istilah patologi

1. Apoptosis--programmed cell death. Ugeskr Laeger. 1999 Oct 18;161(42):5778-82.

The health of multicellular organisms depends not only on the body's ability to produce new cells but also on controlled cell death. Apoptosis, or programmed cell death, is the opposite of mitosis. It is an active process for destruction of unwanted and superfluous cells. Changes in cell survival contribute to the pathogenesis of such varied disorders as cancer, many viral infections, neuropathies and immunopathies. The growing understanding of apoptosis forms the basis for development of new therapeutic strategies controlling cell death. This article describes mechanisms involved in the programmed cellular suicide. Apoptosis is the elimination of unwanted cells with minimum disruption of the surrounding tissue. This physiological death is caused by the activation of internal mechanism. Morphologically there is condensation and fragmentation of the chromatin. Apoptosis occurs in single or small clusters of cells with elimination of unwanted cells during embryogenesis and in various physiological and pathological states. Separation of apoptotic cells from its adjacent normal cells is caused by fragmentation of its nucleus and cytoplasm and removal by shedding or lysis after phagocytosis. Example: (i) Healthy adult tissue ; (ii) Embryonic development ; (iii) Malignant tumours - spontaneous or induced regression by therapy ; (iv) Involution and atrophy of tissues and organs.

2. Autolysis

If enzymatic degradation is the dominant element then dead cells are likely to be completely removed. This process may be accomplished by the activation of enzymes which are normally present within the affected cell. This process of self-digestion is known as autolysis. The enzymes are derived largely from lysosomes. The precise sequence of events leading to the activation and release of lysosomal enzymes is not known, but it is likely that a decrease in the intracellular pH is an important factor. Release of lysosomal enzymes in cell death can be inferred from the following: - Ultracentrifugal fractionation of dead cells shows that lysosomal enzymes are no longer particle-bound but appear in the supernatant. - There is evidence of enzymatic digestion of cell components in the loss of both DNA and RNA protein and glycogen.

3. Caseous necrosis is found characteristically in tuberculosis

It is a form of coagulative necrosis, in that no liquefaction has occurred, but microscopically the affected tissue appears completely structureless, under the microscope and exhibits a greater than usual affinity for acidic dyes such as eosin. It owes its name (caseous=cheese-like) to its macroscopic appearance, large areas of caseous necrosis bearing some resemblance to white, crumbly goat cheese. On chemical analysis, large amounts of lipid are found to be present in these necrotic areas in addition to the coagulated protein.

4. cell injury

Cells encounter many stresses as a result of changes in their internal and external environments. The patterns of response to this stress constitute the cellular basis of disease. If an injury exceeds the adaptive capacity of the cell, it dies. Pathology is the study of cell injury and the expression of a pre-existing capacity to adapt to such injury, on the part of either injured or intact cells. Causes of Cellular Injury: Diagram showing Structural Changes in Reversible and Irreversible Cell Injury: click here 1. Lack of O2 supply (Hypoxia)- e.g. Ischemia, Cardio-respiratory failure. 2. Loss of O2 carrying capacity of blood as in Anemia, CO poisoning 3. Physical agents - heat, cold, radiation etc. Hypothermia ; Hyperthermia. 4. Chemical agents including - acids, alkali, drugs, insecticides etc. 5. Infections - bacteria, virus, fungus, parasites etc. Infectious Disease Online 6. Immunologic reactions such as autoimmune diseases 7. Genetic disorders: chromosomal alteration or mutation - e.g. Sickle cell disease 8. Nutritional injury [e.g. Protein Calorie Malnutrition (Kwashiorkor), Vitamin A Deficiency causing Xerophthalmia, Keratomalacia and Night blindness].Nutritional Pathology Online Normal cell contains higher K+ and low Na+ than extra-cellular fluid maintained by Sodium Pump (ATP dependent Cell membrane Transport system). A cell needs ATP to maintain its normal metabolic functions: i) Membrane transport system (Failure of Na pump causes swelling of cell). ii) Protein synthesis (Reduced protein synthesis causes lipid deposition). iii) Phospholipid turnover (lack of peroxidation causes damage of cell membrane). Lesions: Gross features: The organ involved is pale and increased in weight. Microscopic features: Injured cells show cellular swelling due to increased volume of water, sodium and potassium and are characterized by a large, pale cytoplasm and a normally located nucleus called hydropic or vacuolar degeneration. Lipid vacuoles appear later mainly in cells participating in metabolism (e.g. hepatocytes, myocardial cells). Ultrastructural Structures: i) Plasma membrane shows alteration, blebbing, blunting or distortion of microvilli and loosening of intercellular attachment. ii) Mitochondria show swelling and there is appearance of phospholipid-rich amorphous densities. Reversible cell injury: These are the pathologic changes that can be reversed when the stimulus is removed or if the cause of injury is mild. Reversible cell injury is characterized by the cellular swelling with accumulation of fat, protein and other substances e.g. steatosis, cholesterosis, glycogen, and others. If the injury persists the changes become irreversible. Irreversible cell injury (Cell Death): Injury to cell causes: 1. Change in mitochondria : Swelling and abnormal cristae. 2. Damage of the plasma membrane causing leakage of soluble enzymes (detected in serum in myocardial injury). 3. Fragmentation of the nuclear membrane. Cell death: This means the series of morphological changes which occur in relation to a cell or group of cells following lethal injury. It is the element of time and the action of enzymatic degradation and protein denaturation which determine the differences between functional cell death and cell death as morphologically defined. Two main types: 1. Necrosis 2. Apoptosis

5. coagulative necrosis

In coagulative necrosis, denaturation of intra-cytoplasmic protein is the dominant process. The dead tissue becomes firm and slightly swollen. The protein molecules within the cytoplasm becomes unfolded and this renders the tissue both more opaque than normal and more reactive to certain dyes such as eosin. Microscopically, the cells show the signs of nuclear death , but the most noteworthy feature is the retention of the general architectural pattern of the tissue, despite the death of its constituent elements. Coagulative necrosis occurs typically in ischemic injury, such as may occur in the heart and kidney. However, for reasons which are not clear, ischemic injury in the central nervous system leads to necrosis dominated by enzymatic digestion and liquefaction of the dead tissue.

7. fat necrosis

This is almost exclusively seen in the female breast especially, if the breast is heavy and pendulous. Essentially it results from the rupture of adipocytes with release of their contents. The released fat undergoes lipolysis and is converted to fatty acids and glycerol. Clinically the lesion appears as a hard lump in the breast, which may give the impression that a malignant neoplasm is present. On slicing the excised specimen one may see a small central cystic area in which some oily droplets are present. At the periphery the adipose tissue is much firmer and also more opaque than usual. Histological examination of conventionally prepared material shows the presence of numerous granular macrophages which contain phagocytosed lipid. Fatty acid crystals are also often present and these excite a foreign body giant cell reaction (multinucleate cells formed as a result of the fusion of macrophages).

8. Gangrene:

Gangrene is characterized by extensive necrosis superadded with putrifaction. Visit: Necrosis Dry gangrene (mummification): This is due to arterial obstruction, commonly in old age with atherosclerosis followed by thrombosis of the large and medium size arteries of the limbs, slowly over a long period. Venous drainage is normal. Visit: Hemostasis and Thrombosis Dry gangrene usually starts in the most distal part of the extremities. Skin of the affected areas is dry, shrivelled and black like that of mummy due to diffusion of hemoglobin from small vessels into the extra-vascular space (Example: Senile gangrene, diabetic gangrene). Gangrene extends upwards till it reaches a point where circulation is sufficient to keep the part alive. This junction of living and dead tissue is called line of demarcation and consists of granulation tissue formed due to irritation of dead tissue. Granulation tissue erodes the dead tissue finally causing complete detachment (spontaneous amputation). In younger age, it is seen in thrombo-angiitis-obliterans (Buerger’s disease)- due to inflammatory occlusion of both artery and vein. Wet Gangrene: This is due to obstruction of vein with intact arterial supply (Example: strangulated loop of gut in hernia, prolonged application of tourniquet etc). Gangrene is distal to the site of obstruction. Marked edema allows rapid growth of bacteria often with gas formation. Absorption toxin causes profound toxemia. Gas Gangrene: Gas Gangrene:click here This is rapidly spreading tissue necrosis, often involving muscle as in crush injury in road accident. This is due to infection by saccharolytic and proteolytic Clostridia along with other pyogenic bacteria. This may be rarely seen in suppurative appendicitis, strangulated loop of intestine, puerperium. Affected muscles and soft tissues are edematous, crepitant on palpation due to gas bubbles in the tissue and commonly develops profound toxemia and septicemia. Microscopic features of Gangrene: i) Absence of inflammation. ii) Cell shrinkage. iii) Chromatin -condensation and fragmentation. iv) Cellular blebbing and fragmentation are followed by removal by shedding or phagocytosis by macrophage.

9. Edema:

Diagram showing Capillary System and Mechanisms of Edema Formation Edema is the increased fluid in the interstitial tissue spaces or body cavities [e.g. hydrothorax, hydropericardium, hydroperitoneum (ascites)] . Edema may be: i) Localized due to isolated venous or lymphatic obstruction or ii) Systemic (generalized) Severe generalized edema with marked subcutaneous tissue swelling is called anasarca as seen in heart failure. Causes of edema: 1. Increased capillary permeability. (disebabkan karena panas yang ekstrim ex : tersiram air panas) 2. Increased capillary hydrostatic pressure. (Disebabkan panas dalam tubuh yang meningkat, penyakit kekurangan gizi ex: kwarsiokhor) 3. Decreased colloid osmotic pressure of blood plasma (oncotic pressure) (Disebabkan hipoproteinemia) 4. Lymphatic obstruction (disebabkan oleh virus hepatitis, parasit yang bermigrasi, tumor) 5. Increased tissue osmotic pressure 6. Retention of Na+ in tissues. 1. Increased capillary permeability: Normally capillary walls are permeable to water and electrolytes but impermeable to plasma proteins which maintain the colloid osmotic pressure of the blood. When capillaries are damaged by toxic or anoxic causes, it becomes permeable to proteins. Plasma proteins move into tissue space lowering the colloid osmotic pressure of blood and raising that of the tissue. As a result there is escape of more fluids which is retained in the tissue by the protein molecules. Example: Acute inflammation, burns, severe anemia, allergic reactions etc 2. Increased capillary hydrostatic pressure of blood: - Capillary hydrostatic pressure depends upon venous pressure and not upon arterial pressure. So, when there is obstruction in venous return, capillary hydrostatic pressure rises at both ends of the capillaries, resulting in more output of fluid at arterial end and no absorption at venous end ( more over some fluid may come out at venous end). This causes retention of fluid in tissue leading to edema e.g. - Congestive cardiac failure - Constrictive pericarditis - Cirrhosis of liver - Venous thrombosis etc 3. Decreased colloid osmotic pressure of blood: Colloid osmotic pressure of blood is the force that retains fluid in the capillaries against the driving force of capillary hydrostatic pressure. Colloid osmotic pressure of blood depends partly on total amount of plasma proteins and partly on their relative proportion. Colloid osmotic pressure depends upon the number of molecules per unit volume of solution. Hence, of the protein, albumin having the smallest molecular weight exerts greater influence than globulins (albumin exerts 4 times stronger effect than globulins). Loss of proteins particularly albumin results in edema. When total proteins go below 4 gm% or there is loss of albumin with alteration of Albumin : Globulin ratio, from normal 2-3:1 to 1:1, edema will result. Examples: Cirrhosis of liver Severe protein malnutrition as in Kwashiorkor (reduced synthesis), Protein losing glomerulopathies (Nephrotic syndrome) Protein losing gastroenteropathies 4. Lymphatic obstruction: Some of the intercellular fluid is drained out by lymph vessels and any obstruction in its outflow will usually cause local edema e.g. Filariasis : It often causes massive lymphatic obstruction in inguinal region. This edema extends to external genitalia and lower limbs producing elephantiasis. Long standing edema causes proliferation of connective tissue causing solid edema. Breast carcinoma: After removal and/or irradiation of breast, there may be severe edema of the arm and the overlying skin may show accentuation of the depression of hair follicles -called “peau d’orange” (orange peel). 5. Increased Tissue Osmotic Pressure: In acute inflammation there is increased tissue colloid osmotic pressure due to break down of tissue proteins into osmotically active small particles and leakage of serum proteins through damaged capillary walls raising colloid osmotic pressure of tissue. 6. Primary Sodium retention: Retention of Na+ & water causes both increased hydrostatic pressure and reduced osmotic pressure. This occurs in excessive salt intake with renal insufficiency, such as acute renal failure. Retention of Na+ also causes increased renin-angiotensin-aldosterone secretion.

10 Morphology of Edema:

Diagram showing Capillary System and Mechanisms of Edema Formation (i) Localized (e.g. Pulmonary edema ; Inflammatory edema ; Cerebral edema). (ii) Generalized (e.g. Cardiac edema ; Renal edema). Edema is most commonly seen in subcutaneous tissue. Subcutaneous Edema may be diffuse or mainly at the dependent part of the body e.g. legs when standing, sacrum when recumbent (influenced by gravity). This is characteristically seen in congestive heart failure. Renal edema due to nephrotic syndrome is more severe and affects all parts of the body equally. However, initially it may affect loose connective tissue, such as eyelids causing periorbital edema. Finger pressure displaces interstitial fluid and leaves finger shaped depression, called pitting edema. Pulmonary Edema is typically seen in - ( Visit: Pulmonary Edema ) Diagram showing pathogenesis of Pulmonary Edema: click here i) Left ventricular failure, but also seen in ii) Over transfusion, iii) Inhalation of poisonous gas, iv) Nephritic syndrome v) Adult respiratory distress syndrome, ( Visit: Acute Respiratory Distress Syndrome ) vi) Infections and vii) Hypersensitive reactions. Fluid not only accumulates in tissue spaces but also in lung alveoli. As a result gaseous exchange is interfered leading to death. Gross features: Lungs are two to three times normal weight. Sectioning reveals a frothy blood tinged mixture of air and edema fluid. Microscopic features : Widening of alveolar septal wall with congestion of the alveolar capillaries. Protein-rich edema fluid in the alveoli are almost cell-free. Renal edema: 2 types- 1. Nephritic edema in acute nephritis: Edema is not extensive, does not depend on the gravity and protein content is low. Moderate edema is seen as puffiness of face and eyelids. This is due to the retention of Na+ and water due to oliguria resulting from damage of glomeruli. Na+ retention causes increased secretion of renin followed by angiotensin and aldosterone. Congestive cardiac failure is due to associated hypertension, also contribute to edema. (Visit: CONGESTIVE HEART FAILURE ) 2. Nephrotic edema in nephrotic syndrome: Hypoproteinemia due to massive proteinuria causes low osmotic pressure of plasma resulting in edema. Associated hyper-aldosteronism releases renin-angiotensin-aldosterone in the system causing edema. Cerebral edema: It may be: 1. Localized to the site of injury (Example: abscess, neoplasm) or 2. Generalized ( Example: encephalitis, hypertensive crisis, obstruction to the venous outflow of brain ). Grossly, brain is swollen with narrowing of sulci and flattening of gyri due to pressure of swollen brain against the skull. Cardiac edema: (Visit: Cardiac Path Online ) Cardiac edema is due to congestive cardiac failure. Edema is influenced by gravity and is seen in the depending parts of the body (i.e. dorsum of the foot, ankle). Protein content of the edema fluid is low (2%). (Visit: CONGESTIVE HEART FAILURE ) Mechanisms: 3 factors- 1. Reduced left heart output (forward failure) causes diminished renal blood flow producing increased aldosterone secretion with retention of Na+ and water followed by increased blood volume resulting in edema. 2. Right ventricular failure (backward failure) causes increased capillary hydrostatic pressure with increased outflow of fluid from capillary and diminished absorption of tissue fluid producing edema. 3. Retention of tissue metabolites increases tissue osmotic pressure produce edema.

11. Hyperemia and Congestion:

Hyperemia and congestion mean increased volume of blood in a particular site. Hyperemia is an active process: There is increased blood inflow caused by arteriolar dilation. (Example: skeletal muscle during exercise or at sites of inflammation). Tissues are redder due to engorgement with oxygenated blood. Normally, a fraction of the capillaries of an organ or tissue functions, others remain closed. When capillaries are injured (toxic or anoxic) or when more blood is required due to functional over activity, all the capillaries open up resulting in more blood in the part. In chronic cases the capillary may rupture. This may cause focal hemorrhage and breakdown of erythrocytes at these sites. Hemosiderin-laden macrophages are often present. Parenchymal cell atrophy or death may cause scarring. Gross features: The involved organs appear brown with contraction and fibrosis - Example: Lungs ; Liver. Congestion is a passive process: It is caused by impaired outflow from a tissue. Isolated venous obstruction may cause local congestion. Systemic venous obstruction occurs in congestive heart failure. Tissues acquire a blue-red color (cyanosis) due to accumulation of deoxygenated hemoglobin. Long-standing stasis may result in cell death. (Visit: CONGESTIVE HEART FAILURE ) Causes: (Visit: Cardiac Path Online ; Pulmonary Pathology Online ) a) Heart: Mitral valve disease (Example: stenosis/incompetence). Congenital heart disease (e.g. pulmonary stenosis, tricuspid regurgitation) and Myocardial infarct ; Cardiomyopathy. (Visit: congenital heart disease ; CARDIOMYOPATHY ; Myocardial infarction ) b) Lung: Emphysema ; Pulmonary fibrosis. It causes reduction of pulmonary circulatory bed producing right heart failure leading to passive venous congestion. Morphology: Heart: In mitral stenosis heart shows hypertrophy and dilation of left atrium with formation of ball thrombus. Lungs: Gross features: Grossly, lung is voluminous with impression of ribs, pits on pressure, dark brown in color, and feels firm. Microscopic features: Microscopically, alveoli contain edema fluid with intra alveolar hemorrhage (cause of hemoptysis) and "Heart failure cells" (hemosiderin filled macrophages). Histopathology Image of Heart Failure Cells: click here (Hemolysis of alveolar RBC liberates hemosiderin and bilirubin. Alveolar phagocytes engulf hemosiderin and carry them throughout the framework of lung, which stimulates fibrosis producing brown induration of lung and bilirubin cause latent jaundice). Liver: Gross features: Liver is enlarged and soft. Cut surface shows alternate dark and pale areas ("Nutmeg liver") - dark area represent congested centrilobular zone and pale areas represent fatty middle zone and normal periportal areas. Macroscopic image of Nutmeg Liver: click here Microscopic features: Histopathology Image of Liver showing Nutmeg Pattern due to Congestion around the Central Veins: click here 1. In centrilobular zone central vein and sinusoids are distended with blood and liver cells show necrosis (due to anoxia and pressure). 2. Mid zone shows fatty change. 3. Periportal zone is relatively normal (better oxygenated due to their proximity to hepatic arterioles. In long-standing cases central vein is thickened with extension of fibrous tissue in to the surrounding lobules Persistent hypoxia prevents regeneration of liver cells hence called cardiac sclerosis instead of cardiac cirrhosis.

12 Hemostasis and Thrombosis:

Hemostasis is a normal physiologic process. It maintains blood in fluid condition and clot-free state in normal vessels by inducing a rapid and localized hemostatic plug at sites of vascular injury. Thrombosis represents a pathologic state in which there is formation of intra-vascular solid mass (thrombus) from the elements of circulating blood. The vessel may be uninjured or with minor injury. Thrombosis: Three primary factors influence thrombus formation (Virchow’s triad): 1. Endothelial injury. 2. Slowing of blood flow. 3. Hyper coagulability of blood. 1. Endothelial injury commonest cause, mainly in the heart and arterial circulation (e.g. Myocardial infarction, endocarditis, ulcerated atherosclerosis). Injury may occur from diverse causes e.g. hemodynamic stress (hypertension or turbulent flow in aneurysms), radiation, products absorbed from cigarette smoke, extensive burn etc. 2. Slowing of circulation (alteration in normal blood flow): Normal blood flow is laminar (i.e., the cellular elements flow centrally inside the vessel, separated from endothelium by a clear zone of plasma). Stasis and turbulence disrupt laminar flow and bring platelets into contact with the endothelium. They prevent dilution of activated clotting factors by fresh flowing blood, retard the inflow of clotting factor inhibitors and permit the build-up of thrombi. Stasis is important in causing thrombosis in veins, cardiac chambers and arterial aneurysms. Hyperviscosity syndrome - Example: In polycythemia or deformed RBC as in sickle cell anemia causes stasis in small blood vessels predisposing to thrombosis. 3. Hypercoagulability of blood may be due to heritable gene mutation or acquired. Example: Severe burn, shock, oral contraceptive, increased hepatic synthesis of coagulation factors and reduced synthesis of anti-thrombin III. Mechanism: Normally, in a blood vessel, cellular elements flow centrally, forming axial stream separated from endothelium by a clear, cell-free, plasmatic zone. Due to slowing of the circulation, platelets come in contact with endothelium and are activated to liberate tissue factors. Tissue factors recruit more platelets, which are deposited in the form of ridges at right angles to the blood flow forming corrugations, known as line of Zahn. Coming in contact with sub-endothelial collagen, platelets are activated to release ADP, Thromboxanes etc. ADP aggregate more platelets. Thromboplastin, liberated from platelets and injured endothelium initiate precipitation of fibrin on the surface of platelets. Fibrin network may entangle RBC and leucocytes. A thrombus is thus formed, on the basis of platelets and fibrin, with varying number of RBC and leucocytes. Thrombi may form anywhere in the cardiovascular system. Aortic and cardiac thrombi are typically nonocclusive (mural) as a result of rapid and high-volume flow. Smaller arterial thrombi may be occlusive. All these thrombi usually begin at sites of endothelial injury (e.g. atherosclerotic plaque) or turbulence (vessel bifurcation). Venous thrombi characteristically occur in sites of stasis and are occlusive. At sites of origin, thrombi are generally firmly attached. Arterial thrombi tend to extend retrograde from the attached point, where as venous thrombi extend on the direction of blood flow. The propagating tail may not be well attached and may fragment to create an embolus. Sites of thrombus formation: Cardiac and arterial thrombi are formed slowly in rapid circulation. They are pale-gray and tend to have gross and microscopic lamination (lines of Zahn) produced by pale layers of plates and fibrin alternating with darker red cell-rich layers. These are mostly seen in the left ventricle overlying an infarct, ruptured atherosclerotic plaques, and aneurysmal sacs. Venous thrombosis (phlebothrombosis) often created a long red-blue cast of the vein lumen as it occurs in a relatively slow circulation. The thrombus contains more enmeshed erythrocytes among sparse fibrin strands (red or stasis thrombus). Fibrin and attachment to the vessel wall distinguish stasis thrombus from postmortem clot. Phlebothrombosis is most commonly (more than 90 %) seen in the veins of the lower extremities. Thrombi may also form on heart valves. In infective endocarditis, bacteria or fungi form large infected thrombi (vegetations), causing underlying valve damage and systemic infection. Sterile vegetations (nonbacterial thrombotic endocarditis) can also develop on noninfected valves in patients with hypercoagulable states, particularly in those with disseminated cancer. Noninfective, verrucous(Libman-Sacks) endocarditis is seen in patients of SLE due to circulating immune complex. Heart: i) Ball thrombus is seen in left atrium in mitral stenosis. It is large and spherical. ii) Mural thrombus is seen over the wall of heart in cardiac infarct, cardiomyopathy iii) Agonal thrombus is seen in right ventricle in case of death due to pneumonia. iv) Vegetations over the cardiac valves are seen in endocarditis. Artery: i) On the atheromatous patch in coronary, cerebral, spleen, and renal arteries. ii) Laminated thrombus is seen in aneurysmal sac. iii) Marasmic thrombus is seen in marasmic children, in mesenteric artery (stasis) Vein: Veins are the commonest sites of thrombus formation due to slow circulation. Other causes of venous thrombosis are: i) Trauma, burn, due to reduced physical activity, injury to vessels and release of pro-coagulants from tissue. ii) Puerperal and postpartum thrombosis occurs mainly due to amniotic fluid infusion into blood and hypercoagulability in late pregnancy and in postpartum period. . iii) Disseminated cancer, due to release of tumour-associated -procoagulants. iv) Advanced age, bed rest, immobilization, reduced physical activity diminishes milking action of muscle. v) Thrombophlebitis is the inflammation of the venous wall due to septic thrombus. Example: a) Pelvic veins in puerperal sepsis ; b) Portal vein in acute appendicitis ; c) Cavernous sinus in facial infection Fate of a thrombus: Septic thrombus causes abscess formation. Aseptic thrombus may show: i) Propagation causing complete vessel obstruction. ii) Dissolution by fibrinolytic action. iii) Detachment- with embolism. iv) Organization and recanalization, re-establishing vascular flow by in-growth of endothelial cells, smooth muscle cells and fibroblasts to create through-and through capillary channels or by incorporating the thrombus as a sub-endothelial swelling of the vessel wall. Effect of thrombosis: Septic: Forms abscess and may cause pyaemia. Aseptic: Effect will depend upon the vessel involved and efficiency of the collateral circulation of the area. 1. Arterial thrombus - in a small vessel is occlusive and usually causes infarction. This is particularly seen when it involves organs supplied with end-arteries (Example: cerebral, coronary, splenic, mesenteric and renal arteries). 2. Venous thrombosis - rarely causes infarction, as collateral channels soon enlarge to maintain the venous drainage. Superficial venous thrombosis, as in varicose saphenous veins, causes local edema and impaired venous drainage, predisposing to skin infection and varicose ulcer. Deep thrombi in larger leg veins above the knee (Example: popliteal, femoral and iliac veins), have good collateral circulation but commonly embolize (about 50 % cases). Occlusive venous thrombi with poor collateral channels cause increased venous and capillary pressure forming edema (Example: ascites in portal vein thrombosis). Beneficial effect of thrombosis: Thrombosis causes hemostasis and sealing of the vessel wall after erosion by malignant tumours and attempts to prevent hematogenous spread. Blood clot: Coagulation of dead blood (Example: in a test tube, in a blood vessel after death or after ligature). Types of clot: 1. Current jelly clot (soft and red) forms rapidly in great vessels or heart. All the elements of blood are involved. 2. Chicken fat clot (lower part dark, upper part yellow) forms slowly, RBC settles at the bottom and pale upper part consists of leucocytes and fibrin.

13 Embolism:

1)Diagram showing Sources of Arterial Emboli: click here 2)Diagram showing Sources of Venous Emboli: click here Embolism is the intra-vascular impaction of an undissolved material (solid, liquid or gaseous) carried by the blood stream to a site distant from its point of origin. Material impacted is called embolus. Most (99%) emboli arise from thrombi, hence the term thromboembolism. Other forms include droplets of fat, gas bubbles, atherosclerotic debris ( atheroemboli ), tumour fragments, bone marrow, or foreign bodies such as bullets. Emboli lodge in vessels too small to permit further passage, resulting in partial or complete vascular occlusion and ischemic necrosis of the distal tissue ( infarction ). Pulmonary Thromboembolism: In more than 95 %, pulmonary emboli originate from deep leg vein thrombi. Depending on the size, a pulmonary embolus may occlude the main pulmonary artery, impact across the bifurcation (saddle embolus), pass into smaller arterioles. Multiple emboli may occur, either sequentially or as a shower of small emboli from a single large mass. In general, one pulmonary embolism puts a patient at risk for more. Rarely, emboli pass through atrial or ventricular defects into the systemic circulation (paradoxical embolism) - Example: cerebral embolism with hemiplegia due to puerperal thrombosis of pelvic veins. Fat Embolism: Air Embolism: Decompression Sickness: Amniotic Fluid Embolism: Source of Emboli: Left Cardiac thrombi (80 %) are mural thrombi in myocardial infarct and thrombi in left atrium in rheumatic mitral valve disease. Systemic artery thrombi, from aortic aneurysm, and ulcerated atherosclerotic plaques in aorta and other arteries are impacted in organs like liver, brain, viscera and in extremities. Venous and right cardiovascular thrombi produce pulmonary embolism e.g. detached venous thrombi, tumour cells invading veins, fat embolism, air embolism amniotic fluid embolism. Portal and mesenteric vein thrombi due to inflammation in gastrointestinal tract are impacted in liver. Effects of Embolism: Depends on the type and site of embolism. i) Septic emboli produce abscess. ii) Tumor emboli cause metastatic tumor iii) Organ with end-arteries/poor collateral circulation produces infarct. iv) Condition of heart and collateral circulation e.g., femoral artery with sound heart causes temporary paresis with re-establishment of circulation by collaterals. Femoral artery embolism with feeble heart in old age causes dry gangrene Retrograde Embolism: Normally emboli move in the direction of the flow. If it moves to opposite direction and gets impacted, it is called retrograde embolism. Examples: i) Virchow’s gland-(deep supra-clavicular lymph node) in gastric carcinoma. ii) Inguinal lymph nodes in testicular tumour. iii) Krukenburg’s tumor in mucoid carcinoma of gastrointestinal tract.

14. Infarct

Infarction: Infarct is an area of ischemic necrosis due to occlusion of arterial supply in most cases. Diagram showing common sites of Systemic Infarction from Arterial Emboli: click here The word "infarction" comes from the Latin "infarcire" meaning "to plug up or cram." - Total occlusion of an artery produces an area of coagulative necrosis called an infarct. - Partial occlusion - that is, stenosis - occasionally causes necrosis, but more commonly leads to a variety of degenerative cell changes. These changes include vacuolization of cells, atrophy, loss of muscle cell myofibrils, and interstitial fibrosis. Infarction of vital organs such as the heart, brain, and intestine may be life-threatening. If the individual survives, the infarct heals with a scar, which is the common occurrence in less vital organs. Most cases of infarction are due to thrombosis or embolism. Rarely, there are other causes - Examples: vasospasm, extrinsic compression of a vessel by tumour, edema, or entrapment in a hernia sac, and twisting of vessels, such as testicular torsion or bowel volvulus. Traumatic vessel rupture is a very rare cause. Occluded venous drainage (e.g. venous thrombosis) can cause infarction but more often induce congestion only (due to rapid blood flow through collaterals).Infarcts due to venous thrombosis are more likely in organs with single venous outflow, such as testis or ovary. Pulmonary Infarction ; Myocardial Infarction Factors that influence development of an infarct: 1. Pattern of vascular supply: Organs with dual circulation (lung, liver) or anastomosing circulation (radial and ulnar arteries, circle of Willis, small intestine) protect against infarction. Organs supplied with end arteries (spleen, kidneys) usually develop infarct after occlusion of the arterial supply. 2. Rate of development of occlusion: Slowly developing occlusions less often cause infarction by providing time to develop alternate perfusion pathways. (Example: collateral coronary circulation). 3. Changes due to hypoxia: Neurons undergo irreversible damage after 3 to 4 minutes of ischemia, myocardial cells die only after 20 to 30 minutes. In contrast, fibroblasts within ischemic myocardium are viable even after many hours. 4. Oxygen content of blood: Anemia, cyanosis, or congestive heart failure (with hypoxia) may cause infarction. Infarct morphology: Morphologically, the necrotic tissue of an infarct swells, and the infracted area often protrudes above the surface of the organ. As an infarct ages it undergoes fibrosis, reduces in size, and ultimately shrinks below the surface of the organ. A fresh infarct is pale because of the loss of red blood cells, an appearance reflected in the terms “white” or “pale” infarct. Infarcts can also be red (hemorrhagic), particularly in the lung and the intestine. With time, the tissue surrounding an infarct forms granulation tissue rich in sprouting capillaries that bleed easily. Therefore, the border of a healing infarct frequently is hemorrhagic. Infarcts may also be either septic or bland Red infarcts occur: - In venous occlusion ( Example: ovarian torsion) - In loose tissues (such as lungs, placenta) - In tissues with dual circulation (Example: lungs and small intestine) - In tissues previously congested because of sluggish venous outflow. - At a site of previous occlusion and necrosis when flow is re-established. White infarcts occur in solid organs - Examples: heart, spleen and kidney, with end arterial circulation. Pathogenesis and pathology: Arterial obstruction causes fall of distal blood pressure to capillary pressure with dilation of capillaries causing injury due to anoxia. This is the commonest cause. Blood from the veins accumulates in the dilated and injured capillaries with outpouring of fluid and RBC into the surrounding tissue. Thus, the area becomes red, engorged and even hemorrhagic with venous blood, hence the term infarction. Gross features: -All infarcts tend to be wedge-shaped, the occluded vessel marks the apex, and the organ periphery forms the base. -Lateral margins may be irregular reflecting the pattern of adjacent vascular supply. Microscopic features: - Features of ischemic coagulative necrosis. - An initial inflammatory response. This may last for hours to days. - This is followed by a reparative response. This may last from days to weeks. - The changes usually begin in the preserved margin. - In stable or labile tissues, some parenchymal regeneration may occur where the underlying stromal architecture is spared. - Most infarcts are ultimately replaced by scar tissue. The brain is an exception. In the brain there is liquifaction followed by absorption and cyst formation. - Septic infarctions occur with embolization of infected cardiac vegetations or when microbes seed an area of necrosis. - The infarct becomes an abscess. - Abscess slowly organize to scar.

15. Hemorrhage

Hemorrhage (i.e. bleeding) is a discharge of blood from the vascular compartment to the exterior of the body or into nonvascular body spaces. The most common and obvious cause is trauma - usually accidental, but often by the surgeon's scalpel. A blood vessel may be ruptured in ways other than laceration. For instance, severe atherosclerosis may so weaken the wall of the abdominal aorta that it balloons to form an aneurysm, which then bleeds into the retroperitoneal space. The aneurysm may complicate a congenitally weak cerebral artery (berry aneurysm) and lead to cerebral (subarachnoid) hemorrhage. Certain infections - for example, pulmonary tuberculosis erode blood vessels ; a similar vascular injury is caused by invasive tumours. Hemorrhage also results from damage at the level of the capillaries - for instance, the rupture of capillaries by blunt trauma. Increased venous pressure also causes extravasation of blood from capillaries in the lung. Pulmonary Hemorrhage (Eg. Goodpasture's Syndrome) Vitamin C deficiency is associated with capillary fragility and bleeding, owing to a defect in the supporting structures. It is important to recognize that the capillary barrier by itself is not sufficient to contain the blood within the intravascular space. The minor trauma imposed on small vessels and capillaries by normal movement requires an intact coagulation system to prevent hemorrhage. Thus, a severe decrease in the number of platelets (thrombocytopenia) or a deficiency of a coagulation factor (Eg: Factor VIII in hemophilia) is associated with spontaneous hemorrhages unrelated to any apparent trauma. An individual may exsanguinate into an internal cavity, as in the case of gastrointestinal hemorrhage from a peptic ulcer (arterial hemorrhage) or esophageal varices (venous hemorrhage). In such case large amounts of fresh blood fill the entire gastrointestinal tract. When a large amount of blood accumulates in soft tissue, it is known as hematoma. Such a collection of blood can be merely painful, as in a muscle bruise, or fatal, if located in the brain. Diffuse superficial hemorrhages in the skin are termed purpura or ecchymoses. Following a bruise or in association with a coagulation defect, an initially purple discoloration of the skin turns green and then yellow before resolving, a sequence that reflects the progressive oxidation of bilirubin released from the hemoglobin of degraded red blood cells. A good example of an ecchymosis is a "black eye". A minute punctuate hemorrhage, usually in the skin or conjunctiva, is labelled a petechia. This lesion represents the rupture of a capillary or arteriole and is seen in conjunction with coagulopathies or vasculitis ,the latter is classically associated with bacterial endocarditis. ( Visit: INFECTIVE ENDOCARDITIS )