or gray consolidation affecting one or more lobes.
  • 104They are frequently found bilaterally and more often involve lower zones of the lungs due to gravitation of the secretions.
  • On cut surface, patchy consolidations are dry, granular, firm red or gray in color, 3–4 cm in diameter, slightly elevated over the surface and are often centered on a bronchiole.
Microscopic Examination
  • A cute bronchiolitis.
  • Suppurative exudates consisting chiefly of neutrophils in the peribronchiolar alveoli.
  • Thickening of the alveolar septa by congested capillaries and leukocytic infiltration.
  • Less involved alveoli contain edema fluid.
Clinical Features
  • Bronchopneumonia is particularly frequent at extremes of life, i.e. in infancy and old age, as a terminal event in chronic debilitating diseases or as a secondary infection following viral respiratory infection.
  • History of preceding bedridden illness, chronic debility, aspiration of gastric content or upper respiratory infection.
  • Initial 2–3 days show features of acute bronchitis followed by features similar to lobar pneumonia.
Laboratory Findings
  • Neutrophilic leukocytosis on blood examination.
  • Mottled, focal opacities in both lungs in lower zones on X-ray chest.
  • Bronchiectasis due to bronchiolar fibrosis because of some degree of destruction of bronchioles.
  • Complete resolution uncommon.
Q. Differences between lobar and bronchopneumonia.
A. The differences between two are as follows:
Lobar pneumonia
● It is seen as uniform, homogeneous; Nonsegmental consolidation the airways
● It is initially patchy and later distributed along—thus it is segmental and nonhomogeneous
● Unifocal in distribution
● Multifocal in distribution
● Mainly involves distal airspaces and spares distal airways
● Airways are affected by bron-chiolitis. inflammatory involve-ment of airways leads to obstruction, atelectasis and occasionally pneumatocele
● Air bronchogram is seen
● Air bronchogram is not seen
● Airways are patent so there is no volume loss
● Volume loss is seen
● Commonly seen with streptococcal pneumonia
● Commonly seen with staphylococcal aureus pneumonia
Q. What is pathology of TB and what are precautions to be taken by nurses?  (MUHS Nov/Dec 09)
A. Definition: Primary complex also known as Ghon's complex is the tuberculous lesion produced at the portal of entry with foci in the draining lymphatic vessels and lymph nodes.
Sites: The most common sites for primary complex are lungs and hilar lymph nodes.
  • The other sites are tonsils and cervical lymph nodes.
  • In case if the mycobacterium is ingested, the primary complex can be found in small intestine and mesenteric lymph nodes.
Components of Gohn's Focus
The primary complex in lungs consists of three components
a. Pulmonary component
  • Lesion in the lung is the primary focus or Ghon's focus.
  • 106It is a 1–2 cm solitary area of tuberculous pneumonia.
  • It is usually located under the pleura in the lower part of the upper lobe.
  • Microscopically the pulmonary component consists of tuberculous granuloma with caseation necrosis.
b. Lymphatic vessel component
  • The lymphatics draining the pulmonary lesion contain phagocytes containing bacilli and may develop beaded miliary tubercles along the path of the hilar lymph nodes.
c. Lymph node component
  • This consists of enlarged hilar and tracheobronchial lymph nodes in the area drained.
  • The affected lymph nodes are matted and show caseation necrosis.
  • Microscopically, these lesions are characterized by extensive caseation, tuberculous granulomas and fibrosis.
  • These nodal lesions are potential source of reinfection later.
    • In case of primary tuberculosis of alimentary tract due to ingestion of tubercle bacilli, the primary complex is small seen intestine with enlarged mesenteric lymph nodes producing tabes mesenterica.
Nurses and Precaution Against Tuberculosis
Nurses and health visitors are key contributors to locally organized health delivery system, which must aim to reach the people at risk. Tuberculosis is most likely to develop among people in whom the following conditions are present: Malnutrition, alcohol dependency, old age, immunodeficiency including HIV, exposure to dust and silica. It is, therefore, important to develop individual assessment, planning, implementation and evaluation of holistic individual care in a way which is sensitive to individual and cultural needs.
Protection for Cariers
All staff in regular contact with patients and laboratory workers handling specimens are at potential risk to contracting tuberculosis, with a higher risk in those who have regular 107contact with tuberculosis patients or laboratory specimens infected with tuberculosis. AIDS epidemic has led to an increased incidence of tuberculosis in immunocompromised patients, and this may put staff at higher risk of contracting the disease. Staff protection begins with preemployment screening and on employment measures. It also includes the adoption of safe practices for patient care and methods of detecting possible tuberculosis infection in staff at an early stage. Preemployment and onemployment measures include recording any symptoms of tuberculosis, details of previous BCG vaccination and the presence or absence of a BCG scar and tuberculin skin testing and chest radiography. A tuberculin skin test is only necessary in new employees who do not have a definite BCG scar, virtually all those with a BCG scar have positive skin test even after many years. Recent evidence confirms that strongly positive tuberculin skin reactions are common in asymptomatic health care workers and does not indicate active tuberculosis. The requirement of chest radiography should not be based on tuberculin-test, but rather on the presence of symptoms after careful enquiry. Routine periodic chest radiography is not necessary for any group of staff and is not effective in early detection of tuberculosis. Staff concerned should be reminded of the possible symptoms of tuberculosis and the importance of reporting such symptoms promptly. Staff should be encouraged to report HIV infection to the department so that they can receive advice about any modification to their work. As they become immunocompromised, they should be offered a move away from work with a high-risk of infection, such as onwards with numerous patients with tuberculosis or laboratory work with known tuberculosis material. Proper infection control measures are important in protecting staff on employment. These include isolation of infectious patients, as previously described and minimal staff presence with adequate ventilation during activities like sputum induction during all procedures of analysis and management.108
Gastrointestinal Tract
Q. Give differences between a peptic, gastric and duodenal ulcer and natural ways to deal with it.
Q. Give the distinguishing features between gastric peptic ulcer and duodenal peptic ulcer. (MUH May/Jun 08)
A. Gastric ulcer: Ulceration of the gastric mucosa due to contact with gastric juice. It is often associated with Helicobacter pylori infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDs).
Symptoms are:
  1. Recurrent abdominal pain which is dull and burning type pain usually located in epigastric area (area between belly button and rib cage)
  2. Abdominal pain after food
  3. Abdominal pain at night
  4. Blood in vomit
  5. Nausea
  6. Anorexia
  7. Black stools
  8. Fatigue
  9. Breathlessness.
The list of conventional treatments are:
  • Symptomatic relief: Antacid preparations
  • Antiacid medications: “Proton-Pump” inhibitors (e.g. omeprazole, lansoprazole), H2 antagonists (e.g. ranitidine, cimetidine)
  • Eradication of Helicobacter pylori infection: Oral antibiotics, proton pump inhibitor
  • Avoidance of NSAID medications (e.g. aspirin, ibuprofen, nurofen, brufen, etc.)
  • Surgery: Partial gastrectomy.109
Peptic Ulcers
A peptic ulcer is a sore on the lining of the stomach or duodenum, which is the beginning of the small intestine.
List of causes or underlying conditions:
  1. Helicobacter pylori bacteria
  2. Excess stomach acid
  3. Stomach cancer
  4. Pancreatic cancer
  5. GERD—a cause of esophageal ulcers
  6. Zollinger-Ellison syndrome.
Treatments for Gastrointestinal Bleeding
Emergency treatment: If gastrointestinal bleeding from a bleeding ulcer is suspected.
  • Blood transfusions
  • See also treatment of anemia because anemia can result from gastrointestinal bleeding and its blood loss.
  • Discontinue causative medications for NSAIDs and other secondary causes
  • Antibiotics: Mainly for the treatment of H. pylori infections.
Natural Methods of Treatment
  • Lifestyle changes
  • Diet changes
  • Avoid ulcer triggering foods
  • Avoid spicy food
  • Avoid fatty foods
  • Avoid alcohol
  • Avoid caffeine
  • Quit smoking
  • Reduce stress
Duodenal Ulcer
A peptic ulcer located in the duodenum.
Some of the possible causes of duodenal ulcer include:
  • Excess stomach acid
  • Helicobacter pylori bacteria
  • Mostly similar to symptoms of peptic ulcers
  • 110Abdominal pain
  • Abdominal pain after meals
  • Pain below the ribs
  • Gastrointestinal bleeding.
Q. What is peptic ulcer? Describe the sites, pathogenesis, pathology and complications of chronic gastric ulcer.
A. Definition: Peptic ulcers are the areas of degenerations and necrosis of gastrointestinal mucosa exposed to acid peptic secretions.
  • They can occur at any level of the alimentary tract that is exposed to hydrochloric acid and pepsin.
  • However, they occur most commonly (98–99%) in either the duodenum or the stomach in ratio of 4:1.
Gastric Ulcers
Ulcers occurring in the stomach due to exposure to acid peptic secretions are the gastric ulcers.
  1. Acute
  2. Chronic.
Acute Gastric Ulcer
Acute peptic ulcer or acute stress ulcer are multiple, small mucosal erosions.
It is seen commonly in the stomach and occasionally in the duodenum.
a. Psychological stress
b. Physiological stress
  1. Shock
  2. Severe trauma
  3. Septicemia
  4. 111Extensive burns (Curling's ulcer)
  5. Intracranial lesions (Cushing's ulcer)
  6. Drug intake (Analgesics, steroids)
  7. Local irritants (Alchohol, smoking, coffee).
  • Ischemic hypoxic injury to mucosal cells
  • Depletion of gastric mucus barrier rendering the mucosa susceptible to attack by acid–peptic secretions.
Gross Examination
  • Acute stress ulcers are multiple.
  • Common anywhere in stomach followed in decreasing frequency by occurrence in first part of duodenum.
  • Oval or circular in shape and less than 1 cm in diameter.
Microscopic Examination
  • Ulcers are shallow and do not ivade the muscular layer.
  • Margins and base show some inflammatory reaction.
  • Heal by complete reepithelialization without leaving any scar.
Chronic Gastric Ulcer
  • Chronic gastric ulcer is one of the forms of peptic ulcer disease of the upper GI tract.
  • Pathogenesis of gastric ulcer is mainly based on the impaired gastric mucosal defenses against acid-pepsin secretions.
  • May also occur due to hyperacidity because of increased serum gastrin levels in response to ingested food in an atonic stomach.
  • Damaging influences of other factors such as gastritis, bile reflux, cigarette smoke, etc. may also play a role in ulcerogenesis.
  • In gastric ulcer, the normally protective gastric mucus barrier against acid pepsin is deranged. There is qualitative and quantitative depletion of the gastric mucus.
  • 112H. pylori infection seen in 75–80% patients plays an important role in pathogenesis of gastric ulcer as follows
    • H. pylori secrete a urease, which generates free ammonia and a protease which breaks down glycoprotein in the gastric mucus. It also elaborates phospholipases, which damaged the surface epithelial cells.
    • The free ammonia stimulates gastrin release thereby increasing acid.
    • H. pylori attracts neutrophils. These neutrophils release myeloperoxidase which produce hypochlorous acid yielding monochloramine in presence of ammonia. Both these hypochlorous acid and monochloramine destroy the mammalian cells.
    • Both mucosal epithelial cells and lamina propria endothelial cells are prime targets for the destructive action of H. pylori colonization.
    • H. pylori antigens recruit inflammatory cells to the mucosa thus damaging it and making it susceptible to acid injury.
    • Increased parietal cell mass, increased sensitivity to secretory stimuli, increased basal acid secretory drive or impaired inhibition of stimulatory mechanism such as gastrin release.
    • Finally damage to mucosa permits leakage of tissues nutrients into the surface microenvironment thereby sustaining the bacillus.
  • Chronic use of NSAIDs suppresses mucosal prostaglandins synthesis and aspirin acts as direct irritant.
  • Chronic gastric ulcers are found predominantly along the lesser curvature in the region of pyloric antrum, more commonly on the posterior than the anterior wall.
  • Uncommon location is cardia.
Gross Examination
Typical ulcers are commonly solitary (80%) small (1–2.5 cm in diameter), round to oval and characteristically punched out.
  • Benign gastric ulcers usually have flat margins in level with the surrounding mucosa.
  • 113The mucosal folds converge towards the ulcer.
  • The ulcers vary in depth from being superficial to deep.
  • Malignant gastric ulcers are larger, bowl shaped with elevated and indurated mucosa at the margin.
  • Malignant gastric ulcers are larger, bowl shaped with elevated and indurated mucosa at the margin.
Microscopic Examination
Chronic gastric ulcer has following four histological zones from within outside.
i. Necrotic zone
  • It lies on the floor of the ulcer and is composed of fibrinous exudates containing necrotic debris and a few leukocytes.
ii. Superficial exudative zone
  • It lies underneath the necrotic zone.
  • The tissue elements here show coagulative necrosis giving eosinophilic smudgy appearance with nuclear debris.
iii. Granulation tissue zone
  • It is seen merging to the necrotic zone.
  • It is composed of nonspecific inflammatory infiltrate and proliferating capillaries.
iv. Zone of cicatrization
  • It is seen merging into thick layer of granulation tissue.
  • It is composed of dense fibrocollagenic scar tissue over which granulation tissue rests.
  • Thrombosed or sclerotic arteries may cross the ulcer which on erosion results in hemorrhage.
Complications of Peptic Ulcer
  • Acute and subacute peptic ulcers usually heal without leaving any visible scar.
  • Complications are produced due to chronic, larger and deeper ulcers.
a. Obstruction
  • Fibrous scarring at or near the pylorus results in pyloric stenosis.
  • Healed duodenal ulcers cause duodenal stenosis.
  • 114Healed ulcers along the lesser curvatures produce hour glass deformity due to fibrosis and contraction.
b. Hemorrhage
  • Erosion of small blood vessels in the ulcer base results in minor bleeding.
  • Chronic blood loss may result in iron deficiency anemia.
  • Severe bleeding may cause coffee ground vomitus or melena.
  • A penetrating chronic ulcer may erode a major artery like left gastric, gastroduodenal or splenic artery and causes a massive and severe hematemesis and sometimes death.
c. Perforation
  • Perforation occurs more commonly in chronic duodenal ulcers than chronic gastric ulcer.
  • A perforation may result in
    • Escape of contents of stomach into the lesser sac or into the peritoneal cavity causing acute peritonitis.
    • Escapes of air from the stomach and to be lied between the liver and the diaphragm (air under the diaphragm on X-ray).
    • Subphrenic abscess between the liver and the diaphragm due to infection.
    • Extension to involve the adjacent organs like liver, pancreas.
d. Malignant transformation
  • Cancer ulcerates but ulcers rarely cancerate.
  • A chronic duodenal ulcer never turns malignant.
  • While less than 1% of chronic gastric ulcer may transform into carcinoma.
Q. Acute appendicitis
A. Definition: Acute appendicitis is the acute inflammation of the appendix.
a. Obstructive causes
  • Fecolith
  • Calculi
  • Foreign body
  • Tumor
  • Worms especially Enterobius vermicularis
  • Diffuse lymphoid hyperplasia especially in children.
b. Nonobstructive causes
Hematogenous spread of generalized infection
  • Vascular occlusion
  • Inappropriate diet lacking roughage.
  • Obstruction of the lumen
  • Increased intraluminal pressure
  • Pressure on the blood vessels
  • Ischemic injury
  • Bacterial proliferation
  • Acute appendicitis.
Gross Examination
• Early acute appendicitis
  • Organ is swollen and serosa shows hyperemia.
• Acute suppurative appendicitis
  • Serosa is coated with fibrinopurulent exudate and engorged vessels on the surface.
• Acute gangrenous appendicitis
  • Necrosis and ulcerations of mucosa which extend through the wall so that the appendix becomes soft and friable and surface is coated with greenish black gangrenous necrosis.
Microscopic Examination
  • Neutrophilic infiltration of the muscularis.
  • 116Congestion and edema of appendiceal wall in early stage.
  • Mucosa is sloughed off and wall becomes necrotic, blood vessels may get thrombosed and neutrophilic abscesses in wall in later stages.
  • Impacted foreign body, fecolith or concretions may be seen in the lumen.
Clinical Features
  • Acute appendicitis is an important acute abdominal condition seen commonly in older children and young adults.
  • Clinical presentation is colicky pain, initially around umbilicus but later localized to right iliac fossa
  • Nausea and vomiting
  • Pyrexia of mild grade
  • Abdominal tenderness
  • Increased pulse rate
  • Neutrophilic leukocytosis
  • Peritonitis
  • Appendix abscess
  • Adhesions
  • Portal pylephlebitis
  • Mucocele.
Q. Write in brief the Barrett's esophagus.
A. Definition:Barrett's esophagus is the condition of esophagus where the stratified epithelium of the lower esophagus is replaced by columnar epithelium.
  • Irritation of esophageal mucosa by gastric acid due to reflux esophagitis.
Gross Examination
  • Affected area is red and velvety.
  • It is frequently associated with hiatus hernia and peptic ulcer at squamocolumnar junction called Barrett's ulcer.
Microscopic Examination
  • Replacement of squamous epithelium columnar cells.
  • Barrett's esophagus may be composed of
    • Intestinal epithelium
    • Fundic gastric glands
    • Cardia mucous glands.
  • Other cells present in the glands are Paneth cells, goblet cells, chief cells, parietal cells, mucous secreting cells and endocrine cells.
  • Commonly accompanied by acute or chronic inflammatory cells.
  • Dysplastic changes of the columnar epithelium or glands may be present.
  • It is a premalignant condition showing dysplastic changes or 5–8% cases have risk of developing into adenocarcinomia.
Q. Difference between (macroscopic) benign and malignant gastric ulcer.
A. The following are the differences in two categories:
Benign gastric ulcer
Malignant gastric ulcer
● Solitary, small, round to oval with flat
● Larger bowl shaped with elevated end
● Margins in level with the surrounding
● Indurated mucosa at the margins
● Mucosa and mucosal folds converge
● Towards the ulcer.
Liver, Biliary Tract and Pancreas
Q. Define cirrhosis. Describe classification. Mention pathology and complications of alcoholic cirrhosis.
A. Definition: Cirrhosis is a diffuse liver disease having following five features:
  • It involves the entire liver.
  • The normal lobular architecture of hepatic parenchyma is disorganized.
  • The normal lobular architecture of hepatic parenchyma is disorganized.
  • There is formation of nodules separated from one another by irregular bands of fibrosis.
  • It occurs following hepatocellular necrosis of varying etiology so that there are alternate areas of necrosis and regenerative nodules.
  • Cirrhosis can be classified on the basis of morphology and etiology.
a. Morphological classification
  • There are three morphological types of cirrhosis each having an active form and an inactive form.
  • Active form is characterized by continuing hepatocellular necrosis and inflammatory reaction.
  • Inactive form has no evidence of continuing hepatocellular necrosis and has sharply defined nodules of surviving hepatic parenchyma without any significant inflammation.
i. Micronodular cirrhosis
  • Nodules are usually regular and small less than 3 mm in diameter
  • 119Diffuse involvement of all the hepatic lobules.
  • Nodules are formed by thick fibrous septa either portal-portal, portal-central or both.
ii. Macronodular cirrhosis
  • Nodules are of variable size and are larger than 3 mm in diameter.
  • Involvement is more irregular sparing some portal tracts and central veins.
  • There is more marked evidence of regeneration.
iii. Mixed cirrhosis
  • Some parts show micronodular appearance while other part shows macronodular appearance.
  • Some of the central veins and portal tracts are spared.
b. Etiological classification:
  1. Alcoholic cirrhosis
  2. Postnecrotic cirrhosis
  3. Biliary cirrhosis
  4. Pigment cirrhosis in hemochromatosis
  5. Cirrhosis in Wilson's disease
  6. Cirrhosis in α-1 antitrypsin deficiency
  7. Cardiac cirrhosis
  8. Indian childhood cirrhosis
  9. Miscellaneous forms of cirrhosis
  10. Cryptogenic cirrhosis.
Alcoholic cirrhosis
  • Alcoholic cirrhosis is the most common form of lesion, constituting 60–70% of all cirrhosis cases.
  • It is also known as Laennec's cirrhosis, portal cirrhosis, hobnail cirrhosis, nutritional cirrhosis, diffuse cirrhosis and micronodular cirrhosis.
Gross Examination
  • It classically begins as micronodular cirrhosis (nodules 3 mm diameter).
  • Liver is large, fatty and weighs above 2 kg.
  • 120Over the years, it's shrinks to less than a kilo and becomes nonfatty.
  • It becomes macronodular cirrhosis (nodules 3 mm in diameter).
  • The nodules are tawny-yellow due to their fat content.
  • The liver surface is studded with diffuse nodules varying little in size producing hobnail liver.
  • On cut section, spheroid or angular nodules of fibrous septa are seen.
Microscopic Examination
  • Alcoholic cirrhosis is a progressive alcoholic liver disease.
  • It's microscopic features are
    • Lobular architecture
    • No normal lobular architecture can be identified
    • Central veins are hard to find.
  • Fibrous septa
  • Initially the fibrous septa dividing the hepatic parenchyma into the nodules are delicate and extend from central vein to portal regions or portal tract to portal tract or both.
  • As the fibrous scarring increases with time the fibrous septa become dense and more confluent.
  • Hepatic parenchyma.
  • Hepatocytes in tne islands of surviving parenchyma undergo slow proliferation forming regenerative nodules having disorganized masses of hepatocytes.
  • Within the nodule, the hepatic parenchyma shows extensive fatty changes early in the disease.
  • Fat in the hepatocytes reduces as septa become thicker.
  • Thus, there exists an inverse relationship between the fat and the fibrous scarring in the nodules.
  • Necrosis, inflammation and bile duct proliferation
  • Etiological clue in form of mallory bodies are hard to find.
  • Fibrous septae contain spare infiltrate of mononuclear cells with some bile duct proliferation.
  • 121Other findings are bile stasis and increased cytoplasmic hemosiderin deposits because of enhanced iron absorption.
The complications which are developed in advanced stages are as follows:
  • Portal hypertension and its major effect like ascites, splenomegaly and portosystemic anastomosis
  • Progressive heart failure
  • Hepatocellular carcinoma
  • Chronic relapsing pancreatitis
  • Steatorrhea
  • Gallstone
  • Infection
  • Hematological derangements, i.e. bleeding disorder and anemia.
  • Cardiovascular, i.e. atherosclerosis and myocardial infarction.
  • Abnormalities of musculoskeletal system, i.e. digital clubbing, hypertrophic osteoarthropathy, Dupuytren's contracture.
  • Endocrine disorder
  • Male: Gynecomastia, testicular atrophy, impotence, changes in pattern of pubic hair.
    Female: Amenorrhea
  • Hepatorenal syndrome.
  • Hepatic coma.
  • Massive GIT hemorrhage.
  • Death.
Q. Amoebic liver abscess (short answers)
    • It is caused by Entamoeba histolytica, a protozoan.
    • The source of infection is the intestinal lesions or flask-shaped ulcers by the trophozoites which are carried to liver by the portal vein.
    • Amoebae multiply and block small intrahepatic portal radicals resulting in infarction necrosis of the adjacent liver parenchyma.
Gross Examination
  • Usually solitary and more often located in the right lobe in the posterosuperior portion.
  • Vary in size greatly but generally are size of orange.
  • Center contains large necrotic area having reddish-brown, thick pus resembling anchovy or chocolate sauce.
  • Abscess wall consists of irregular shreds of necrotic liver tissue.
Microscopic Examination
  • Necrotic area contains degenerated liver cells, leukocytes, red blood cells and strads of connective tissue and debris.
  • Amoebae are found in the margin of the abscess, not in center or in pus.
Clinical Features
  • Patient is from tropical and subtropical country with history of amoebic dysentery.
  • Intermittent low grade fever, pain and tenderness in the liver area.
Laboratory Findings
  • Cysts of E. histolytica in feces of 15% patients.
  • Positive hemagglutination test.
Q. Tabulate the differences between prehepatic and posthepatic jaundice.
Prehepatic jaundice
Posthepatic jaundice
Laboratory findings
a. Blood
i. Total serum bilirubin
ii. (Direct) conjugated
iii. (Indirect) unconjugated
iv. Serum alkali phosphatase
b. Urine
i. Urobilinogen
ii. Bile pigments
iii. Conjugated bilirubin
c. Stool
Yellow or dark
brown colored
Clay colored
Q. Discuss fatty liver in detail. (MUHS May/June 08)
A. Definition: Fatty liver disease can range from fatty liver alone (steatosis) to fatty liver associated with inflammation (steatohepatitis). This condition can occur with the use of alcohol (alcohol-related fatty liver) or in the absence of alcohol [nonalcoholic fatty liver disease (NAFLD)].
Fatty liver disease is now the most common cause for elevated liver function tests in the United States. This is mainly due to the ongoing obesity epidemic in the United States.
Fatty liver can be associated with the use of alcohol. This may occur with as little as 10 oz of alcohol ingested per week. Identical lesions also can be caused by other diseases or toxins.
If steatohepatitis is present but a history of alcohol use is not, the condition is termed as nonalcoholic steatohepatitis (NASH). Fatty change in the liver results from excessive accumulation of lipids within hepatocytes. Simple fatty liver is believed to be benign, but NASH can progress to cirrhosis and can be associated with hepatocellular carcinoma. The main risk factors for simple fatty liver (NAFLD) and NASH are obesity, diabetes and high triglyceride levels.
Fatty liver is the accumulation of triglycerides and other fats in the liver cells. In some patients, this may be accompanied by hepatic inflammation and liver cell death (steatohepatitis).
Potential pathophysiological mechanisms include the following: (1) Decreased mitochondrial fatty acid betaoxidation, (2) Increased endogenous fatty acid synthesis or enhanced delivery of fatty acids to the liver, and (3) Deficient incorporation or export of triglycerides as very low-density lipoprotein.
Steatosis affects approximately 25–35% of the general population. Steatohepatitis may be related to alcohol-induced hepatic 124damage or may be unrelated to alcohol (i.e. NASH). NASH has been detected in 1.2–9% of patients undergoing routine liver biopsy. NAFLD is found in over 80% of patients who are obese. Over 50% of patients undergoing bariatric surgery have NASH.
Australian studies show less intense disease progression than studies in the United States. Asian studies reveal NASH and NAFLD at lower body mass indexes (BMIs).
A natural history study from Olmsted County, Minnesota, revealed that 10% more patients with NAFLD died versus control subjects over a 10-year period. Malignancy and heart disease were the top 2 causes of death. Liver-related disease was the third cause of death (13%), as compared to the 13th cause of death (<1%) for control subjects.
  • Steatosis was once believed to be a benign condition, with rare progression to chronic liver disease. Steatohepatitis may progress to liver fibrosis and cirrhosis and may result in liver-related morbidity and mortality.
  • Fibrosis or cirrhosis in the liver is present in 15–50% of patients with NASH. Approximately 30% of patients with fibrosis develop cirrhosis after 10 years. Many cases of cryptogenic cirrhosis may represent so-called burnt-out NASH because a high proportion is associated with obesity, type II diabetes or hyperlipidemia.
  • Some patients with drug-induced fatty liver present dramatically with the rapid evolution of hepatic failure. Some patients with inborn errors of metabolism, such as tyrosinemia, may rapidly progress to cirrhosis.
Fatty liver has been found across all races, but most of the research and the highest prevalence appear in the Caucasian race.
A small study evaluating fatty liver disease in the Indian population found its association with the nonobese and its recovery with simple lifestyle habits. However, obesity, when 125present, was a significant risk factor for NASH in Indians as well as in Koreans.
Interestingly and as supported in the author's clinical practice, Asian patients often develop NAFLD and NASH at normal BMIs, but BMIs on the higher range for a patient's ethnicity. A diagnosis of cirrhosis in an 80-year-old, 5-foot, 110-lb Asian female, with a BMI of 21, is not unusual. Mutations for hemochromatosis appear to put Caucasians at a higher risk of more advanced fibrosis.
  • As many as 75% of patients in initial reported studies were females.
  • In more recent studies, 50% of patients are females.
  • Fatty liver occurs in all age groups.
  • NAFLD is the most common liver disease among adolescents in the United States. Older age often is predictive of more severe grading of fibrosis.
  • NASH is the third most common cause of chronic liver disease in adults in the United States (after hepatitis C and alcohol). It is now probably the leading reason for mild elevations of transaminases.
  • NASH has recurred within 6 months after pediatric or adult liver transplant.
  • Most patients with fatty liver are asymptomatic. However, if questioned, more than 50% of patients with fatty liver or NASH report persistent fatigue, malaise, or upper abdominal discomfort.
  • Symptoms of liver disease, such as ascites, edema, and jaundice, may arise in patients with cirrhosis due to progressive NASH. Laboratory abnormalities during blood donations or life insurance physical examinations often reveal elevated alanine aminotransferase (ALT) levels and ultimately lead to the diagnosis of fatty liver disease.
  • Hepatomegaly is common.
  • Splenomegaly and stigmata of portal hypertension (e.g. ascites, edema, spider angiomas, varices, gynecomastia and menstrual disorders) may occur in patients with cirrhosis.
  • Patients with drug-induced fatty liver may present with rapid fulminant liver failure.
  • In patients who abuse alcohol, extrahepatic effects, such as skeletal muscle wasting, cardiomyopathy, pancreatitis, or peripheral neuropathy may be present.
The most common association with fatty liver disease is metabolic syndrome. This includes carrying the diagnosis of type II diabetes, obesity, and/or hypertriglyceridemia. Other factors, such as drugs (e.g. amiodarone, tamoxifen, methotrexate), alcohol, metabolic abnormalities (e.g. Galactosemia, glycogen storage diseases, homocystinuria, tyrosinemia), nutritional status (e.g. overnutrition, severe malnutrition, total parenteral nutrition [(TPN), starvation diet], or other health problems (e.g. celiac sprue, Wilson disease) may contribute to fatty liver disease. There are reports of lean NASH families.
Q. Describe the tests which should be done in case of hepatitis. (MUHS Nov/Dec09)
A. Definition: The hepatitis virus panel is a series of blood tests used to detect current or past infection by hepatitis A, hepatitis B, or hepatitis C. It can screen blood samples for more than one kind of hepatitis virus at the same time.
Antibody and antigen tests can detect each of the different hepatitis viruses.
Note: Hepatitis D only causes disease in people who also have hepatitis B. It is not routinely checked on a hepatitis antibody panel.
How the Test is Performed?
Blood is typically drawn from a vein, usually from the inside of the elbow or the back of the hand. The site is cleaned with 127germ-killing medicine (antiseptic). The health care provider wraps an elastic band around the upper arm to apply pressure to the area and make the vein swell with blood.
Next, the health care provider gently inserts a needle into the vein. The blood collects into an airtight vial or tube attached to the needle. The elastic band is removed from your arm. Once the blood has been collected, the needle is removed and the puncture site is covered to stop any bleeding.
In infants or young children, a sharp tool called a lancet may be used to puncture the skin and make it bleed. The blood collects into a small glass tube called a pipette, or onto a slide or test strip. A bandage may be placed over the area if there is any bleeding.
The blood sample is sent to a laboratory for examination. Blood (serology) tests are used to check for antibodies to each of the hepatitis viruses.
Preparation for the Test
No special preparation is needed. When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.
Test is Performed
When the doctors do feels signs of hepatitis. It is advised and usefull to
  • Detect current or previous hepatitis infection.
  • Determine how contagious a person with hepatitis.
  • Monitor a person who is being treated for hepatitis.
Other conditions under which the test may be performed
  • Chronic persistent hepatitis
  • Delta agent (hepatitis D)
  • Nephrotic syndrome.
Normal Results
A normal result means no hepatitis antibodies are found in the blood sample. This is called a negative result.
128Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.
What Abnormal Results Mean
There are different tests for hepatitis A and B. A positive test is considered abnormal.
Abnormal results on hepatitis A tests
  • IgM antihepatitis A virus (HAV) antibodies: Recent infection with hepatitis A
  • Total (IgM and IgG) antibodies to hepatitis A: Previous or current infection, or immunity to hepatitis A.
Abnormal results on hepatitis B tests
  • Hepatitis B surface antigen (HBsAg): Acute or chronic hepatitis B infection
  • Antibody to hepatitis B core antigen (Anti-HBc): Previous hepatitis B infection
  • Antibody to HBsAg (Anti-HBs): Immunity to hepatitis B
  • Hepatitis B type E antigen (HBeAg): Chronic, contagious hepatitis B infection or acute infection.
Antibodies to hepatitis C can usually be detected 4–10 weeks after the infection occurs.
Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.
Other risks associated with having blood drawn are slight but may include:
  • Excessive bleeding
  • Fainting or feeling light-headed
  • Hematoma (blood accumulating under the skin)
  • Infection (a slight risk any time the skin is broken).129
Kidney and Lower Urinary Tract
Q. Describe the etiopathogenesis, gross and microscopy of chronic pyelonephritis.
A. Definition: Chronic pyelonephritis is a chronic tubulointerstitial disease resulting from repeated attacks of inflammation and scarring.
  • There are two types of chronic pyelonephritis, depending upon the etiopathogenesis.
a. Reflux Nephropathy
  • Major cause of chronic pyelonephritis is reflux of urine from the bladder into one or both the ureters and during micturition (vesicoureteric reflux).
  • It is particularly common in children especially in girls due to congenital absence or shortening of the intravesical portion of the ureter so the ureter is not compressed.
During micturition
  • Because of the reflux, the pressure in the renal pelvis is increased so that the urine is forced into renal tubules which eventually followed by damage to the kidney and scar formation.
  • Even bacterial infection can ascend into the kidneys by vesicoureteric reflux in patients with urinary tract infection.
b. Obstruction Pyelonephritis
  • Obstruction to the outflow of urine predisposes kidney to infection due to stasis of urine.
  • Recurrent obstruction and inflection results in renal damage and scarring.
  • Rarely even recurrent attacks of acute pyelonephritis may cause renal damage and scarring.
Gross Examination
  • The affected kidneys are usually small and contracted showing unequal reduction and weighs less than 100 gm.
  • The kidney surface is irregularly scarred and the capsule can be stripped off with the difficulty due to adherence to scars.
  • The scars are of variable size and show characteristic U-shaped depressions on the cortical surface.
  • The pelvis is usually dilated and calyces are blunted.
Microscopic Examination
  1. Interstitium
    • Chronic inflammatory reaction chiefly composed of lymphocytes, macrophages with pronounced interstitial fibrosis.
  2. Tubules
    • A trophy and dilation of varying degree.
    • Eosinophilic colloid casts in dialated tubules producing thyroidization.
    • Few contain neutrophils.
  3. Pelvicalyceal system
    • Renal pelvis and calyces are dilated.
    • Chronic inflammation and fibrosis of walls of pelvis and calyces.
    • Lymphoid follicles with germinal centers in pelvicalyceal walls.
  4. Blood vessels
    • Obliterative endarteritis in vessels entrapped in scarred areas
    • Hypertensive hyaline arteriolosclerosis
  5. 131Glomeruli
    • Periglomerular fibrosis
    • Hyalinization of glomeruli in advanced cases.
Q. Definition and causes of nephritic syndrome
A. Nephritic syndrome is a syndrome characterized by hematuria, proteinuria, hypertension, edema and oliguria following an infective illness about 10–20 days earlier.
  1. Primary glomerulonephritis
    1. Acute glomerulonephritis
      • Poststreptococcal
      • Nonstreptococcal.
    2. Rapidly progressive glomerulonephritis
    3. Membranoproliferative glomerulonephritis
    4. Focal glomerulonephritis
    5. IgA nephropathy.
  2. Systemic diseases
    1. SLE
    2. Polyarteritis nodosa
    3. Wegener's granulomatosis
    4. Henoch-Schönlein purpura
    5. Cryoglobulinemia.
Q. End stage kidney.
A. Definition: End stage kidney or chronic glomerulonephritis is a last stage of variety of glomerular diseases which result in irreversible impairment of renal function (glomerular filtration rate is less than 5% of normal).
  1. Diseases causing glomerular pathology
    1. Primary
      • Membranous GM
      • Membranoproliferative GM
      • Minimal change GM
      • Antiglomerular basement membrane nephritis
    2. 132Secondary
      • SLE
      • Serum sickness nephritis
      • Diabetic nephropathy
  2. Diseases causing tubulointerstitial pathology
    1. Vascular causes
      • Nephrosclerosis due to hypertension.
    2. Infections causes
      • Chronic pyelonephritis.
    3. Toxic causes
      • Analgesics (aspirin, phenacetin, acetaminophen)
      • Lead, cadmium and uranium.
    4. Obstructive causes
    • Calculi
    • Blood clots
    • Tumors
    • Strictures
    • Enlarged prostate.
Gross Examination
  • The kidneys are usually small and contracted (<50 gm).
  • The capsule is adherent to the cortex.
  • The cortical surface is generally diffusely granular.
  • On cut section, cortex is narrow and atrophic, while the medulla is unremarkable.
Microscopic Examination
  1. Glomeruli
    • Glomeruli are reduced in number.
    • They show completely hyalinized tufts giving appearance of acellular, eosinophilic masses which are PAS positive.
  2. Tubules
    • Tubules completely disappear and there is atrophy of tubules close to scarred glomeruli.
    • 133Tubular cells show hyaline droplets, degeneration and tubular lumina frequently contain eosinophilic, homogeneous casts.
  3. Interstitium
    • Interstitial tissue shows fine and arteriolar sclerosis point towards associated hypertension.
  4. Vessels
    • Conspicuous arterial and arteriolar sclerosis point towards associated hypertension.
Clinical Features
  • Patients are usually adults.
  • The terminal stage is characterized by hypertension, uremia and progressive deterioration of renal functions.
Q. Renal changes in diabetes mellitus
A. Renal changes in diabetis mellitus are as follows:
  • Involvement of kidney is an important complication of diabetes mellitus.
  • Renal complications are more severe and appear early in IDDM than NIDDM.
  • Symptoms of diabetic nephropathy include asymptomatic proteinuria, nephritic syndrome, progressive renal failure and hypertension.
  • About 10% diabetics die due to end stage kidney with renal failure.
Renal Changes
  1. Diabetic glomerulosclerosis
    • Particulary common and account for majority of abnormal findings.
    • It's pathogenesis is linked to pathogenesis of diabetic microangiopathy. Other metabolic defects such as insulinopenia, hyperglycemia and glycosuria, increased collagen type TV fiber and fibronectin synthesis, hemodynamic changes are also implicated in the pathogenesis.134
    1. Diffuse glomerulosclerosis
      • It is most common and involves all parts of glomeruli.
      • There is thickening of glomerular basement membrane and diffuse increase in mesangial matrix with mild proliferation of mesangial cells.
      • Various exudative lesions like capsular hyaline drop and fibrin caps may be present.
      • Capsular hyaline drop is an eosinophilic hyaline thickening of the parietal layer of Bowman's capsule and bulges into glomerular space.
      • Fibrin cap is homogeneous, brightly eosinophilic material appearing on the wall of a peripheral capillary of a lobule.
    2. Nodular glomerulosclerosis
      • It is also called Kimmelstiel-Wilson (KW) lesions or intercapillary glomerulosclerosis.
      • It is specific for juvenile onset or islet cell antibody positive diabetes.
      • There are one or more nodules in few or many glomeruli.
      • Nodule is an ovoid or spherical, laminated, hyaline, acellular mass located within a lobule of the glomerulus.
      • Nodules are surrounded by glomerular capillary loops having normal or thickened glomerular basement membrane.
      • Nodules are PAS positive and contain lipid and fibrin.
      • As they enlarge, they compress glomerular capillaries and obliterate glomerular tuft.
      • Consequently, renal ischemia occurs leading to tubular atrophy and interstitial fibrosis and grossly small contracted kidney.
  2. Vascular lesions
    • Atheroma of renal artery is very common and severe in diabetes mellitus.
    • Hyaline arteriosclerosis severely affects afferent and efferent arterioles of the glomeruli.
    • 135These changes cause renal ischemia resulting in tubular atrophy and interstitial fibrosis.
  3. Diabetic pyelonephritis
    • Bacterial infections are quite common in poorly controlled diabetes.
    • Papillary necrosis may result in acute pyelonephritis.
    • Chronic pyelonephritis is 10–20 times more common in diabetics.
  4. Tubular lesion (Armanni-Ebstein lesions)
    • Epithelial cells of proximal convulated tubules develop extensive glycogen deposit as vacuoles in untreated diabetics with extremely high blood sugar levels.
    • These are called Armanni-Ebstein lesions.
    • On control of hyperglycemic state, tubules return to normal.
Q. Name renal function tests
  1. Urine analysis
    1. Physical examination
    2. Chemical examination
    3. Bacteriological examination
    4. Microscopy.
  2. Concentration and dilution tests
  3. Blood biochemistry
    1. Blood urea
    2. Blood nitrogen
    3. Serum creatinine.
  4. Renal clearance tests
    1. Urea clearance tests
    2. Inulin clearance test
    3. Creatinine clearance test
    4. Pap aminohippuric acid clearance test.
Q. Laboratory findings in nephritic syndrome
A. Definition: Nephritic syndrome is a syndrome, which is, characterized by hematuria, proteinuria, hypertension, edema and oliguria following an infective illness about 10–20 days earlier.
Laboratory Findings
Blood Findings
  • Hypertension: Depending upon the severity of disease, hypertension is variable but is generally mild.
  • Edema: It is usually mild and results from sodium and water retention.
  • Azotemia.
Urinary Findings
  • Oliguria: Oliguria is variable and reflects the severity of the disease.
  • Hematuria: Hematuria is generally slight giving the urine smoky appearance and erythrocytes are detected by microscopy or by chemical testing for hemoglobin. Red cell casts appear in the urine which is a classical feature of nephritic syndrome.
  • Proteinuria: Proteinuria is generally less than 3 gm per 24 hours (mild) and is non-selective.
Q. Renal calculi
A. Renal calculi or urinary calculi are of the following types.
Calcium Stones
  • They are common comprising about 75% of renal calculi.
  • They may be pure stones of calcium oxalates (50%) or calcium phosphate (5%) or mixture of calcium oxalate and calcium phosphate (45%).
  • Idiopathic hypercalciuria without hypercalcemia (50%)
  • Hypercalcemia and hypercalciuria, most commonly due to hyperparathyroidism or defect in the bowel or in the kidney (10%)
  • Hyperuricosuria with normal blood uric acid level and with normal calcium metabolism (15%)
  • Idiopathic calcium stone disease (25%).
  • Calcium urolithiasis results due to imbalance between the degree of supersaturation of the ions forming the stone and the concentration of inhibitors in the urine.
  • Calcium stones are precipitated mostly at tubular lining or around some fragments of debris in the tubules acting as nidus of the stone.
  • As more and more crystals are deposited around the nidus, the stone grows larger.
  • Factors which predispose to stone formation are alkaline urinary pH, decreased urinary volume and increased excretion of oxalates and uric acid.
Calcium stones are usually small (<1 cm), ovoid, hard with granular rough surface.
  • They are dark brown due to old blood pigment deposited in them as a result of repeated trauma caused to urinary tract by these sharp edged stones.
Mixed (Struvite) Stones or Triple Phosphate Stones
  • They comprise 15% stones of urinary calculi.
  • They are made up of magnesium ammonium calcium phosphate often called struvite.
  • Urinary tract infection due to urea splitting organisms that produce urease such as Proteus, Klebsiella, Pseudomonas and Enterobacter.
  • Therefore, they are called as infection induced stones.
  • Struvite stones are yellow white or gray.
  • They are soft and fiable and irregular in shape.
  • Staghorn stone is a large, solitary stone that takes shape of the renal pelvis where it is often formed.
Uric Acid Stones
They make 6% of urinary calculi and are radiolucent.
Hyperuricemia and hyperuricosuria due to:
  • Primary gout
  • Secondary gout due to myeloproliferative disorders
  • Uricosuric drugs
  • Contributing factors are acidic urinary pH and low urinary volume.
  • Solubility of uric acid in urine decreases with increase in acidity of urine (solubility at pH of 7 is 200 mg/dl and at of 5 is 15 mg/dl).
  • Precipitation of uric acid crystals increases favoring the formation of uric acid stones.
  • Hyperuricosuria is the most important factor in pathogenesis of uric acid stones.
  • Uric acid stones are smoothing, yellowish-brown, hard and often multiple.
  • On cut section, they show laminated structure.
Cystine Stones
  • Comprise less than 2% of urinary calculi.
  • Cystiuria due to genetically determined defect in transport of cysteine and other amino acids across cell membrane of renal tubules and small intestinal mucosa.
  • Excessive excretion of cystine is least soluble of the naturally occurring amino acid leads to formation of crystals and eventually cystine calculi.139
  • Cystine stones are yellow, small, rounded, smooth, waxy and often multiple.
Other Calculi
  • Less than 2% of urinary calculi consist of other rare types such as due to inherited abnormality of xanthine metabolism resulting in xanthinuria and consequently xanthine stones.
Q. Wilms’ tumor.
A. Wilms’ tumor or nephroblastoma is an embryonic tumor derived from primitive real epithelial and mesenchymal components.
  • It is the most common abdominal tumor of young children.
  • It is most commonly in age group of 1–6 years with equal sex incidence.
Gross Examination
  • Tumor is usually quite large, spheroidal replacing most of the kidney.
  • Generally solitary and unilateral but in 5–10% cases bilateral.
  • On cut section, characteristic variegated appearance, i.e. soft fish flesh like gray white to cream yellow tumor with foci necrosis and hemorrhages and grossly identifiable myxomatous or cartilaginous elements.
  • 50% cases show invasion into renal rein.
Microscopic Examination
  • Nephroblastoma shows mixture of primitive epithelial and mesenchymal elements.
  • Mostly consists of small, round to spindle-shaped anaplastic sarcomatoid tumour cells.
  • 140These areas contain abortive tubules and poorly formed glomerular structures.
  • Sometimes, mesenchymal elements such as smooth and skeletal muscle, cartilage and bone, fat cells and fibrous tissue may be seen.
Clinical Features
  • Palpable abdominal mass (most common)
  • Hematuria, pain, fever and hypertension
  • Spreads via blood especially to lungs.141
Male Genital Tract and Prostate
Q. What are the causes of male infertility?
A. Definition: Infertility means inability to conceive or beget children.
Causes of male infertility
  • It can be divided into three groups.
a. Pretesticular causes
i. Hypopituitarism
: Prepubertal or postpubertal hypopituitarism such as from tumor, trauma, infection, cyst and genetic deficiency of FSH and LH secretion.
ii. Estrogen excess
: Endogenous excess such as from cirrhosis, adrenal tumor, Sertoli and Leydig cell tumor exogenous excess such as in treatment of carcinoma prostate.
iii. Glucocorticoid excess
: Endogenous excess as in Cushing's syndrome exogenous excess as in treatment of ulcerative colitis, bronchial asthma, rheumatoid arthritis, etc.
iv. Other endocrine disorders
: Hypothyroidism and diabetes mellitus are associated with hypospermatogenesis.
b. Testicular causes:
i. Agonadism
: Total absence of the testes.
ii. Cryptorchidism
: Undescended testis.
iii. Maturation arrest
: Failure of spermatogenesis beyond one of the immature stages.
iv. Hypospermatogenesis
: Presence of all the maturation stages of spermatogenesis but in decreased number.
v. Sertoli cell only syndrome
: Congenital or acquired absence of all germ cells so that the seminiferous tubules are lined by Sertoli cell only.
vi. Klinefelter's
: A XXY intersexuality characterized by primary hypogonadism, azoospermia, gynecomastia, eunuchoid built and subnormal intelligence.
vii. Mumps orchitis
: Complication of parotitis.
viii. Irradiation damage
: Resulting in permanent germ cell destruction.
c. Post-testicular causes:
i. Congenital block
: For example, absence or atresia of vas deferens.
ii. Acquired block
: For example, due to gonorrhea and surgical intervention.
iii. Impaired sperm motility
: For example, immotile cilia syndrome.
Q. Seminoma.
A. Definition: Seminoma is the commonest malignant tumor of the testis.
  • 143Constitutes about 45% of all germ cell tumors and 15% of mixed germ cell tumor
  • Peak incidence in 4th decade of life and rare before puberty
  • Common in undescended testis.
  • 10% show rise in AFP or HCG levels.
Gross Examination
  • Testis enlarged 10 times its normal size
  • Normal contour retained as rarely tunica is invaded
  • Large tumor entirely replaces testis whereas small tumor appears as circumscribed mass in the testis
  • Cut section shows homogeneous, gray-white lobulated appearance
  • Necrosis and hemorrhage in tumor is rare.
Microscopic Examination
  1. Tumor cells
    • Seminoma cells generally lie in cords, sheets or columns forming lobules.
    • In classic seminoma, the tumor cells are fairly uniform in size with clear cytoplasm and well-defined cell.
    • Cytoplasm contains variable amount of glycogen that stain positively with PAS reaction.
    • Nuclei are centrally located, large, hyperchromatic and usually contain 1–2 prominent nucleoli.
    • Tumor gaint cells may be present.
    • About 10% have increased mitotic activity and aggressive behavior.
  2. Stroma
    • It is delicate fibrous stroma which divides tumor into lobules.
    • There is characteristic lymphocytic infiltration indicative of immunologic response of the host to the tumor.
    • About 20% show granulomatous reaction.
144Q. What is hyperplasia? Discuss benign hyperplasia of prostate.
(May/June 08)
A. Definition: The hyperplasia is increase in the number of parenchymal cells resulting in enlargement of the organ or tissue. Hyperplasia occurs due to increased recruitment of cells from G0 (resting) phase of the cell cycle to undergo mitosis when stimulated. All cells do not possess hyperplastic growth potential. Labile cells (epithelial cells of the skin and mucous membranes, cells of the bone marrow and lymph nodes) and stable cells (parenchymal cells of the liver, pancreas, kidney, adrenal and thyroid) can undergo hyperplasia. Permanent cells (neurons, cardiac and skeletal muscles) have little or no capacity for regenerative hyperplastic growth.
Benign Prostatic Hyperplasia
  • Benign prostatic hyperplasia (BPH) or benign nodular hyperplasia (BNH) or benign enlargement of prostate (BEP) is a nonneoplastic tumor like enlargement of the prostate.
  • It is a very common condition in men and becomes increasingly more frequent above age of 50 years and incidence approaches 75–80% in men above 80 years.
  • The etiology of BPH is endocrinal in origin.
  • With advancing age, there is decrease in the level of androgens and a corresponding rise of estrogen in the female.
  • The periurethral inner prostate is responsive to rising level of estrogen thus producing hyperplasia.
Gross Examination
  • Enlarged prostate is nodular, smooth and firm and weights 40–80 gm (2–4 times normal).
  • 145Hyperplastic nodule forms a mass mainly in the inner periurethral prostatic gland so that the surrounding prostatic tissue forms a false capsule which enables the surgeon to enucleate the nodular masses.
  • Left over peripheral prostatic tissue may sometimes undergo recurrent nodular enlargement or may develop carcinoma later.
  • There are two morphological types depending on the predominance of glandular or fibromuscular tissue.
  • Predominantly glandular: Cut section is yellow-pink, soft, honeycombed and milky fluid exudes.
  • Predominantly fibromuscular: Cut section is firm, homogeneous and does not exude milky fluid.
Microscopic Examination
Glandular hyperplasia
  • It predominates in most cases.
  • It is identified by exaggerated intraacinar papillary in foldings with delicate fibrovascular cores.
  • The lining epithelium is two-layered.
    • Outer cuboided to flattened epithelium with basal nuclei.
    • Inner tall columnar mucous secreting with poorly defined borders.
Fibromuscular hyperplasia
  • It appears as aggregates of spindle cells forming an appearance akin to fibromyoma of the uterus.
  • Besides these, there are other histological features such as foci of lymphocytic aggregates, small areas of infarction, corpora amylacea and foci of squamous metaplasia.
Clinical Features
  • Presenting features are frequency, nocturia, difficulty in micturition, pain hematuria and sometimes acute retention of urine.
  • The symptoms are due to complications such as urethral obstruction and secondary effects on bladder (e.g. Hypertrophy, cystitis), ureter (e.g. hydroureter) and kidneys (e.g. Hydronephrosis).
146Q. Cryptorchidism
A. Definition
  • Cryptorchidism or undescended testis is a condition where the dexcent of the testis is arrested at some point in the route of descent from intra-abdominal location to scrotal sac.
  • The undescended testis lies in inguinal canal in 70% cases, abdomen in 25% cases and other sites in remaining 5% cases.
a. Mechanical factors
  • Short spermatic cord
  • Narrow inguinal canal
  • Adhesions to the peritoneum.
b. Genetic factors
  • Trisomy 21
  • Maldevelopment of scrotum or cremaster muscles.
c. Hormonal factors
  • Deficient androgenic secretions.
Gross Examination
  • Cryptorchid testis is small in size, firm and fibrotic.
Microscopic Examination
  • By 2 years of age, atrophic changes begin to appear in the testis.
  • These change are
  1. Seminiferous tubules
    • There is progressive loss of germ cell elements so that the tubules may be lined by only spermatogonia and spermatids but foci of spermatogenesis are discernible in 10% cases.
    • 147Tubular basement membrane is thickened.
    • Advanced cases show hyalinized tubules with a few Sertoli cells only, surrounded by prominent basement membrane.
  2. Interstitial stroma
    • There is usually increase in the interstitial fibrovascular stroma and conspicuous presence of Leydig cells, seen singly or in small clusters.
Clinical Features
  • Cryptorchidism is seen in 0.2% of adult male population and it is unilateral in majority of cases but bilateral in 25% of cases.
  • As such cryptorchidism is completely asymptomatic and is discovered only on physical examination.
If surgical correction of cryptorchidism is not done by about 2 years of age following adverse outcome may follow.
a. Sterility infertility
  • Bilateral cryptorchidism is associated with sterility while unilateral disease may result in infertility.
b. Inguinal hernia
  • Concomitant inguinal hernia is frequently present along with cryptorchidism.
c. Malignancy
  • Cryptorchidism testis is at 35 times increased risk of developing testicular malignancy, most commonly seminoma and embryonal carcinoma.
Q. Complications of undescended testis.
A. Complications of undescended testis or cryptorchidism are:
  • Sterility: Associated with bilateral cryptorchidism.
  • Infertility: Associated with unilateral cryptorchidism.
  • Inguinal hernia.
  • Malignancy: Risk is 35 times and common malignancies are seminoma and embryonal carcinoma.148
Female Genital Tract
Q. Describe the etiology, pathology and spread of carcinoma cervix.
A. Definition: Carcinoma cervix can be studied under the following types:
● Cervical dysplasia
: A typical cytological changes in the squamous epithelial layers changes being progressive.
It is graded into mild, moderate and severe depending upon the thickness of involved squamous epithelium.
● Carcinoma in situ
: Full thickness involvement by atypical cells or carcinoma confined to layers above the basement membrane.
● Invasive cervical cancer
: Carcinoma extended beyond the basement membrane and evolves through progressive stages of dysplasia and carcinoma in situ.
  • Dysplasia arises in young women between 25–30 years whereas carcinoma in situ develops a decade later.
  • Invasive cervical cancer is at peak in 4th–6th decades of life.
149a. Epidemiologic factor (or) risk factors
  • Early sexual activity especially with multiple partners.
  • Venereally transmissible etiological factors like oncogenic virus, spermatozoa, mycoplasma, squama and other agents.
  • Sex with potential high-risk males such as promiscuous male with history of penile condyloma or who had previous spouse with cervical cancer.
  • Lower socioeconomic condition, multiparity, promiscuous women, cigarette smoking, use of oral contraceptive and immunosuppression.
b. Virus
  • Human papilloma virus most commonly types 16, 18 and 31 termed high-risk types are seen in 75–100% cases of cervical cancer.
  • Human papilloma virus types 6 and 11 called low-risk types are found in condylomas.
  • Mixed high and low-risk types of HPV are found in dysplasias.
c. Cytogenetic factors
  • Dysplastic cells look morphologically different and have altered chromosomal number and appearance.
  • Viral oncogenes e6 and e7 of HPV inactivate suppressor gene products, p53 and rb gene and induce intraepithelial lesion and subsequent invasive cancer.
d. Immunology
  • Carcinoma cervix patients have shown circulating tumor specific antigens and antibodies and also antibodies to virus specific antigens on tumor cells.
e. Ultrastructural changes
  • 150Dysplastic cells show increased mitochondria and free ribosomes and depletion of normally accumulated glycogen in the surface cells.
A. Cervical Intraepithelial Neoplasia
Gross Examination
  • There is no specific picture of cervical intraepithelial neoplasia.
  • However, the changes begin at the squamocolumnar junction or transitional zone.
Microscopic Examination
  • Mild dysplasia: The abnormal cells extend up to one-third thickness from the basal to the surface layer.
  • Moderate dysplasia: The abnormal cells extend up to two-third thickness from the basal to the surface layer.
  • Severe dysplasia: The abnormal cells extend up to 75–90% thickness of epithelium.
  • Carcinoma in situ: The entire thickness from basement membrane to the surface shows dysplastic cells.
B. Invasive Carcinoma
Gross Examination
  • Invasive cervical carcinoma presents three types of patterns namely fungating, ulcerating and infiltrating.
  • Fungating or exophytic pattern is most common and appears as cauliflower-like growth infiltrating the adjacent vaginal wall.
  • The invasive cervical carcinoma arises characteristically from the squamocolumnar junction.
Microscopic Examination
Squamous Cell (epidermoid)
  • Carcinoma (80%): Most common pattern (70%) is moderately differentiated non-keratinizing large cell type and has better prognosis.
  • Next (25%) is well-differentiated keratinizing epidermoid carcinoma (neuroendocrine or oat cell carcinoma).
  • Adenocarcinoma (10%): These may be well-differentiated mucus secreting adenocarcinoma or clear cell type containing glycogen but no mucin.
  • 151Others (5%): These may be adenosquamous carcinoma, verrucous carcinoma or undifferentiated carcinoma.
  • Inadvanced stages of carcinoma cervix, there is widespread destruction and local infiltration into adjacent structures including urinary bladder, rectum, vagina and regional lymph nodes.
  • Distant metastases occur in lungs, liver, bone marrow and kidneys.
  • Carcinoma cervix is classified into following stages by FIGO staging:
Stage 0
: Carcinoma in situ.
Stage I
: Carcinoma strictly confined to the cervix.
: Preclinical carcinomas diagnosed only by microscopy.
Maximum size 5 mm deep and 7 mm across measured from the base of epithelium.
: Stromal invasion of less than 3 mm in depth and 7 mm in horizontal axis.
: Stromal invasion of 3 to 5 mm depth and horizontal 7 mm or less.
: Clinical lesion confined to cervix or preclinical lesions greater than Ia.
: Clinical lesions not greater than 4 cm in size.
: Clinical lesions greater than 4 cm in size.
Stage II
: Carcinoma extends beyond the cervix but has not extended to the pelvic wall involvement of vagina limited to upper 2/3rd.
: No obvious parametrial involvement.
: Obvious parametrial involvement.
Stage III
: The carcinoma extended to pelvic wall.
The tumor invades lower third of vagina.
: No extension to the pelvic wall.
: Extension to the pelvic wall and or hydronephrosis or nonfunctioning kidney.
Stage IV
: The carcinoma has extended beyond the true pelvis or has clinically involved the mucosa of the bladder or rectum.
: Spread of growth to adjacent organs.
: Spread to distant organs.
  • Diagnosis of cancer cervix is done by Pap smear (exfoliative cytology) and colposcopy.
Q. Classify tumors of the uterus. Discuss the pathology of leiomyoma.
Add a note on the secondary changes in leiomyoma.
A. Classification of tumors of uterus
  1. Benign
    1. Endometrial glands
      • Endometrial polyp
    2. Endometrial stroma
      • Stromal nodules
    3. Myometrial smooth muscle leiomyoma.
  2. Malignant
    1. Endometrial glands
      • Endometrial carcinoma
    2. Endometrial stroma
      • Stromal sarcoma
    3. Myometrial smooth muscle
      • Leiomyosarcoma
    4. Müllerian mesoderm
      • Mixed mesodermal or müllerian tumors
  • Leiomyoma or fibromyomas or fibroids is a benign and most common uterine tumor of the smooth muscle origin.
  • They are mostly caused by stimulation be estrogen.
  • Leiomyoma are mostly frequently located in the uterus where they occur within the myometrium (intramural or interstitial), serosa (subserosal) or just underneath the endometrium (submucosal).
Gross Examination
  • The leiomyomas are often multiple, circumscribed, firm, nodular, gray white masses of variable size.
  • On cut section they exhibit characteristic whorled pattern.
Microscopic Examination
  • It's appearance as whorled bundles of smooth muscle cells admixed with variable amount of connective tissue.
  • The smooth muscle cells are uniform in size and shape with abundant cytoplasm and central oval nuclei.
  • Cellular leiomyoma has preponderance of smooth muscle element.
Secondary Changes in Leiomyoma
  • Secondary changes alter the pathological appearance of the leiomyoma.
  • They are as follows:
    • Hyaline degeneration
    • Cystic degeneration
    • Infarction
    • Calcification
    • Infection and suppuration
    • Necrosis
    • Fatty change
    • Sarcomatous change (rarely).
Q. Differences between adenomyosis and endometriosis
A. The underlying tabulation shows the difference in between above condition, i.e. adenomyosis and endometriosis.
● Abnormal distribution of histologically benign endometrial tissue within the myometrium.
● Presence of endometrial glands and stroma in abnormal locations outside the uterus.
● Seen in elderly women.
● Seen in women in childbearing age group.
● Seen in the uterus only.
● Seen widely spread in lower pelvis but most common sites are the ovaries, cul-de-sac, sigmoid colon, appendix, etc.
● Women are parous.
● Women are infertile.
Q. Krukenberg's tumor.
  • Krukenberg's tumor is a distinctive bilateral metastatic tumor to the ovaries by transcelomic spread characterized by the presence of mucus filled signet ring cells accompanied by sarcoma, like proliferation of ovarian stroma.
  • It is generally secondary to a gastric carcinoma but can also occur secondary to mucinous carcinoma of colon, appendix and breast.155
Q. Classify tumors of the breast. Discuss the etiopathogenesis and pathology of carcinoma breast.
A. Benign tumors
  1. Stromal tumors
    1. Fibroadenoma
    2. Phyllodes tumor (cystosarcoma phyllodes)
    3. Sarcomas.
  2. Epithelial tumors
    1. Intraductal papilloma (large duct papilloma).
B. Malignant tumors
  1. Noninvasive (in situ) carcinoma
    1. Intraductal carcinoma
    2. Labular carcinoma in situ.
  2. Invasive carcinoma
    1. Infiltrating (invasive) duct carcinoma
    2. Inflitrating (invasive) tubular carcinoma
    3. Medullary carcinoma
    4. Colloid (mucinous)
    5. Papillary carcinoma
    6. Tubular carcinoma
    7. Adenoid cystic (invasive cribriform) carcinoma
    8. Secretory (juvenile) carcinoma
    9. Carcinoma with metaplasia.
  3. Paget's disease of the nipple
156Carcinoma of Breast
  • The following factors play an important role in pathogenesis of breast carcinoma.
a. Geography
  • Incidence of breast cancer is six times higher in developed countries except Japan than developing countries.
  • This fact indicates role of large amount of animal fats and high calorie diet in pathogenesis which is mostly consumed by western population than the Asians and Africans.
b. Genetic factors
  1. Family history
    • A women is 2–6 times at higher risk of developing breast carcinoma if any of her first degree relatives like mother, sister and daughter has history of breast carcinoma.
    • The risk is proportionate to:
      • Number of close relatives with breast cancer.
      • Younger age at the time of development of breast cancer.
      • Bilateral cancers.
      • Simultaneous breast and ovarian carcinomas.
  2. Inherited mutations
    • P53 tumor suppressor gene on chromosome 17
    • Breast carcinoma 1 gene on chromosome 17
    • Simultaneous breast and ovarian carcinomas.
c. Estrogen excess
  • Excess endogenous estrogen or exogenously administered estrogen for prolonged duration plays an important role in pathogenesis. Fact that favors this theory are:
    • Women with prolonged reproductive life, i.e. with early menarche and late menopause are at relatively greater risk.
    • Unmarried and nulliparous women are at higher risk than married and multiparous women.
    • Women with first childbirth at an age over 30 years are at higher risk.
    • 157Lactation reduces the risk of breast cancer.
    • Bilateral oophorectomy reduces the risk of developing breast carcinoma.
    • Estrogen secreting ovarian tumors is associated with high incidence of breast carcinoma.
    • Postmenopausal women on estrogen replacement therapy are at increased risk of breast carcinoma.
    • Males treated with estrogen for prostatic cancer can develop breast carcinoma.
  • Normal breast epithelium possesses estrogen and progesterone receptors.
  • A variety of growth promoters like transforming growth factor-α, epidermal growth factor, platelet derived growth factor and fibroblast growth factor and growth inhibitors like transforming growth factor-b are secreted by human breast cancer cells and these factors are involved in an autocrine mechanism of tumor progression.
  • Production of these factors is dependent on estrogen and it is the interaction between circulating estrogen, hormone receptors on cancer cells and autocrine growth factors induced by tumor cells are involved in breast cancer progression.
d. Environmental and dietary factors
  • Consumption of large amounts of animal fat, high calorie foods, cigarette smoking and alcohol increases the risk of breast carcinoma.
  • Mouse mammary tumor virus, a transmissible retrovirus also called bittner milk factor induced breast cancer in the daughter mice breastfed on the mother mice already having breast cancer.
e. Fibrocystic change
  • Atypical epithelial hyperplasia has 2–6 times higher risk of developing breast carcinoma subsequently.
f. Cellular changes
  • One of the earliest detectable changes is loss of normal regulation of cell number, resulting in epithelial hyperplasia or sclerosing adenosis.
  • 158Next genetic instability occurs in multiple small clonal populations of cells recognizable histologically as a typical hyperplasia.
  • After progression to carcinoma numerous cellular alteraaions can be identified including
    • Increased expression of oncogenes
    • Decreased expression or function of tumor suppressor genes
    • Alterations I cell structure
    • Loss of cell adhesion
    • Increased expression of cell cycle proteins
    • Increased expression of angiogenic factors
    • Increased expression of proteases.
Gross Examinaton
  • The tumor may vary from a small poorly defined focus to 3–5 cm diameter mass.
  • On cut section, the involved area shows cystically dilated ducts containing cheesy necrotic material (comedo pattern) or the intraductal tumor may be polypoid and friable resembling intraductal papilloma (papillary pattern).
Microscopic Examination
  • The proliferating tumor cells within the ductal lumina has four types of patterns in different combinations.
  1. Solid pattern
  2. Comedo pattern
  3. Papillary pattern
  4. Cribriform pattern
  • It is characterized by filling and plugging of the ductal lumina with tumor cells.
  • It is centrally placed necrotic debris surrounded by neoplastic cells in the duct.
  • It has formation of intraductal papillary projections of tumor cells which lack a fibrovascular stalk so as to distinguish it from intraductal papilloma.
  • It is recognized by neat punched out fenestrations in the intraductal tumor.
Q. Fibroadenoma.
A. Definition: Fibroadenoma or adenofibroma is a benign tumor of fibrous and epithelial elements of breast. It is the most common benign tumor of the female breast.
Gross Examination
  • Typical fibroadenoma is a small (2–4 cm diameter), solitary, well-encapsulated, spherical or discoid mass.
  • Cut surface is firm, gray-white, slightly myxoid and may show slit-like spaces formed by compressed ducts.
  • Occasionally, multiple fibroadenomas may form part of fibrocystic disease and is called fibroadenomatosis.
  • Giant fibroadenomas are fairly large in size up to 15 cm in diameter but are less common.
Microscopic Examination
  • Fibroadenoma is mostly comprised of fibrous tissue.
  • There are two types of patterns of arrangement of fibrous overgrowth and ducts.
  1. Intracanalicular pattern
    • It is characterized by compression of ducts by stroma so that they are reduced to slit-like clefts lined by ductal epithelium or may appear as cord of epithelial elements surrounding masses of fibrous stroma.
  2. Pericanalicular pattern
    • It is characterized by encircling masses of fibrous stroma around the patent or dilated ducts.160
    • Fibrous stroma may be quite cellular or there may be areas of hyalinized collagen.
    • The stroma is loose and myxomatous.
    • Tubular adenoma is a special form of fibroadenoma where fibrous tissue elements are scanty and tumor in pregnancy or lactation.
    • Juvenile fibroadenoma is an uncommon variant of fibroadenoma which is larger and rapidly growing mass seen in adolescent girls.
Clinical Features
  • Fibroadenoma can occur at any stage during reproductive life but most patients are between 15–30 years of age.
  • Clinically it appears as solitary, discrete, freely mobile nodule within the breast.
Q. Galactocele
  • Galactocele is cystic dilatation of one or more ducts occurring during lactation.
  • Mammary duct is obstructed and dilated to form a thin-walled, cyst-filled with milky fluid.
  • Rarely, it may get infected.
Q. Gynecomastia
A. Gynecomastia is the unilateral or lateral enlargement of the male breast due to proliferation of ducts and increased periductal stroma in response to hormonal stimulation, mainly estrogen.
  • It is of four types
    • Pubertal: Seen in men over 50 years.
    • Senescent: Seen in over 50 years.
    • Secondary endocrine disorders with increased estrogenic or decreased androgenic activity, e.g. cirrhosis, testicular tumors, pituitary tumors, carcinoma of lungs, exogenous estrogen therapy as in a carcinoma prostate and testicular atrophy in Klinefelter's syndrome.
    • Idiopathic.
Gross Examination
  • One or both the male breasts are enlarged having smooth glistening white tissue.
Microscopic Examination
  • Proliferation of branching duct which display epithelial hyperplasia with formation of papillary projections at places.
  • Increased fibrous stroma with myxoid with appearance.
Q. List the benign tumors of breast and write their features?
(MUHS Nov/Dec 09)
A. Benign breast conditions are as follow:
  • Nipple discharge
  • Lobular carcinoma in situ (LCIS)
  • Fibrocystic breast condition
  • Simple cysts
  • Galactoceles
  • Fibroadenomas
  • Phyllodes tumors
  • Intraductal papillomas
  • Granular cell tumors
  • Duct ectasia
  • Fat necrosis
  • Breast inflammation: Mastitis.
A benign breast condition is any noncancerous breast abnormality. According to the American Cancer Society, when breast tissue is examined under a microscope some type of abnormality is common in nine out of every ten women. Though not life-threatening, benign conditions may cause pain or discomfort for some patients. Some (not all) benign conditions can signal an increased risk for breast cancer. The most common benign breast conditions include fibrocystic breast condition, benign breast tumors, and breast inflammation. Depending on the type of benign breast condition and the patient's medical situation, treatment may or may not be necessary.
162Breast tissue changes
The breast is composed of two main types of tissues: Glandular tissues and stromal (supporting) tissues. The glandular tissues house the milk-producing lobules and the ducts (the milk passages). The stromal tissues include fatty and fibrous connective tissue. Any changes in the glandular or stromal areas may cause symptoms of benign breast conditions.
Some women experience changes to their breast tissue over their lifetime. These changes can include an increase in the number of breast cells (hyperplasia) or the emergence of atypical breast cells (atypical hyperplasia). In some instances, a portion of breast tissue that exhibits abnormal characteristics can eventually develop into a cancerous tumor. That is why physicians carefully monitor patients with abnormal breast cells, to ensure that if cancer develops at a later date, it is detected and treated early. Some patients with atypical hyperplasia may also be recommended to take the drug tamoxifen to help prevent breast cancer. While the appearance of atypical hyperplasia increases the risk of breast cancer, not all women with abnormal breast cells go on to develop breast cancer.
The following chart summarizes the typical progression of breast tissue from “normal” to “cancer”
Breast disease “Continuum”
Hyperplasia (increase in number of cells)
Atypical hyperplasia (abnormal increase in number of cells, a marker for breast cancer)
Carcinoma in situ (cancer exists but confined to the ducts or lobules where it originally developed)
Invasive cancer (cancer exist and has spread beyond the breast duct or lobule where it originally developed)
While many cases of breast cancer arise from the above sequence some breast tumors may skip one or more 163intermediate steps (for example, cells may proceed from “normal” directly to “carcinoma in situ”). In general, anything farther along than atypical hyperplasia is usually classified as a cancer. Abnormalities beginning with ductal carcinoma in situ (DCIS) usually require treatment as cancers. The treatment of benign breast conditions varies depending on a number of factors including the exact diagnosis, potential for developing breast cancer, and a woman's discomfort.
How are benign breast conditions detected?
Benign breast lumps are often first detected by physicians during clinical breast examination, routine mammogram or by patients practicing breast self-examination (BSE). Focal pain (pain confined to one spot in the breast) or nipple discharge (other than milk) may also alert a woman to have her condition checked by a doctor. Benign breast lumps are usually confirmed by imaging tests (mammogram, ultrasound/sonogram), observing the lump over a period of time, or doing fine needle aspiration biopsy (FNAB), core needle biopsy (CNB) or surgical biopsy.
Nipple Discharge
Nipple discharge, fluid coming from the nipple(s), is the third most common breast complaint for which women seek medical attention, after lumps and breast pain. The majority of nipple discharges are associated with noncancerous changes in the breast such as hormonal imbalances or papillomas. However, because a small percentage of nipple discharges can indicate breast/nipple cancer, any persistent discharge from the nipple(s) should be evaluated by a physician.
Up to 20% of women may experience spontaneous milky, opalescent, or clear fluid nipple discharge. During breast self-examination, fluid may normally be expressed from the breasts of 50% to 60% of Caucasian (white) and African-American women and 40% of Asian-American women. Usually, a discharge that is clear, milky, yellow, or green, and is noted from both nipples, is not associated with breast cancer. Bloody or watery nipple discharge, especially if limited to one side 164and/or a single breast duct, is considered abnormal; however, only around 10% of abnormal discharges are found to be cancerous.
Nipple discharge may be a concern if it is:
  • Bloody or watery (serous) with a red, pink, or brown color
  • Sticky and clear in color or brown to black in color (opalescent)
  • Appears spontaneously without squeezing the nipple
  • Persistent
  • On one side only (unilateral)
  • A fluid other than breast milk.
Women should report persistent nipple discharge to their doctors for analysis. To examine nipple discharge, a small amount of the fluid is placed on glass slides under a microscope to determine if cancer cells are present.
Q. What is the benign breast tumors?
A. Definition: A benign breast tumor is an area of abnormal cell growth in the breast which is not considered to be cancerous. A very high percentage of breast lumps turn out to be benign, meaning that they should cause few or no health problems to the owner of the breast, but all breast lumps should be examined by a doctor to check for malignancies. Monthly breast self-examinations are strongly recommended for all women, so that changes in the breast tissue can be detected as early as possible. Mammograms for cancer screening purposes are also recommended for older women.
Tumors are caused by a genetic defect in a cell which causes it to multiply uncontrollably, leading to the formation of a lump of tissue. In some cases, tumors are benign, with little risk of spreading to neighboring organs and some check on their growth. Benign tumors can still cause health problems, depending on their location, and 165they may also be viewed as cosmetic defects. Malignant tumors, on the other hand, have the potential to metastasize and they grow very rapidly and aggressively.
There are several different forms of benign breast tumors, including phyllodes tumors, granular cell tumors, papillomas, and fibroadenomas. All of these benign growths can cause lumps in the breast or around the milk duct. Classically, a benign breast tumor has smooth edges when it is palpated and it can be moved around in the breast tissue. Some women also experience fibrocystic changes, lumps in their breasts which wax and wane with the menstrual cycle.
Many breasts naturally have a few lumps and sometimes it can be difficult to discern the precise nature of a lump. In these cases, a doctor may request a breast biopsy. Breast biopsies are used to collect a small sample of the suspected tumor, so that it can be examined under a microscope by a pathologist. The pathologist can determine whether the lump is benign or malignant and a treatment plan can be developed accordingly.
Although a benign breast tumor is not cancerous, it can cause pain, irritation, or discomfort. Some women choose to have benign tumors removed in a lumpectomy procedure. Some lumps may also indicate an increased risk of developing breast cancer, in which case routine follow-up examinations may be recommended to monitor the breast closely for any changes. A doctor can discuss a benign breast tumor and its implications with patients on an individual basis.166
Musculoskeletal System
Q. Enumerate lytic lesions of bone. Discuss gross and microscopy of osteoclastoma.
A. Lytic lesions of bone are as follows:
  • Simple bone cyst
  • Aneurysmal bone cyst
  • Degenerative cyst
  • Intraosseous ganglio cyst
  • Ewing's sarcoma
  • Giat cell tumor
  • Osteosarcoma
  • Osteoid osteoma/osteoblastoma
  • Enchondroma
  • Langerhans cell histocytosis
  • Intraosseous lipoma
  • Vertebral body hemangioma
  • Multiple myeloma
  • Paget's disease
  • Ossifying fibroma
  • Metastatic neuroblastoma
  • Secondary metastasis.
  • Osteoclastoma or giant cell tumor is a distinctive neoplasm of bone with uncertain histogenesis.
Cell of Origin
  • True tumor cells are round to spindled mononuclear cells.
  • They are possibly of mesenchymal origin and perhaps derived from fusion of monocytes.
  • Tumor arises in the epiphysis of long bones close to the articular cartilage.
  • Most common sites of involvement are lower end of femur and upper end of tibia (i.e. about the knee), lower end of radius and upper end of fibula.
Gross Appearance
  • Giant cell tumor is eccentrically located in the epiphyseal end of long bone which is expanded.
  • Tumor is well-circumscribed, dark tan and covered by thin shell of subperiosteal bone.
  • Cut surface is characteristically hemorrhagic, necrotic and honeycombed due to focal areas of cystic degeneration.
Microscopic Examination
  • Hallmark is presence of large number of multinucleate osteoclast like giant cells which are regularly scattered throughout the stromal mononuclear cells.
i. Giant cells
  • They contain as many as 100 benign nuclei and have many similarities to normal clasts.
  • They have very high acid phosphatase activity.
ii. Stromal cells
  • These are mononuclear cells and are real tumor cells
  • They are uniform, plump, spindle-shaped or round to oval with numerous mitotic figures.
  • Their histologic appearance determines the biological behavior of the tumor.
168iii. Other features of stroma
  • Scanty collagen content, rich vascularity, areas of hemorrhages and presence of macrophages.
Clinical Features
  • It commonly occurs in patients between 20 and 40 years of age with no sex predilection.
  • Pain, especially on weight-bearing and movement, noticeable swelling and pathological fracture.
Laboratory Findings
  • Radiologically, it appears as a large, lobulated and osteolytic lesion at the end of an expanded log bone with characteristic soap bubble appearance.
Q. Pyogenic osteomyelitis.
A.An infection of the bone by bacteria is called pyogenic osteomyelitis.
  • Staphylococcus aureus in major etiological agent implicated in vast majority of cases.
  • Streptococci, E. coli, Pseudomonas, Klebsiella and anaerobes are less often involved.
  • Mixed infections are common in post-traumatic cases.
Mode of Spread
  • Hematogenous pyogenic osteomyelitis occurs most commonly in the long bones of infant or young children.
  • Direct extension of infection from the adjacent areas frequently involving the jaws and skull in adults is more common mode of spread.
  • It may be a complication of compound fractures, surgical procedures involving prosthesis or implants, gangrene of the limb in diabetics, debilitation and immunosuppression at any age.
  • Depending upon the duration, osteomyelitis may be acute, subacute or chronic.
  • Basic pathological change in any stage suppuration, ischemic necrosis, healing by fibrosis and bony repair.
  • The sequence of event in pathogenesis is:
    • Infection begins in the metaphyseal end of the marrow cavity which is largely occupied by pus. At this stage microscopy reveals congestion, edema and an exhudate of neutrophils.
    • Tension in the marrow cavity is increased due to pus resulting in spread of infection along the marrow cavity into the endosteum and into the haversian and Volkmann's canal causing periostitis.
    • Infection may reach the subperiosteal space forming subperiosteal abscesses. I may penetrate through the cortex creating draining skin sinus tracts.
    • Combination of suppuration and impaired blood supply to the cortical bone results in erosion, thinning and infarction necrosis of the cortex called sequestrum.
    • With passage of time, there is formation of new bone and is known as involucrum. Involucrum has irregular surface and has perforations through which discharging sinus tracts pass.
    • Long continued neo-osteogenesis gives rise to dense sclerotic pattern of osteomyelitis called chronic sclerosing nonsuppurative osteomyelitis of Garre.
    • Occasionally, acute osteomyelitis may be contained to a localized area and walled off by fibrous tissue. This is termed Brodie's abscess.
    • Occasionally, vertebral osteomyelitis may occur in which case, infection begins from disk and spreads to involve the vertebral bodies.170
Clinical Features
  • Painful and tender limbs
  • Fever, malaise and leukocytosis
  • Bony destruction on X-ray.
  • Septicemia
  • Acute bacterial arthritis
  • Pathologic fractures
  • Squamous cell carcinoma I long-standing cases
  • Secondary amyloidosis in long-standing cases
  • Vertebral collapse, paravertebral abscess, epidural abscess, cord compression and neurological deficits.
Q. Tuberculous osteomyelitis.
A. Definition: Osteomyelitis or infection of bone caused by Mycobacterium tuberculosis is called tuberculous osteomyelitis.
  • The bacterial reach the bone marrow and synovium most commonly by hematogenous dissemination from infection elsewhere usually lungs.
  • Infrequently, it is caused by direct extension from the pulmonary or gastrointestinal tuberculosis.
  • It commonly involves spine and bones of extremities and often affects adolescents and young adults.
  • Bone lesion consists of tuberculous granulomas consisting of central caseation necrosis surrounded by tuberculous granulation tissue.
  • Tuberculous lesion appears as a focus of bone destruction and replacement of the affected tissue by caseous material and formation of multiple discharging sinuses through the soft tissues and skin.
  • 171Involvement of joint space and intervertebral disk is frequent.
  • Pott's disease or TB spine often commences in vertebral bodies and is associated with compression fracture and destruction of intervertebral disks producing permanent damage and paraplegia.
  • Extension of caseous material along with pus from the lumbar cold abscess.
  • The cold abscess may burst through the skin and form sinus.
  • Long-standing cases develop systemic amyloidosis.
Q. Ewing's tumor.
A. Definition: Ewing's tumor or sarcoma is a highly malignant small cell tumor.
  1. Classic (skeletal) Ewing's sarcoma
  2. Soft tissue Ewing's sarcoma
  3. Primitive neuroectodermal tumor (PNET)
  • Skeletal Ewing's sarcoma arises in medullary canal diaphysis or metaphysis.
  • Common sites are shafts and metaphysic of long bones, particularly femur, tibia, humerus, and fibula.
  • Flat bones like pelvis and scapula may also be involved.
  • The origin of cells of Ewing's sarcoma is suggested as endothelial, pericytic, bone marrow, osteoblastic and mesenchymal.
  • More recently primitive neuroectodermal cells are suggested.
  • All the three types have a common cytogenetic abnormality t(11; 22) (q24; q12) suggesting a phenotypic spectrum.
Gross Examination
  • Ewing's tumor is typically located in medullary cavity.
  • Produces expansion of the affected diaphysis (shaft) or metaphysic often exceeding into the adjacent soft tissue.
  • Tumor tissue is characteristically gray-white, soft and friable.
Microscopic Examination
  1. Pattern
    • Tumor is divided by fibrous septa into irregular lobules of closely packed tumor cells.
  2. Tumor cells
    • Tumor cells are small and uniform resembling lymphocytes and have ill-defined cytoplasmic outlines, scanty cytoplasm and round nuclei with frequent mitoses.
    • Based on these cytological features, Ewing's tumor is also called round cell tumor or small blue cell tumor.
    • Cytoplasm contains glycoprotein staining with PAS reaction.
    • Tumor cells may be arranged around blood vessels forming pseudorosettes.
  3. Other features
    • Tumor is richly vascularized and lacks intercellular network of reticulin fibers.
    • There may be areas of necrosis and acute inflammatory cell infiltration.
    • Focal areas of reactive bone formation may be present.
Clinical Features
  • Ewing's tumor occurs in patients of age 5 to 20 years with predilection for females.
  • Pain, tenderness and swelling of the affected area accompanied by fever.
  • It metastasises early by hematogenous route to lungs, liver, other bones and brain.
Laboratory Findings
  • Leukocytosis and elevated ESR
  • On X-ray examination, osteolytic lesions with patchy subperiosteal reactive bone formation producing characteristic “Onion skin appearance”.
Q. Sequestrum
A. Definition
  • Sequestrum is erosion, thinning and infarction necrosis of a small or large fragment of cortex of bone due to suppuration and impaired blood supply to cortical bone.
  • It is seen in the pyogenic osteomyelitis.
  • This devitalized sequestrum in the course of time may be reabsorbed or is sometimes sloughed to form a free foreign body that on occasion dissects through the skin.
Q. Chordoma
A. Definition
  • Chordoma is slow growing malignant tumor arising from remnants of notochord.
  • It occurs in axial skeleton particularly sacral and sphenooccipital region and infrequent in vertebrae.
Gross Examination
Tumor is soft, lobulated, translucent and gelatinous with areas of hemorrhages.
Microscopic Examination
Chordoma is composed of highly-vacuolated physaliphorous cells surrounded by a sea of intercellular mucoid material.
  • It is usually found in patients over the age of 40 years with no sex predilection.
  • It may present with symptoms of spinal cord compression.
  • Tumor grows slowly and infiltrates adjacent structures.
  • Radiologically, it appears as osteolytic lesion.
174Q. Gout
A. Definition: Gout is a disorder of purine metabolism manifested by the following features occurring singly or in combination.
  • Increased serum uric acid concentration.
  • Recurrent attacks of characteristic type of acute arthritis where monosodium urate monohydrate crystals are demonstrable in the leukocytes present in synovial fluid.
  • Aggregated deposits of monosodium urate monohydrate or tophi in an around the joints of extremities.
  • Renal disease involving interstitial tissue and blood vessels.
  • Uric acid nephrolithiasis.
  • Gout is produced due to hyperuricemia (uric acid level 7 mg/dl).
  • Thus pathogenesis of gout lies in pathogenesis of hyperuricemia.
  • Gout is of two types: Metabolic and renal; each of which may be primary or secondary.
a. Hyperuricemia of metabolic origin
  • Comprise 10% of cases characterized by overproduction of uric acid
  • There is either accelerated rate of purine biosynthesis de novo or an increased turnover of nucleic acids.
  1. Primary metabolic gout
    • Inherited X-linked recessive metabolic defect in purine metabolism such as defect in PRPP synthetase.
  2. Secondary metabolic gout
    • Increased purine biosynthesis
    • Deficiency of glucose-6-phosphatase.
b. Hyperuricemia of renal origin
  • Comprise 90% of cases resulting due to decreased renal excretion of uric acid.
  • Altered renal excretion could be due to reduced glomerular filtration of uric acid enhanced tubular reabsorption or decreased secretion.
  • Diuretic therapy, drug induced (aspirin, pyrazinamide, nicotinic acid, ethambutol and ethanol), adrenal insufficiency, starvation, diabetic ketosis and disorders of parathyroid and thyroid.
  1. Acute gouty arthritis
    • Characterized of acute synovitis triggered by precipitation of sufficient amount of needle-shaped crystals of monosodium urate from serum or synovial fluid.
    • There is joint effusion containing numerous polymorphs, macrophages and microcrystals of urates.
    • Mechanism of acute inflammation appears to include phagocytosis of crystals by leukocytes, activation of the kallikrein system, activation of the complement system and urate mediated disruption of lysosomes within the leukocytes leading to release of lysosomal products in the joint effusion.
    • Initially there is monoarticular involvement accompanied with intense pain but later it becomes polyarticular along with constitutional symptoms.
    • It is predominately a disease of lower extremities, affecting great toe most commonly.
    • Other joints involved in decreasing order are ankles, heels, knees, wrists and fingers and elbows.
  2. Chronic tophaceous arthritis
    • It is produced due to repeated attacks of acute gouty arthritis.
    • Urate deposits encrust the articular cartilage.
    • There is synovial proliferation, pannus formation and progressive destruction of articular cartilage and subchondral bone.
    • Tophi (deposits of urate) may be found in periarticular tissues.
  3. Tophi in soft tissue
    • Tophus is a mass of urate measuring a few millimeters to a few centimeters in diameter.
    • 176Tophi are located in the periarticular tissues as well as subcutaneously such as on the hands and feet
    • Tophi are surrounded by inflammatory reaction consisting of macrophages, lymphocytes, fibroblasts and foreign body giant cells.
  4. Renal lesions
    Three types of renal lesions are:
    ● Acute urate nephropathy
    Intratubular deposition of monosodium urate crystals in the renal interstitial tissue.
    ● Chronic urate nephropathy
    Deposition of urate crystals in the renal interstitial tissue.
    ● Uric acid nephrolithiasis
    Hyperuricemia resulting in hyperuric aciduria.
Q. Rheumatoid nodule
  • Rheumatoid nodule is a characteristic extracardiac lesion of rheumatoid arthritis.
  • It is a nonspecific inflammatory change seen in the skin, particularly subcutaneous tissue over pressure points such as elbows, occiput and sacrum.
  • They may also be found in lung parenchyma, pleura, heart valves, myocardium and other organs.
  • Center of these nodules consist of an area of fibrinoid necrosis and cellular debris surrounded by several layers of palisading large epithelioid cells and peripherally there are numerous lymphocytes, plasma cells and macrophage.177
Central Nervous System
Q. Subarachnoid hemorrhage
A. Definition: Subarachnoid hemorrhage is the hemorrhage between the arachnoid and the pia mater.
  • It usually arises from the rupture of cerebral arteries or cerebral veins.
  • Blows to the neck can cause lacerations of vertebral artery with dissection of blood superiorly into subarachnoid space.
  • Spontaneous subarachnoid hemorrhage can occur from natural causes as in rupture of congenital (berry) or infective (mycotic) aneurysms, in arteriovenous malformations and also in bleeding disorders.
  • Even minor trauma can precipitate subarachnoid hemorrhage if the arteries are weak, as in atherosclerosis.
  • Minor trauma can also rupture basilar arteries in chronic alcoholics.
  • Subarachnoid hemorrhage is said to be the most common intracranial lesion following injury.
  • The blood mixes with the CSF and gets distributed over the whole of the brain surface.
  • Subarachnoid hematoma formation is extremely rare.
  • It can be unilateral or bilateral and may localized or diffuse.
  • 178Blood in the subarachnoid space is usually removed by phagocytosis, following the lysis of blood cells.
  • About one month after injury, only yellowish-brown areas of discoloration of the arachnoid may be left behind, which are referred to as plaques jaunes.
Q. Meningioma
    • Meningioma is the most common tumor arising from the piarachnoid and accounts for 20% of intracranial tumors.
    • They arise from the cap cell layer of the arachnoid.
    • They are usually found in 2nd to 6th decade of life with slight female preponderance.
Meningioma is most common site in front half of the head and includes:
  • Lateral cerebral convexities
  • Midline along the flax cerebri adjacent to the major venous sinuses parasagittally
  • Olfactory groove.
  • Less frequent sites are:
    • Within cerebral ventricles
    • Foramen magnum
    • Cerebellopontine angle
    • Spinal cord.
Gross Examination
  • Meningiomas are generally solitary but infrequently they may be multiple especially in von Recklinghausen's neurofibromatosis.
  • They are well-circumscribed, solid, spherical or hemispherical mass of varying size (1–10 cm).
  • It is firmly attached to the dura and indents the surface of the brain but rarely invades it.
  • Overlying bone shows hyperostosis.
  • Cut surface is firm and fibrous, sometimes with foci of calcification.179
Microscopic Examination
  • Meningiomas are divided into five subtypes.
a. Meningotheliomatous (syncytial) meningioma
  • Tumor consists of solid masses of polygonal cells with poorly-defined cell membranes (syncytial appearance).
  • Pattern resembles normal arachnoid cap cells.
  • Cells have round to oval, central nuclei with abundant, finely granular cytoplasm.
  • Tumor is divided into irregular lobules by the collagenous stroma.
b. Fibrous (fibroblastic) meningioma
  • Pattern is of a spindle shaped fibroblastic tumor.
  • Tumor cells form parallel or interlacing bundles.
  • Whorled pattern and psammoma bodies are less common.
c. Transitional (mixed) meningioma
  • Pattern characterized by combination of cells with syncytial and fibroblastic features with whorled pattern of tumor cells around a central capillary sized blood vessels.
  • Some whorled contain psammoma bodies due to calcification of the central core of whorls.
  • Xanthomatous and myxomatous degeneration may also be encountered.
d. Angioblastic meningioma
  • Hemangioblastic pattern resembles hemangioblastoma of the cerebellum.
  • Hemangiopericytic pattern resembles hemangio-pericytoma elsewhere in body.
e. Anaplastic malignant meningioma
  • Displays features of anaplasia and invade underling bone or spinal cord.
  • Associated with extraneural metastases mainly to the lungs.180
Clinical Pathology
Q. Test to detect diabetes mellitus. (MUHS Nov/Dec 08, May/June 10)
A. The list of diagnostic tests mentioned in various sources as used in the diagnosis of diabetes includes:
  • Physical examination
  • Urine sugar test
  • Urine ketones test
  • Oral glucose tolerance test (OGTT) also called “glucose challenge” test.
  • Blood glucose tests
    • Fasting plasma glucose (FPG)
    • Random plasma glucose
  • C-peptide blood test
  • Insulin level blood test
  • Self-managed blood glucose testing
    • Fingerprick blood drop blood glucose tests
    • Urine glucose home testing
    • Urine ketone home testing.
  • See also the various tests for complications of diabetes such as–
    • Diabetes eye tests (See also tests for diabetic retinopathy)
    • Kidney tests (See also tests for diabetic nephropathy)
    • Nerve tests (See also tests for diabetic neuropathy)
    • Foot tests (See also tests for diabetic peripheral neuropathy)
    • Reflex tests (See also for diabetic neuropathy)
    • 181Foot reflex test
    • Knee reflex test
  • Other tests for associated conditions or other problems
    • Cholesterol blood tests
    • Blood lipid tests
    • Liver function tests
    • Thyroid tests (See also tests for thyroid conditions).
  • Type 1 diabetes antibody tests
    • Glutamic acid decarboxylase (GAD) antibody tests—tests for type 1 diabetes antibodies.
    • Islet cell antibody (ICA) tests
    • Insulin antibody tests.
  • Tests for conditions related to type 1 diabetes
    • TSH blood test—tests thyroid function; see tests for thyroid conditions
    • Vitamin B12 blood test—test for pernicious anemia and other digestive problems
  • Tests for ongoing monitoring of diabetes control:
    • hba1c blood test—an average blood sugar measure over about 3 months.
    • Fructosamine blood test—an average blood sugar measure over about 2 weeks.
  • Tests to detect initially and then regularly screen for diabetes complications:
    • Lipids and cholesterol—used to test risks of heart disease from diabetes
    • Blood pressure tests
    • Eye tests
    • Foot tests
    • Urine protein test—tests for kidney problems.
    • Microalbumin urine test—also called “micro-albuminurea” test; detects early kidney problems.
Q. Blood culture. (MUHS Nov/Dec 08, May /June 10)
A. Blood culture is a microbiological culture of blood. It is employed to detect infections that are spreading through the bloodstream (such as bacteremia, septicemia amongst others). This is possible because the bloodstream is usually a sterile environment.182
Blood cultures were pioneered in the early 20th century.
When a patient shows signs or symptoms of a systemic infection, results from a blood culture can verify that an infection is present and they can identify the type (or types) of microorganism that is responsible for the infection. For example, blood tests can identify the causative organisms in severe pneumonia, puerperal fever, pelvic inflammatory disease, neonatal epiglottitis, sepsis and fever of unknown origin (FUO). However, negative growths do not exclude infection.
The usual risks of venipuncture and the occurrence of false-positive results (3+%) leading to inappropriate treatment (Madeo et al., 2003).
A minimum of 10 ml of blood is taken through venipuncture and injected into two or more “blood bottles” with specific media for aerobic and anaerobic organisms.
Care needs to be taken that the bottles are not contaminated with bacteria from staff members or other patients. To that end, the patient's skin is rubbed or sprayed with denaturated alcohol and betadine applied to the sampling site. Sterile gloves should be used to minimize contamination.
To maximize the diagnostic yield of blood cultures multiple sets of cultures (each set consisting of aerobic and anaerobic vials filled with 3–10 ml) may be ordered by medical staff. A common protocol used in US hospitals includes the following:
Set 1 = L. antecubital fossa at 0 minutes
Set 2 = R. antecubital fossa at 30 minutes
Set 3 = L. or R. antecubital fossa at 90 minutes.
Ordering multiple sets of cultures increases the probability of discovering a pathogenic organism in the blood and reduces the probability of having a positive culture due to skin contaminants.
183After inoculating the culture vials on the hospital floor, they are sent to the clinical pathology microbiology department. Here the bottles are entered into a blood culture machine, which incubate the specimens at body temperature. The blood culture instrument reports positive blood cultures (cultures with bacteria present, thus indicating the patient is “bacteremic”) by monitoring carbon dioxide levels produced by bacteria in the vials via fluorescence detected by a light emitting diode (LED). Most cultures are monitored for 5 days after which negative vials are removed.
If a vial is positive, a microbiologist will perform a Gram stain on the blood for a rapid, general ID of the bacteria, which they will report to the attending physician of the bacteremic patient. The blood is also subcultured or “subbed” onto agar plates to isolate the pathogenic organism for culture and susceptibility testing, which takes up to 3 days. This culture and sensitivity (C and S) process identifies the species of bacteria. Antibiotic sensitivities are then assessed on the bacterial isolate to inform clinicians on appropriate antibiotics for treatment. Some guidelines for infective endocarditis recommend taking up to 6 sets of blood for culture (around 60 ml).
Q. Write in brief on urine examination. (MUHS Nov/Dec 09)
Q. Discuss urine examination. (MUHS May/June 09)
A. Introduction
Routine urine examination is detailed analysis of urine. It helps detect alterations in the composition of the urine which help in the diagnosis of many disorders. When a sample of urine is submitted to a pathological laboratory, the following examinations are done:
Routine Urine Examination
Physical Examination
  • Normal volume of an early morning midstream sample is 50–300 ml.184
  • If it is more than 500 ml, it indicates diabetes or polyuria (frequent passing of urine).
  • If it is less than 20 ml, it indicates some kidney disorder.
  • The normal color of urine is pale yellow.
  • If it is dark yellow to orange, it indicates some liver disorder.
  • If it is white, it shows the presence of pus.
  • If it is pink to red, it indicates the presence of red blood cells.
  • If it is brownish-black, it indicates the presence of melanin or homogenistic acid (a rare disorder).
  • If it is blue to green, it is a liver disorder.
Sometimes, due to the intake of some food or medicines also, one could notice a change in the color or their urine, e.g. the intake of beet imparts a reddish color to urine. The intake of vitamin B capsules gives a dark-yellow color to it, if rifampicin is taken; it gives an orange tinge to the urine.
  • Usually, it is clear, sometimes, it is cloudy.
  • Sometimes, it is turbid due to the presence of WBCs (White blood cells), epithelial cells.
  • Sometimes, it is hazy due to mucus.
  • Smoky due to red blood cells.
  • Milky due to chyle (lymph).
  • Usually acidic pH range 4.5–7.5.
  • If pH less than 4.7 it is more acidic.
  • If pH more than 7.5 it is more alkaline.
  • Usually, it is aromatic in normal conditions.
  • It has a fruity odor in diabetes.
  • Ammoniacal odor in cases of urine retention.
  • Foul smelling due to urinary tract infection.
Sediment formation at the bottom of a container after collection
  • Usually, there is no or very little formation of sediment in normal conditions.185
  • If pus cells, red blood cells, cysts or epithelial cells are present, the sedimentation rate ranges from moderate to high.
Specific gravity
  • Usually varies from 1.003 to 1.060.
  • A low special gravity indicates diabetes insipidus or kidney infection (chronic).
  • High specific gravity indicates diabetes mellitus or acute kidney infection.
Chemical Examination of Urine
  • Normally absent.
  • Present in kidney disorders, dehydration, heart disease, and severe diarrhea.
Sometimes, due to an excessive muscular exercise, prolonged cold baths, excessive protein intake or vaginal discharge in the urine, the test shows the presence of protein.
  • Normally absent.
  • If present, it indicates diabetes mellitus or hyperactivity of the endocrine glands.
  • It can be present after brain injury or coronary thrombosis.
Ketone bodies
  • Normally absent.
  • If test shows ketones, it is due to severe diabetes mellitus, fevers, certain nervous disorders or prolonged diarrhea and vomiting.
  • Even when a person starves, the urine shows a presence of ketone bodies.
Bile pigments
  • Normally absent
  • Present in liver disorders.186
Bile salts
  • Normally absent
  • Present in liver disorders.
  • Normally present in very low concentrations
  • Increased in liver disorders.
  • Normally absent.
  • Present in acute kidney infections, kidney cancer and tuberculosis of the kidneys, chronic infections and stone formation in the kidneys, severe burns or a reaction to blood transfusion.
Additional Chemical Tests
Nonglucose Sugars
  • Lactose: May be present normally. It is present in lactating women.
  • Fructose: Present in liver disorders.
  • Pentoses: Are present due to drug therapy or hereditary conditions.
Nonglucose Reducing Substances
  • Ascorbic acid: Present in vitamin C therapy.
  • Salicylic acid: Due to drugs having salicylates.
  • Menthol: Due to the intake of food containing menthol.
Present Due to Bacterial Infection
  • It is present in very low concentrations.
  • It is increased due to intestinal obstruction, cholera, typhoid fever or peritonitis.
  • Sometimes, it is due to the intake of diets rich in proteins.
Microscopic Examination
Pus cells
  • Normally 2 to 3 pus cells are present in HPF (high power field of microscope).
  • 187If more than 5, it indicates urinary tract infection or noninfectious condition such as fever, stress and dehydration, irritation to urethra, bladder or urethra.
Epithelial cells
  • Normally two to three present in males.
  • Normally two to five present in females.
  • More than five epithelial cells per HPF indicate tubular damage, pyelonephritis or kidney transplant rejection.
  • Normally absent.
  • There are hyaline cysts, red cell cysts, white cell cysts, granular cysts, waxy cysts and fatty cysts. They are present due to kidney disorders.
  • Occasional hyaline cysts may be present due to physical exercise and physiological dehydration.
  • Granular cysts may be present after strenuous exercise for a short duration.
Amorphous Material
  • Amorphous urates of sodium, potassium or calcium are present normally.
  • Amorphous phosphates of calcium and magnesium are present normally.
  • Uric acid, calcium sulfate, calcium oxalate and ammonium magnesium phosphate (triple phosphate) crystals are indicative of the presence of kidney stones.
  • Hippuric acid, calcium carbonate, ammonium biurate and calcium phosphate crystals are nonsignificant.
  • Following crystals, found in acidic urine indicate abnormal metabolism—cystine, cholesterol, leucine, tyrosine, bilirubin, hematoidin and sulfonamides.
  • Normally absent.
  • If present indicates infection.
Yeast Cells
  • Normally absent.
  • May be present in acidic urine containing sugar.
  • Normally absent.
  • If present, they are Trichomonas vaginalis (from vagina) or Trichomonas hominis (from rectum).
Q. Sputum examination
A. Sputum Examination
Sputum is usually collected in a sterile plastic container given to the patient from the lab.
Naked Eye Examination
  • Quantity: This varies from a few ml in the morning sample to a liter in 24 hours. Large quantities are seen in bronchiectasis, lung abscess and tuberculosis.
  • Odor: It is usually offensive in bronchiectasis, lung abscess and gangrene of the lung.
  • Consistency: It may be serous, purulent, blood streaked, hemorrhagic or viscid, depending on the underlying disorder.
Microscopic Examination
  • Normally there may be epithelial cells, leukocytes, fibrinous strands and bacteria.
  • Abnormal contents include large number of epithelial cells, pus cells, elastic fibers, malignant cells, Charcot-Leyden crystals, fibrinous casts and parasites.
189The specimen of the sputum is treated with an equal amount of 4% sodium hydroxide. Keep at 37° for half an hour until the mixture is homogenous. The mixture is neutralized with 8% hydrochloric acid and centrifuge. The smear is prepared from the deposit of centrifuge.
  1. Unstained preparation
    1. Curshman's spiral: Characteristic of bronchial asthma, catarrhal conditions and pulmonary tuberculosis.
    2. Bronchial cast: Seen in fibrinous bronchitis.
    3. Dittrich's plugs: Seen in chronic bronchitis, brochiectasis and bronchial asthma.
    4. Elastic tissue: Seen in destructive lung diseases as abcess of lung, gangrene, malignant ulcerative tumors and tuberculosis with cavity
    5. Pneumoliths: Seen in calcified nodule of tuberculosis tissue or may be foreign body.
    6. Asbestos bodies: Seen in asbestosis.
    7. Hemosiderin pigment: Seen in heart failure cells of congestive cardiac failure.
    8. Charcot-Leyden crystals: Seen in bronchial asthma.
    9. Myelin globules: Seen in bronchitis.
    10. Malignant cells: Seen in pulmonary neoplasm as minute fragments of growth.
    11. Parasites: Hydatid hooklets or amoeba may be seen in case of hydatid cyst of lung or amoebic liver abcess rupturing in to lung respectively.
  2. Gram's stain: This is done to visualize gram-positive or gram-negative bacteria.
  3. Ziehl-Neelsen‘s stain: This is done to visualize acid fast bacteria, e.g. M. tuberculosis and M. leprae.
  4. Culture: Sputum is cultured on appropriate media and subcultured on selective media to find out the any bacteria.
Q. What causes anemia?
Q. Causes of anemia? (MUHS Nov/Dec 08 May/June 10)
A. How the body normally regulates red blood cell levels?
  • Red blood cells have a limited lifespan—about four months, after which they are removed from the blood. New red blood 190cells are formed out of stem cells of the bone marrow the rate of new-formation is controlled by a hormone called erythropoietin.
  • Erythropoietin is produced and secreted into the blood by specialized kidney cells. The rate at which erythropoietin is secreted depends on the amount of oxygen in the blood.
  • When the level of oxygen is low, more erythropoietin is secreted. High levels of erythropoietin stimulate the bone marrow to increase production of red blood cells.
  • When the oxygen level returns to normal, the signal to secrete erythropoietin diminishes.
There are many causes of anemia, but in all cases, red blood cells are lost more rapidly than they are replaced. The three main classes of anemia are:
  • Excessive blood loss
  • Excessive red blood cell destruction (‘hemolysis’)
  • Deficient red blood cell production.
Several conditions are associated with decreased red blood cell levels:
  • Iron deficiency, due to insufficient dietary intake or absorption from the digestive tract bleeding lesions in the digestive tract, like gastric ulcers blood loss during menstruation.
  • Heavy bleeding during surgery or after a trauma.
  • Chronic renal failure cancer.
The latter two are discussed below in details.
Anemia and Kidney Disease
People with chronic renal failure may suffer from severe anemia from various causes:
  • When kidney function stops working, waste products are stored in the blood. Some of these inhibit the new formation of red blood cells.
  • During hemodialysis, patients lose some blood every time they undergo treatment. Kidney disease can also include hidden bleeding from the digestive tract. Checks in the form of blood tests, is also a cause.
  • 191Reduced production of erythropoietin. Erythropoietin is a hormone that is produced in the kidneys, if the oxygen content in the kidney tissue is too low. It stimulates the new formation of red blood cells in the bone marrow. When the kidney tissue, due to disease, eventually perishes, the body's own production of erythropoietin also ceases. This is one of the most important causes.
Anemia and Cancer
It is common for cancer patients to develop anemia as a side effect of the disease itself or its treatment. The underlying causes include the following:
  • The cancer itself can affect the body's ability to produce red blood cells, e.g. bone marrow cancers, like leukemia and myeloma.
  • Loss of blood, due to surgery or hemorrhaging from the tumor itself. Especially in patients with colon cancer, hemorrhaging can cause a substantial loss of blood without tangible symptoms.
Treatment with chemotherapy or radiation therapy can also cause a reduction in the number of red blood cells. Over 60% of patients, who take cytotoxic drugs, suffer from anemia as a side effect.
Q. Write in brief on semen examination (MUHS Nov/Dec 10)
A. Semen analysis consists of the following procedures:
● Urethral and bulbourethral glands
0.1–0.2 cc
Viscous, clear
● Testes, epididymides, vasa deferentia
0.1–0.2 cc
Sperm present
● Prostate
0.5–1.0 cc
Acidic, watery
● Seminal vesicles
1.0–3.0 cc
Gelatinous, fructose positive
● Complete ejaculate
2.0–5.0 cc
Liquefies in 20–25 min
The male factor infertility is most commonly defined as abnormalities in the number of sperm present, proportion of the motile and morphologically normal sperm. WHO has defined normal values for human ejaculate?192
Commonly used normal semen parameters
>2.0 ml
>20 × 106/ml
>30% with normal morphology
<1 × 106/ml
Semen analysis is not a test for fertility: Fertility determination is a couple-related phenomenon that requires the initiation of a pregnancy. The patient cannot be considered fertile based only on normal semen analysis. It was shown that 30% of all patients with normal semen analysis have abnormal sperm function.
Semen specimen are obtained by masturbation into a sterile wide-mouth container after 2–5 days of abstinence and analyzed within 1 hour of collection. Therefore, the patients should be strongly recommended to collect samples within clinic area. If intercourse is the only way to collect sample, special nonreactive condoms are available.
Typically two to three semen analyses are obtained over a 3 months period prior to making any final conclusion regarding baseline sperm quality or quantity. However, if the first semen analysis is normal, the repeat test is not required. Recent febrile illness or exposure to gonadotoxic agents may affect spermatogenesis for up to 3 months; therefore, semen analysis has to be postponed.
Normal ejaculate volume is between 2 and 6 ml. 65% of the volume is from seminal vesicles, 30–35% is from the prostate and only 5% from the vasa. Low volume is associated with absence or decrease of seminal vesicle component of ejaculate (absence of SV, complete or partial obstruction of ejaculatory ducts) or retrograde ejaculation.
Normal semen pH is 7.2–8.0. Prostatic secretion is acidic while seminal vesicle fluid is alkaline (seminal fructose is derived from seminal vesicles). Acidic ejaculate (pH 7.2) may be associated with blockage of seminal vesicles. Infection is usually 193associated with alkaline ejaculate (pH 8.0). Azoospermia with low ejaculate volume; fructose negative and acidic may imply obstruction of the ejaculatory ducts. pH over 8.0 may indicate infection. The semen is initially in liquefied state but quickly coagulate by the action of protein kinase secreted by the seminal vesicles. Proteolytic enzymes from the prostate liquefy coagulum in 20–25 minutes. Abnormal liquefaction may be caused by prostatic abnormalities, e.g. prostatitis. Increased viscosity may affect sperm motility.
Evaluated in Mackler or Cell-VU chambers. Azoospermic specimen contains no sperm, oligospermic specimen reveals concentration of less than 20×106 and normospermic specimen contains more than 20×106.
Motility and Forward Progression
Normally 50% of sperm in the specimen are motile. Forward progression describes how fast the motile sperm are moving (normal 2+ in the scale from 0 to 4).
No movement
Movement, none forward
Occasional movement of a few sperm
Slow, undirected
Slow, directly forward movement
Fast, but undirected movement
Fast, directed forward movement
Very fast forward movement
Extremely fast forward movement
Shape of Spermatozoa
Several techniques have been described to evaluate sperm morphology. Sperms are classified into normal-oval-shaped, tapered, amorphous, duplicated and immature. Normal spermatozoid must have an oval form with smooth contour, acrosomal cap encompassing 40–70% of head, no abnormalities 194of midpiece, or tail and no cytoplasmic vacuoles of more than half of the sperm head. Head size is 5–6 μm × 2.5–3.5 μm. Any borderline sperm are counted as abnormal (amorphous, tapered, duplicated, immature, coiled tail, blunted tail, midpiece abnormalities). The predictive value of sperm morphology in determining pregnancy rates is low.
  1. WHO criteria: >30% normal forms (100 cells evaluated)
  2. Strict criteria: (Higher predictive value in determining rates of pregnancy in IVF program) are based on the morphology of postcoital spermatozoa found at the level of the internal cervical os. 100 cells evaluated for only normal sperm (>14% normal forms). Men with fewer than 4% normal forms usually failed to fertilize without micromanipulation. Strict criteria for normal sperm morphology include.
Sperm head: Smooth oval configuration. Length: 5–6 microns. Width: 2.5–3.5 microns. Acrosome comprises 40–70% of the anterior sperm head.
Midpiece: Axially attached, 1.5 times the head length, ≤ 1 μm in width.
Tail: Straight, uniform, slightly thinner than the midpiece, uncoiled, ± 45 μm long.
White Blood Cells (WBC)
All semen samples have WBC in them. If greater than 1 million WBC per 1 ml are present, there is concern of infection. Generally leukocytospermia (WBC in the semen) affects 5–10% of the patient population, but can rise to 20% in certain patients groups. Semen has to be cultured for aerobic and anaerobic infection as well as Chlamydia and Mycoplasma. Additionally, leukocytes have to be differentiated from immature germ cells using immunohistochemical methods. WBC cells are deleterious because of their ability to stimulate the release of reactive oxygen species (ROS), thereby inhibiting sperm motility and sperm function. Reactive oxygen species (ROS) are produced by polymorphonuclear cells. The three main ROS are superoxide anion, hydrogen peroxide, and the hydroxyl radical. On the other hand, seminal plasma contains a number of antioxidants that protect sperm from oxidative damage from exposure to 195ROS. Men who have higher concentrations of such antioxidants may be able to tolerate greater concentrations of seminal leukocytes. Despite an apparently abnormal threshold level for leukocytes within the semen, a wide range of conflicting evidence exists as to the significance of seminal leukocytes and infertility. The impact of this condition and its treatment on semen quality are extremely controversial.
Viability tests are used in cases of low motility to determine the presence of live sperm vs necrozoospermia. The eosin test is based on the fact that eosin is excluded by live cells which are not stained. The tail of only live spermatozoa is swelling in the hypoosmotic solution (Hypoosmotic swelling test).
Fructose (13 μ mol or more per ejaculate): Fructose is androgendependent and is produced in the seminal vesicles. Fructose levels should be determined in any patient with azoospermia and especially in those whose ejaculate volume is less than 1 ml, suggesting seminal vesicle obstruction or atresia. Absence of fructose, low semen volume and failure of the semen to coagulate indicate either congenital absence of the vas deferens and seminal vesicles or obstruction of the ejaculatory duct.
Semen analysis has comparatively limited predictive value for the ability of the individual to achieve pregnancy. Additionally, 10–20% of infertile couple will not have any abnormalities. In order to enhance the diagnostic power of semen analysis, new tests have been developed to identify functional defects and fertilizing potential of the sperm. The clinical data to support their use are not conclusive.
  1. Antisperm antibodies test: Sperm agglutination, reduced sperm motility, abnormal postcoital test are suspicious for the presence of antisperm antibodies. Several tests are presently available including sperm immobilization test, sperm agglutination tests, indirect immunofluorescence test, enzyme-linked immunosorbent assay, radiolabelled antiglobulin assay. Immunobead rosette test is one of the most informative and specific and can identified different 196antibody classes involved (IgG, IgA, IgM) and location on the sperm cell (head, body or tail).
  2. CASA: Computer-assisted semen analysis. Mostly for assessment of sperm concentration and specific patterns of sperm motility (velocity, linearity, etc.). The available clinical data show that the measurement obtained by CASA are correlated with conception in vivo and fertilization in vitro, but comprehensive quality control and quality assurance programs are necessary to ensure accuracy. The equipment is highly expensive.
  3. Acrosome reaction: Absence of acrosome reaction implies poor prognosis for fertilization. The test for acrosome reaction is very expensive, labor intensive, subjective and not cost-effective since only 5% of infertile patients do not demonstrate an acrosome reaction.
  4. Hamster egg penetration test: To check sperm fusion ability. The diagnostic value is controversial because of difficulty in optimizing protocol. However, a zero test score may indicate a major impairment of sperm fusion capacity.
  5. In Hemizona test (to evaluate sperm zona-binding capacity): The two halves of human zona pellucida is incubated with patient's capacitated sperm and control fertile donor's sperm.
  6. PCR-based detection: The pathogens in the semen in patients with asymptomatic genital infection.
  7. Biochemical markers: Creatine kinase, reactive oxygen species.
Postejaculate Urine Analysis
Retrograde ejaculation is commonly seen in patients with diabetes, after transurethral surgery, retroperitoneal lymph nodes dissection and spinal cord injuries. When bladder neck coaptation is not complete, the seminal fluid may travel retrograde into the bladder during periurethral muscular contraction. Patient may present with low semen volume, low motility and sperm concentration.
197Urinalysis performed immediately after ejaculation. Unspun specimen examined for sperm under the microscope. If sperms are present, specimen is processed further to evaluate concentration, motility and morphology. In certain situations sperm retrieved from the urine may be used for assisted reproduction.
Q. CSF findings in tuberculous meningitis.
Pressure (in mm of water)
- Elevated (>300 mm of water)
Queckenstedt's test
- +ve
- Clear or slightly-turbid
- Forms fibrin coagulum on standing
Types and number of cells
- Mainly mononuclears
- 100–1,000
- Raised
- _ ve
- +ve
Z N staining
- AFB bacilli may be seen
-Mycobacterium tuberculosis bacilli may be seen.
Q. Chyluria
A. Definition: Chyluria or chylous urine is the presence of chyle in the urine stream resulting in urine appearing milky white.
  • Bancroftian filariasis
  • Pregnancy or childbirth.
  • Due to presence of microfilaria the lymphatic channels are blocked and the blocked lymphatic channel may open into the kidney or ureter or sometimes into the bladder and chyle leaks into the urinary tract resulting in chyluria.
198Q. CSF findings in pyogenic meningitis.
Pressure (in mm of water)
- 200–500
Queckenstedt test
- +ve
- Opalescent/purulent
- May clot
- Turbid
Types and number of cells
- Mainly polymorphs
- 500–20,000
- 50–500 mg
- Decreased or absent
- _ve
- +ve
- Pneumococci/Streptococci/E. coli may be isolated
Q. Universal precaution regarding collection of blood. (MUHS May/June 09)
Q. Nurses’ role in collection and dispatch of various laboratory tests. (MUHS Nov/Dec 09)
A. The occupational safety and health administration offer guidelines for the use of universal precautions. This approach to infection control considers all human blood and body fluids as though they were infectious. In some situations, blood and body fluids might be indistinguishable, so the entire scenario is considered biohazard and certain universal or standard precautions should be observed.
Transmission occurs by three routes:
  1. Nonintact skin
    • Cuts
    • Scratches
    • Chapped hands
    • Wear a band-aid over the cut or scratch.
  2. Percutaneous
    • Needle stick
    • Broken glass
    • Dispose of sharps immediately and handle specimens with caution.
  3. 199Mucous membrane
    • Droplets
    • Splashes
    • Touching mouth, eyes or nose with contaminated hands
    • Use gloves, pipettes and splash guards and wash hands.
Universal Precautions to Prevent Exposures
  1. Prescribe slib and data/any advise for universal precaution.
  2. Gloves: Wear when there is potential for skin contact with blood and other potentially infectious materials, or items and surfaces contaminated with these materials. Change gloves in between different patients and when handling different types of specimens from the same patient.
  3. Face shields: Wear during procedures that are likely to generate droplets of blood or other potentially infectious materials.
  4. Wash hands: Whenever gloves are removed and before each patient.
  5. Be aware: Avoid accidental injuries by paying attention when handling sharps, performing procedures, or cleaning instruments.
  6. Put sharps in their place: Always put needles, syringes, scalpel blades, pipettes and other sharps in puncture resistant containers marked with a biohazard symbol (orange or red color).
Important rule of universal precautions is to treat all body fluids as potentially infectious
Safety in the Laboratory
  1. No open-toed shoes or sandals.
  2. No skirts or shorts.
  3. No oversized clothing.
  4. Immediately dispose of sharps after use.
  5. Do not place lancets or needles on station after use.
  6. Never recap used needles using both hands.
200Preventing transmission of what?
Blood-borne pathogens: Hepatitis viruses, human immunodeficiency virus (HIV), cytomegalovirus (CMV) and other microorganisms that cause syphilis, malaria, relapsing fever, and Creutzfeldt-Jakob disease.
Two most worrisome
  1. Hepatitis B
    • Most frequently occurring laboratory associated infection
    • Causes hepatitis B
    • It is a pathogen that targets the liver
    • Can survive, and therefore remain infectious, for up to a week on surfaces
    • Approximately 8,700 health care workers contract hepatitis B annually
    • 200 health care workers die annually as a result of transmission.
  2. Human immunodeficiency virus (HIV)
    • The virus responsible for causing AIDS
    • Incidence of work-related infection is low
    • Phlebotomy procedures account for 50% of HIV exposures in health care setting
    • Prognosis is very poor once infected.
What if an exposure does occur?
  1. Don't panic!
  2. Carefully dispose of sharp (if applicable) to prevent a second exposure.
  3. If it is a puncture wound to skin, “milk” site of exposure under running water.
  4. After milking site, wash thoroughly with soap and water.
  5. Dry site well and bandage wound appropriately.
  6. If it is a mucous membrane exposure, flush site with copious amounts of water.
  7. If it's exposure is to the eyes, discard any contact lenses before flushing site.
  8. 201Do not rub mucous membranes!
  9. Pat mucous membranes dry.
  10. Immediately report to RN on site and notify clinic coordinator.
  11. Follow the community health blood and body fluid exposure policy.
Community Health Blood and Body Fluid Exposure Policy
  1. All staff and volunteers exposed to blood or body fluids must
    1. Report immediately to RN on site.
    2. Complete an injury/accident report.
    3. Receive wound care.
    4. Be offered postexposure testing, prophylaxis and counseling as outlined.
  2. The RN on site will:
    1. Immediately evaluate the significance of the exposure.
    2. Provide wound care. All skin wounds should be washed thoroughly with running water and soap. All mucous membrane exposures should be rinsed thoroughly with running water.
    3. Assist in completing injury/accident report. Following this, a copy will be delivered to the clinic coordinator.
    4. Identify relevant health history of source and exposed and recommend testing and prophylaxis based on these guidelines.
    5. If the exposed is referred to the emergency department (ED), the RN will contact the ED and provide all pertinent information required.
    6. Provide counseling to source and exposed.
  3. If any of the following criteria are met, the exposure is of high risk and the exposed must immediately be referred to the nearest ED for all care:
    1. Source or partner known to be positive for HIV, HBV, or HCV.
    2. Source or partner engaged in high-risk behavior: Men who have sex with men (MSM), intravenous (IV) drug use, or multiple sex partners.
    3. 202Intravenous or intramuscular injury with blood/body fluid contaminated needle.
    4. Wound produced by blood/body fluid contaminated instrument which causes uncontrolled bleeding.
    5. Fresh wound inoculated with blood/body fluids.
    6. Mucous membranes inoculated with blood/body fluids.
      All other exposures are considered low risk for transmission of HIV, HBV and HCV. Testing and counseling should occur in all scenarios.
  4. The clinic coordinator will follow-up to ensure correct laboratory tests have been drawn, received and processed on the source.
  5. All exposed will be offered a one-week follow-up appointment by community health to review test results and receive counseling.
  6. Postexposure testing and follow-up
    1. All source and exposed should be tested for HIV, HBV-Ab, HBV-Ag and HCV-Ab.
    2. The source does not need to consent to such testing.
    3. If the exposed fall in the high-risk exposure category, testing and all measures should be performed at the nearest emergency department.
    4. In all other cases, testing should be performed at community health after signing consent forms.
    5. Test results from the source will be disclosed to the exposed and their physician.
    6. The clinic coordinator will follow-up on all test results performed at community health.
    7. If the source or exposed test positive, they will be immediately contacted and given a prompt appointment for further testing, treatment and counseling.
    8. Follow-up testing of the exposed is recommended as follows:
      • At 6 weeks for HIV-Ab
      • At 3 and 6 months for HIV, HBV-Ab, HBV-Ag and HCV-Ab.
  7. 203Postexposure immunization and prophylaxis of exposed
    1. Tetanus and diphtheria toxoid (0.5 ml) should be administered unless a documented Tb booster or completed series have been given within 5 years or if the exposed refuses.
    2. If the source fulfills any of the following criteria, there is a high risk of HBV transmission and the exposed will be referred to the nearest ED for hepatitis B immunoglobulin
      • Source or partner is known HBV positive
      • Source or partner has high-risk behavior: MSM, IV drug use, or multiple sex partners.
    3. If the source is HBV negative or unknown and is not in the high-risk category, the exposed should receive HBV immunizations (1.0 ml) regardless of prior immunization status.
    4. If the exposed has not completed a 3-dose series before, it should be encouraged now.
    5. A consent form will not be signed to accept or refuse vaccination.
    6. Hepatitis B immunoglobulin is most effective when given within 48 hours exposure.
    7. Hepatitis B immunization is recommended for all health care workers and should be provided unless serology to prove immunity is available within 48 hours.
    8. Currently there is no immunization or prophylaxis that exists for HCV.
    9. All “significant exposure” victims to HIV will immediately be referred to the nearest ED for antiretroviral prophylaxis.
    10. If the source is HIV negative or unknown, it is not considered a “significant exposure” and antiretroviral prophylaxis is not recommended
    11. The clinic coordinator will follow-up with those referred to the ED for care within 24 hours.
    12. Antiretrovirals are most effective when started within 2 hours of exposure.
  8. 204Postexposure counseling:
    1. All sources will sources will receive counseling by the RN on site regarding tests required, follow-up, and disclosure of their results to the exposed and their physician.
    2. All exposed will receive counseling by the RN on site and if available, the physician.
    3. The exposed will also receive a copy of “postexposure recommendations”.
The Community Health Laboratory Requisition
On-site Tests
  • The left column of the community health lab requisition
  • Will be performed by you in the lab
  • Write results on the community health lab requisition
  • Show the results to the physician
  • Ask the physician if the patient can leave or if they need to return to their room.
Off-site Tests
  • The right column of the community health lab requisition
  • Will be collected and processed for transport by you and then sent to quest diagnostics for further processing and result reporting to physician.
Specimen Collection and Processing
24-hour urine
  1. Instruct the patient to drink less liquid than usual, unless there are medical contraindications and to abstain from alcoholic beverages during the collection period.
  2. Instruct the patient that the urine container needs to be refrigerated and they should keep the container out of the reach of children.
  3. Look up handling instructions for the type of 24-hour urine test ordered in the Quest Lab Manual.
  4. Follow instructions for the specific test ordered.
  5. 205Label the container with the patient name and chart number.
  6. Instruct the patient that the 1st morning urine (on the 1st day of collection), must be discarded.
  7. Have the patient write the time of this void on the specimen container.
  8. The patient then must collect all urine voided for the next 24 hours.
  9. The final collection should be the 1st morning urine of the 2nd day of collection.
  10. Write the time of this void on the specimen container.
  11. Have patient return container to community health laboratory.
  12. Order and print 24-hour urine quest requisition on the computer.
  13. Write total volume of urine collected and send sample in sterile urine container.
  14. Place container with a biohazard bag, containing the quest requisition, in the refrigerator.
  15. Place the “specimens in refrigerator” sign on top of the quest specimen collection box.
  16. Complete the appropriate sections of the community health lab requisition.
  17. File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  18. Most recent requisition goes in back (the last requisition in the laboratory section).
  1. Always label sterile urine containers with patient name and chart number, before giving to patient for urine collection.
  2. Have patient void in container.
  3. Have patient cover the container with the lid and give specimen to you.
  4. Remove lid from urine container.
  5. Pipette urine from the container into the urinalysis tube until it reaches the max fill line.
  6. 206Replace lid on urine container.
  7. If no other tests are ordered, dispose of the urine container and remaining urine, in the biohazard trash can.
  8. Order and print the urinalysis test on the quest requisition on the computer.
  9. Label the urinalysis tube.
  10. Place the urinalysis tube in a biohazard bag with the quest requisition.
  11. Place biohazard bag in the quest specimen collection box.
  12. Complete the appropriate sections of the community health laboratory requisition.
  13. File the community health lab requisition in the patient's chart under the laboratory tab (green).
  14. Most recent requisition goes in back (the last requisition in the laboratory section).
Urine Dipstick
  1. Always label sterile urine containers with patient name and chart number, before giving to patient for urine collection.
  2. Have patient void in container.
  3. Have patient cover the container with the lid and give specimen to you.
  4. Remove lid from urine container.
  5. Dip chemistry stick in urine until all pads are covered.
  6. Remove stick from urine and lie flat on paper towel.
  7. Remove excess urine from stick.
  8. Record results on the community health lab requisition after 30–120 seconds. Please see chemistry stick container for more specific timing.
  9. Dispose of chemistry stick in a biohazard sharps container and reseal the urine container.
  10. Throw paper towel away in biohazard trash can.
  11. Complete the appropriate sections on the community health laboratory requisition.
  12. Show the patient's physician the test results and ask if the patient may leave or if they need to return to their room.
  13. 207File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  14. Most recent requisition goes in back (the last requisition in the laboratory section).
  1. Follow all directions outlined for urine dipstick except use a keto-diastix instead of a chemistry stick.
  2. Follow results recording procedure for urine dipstick.
Urine Pregnancy Testing
  1. If available use Dixie cup for urine collection if no other tests are ordered.
  2. Always label urine collection container with patient name and chart number before giving to patient.
  3. Open an HCG kit, making sure mini pipette does not touch anything.
  4. Place the test device on a clean and level surface.
  5. Pipette urine and add 3 drops to the “S” (sample) well on the pregnancy test device.
  6. Start timer and wait 3 minutes to read the results.
  7. Read the test device
    • There always has to be a single line next to the “C” (control) region. If no line appears, repeat the test with a new test device. If the problem persists, contact technical marketing at 800-877-6242.
    • Negative (–) result: Only one line next to the “C” region should appear.
    • Positive (+) result: Two lines should appear, one next to the “C” region and one next to the “T” (test) region.
  8. Complete the pregnancy test log in its entirety (located in cabinet by refrigerator).
  9. Dispose of test device, mini-pipette, and urine container in biohazard trash can.
  10. Complete the appropriate sections on the community health lab requisition.
  11. Notify physician of test result and ask if patient may leave.
  12. 208File the community health lab requisition in the patient's chart under the laboratory tab (green).
  13. Most recent requisition goes in back (the last requisition in the laboratory section).
Community Health Pregnancy Test Policy
  • A pregnancy test can be ordered and performed by a medical assistant, nurse, phlebotomist, medical student, trained volunteer or front desk person
  • It must be tracked according to the pregnancy protocol
  • It is strongly encouraged for all females that have one or more of the following symptoms—missed period, morning sickness and/or breast soreness.
  • Any patient with a positive (+) result, will be referred to another agency for care and given a list of referral sites
  • Documentation must occur in the patient's chart if positive (+)
Clean Catch Instructions for Urine Cultures/URCC/Sterile/Midstream Specimens
  1. Wash hands thoroughly.
  2. Cleanse the tip of the penis with a towelette, beginning with the urethral opening and making concentric circles outward.
  3. For uncircumcised males, the foreskin must first be retracted.
  4. Repeat the above procedure with a 2nd towelette.
  5. Void the first portion of the urine into the toilet.
  6. Stop the urine flow momentarily.
  7. Resume flow and collect a portion in a sterile urine container.
    Be sure not to touch the inside or lip of the sterile urine container with anything.
  8. Stop the urine flow momentarily.
  9. Void remaining urine into the toilet.
  10. Cover the sterile urine container with the lid, making sure to touch only the outside surfaces of the lid and container.
  1. Wash hands thoroughly.
  2. Stand in a squatting position over the toilet.
  3. Separate the folds of the labia majora.
  4. Cleanse the area with a towelette, beginning with the urethral opening and making concentric circles outward.
  5. Cleanse the area again with a towelette, wiping front to back once.
  6. Void the first portion of the urine into the toilet.
  7. Stop the urine flow momentarily.
  8. Resume flow and collect a portion in a sterile urine container.
    Be sure not to touch the inside or lip of the sterile urine container with anything.
  9. Stop the urine flow momentarily.
  10. Void remaining urine into the toilet.
  11. Cover the sterile urine container with the lid, making sure to touch only the outside surfaces of the lid and container.
Processing of Urine Cultures/URCC/Midstream Specimens
  1. Uncover the sterile urine container.
  2. Open a midstream collection kit, making sure not to touch the stick.
  3. Place the tip of the stick in the urine.
  4. Push the gray top tube into the holder attached to the stick.
  5. Urine will automatically fill in the tube until full.
  6. Once full, remove tube using the wings on the holder.
  7. Gently agitate urine in tube, mixing the additive well.
  8. Recover the sterile urine container and dispose in the biohazard trash can if no other urine tests are ordered.
  9. Dispose of collection container in the biohazard sharp container.
  10. Order and print the urine culture test on the quest requisition on the computer.
  11. 210Label tube containing the urine.
  12. Place the culture tube in a biohazard bag with the quest requisition.
  13. Place biohazard bag in the quest specimen collection box.
  14. Complete the appropriate sections of the community health laboratory requisition.
  15. File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  16. Most recent requisition goes in back (the last requisition in the laboratory section).
O and P (ova and parasites)
  1. Label both containers in O and P kit with patient name and chart number before you give to patient to take home.
  2. Place O and P kit in biohazard bag with community health requisition.
  3. Instruct patient that they should collect the specimen in a clean, plastic container (e.g. margarine tub, milk jug cut in half).
  4. On the day of specimen collection, instruct the patient to record the date and consistency of the sample on each bottle in the O and P kit.
  5. Instruct the patient to unscrew the lid of the 1st bottle and use attached “pooper scooper” to place small amounts of sample into it.
  6. Patient should fill bottle with sample until the contents reach the fill line.
  7. The patient should then rescrew the lid on the 1st bottle and repeat the same procedure for the 2nd bottle.
  8. Patient should then place the O and P kit back in the biohazard bag and return to community health laboratory that day.
  9. After receiving the O and P kit, remove the Community Health Requisition and complete the appropriate sections.
  10. Order and print the O and P test(s) on the quest requisition on the computer.
  11. Label the bottles.
  12. 211Place the O and P kit back in the biohazard bag with the quest requisition.
  13. Place biohazard bag in the quest specimen collection box.
  14. Complete the appropriate sections of the community health laboratory requisition.
  15. File the community health lab requisition in the patient's chart under the laboratory tab (green).
  16. Most recent requisition goes in back (the last requisition in the laboratory section).
Hemoccult Cards/Occult Blood Test
Patient Preparations
  • Diet may include only small amounts of well-cooked chicken, turkey, or tuna
  • Patient should eat generous amounts of both raw and cooked vegetables except raw vegetables high in peroxidase activity (e.g. turnips, broccoli, horseradish, cauliflower, cantaloupe, parsnip, red radishes).
  • Patient should eat plenty of fruits, especially prunes and apples.
  • Patient should eat bran and bran-containing cereals.
  • Patient can consume moderate amounts of peanuts and popcorn daily.
  • If any of the above mentioned foods are known to cause discomfort, the patient is instructed to consult their physician.
  • Patients should avoid any red or rare meat.
  • For 7 days prior and during testing, patients should avoid taking aspirin or other inflammatory medications.
  • For 2 days prior and during testing, patients should not use rectal medicines, tonics, or vitamin preparations with contain vit C in excess of 250 mg per day.
Specimen Handling and Developing
  1. Label all 3 occult cards with patient name and chart number before you give to the patient to take home.
  2. Place hemoccult kit with community health laboratory requisition in biohazard bag and give to patient.
  3. 212Instruct the patient to place the provided tissue paper in the toilet bowel just prior to specimen collection.
  4. Patient should lift tissue paper with specimen out of toilet and use one end of the provided applicator to obtain a small sample of stool from the beginning of the bowel movement.
  5. Stool should be applied as a very thin smear on window A of a single hemoccult card.
  6. With the other end of the applicator, a 2nd sample should be taken and applied as a very thin smear on window B of the same hemoccult card.
  7. The patient should close the flap on the hemoccult card and label with date of collection.
  8. Repeat the above procedures for the remaining cards and place in biohazard bag.
  9. Patient should return hemoccult cards to the community health lab as soon as possible.
  10. After receiving hemoccult cards flip them over and lie on flat surface.
  11. Open back window and apply 2 drops of occult blood developer to boxes A and B.
  12. Read results after 30 seconds and within 2 minutes.
  13. Any blue color within or on the outer rim of the specimen is positive (+).
  14. Lack of blue color indicates a negative (–) test result.
  15. For comparison/controls, place 1 or 2 drops of occult blood developer between the positive and negative monitor boxes.
  16. The positive monitor box should turn blue and the negative monitor box should not have any trace of blue.
  17. If comparison/controls do not meet these standards, notify physician.
  18. Complete the appropriate sections on the community health laboratory requisition.
  19. Notify physician of results and ask if patient may leave.
  20. File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  21. 213Most recent requisition goes in back (the last requisition in the laboratory section).
Rapid Strep
  1. Obtain a rapid strep kit and a sterile swab.
  2. Using the sterile swab, gently collect a sample from the patient's throat. Be careful not to elicit a Gag Reflex.
  3. Place swab in the sample well of the strep kit testing device.
  4. Break the developer and gently agitate to mix well.
  5. Squeeze contents of developer into sample well over swab.
  6. Wait 5 minutes or indicated time on packaging before reading results.
  7. Read the test device:
    1. There always has to be a single line next to the “C” (control) region. If no line appears, repeat the test with a new test device. If the problem persists, notify the physician and clinic coordinator.
    2. Negative (–) result: Only one line next to the “C” region should appear.
    3. Positive (+) result: Two lines should appear, one next to the “C” region and one next to the “T” (test) region.
  8. Dispose of test device, swab and developer bottle in biohazard trash can.
  9. Complete the appropriate sections on the community health laboratory requisition.
  10. Notify physician of test result and ask if patient may leave.
  11. File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  12. Most recent requisition goes in back (the last requisition in the laboratory section).
Pap Smears
  1. Complete both the community health lab requisition and the hardcopy of the quest requisition.
  2. 214Order the test on the quest requisition on the computer.
  3. Print 2 copies of the requisition and place one in the biohazard bag with specimen and one in the accordion file with the hardcopy of the quest requisition.
  4. Place biohazard bag in the quest specimen collection box.
  5. File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  6. Most recent requisition goes in back (the last requisition in the laboratory section).
Specimen Collection
Blood glucose fingerstick
Select finger for puncture (e.g. noncalloused index or middle finger).
  1. Clean side of finger with alcohol prep pad.
  2. Allow to air dry.
  3. Put glucometer testing strip into glucometer.
  4. The glucometer should automatically turn on.
  5. Ensure the lot number calibrated on the glucometer, matches the lot number on the testing strip.
  6. Remove safety from lancet.
  7. Squeeze hand and finger tightly while holding lancet firmly against side of finger selected for puncture. Make sure lancet is aligned against the grain of the fingerprint before puncture.
  8. Push back of lancet to activate and puncture selected finger.
  9. Wipe away 1st drop of blood.
  10. Apply blood to glucometer strip until it beeps.
  11. Apply pressure to wound with gauze while glucometer reads results.
  12. Apply band aid to wound.
  13. Complete the appropriate sections on the community health laboratory requisition.
  14. Notify physician of test result and ask if patient may leave.
    For your information:
    • Normal glucose levels 60–100 mg/dl.
  15. 215File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  16. Most recent requisition goes in back (the last requisition in the laboratory section).
  1. Follow the above procedures for blood glucose fingerstick except wipe away the first 3 drops of blood.
  2. Using a microcuvette, fill the optical eye by capillary action. Make sure to handle microcuvette appropriately by utilizing the wings.
  3. Bandage patient according to above procedure for blood glucose fingerstick.
  4. Turn on the Hemocue Photometer.
  5. Once display flashes “Ready”, place microcuvette in cuvette holder and slide it in.
  6. The machine will automatically flash the results.
  7. Complete the appropriate sections on the community health laboratory requisition.
  8. Notify physician of test result and ask if patient may leave.
  9. File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  10. Most recent requisition goes in back (the last requisition in the laboratory section).
Fasting vs Nonfasting
  • Patient has not had anything, except plain water, for 8–12 hours.
  • Patient has had something to eat or drink within past 8 hours.
Note: If a lipid or cholesterol test is ordered and patient is Nonfasting, ask physician if they still want blood drawn or if the patient needs to reschedule.
216Venipuncture Procedure
  1. Double identify patient, (e.g. full name and date of birth).
  2. Review community health laboratory requisition for tests ordered.
  3. Determine if patient is fasting and indicate it on the community health laboratory requisition.
  4. Select appropriate tubes for tests and place in the correct order of draw.
  5. Check to make sure no tubes are expired.
  6. Secure tourniquet.
  7. Select venipuncture site by palpating for a vein in the antecubital area.
    • Use median cubital then, basilic, then, cephalic veins
    • Never draw blood from the same side as a mastectomy
    • Never draw blood from the same side as a working AV-fistula
    • You may draw blood from the same side of a non-working AV-fistula below its anastomotic site.
  8. Release tourniquet.
  9. Cleanse the site with an alcohol prep pad by starting at venipuncture site and making concentric circles outward.
  10. Allow the site to air dry.
  11. Select appropriate sized needle and attach to holder.
  12. Reapply the tourniquet.
  13. Anchor the vein selected using your finger or thumb below the venipuncture site.
  14. Needle should enter the skin at a 15–30° angle or very parallel to the vein with the bevel up.
  15. Enter in one smooth motion.
  16. Anchor your hand on the patient's forearm.
  17. Push the evacuated tube onto the back of the needle using the wings on the holder.
  18. Allow the tube to fill.
  19. While continuing to anchor your hand, remove evacuated tube off the back of the needle using the holder's wings.
  20. Release the tourniquet within one minute of application.
  21. Additional evacuated tubes may be pushed onto the back of the needle and allowed to fill.
  22. 217Once finished collecting all specimens, place a piece of gauze over the puncture site.
  23. Do not press down until after you have withdrawn the needle.
  24. Instruct the patient to apply pressure to the puncture site.
  25. Dispose of needle in sharps container.
  26. If the evacuated tube(s) contains an additive, gently invert the tube(s) 10 times to mix.
  27. Place a pressure bandage (band-aid) over site.
  28. The patient may leave now if no other testing is ordered.
  29. Complete the appropriate sections on the community health lab requisition.
  30. Order the appropriate tests on the computer and print 2 copies of the quest requisition.
  31. Print labels for each evacuated tube and one for the community health laboratory requisition.
  32. Label specimens.
  33. Follow handling instructions according to the quest laboratory manual for each tube.
  34. Place gel separator tubes in the rack next to the centrifuge.
  35. Centrifuge tubes for 15 minutes within 45 minutes of being drawn.
  36. Once appropriate tubes are centrifuged, place all tubes and other specimens, if applicable, for one patient in a biohazard bag.
  37. Seal the bag and place in the quest specimen collection box along with requisition.
  38. File 2nd copy of quest requisition in accordion folder.
  39. File the community health laboratory requisition in the patient's chart under the laboratory tab (green).
  40. Most recent requisition goes in back (the last requisition in the laboratory section).
    • After 2 unsuccessful attempts at obtaining the blood specimen from a patient, you must get someone more experienced to attempt, called a “1 by 2”.
    • If a 2nd, more experienced person attempts 2 more times unsuccessfully, then it is called a “2 by 2” and the physician should be notified to determine the next appropriate steps.
218Centrifuging Specimens
  1. Balance centrifuge by placing tubes across from one another.
  2. If spinning an odd number of tubes, use balancers.
  3. Specimens should stand for 15–30 minutes prior to being centrifuged.
  4. Specimens should be centrifuged within 45 minutes of being drawn.
  5. Specimens should be centrifuged for 10–15 minutes.
Remember: All PT/PTT/INRs (blue top) are required to be centrifuged, aliquoted, labeled and frozen.
Criteria for Specimen Rejection
  • Inadequate, inaccurate, or missing specimen identification
  • Additive tubes containing an inadequate volume of blood
  • Hemolysis
  • Inappropriate tube for test ordered
  • Expired tube
  • Improper handling
  • Contaminated specimen
  • Quantity not sufficient (QNS) for the test ordered
  • Collected at wrong time.
If a patient passes out: Immediately discontinue the blood draw. Bandage patient appropriately. Send someone to notify the clinic coordinator. It's best to lay the patient down with an ice pack on the back of their neck and elevate their feet. Follow all instructions from clinic coordinator or health care provider in charge.
Q. Write short note”role of nurses in hyponatremia”. (MUHS Nov/Dec 09)
A. The following are the determination of hyponatremia and the role to be played by nurses are given.
Definition: Serum sodium concentration plays a major role in the body's volume status. Low serum sodium levels can be dangerous and even fatal if hyponatremia is severe. The key to understanding hyponatremia is relating it to volume status. Hyponatremia is frequently associated with hypovolemia or fluid overload. Sharp assessment skills and client teaching can 219prove invaluable in the prevention and treatment of hyponatremia.
Purpose of nurses practitioners in hyponatremia are as follow:
To review the assessment, diagnosis, and management of hyponatremia (serum sodium 135 mEq/L), the most common electrolyte disturbance as a result of dysregulation of water balance in hospitalized or institutionalized patients.
A diagnosis of hyponatremia requires thorough investigation for underlying causes and prompts treatment to prevent poor patient outcomes. In clinical trials, a new class of drugs called the arginine vasopressin (AVP) receptor antagonists or aquaretics has been shown to be safe and effective for the treatment of hyponatremia. Among this class of agents, intravenous conivaptan hydrochloride, indicated for the treatment of euvolemic hyponatremia in hospitalized patients, is the first drug in class approved for use.
Implications for Practice
Elderly patients and those with certain conditions such as heart failure, tuberculosis, cirrhosis and head injury, may be at increased risk for hyponatremia. In hospitalized patients following surgery and the use of certain medications, hyponatremia is a common condition. A thorough understanding of the physiology of water balance and the risk factors associated with hyponatremia is essential for prompt and effective intervention. Awareness of the limitations of conventional therapies and the availability of new treatment options for hyponatremia allows clinicians to optimize patient care.
Q. Stool examination (MUHS, Nov/Dec08, May/June 10)
A. Usual Collection
  1. Universal precaution
  2. Collect stool in a dry, clean container
  3. Uncontaminated with urine or other body secretions, such as menstrual blood
  4. Collect the stool with a clean tongue blade or similar object
  5. Deliver immediately after collection.
220 Collection for Parasites
  1. Do warm stools are best for detecting ova or parasites. Do not refrigerate specimen for ova or parasites.
  2. If the stool should be collected in 10% formalin or PVA fixative, storage temperature is not critical.
  3. Because of the cyclic life cycle of parasites, three separate random stool specimens are recommended.
Enteric Pathogen Collection
  1. Some coliform bacilli produce antibiotic substances that destroy enteric pathogen. Refrigerate specimen immediately.
  2. A diarrheal stool will usually give accurate results.
  3. A freshly passed stool is the specimen of choice.
  4. Stool specimen should be collected before antibiotic therapy, or as early in the course of the disease.
  5. If blood or mucous is present, it should be included in the specimen.
Normal values in stool analysis
Macroscopic examination
Normal value
100–200 g/day
Varies with pH of stool and depend on bacterial fermentation
Plastic, not unusual to see fiber, vegetable skins
Size and shape
Gross blood, mucous, pus, parasites
[Colorless, neutral fat (18%) and fatty acid crystals and soaps]
Undigested food
None to small amount
Meat fibers, starch, trypsin
eggs and segments of parasites
Chemical examination
Normal values
Up to 75%
Occult blood
50–300 mg/24 hr
Coporphyrins: 400–1200 mg/24 hr
Uroporphyrins: 10–40 mg/24 hr221
2.5 g/24 hr
Negative in adults: positive in children
20–950 units/gm (positive in small amounts in adults; present in greater amounts in normal children.
Used 200–250 mOsm with serum osmolarity to calculate osmotic gap
5.8–9.8 mEq/24 hr
2.5–3.9 mEq/24 hr
15.7–20.7 mEq/24 hr
Lipids (fatty acid)
0–6 g/24 hr
Stool Odor
Normal value varies with pH of stool and diet. Indole and skatole are the substances that produce normal odor formed by intestinal bacteria putrefaction and fermentation.
Clinical implication
  1. A foul odor is caused by degradation of undigested protein.
  2. A foul odor is produced by excessive carbohydrate ingestion.
  3. A sickly sweet odor is produced by volatile fatty acids and undigested lactose.
Stool pH
Normal value: Neutral to acid or alkaline.
Clinical Implication
  1. Increased pH (alkaline)
    1. Protein breaks down
    2. Villous adenoma
    3. Colitis
    4. Antibiotic use
  2. Decreased pH (acid)
    1. Carbohydrate malabsorption
    2. Fat malabsorption
    3. Disaccharidase deficiency
Stool Color
Normal Value: Brown
Clinical implication
  1. Yellow to yellow-green: Severe diarrhea.
  2. Green (Severe diarrhea black): Resulting from bleeding into the upper gastrointestinal tract (>100 ml blood)
  3. 222Tan or clay-colored: Blockage of the common bile duct.
  4. Pale greasy acholic (no bile secretion) stool found in pancreatic insufficiency.
  5. Maroon-to-red-to-pink: Possible result of bleeding from the lower gastrointestinal tract (e.g. tumors, hemorrhoids, fissures, inflammatory process).
  6. Blood streak on the outer surface of usually indicates hemorrhoids or anal abnormalities.
  7. Blood in stool can arise from abnormalities higher in the colon. In some case the transit time is rapid blood from stomach or duodenum can appear as bright or dark red or maroon in stool.
Blood in Stool
Normal Value: Negative
Clinical implication
  1. Dark red to tarry black indicates a loss of 0.50 to 0.75 ml of blood from the upper GI tract.
  2. Positive for occult blood may be caused by:
    1. Carcinoma of colon
    2. Ulcerative colitis
    3. Adenoma
    4. Diaphragmatic hernia
    5. Gastric carcinoma
    6. Diverticulitis
    7. Ulcers
Mucus in Stool
Normal value: Negative for mucus
Clinical implication
  1. Translucent gelatinous mucus clinging to the surface of formed stool occurs in:
    1. Spastic constipation
    2. Mucous colitis
    3. Emotionally disturbed patients
    4. Excessive straining at stool
  2. Bloody mucus clinging to the surface suggests
    1. Neoplasm
    2. Inflammation of the rectal canal.
223Fat in Stool
Normal value: Fat in stool will account for up to 20% of total solids.
Lipids are measured as fatty acids (0–6.0 g/24 hr).
Clinical Implication
Increased fat or fatty acids is associated with the malabsorption syndromes
  1. Nontropical sprue
  2. Crohn's disease
  3. Whipple's disease
  4. Cystic fibrosis
  5. Enteritis and pancreatic diseases
  6. Surgical removal of a section of the intestine.
Urobilinogen in Stool
Normal value:125–400 Ehrlich units/24 hr
75–350 Ehrlich units/100 gm.
Clinical Implication
  1. Increased values are associated with hemolytic anemias
  2. Decreased values are associated with
    1. Complete biliary obstruction
    2. Severe liver disease, infectious hepatitis
    3. Oral antibiotic therapy that alters intestinal bacteria flora
    4. Infants are negative up to 6 months of age.
Bile in Stool
Normal value: Adults—negative
: Children—may be positive.
Clinical Implication
  1. Bile may be present in diarrheal stools.
  2. Increased bile levels occur in hemolytic anemia
Trypsin in Stool
Normal value: Positive in small amounts in 95% of normal  persons.224
Clinical Implication
Decreased amounts occur in:
  1. Pancreatic deficiency
  2. Malabsorption syndromes
  3. Screen for cystic fibrosis.
Leukocytes in Stool
Normal value: Negative
Clinical implication
  1. Large amounts of leukocytes
    1. Chronic ulcerative colitis
    2. Chronic bacillary dysentery
    3. Localized abscess
    4. Fistulas of sigmoid rectum or anus.
  2. Mononuclear leukocytes appear in typhoid
  3. Polymorphonuclear leukocytes appear in
    1. Shigellosis
    2. Salmonellosis
    3. Yersinia
    4. Invasive Escherichia coli diarrhea
    5. Ulcerative colitis.
  4. Absence of leukocytes is associated with:
    1. Cholera
    2. Nonspecific diarrhea
    3. Viral diarrhea
    4. Amebic colitis
    5. Noninvasive E. Coli diarrhea
    6. Toxigenic bacteria—Staphylococci spp., Clostridium, Cholera
    7. Parasites—giardia.
Porphyrins in Stool
Normal value: Coproporphyrin 400–1200 μg/24 hr
Urophorphyrin 10–40 μg/24 hr.
These values vary from lab to lab.
225 Clinical Implication
  1. Increased fecal coproporphyrin is associated with:
    1. Coproporphyria (hereditary)
    2. Porphyria variegata
    3. Protoporphyria
    4. Hemolytic anemia
  2. Increased fecal protoporphyrin is associated with:
    1. Porphyria veriegata
    2. Protoporphyria
    3. Acquired liver disease
Stool Electrolytes
Normal values
5.8–9.8 mEq/24 hr
2.5–3.9 mEq/24 hr
15.7–20.7 mEq/24 hr
Clinical Implication
  1. Idiopathic proctocolitis sodium and chloride normal potassium
  2. Cholera sodium and chloride
Microbiological Examination of Stool
Collection of fecal sample: The examination of feces for parasitological diagnosis is done to detect
  • Adult worms
  • Segments of tapeworms
  • Ova and cysts
  • Larvae
  • Trophozoites.
Cellular exudates such as WBCs, RBCs, macrophages and Charcot-Leyden (CL) crystals.
For this, the sample should be properly collected and preserved.
Ask the patient to pass the stool sample directly into a waxed cardboard or a plastic cup with a tight fitting lid. Collection of sample in a match box or on plant leaves is not a satisfactory method.
About 20–40 gm of well-formed stool or 5–6 tablespoonful of watery stool will suffice for a routine examination.
226Ingestion of some medicines prior to collection of fecal sample may interfere with the detection of parasites. These include tetracyclines, sulfonamides, antiprotozoal agents, laxatives, antacids, castor oil, magnesium hydroxide, barium sulfate, bismuth kaolin compounds and hypertonic salts, etc. These should not be taken 1–2 weeks before the examination of stool sample.
All specimens must be properly labelled with patient's name, age, sex and date of collection.
The specimen must reach the laboratory within 30 minutes of passing of the stool, since amebic trophozoites die and become unrecognizable after that.
Do not keep the specimen at warm temperatures. Try to keep it in cool, shady places.
Prevent the drying of the specimen.
Prevent contamination with urine or dirt particles.
Multiple stool examinations are required before the presence of parasitic infections is ruled out.
Stool should not be collected from bed-pans containing disinfectants.
Transportation of Samples
If looking for trophozoites, stool specimen must be transported very rapidly to the laboratory to avoid disintegration of trophozoites. Stool samples should be examined within 30 minutes of collection of the specimen and not receipt of the specimen in the laboratory. Stool specimens should never be frozen and thawed or placed in an incubator because parasitic forms deteriorate very rapidly.
For permanent fixation of the stool specimen, 10% formolsaline (prepared by adding 100 ml formaldehyde to 900 ml of 0.85% sodium chloride) is a well known preservative. Polyvinylalcohol (PVA) is a widely-used preservative because the performance of concentration procedures and preparation of permanent stained smears are both possible with this.227
Macroscopic Examination
Various points to be noted are:
  • The consistency of the stool could be formed, soft, loose or watery. The cysts are found maximum in the formed stool while trophozoites are most abundant in watery stool.
  • Presence of blood and mucus.
  • Presence of roundworms, threadworms or tapeworm proglottids.
  • Color and smell of the stool.
Microscopic Examination (Temporary Wet Mounts)
It is the simplest and easiest technique. A wet mount can be prepared directly from fecal material or from the concentrated specimens. The basic types of wet mounts that should be made from each sample include:
  1. Saline wet mount: It is used to detect worm eggs or larvae, protozoan trophozoites and cysts.
    In addition it can reveal the presence of RBCs and WBCs.
  2. Iodine wet mount: It is used to stain glycogen and nuclei of the cysts.
Place a drop of saline on left half of the slide and one drop of iodine on the right half.
With an applicator stick pickup a small portion of the specimen (equivalent to the size of a match head) and mix with saline drop.
Similarly pickup similar amount and mix with a drop of iodine.
Put the cover slip separately on both and examine under the microscope.
Ova, cysts, trophozoites and adult worms can be identified as per their characteristic features.
Iodine wet mount is examined for amoebic and flagellar cysts.228
Concentration Techniques
If the number of parasites in the stool specimens is low, examination of a direct wet mount may not detect them, hence the stool should be concentrated. Eggs, cysts and larvae are recovered after concentration procedures whereas trophozoites get destroyed during the procedure. This makes direct wet mount examination obligatory as the initial phase of microscopic examination.
The concentration procedures can be grouped under 2 categories:
  1. Sedimentation procedures: In which the eggs and cysts settle down at the bottom.
  2. Flotation procedures: In which the eggs and cysts float at the surface due to specific gravity gradient.
The basic disadvantage of sedimentation technique is that examination of the sediment is often difficult due to the presence of excessive fecal debris that may mask the presence of the parasites. The basic disadvantage of flotation technique is that not all eggs and cysts float in the flotation procedures.
Two commonly used concentration techniques are formalin ether and saturated salt solution technique.
Formal Ether Sedimentation Technique
Transfer half teaspoonful of feces in 10 ml of water in a glass container and mix thoroughly.
Place 2 layers of gauze in a funnel and strain the contents into a 15 ml centrifuge tube.
Centrifuge for 2 minutes at about 500 gm.
Discard the supernatant and resuspend the sediment in 10 ml of physiological saline. Centrifuge at 500 gm and discard the supernatant.
Resuspend the sediment in 7 ml of 10% formaldehyde (1 part of 40% formalin in 3 parts of saline).
Add 3 ml of ether (or ethyl acetate).
Close the tube with a stopper and shake vigorously to mix. Remove the stopper and centrifuge at 500 gm for 2 minutes.229
Rest the tube in a stand. Four layers now become visible the top layer consists of ether, second is a plug of debris and third is a clear layer of formalin and the fourth is the sediment.
Detach the plug of debris from the side of the tube with the aid of a glass rod and pour off the liquid leaving a small amount of formalin for suspension of the sediment.
With a pipette, remove the sediment and mix it with a drop of iodine. Examine under the microscope.230