General Pathology Lecture 4 PDF

# General Pathology Lecture 4 Dr. Kareem Eldin Mohammed Ahmed ## Hemostasis - **Hemostasis** is the process of blood clotting that prevents excessive bleeding after blood vessel damage. - Inadequate hemostasis may result in **hemorrhage**, which can compromise regional tissue perfusion and, if ma...

# General Pathology Lecture 4 Dr. Kareem Eldin Mohammed Ahmed ## Hemostasis - **Hemostasis** is the process of blood clotting that prevents excessive bleeding after blood vessel damage. - Inadequate hemostasis may result in **hemorrhage**, which can compromise regional tissue perfusion and, if massive and rapid, may lead to hypotension, shock, and death. - Conversely, inappropriate clotting (**thrombosis**) or migration of clots (**embolism**) can obstruct blood vessels, potentially causing ischemic cell death (**infarction**). - **Thromboembolism** lies at the heart of three major causes of morbidity and death in developed countries: myocardial infarction, pulmonary embolism, and cerebrovascular accident (stroke). ## Hyperemia and Congestion - Hyperemia and congestion both refer to an increase in blood volume within a tissue but they have different underlying mechanisms. - **Hyperemia** is an active process resulting from arteriolar dilation and increased blood inflow, as occurs at sites of inflammation or in exercising skeletal muscle. - Hyperemic tissues are redder than normal because of engorgement with oxygenated blood. - **Congestion** is a passive process resulting from impaired outflow of venous blood from a tissue. - It can occur systemically, as in cardiac failure, or locally as a consequence of an isolated venous obstruction. - Congested tissues have an abnormal blue-red color (**cyanosis**) that stems from the accumulation of deoxygenated hemoglobin in the affected area. ## Oedema - The Greek word "oidema" means swelling. - **Oedema** is defined as abnormal and excessive accumulation of "free fluid" in the interstitial tissue spaces and serous cavities. - **Free fluid in body cavities**: Commonly called as effusion, it is named according to the body cavity in which the fluid accumulates. For example, ascites (if in the peritoneal cavity). - **Free fluid in interstitial space**: Commonly termed as oedema, the fluid lies free in the interstitial space between the cells and can be displaced from one place to another. - Oedema may be of 2 main types: - **Localized** when limited to an organ or limb e.g., lymphatic oedema, inflammatory oedema, allergic oedema. - **Generalized** (anasarca) when it is systemic in distribution, particularly noticeable in the subcutaneous tissues e.g., renal oedema, cardiac oedema. - Depending upon fluid composition, oedema fluid may be **transudate** which is more often the case, such as in oedema of cardiac and renal disease or **exudate** such as in inflammatory oedema. - Oedema is caused by mechanisms that interfere with normal fluid balance of plasma, interstitial fluid and lymph flow: - Increased capillary hydrostatic pressure. - Lymphatic obstruction. - Increased capillary permeability. - Sodium and water retention. ## Table 4.1 Differences between transudate and exudate. | FEATURE | TRANSUDATE | EXUDATE | |---|---|---| | Definition | Filtrate of blood plasma without changes in endothelial permeability | Oedema of inflamed tissue associated with increased vascular permeability | | Character | Non-inflammatory oedema | Inflammatory oedema | | Protein content | Low (less than 1 gm/dl), mainly albumin, low fibrinogen, hence no tendency to coagulate | High (2.5-3.5 gm/dl), readily coagulates due to high content of fibrinogen and other coagulation factors | | Glucose content | Same as in plasma | Low (less than 60 mg/dl) | | Specific gravity | Low (less than 1.015) | High (more than 1.018) | | pH | > 7.3 | < 7.3 | | LDH | Low | High | | Effusion LDH/ Serum LDH ratio | < 0.6 | > 0.6 | | Cells | Few cells, mainly mesothelial cells and cellular debris | Many cells, inflammatory as well as parenchymal | | Examples | Oedema in congestive cardiac failure | Purulent exudate such as pus | ## Dehydration - Dehydration is a state of pure deprivation of water leading to sodium retention and hence a state of hypernatraemia. - In other words, there is only loss of water without loss of sodium. - Clinically, the patients present with intense thirst, mental confusion, fever, and oliguria. - **Etiology:** - **GI excretion** (Severe vomiting, Diarrhea) or **Renal excretion** (diabetes insipidus, Extensive use of diuretics) - **Loss of blood and plasma** (Severe injuries, severe burns) - **Loss through skin** (Excessive perspiration, Hyperthermia). - **Morphological:** There are no particular pathological changes in organs, except in advanced cases when the organs are dark and shrunken. In late stage, Renal shutdown and a state of shock may develop. ## Overhydration - Overhydration is increased extracellular fluid volume due to pure water excess or water intoxication. - Clinically, the patients present with disordered cerebral function e.g., nausea, vomiting, headache, confusion and in severe cases convulsions, coma, and even death. - **Etiology:** Overhydration is generally an induced condition, such as: - **Excessive unmonitored intravascular infusion.** - **Renal retention of sodium and water** (Congestive heart failure, Chronic renal failure) - **Morphology:** Sudden weight gain is a significant parameter of excess of fluid accumulation. Haematological and biochemical changes: reduced plasma electrolytes and lowered plasma proteins. ## Disturbances in the volume of circulating blood - **Hyperemia and congestion** are the terms used for localized increase in the volume of blood within dilated vessels of an organ or tissue. - **Increased volume of blood from arterial and arteriolar dilatation** (i.e., increased inflow) is referred to as **hyperemia** or **active hyperemia.** - **Impaired venous drainage** (i.e., diminished outflow) is called **venous congestion** or **passive hyperemia.** ## Active Hyperemia - The dilatation of arteries, arterioles and capillaries is effected either through sympathetic neurogenic mechanism or via the release of vasoactive substances. - The affected tissue or organ is pink or red in appearance (erythema). - **Examples:** - **Inflammation**, e.g., congested vessels in the walls of alveoli in pneumonia - **Blushing**, i.e., flushing of the skin of face in response to emotions. - **Clinically,** hyperemia is characterized by redness and raised temperature in the affected part. ## Passive Hyperemia (Venous Congestion) - The dilatation of veins and capillaries due to impaired venous drainage results in passive hyperemia or venous congestion, commonly referred to as passive congestion. - The affected tissue or organ is bluish in color due to accumulation of venous blood (cyanosis). - Obstruction to the venous outflow may be local or systemic. - **Venous congestion** is of 2 types: - **Local venous congestion** results from obstruction to the venous outflow from an organ or part of the body (portal venous obstruction in cirrhosis of the liver). - **Systemic (General) venous congestion** is engorgement of veins (in left-sided and right-sided heart failure). - **Grossly:** the lungs are heavy and firm in consistency. - **Histologically:** Rupture of dilated and congested capillaries may result in minute intra-alveolar hemorrhages. The breakdown of erythrocytes liberates hemosiderin pigment. ## Haemorrhage - Haemorrhage is the escape of blood from a blood vessel. - The bleeding may occur externally, or internally into the serous cavities e.g. haemothorax, haemoperitoneum. - Extravasation of blood into the tissues with resultant swelling is known as **haematoma**. - **Petechiae** are small areas of haemorrhages (1 to 2 mm in diameter) into the skin and mucous membrane. - **Purpuras** (3 to 5 mm) are minute pinhead-sized haemorrhages. - **Ecchymoses** are larger (1 to 2 cm) subcutaneous hematomas (colloquially called bruises). - **Etiology:** The blood loss may be large and sudden (acute), or small repeated bleeds may occur over a period of time (chronic). Causes of haemorrhage: - Trauma to the vessel wall. - Spontaneous haemorrhage (ruptured aneurysm). - Inflammatory lesions of the vessel wall. - Neoplastic invasion. - The effects of blood loss depend upon 3 main factors: - The amount of blood loss. - The speed of blood loss. - The site of haemorrhage. - The loss up to 20% of blood volume suddenly or slowly generally has little clinical effects because of compensatory mechanisms. - A sudden loss of 33% of blood volume may cause death. - Rapid loss of above 33% of blood volume is more serious than gradual blood loss of 50% in 24 hours. - Chronic blood loss produces iron deficiency anaemia, whereas acute haemorrhage may lead to hypovolaemic shock. ## Hemostasis and Thrombosis - Normal *hemostasis* comprises a series of regulated processes that maintain blood in a fluid, clot-free state in normal vessels while rapidly forming a localized hemostatic plug at the site of vascular injury. - The pathologic counterpart of hemostasis is *thrombosis*, the formation of blood clot (thrombus) within intact vessels. - Both *hemostasis* and *thrombosis* involve three elements: the vascular wall, platelets, and the coagulation cascade. - Endothelial injury exposes highly thrombogenic subendothelial extracellular matrix, facilitating platelet adherence, activation, and aggregation. - The formation of the initial platelet plug is called **primary hemostasis**. - Exposed tissue factor, acting in conjunction with factor VII, is the major trigger of the **coagulation cascade** and its activation eventually culminates in the activation of thrombin, which has several roles in regulating coagulation. - **Secondary hemostasis** is the formation of the stable fibrin clot. - **Antithrombotic counterregulation** is the process of dissolving the fibrin clot and restoring blood flow. ## Coagulation Cascade - The coagulation cascade is a series of enzymatic reactions that result in the formation of a stable fibrin clot. - The cascade can be activated by two pathways: - **Intrinsic pathway** is initiated by contact with a negatively charged surface, such as collagen or glass. - **Extrinsic pathway** is initiated by tissue factor, which is released from damaged cells. - Both pathways converge at the activation of factor X, which converts prothrombin to thrombin. - Thrombin then converts fibrinogen to fibrin, which forms the stable fibrin clot. ## Thrombosis - Thrombosis is the process of formation of solid mass in circulation from the constituents of flowing blood; the mass itself is called a thrombus. - A term commonly used erroneously synonymous with thrombosis is blood clotting. - Thrombosis is characterized by events that essentially involve activation of platelets and the process of clotting. - **Turbulence** contributes to arterial and cardiac thrombosis by causing endothelial injury or dysfunction. - **Stasis** is a major factor in the development of venous thrombi. Under conditions of normal laminar blood flow, platelets (and other blood cells) are found mainly in the center of the vessel lumen, separated from the endothelium by a slower-moving layer of plasma. ## Morphology of Thrombi - **Arterial thrombi** are typically relatively rich in platelets. - **Venous thrombi**, on the other hand, tend to contain more enmeshed red cells (Red or stasis, thrombi). - At autopsy, **postmortem clots** can sometimes be mistaken for venous thrombi. - However, the former are gelatinous and due to red cell settling have a dark red dependent portion and a yellow “chicken fat” upper portion; they also are usually not attached to the underlying vessel wall. - By contrast, red thrombi typically are firm, focally attached to vessel walls, and contain gray strands of deposited fibrin. - Thrombi on heart valves are called **vegetations**. ## Embolism - An embolus is an intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin. - The vast majority of emboli derive from a dislodged thrombus hence the term **thromboembolism**. - Less common types of emboli include fat droplets, bubbles of air or nitrogen. - Inevitably, emboli lodge in vessels too small to permit further passage, resulting in partial or complete vascular occlusion; depending on the site of origin, emboli can lodge anywhere in the vascular tree. - The primary consequence of systemic embolization is **ischemic necrosis (infarction)** of downstream tissues. - While embolization in the pulmonary circulation leads to hypoxia, hypotension, and right-sided heart failure. ## Infarction - An infarct is an area of ischemic necrosis caused by occlusion of the vascular supply to the affected tissue; the process by which such lesions form termed infarction. - **Morphology:** infarcts may be either **red (hemorrhagic)** or **white (anemic)** and may be either septic or bland. - **Red infarcts** occur with venous occlusions or in loose tissues (lung) where blood can collect in infarcted zones. - **White infarcts** occur with arterial occlusions in solid organs with end-arterial circulations (e.g., heart, spleen, and kidney), and where tissue density limits the seepage of blood from adjoining patent vascular beds ## Shock - Shock is characterized by systemic hypoperfusion of tissues; it can be caused by diminished cardiac output or by reduced effective circulating blood volume. - The consequences are impaired tissue perfusion and cellular hypoxia. - Shock initially is reversible, prolonged shock eventually leads to irreversible tissue injury that often proves fatal. - **Cardiogenic shock** results from low cardiac output due to myocardial pump failure. It may be caused by myocardial damage (infarction). - **Hypovolemic shock** results from low cardiac output due to loss of blood or plasma volume (e.g., due to hemorrhage or fluid loss from severe burns). - **Septic shock** results from arterial vasodilation and venous blood pooling that stems from the systemic immune response to microbial infection.