1. Coagulative necrosis
2. Liquefaction necrosis
3. Caseous necrosis
4. Fat necrosis
5. Fibrinoid necrosis.

• Ischemia (sudden cessation of blood flow): Most common
• Bacterial agents
• Chemical agents.

• Ischemia
• Bacterial or fungal infection.

• Tuberculosis
• Chronic granulomatous diseases.

• 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.

• Immunological tissue injury
• Hypertension
• Peptic ulcer.

 

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.

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

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.

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.

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.

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.

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.

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.

Points of difference	Dry gangrene	Wet gangrene
Site	Commonly limbs	More common in bowel
Mechanisms	Arterial occlusion	More commonly venous obstruction less often arterial occlusion
Macroscopy	Organ is dry, shrunken and black	Part is moist, soft, swollen, rottenand dark
Putrefaction	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	Bacteria fail to survive	Numerous present
Prognosis	Generally better due to little septicemia	Generally poor due to profound toxemia

1. Dystrophic calcification
2. Metastatic calcification.

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.

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.

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

Kidney	:	The common sites are the basement mem- brane of tubular epithelium and tubular lamina causing nephrocalcinosis
Lungs	:	In the alveolar walls
Stomach	:	On the acid secreting fundal glands
Blood vessels	:	Especially on the internal elastic lamina.

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.

Points of difference	Atrophy	Hypertrophy	Hyperplasia
Definition	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	Reduced	No change	Increased
Cell size	Reduced	Increased	No change
Cell organelles	Reduced	Increased	No change
Rate of cell division	_	_	Increased
DNA and RNA synthesis	_	Increased	Increased
Protein synthesis	_	Increased	Increased
Size of affected organ	Small and shrunken	Enlarged and heavy	Enlarged

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.

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.

1. Uterine cervix
2. Respiratory tract.

 

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.

   

1. Endothelial injury
2. Alteration in flow of blood
3. Hypercoagulability of blood.

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

• 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.

• 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.

• 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.

• Activated platelets undergo release reaction, releasing the platelet granules to the exterior.
• There is two types of granules released.

• It contains fibrinogen, fibronectin; platelet derived growth factor, platelet factor 4 and cationic proteins.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

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.

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.

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.

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 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.

• 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.

• In stress, some factors may activate disseminated intravascular coagulation (DIC) and aggregation of fat emboli.

• 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

• 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.

• 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.

• 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.

 

• 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.

 

Points of difference	Exudate	Transudates
Definition	flamed tissue associated with increased vascular permeability.	Filtrate of blood plasma without changes in endothelial permeability
Character	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
Glucose	Low in neoplasms and infections	Same as in blood
Specific gravity	High (>1.018)	Low (<1.015)
pH	<7.3	>7.3
LDH	High	Low
Effusion LDH/ serum LDH ratio	>0.6	<0.6
Cells	Many cells (inflammatory as well as parenchymal)	Few cells, mainly mesothelial cells and cellular debris
Examples	Purulent exudate such as pus	Edema in congestive cardiac failure

Features	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 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.

1. Hemodynamic changes
2. Changes in vascular permeability.

• 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.

• 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.

• 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.

• 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.

• 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

• 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.

• Exudation of leukocytes
• Phagocytosis.

• 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.

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.

• 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. C_3b opsonins fragment of complement and corresponding receptor for C_3b 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.

• 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.

• Tuberculosis
• Leprosy
• Syphilis
• Granuloma inguinale
• Brucellosis
• Cat scratch disease
• Tularemia
• Glanders.

• Actinomycosis
• Blastomycosis
• Cryptococcosis
• Coccidioidomycosis.

• Schistosomiasis

• Sarcoidosis
• Crohn's disease
• Silicosis
• Berylliosis
• Foreign body granuloma.

1. Clean and uninfected
2. Surgically incised
3. Without much loss of cells and tissue
4. Edges of wound are approximated by surgical sutures.

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.

1.	Rubor	:	Redness
2.	Tumor	:	Swelling
3.	Calor	:	Heat
4.	Dolor	:	Pain

5.

Functio laesa:

Loss of function.

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.

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.

 

Type	Morphology	Examples
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 •Leprosy •Tuberculosis
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.	•Tuberculosis •Sarcoidosis
Touton's giant cells	•These multinucleated cells have vacuolated cytoplasm due to lipid content.	•Xanthoma
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. •Osteoclasts	•Aschoff cells in rheumaric nodule •Reed-Sternberg cells of Hodgkin's disease.

 

1. Rubor	:	Redness
2. Tumor	:	Swelling
3. Calor	:	Heat
4. Dolor	:	Pain

47

• 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.

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.

• 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.

   

• Plasmodium falciparum
• Plasmodium vivax
• Plasmodium ovale
• Plasmodium malariae
• Leishmania donovani
• Ancylostoma duodenale
• Diphyllobothrium latum
• Necator americanus
• Taenia solium.

   

• 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.

• 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.

• 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.

"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.

• 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

• Fallopian tube from the endometrium to ovaries or vice versa.
• Bronchus into alveoli.
• Ureters from the kidneys into lower urinary tract.

• 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.

• 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.

 

• Fallopian tube from the endometrium to ovaries or vice versa.
• Bronchus into alveoli.
• Ureters from the kidneys into lower urinary tract.

• 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.

• 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.

• 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.

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.

i.	Keratin	:	Carcinomas, mesotheliomas, germ cell
ii.	Vimentin	:	Sarcomas, melanomas, lymphomas
iii.	Desimin	:	Myogenic tumors
iv.	Neurofilaments	:	Neural tumors
v.	Glial fibrillary acidic protein (GFAP)	:	Glial tumors

• Alpha fetoprotein
• Carcinoembryonic antigen.

• Immunoglobulins
• Prostate specific antigen.

• Prostate acid phosphatase
• Neuron specific enolase.

• Human chorionic gonadotropin
• Calcitonin
• Catecholamines and Vanillyl mandelic acid(VMA).
• Ectopic hormone production.

• Ca - 125
• Ca - 15-3

1. Flow cytometry
2. In situ hybridization
3. Molecular diagnostic techniques.

     

1. Congenital
2. Acquired
   1. Infective causes: Syphilis, mycotic
   2. Noninfective causes: Atherosclerosis, cystic medial necrosis, polyarteritis nodosa
   3. Trauma.

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.

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

1. Atherosclerotic (most common)
2. Syphilitic
3. Dissecting
4. Mycotic.

1. Hypertension (90%)
2. Nonhypertensive causes (local or systemic connective tissue disorder).

• Aortic incompetence due to involvement of aortic valve
• Fatal myocardial infarction due to obstruction of coronaries
• Extension of dissection into the cardiac chambers (rare).

   

• 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.

• 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.

• 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.

• Antiheart antibodies detectable in patients of rheumatic fever.
• Experimental induction in rat's by injecting mixture of killed streptococci and emulsions of target tissues.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

 

• It accounts for 10% of congenital heart disease.

• Ventricular septal defect (VSD) (shunt)
• Overriding of the aorta
• Pulmonary stenosis (obstruction)
• Right ventricular hypertrophy.

• 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.

• Pressure hypertrophy of the right atrium and ventricle
• Small and abnormal tricuspid valve
• Smaller left atrium and ventricles
• Enlarged aortic orifice.

• Pressure hypertrophy of the right ventricles and right atrium
• Volume hypertrophy of the left atrium and ventricle
• Enlargement of mitral and aortic orifices.89

• Both sexes are affected equally.
• Seen more commonly in poor socioeconomic strata.

• 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.

• 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.

• 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.

1. Carditis
2. Polyarthritis
3. Chorea (Sydenham's chorea)
4. Erythema marginatum
5. Subcutaneous nodules.

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.

 

• Pulmonary embolism
• Chronic bronchitis
• Pulmonary tuberculosis
• 92Pneumoconiosis
• Cystic fibrosis
• Hyperventilation in marked obesity (pickwickian syndrome)
• Multiple organized pulmonary emboli.

 

• 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.
  93

   

• 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.

• The two sidely accepted classifications are based on the pathophysiology and morphology. Pathophysiological classification (based on pathophysiological mechanism).

1. Acute posthemorrhagic anemia
2. Chronic blood loss.

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.

1. Extrinsic (extracorpuscular) red cell abnormalities
2. Intrinsic (intracorpuscular) red cell abnormalities.

1. Microcytic, hypochromic anemia
2. Normocytic, normochromic anemia
3. Macrocytic, normochromic 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.

1. General laboratory investigations of anemia
2. Special tests to establish the deficient nutrient either vitamin B₁₂ or folic acid.

1. Blood picture and red cell indices95

   i.	Hemoglobin	:	Hemoglobin values are below normal.
   ii.	Red cells	:	Blood picture shows characteristic macrocytosis. Basophilic stippling and occasional normoblast may be seen.
   iii.	Reticulocyte count	:	The reticulocyte count is generally low to normal in untreated cases.
   iv.	Absolute values	:	Red cell indices show MCV—elevated (above 120 fl) MCH—elevated (above 50 pg) MCHC—normal or reduced.
   v.	Leukocytes	:	Blood film may show characteristic hypersegmented neutrophils.
   vi.	Platelets	:	Platelet count may be moderately reduced and bizarre forms of platelets may also be seen.

2. Bone marrow findings

   i.	Marrow cellularity	:	The marrow is hypercellular with a decreased myeloid-erythroid ratio.
   ii.	Erythropoiesis	:	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.
   iii.	Other cells	:	Giant forms of metamyelo-cytes and band cells may be present.
   iv.	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.

• 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.

• 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

• 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.

• A lower quantity of hot B12 is excreted in case of deficiency of 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.

• 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.

• 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

• 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.

• 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.

• 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.

   

• 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.

• 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.

• This stage lasts for 1–2 days.
• Represents the early acute inflammatory response to bacterial infection.

• Affected lobe is enlarged heavy, darkred and congested.
• Cut surface exudes blood-stained frothy fluid.

• 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.

• This phase lasts for 2–4 days.

• Cut section is airless red pink, dry granular and shows liver like consistency.
• There is accompanied serofibrinous pleurisy.

• 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.

• This phase lasts 4–8 days.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• Seen in less than 1% cases.
• It is encystment of pus in the pleural cavity.

• A rare complication due to secondary infection by other organisms.

• 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.

• 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.

• 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.

• 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.

• 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.

 

• 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.

• 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.

• The lymphatics draining the pulmonary lesion contain phagocytes containing bacilli and may develop beaded miliary tubercles along the path of the hilar lymph nodes.

• 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.

 

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.

• 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

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.

• 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.

• Lifestyle changes
• Diet changes
• Avoid ulcer triggering foods
• Avoid spicy food
• Avoid fatty foods
• Avoid alcohol
• Avoid caffeine
• Quit smoking
• Reduce stress

• 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.

 

• 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.

1. Acute
2. Chronic.

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.

• 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.

• 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 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.

• 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.

• It lies on the floor of the ulcer and is composed of fibrinous exudates containing necrotic debris and a few leukocytes.

• It lies underneath the necrotic zone.
• The tissue elements here show coagulative necrosis giving eosinophilic smudgy appearance with nuclear debris.

• It is seen merging to the necrotic zone.
• It is composed of nonspecific inflammatory infiltrate and proliferating capillaries.

• 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.

• Acute and subacute peptic ulcers usually heal without leaving any visible scar.
• Complications are produced due to chronic, larger and deeper ulcers.

• 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.

• 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.

• 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.

• 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.

 

• Fecolith
• Calculi
• Foreign body
• Tumor
• Worms especially Enterobius vermicularis
• Diffuse lymphoid hyperplasia especially in children.

• Vascular occlusion
• Inappropriate diet lacking roughage.

• Obstruction of the lumen
• Increased intraluminal pressure
• Pressure on the blood vessels
• Ischemic injury
• Bacterial proliferation
• Acute appendicitis.

• Organ is swollen and serosa shows hyperemia.

• Serosa is coated with fibrinopurulent exudate and engorged vessels on the surface.

• 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.

• 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.

• 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.

 

• Irritation of esophageal mucosa by gastric acid due to reflux esophagitis.

• Affected area is red and velvety.
• It is frequently associated with hiatus hernia and peptic ulcer at squamocolumnar junction called Barrett's ulcer.

• 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.

   

• 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.

• 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.

• 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.

• 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.

• Some parts show micronodular appearance while other part shows macronodular appearance.
• Some of the central veins and portal tracts are spared.

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 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.

• 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.

• 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.

• 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.

1. • 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.

• 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.

• 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.

• Patient is from tropical and subtropical country with history of amoebic dysentery.
• Intermittent low grade fever, pain and tenderness in the liver area.

• Cysts of E. histolytica in feces of 15% patients.
• Positive hemagglutination test.

 

• 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.

• 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.

• Detect current or previous hepatitis infection.
• Determine how contagious a person with hepatitis.
• Monitor a person who is being treated for hepatitis.

• Chronic persistent hepatitis
• Delta agent (hepatitis D)
• Nephrotic syndrome.

• 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.

• 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.

• Excessive bleeding
• Fainting or feeling light-headed
• Hematoma (blood accumulating under the skin)
• Infection (a slight risk any time the skin is broken).129

   

• There are two types of chronic pyelonephritis, depending upon the etiopathogenesis.

• 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.

• 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.

• 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.

• 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.

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.

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.

 

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.

• 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.

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.

• Patients are usually adults.
• The terminal stage is characterized by hypertension, uremia and progressive deterioration of renal functions.

• 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.

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.

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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

 

• 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.

• 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.

• 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.

• Palpable abdominal mass (most common)
• Hematuria, pain, fever and hypertension
• Spreads via blood especially to lungs.141

   

• 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.

 

• 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.

• 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.

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.

• 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.

• 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.

• 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.

• 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.

• 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).

• 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.

• Short spermatic cord
• Narrow inguinal canal
• Adhesions to the peritoneum.

• Trisomy 21
• Maldevelopment of scrotum or cremaster muscles.

• Deficient androgenic secretions.

• Cryptorchid testis is small in size, firm and fibrotic.

• 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.

• 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.

• Bilateral cryptorchidism is associated with sterility while unilateral disease may result in infertility.

• Concomitant inguinal hernia is frequently present along with cryptorchidism.

• Cryptorchidism testis is at 35 times increased risk of developing testicular malignancy, most commonly seminoma and embryonal carcinoma.

• 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

   

• 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.

• 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.

• 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.

• 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.

• Carcinoma cervix patients have shown circulating tumor specific antigens and antibodies and also antibodies to virus specific antigens on tumor cells.

• 150Dysplastic cells show increased mitochondria and free ribosomes and depletion of normally accumulated glycogen in the surface cells.

• There is no specific picture of cervical intraepithelial neoplasia.
• However, the changes begin at the squamocolumnar junction or transitional zone.

• 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.

• 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.

• 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.
Ia	: Preclinical carcinomas diagnosed only by microscopy. Maximum size 5 mm deep and 7 mm across measured from the base of epithelium.
Ia1	: Stromal invasion of less than 3 mm in depth and 7 mm in horizontal axis.
Ia2	: Stromal invasion of 3 to 5 mm depth and horizontal 7 mm or less.
Ib	: Clinical lesion confined to cervix or preclinical lesions greater than Ia.
Ib1	: Clinical lesions not greater than 4 cm in size.
Ib2	: 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.
IIa	: No obvious parametrial involvement.
IIb	: Obvious parametrial involvement.
Stage III	: The carcinoma extended to pelvic wall. The tumor invades lower third of vagina.
IIIa	: No extension to the pelvic wall.
IIIb	: 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.
IVa	: Spread of growth to adjacent organs.
IVb	: Spread to distant organs.

• Diagnosis of cancer cervix is done by Pap smear (exfoliative cytology) and colposcopy.

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).

• The leiomyomas are often multiple, circumscribed, firm, nodular, gray white masses of variable size.
• On cut section they exhibit characteristic whorled pattern.

• 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 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).

 

• 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

   

1. Stromal tumors
   1. Fibroadenoma
   2. Phyllodes tumor (cystosarcoma phyllodes)
   3. Sarcomas.
2. Epithelial tumors
   1. Intraductal papilloma (large duct papilloma).

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

• The following factors play an important role in pathogenesis of breast carcinoma.

• 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.

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.

• 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.

• 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.

• Atypical epithelial hyperplasia has 2–6 times higher risk of developing breast carcinoma subsequently.

• 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.

• 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).

• The proliferating tumor cells within the ductal lumina has four types of patterns in different combinations.

Solid pattern Comedo pattern Papillary pattern 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.

 

• 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.

• 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.

• 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.

• 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.

• 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.

• One or both the male breasts are enlarged having smooth glistening white tissue.

• Proliferation of branching duct which display epithelial hyperplasia with formation of papillary projections at places.
• Increased fibrous stroma with myxoid with appearance.

• 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.

• 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.

   

• 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.

• 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.

• 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.

• Hallmark is presence of large number of multinucleate osteoclast like giant cells which are regularly scattered throughout the stromal mononuclear cells.

• They contain as many as 100 benign nuclei and have many similarities to normal clasts.
• They have very high acid phosphatase activity.

• 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.

• Scanty collagen content, rich vascularity, areas of hemorrhages and presence of macrophages.

• 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.

• Radiologically, it appears as a large, lobulated and osteolytic lesion at the end of an expanded log bone with characteristic soap bubble appearance.

 

• 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.

• 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

• 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.

 

• 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.

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.

• 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.

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.

• 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.

• Leukocytosis and elevated ESR
• On X-ray examination, osteolytic lesions with patchy subperiosteal reactive bone formation producing characteristic “Onion skin appearance”.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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

   

• 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.

• 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.

• 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

• Meningiomas are divided into five subtypes.

• 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.

• Pattern is of a spindle shaped fibroblastic tumor.
• Tumor cells form parallel or interlacing bundles.
• Whorled pattern and psammoma bodies are less common.

• 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.

• Hemangioblastic pattern resembles hemangioblastoma of the cerebellum.
• Hemangiopericytic pattern resembles hemangio-pericytoma elsewhere in body.

• Displays features of anaplasia and invade underling bone or spinal cord.
• Associated with extraneural metastases mainly to the lungs.180

   

• 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.

• 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.

• 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.

• 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.

• 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.

• Normally absent.
• Present in kidney disorders, dehydration, heart disease, and severe diarrhea.

• Normally absent.
• If present, it indicates diabetes mellitus or hyperactivity of the endocrine glands.
• It can be present after brain injury or coronary thrombosis.

• 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.

• Normally absent
• Present in liver disorders.186

• 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.

• 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.

• Ascorbic acid: Present in vitamin C therapy.
• Salicylic acid: Due to drugs having salicylates.
• Menthol: Due to the intake of food containing menthol.

• 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.

• 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.

• 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 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.

• 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).

 

• 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.

• 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.

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.

• 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.

• Excessive blood loss
• Excessive red blood cell destruction (‘hemolysis’)
• Deficient red blood cell production.

• 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.

• 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.

• 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.

Source	Volume	Characteristics
● 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

Commonly used normal semen parameters
Volume	>2.0 ml
pH	7.2–7.8
Concentration	>20 × 106/ml
Motility	>50%
Morphology	>30% with normal morphology
WBC	<1 × 106/ml

0	No movement
1	Movement, none forward
1+	Occasional movement of a few sperm
2	Slow, undirected
2+	Slow, directly forward movement
3-	Fast, but undirected movement
3	Fast, directed forward movement
3+	Very fast forward movement
4	Extremely fast forward movement

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.

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.

 

• 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.

Pressure (in mm of water)	- 200–500
Queckenstedt test	- +ve
Appearance	- Opalescent/purulent - May clot - Turbid
Types and number of cells	- Mainly polymorphs - 500–20,000
Protein	- 50–500 mg
Sugar	- Decreased or absent
VDRL	- _ve
Bacteria	- +ve
Culture	- Pneumococci/Streptococci/E. coli may be isolated

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.

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).

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.

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.

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.

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 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.

• 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.

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).

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.

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).

• 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 (+)

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.

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).

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).

• 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.

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).

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).

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).

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).

• Patient has not had anything, except plain water, for 8–12 hours.

• Patient has had something to eat or drink within past 8 hours.

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.

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.

• 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.

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.

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.

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.

Macroscopic examination	Normal value
Amount	100–200 g/day
Color	Brown
Odor	Varies with pH of stool and depend on bacterial fermentation
Consistency	Plastic, not unusual to see fiber, vegetable skins
Size and shape	Formed
Gross blood, mucous, pus, parasites	None
fat	[Colorless, neutral fat (18%) and fatty acid crystals and soaps]
Undigested food	None to small amount
Meat fibers, starch, trypsin	None
eggs and segments of parasites	None
Yeasts	None
Leukocytes	None
Chemical examination	Normal values
Water	Up to 75%
pH	6.5–7.5
Occult blood	Negative
Urobilinogen	50–300 mg/24 hr
Porphyrins	Coporphyrins: 400–1200 mg/24 hr Uroporphyrins: 10–40 mg/24 hr221
Nitrogen	2.5 g/24 hr
Bile	Negative in adults: positive in children
Trypsin	20–950 units/gm (positive in small amounts in adults; present in greater amounts in normal children.
Osmolarity	Used 200–250 mOsm with serum osmolarity to calculate osmotic gap
Sodium	5.8–9.8 mEq/24 hr
Chloride	2.5–3.9 mEq/24 hr
Potassium	15.7–20.7 mEq/24 hr
Lipids (fatty acid)	0–6 g/24 hr

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.

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

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.

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

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.

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.

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.

1. Bile may be present in diarrheal stools.
2. Increased bile levels occur in hemolytic anemia

1. Pancreatic deficiency
2. Malabsorption syndromes
3. Screen for cystic fibrosis.

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.

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

Normal values	Sodium	5.8–9.8 mEq/24 hr
	Chloride	2.5–3.9 mEq/24 hr
	Potassium	15.7–20.7 mEq/24 hr

1. Idiopathic proctocolitis sodium and chloride normal potassium
2. Cholera sodium and chloride

• Adult worms
• Segments of tapeworms
• Ova and cysts
• Larvae
• Trophozoites.

• 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.

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.

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.