Case Analysis: 55-Year-Old Male with Acute Chest Pain

a) Diagnosis

• Acute-onset chest pain in a middle-aged male
• Radiation to the left shoulder and arm (referred pain via C8-T4 dermatomes)
• ECG showing ST-segment elevation and T-wave inversion

b) Etiopathogenesis

1. Atherosclerotic plaque formation - Years of lipid deposition, foam cell accumulation, and chronic inflammation create an atheromatous plaque within a coronary artery. Importantly, the culprit plaque often does NOT cause a critical stenosis (>70%) beforehand.
2. Plaque disruption - Endothelial injury, mechanical forces, or intraplaque hemorrhage causes sudden erosion or rupture of the fibrous cap, exposing subendothelial collagen and necrotic plaque contents to circulating blood.
3. Platelet activation and aggregation - Exposed collagen triggers platelet adhesion. Activated platelets release thromboxane A2, ADP, and serotonin, which amplify further platelet aggregation and induce vasospasm.
4. Coagulation cascade activation - Exposed tissue factor activates the extrinsic coagulation pathway, generating thrombin and adding to the growing thrombus.
5. Complete luminal occlusion - Within minutes, the enlarging thrombus totally occludes the coronary artery, cutting off blood supply to the downstream myocardium.
6. Myocardial ischemia and necrosis - Loss of aerobic metabolism occurs within seconds. ATP falls and toxic metabolites (lactate) accumulate. Contractility is lost within 1-2 minutes. If ischemia persists beyond 20-40 minutes, irreversible coagulative necrosis of myocytes ensues. Necrosis begins in the subendocardial zone (most vulnerable, furthest from epicardial vessels and under highest intramural pressure) and progresses as a "wavefront" toward the epicardium.

c) Immediate Complications

Case Analysis: 60-Year-Old Chronic Alcoholic with Hematemesis, Drowsiness, Icterus, and Ascites

a) Diagnosis

b) Gross and Microscopic Morphology of the Liver

Gross Morphology

• Liver is large, soft, yellow, and greasy - may weigh 4-6 kg or more
• Yellow-tan discoloration from accumulated fat
• Surface is smooth at this stage

• Liver is small, brown, and shrunken
• Surface is covered by diffuse micronodules (nodules typically < 0.3 cm in diameter - smaller than in viral hepatitis-related cirrhosis - hence micronodular cirrhosis)
• Fibrous bands are visible separating the nodules
• The "burned-out" cirrhotic liver may lose its fatty appearance

Cirrhotic liver - note the diffuse nodular surface and fibrous scarring

Microscopic Morphology

• Small (microvesicular) and large (macrovesicular) lipid droplets within hepatocytes
• Begins in centrilobular hepatocytes (zone 3), spreads outward
• Large droplets displace the nucleus to the periphery of the cell
• Characteristic perisinusoidal fibrosis in a "chicken-wire fence" pattern

• Hepatocyte ballooning - cell swelling and necrosis, most pronounced in centrilobular regions
• Mallory hyaline bodies (Mallory-Denk bodies) - tangled skeins of ubiquitinylated keratins 8 and 18, seen as eosinophilic cytoplasmic inclusions in degenerating hepatocytes - a hallmark of alcoholic hepatitis
• Neutrophilic infiltration - neutrophils permeate the lobule and accumulate around hepatocytes containing Mallory bodies; lymphocytes and macrophages in portal tracts

• Begins as central vein sclerosis and perisinusoidal fibrosis
• Fibrous bands link central veins to portal tracts (central-portal bridging fibrosis)
• Progressive subdivision of parenchyma into micronodules surrounded by fibrous septa
• Complete architectural distortion of the normal lobular pattern
• Ductular reactions (duct-like structures from stem cell activation) increase with progression

Left (A): Active cirrhosis - thick collagen bands separating rounded micronodules (Masson trichrome). Right (B): After abstinence - scars regress, nodules enlarge

c) Complications of Alcoholic Liver Cirrhosis

From Portal Hypertension:

1. Esophageal/gastric varices - dilated portosystemic collateral veins that can rupture, causing massive hematemesis (the presenting symptom here). Occur in ~40% of advanced cirrhosis cases.
2. Ascites - transudative fluid accumulation in the peritoneal cavity (serum-to-ascites albumin gradient ≥1.1 g/dL). About 85% of all ascites cases are due to cirrhosis.
3. Congestive splenomegaly - splenic weight may reach up to 1000 g (5-6x normal), leading to hypersplenism with thrombocytopenia and pancytopenia.
4. Caput medusae - dilated periumbilical veins from recanalized umbilical vein.

From Hepatocellular Failure:

1. Hepatic encephalopathy - failure to detoxify ammonia and other gut-derived toxins; presents as confusion, drowsiness, and disorientation (as in this patient).
2. Jaundice / coagulopathy - impaired bilirubin conjugation and reduced synthesis of clotting factors (II, VII, IX, X).
3. Hypoalbuminemia - reduced synthetic function contributing to peripheral edema and ascites.
4. Hyperestrogenemia (in males) - impaired estrogen metabolism causes palmar erythema, spider angiomas, gynecomastia, and hypogonadism.

Infective and Renal Complications:

1. Spontaneous bacterial peritonitis (SBP) - infection of ascitic fluid; increased susceptibility due to impaired immune function.
2. Hepatorenal syndrome - functional renal failure from splanchnic vasodilation and reduced effective renal perfusion; a pre-terminal event.

Neoplastic Complication:

1. Hepatocellular carcinoma (HCC) - develops in 10-20% of patients with alcohol-related cirrhosis.

Terminal causes of death:

• Hepatic failure
• Massive GI hemorrhage (variceal bleed)
• Intercurrent infection
• Hepatorenal syndrome
• Hepatocellular carcinoma (3-6% of cases)