Concise Notes on Hemodynamic Disorders

Hemodynamic Disorders

Objectives

• Edema: Definition, types, pathogenesis, morphology.
• Hyperemia and congestion: Definition, pathogenesis, morphology.
• Hemorrhage: Definition, clinical presentation. Types of brain hemorrhage.
• Thrombosis: Definition, pathogenesis, gross and microscopic morphology.
• Differences between venous and arterial thrombus.
• Differences between antemortem and postmortem thrombus.
• Fate of thrombus.
• Embolism: Definition, pathogenesis, gross and microscopic morphology.
• Infarct: Definition. Classification. Gross and microscopic morphology.

Cardiovascular Diseases

• Leading cause of death worldwide (17.9 million lives each year).
• Include: coronary heart disease, cerebrovascular disease, and rheumatic heart disease.
• Major causes of death: coronary heart disease and stroke.
• One-third of these deaths occur prematurely in people under the age of 70.

Disorders of Hemodynamics

• Edema, congestion, and shock.
• Hemostasis: Hemorrhage and thrombosis
• Embolism

Body Water Composition

• Water content varies by organ and individual characteristics (age, sex).
• Kidneys regulate water balance (2.0-2.5 liters/day output).

Starling Forces

• Hydrostatic pressure: Pushes fluid out of capillaries.
• Plasma colloid osmotic pressure: Pulls fluid into capillaries.
• Lymphatics: Collect excess interstitial fluid and return it to circulation.

Edema

• Definition: Accumulation of interstitial fluid within tissues or body cavities.

Causes of Edema

1. Increased hydrostatic pressure:
   • Impaired venous return (e.g., congestive heart failure, constrictive pericarditis).
   • Arteriolar dilation.
2. Reduced plasma osmotic pressure (hypoproteinemia):
   • Protein-losing glomerulopathies, liver cirrhosis, malnutrition.
3. Sodium retention:
   • Excessive salt intake, increased tubular reabsorption.
4. Lymphatic obstruction:
   • Inflammatory, neoplastic, postsurgical, radiation therapy.
5. Inflammation:
   • Acute, chronic; angiogenesis.

Pathophysiology of Edema

• Heart failure: Increased capillary hydrostatic pressure.
• Malnutrition/Hepatic synthesis/Nephrotic syndrome: Decreased plasma albumin.
• Renal failure: Sodium and water retention; increased blood volume.
• Lymphatic obstruction: Impaired fluid drainage.

Edema Types

• Local edema: Result of vascular effects of inflammation.
• Generalized edema: Affects visceral organs and skin (heart failure, nephrotic syndrome).
• Anasarca: Extreme generalized edema.

Edema in Body Cavities

• Hydropericardium: Pericardial effusion.
• Hydroperitoneum (ascites): Peritoneal effusion.
• Hydrothorax: Pleural effusion.

Gross Morphology of Edema

• Subcutaneous edema: Diffuse, accumulates in dependent areas (legs, sacrum).
• Pitting edema: Finger pressure leaves a depression.
• Pulmonary edema: Heavy lungs with frothy, blood-tinged fluid.
• Brain edema: Softer consistency, larger size, flattened gyri, slit-like ventricles.

Brain Edema

• Can be localized or generalized.
• Gross Morphology:
  • Softer consistency
  • Larger size
  • Heavier weight
  • Flattened gyri
  • Narrowed sulci
  • Slit-like ventricles

Microscopic Morphology of Brain Edema

• Dilation of perivascular and cellular spaces.
• Vacuolated appearance of gray matter.

Brain Herniations

• Displacement of brain tissue due to increased intracranial pressure.
• Causes:
  • Space-occupying lesions (tumors, hematomas, abscesses).
  • Cerebral edema (trauma, stroke, encephalitis).
  • Hydrocephalus.

Types of Brain Herniations

• Subfalcine herniation: Cingulate gyrus under the falx cerebri.
• Transtentorial (uncal) herniation: Temporal lobe uncus through the tentorium.
• Tonsillar herniation: Cerebellar tonsils through the foramen magnum.

Microscopy of Edema

• Clearing and separation of extracellular matrix elements.

Hyperemia and Congestion

• Hyperemia: Active process; arteriolar dilation & increased blood inflow (e.g., exercise).
• Congestion: Passive process; impaired venous outflow (e.g., cardiac failure, venous obstruction).

Gross Morphology of Hyperemia/Congestion

• Wet cut surfaces oozing blood.

Microscopic Morphology of Hyperemia/Congestion

• Acute pulmonary congestion: Blood-engorged alveolar capillaries, alveolar edema.
• Chronic pulmonary congestion: Thickened septa, hemosiderin-laden macrophages ("heart failure cells").
• Chronic passive congestion of the liver: "Nutmeg liver"; centrilobular necrosis & hemorrhage.

Hemorrhage

• Extravasation of blood from vessels due to damage or defective clot formation.

Clinical Consequences of Hemorrhage

• External hemorrhage or hematoma (localized collection of blood).
• Body cavity effusions: hemothorax, hemopericardium, hemoperitoneum.
• Petechiae: Minute hemorrhages (1-2 mm).
• Purpura: Slightly larger hemorrhages (3-5 mm).
• Ecchymoses: Larger subcutaneous hematomas (1-2 cm).

Clinical Significance of Hemorrhage

• Depends on volume, speed, and localization.

Types of Brain Hemorrhage

• Epidural hematoma: Between skull and dura mater.
• Subdural hematoma: Under the dura mater.
• Subarachnoid hemorrhage: Between pial and arachnoid membranes.
• Intracerebral hemorrhage: Within brain tissue.

Thrombosis

• Formation of a clotted mass of blood within the cardiovascular system in a living organism.
• Consequence of inappropriate activation of normal hemostasis.

Pathogenesis of Thrombosis (Virchow's Triad)

1. Endothelial injury
2. Abnormal blood flow (stasis or turbulence)
3. Hypercoagulability

Endothelium

• Inner lining of blood vessels, controls blood fluidity, platelet aggregation, and vascular tone.
• Regulates immunology, inflammation, and angiogenesis.

Endothelial Injury

• Physical damage leading to subendothelial ECM exposure, platelet aggregation and tissue factor release.

Endothelial Cell Dysfunction

• Altered balance of thrombotic and antithrombotic activity.
• Causes: Hypercholesterolemia, homocystinemia, toxins, bacterial endotoxins, radiation damage.

Abnormal Blood Flow

• Turbulence or stasis leading to endothelial dysfunction.
• Causes countercurrents and local stasis pockets of blood.

Effects of Turbulence and Stasis

• Endothelial cell activation, enhanced procoagulant activity, changes in gene expression.
• Platelet and leukocyte interaction with endothelium.
• Reduced washout of clotting factors and impeded inflow of inhibitors.

Clinical Settings of Abnormal Blood Flow

• Ulcerated atherosclerotic plaques: Turbulence.
• Aneurysms: Stasis.
• Acute myocardial infarction: Ventricular remodeling causes aneurysms and stasis.
• Mitral valve stenosis: Atrial dilation with stasis.
• Hyperviscosity syndromes: Increased resistance to blood flow and stasis.

Hypercoagulability

• Abnormally high tendency of blood to clot.

Causes

• Genetic mutations.
• Acquired conditions: prolonged bed rest, myocardial infarction, cancer.

Hypercoagulable States: Primary (Genetic)

• Common: Factor V Leiden mutation, prothrombin mutation.
• Rare: Antithrombin III, protein C, or protein S deficiency.

Hypercoagulable States: Secondary (Acquired)

• High Risk: Prolonged bed rest, myocardial infarction, cancer, antiphospholipid antibody syndrome.
• Lower Risk: Cardiomyopathy, nephrotic syndrome, hyperestrogenic states, smoking.

Thrombi Morphology

• Focally attached to vascular surface.
• Arterial thrombi grow retrograde; venous thrombi extend in blood flow direction.
• Lines of Zahn: Laminations of pale platelet/fibrin layers alternating with darker red cell layers.
• Mural thrombi: Occur in heart chambers or aorta.

Arterial vs. Venous Thrombi

• Arterial: Mainly platelets & fibrin; caused by endothelial injury.
• Venous: Mainly red blood cells & fibrin; caused by stasis & hypercoagulability.

Microscopic Morphology of Thrombi

• Lines of Zahn with layers of fibrin, red blood cells, leukocytes, and platelets.

Postmortem Clot

• Not attached to vessel wall, gelatinous consistency, no lines of Zahn.

Antemortem vs. Postmortem Thrombus

• Antemortem: Firm, attached to vessel wall, lines of Zahn.
• Postmortem: Gelatinous, not attached, no lines of Zahn.

Fate of Thrombus

• Resolution: Thrombus may be removed by fibrinolytic activity.
• Propagation: Thrombus enlarges.
• Thromboembolism: Thrombus detaches and travels elsewhere.
• Organization: Ingrowth of cells into thrombus to produce scar tissue, and recanalization, which is the re-establishment of a blood flow channel.

Embolism

• A detached intravascular solid, liquid, or gaseous mass carried by blood to a distant site causing dysfunction or infarction.

Types of Emboli

• Thromboemboli (most common).
• Fat droplets.
• Air or nitrogen bubbles.
• Atherosclerotic debris (cholesterol emboli).
• Tumor fragments.
• Bone marrow.
• Amniotic fluid.

Pulmonary Thromboembolism

• Originate from deep venous thromboses (usually from deep leg veins proximal to the popliteal fossa).

Clinical Significance of Pulmonary Embolus

• Small: Clinically silent.
• Medium: Pulmonary hemorrhage.
• Large: Sudden death.
• Multiple: Pulmonary hypertension and right ventricular failure (cor pulmonale).
• Saddle embolus: Straddles the arterial bifurcation, blocking both arterial branches to the lungs.

Fat Embolism

• Fat emboli in the bloodstream, often after long bone fractures.

Fat Embolism Syndrome

• Multisystem dysfunction; complication of skeletal trauma/orthopedic surgery.

Pathogenesis of Fat Embolism Syndrome

• Mechanical obstruction and biochemical injury (free fatty acids damage pneumocytes; toxic endothelial injury).

Amniotic Fluid Embolism

• Amniotic fluid enters maternal circulation during labor/postpartum.

Air Embolism

• Air or gas bubbles block blood vessels.
• Causes: Neurosurgery, obstetric/laparoscopic procedures, chest wall injury, scuba diving, rapid ascent in unpressurized aircraft.

Infarction

• Area of ischemic necrosis caused by occlusion of vascular supply.

Causes of Infarction

• Major: Arterial thrombosis and embolism.
• Minor: Vasospasm, atheroma expansion, extrinsic compression.

Factors Affecting Infarct Formation

• Anatomy of vascular supply.
• Rate of occlusion.
• Tissue vulnerability to hypoxia.

Infarct Classification

• Based on color and presence/absence of microbial infection.
  • Red (hemorrhagic).
  • White (anemic).
  • Bland.
  • Septic.

White Infarcts

• Arterial occlusions in solid organs (heart, kidneys, spleen).
• Wedge-shaped with occluded vessel at apex.

Red Infarcts

• Occur in venous occlusions, loose tissues, dual circulations, congested tissues, or after flow reestablishment.

Septic Infarct

• Infected cardiac valve vegetations embolize; microbes seed necrotic tissue.
• Evolution: Abscess, healing by organization and fibrosis.