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Disorders of the Liver, Gallbladder

and Pancreas

• Disorders of the liver

• Disorders of the gall bladder

• Disorders of the pancreas

Objectives:

Part 1: Disorders of the Liver

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Jaundice:is a manifestation associated with various disease

conditions and is characterized by the yellow

discoloration of skin and mucosa.

• Jaundice is caused by hyperbilirubinemia (an elevation of blood bilirubin levels).

Jaundice:Classification of jaundice based on etiology:Prehepatic: anything that increases the rate of hemolysis of red blood cells (heme)

• Excessive hemolytic destruction of RBCs and the liberation of hemoglobin

• Large hematoma• Gilbert Disease (defect in the uptake of bilirubin by

the liver)• Newborn jaundice (immature liver can’t break down

bilirubin)

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Jaundice:Hepatic: • Viral hepatitis• Alcoholic or drug-induced liver disease• Cirrhosis of the liverPost-Hepatic: (obstructive)• Gallstones/gallbladder disease• Carcinoma of the pancreas or bile ducts• pancreatitis

Acute Viral Hepatitis: inflammation of liver as

caused by hepatotropic viruses.

• A clinical syndrome of variable severity caused by hepatitis A (HAV), B (HBV), C (HCV), D (HDV) and E (HEV).

• Mechanisms of liver injury: direct cell injury and bodily immune responses against the viral antigens in certain cases lead to scarring.

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Acute Viral Hepatitis: 2 weeks- 4 monthsManifestations:

• Prodromal phase (preicteric): malaise/fatigue, headache, low grade fever, joint/muscle pain, nausea/vomiting/anorexia/constipation/diarrhea.

• Icteric phase: onset of jaundice, enlarged liver and spleen, lymphadenopathy, dark urine, pale stools, extreme fatigue, liver tenderness, mild weight loss, skin rash.

• Recovery phase: fatigue, lessoning of jaundice, urine and stool color returns to normal, return of normal appetite

• Carrier State

Acute Viral Hepatitis: Pathogenesis:

• Changes that occur in the liver may be reversible or irreversible, depending on the level of necrosis and inflammation (as determined individually by the individual’s immune system) in the liver cells.

• Particular types of hepatitis cause piecemeal necrosis, the formation of fibrous connective tissue (fibrosis) which can progress to cirrhosis.

Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E

Transmission Oral/fecal Blood/Sexual Fluids

Blood/Sexual Fluids

Blood/Sexual Fluids

Oral/Fecal

Vaccine Yes Yes No Yes Yes

Associated Complications

• Usually self-limiting

• Very few complications

• Chronic hepatitis (persistent orrelapsing)

• Cirrhosis• Liver

Failure• Liver

Cancer

• Chronic hepatitis (persistent orrelapsing)

• Cirrhosis• Liver

Failure• Liver

Cancer

• Chronic hepatitis (persistent orrelapsing)

• Cirrhosis• Liver

Failure• Liver

Cancer• Fulminant

Hepatitis

• Usually self-limiting

• Very few complications

• Tends to be more severe in pregnant women

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Acute Viral Hepatitis: Diagnosis:

• Blood tests (presence of antibodies and viral DNA to specific viruses)

• Liver biopsy

Treatment:

• Preventative vaccines

• Interferons, antiviral drugs (for chronic and acute viral hepatitis)

• Liver transplantation

Cirrhosis: a chronic liver disease characterized by

loss of normal liver structure and function. This is a

progressive disease that destroys liver cells and is

irreversible and incurable except by liver

transplantation. It is characterized by nodular

development in which fibrosis nodules contain

proliferating hepatocytes.

Etiologies: hepatitis (viral, alcoholic/drug-induced,

autoimmune, metabolic diseases (Wilson disease,

hemochromatosis), biliary obstruction, idiopathic.

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Cirrhosis: Manifestations:

• Weight loss, weakness, anorexia

• Diarrhea/constipation

• Hepatomegaly, jaundice

• Pain in the epigastric upper right (dull, aching, bloated)

Cirrhosis: Later Manifestations:• Constriction of vascular channels and the biliary duct systems in

the liver leading to portal hypertension and the stasis of bile.• Ascites• Splenomegaly (thrombocytopenia)• Portosystemic shunts between the portal and systemic circulation.

(esophageal varices, hemorrhoids, caput medusae)• Bleeding (decreased clotting proteins), anemia• Endocrine disruption (liver fails to metabolize steroid hormones)• Skin disorders: skin lesions on upper half of body, finger clubbing• Hypoglycemia• Encephalopathy

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Liver Failure:

• Due to sudden and massive liver destruction (fulminant hepatitis) or progressive damage (cirrhosis).

• 80—90% of liver function must be affected before liver failure occurs

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Liver Failure: Manifestations:• Fetor hepaticus: musty, sweet odor on breath• Hematological disorders• Endocrine disorders• Skin disorders• Hepatorenal syndrome: renal failure many times

accompanies liver failure• Encephalopathy: confusion, personality changes,

convulsions, coma• Hypoglycemia

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Liver Failure: Treatment:

• Discontinue alcohol (or offending drug) if that is the cause of failure

• Prevent infections

• High calorie diet, restricted protein intake

• Correct fluid/electrolytes (especially hypokalemia)

• Liver transplant

Drug or Toxin-induced Liver Disease:The toxic effects of drugs on the liver depends on:• Age• Dose• Most drugs lead to the generation of the toxic

metabolites by the liver leading to centrilobular necrosis.

Examples: acetaminophen, NSAIDs, statins, drugs used in the treatment of TB, Parkinson Disease, arthritis, certain antibiotics and anesthetics may adversely affect the liver with symptoms of hepatitis or tumor formation.

Alcohol-induced Liver Disease:Alcoholic liver disease may manifest as fatty liver, alcoholic hepatitis, cirrhosis and potentially liver failure.

• The metabolic end products (acetaldehyde and free radicals, etc.) of alcohol metabolism lead to liver disease.

• Women are more prone to alcohol-induced liver damage than men.

• The elderly have less resistance to the hepatotoxic effects of alcohol.

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Alcohol-induced Liver Disease:Fatty Liver: accumulation of fat in the hepatocytes (steatosis)

• The liver enlarges and becomes yellowed by the fat accumulation.

• Usually asymptomatic and reversible after cessation of alcohol.

• Non-alcoholic fatty liver: caused by obesity, type 2 diabetes, metabolic syndrome and hyperlipidemia.

Alcohol-induced Liver Disease:Alcoholic Hepatitis: • Intermediate stage between fatty liver and cirrhosis.• It can come on with an increase in alcohol intake.• Inflammation and necrosis of liver cells occurs with

manifestations of hepatitis (abdominal tenderness, pain, anorexia/nausea, fever, jaundice, ascites)

• In a small percentage of cases, this hepatitis can lead to liver failure and be fatal. In other situations, chronic drinking can lead to frequent bouts of hepatitis and liver injury progressing to cirrhosis.

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Liver Carcinoma: two primary types: hepatocellular carcinoma and

cholangiocarcinoma of the bile duct cells

Risk factors: chronic viral hepatitis, chronic alcoholism, arsenic, aflatoxin

Manifestations:

• Initially silent, if present: weakness, anorexia, weight loss, fatigue, abdominal swelling/fullness, dull aching abdominal pain, mild jaundice.

• Advanced: hepatomegaly, ascites, paraneoplasticsyndromes, AFP in the blood, hypoglycemia

Part 2: Disorders of the

Gallbladder

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Gallbladder Disease: Any disease that affects

your gallbladder is considered a gallbladder disease.

• Cholecystitis: inflammation of the gallbladder. Cholecystitis can be either chronic (long-term) or acute (short-term). Chronic inflammation is the result of several acute cholecystitis attacks which can eventually damage the gallbladder.

• Gallstones: (cholethiasis) will obstruct the flow of bile and cause inflammation and may eventually lead to jaundice, gangrene, secondary biliary cirrhosis and ascending infections.

Gallbladder Disease:

Types of gallstones:

• Cholesterol

• Black Stones

• Brown stones

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Gallstones: Manifestations:

• Sudden, intense pain in the upper right quadrant (may radiate to breast bone and the center of the abdomen, back and shoulder)

• Jaundice

• High fever, chills

Treatment:

• Surgery to remove gallstones

• Extra-corporeal shock wave therapy (lithotripsy)

• Drugs to help dissolve gallstones

Part 3: Disorders of the

pancreas

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Pancreatitis: inflammation of the pancreas

Acute Pancreatitis: characterized by inflammation, hemorrhage and necrosis of pancreatic acini cells due to the inappropriate activation of proteolytic enzymes within the pancreas.

Etiologies: gallstones (biliary obstruction), alcohol abuse, viral infections, shock, tumors, trauma, autoimmune disorders.

Manifestations: abdominal pain and tenderness (especially after eating food or drinking alcohol), abdominal distention, hypocalcemia

Pancreatitis:Acute Pancreatitis:

Complications:

• Acute inflammatory response can lead to sepsis and multi-organ failure.

• Acute respiratory distress syndrome

Diagnosis:

• Blood tests (serum amylase and lipase, increased WBCs, hyperglycemia, elevated bilirubin)

• Imaging (ultrasound, CT scans)

Pancreatitis:Acute Pancreatitis: Treatment:• Pain relief• Withhold oral foods and fluids (to rest pancreas) and restore

lost plasma volume• IV fluids & electrolytes • Antibiotics

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Pancreatitis:Chronic Pancreatitis: irreversible, progressive destruction of the exocrine pancreas by fibrosis and in the later stages by the destruction of the endocrine portions of the pancreas.

Etiologies:

• Long-term alcoholism, tumors, pancreatic duct obstruction,

autoimmune disorders

Pancreatic Cancer:adenocarcinomas of ductal epithelium

• Is a very aggressive cancer with a poor prognosis

• Risk factors: age, smoking, diabetes, chronic pancreatitis

• Manifestations: jaundice, pain (epigastric, back), weight loss

• Tumors occur more often in the head of the pancreas

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