Disseminated Intravascular Coagulation (DIC):

1. Disseminated Intravascular Coagulation (DIC):

2. Disseminated Intravascular Coagulation (DIC): • Appearance of numerous fibrin thrombi within small blood vessels. • It is usually a complication of systemic diseases, malignancies, extensive trauma and burns. • In cattle, it has been associated with acute sarcocystosis from endothelial damage by schizonts.

3. Pathogenesis: • DIC is due to release of tissue factor (thromboplastin) and factors from damaged endothelium or by direct activation of clotting factors. • Activation of coagulation system leads to generation of thrombin which converts fibrinogen into fibrin. • Thrombi are most commonly seen in lungs, kidney, liver, spleen, adrenal, heart and brain. • Extensive thrombosis depletes platelets and fibrinolytic mechanism (plasminogen) digests fibrin, fibrinogen and factors V and VIII. • Eventually there is failure of blood clotting and severe bleeding occurs.

4. Embolism: • An embolus is any foreign body floating in the blood. • The process of a foreign body moving through the circulatory system and becoming lodged in a vessel causing obstruction, ischemia and infarction is called embolism.

5. Location: • Emboli may occur anywhere in the arterial or venous circulation but they usually lodge in an artery or a capillary due to decrease of diameter. • Venous emboli pass through large veins and are brought to right side of the heart and become lodged in the pulmonary circulation, called pulmonary embolism – has serious consequence. • An embolus originating from venous thrombi rarely passes through a congenital inter-auricular or interventricular defect and enters into general circulation – called paradoxical embolism.

6. Causes and Types of Emboli: Thrombi: • Great majority of emboli arise from thrombi. The thrombi disintegrate and the fragments are carried away as emboli. Emboli originating from the thrombi in the hearth and aorta maybe scattered throughout the body. Bacteria: • Bacterial emboli are seen in many diseases. Bacteria spread as single cells, clumps or inside the phagocytic cells. This mode of spread of infection is called metastasis – commonly seen in lung, liver and kidney.

7. Cont… • Parasites: • Whole parasites or fragments commonly form emboli, including dog heartworm Dirofilaria immitis in pulmonary artery, schistosomes in cattle, sheep and goats, agglutinated trypanosomes, and larvae of hookworms, ascarids, strongyles etc. • Neoplams: • Malignant tumours commonly spread in the body as emboli. Malignant tumours grow through the walls of arteries and lymphatics and clumps of tumour cells are carried away as emboli – metastatic spread. • Fat Emboli: • These appear following fracture of long bones. Fat globules from bone marrow enter ruptured blood vessels and are transported to lungs.

8. Air or Gas Emboli: • Small bubbles of air or gas gain access to the circulation following injuries, particularly in the neck region. Approximately 100ml air is necessary to produced clinical effects. Caisson disease or bends is seen in underwater workers due to rapid decompression of their chambers and appearance of nitrogen bubbles in the circulation may cause necrosis in the brain, heart etc. • Other Types of Emboli: • Fragments of bone, hair, fibrocartilaginous material may form emboli. Amniotic fluid embolism is a serious complication in humans.

9. Significance and Results: • Importance of embolism depends upon several factors: i)Nature of emboli: a) Size of embolus – large emboli are more harmful. b) Septic or bland: Septic emboli set up new foci of infection and these have more serious effects. c) Neoplastic emboli start neoplastic growths wherever they lodge. ii) Number of emboli: Greater number of emboli causes larger number of vascular obstructions and infarcts. • Organs involved: Organ with extensive collateral circulation and vascular anastosomosis like lung and liver show less injury from emboli as compared to organs with more end arteries and less collateral circulation e.g. heart, kidney and spleen. The clatter organs show necrosis (infarction of the affected parts).

10. Infarction: • An infarct is an area of ischemic necrosis caused by occlusion of an artery or rarely of the venous drainage of a tissue.

11. Causes: • Obstruction in the blood flow maybe within the lumen of the blood vessel, pressure from outside (perivascular) or in the wall of blood vessel. • Thrombi and emboli cause obstruction within the lumen and are the most common cause of infarction. Venous emboli in the pulmonary arterial system and those arising in the heart and major arteries cause obstruction in the systemic arteries. • Tumours, abscesses and cysts cause compression of arteries from outside. • Narrowing of an artery and infarction maybe caused be a vascular disease like atherosclerosis. • Narrowing or occlusion may also be caused by drugs such as ergot inducing contraction of musculature in the arterial wall. This usually affects extremities like tail, ear, hooves etc. • Occlusion of venous outflow may cause infarction in case of strangulated intestine (torsion) testis and ovary.

12. Types of Infarcts: • Two types of infarcts are recognized, according to the colour of infarct, density of the organ and type of vascular occlusion i.e. artery or vein. • Pale, white or anemic infarcts: These occur in dense organs like heart, kidney and spleen due to limited amount of haemorrhage in the areas of ischemic necrosis. • Red or haemorrhagic infarcts are found in loose, spongy organs like lungs.

13. Pathogenesis: • Immediately after obstruction of an artery the area supplied by the vessel undergoes ischemia. • Blood is forced from the neighbouring arterial system by blood pressure in the ischemic area which becomes red infarct. • The capillaries dilate and become engorged with blood. • Due to hypoxia, changes occur in the capillary endothelium and there is haemorrhage by diapedesis. • Within 24 hours, cells at the centre of infarct undergo coagulation necrosis which later spreads towards the periphery of infarct. The entire area of infarction becomes necrotic and sharply defined within 72 hours. Cont….

14. Erythrocytes undergo lysis and release hemoglobin which either diffuses out or is transformed to hemosiderin. • At this stage infarcts in the dense organs are called pale or anemic infarcts. • In the spongy organs like lungs, the infarcts do not become pale i.e. they remain red. • Dead tissue is irritating and inflammatory reaction appears between the healthy and dead tissue. • Macrophages accumulate in the area and fibroblasts and new blood vessels proliferate. • Most infarcts are ultimately replaced by scar tissue. • If the embolus is infected, abscess formation takes places.

15. Microscopic Appearance: • Generally, infarcts are wedge-shaped with apex at the point of arterial obstruction and its base at the periphery of the organ. • Red and haemorrhagic infarcts are raised whereas pale and anemic infarcts are slightly depressed. Contraction of connective tissue in an organized infarct causes marked depression and irregular surface. • Infarcts in spleen are usually red because of large amount of blood and many vascular sinuses in t his organ.

16. Significance and Outcome: • According to its size and location the outcome of infarct maybe: • Death of small area may have no clinical effects. • Organization and production of a scar. • Shock from absorption of toxic products when area of infarction is large. • Saprophytic bacterial invasion of necrotic tissue may cause moist gangrene. • If pyogenic bacteria are present, an abscess maybe formed. • Death may occur if infarct involves a vital organ like heart, brain or intestine.

17. Edema: • There is excessive accumulation of fluid in the interstitial tissue spaces and body cavities. Edema maybe local or general.

18. Terminology: • Anasarca (made of wood) it is generalized edema of whole body with swelling of subcutaneous tissue. • Collection of edema fluid is indicated by prefix “hydro” e.g. hydorperitoneum or ascites is accumulation of edema fluid in the peritoneal cavity.

19. Hydrothorax – in the plural (thoracic) cavity, Hydropericardium – in the pericardial sac, Hydrocephalus – in the ventricles of brain, Hydronephrosis – in the renal pelvis, • Hydrocele – in the tunica vaginalis. • Edema fluid is non-inflammatory and is referred to as transudate. It is low in protein contents and other alkaloids with a specific gravity below 1.012. Inflammatory edema is called exudate which is rich in proteins and its specific gravity is over 1.020.

20. Pathogenesis: • Edema results from disturbance of normal fluid exchange between intravascular and interstitial compartments. • Fluid exchange is necessary for supply of oxygen and nutrients to cells and tissue and removal of waste products from blood. • It takes place in the capillaries and is governed by Starling’s law (forces). According to this hypothesis most of the fluid comes out of the vessels at the arteriolar end of capillaries and it returns to the vessel at the venular end. • Normally, the amounts of fluid leaving the blood vessel and returning to it are almost equal and whatever fluid remains in the tissues is drained out by the lymphatics, so that no fluid accumulates in the tissues. • The forces expelling the fluid out of the blood vessels are hydrostatic pressure inside the blood vessels and osmotic pressure of the tissue fluid.

21. The forces pulling the fluid into the blood vessels are plasma colloid osmotic pressure inside the blood vessels and hydrostatic pressure of the tissue fluid. • Hypothetically, the hydrostatic pressure at the arteriolar end of the capillary is 45mm Hg which drops to 15mm Hg at the venular end. • The plasma colloid osmotic pressure at the arterial end is considered to be 30mm Hg and since large molecular proteins do not leave the blood vessel, this osmotic pressure remains almost same or a little more at the venous end of the capillary. • Accordingly, fluid flows into the tissues at the arterial end with a force of 15mm Hg and it flows into the capillary with an almost equal force viz 15mm Hg. Thus, there is a continuous exchange of fluid between the two compartments and there is no accumulation of fluid in the interstitial space (edema). Edema occurs when this normal fluid exchange is deranged due to increased hydrostatic pressure, decreased colloid osmotic pressure and obstruction of lymphatic drainage etc.

22. Causes of Edema: • Increased hydrostatic pressure: This occurs in local or general passive congestion. The impaired venous return increases the venous hydrostatic pressure from 15mm Hg to 20mm Hg. If the other factors remain normal then the fluid will leave capillaries with a force of 15mm Hg and will return with a force of 10mm Hg. Therefore it will accumulate in the tissue spaces at the rate of 5mm Hg. Since the usual cause of venous stasis is impaired cardiac function, edema caused in this way is call cardiac edema.

23. Reduced plasma osmotic pressure: This results from excessive loss or reduced synthesis of serum albumin i.e. hypoproteinemia. The common causes of hypoproteinemia are a) Blood sucking parasites like haemonchosis and trichostrongyles called parasitic edema in cattle, sheep and goats. b) Loss of proteins in urine (proteinuria) in renal diseases – called renal edema. c) Hypoproteinemia maybe caused by decreased synthesis of plasma proteins in liver diseases like cirrhosis. d) Plasma osmotic pressure also decreases in starvation, malnutrition and cachexia – called nutritional edema or cachectic edema. In this case the plasma osmotic pressure maybe decreased to 20mm Hg and if the other factors remain normal then the fluid will leave capillaries with a force of 25mm hg and return with a force of only 5mm hg. Therefore, fluid will accumulate in the tissues with a force of 20mm Hg.

24. 3. Lymphatic obstruction: This usually causes local edema. Obstruction of lymphatics maybe due to inflammation, neoplasms, cysts or abscesses. Filarial worms cause inflammation of lymph nodes and lymphatics and massive edema of lower limbs called elephantiasis. • Sodium and water retention: Decreased urinary excretion of sodium occurs in congestive heart failure, in nephrosis and in acute renal failure. Retention of sodium causes water retention and generalized edema.

25. Gross Appearance: • Edematous part is swollen, firm and doughy in consistency. It “pits on pressure” – if a finger is pressed into edematous tissue, it leaves a small depression for a moment. • Upon incision, clear edema fluid flows out. • The swollen part is usually cold and painless. • Fibrosis occurs when edematous fluid persists in a tissue for a considerable time.

26. Microscopic Appearance: • The interstitial spaces are increased. Edema fluid in tissues sections is indicated by a faintly stained granular material. The intensity of eosin staining depends on the amount of protein (albumin) in the transudate. Atrophy of parenchyma cells and fibrosis occur in the areas of edema. • Significance: Edema disappears if the cause is removed. Removal of edema fluid is not useful unless the cause of edema is removed.