Understanding Liver Disorders: Jaundice, Hepatitis, and Failure

Posted on Dec 25, 2025 in Medicine & Health

Liver and Biliary System Pathophysiology

Jaundice (Icterus)

Yellow discoloration of skin and sclerae resulting from elevated bilirubin levels (typically 2–3 mg/dL).

1. Pre-hepatic Jaundice

  • Location: Prior to the liver (blood).
  • Cause: Increased Red Blood Cell (RBC) destruction.
  • Pathologic Conditions: Sickle cell disease, hemolytic blood transfusion reaction.
  • Labs: Increased unconjugated bilirubin.

2. Intra-hepatic Jaundice

  • Location: Within the liver.
  • Cause: Hepatocyte injury leading to decreased uptake of unconjugated bilirubin and/or decreased secretion of conjugated bilirubin into bile.
  • Pathologic Conditions: Viral hepatitis, alcohol or drug-induced liver damage, liver cancers.
  • Labs: Increased unconjugated and conjugated bilirubin.

3. Post-hepatic Jaundice

  • Location: Beyond the liver (hepatobiliary tree).
  • Cause: Hepatobiliary tree obstruction.
  • Pathologic Conditions: Gallstones, biliary strictures.
  • Labs: Increased conjugated bilirubin.

Neonatal Jaundice

Yellowing of a newborn’s skin and sclerae due to immature liver processing of bilirubin, typically appearing within 2–4 days after birth.

  • Cause: Hepatic mechanisms for conjugating and excreting bilirubin are immature around birth.
  • Complication: Kernicterus or bilirubin encephalopathy—unconjugated bilirubin crosses the blood-brain barrier, causing damage.
  • Treatment: Phototherapy (blue-green light converts bilirubin into an excretable form).

Cholestasis

Impaired bile flow from the liver to the duodenum, causing bile buildup.

1. Intra-hepatic Cholestasis

  • Location: In the liver.
  • Cause: Damage to bile canaliculi or terminal bile ducts.
  • Pathologic Conditions: Viral hepatitis, alcohol/drug damage, liver cancers.

2. Extra-hepatic Cholestasis

  • Location: Outside the liver.
  • Cause: Hepatobiliary tree obstruction.
  • Pathologic Conditions: Gallstones, biliary strictures.

Signs and Symptoms (S/S): Itching (pruritus), jaundice, fat deposits (xanthomas in joints, xanthelasmas on eyelids).

Treatment: Medications to decrease itching and lipid levels; surgery.

Viral Hepatitis

Inflammation of the liver.

  • Cause: Viruses (HAV, HBV, HCV, HDV, HEV), increased alcohol, drugs.

1. Acute Viral Hepatitis (HAV/HEV)

Duration less than 6 months.

  • Pre-icterus Phase: Myalgia, arthralgia, nausea and vomiting (N&V), appetite loss, fatigue, abdominal pain, increased ALT/AST.
  • Icterus Phase: Abdominal pain, high bilirubin in the blood.
  • Convalescent Phase: Increased well-being, increased appetite, decreased jaundice.

2. Chronic Viral Hepatitis (HBV/HCV/HDV)

Duration greater than 6 months.

May lead to cirrhosis, followed by portal hypertension, liver failure, or hepatocellular carcinoma.

Prevention and Treatment:

  • Vaccines: Available for HAV and HBV (HBV vaccine also prevents HDV).
  • No vaccines for HCV or HEV.
  • Treatment: Supportive care for HAV/HEV; Antivirals for HBV and HCV.

Alcohol-Induced Liver Damage

Progressive liver damage resulting from excessive alcohol consumption.

Alcohol Metabolism Pathway: Alcohol dehydrogenase system or microsomal ethanol-oxidizing system converts alcohol to acetaldehyde (toxic).

Risk Factors (BAC): Alcohol amount, food amount, sex (heavy drinking defined as males $\ge$ 15 units/females $\ge$ 8 units).

Stages of Damage

  1. Steatosis (Alcoholic Fatty Liver):
    • Cause: Triglycerides accumulate in hepatocytes.
    • Hallmark: Signet ring appearance (increased triglycerides push the nucleus to the periphery).
    • S/S: Often asymptomatic, increased ALT and AST levels.
  2. Steatohepatitis (Alcoholic Hepatitis):
    • Cause: Hepatocyte necrosis and neutrophilic invasion leading to inflammation.
    • S/S: Jaundice, decreased appetite, N&V, liver tenderness.
  3. Cirrhosis:
    • S/S: Fibrosis (scarring) and nodules (attempted repair).
    • Complications: Portal hypertension, liver failure, hepatocellular carcinoma.

Types of Cirrhosis

  • Micronodular Cirrhosis: Nodules $< 3$ mm, uniform; typically alcohol-induced.
  • Macronodular Cirrhosis: Nodules $\ge 3$ mm, irregular; often virus-induced (HBV, HCV, HDV).
  • Mixed Cirrhosis: Features of both micronodular and macronodular cirrhosis.

Prevention: Avoid or limit alcohol consumption.

Treatment: Eliminate alcohol, corticosteroids, liver transplant.

Drug-Induced Liver Damage

The liver detoxifies drugs through biotransformation reactions.

  • Phase I: Oxidation, reduction, hydrolysis; breaks down drugs into impaired metabolites.
  • Phase II: Conjugation, methylation, sulfation; binds hydrophilic molecules to drugs, converting them into water-soluble substances for excretion.

Cause: Most commonly acetaminophen overdose.

Mechanisms

  • Intrinsic: Predictable, dose-dependent course following toxic metabolite accumulation.
  • Idiosyncratic: Unpredictable, dose-independent.

Risk Factors: Females $> 55$ years, certain genes, increased alcohol use, interacting drug use, comorbidities (pre-existing liver disease, HIV).

Prevention: Patient education regarding over-the-counter and prescription drugs.

Treatment: Discontinuation of the implicated drug.

Fulminant Hepatitis

Rapid liver failure due to massive hepatocyte necrosis.

  • The liver cannot form urea, leading to increased blood ammonia (hyperammonemia). Ammonia crosses the blood-brain barrier, causing confusion and coma.
  • Cause: Acetaminophen overdose, mushroom poisoning.
  • Treatment: Counteractive drugs for the causative agent; liver transplant.

Portal Hypertension (PHTN)

Hypertension in the hepatic portal system, including the portal vein (HPV) and its tributaries.

  • Blood Inflow: Superior Mesenteric Vein (SMV – small intestine), Inferior Mesenteric Vein (IMV – colon), Splenic Vein (SV – spleen/pancreas).
  • Blood Outflow: Drained by hepatic veins to the inferior vena cava.
  • Cause: Increased venous flow resistance within the hepatic portal system.

Types of Portal Hypertension

  • Pre-hepatic: Issues with the HPV or its tributaries (e.g., tumors or thrombi in hypercoagulable states like obesity or pregnancy).
  • Intra-hepatic: Issues with sinusoids or central veins (e.g., tumors or vein compression by fibrosis/nodules in cirrhosis).
  • Post-hepatic: Issues with hepatic veins or the inferior vena cava (e.g., tumors or thrombi due to right ventricular failure).

Signs and Symptoms (S/S)

  • Ascites: Excess fluid in the peritoneal cavity ($> 25$ mL). Increased resistance leads to increased capillary pressure and fluid leakage. Manifests as abdominal distention, weight gain, and dyspnea.
  • Caput Medusae: Engorged superficial veins on the abdominal wall. Preexisting anastomoses dilate to shunt blood away. (Latin for “head of Medusa”).
  • Hemorrhoids: Engorged veins of the submucosa in the rectum/anus. Preexisting anastomoses dilate to shunt blood away. Causes itching/irritation, pain/discomfort, and bleeding.
  • Esophageal Varices: Engorged veins in the esophageal submucosa. Preexisting anastomoses dilate to shunt blood away. Can rupture, causing hematemesis (common) or melena (rare).
  • Hepatic Encephalopathy: Cognitive disturbance. Ammonia/toxins shunt from the intestines to the brain, causing neurotoxicity. Characterized by loss of motor control and a flapping tremor upon arm extension (asterixis).
  • Hypersplenism: Blood cell destruction (decreased RBC, WBC, platelets). Increased resistance leads to increased blood in the spleen, causing splenomegaly.

Liver Failure

Occurs when more than 80% of liver function is lost.

  • Acute: Sudden impairment (e.g., from virus or drug).
  • Chronic: Gradual loss (e.g., from alcohol).

S/S: Musty breath odor (fetor hepaticus) due to increased blood sulfur.

Treatment: Address the underlying cause, support nutrition, liver transplant.

Liver Cancers

Malignant tumors originating in the liver.

Types

  1. Primary Cancers:
    • Hepatocellular Carcinoma (HCC): Originates from hepatocytes (most common).
      • Risk Factors: Chronic hepatitis (HBV, HCV, HDV), alcohol, aflatoxins (mold from crops).
      • S/S: Weight/appetite loss, abdominal pain, weakness/fatigue.
      • Treatment: Surgery, liver transplant.
      • Note: Tumor on the left; infiltration on the right.
    • Cholangiocarcinoma: Originates from cells lining bile ducts (rare).
      • Risks: Primary sclerosing cholangitis (inflammation leading to scarring), liver fluke infection (ingesting parasitic raw fish).
      • S/S: Weight/Appetite loss, abdominal pain, weakness/fatigue.
      • Treatment: Surgery, liver transplant.
      • Note: Tumors unseen in bile ducts; abscess in the middle.
  2. Metastatic Cancers: 20 times more common due to the liver’s dual blood supply. Originates in the GI tract, breasts, ovaries, lungs, or kidneys.