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  1. Liver Chapter 19 Candice Quillin, BSN, CGRN 2 March 2011

  2. Objectives • Describe Anatomy and Physiology of normal liver • Name three (3) diseases or diagnosis of the liver and treatment for them.

  3. Healthy Liver

  4. Hepatocytes • Hepatocytes – secrete bile • Sinusoid cavities are between rows of hepatocytes • Sinusoids are lined with Kupffer cells • Kupffer cells remove amino acids, nutrients, sugars, broken down RBC’s, bacteria, and debris from blood. Detoxifies the blood. • Secrete bile

  5. Physiological Functions of the Liver • Bile formation and secretion • Metabolism of carbohydrates, proteins, fats, and steroids • Manufacturer of substances necessary for coagulation and anticoagulation • Detoxification of foreign and toxic substances • Vitamin and mineral storage

  6. Bile Formation and Secretion • Bile is secreted into the bile canaliculi, which branch and combine to form the right and left hepatic ducts. The right and left hepatic ducts merge into the common hepatic duct. The cystic duct joins the common hepatic duct to form the common bile duct. The common bile duct joins the duct of Wirsung at the ampulla of vater. Bile then empties out into the duodenum.

  7. Metabolism • Carbohydrate metabolism converts glucose, fructose, and galactose to glycogen for storage in the liver • Breaks down glycogen to glucose to maintain blood glucose levels when carbohydrate intake decreases • Synthesizes glucose from noncarbohydrate nutrients to maintain blood glucose levels. • Breaks down amino acids to produce ketoacids and ammonia. • Synthesizes proteins • Hydrolyzes fats to glycerol and fatty acids. • Metabolizes steroids, glucocorticosteroids, estrogen, testosterone, progesterone, and aldosterone.

  8. Coagulation and Anticoagulation • The liver produces and synthesizes most of the bodies clotting factors like prothrombin, fibrinogen, Factor 5,7,9, and 10. • Anti-coagulant heparin and vasopressor substances after hemorrhage.

  9. Detoxification • Mechanisms of detoxification include: • Reduction • Hydrolysis • Conjugation • Oxidation • Excretion • Degradation • Phagocytosis of viruses, bacteria, dyes, and foreign proteins also occurs in detoxification.

  10. Vitamin and Mineral Storage • Vitamins A, B, C, D, E, and K • Minerals copper and iron.

  11. Liver Pathology-Cirrhosis • A liver disease that is characterized pathologically by loss of the normal microscopic lobular architecture, with fibrosis and nodular regeneration. • Alcoholic cirrhosis • Up to 50% of adult cases of cirrhosis are alcohol related • Liver is enlarged and there is altered lipid metabolism causing fatty infiltration. • Treatment includes abstinence, counseling, and high-caloric nutrient dense diet.

  12. 2. Immune-related bile duct injury • Primary Biliary Cirrhosis (PBC) - Inflammation of the bile ducts of the liver, which eventually blocks the flow of bile. This obstruction damages liver cells and leads to cirrhosis. • Primary Sclerosing Cholangitis (PSC) – A rare and serious condition in which inflammation involves the entire biliary tract; often related to GI or biliary tract infection. 3. Postnecrotic cirrhosis • May be related to hepatitis, infection, metabolic liver disease, or hepatotoxins or industrial chemicals.

  13. History symptoms of Cirrhosis • Weight loss • Anorexia • Abdominal pain • Red spider veins under skin • Ascites • Itching especially of hands and feet at first • Bruising • Jaundice • Mental confusion • Difficulty concentrating

  14. Portal Hypertension • Abnormally increased blood pressure in the portal venous system. • Signs and Symptoms include: • Melena • Hematoemesis • Jaundice • Peripheral edema • Palmar erythemia • Bleeding tendencies • Fetor hepaticus – sweet and fetid breath odor • Spleenomegaly • Varicies • Dilated abdominal veins • Spider nevi • Venous patterns on flanks

  15. The goal of treatment for portal hypertension is to divert blood flow around the liver and away from collateral vessels. • Treatment options include • Portacaval shunt • Splenorenal shunt • Mesocaval shunt • Transjugular intrahepatic portosystemic shunt (TIPS) • Vasoconstriction Medications: Somatostatin, Octreotide, Nitroglycerin, Vasopressin, and Terlipressin.

  16. Varices

  17. Ascites • The effusion and accumulation of serous fluid in the abdominal cavity

  18. Causes and Treatment for Ascites • Causes: • Portal hypertension, cancer, cardiac failure, pancreatic causes, trauma • Treatment: • Sodium restriction, diuretics, bed rest. • Peritoneal jugular shunt • Paracentesis.

  19. Hepatorenal Syndrome • A syndrome characterized by functional renal failure, oliguria, and low urinary sodium concentration, without pathological renal changes. • Associated with cirrhosis and ascites or with obstructive jaundice. • Management is to diagnosis, remove cause, treat factors known to cause the renal failure. • High calorie, low protein, low sodium diet. • Fluid challenge may help. • Dialysis • Liver transplant

  20. Hepatic Encephalopathy • A condition usually occurring secondary to advanced liver disease. • Stage 1 – mild confusion, mood changes, sleep disturbance, mild acterixis(rapid wrist flap) • Stage 2 – confusion, apathy, obvious asterixis, personality changes, disorientation, apraxia. • Stage 3 – sever confusion, incoherence, hyperactive deep tendon reflexes, muscular rigidity • Stage 4 – No reaction to stimuli, no corneal reflex, dilated pupils, flexion or extension posture, coma.

  21. Treatment may include correcting pH and electrolyte imbalances, restricting dietary protein, removing excess protein from gut, preventing constipation, and preventing GI bleed so that protein does not get in bowel to be absorbed. • Treatment can include medications like lactulose which causes osmotic diarrhea which will promote excretion of ammonia and proteins through GI tract. • Antibiotics such as Metronidazole, Xifaxan or Rifaximin may decrease the number of bacteria that breakdown amino acids.

  22. Hepatitis • Inflammation of liver • See chart for description of each type, Hepatitis A,B,C,D,E,F, and G.

  23. Alcoholic Hepatitis • Inflammation of liver due to alcohol consumption. • Symptoms include: RUQ abdominal pain, fever, vomiting, anorexia, and dark urine. Patients do not present with jaundice. • Signs include tender liver, spleenomegaly, signs of chronic alcohol abuse, cirrhosis, and mental status changes. • Treatment includes supportive care, counseling, abstinence from alcohol.

  24. Drug Induced Hepatitis • Drugs can cause hepatic injury including • Dose-related hepatotoxic reaction (Tylenol, methotrexate, carbon tetrachloride) • Non-dose related viral-like hepatitis(Isoniazid, Flurazepam, Methyldopa, I.V. tetracycline) • Cholestasis due to drugs like birth control pills.

  25. Fulminant Hepatic Failure • Massive liver cell death • Cause include poisoning, infectious disease, ischemia, cyanotic heart, severe asphyxia, cardiomyopathy, shock, metabolic disease. • Sx’s – jaundice, flu like symptoms, fever, anorexia, vomiting, abdominal pain, confusion, coagulopathy, ascites, coma

  26. Budd-Chiari Syndrome • Rare condition characterized by an obstruction of the hepatic venous outflow. • Causes include: malignancy, thrombogenic disorders, inflammation disorders, and hormone disorders. • Diagnostic imaging is used to confirm. • Treatment is based on cause and include: anticoagulation, angioplasty, TIPS procedure and liver transplant.

  27. Non-Alcoholic Fatty Liver Disease • NAFLD is any liver condition arising without association of alcohol exposure. • Non-Alcoholic Steatohepatitis or NASH is stage 3 and 4 of NAFLD and is detected by ultrasound and diagnosed by liver biopsy. It is fat accumulation in the liver. • Risk factors – obesity, type 2 diabetes and hyperlipidemia. • Treatment for NASH can include weight loss and exercise.

  28. Stages of Liver Damage

  29. Tumors • Benign vs. malignant • Most benign liver tumors are hemangiomas which rarely require any form of treatment. • Hepatocellular carcinoma is the most common primary malignant tumor of the liver. • Risk factors for HCC include: HBV carriers, HBV cirrhosis, HCV cirrhosis, cirrhosis from hemochromatosis, PBC, cirrhosis from auto-immune hepatitis, PSC, or repeated dietary exposure to aflatoxin B1.

  30. Wilson’s Disease • Autosomal-recessive disorder • Inability to metabolize copper • (Kayser-Fleischer ring) a pigmented ring at the outer margin of the cornea is the most unique sign • Cirrhosis of the liver, liver necrosis, dementia, brain damage and kidney failure are among the advanced symptoms of the disease.

  31. Porphyria • Any of a group of disturbances of porphyrin metabolism, characterized by marked increase in formation and excretion of porphyrins or their precursors. • Acute intermittent porphyria (AIP)-autosomal dominant, most do not develop symptoms, high intake of glucose or carbohydrates causes disease suppression. Monitor H2O and sodium intake during an attack • Hereditary coproporphyria (HCP)- characterized by large amounts of coproporphyrin III in the feces and lesser amounts in urine. Photosensitivity. Monitor H2O and sodium intake during an attack. • Variegate porphyria (VP)-autosomal dominant, characterized by large amounts of coproporphyrin in the feces and urine. Photosensitivity. • Porphyria cutanea tarda (PCT)-hereditary or acquired, characterized by chronic skin lesions especially on light exposed skin, increased hair growth, and mild liver disease with fatty infiltration, focal necrosis.

  32. Hemochromatosis • A disorder of iron metabolism characterized by excess deposition of iron in the tissues • Sx’s -bronze pigmentation of the skin, weakness, weight loss, malaise, joint pain, symptoms related to diabetes, loss of hair, congestive heart failure. • Primary – Inherited – recessive gene • Secondary – Acquired during life

  33. Diagnosis and Treatment • Diagnosis includes elevated serum ferritin, elevated serum iron, hereditary hemochromatosis DNA mutation analysis, MRI and liver biopsy. • Treatment includes: Therapeutic phlebotomy and Deferoxamin which binds with iron in the bloodstream and enhances its elimination via urine and feces.

  34. Developmental Diseases • Intrahepatic biliary dysplasia (IHBD) or Alagille syndrome is a rare autosomal-dominant liver disease that incorporates a combination of anomalies in conjunction with chronic cholestasis.

  35. Biliary atresia - Rare condition in newborn infants in which extrahepatic duct is blocked or absent. • Kasai (hepatoportoenterostomy) procedure allows for excretion of bile from the liver into the intestine via a surgically created duct, not a cure. • Biliary atresia is the most common indication for liver transplant in infants.

  36. Neonatal Hepatitis • Inflammation of the liver which occurs in early infancy. 20% due to viruses including CMV, rubella, and hepatitis A, B, or C.

  37. Gilbert Syndrome • Common and benign congenital disorder • Characterized by elevation in unconjugated bilirubin • All other liver tests are normal • Rarely develop jaundice

  38. Orthotopic Liver Transplantation • The severity of chronic liver disease is determined by the Model for End Stage Liver Disease (MELD) score. Based on serum bilirubin, INR, and creatinine. • UNOS has made modifications to the score • A quick reference site to calculate MELD scores and 90 day survival rates is

  39. Liver Puzzle • Cells remove amino acids, nutrients, sugars, broken down RBC’s, bacteria, and debris from the blood.

  40. Liver Puzzle • Most vascular organ of the body.

  41. Liver puzzle • Secreted from the liver

  42. Liver Puzzle • Transmitted by the ingestion of contaminated food.

  43. Liver Puzzle • Most common cause of Cirrhosis

  44. Liver Puzzle • Vascular lesion that is a presenting sign of chronic liver disease

  45. Liver Puzzle • Rare condition characterized by an obstruction of the hepatic venous outflow

  46. Liver Puzzle • Autosomal recessive trait in which pt can not metabolize copper

  47. Liver Puzzle • Disorder of iron metabolism

  48. Liver Puzzle • Developmental bile duct disorder in infants that results in obstruction of the bile flow through the extrahepatic duct system

  49. Liver Puzzle • Protein produced by the liver converted by thrombin into fibrin during blood coagulation in presence of ionized calcium.