Pathology of Infarcts and Edema

Impaired Blood Flow and Other Bodily Fluids

• Lecture objectives include describing haemodynamic disorders, thromboembolism, and shock.

Introduction

• Normal condition: plasma proteins remain in blood vessels, minimal water and electrolyte movement into tissues.
• Pathologic condition: protein may leak out of blood vessels, altering the balance of fluid between blood vessels and tissues.
• This imbalance occurs due to factors such as altered endothelial function, increased vascular pressure, or reduced plasma protein content.

Hyperaemia and Congestion

• Hyperaemia: active process, increased arteriolar dilation and blood inflow, occurs at inflammation sites or during skeletal muscle exercise (red).
• Congestion: passive process, impaired venous blood outflow from a tissue (blue).

Oedema

• Edema: fluid accumulating in interstitial spaces; can be protein-poor (transudate) or protein-rich (exudate).
• Fluid may accumulate in body cavities (hydrothorax, hydropericardium, hydroperitoneum/ascites).
• Massive generalized edema is called anasarca.

Causes of Oedema

• Increased hydrostatic pressure (impaired venous return, local venous pressure, generalized venous pressure; e.g., DVT, congestive heart failure, increased arteriolar dilation).
• Reduced plasma osmotic pressure (reduced albumin synthesis, e.g., cirrhosis, malnutrition, increased albumin loss, e.g., nephrotic syndrome).
• Lymphatic obstruction (inflammation, neoplasia).
• Sodium and water retention (renal failure).
• Increased vascular permeability (inflammation).

Increased Hydrostatic Pressure

• Impaired venous return: reduced blood flow back to the heart.
• Local venous pressure: a blockage in a vein, e.g., deep vein thrombosis (DVT), causing edema.
• Generalized venous pressure: whole-body edema, e.g., congestive heart failure.
• Increased arteriolar dilation: widening of the small arteries.

Congestive Heart Failure

• Reduced cardiac output leads to increased venous pressure, causing fluid to leak into tissues.
• Symptoms include edema and difficulty breathing.
• Imbalance of heart function.

Reduced Plasma Osmotic Pressure

• Albumin is crucial for maintaining colloid osmotic pressure.
• Reduced albumin synthesis reduces the pressure that draws fluid into blood vessels from surrounding tissues.
• Impaired liver function or malnutrition can lead to low albumin levels.
• Loss of albumin in urine (e.g., nephrotic syndrome) results in fluid leaking out of blood vessels into tissues.

Lymphatic Obstruction

• Impaired lymphatic drainage causes lymphedema.
• Localized edema due to inflammation, therapy complications, or neoplastic obstructions.
• Examples include parasitic infection affecting inguinal lymphatics, radiation to axillary lymphatics in breast cancer patients, or breast cancer.

Morphology of Oedema

• Gross inspection: organ enlargement noticeable.
• Microscopic examination: extracellular matrix elements separate and clear.

Haemorrhage

• Hemorrhage: blood leaking from blood vessels.
• In haemorrhagic diatheses, trauma, atherosclerosis and thrombocytopenia can cause extravasation of blood.
• Causes such as colonic mucosa hemorrhages, intracerebral hemorrhage and other conditions.

Haemostasis and Thrombosis

• Normal haemostasis: maintaining blood in a fluid, clot-free state within vessels.
• Rapid localized haemostatic plug formation occurs at injury sites.
• Pathologic haemostasis: thrombus formation within intact blood vessels.

Haemostasis

• Vasoconstriction: Reduces blood flow.
• Primary hemostasis: Platelet aggregation forms a plug.
• Secondary hemostasis: More stable plug formed from RBCs and leukocytes.
• Antithrombotic: Fibrinolysis degrades thrombi.

Roles of Endothelium

• Central regulator of hemostasis.
• Antithrombotic properties (inhibiting platelet aggregation, coagulation factors, and activating fibrinolysis).
• Prothrombotic properties (activating platelets and clotting factors).
• Antifibrinolytic effect.

Roles of Platelets

• Platelet adhesion: Platelets adhere to the damaged blood vessels.
• Platelet activation: Activated platelets release granules containing factors for aggregation and plug formation.
• Platelet aggregation: Platelets aggregate to form a plug.

Roles of Coagulation Cascade

• Tissue factor initiates the cascade.
• Thrombin converts fibrinogen into fibrin, forming a hemostatic plug.

Thrombosis

• Endothelial injury, abnormal blood flow, or hypercoagulability causes thrombosis.
• Common causes like abnormal blood vessel flow, blood clots and conditions such as deep vein thrombosis.

Morphology

• Arterial or cardiac thrombi: arise in arteries or the heart due to endothelial injury.
• Venous thrombi: frequently form at stasis sites, e.g., deep vein thrombosis (DVT).
• Mural thrombi: within heart chambers or aorta.
• Vegetations: thrombi in heart valves.

Fate of Thrombus

• Propagation: Thrombus grows larger.
• Embolization: Thrombus breaks free and travels to other sites.
• Dissolution: Thrombus dissolves.
• Organization & recanalization: Thrombus becomes incorporated into surrounding tissue; vessels may reform.

Clinical Correlation

• Arterial thrombosis: results in myocardial infarction or stroke.
• Venous thrombosis: predisposes to pulmonary embolism.

Embolism

• An embolus is an intravascular solid, liquid, or gaseous mass carried from one location to another within the blood stream.
• Thromboembolism is the most common form.
• Embolism can lead to systemic infarction and/or pulmonary circulation problems such as hypoxia or right-sided heart failure.

Two Types of Emboli

• Pulmonary embolus: travels via venous system, typically from deep vein thrombosis, causing pulmonary blockage and right heart failure.
• Systemic embolus: arises from cardiac mural or valvular thrombi or from atherosclerotic plaques.

Fat, Amniotic Fluid, and Air Emboli

• Fat embolism: soft-tissue injury or long bone fractures release fat particles that travel through the circulation.
• Amniotic fluid embolism: amniotic fluid enters the maternal circulation during labor, causing immediate respiratory distress or circulatory collapse.
• Air embolism: gas bubbles in the blood stream cause blockage of blood vessels, typically occurring during bypass surgery or scuba diving accidents.

Infarction

• An infarct is an area of ischemic tissue death caused by reduced blood flow.
• Common causes are blood clots (thromboses) or travelling blood clots (emboli).
• Affected tissue, which may require surgical intervention.

Morphology of Infarcts

• Classified by colour: red (haemorrhagic) or white (anaemic), primarily related to the type of blood supply interruption.
• Presence or absence of infection: septic infarcts are infected, bland infarcts are not.

Morphology-Histology of Infarcts

• Ischemic coagulative necrosis is common in most tissues.
• Brain infarcts exhibit liquefactive necrosis.
• Septic infarctions convert into abscesses.

Factors that Influence Infarct Development

• Anatomy of vascular supply.
• Rate of occlusion (rapid blockage leads to more severe effects).
• Tissue vulnerability to ischaemia (some tissues are more susceptible).
• Hypoxemia (reduced oxygen levels further harm tissues).

Shock

• Shock: final common pathway for several potentially lethal events.
• Examples include exsanguination (blood loss), extensive trauma, myocardial infarction, pulmonary embolism, and sepsis.

Three Major Types of Shock

• Cardiogenic shock: heart is unable to pump effectively.
• Hypovolemic shock: a reduced blood volume.
• Septic shock: body's response to infection.

Multiple Organ Failure

• Multiple-organ dysfunction syndrome: failure of multiple organs due to shock and other severe events.
• Resulting in reduced blood pressure.