Pathophysiology of Hepatic Congestion

Hepatic Congestion and Ischemic Necrosis

• Thickened and fibrotic lungs with alveolar macrophages containing hemosiderin indicate chronic conditions, often seen in heart failure.
• Central veins and sinusoids in the liver become distended during acute hepatic congestion.
• Centrilobular hepatocytes are distal to the hepatic blood supply and may undergo ischemic necrosis, while periportal hepatocytes are better oxygenated and may only show fatty changes.
• Chronic passive hepatic congestion leads to centrilobular regions being grossly red and depressed due to cell death, a condition known as "nutmeg liver."
• Microscopically, centrilobular congestion and hemorrhage, along with hemosiderin-laden macrophages and hepatocyte necrosis, are observed.

Hemostasis Process

• Hemostasis is a complex process involving platelets, clotting factors, and endothelium to form blood clots and prevent bleeding.
• Initial response includes arteriolar vasoconstriction to reduce blood flow at injury sites, which is mediated by neurogenic mechanisms and local factors like endothelin.
• Primary hemostasis involves formation of a platelet plug, primarily through the binding of GpIb receptors to von Willebrand factor (VWF) on the extracellular matrix.

Platelet Activation and Coagulation

• Platelet activation is triggered by factors such as thrombin and ADP, resulting in granule secretion and shape changes, leading to aggregation.
• Thrombin plays a crucial role in stabilizing the platelet plug by converting fibrinogen into insoluble fibrin.
• Hemostatic plugs may entrap red cells and leukocytes due to their adherence to activated platelets.

Deficiencies and Syndromes

• Bernard-Soulier syndrome involves a deficiency in GpIb receptors affecting platelet adhesion.
• Glanzmann thrombasthenia is caused by a deficiency in GpIIb-IIIa, impairing platelet aggregation.

Risk Factors for Thrombosis

• Common risk factors include prolonged bed rest, myocardial infarction, atrial fibrillation, tissue injury, cancer, and pregnancy.
• Acquired conditions like antiphospholipid antibody syndrome and heparin-induced thrombocytopenia increase thrombosis risk.
• Hypercoagulability associated with aging is often linked to reduced production of endothelial prostacyclin (PGI2).
• Genetic risk factors such as factor V Leiden mutation and prothrombin gene mutation significantly increase the likelihood of venous thrombosis.

Heparin-Induced Thrombocytopenia (HIT)

• HIT is a serious condition occurring after unfractionated heparin administration, characterized by antibodies forming against heparin-PF4 complexes.
• PF4, found in platelet granules, binds to heparin and alters its conformation, leading to neoantigen formation and antibody production.

Hemostasis Mechanisms

• The coagulation cascade requires calcium ions, which bind to γ-carboxylated residues on clotting factors for effective function.
• Activated enzyme complexes are essential for converting prothrombin to thrombin, forming the basis of secondary hemostasis.

This quiz explores the pathophysiological changes occurring in hepatic congestion, detailing the role of macrophages and the structure of the hepatic blood flow. Understand the consequences of heart failure on the liver and analyze the significance of hemoglobin breakdown in the condition. Ideal for students in medical and health science fields.