Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Egypt.
Hemodynamic Disorders BY
Prof. Dr. Mohamed Hamed Mohamed mohamedelariny@yahoo.com +20124067373
2011
Hemodynamic Disorders Disturbance in Circulation Definition of Hemostasis: It is arrest bleeding, either by the physiological properties of vasoconstriction and coagulation or by surgical means. Homeostasis: Normal fluid homeostasis encompasses maintenance of vessel wall integrity as well as intravascular pressure and osmolarity within certain physiologic ranges.
NB: "The metabolism of organs and cells depends on an intact circulation for continuous delivery of oxygen, nutrients, hormones, electrolytes, and water; and for the removal of metabolic waste and carbon dioxide. Delivery and elimination at the cellular level are controlled by exchanges between the intravascular space, interstitial space, cellular space, and lymphatic space." 'The survival of cells and tissues is exquisitely dependent on the oxygen provided in a normal blood supply and therefore on delivery of sufficient blood through a patent circulatory system.' “The well-being of tissues requires a normal fluid balance. Abnormalities in vascular permeability and hemostasis can result in cellular injury even if the blood supply is intact.� Changes in vascular volume, pressure, or protein content (or alteration in endothelial function) affect the net movement of water across the vascular wall
Important Items: i-Distribution of fluid is a carefully controlled homeostatic mechanism. ii-Deviations from normal may have profound pathological effects. iii-Normal functions require intact blood and lymph vessels. iv-Endothelial cells play an important role in hemostasis, inflammation and healing
1-Capillary bed: - Enormous volume. - Site where fluid exudes from circulating blood.
2-Endothelial Cells Synthesize and Secrete Glycoproteins: Functions of endothelial glycoproteins: i-Inhibit clotting. Protect endothelial cells. NB: When injury occurs to the endothelium; synthesis and release of glycoproteins impaired which results in problems with hemostasis and fluid transport.
Mechanisms for substance to transport across capillary endothelium:
1-Direct diffusion: (ions, water and small molecules) Passive diffusion across vessel wall.
2-Active transport:
2-Active transport: Occurs via special protein-ion pumps embedded in plasma membranes at cell surface
3-Transcytosis: 4. Expansion of cell junctions: Allows large molecules and excess fluids to pass into the Interstitium.
NB: Movement of substances through junctions and cell membranes is generally passive in response to concentration and pressure gradients.
3-Precapillary arterioles: -Contain small, innervated myocyte sheaths. -Contract to control blood flow (regulation of blood flow).
4-Postcapillary Venules: -Sites of fluid exudation. -Susceptible to some toxins.
5-Capillaries: -Sites of fluid exudation.
NB: There are regional differences in capillary lining dependant on the structural variation in the vascular wall. i-Continuous capillary: as in blood-brain barrier restricted transport -Tight (occluding) intercellular junctions. -Reinforced by astrocyte foot processes. ii-Fenestrated capillary as in intestinal villi assists in substantial fluid transport. iii-Discontinuous capillary as spleen capillaries where the endothelium open to passage large molecules. Example of a disease process: Elevations of blood pressure results in an increase in passage of low-molecular proteins into interstitium. This can result in failure of the normal barrier function of the endothelium.
They have 2 broad headings: 1-Disturbances in the volume of the circulating blood: These include hyperemia, congestion, hemorrhage, edema, dehydration and shock. 2-Circulatory disturbances of obstructive nature: These are thrombosis, embolism, ischemia and infarction.
1-Disturbance in the volume of circulating blood Hyperemia and Congestion = increased amount of blood in any portion of the circulatory system. Active (arterial)
Physiological
Passive (venous congestion)
Pathological
Local
(venous obstruction) Muscular exercise, Acute inflammation Lactating udder, (usually local) GIT after meal, Pregnant uterus
General (heart or lung failure)
Active Hyperemia Definition: It is an increased amount of blood in the arterial side and capillaries with increased the blood flow. It is usually local and with the acute inflammation; but rarely general with some systemic generalized diseases. NB: Active means change in the muscle tone of the vessels (dilation). I-Common arterial or active hyperemia is a result of: -Increasing volume of circulating blood (excess). -Increasing of amount of erythrocytes. -Vacatic (vacuum) because of decreased atmospheric pressure. II-Local arterial hyperemia can be: -Angioneurotic: because of dilation of arteries and arterioles. -Collateral: It is seen in case of paralysis of vasoactive nerve or stimulation of vasodilators and interference with the blood flow as in case of thrombosis. -Hyperemia after anemia -Inflammatory Types and causes of Active hyperemia: 1-Physiological Hyperemia: it occurs in the active organs such as:
1-Physiological Hyperemia: it occurs in the active organs such as: i-GIT after during digestion. ii-Lactating mammary glands. iii-Testes at mating seasons. iv-Muscles of athletes during exercise. v-Skin to dissipate heat.
2-Pathological Hyperemia: occurs in response to inflammatory stimuli as in the following causes:
i-Physical causes as heat, cold, sun rays. ii-Chemicals as acids or alkalizes. iii-Mechanical as trauma. iv-Infection as Bacteria, viruses, fungi,. v-Toxins and others.
Macroscopic Pictures: i-The affected tissue is red, swollen and warm (AM). ii-On cut sections, blood oozed.
Microscopic Pictures: i-Arterioles and capillaries are filled (engorged or dilated) with blood ii-Capillaries (normally contain one row of erythrocytes) become contain several rows of erythrocytes (up to 20 rows).
Passive Hyperemia Definition: It is an increase in the amount of blood in the venous side of vascular system generally caused by a decrease outflow with normal or increase inflow of blood). Two factors used in defining the types of congestion: 1-Duration: (acute/ chronic) i-Acute: implies abrupt onset with rapid development. ii-Chronic: slowly developing and/or present for a long time. 2-Extent: localized/generalized i-Local: change confined to a discrete area (localized or limited). It can be a result of: i-Venous obstruction by thrombosis. ii- Compression of veins by tumor, abscesses, cysts or enlarged Lns iii-Development of collateral blood circulation.
ii-General: indicates a systemic change within an organ. It can be a result of i-Left-sided and right-sided heart failure. ii-Diseases of lungs (interfere with blood flow) as pulmonary fibrosis and emphysema. iii-Cardiac decompensation.
1-Acute General Passive Hyperemia Definition: It is sudden increase in the amount of blood in the venous side of circulatory system (allover the body). Causes: interference with the function of one or more of the so called blood pumps. i-Heart ii-Movement of the respiration including diaphragm. iii-The movement of the muscles.
Macroscopic Pictures: i-The affected organs become swollen, heavier and purplish (bluish). ii-Blood oozed from its cut surfaces.
Microscopic Pictures: The veins, venules and capillaries are engorged with blood.
2-Chronic General Passive Hyperemia Definition: It is gradual increase in the amount of the blood in the whole venous system and persists for long period of time. Causes: They are present in two main organs (heart and lungs). I-Heart: Valvular Stenosis A-Valvular diseases: Valvular insufficiency Valvular incompetency B-Myocardial weakness: as in case of degeneration or necrosis (myocarditis). C-Anomalies of the heart: as persistent foramen ovale, interventricular defect. D-Constrictive lesions of the pericardium: as hydropericardium, traumatic pericarditis.
II-Lung: A-Causes from obliteration of capillary bed: prevent the blood flow through the lungs as in case of i-Chronic alveolar emphysema. ii-Pneumonia (alveoli filled with exudates). iii-Pulmonary fibrosis as in case of pneumoconiosis. B-Causes from compression of major blood vessels either by tumors, cysts,..
Macroscopic Pictures: i-Size: the affected organs are enlarged with round border at first and atrophied later on. ii-Color: dark red to brown due to congestion and lysis of erythrocytes (hemosiderosis). iii-Consistency: firm. iv-Cut sections: oozed blood.
Microscopic Pictures: i-Long standing congestion of the whole body veins with thickening in the wall of venules and mild interstitial fibrosis (CT proliferation). ii-Pressure atrophy of the parenchymal tissue.
3-Acute Local Venous Congestion Definition: It is a temporary increase in the amount of blood in the veins of an organ or portion of an individual. Causes: sudden obstruction of veins due to the following: i-Intravenous thrombus. ii-Sudden pressure on vein as in intestinal torsion. Macroscopic Pictures: the affected organ is i-Dark red in color and cold. ii-Edematous. iii-Oozed blood from its cut sections.
Microscopic Pictures: i-Venules and capillaries are dilated and engorged with blood. ii-In severe cases, some capillaries are ruptured. iii-The tissue spaces are filled with fluid (transudate) Edema.
Chronic Local Venous Congestion (CVC) Definition: It is the increase in the amount of blood in the veins for a long period of time. Causes: It is due to pressure on veins which causes obstruction as tumors, cyst, enlarged Lns.
Brown Induration of lungs CVC of Lungs Causes: i-Myocardial weakness. ii-Valvular disease of bicuspid valve. iii-Increase the intra-abdominal pressure as in case of tympany.
Macroscopic Pictures: i-Color: is dark brown due to stasis of blood and hemosiderosis. ii-Size: increase. iii-Consistency: firm (indurated). iv-Cut sections: blood oozed.
Microscopic Pictures: i-Peribronchial veins and perialveolar capillaries are dilated and engorged with blood. ii-The lumen of alveoli filled with transudate, desquamated epithelium and erythrocytes. iii-Later on, the erythrocytes-lysis is seen and give rise to hemosiderin pigment which engulfed by macrophages (heart failure cells).
iv-Fibrous connective tissue proliferation around the alveoli is seen.
Nut Meg Liver CVC of Liver Causes: i-Interference with the venous circulation of the liver (hepatic veins, posterior vena cava). ii-Lung or heart affections.
Macroscopic Pictures: i-Color: is dark red, brownish or yellowish due to release of hemosiderin. ii-Size: increase in the early stage and decrease (atrophied) later. iii-Consistency: firm. iv-Cut surface: shows characteristic “nutmeg liver� due to red and yellow mottled appearance with blood oozed from cut sections. v-The hepatic lobules can be enumerated and represented by red spots (congested CV).
Microscopic Pictures: i-Congestion of central and portal veins and hepatic sinusoids. ii-Pressure atrophy of the hepatic cords and hepatic cells. iii-Brown pigment (hemosiderin) engulfed by kupffer cells. iv-CT proliferation around the central veins are present. v-Fatty changes in the hepatic cells of peripheral zones (due to hypoxia).
Cyanotic Induration of the spleen Definition: It is chronic venous congestion of the spleen, occurs due to right heart failure and in portal hypertension from cirrhosis of liver. It is characterized by: i-The spleen in early stage is moderately enlarged while in longstanding cases there is progressive enlargement. ii-It is deeply congested, tense and cyanotic (cyanotic induration of the spleen). Sectioned surface is gray tan. iii-The red pulp shows congestion and marked sinusoidal dilation with areas of recent and old hemorrhages. These hemorrhages may get organized. This advanced stage seen more commonly in hepatic cirrhosis is called congestive splenomegaly.
Outcomes of Congestion: i-Edema. iii-Hemorrhage. v-Induration of organs.
ii-Stasis. iv-Thrombosis. vi-Atrophy of organs.
NB: Hypostatic Congestion: It is the gravitation of blood in the lowermost portion of the body. It is usually caused by cardiac defect, which fail to maintain sufficient blood pressure to overcome the force of gravity. It occurs in debilitating and sick animals and in animals’ short time before and after death or in recumbent-diseased animals. Hemorrhage: blood outside the vessel-wall (extravascular). Hyperemia or congestion: blood inside of the vessel-lumen (intravascular).
Hemorrhage Definition: It is extravasation of blood from any part of cardiovascular system.
Mechanisms of hemorrhages: 1-By destruction or rupture of the wall of blood vessel or heart (by rhexis). 2-Occurs without any rupture of the vascular wall “intact wall” (by diapedesis).
Causes of hemorrhage by rhexis: due to: i-Trauma or cut. ii-Erosion or ulcer. iii-Diseases of the wall of blood vessels as aneurysm or tumor. iv-An increased blood pressure.
Causes of hemorrhage by diapedesis: due to: i-Bacterial toxins as in anthrax and H.S. ii-Chemical poisons as phosphorus. iii-Poisonous plants as sweet clover disease. iv-Intestinal toxins as enterotoxemia. v-Deficiency of vitamins C and K. vi-Defect in coagulation system (thrombocytopenia).
Types of hemorrhages according to the site of origin(by rhexis): 1-Cardiac: as following a penetrating heart wound. 2-Arterial: due to trauma and rupture of a dissecting aneurysm. 3-Capillary: due to trauma, inherent vessel wall weakness, or coagulation defect 4-Venous: caused by trauma or surgical operation.
Types of hemorrhages according to location: A-Internal hemorrhages: in the body cavities
Hemothorax: hemorrhage in the pleural cavity. Hemopericardium: hemorrhage in the pericardium cavity. Hemoperitoneum: hemorrhage in the abdomen cavity. Hemoarthrosis: hemorrhage in the joint cavity. Hematocele: hemorrhage in the tunica vaginalis of testis. B-External hemorrhages: may be such as Epistaxis: hemorrhage from nose Hemoptysis: hemorrhage from lung. Hematomesis: indicates hemorrhage from stomach. Melaena: hemorrhage from intestine. Metrorrhagia: hemorrhage from uterus.
Types of hemorrhages according to integrity of the blood vessels: i-Hemorrhages by rhexis (rupture of the wall). ii-Hemorrhages by diapedesis (intact wall).
Agonal hemorrhage: It is represented by small hemorrhagic areas on epicardium and endocardium (Petechiae or ecchymosis) and appeared just after death due to asphyxia or struggles. Purpura hemorrhagica: It means extensive hemorrhage with edema, which are slightly larger than petechiae. It occurs in serous and mucous membranes as a result of complication of strangles disease in horse due to intoxication that usually associated with disturbances of clotting mechanism and extensive endothelial and platelets damages. Hemophilia: It is hereditary blood disease and is transmitted to males through female and gives rise to extensive and fatal hemorrhage. It occurs due to deficiency of coagulation factor VIII.
Types of hemorrhages according to size and shape: Types of hemorrhages i-Petechial (not more than 1 mm). ii-Ecchymotic (up to 10 mm).
Pathogenesis By diapedesis (capillary injury). By diapedesis (capillary, arteriole and venules injury) iii-Suffusion (irregular area of Hgs). By diapedesis. iv-Hematoma (bloody cyst). By rhexis. v-Linear (zebra-like). By diapedesis. vi-Paint brush (streaks of Hgs.) By diapedesis.
In case of Septicemic diseases (on mucosa, serosa) Toxemic and septicemic diseases. Defect in clotting mechanism Trauma Cattle plague Canine Infectious Hepatitis
Macroscopic Pictures: In early stage: i-The affected organs are swollen, dark-red to purple in color. ii-The borders of organs become round. iii-On cut sections, dark red blood runs out.
In late stage: i-The organ is grayish-red to grayish blue in color due to slowing of the flow of the blood and the increase in CT. ii-The organ becomes small (decrease in size) due to shrinkage of CT. iii-The organ is firm and tough in consistency.
Microscopic Pictures: In early stage: i-Red cells are seen in tissue outside the blood vessels. ii-The venules and capillaries are filled with venous blood.
In late stage: i-Hemosiderin-laden macrophages (siderocytes) are seen. ii-Pressure atrophy of the parenchymatous cells. iii-Proliferation of CT and cholesterol clefts are seen. iv-The blood decrease in the area.
Fate of extravasated blood: The fate of an area of hemorrhage depends on the amount of blood that escaped from the vascular system. I-Small Areas: Small hemorrhage can be resorbed (Resorption).
II-Large Areas: 1-Organization: In generally larger amounts of hemorrhage. The extravasated erythrocytes are usually breakdown and phagocytized by macrophages. Liberate hemoglobin (red-blue), which breaks into hem and globins. Hem breaks into hematoidin (yellow granules) which form the bilirubin (blue-green) and hemosiderin (golden yellow or brown) that engulfed by macrophages.
2-Encapsulation: In larger areas (Hematoma) they are encapsulated and organized with some siderocytes.
Significance and effect of hemorrhage: The importance of hemorrhages is varies according to its size and location as small hemorrhage in brain may lead to paralysis or death. If the cause removed and stopping of hemorrhage, recovery occur, if persist it lead to death.
NB: Outcomes of hemorrhages: 1-Coagulation of the blood. 2-Organization and encapsulation of the hematoma. 3-Brown cystic formation (cerebral hematoma due to accumulation of hemosiderin) 4-Abscess formation of the hematoma by invasion of pyogenic bacteria.
Fluid Disturbances Edema and Dehydration Total Body Fluid: Plasma Interstitial fluid Intracellular fluid Transcellular fluid Total body fluid
Plasma hydrostatic pressure Tissue hydrostatic pressure Plasma colloidal osmotic pressure Tissue colloidal osmotic pressure Net filtration or absorption*
=5% lean body weight. = 15% ,, ,, ,, . = 40% = 5% = 65% of lean body weight
Arteriolar 30 mm Hg 8 mm Hg 25 mm Hg 10 mm Hg (30-8) - (25-10) = 7 mm Hg
Venular 17 mm Hg 8 mm Hg 25 mm Hg 10 mm Hg (17-8) – (25-10) = -6 mm Hg*
NB: Starling's law: Under normal conditions, the amount of fluid filtered out the arterial capillaries roughly equals the fluid returned to the various capillaries.
Edema Definition: It is abnormal and excessive accumulation of fluid in the interstitial tissue spaces and serous cavities. Edema fluid is outside the vascular fluid compartment and outside the cellular fluid compartment (i.e. within interstitium). Edema fluid lies free in the interstitial space between the cells and can be displaced from one place to another. Edema fluid may be:
i-Transudate, which is more often the case such as in edema of cardiac and renal diseases. ii-Exudate such as in inflammatory edema.
Differences between transudate and exudate Criteria Definition
Character Protein content
Cells Examples
TRANSUDATE Infiltrate of blood plasma without changes in endothelial permeability Non inflammatory edema Low (less than 3 gm/dl): mainly albumin, low fibrinogen, has no tendency to coagulate Few cells, mainly mesothelial cells and cellular debris Edema in congestive cardiac failure
EXUDATE Edema of inflamed tissue associated with increased vascular permeability. Inflammatory edema High (more than 3 gm/dl), readily coagulates due to high content of fibrinogen and other coagulation factors Many cells (inflammatory as well as parenchymal) Purulent exudates such as pus
Causes : Four mechanisms that underlie the development of edema: 1-Increase intravascular hydrostatic pressure: It is associated increased blood volume in the microvasculature such as venous congestion due to heart diseases, thrombosis and aneurysm or with active hyperemia in acute inflammation. 2-Increase microvascular permeability: It is associated with the inflammation and occurred due to bacteria and their toxins and snake venom lead to leakage of plasma fluid and edema. 3-Decrease plasma colloidal osmotic pressure (intravascular): It results from decrease plasma proteins mainly albumin, as in case of intestinal parasitic infestation, malnutrition and kidney diseases are the common causes of edema. 4-Lymphatic obstruction (lymphogenic edema): It occurs in case of tumor, abscess and intravascular parasites (filaria) lead to accumulation of edematous fluid.
Macroscopic Pictures: i-The affected organs are swollen, pale and heavy. ii-Soft or doughy in consistency. iii-The cut surface is wet and fluid weeps from it. iv-Edema fluid may yellow (horse and cattle) and gelatinous (inflammatory). v-In lung: the edema fluid is frothy in air passages.
Microscopic Pictures: i-Tissue spaces are distended by pale eosinophilic fluid. ii-Congestion of blood vessels may occur. iii-Lymphatics are dilated. iv-Collagen bundles of interstitial stroma are widely separated by an increase in intercellular fluid.
Types of Edema: according to presence or absence of inflammation. 1-Inflammatory Edema. 2-Non-inflammatory Edema.
Inflammatory Edema (Local) Mechanism: Increased vascular permeability and endothelial damage. Fluid characteristics: rich in protein (exudate). -High concentration of protein >30gm/L -Specific gravity is >1.01725 -Total nucleated cell count > 7.0 x 109 /L
Macroscopic Pictures: is due to acute inflammation. i-The affected tissue is red, hot, swollen and painful. ii-Not pit under pressure due to presence of fibrin. iii-On cut section, bloody fluid oozed. iv-The nature of the fluid is exudate. Microscopic Pictures: i-Congestion of the blood vessels. ii-Presence of eosinophilic fluid containing fibrin, RBCs and leukocytes.
Non-inflammatory Edema (Local and General) Mechanism: It is a result of i-Increase in intravascular hydrostatic pressure (venous obstruction). ii-Decrease of colloid osmotic pressure of the plasma (hypoalbuminemia). iii-Impairment in the flow of lymph (lymphatic obstruction). iv-Renal retention of salt and water. Fluid characteristics: poor in protein (transudate). -Low protein content <30gm/L -Specific gravity below 1.017 -Total nucleated cell count < 1.5 x 109 /L Macroscopic Pictures: i-The affected tissue is cold, pale, swollen and not painful. ii-Pit under pressure and gravitate. iii-The cut surface is wet and straw yellow fluid oozed iv-The nature of the fluid is transudate.
Types of edema: according to propagation: 1-Local Edema. 2-General Edema.
Local Edema i-Inflammatory edema: Edema is a cardinal sign of inflammation. It is caused by increased capillary permeability and hydrostatic pressure due to release of chemical mediators.
ii-Allergic edema: It is caused by increased capillary permeability and hydrostatic pressure due to release of vasoactive substances as histamine.
iii-Edema of venous obstruction: When complete obstruction of vein was seen as in case of thrombosis lead to severe edema and hemorrhage resulted from increased hydrostatic pressure at venous side. When venous drainage is partially impaired, edema is less severe.
iv-Edema of lymphatic obstruction: It is caused by lymphatic damage by surgery, neoplasm, abscess and intravascular parasites.
General edema 1-Cardiac Edema: It means not edema in the heart but it is caused by impaired cardiac function leading to general venous congestion increased hydrostatic pressure general edema 2-Edema of hypoproteinemia: It caused by decreased plasma osmotic pressure and includes
A-Renal Edema: It means not edema in the kidneys but the cause of edema is nephritis, which leads albuminuria decrease the colloidal osmotic pressure general edema.
B-Parasitic Edema: The intestinal and gastric worms take the dietary protein hypoproteinemia leads to decrease the COP general edema.
War or Starvation Edema: due to dietary protein deficiency (malnutrition edema) hypoproteinemia leads to decrease the COP general edema
Sequelae of Edema: i-If the cause is removed; recovery occur. ii-Pressure atrophy of the parenchymal cells. iii-The transudate is suitable media for bacterial growth. iv-Inability of vital organs to function (brain, heart and lung). Hydropericardium: It is edema in pericardial sac.
Hydrothorax: It is edema in thoracic cavity. Hydrocephalus: It is edema in brain.
Anasarca: It is generalized edema prominent in subcutaneous tissue and body cavities Hydrocele: It means edema in tunica vaginalis. Ascites: It means edema in abdominal cavity.
Dehydration Definition: It is deficiency of water resulting from imbalance between the uptake and loss of water from the body. It is opposite of edema.
Causes: i-Uncontrolled diarrhea. iii-Diabetes. v-Water deprivation.
ii-Renal failure. iv-Heat-stroke.
Mechanism: A decrease in the total body water results in water deficit shared among plasma, intracellular, and interstitial fluid compartments. Hypovolemic shock accompanies severe dehydration as plasma water is drawn into the interstitium. Renal perfusion is reduced.
Pathological Findings: i-Folds of skin pulled out from the body hesitate before returning to their normal position, "tentingâ&#x20AC;? ii-Eyes are sunken. iii-Mucous membranes and subcutaneous tissues are dry and sticky
Shock Definition: It is a clinical state of cardiovascular collapse characterized by: 1-An acute reduction of effective circulating blood volume. 2-An inadequate perfusion of cells and tissues. Three General Categories of Shock According to Etiology and Pathogenesis: 1- Hypovolemic 2- Cardiogenic 3-Blood Mal-distribution
NB:
Neurogenic and Anaphylactic shock both result in widespread vasodilation.
Hypovolemic Shock: It is results from decreased circulating blood volume, can be due to blood loss from hemorrhage or fluid loss secondary to vomiting, diarrhea or burns.
Cardiogenic Shock: It is results from failure of the heart to adequately pump blood. It can occur due to myocardial infarction, ventricular tachycardia, arrhythmias, cardiomyopathy, or an obstruction of the flow of blood from the heart. The stroke volume and cardiac output is decreased.
Blood Maldistribution: It is characterized by a decrease in peripheral vascular resistance and resultant pooling of blood in peripheral tissues. Caused by neural or cytokine induced vasodilation. Trauma, emotional stress, systemic hypersensitivity to allergens, or endotoxemia can cause blood maldistribution as in case of: i-Anaphylactic Shock: generalized type I hypersensitivity. ii-Neurogenic Shock: iii-Septic Shock:
Pathogenesis of Septic Shock: i-Results from spread and expansion of an initially localized infection ii-Most cases are from endotoxin-producing gram-negative bacilli endotoxic shock. iii-LPS binds as a complex with a circulating blood protein to leukocytes, endothelial cells, and other cells. iv-LPS-binding protein complex can activate vascular wall cells and leukocytes or initiate a cascade of cytokine mediators. v-LPS can activate complement. vi-High levels of LPS: -Cytokine-induced secondary effectors (NO and PAF) become significant. -Systemic effects of TNF and IL-1 fever, increase synthesis of acute phase reactants. -Causes endothelial cell injury triggers coagulation cascade.
vii-Super-high levels of LPS
Septic shock.
Stages of shock: There are 3 stages. 1-Initial nonprogressive (compensated reversible) stage: In the early stage of shock, an attempt is made to maintain adequate cerebral and coronary blood supply by redistribution of blood. This is achieved by activation of various neurohormonal mechanisms causing widespread vasoconstriction and by fluid conservation by the kidney
2-Progressive (decompensated) stage: This is a stage when the patient suffers from some other stress or risk factors besides persistence of the shock so that there is progressive deterioration 3-Irreversible (decompensated) stage: When the shock is so severe that in spite of compensatory mechanisms and despite therapy and control of etiologic agent, which caused the shock, no recovery takes place it is called decompensated or irreversible shock.
Pathognomonic Lesions: Pulmonary edema: (cattle/horses). Liver Congestion: (dogs). Kidneys: Acute tubular necrosis. Heart: Subendocardial hemorrhage and necrosis. Brain: Neuronal cell death. Adrenal glands: Cortical cell lipid depletion. Degranulation of adrenalin-producing cells. Hemorrhagic with foci of necrosis". Gastrointestinal tract: hyperemia of mucosa with erosions Skeletal muscle: Pallor (peripheral vasoconstriction).
II-Circulatory disturbances of obstructive nature Hemostasis and Thrombosis Hemostasis: (stasis=stop): It is arrest bleeding. Physiologic response to vascular damage and provides a mechanism to seal an injured vessels to prevent the blood loss. Thrombosis can be considered an inappropriate activation of normal hemostatic processes.
There are 3 general components required for hemostasis and thrombosis: 1-Vascular wall (endothelial cells). 2-Platelets. 3-Coagulation cascade.
Normal Hemostasis Sequence of events following vascular injury: 1-Arteriolar vasoconstriction (transient effect): i-Reflex neurogenic mechanism. ii-Local secretion of endothelin.
2-Primary hemostasis (platelet): - Damage to the endothelium exposes platelets to the subendothelial extracellular matrix i-Then the Platelets adhere to the ECM and become activated (Activation): i-Shape Change. ii-Release granules. iii-Recruit other platelets to the site (Aggregation).
ii-Form a Hemostatic plug: 3-Secondary Hemostasis (Coagulation): a-Tissue factor, a membrane-bound procoagulant factor synthesized by endothelium is exposed at the site of injury. It acts in conjunction with the material secreted by platelets to activate the coagulation cascade. b-Phospholipid complex expression. c-Thrombin activation: Formation of thrombin induces more platelet recruitment and granule release. d-Fibrin Polymerization resulting in local fibrin admixed with platelets form plug to prevent further hemorrhage.
4-Antithrombotic Counter-Regulation: -Release of components to limit the size of hemostatic plug.
Vascular Repair: 1-Platelet Derived Growth Factor (PDGF) stimulates smooth muscle and fibroblasts proliferation. 2-Fibroblast Growth Factor (FGF). 3-Transforming Growth Factor (TFG) modulates vascular repair.
Platelets: 1-Play a central role in normal hemostasis. 2-Circulate as round, smooth discs with glycoprotein receptors derived from megakaryocytes. 3-Major role is to form the initial plug that covers and seals a small damaged area. 4-Contain two types of granules: A-Alpha granules: P-selectin on membrane i-Fibrinogen. ii-Fibronectin. iii-Coagulation factors V and VIII. iv-Platelet factor 4. v-Platelet derived growth factor. vi-Transforming growth factor. B-Dense granules (delta granules): i-ADP and ATP: ADP mediates platelet aggregation and activation. ii-Ionized calcium. iii-Histamine. iv-Serotonin. v-Epinephrine.
Platelet Response: Vascular injury exposes Extracellular Matrix (ECM). i-Normally hidden by intact endothelium. ii-Composed of -Collagen, proteoglycans, fibronectin, and other materials.
Platelets + ECM 3 reactions i-Adhesion and shape change: Mediated via interactions with vWF that acts as bridge for platelets and ECM. ii-Secretion: (release reaction) of both granule types. -Release of dense granules is very important because calcium is required for coagulation cascade (Needed binding site for calcium and coagulation factors). -ADP is a very important mediator of platelet aggregation. -Leads to surface expression of a phospholipid complex. iii-Aggregation: -Thromboxane A2 (TxA2) secreted by platelets and induces vasoconstriction and necessary for platelet aggregation. -ADP + TxA2 start reaction leads to 1-Enlarging platelet aggregation = hemostatic plug (primary). 2-Activates coagulation generated thrombin increasing aggregation. 3-Platelet contraction fused mass of platelets, fibrin formed cements mass = hemostatic plug (secondary).
Coagulation Cascade: It is the formation of fibrin: initiated when activated factor X (Xa) cleaves the circulating protein prothrombin into two fragments. The active fragment is thrombin, a proteolytic enzyme that converts plasma fibrinogen to fibrin. The generation of thrombin is probably the most important factor in the progression and stabilization of the thrombus. Thrombin can be generated at the site of injury by either the intrinsic or extrinsic coagulation pathway. INTRINSIC PATHWAY: Although all factors of the intrinsic system are present in normal plasma. The cascade is activated by contact with subendothelial collagen which activate factor XII (Hagman factor). The latter activates XI which activates IX activates X which converts the prothrombin into thrombin. EXTRINSIC PATHWAY: Cell surface protein, termed tissue factor, (Factor III= tissue thromboplastin). Interaction with circulating factor VII initiates the extrinsic pathway in the presence of calcium leading to activation of factor X which converts prothrombin into thrombin that converts fibrinogen to fibrin.
NB: Platelet phospholipid becomes available on platelet surfaces during platelet activation.
Anticoagulant mechanisms: The anticoagulation mechanism is depending on the following: i-Removal of clotting factors by continuous blood flow. ii-The liver and mononuclear cells (phagocytic cells) clear of activated clotting factors. iii-Antithrombin III in the presence of heparin inactivates thrombin. iv-Dissolution of clots by fibrinolytic system.
Coagulation Disorders:
In general, large hematomas suggest a coagulation disorders whereas chronic bleeding from a mucosal surface may indicate a platelet deficiency or abnormality.
Inherited Deficiencies of Coagulation: as in hemophilia. Acquired Deficiencies of Coagulation: i-Accompany many severe diseases. 1-Transitory depression of factors. 2-Excessive utilization or consumption of factors ii-Acquired disorders may general or specific: -Severe trauma or deep burns. -Snake venoms and plant toxins. -Vitamin K deficiency (required for factors II, VII, IX, X and proteins C and S). iii-Liver failure: -Site of synthesis of many coagulation factors. -Acute destruction of hepatocytes may result in bleeding tendencies.
Thrombosis Definition: It is the formation of a solid mass from the elements of circulating blood within the vascular system (thrombus) during life of the patient. Thrombus: It is intravital, intravascular clot of all blood elements and in continuation of tunica intima of the vessel lining. PATHOGENESIS (Causes): 3 primary influences (Virchowâ&#x20AC;&#x2122;s triad).
1-Endothelial injury: Dominant influence = can lead to thrombosis by itself eg: inflammation of heart valves Expose of subendothelial ECM platelet adherence Depletion of prostacyclin
release of tissue factor
primary and secondary hemostatic plug formation.
It is produced by the following causes: i-Bacteria, toxins or chemicals ii-Diseases of the wall of blood vessels (atheroma, arteriosclerosis and parasites as Strongylus valgaris larvae). iii-Pressure from out side by ligature or tumor. 2-Slowing of Blood Stream: turbulence or stasis. Normal laminar blood flow (cellular elements in the middle, surrounded by plasma). Disrupt normal laminar flow: i-allows platelets to contact endothelium. ii-prevents dilution of activated clotting factors by fresh-flowing blood. iii-allows the build up of thrombi (slows the inflow of anticoagulants). iv-promotes endothelial cell activation.
Causes: -It is seen in aneurysms, cardiac anomalies and venous stasis. -Hypercoaguability: any alterations of the coagulation pathways that predisposes to slow the blood flow and thrombosis.
3-Alterations in Blood Composition: Increased in blood elements (increased fibrinogen levels and platelets number) leading to increase viscosity. It is the most important factors in venous thrombus. Presence of abnormal structures as i-Heart worm (D. immitis) ii-Clumps of bacteria in the blood. iii-Fragments of heart-valve thrombus circulating in the blood
Classification of the thrombi I-According to vascular involvement: i-Cardiac thrombi: it may be -Mural thrombi on the wall of the heart. -Valvular thrombi: attach to the valves. ii-Arterial thrombi: mostly seen in case of parasitic thrombus caused by larvae of Strongylus valgaris. iii-Venous thrombi: are more frequent in human than animals. iv-Capillary thrombi: are usually associated with inflammation. v-Lymphatic thrombi: occur in lymph vessels draining area of inflammation.
NB: The predominant constituent of thrombi is platelets. Arterial thrombi are attached and grow away from the heart. Venous thrombi are attached and grow in the direction of the blood flow (to the heart). Capillary thrombi are not true (false) and consist of agglutinated erythrocytes.
II-According to location within the heart or blood vessels: 1-Mural thrombi: are attached to the heart wall. 2- Valvular thrombi: are attached to the heart valves. 3-Lateral thrombi: are attached to one side of a vessel wall. 4-Occluding thrombi: are attached to the entire endothelium of the vessel. 5-Saddle thrombi: occlude just at the bifurcation of the blood vessels. 6-Canalized thrombi: result from partial repair of the clot with formation of a new blood canal. 7-Obturating thrombi: the clotting process continues in the part of thrombus which is distal to its area of attachment without any further connection to the wall. The free end then trails downstream with current and may attain surprising length.
III-According to the infection: 1-Septic thrombi: contain bacteria 2-Aseptic thrombi: do not contain bacteria or parasites 3-Parasitic thrombi: contain parasites.
IV-According to color of thrombi: 1-White or Pale Thrombus: is gray white, small and firmly attached to the intima. It is composed predominantly of platelets and fibrin. It is observed when the blood stream is rapid or fast (arterial). 2-Red Thrombus: it is composed of platelets, fibrin, large numbers of erythrocytes and leukocytes. It is formed when the blood stream is slow (venous). 3-Mixed Thrombus: it is composed of alternating layer of pale and red thrombi. 4-Laminated Thrombus: it is a type of mixed thrombus composed of alternating layers of white and red constituents. It is a result of variations in rapidity of blood stream.
Arterial and venous thrombi differ in appearance: Arterial: Generally due to endothelial injury, initial thrombus is composed of aggregated platelets and fibrin. It is soft, friable and white. As arterial thrombi grow, flow patterns adjacent to the thrombi cause fibrin to be
deposited and the platelet mass that persists that is transformed into a fibrin mass. Fibrin strands polymerize between the separating and degenerating platelets. The alternating lines of yellow platelets and fibrin separating RBCâ&#x20AC;&#x2122;s form the Lines of Zahn. Venous: A venous thrombi is composed of platelets and fibrin strands with entrapped RBC's, since the dominant mechanism of formation is coagulation. NB: Hyaline thrombus: It consists of platelets, destructed erythrocytes, leukocytes and precipitating plasma proteins. They do not contain fibrin. They resemble hyaline and are located in the microcirculatory bed. Agonal thrombus: It consists of the yellowish fibrin and localizes in the apex of the right ventricle of the heart and may extend into pulmonary artery. It is formed in the last minutes of the life when the death occurs slowly. NB: Red clot forms in case of the rapid death.
Postmortem clotting of blood: The postmortem clot occurs after death due to release of thromboplastin from damaged endothelium by lack of oxygen.
There are two types of postmortem clots. 1-Red or current jelly clot: It occurs when there is a rapid clotting of the blood. The blood components are evenly distributed throughout the clot. 2-Yellow or chicken fat clot: The ventral portion of the clot is red and contains erythrocytes, while the dorsal portion is composed of fibrin and serum. The erythrocytes sedimentation to form red zone is due to prolonged coagulation time or increased sedimentation rate.
Criterion
Arterial thrombus
Venous thrombus
PM-Clot
Pale or white (Dry, granular, firm and friable) Lamination Present Attachment to intima + (rough surface) Endothelial injury + Size and location Small (may be mural) Composition Platelets and fibrin Organization May partially occur
Red (Dry, granular, firm and friable) Not frequent + (rough surface) + Often fill lumen Platelets, fibrin and RBCs occur
Yellow in chicken fat Red in Current jelly (elastic and moist) Absent - (smooth surface) Fill lumen Fibrin Not occur
Initiated by Time of thrombus
Damaged endothelium In living animals
thromboplastin After death
Color and features
Damaged endothelium In living animals
Macroscopic Pictures: i-The thrombi tend to be irregular in shape, friable with dull roughened surface. ii-The color usually is a mixture of red and gray or has have a laminated structure in irregular layers or lines of Zahn which contain alternating pale lines (composed of platelets and fibrin) and darker strips of (predominantly red blood cells). iii-Thrombi may vary in size from microscopic (such as fibrin thrombi plugging capillaries) to thrombi that occupy large portions of the aorta or fill a cardiac chamber. iv-At least one side attached to the wall of blood vessel.
Microscopic Pictures: -It composed of blood elements along with fibrin. Platelets are difficult to be observed, except perhaps at the points of attachment.
Effect of thrombosis: i-Beneficial effects: Thrombosis of injured vessels assists in control of hemorrhage.
ii-Negligible effects: when the thrombi are present in blood vessels which are not required. Blood vessels in most organs are very abundant and form anastomosing circulation which accommodates the needs of tissue. iii-Harmful effect: Thrombosis of major blood vessels in areas with insufficient collateral circulation that in vital organs as brain and heart.
Fate of thrombi 1-Lysis: Lysis of the thrombus is due to potent thrombolytic/fibrinolytic activity of blood (plasmin, which activated by factor VII). 2-Contraction: The first alteration occurring in thrombi, containing fibrin, is decrease in size due to contraction of fibrin. 3-Liquefaction: It occurs under the effect of autolytic leukocytic enzymes. 4-Abscessation: when pyogenic bacteria are present.
5-Organization: The presence of a thrombus stimulates reaction which will result in inflammation and fibrosis. Smooth muscle cells and fibroblasts will proliferate and invade. The thrombus will become firm and gray-white 6-Recanalization: occurs by invasion of thrombus mass by newly formed capillaries and allows blood flow the damaged vasculature. 7-Mineralization: of degenerated and necrotic thrombi usually occurs.
8-Embolization: Some time fragment of thrombus is detached and carried in the circulation.
NB: Disseminated intravascular coagulation (DIC) It is the widespread development of small fibrin thrombi in the microcirculation throughout the body with simultaneous reduction of blood coagulability and hemorrhages. It occurs with infectious disease, immunologic injury and snakebite, which lead to diffuse endothelial injury. In animals, it is usually observed with severe burn, extensive trauma and in severe systemic infection as canine hepatitis, blue tongue and hog cholera. It has 3 stages:
i-At the first stage: it is characterized by generalized increase of blood coagulation in the microvessels. Large number of fibrin clots is formed. They close the vessel (fibrinoembolism). ii-At the second stage: the amount of thrombocytes, fibrinogen, prothrombin in the blood decreases sharply because they have already been used at the first stage with the resultant consumption coagulopathy. Thus, hemorrhagic syndrome develops.
iii-At the third stage: fibrinolysis activation takes place in response to generalized increase of coagulation occurring at the first stage, which makes hemorrhagic syndrome more severe.
Embolism Definition: It is the process of moving of solid, liquid, gaseous foreign body
through the circulatory system. Embolus: It is a foreign body circulating in the blood. Causes and Types of Emboli: A-Solid Emboli: 1-Detached thrombi (Thromboemboli): 2-Bacterial emboli: 3-Parasitic emboli: 4-Tumor cell emboli: 5-Foreign bodies emboli: B-Liquid Emboli: 1-Fat-droplet emboli: It is a droplet of endogenous fat that have entered the circulation. A fracture of bone is the most common cause. 2-Amniotic emboli: 3-Spodogenous emboli: occur due incompatible blood transfusion. C-Gaseous Emboli: It is due to i-Decompression Sickness: It is seen following a rapid change in atmospheric pressure in deep-sea divers and in construction workers emerging from underwater compartments (Caisson disease or gas
embolism). ii-Air Emboli: may cause bubbles in the blood that may coalesce and obstruct the flow of blood causing infarction. It may occur when traumatic or surgical wounds rupture large blood vessels.
Significance and Results: The results of embolism depend up on the following factors:
1-Nature of embolism: i-Septic emboli leads to pyemia with multiple abscesses formation. ii-Aseptic emboli leads to ischemia and infarction. iii-Neoplastic emboli produce secondary tumor.
2-Size of embolus: i-Small could induce partial arrest of blood supply and local anemia or ischemia. ii-Large could induce complete obstruction and infarction.
3-Number of emboli: More number of emboli in circulation led to greater blood vessel obstruction and infarctions.
4-Blood vessel involved: The occlusion of blood vessel depends on the efficient collateral circulation or not: i-If efficient collateral circulation: little damage. ii-If not efficient collateral circulation: serous damage and cause sudden death.
Infarction Definition of infarct: It is an area of ischemic necrosis caused by complete occlusion of either the arterial supply (end artery) or occasionally its venous drainage in a particular tissue. The process of development of this lesion is known as infarction.
NB: the end artery means that artery has few collateral branches and anastomosis such as coronary arteries of the heart, afferent artery of glomeruli, splenic artery, central artery of retina and artery supplying the basal ganglia and surface of brain.
Classification of infarct: A-According to color: 1-Red (Hemorrhagic)
infarct:
It filled with blood and characterized by coagulation necrosis and erythrocytes from adjacent arteries and veins. It occurs with venous occlusions or within loose tissue that allow blood to collect in the infarct area or in organs with double blood supply (lung and liver) or extensive collateral circulation (small intestine). 2-Pale (white) infarct: It lacks blood, also called anemic infarct. It usually has a red zone at periphery (line of defense). It occurs with arterial occlusions in solid organs (heart and kidney).
B-According to infection: i-Septic infarcts: When the necrotic tissue of an infarct is invaded by pyogenic bacteria. The tissue becomes a good growth medium for these pathogenic organisms ii-Aseptic infarct: Most infarcts are sterile (no bacteria).
Pathogenesis: 1-Immediately after obstruction of the artery by thrombus or embolus, the area supplied by this vessel is deprived of blood from its normal source. 2-The blood from adjacent arteries is forced to ischemic area through the anastomosing capillaries. 3-The capillaries become dilated and engorged with blood to maintain the need of the affected area. 4-The affected area becomes redder in color than the surrounding tissue and this is known as â&#x20AC;&#x153;red or hemorrhagic infarctâ&#x20AC;?. 5-The blood circulation in the infarct area is stagnant and the blood becomes deficient in oxygen and contains excessive waste products because the blood pressure is not great enough to force all this blood out of the involved area leads to injury of capillary endothelium and parenchyma of the area giving rise to hemorrhage, edema and necrosis.
6-The area undergo coagulative necrosis and the erythrocytes become hemolysed and the hemoglobin derivatives are removed and the area becomes pale instead of red. This is known as â&#x20AC;&#x153;pale or white infarctâ&#x20AC;? which appears after 48-72 hrs. 7-The dead tissue produces toxic substances which induce inflammatory reaction in surrounding tissue. 8-This inflammatory zone is characterized by dilated capillaries, fibrin network and leukocytes infiltration. 9-Later on, the infracted area undergoes autolysis and disappears and replaced by CT.
Macroscopic Pictures: i-Wedge or cone-shaped: the base of the wedge is at periphery and the apex is at the point of obstruction. ii-The color is differs from red to pale or white. The infarcts usually red in the first and then become pale except in the brain it is usually pale. The infarct of intestine lungs and liver is usually red. iii-The infarct is swollen in the early stage and shrinkage below the surface with red margin. iv-The red is soft in consistency and the pale becomes firm or hard.
Microscopic Pictures: i-Infarcts appear as triangular areas of coagulative necrosis. ii-An infarct is separated from the rest tissue by an inflammatory zone (line of defense) iii-This inflammatory zone consists of dilated capillaries, fibrin and leukocytes. iv-In red infarct: The inflammatory zone is not clear. Hemorrhage by diapedesis and dilated capillaries. v-In pale infarct: The inflammatory zone is clear. The RBCs in the red infarct is instead of leukocytes.
Sequelae of infarction: i-The infarct area losses their function of affected area. ii-Infarcts arising from septic emboli or that invaded by pyogenic bacteria may convert to an abscess. iii-Autolysis of the necrotic tissue and absorbed or become encapsulated. iv-Organization by fibrous CT proliferation. v-Deaths may resulted from: -Brain infarct. -Moist gangrene by invasion of saprophytic bacteria as in intestine. -Acute anemia due to extensive blood loss.
Circulatory Exam 1-Active Hyperemia: Two words; the first (active): means…….…………………….…………. and the second (hyperemia) means………………………………...……………………………. 2-Increase the number of erythrocytes (polycythemia) could induce i-Active hyperemia ii-Venous congestion iii-Edema iv-Emboli 3-Microscopicaly, show dilation of blood vessels and leukocytes that describe i-Hemorrhages ii-Hyperemia iii-Inflammation iv-Infarction 4-the causes of chronic general venous congestion are present in two main organs: i-……………………………………………. ii-…………………………………………………. 5-The CVC in the lung is called……………………; while in the liver is……………………… 6-The nut meg liver is characteristic for CVC due to i-…………………….. ii-……………….. 7-Blood outside the vessel-wall is called………………; while that increased inside the vessellumen is called……………………………………………………. 8-List 3 types of hemorrhages according to its size i-……………. ii-………….iii-…………. 9-Define the following: i-Cardiac Tamponade…………………………………………………………. ii-Agonal hemorrhage…………………………………………………………. iii-Purpura hemorrhagica…………...…………………………………………. 10-Causes of Edema: iiiiiiiv11-Mention the mechanisms of inflammatory and non-inflammatory edema. 12-Differentiate between Exudate and Transudate. 13-List 2 types of General Edema. 14-Define Anasarca:
15-Write briefly on the pathological findings of the â&#x20AC;&#x153;Dehydrationâ&#x20AC;?. 16-List 3 types and stages of shock. 17-Mention 3 risk factors (causes) of thrombus. 18-Classify the thrombus according to color. 19-Define: i-Hyaline thrombus: ii-Agonal thrombus: iii-Line of Zahn: 20-List 2 types of PM-clot:
21-Differentiate between Arterial and venous thrombi, and PM-clots. Criterion
Arterial thrombus
Venous thrombus PM-Clot
Color and features Lamination Attachment to intima Endothelial injury Size and location Composition Organization Initiated by Time of thrombus
22-Fate of Thrombus: 23-List types of Emboli: 24-List types of infarction and 3 micro for each type.
25- Mark (true or false) and correct the false statements: i-Hydrothorax means accumulation of fluid in the tunica vaginalis of testis ( ) …………………………………………………………………………………………………….. ii-Local Passive hyperemia is associated with acute inflammation ( ) …………………………………………………………………………………………………….. iii-Red infarction only seen in the brain ( ) …………………………………………………………………………………………………….. iv-Renal edema means accumulation of fluid in renal tissue ( ) …………………………………………………………………………………………………….. v-Lesions in the heart and lungs are associated with general active hyperemia ( ) …………………………………………………………………………………………………….. vi-Animals suffering decrease in platelets count (thrombocytopenia) are associated with DIC( ) ……………………………………………………………………………………………………. vii-Detached thrombus could induce local ischemic area of necrosis ( ) viii-Inflammatory edema is pitted under pressure due to presence of fibrin ( ) ix-Thrombosis in the liver and lungs are fatal ( ) …………………………………………………………………………………………………….. x-Infarction is classified into white or pale, hemorrhagic or red and mixed ( ) …………………………………………………………………………………………………… 26-Macroscopic differences between inflammatory and non-inflammatory edema 27-Define the following: i-End artery: ii-Infarct: iii-Thrombus: iv-Heart failure cells v-Embolus: vi-Thrombocytopenia
1-Mention 3 Macro and 3 Micro of the following: -Nut meg Liver. -Brown Induration of the lung. -Infarction in the kidney. -Non inflammatory edema.
2-List the causes of the followings: -Chronic General Venous Congestion. -Thrombus. -Edema
3-Enumerate the types of the following: -Hemorrhages according to the size and its pathogenesis. -General edema. -Thrombus. -Shock.
4-Write short notes on the following: -Sequelae of thrombosis. -Pathogenesis of infarction. -Differences between arterial and venous thrombus and PM clots.