Disorders of the Liver, Gallbladder and Pancreas Objectives: Disorders of the liver Disorders of the gall bladder Disorders of the pancreas Part 1: Disorders of the Liver 1
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) 2
Jaundice: Hepatic: Viral hepatitis Alcoholic or drug-induced liver disease Cirrhosis of the liver Post-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. 3
Acute Viral Hepatitis: 2 weeks- 4 months Manifestations: 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 Vaccine Yes Yes No Yes Yes Associated Complications Usually selflimiting Very few complicatio ns Chronic hepatitis (persistent or relapsing) Cirrhosis Liver Failure Liver Cancer Chronic hepatitis (persistent or relapsing) Cirrhosis Liver Failure Liver Cancer Chronic hepatitis (persistent or relapsing) Cirrhosis Liver Failure Liver Cancer Fulminant Hepatitis Oral/Fecal Usually selflimiting Very few complicatio ns Tends to be more severe in pregnant women 4
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. 5
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 6
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 7
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 8
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. 9
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. 10
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, paraneoplastic syndromes, AFP in the blood, hypoglycemia Part 2: Disorders of the Gallbladder 11
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 12
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 13
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 multiorgan 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 14
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 15
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