Liver diseases

General Pathology: Diseases of the Liver

• The presentation covers diseases of the liver, including jaundice, hepatitis, alcoholic steatohepatitis, non-alcoholic steatohepatitis, and cirrhosis.
• Learning objectives include the clinical presentation of the patient with liver diseases, pathophysiology of jaundice, hepatitis, alcoholic steatohepatitis, non-alcoholic steatohepatitis, and cirrhosis, as well as clinical exploration of a patient with liver disease.
• Liver's functional anatomy is discussed.

Hematologic Functions of the Liver

• The liver processes food and drugs.
• Hemoglobin breakdown produces substances like bilirubin which are processed by the liver.
• Bilirubin is processed by the liver into a water-soluble form for easier excretion.
• Different forms of bilirubin include unconjugated (insoluble), and conjugated (soluble).
• Measuring bilirubin levels in blood or stool helps diagnose issues.
• Blood clotting depends on liver-produced proteins and ions.

Jaundice

• Jaundice is characterized by yellowish skin and mucous membrane staining due to bilirubin accumulation, typically above 2.5 mg/dL.
• Pre-hepatic jaundice originates before liver involvement, often due to excessive red blood cell breakdown (hemolysis).
• Hepatocellular jaundice results from liver dysfunction, impacting bilirubin processing and transport.
  • Causes include acute and chronic parenchymal diseases/conditions
• Obstructive (cholestatic) jaundice is related to bile duct blockage, affecting bile drainage. Causes can be intrahepatic (within the liver) or extrahepatic (outside the liver).

Pre-hepatic Jaundice

• Hemolysis in newborns and congenital hyperbilirubinemia are two causes.

Hepatocellular Jaundice

• Issues with bilirubin transport to bile duct due to parenchymal disease
• This can be acute or chronic

Obstructive Jaundice

• Blockage of bile to the duodenum (intraor extrahepatic) causes obstructive jaundice.

Investigations in Jaundice

• History collects details like pain, itching, discoloration of urine, and risk factors.
• Clinical exploration involves checking for signs of anemia and evaluating the liver.
• Laboratory tests analyze bilirubin levels, liver function tests, and hemoglobin.
• Imaging methods like ultrasound are used, and biopsies are considered when necessary.
• Endoscopic retrograde cholangiopancreatography (ERCP) is an additional diagnostic test.

Hepatitis

• Hepatitis is liver inflammation.
• It has infectious (viral, bacterial, eukaryotic) and toxic (alcoholic, NASH, autoimmune, ischemic) causes.
• Common symptoms include pain, jaundice, and anorexia (loss of appetite).
• Hepatitis can lead to various complications, including progressive damage, cirrhosis, and potential liver failure.

Alcoholic Steatohepatitis

• Risk factors include alcohol consumption above 30 g/day, gender, genetics, and nutrition.
• Pathophysiology involves alcohol metabolism by alcohol dehydrogenase, leading to acetaldehyde and then acetate.
• A different pathway (Microsomal ethanol-oxidizing system (MEOS) ) contributes in a different percentage.
• Liver cell damage, inflammation, and fibrosis result.

Nonalcoholic Steatohepatitis (NASH)

• Inflammation related to fat buildup within liver cells in the absence of alcohol intake.
• Associated with non-alcoholic fatty liver disease (NAFLD), a metabolic syndrome.
• Condition potentially evolves to cirrhosis.
• Pathophysiology involves factors like obesity, insulin resistance, and cellular injury from fatty acid oxidation.
• Other contributing issues include endoplasmic reticulum stress and metabolite toxicity
• This results in inflammation and potential damage to the liver cells.

Liver Cirrhosis

• Cirrhosis causes are diverse (alcohol, viral hepatitis, etc.).
• Two types of cirrhosis are micronodular and macronodular.
• Consequences include liver insufficiency and portal hypertension (increased pressure in portal vein), often leading to complications like ascites, varices, and hepatorenal syndrome.
• Clinical manifestations include liver dysfunction, jaundice, itching, protein deficiency (albumin), and coagulation problems (clotting).
• Other symptoms include hypoglycemia, endocrine system changes, and possibly confusion or coma.

Clinical Exploration

• The critical method of evaluating cases is described as Davidson's pg 843, a relevant medical text.