HEPATOLOGY

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HEPATOLOGY

  1. 1. Diseases of the Liver & Biliary System
  2. 2. • If individual hepatocytes are destroyed but the architecture of the lobule is not destroyed, the remaining hepatocytes will totally regenerate the liver parenchyma. Liver regeneration
  3. 3. • If whole lobules are destroyed, the remaining lobules will expand. They will function normally, though bile may not be drained quite so well.
  4. 4. • Of course, if scar tissue alters the flow of blood through the liver (i.e., cirrhosis has occurred), regeneration will only produce less-than-fully-perfused nodules of liver cells. – (This will disappoint well-read problem drinkers who understood that their hepatocytes had unlimited capacity to regenerate....)
  5. 5. NORMAL CT SCAN
  6. 6. • Blood enters the liver from the hepatic artery and the portal vein and leaves the liver from the hepatic vein. • The blood from the artery carries oxygen while the portal vein carries nutrients from the intestine. Liver blood supply
  7. 7. • The portal vein is formed by the junction of the splenic & superior mesenteric veins. • Within the liver, the hepatic artery & portal vein come together with the bile ducts & lymphatics. • The branches of all of these vessels extend into the liver into the central lobular vein Functional anatomy
  8. 8. • The acinus make up the primary functional unit of the portal tract which contains branches of the hepatic artery, bile ducts, branches of the portal vein. • Hepatocytes (liver cells) are in the ascini. They contain glycogen. Each cell abuts the sinusoids. • The bile canaliculi run between the liver cells forming a network which end up in the bile ducts. Functional anatomy
  9. 9. • Inside the two lobes is a network of tubes, also called the biliary tree that carries bile from the liver to the intestine. • Bile is a substance that helps carry away wastes and is needed for the breakdown and absorption of dietary fats. Hepatic Ducts
  10. 10. • Each tube is called a duct. Smaller ducts connect to larger ducts. The larger ducts join to form the hepatic duct. • This duct network allows bile to drain out of the liver.
  11. 11. • Concentrate & conduct the 1-1.5L of bile produced by the liver to the intestine • Fasting diversion of bile into the gall bladder for storage & concentration • Food intake releases CCK to relax sphincter of Oddi for delivery of bile into the intestine Gallbladder
  12. 12. • Bile acids & detergents cholesterol & phospholipids to the intestine. • Also solubilizes dietary fat & promotes its digestion & absorption
  13. 13. The liver has multiple functions: • Making bile to help digest foods – Bile acid synthesis & secretion • Stopping cuts from bleeding (coagulation) – Responsible for the synthesis of prothrombin, factor VII, IX, and X from vitamin K absorption. What Does the Liver Do?
  14. 14. • Killing germs, helping keep the body healthy • Filtering toxic chemicals from the body – Remove waste products of nutrient breakdown • Biotransformation, detoxification & excretion of various endogenous & exogenous compounds
  15. 15. • Helps with disposing of bilirubin – excretes bilirubin into the small bowel so that bowel bacteria can change it into the safe green colored biliverdin. – Break down the major nutrients in foods (protein, fats and carbohydrates) Role of Liver (cont)
  16. 16. • Helping to build muscles/ proteins • Plasma protein synthesis • Lipid & lipoprotein synthesis • Glucose homeostasis
  17. 17. • Albumin is synthesized exclusively in the liver • albumin is essential for carrying molecules (and drugs), and for keeping fluid in the blood vessels. • Hypoalbuminemia causes fluid shift into tissue and patient will show signs of edema. • albumin decreases in malabsorption & tumor necrosis, or any form of chronic liver disease. Role of the liver (cont)
  18. 18. • Storing energy – Store vitamins A, D, E and K, & B12 Role of the liver (cont) Fate – Soluble Vitamins Vitamin Function A Visual pigments, normal development of bones D Absorption of Ca++ E Antioxidant, stability of cell membranes K Prothrombin synthesis (clotting)
  19. 19. • Bilirubin is the primary waste product of heme metabolism -degradation of hemoglobin (RBC’s). • Unconjugated bilirubin is transported in the plasma bound to albumin. • The liver is the major site of metabolism of bilirubin & ammonia Liver Physiology
  20. 20. • The metabolism of carbohydrate in the liver is regulated by insulin, glycogen, catecholamines, corticosteroids, & thyroxine • Most drugs are metabolized by the liver, microsomal enzymes such as cytochrome p450 system and rendered water soluble Hepatic Physiology (cont.)
  21. 21. • Liver Function • Hepatic Test • Jaundice • Biliary Tract Disease – Cholelithiasis-Choledocholithiasis – Cholecystitis-Cholangitis – Biliary tract obstruction Disorders
  22. 22. • Hepatic Disease – Hepatitis Acute & Chronic A/B/C/D/E, ETOH/drug – Cirrhosis – Hepatic Failure • Neoplasm (later section)
  23. 23. Functions of the Liver and Manifestations of Altered Function Function Manifestations of Altered Function Production of bile salts Malabsorption of fat and fat- soluble vitamins Elimination of bilirubin Metabolism of steroid hormones Elevation in serum bilirubin and jaundice Sex hormones Disturbances in gonadal function, including gynecomastia in the male Glucocorticoids Signs of increased cortisol levels (i.e., Cushing’s syndrome)
  24. 24. Function Manifestations of Altered Function Aldosterone Signs of hyperaldosteronism (e.g., sodium retention and hypokalemis) Metabolism of drugs Decreased drug metabolism Decreased plasma binding of drugs owing to a decrease in albumin production Carbohydrate metabolism Hyperglycemia may develop when glycogenolysis and gluconeogenesis are impaired Stores glycogen and synthesizes glucose from amino acids, lactic acid, and glycerol Abnormal glucose tolerance curve may occur because of impaired uptake and release of glucose by the liver
  25. 25. Fat metabolism Formation of lipoproteins Conversion of carbohydrates and proteins to fat Impaired synthesis of lipoproteins Synthesis, recycling, and elimination of cholesterol Formation of ketones from fatty acid Protein metabolism Deamination of proteins Altered cholesterol levels Formation of urea from ammonia Elevated blood ammonia levels
  26. 26. Synthesis of plasma proteins Decreased levels of plasma proteins, particularly albumin, which contributes to edema formation Synthesis of clotting factors (fibrinogen, prothrombin, factors V, VII, IX, X) Bleeding tendency Storage of mineral and vitamins Signs of deficiency of fat- soluble and other vitamins that are stored in the liver Filtration of blood and removal of bacteria and particulate matter by Kupffer’s cells Increased exposure of the body to colon bacilli and other foreign matter
  27. 27. Clinical Manifestations of Liver Disease Sign/Symptom Pathogenesis Liver Disease Constitutional Fatigue, anorexia, malaise, weight loss Liver dysfunction Acute or chronic hepatitis Cirrhosis Fever Hepatic inflammation or infection Liver abscess Alcoholic hepatitis Viral hepatitis Fetor hepaticus Sulfur compounds, produced by intestinal bacteria, not cleared by the liver Acute or chronic liver failure
  28. 28. Sign/Symptom Pathogenesis Liver Disease Cutaneous Spider telangiectasias, palmar erythema Altered estrogen and androgen metabolism with altered vascular physiology Cirrohsis Jaundice Diminished bilirubin excretion Biliary obstruction Severe liver disease Pruritus Uncertain Biliary obstruction Xanthomas and xanthelasma Increased serum cholesterol Biliary obstruction / cholestasis
  29. 29. Endocrine Gynecomastia, testicular atrophy, di-minished libido Altered estrogen and androgen metabolism Cirrohsis Hypoglycemia Decreased glycogen stores and gluconeogenesis Acute liver failure Alcohol binge with fasting
  30. 30. Gastrointestinal Right upper quandrant abdominal pain Liver swelling, infection Acute hepatitis Hepatocellular carcinoma Liver congestion (heart failure) Acute cholecystitis Liver abscess Abdominal swelling Ascites Cirrhosis, portal hypertension Gastrointestinal bleeding Esophageal varices Portal hypertension
  31. 31. Hematologic Decreased red cells, white cells, and/or platelets Hypersplenism Cirrhosis, portal hypertension Ecchymoses Decreased synthesis of clotting factors Liver failure Neurologic Altered sleep pattern subtle behavioral changes, somnolence, confusion, ataxia, asterixis, obtundation Hepatic encephalopathy Liver failure, portosystemic shunting of blood
  32. 32. History • FHx: Hx of jaundice or liver disease. • Social Hx-Recent travel. Exposure to alcohol, Exposure to individuals or animals with liver or parasitic disease. Exposure to alcohol. Multiple sex partners. IV drug use. Exposure to alcohol.
  33. 33. • General: – fever & weight loss • Cutaneous: – spider angiomas, telangiectasias, palmar erythema, jaundice, xanthomas & xanthelasma • Endocrine: – gynecomastia, testicular atrophy, hypoglycemia Physical exam
  34. 34. • G.I.: – RUQ pain, abdominal swelling/ascites, heptosplenomegaly, G.I. Bleed • Hematological: – pale skin/mucous membranes, ecchymoses • Neuro: – Ataxia, somnolence, confusion, asterixis & obtundation
  35. 35. Ascites
  36. 36. Telangiectatic Lesions
  37. 37. Xanthelasma
  38. 38. Xanthomata on the abdomen
  39. 39. Splinter hemorrhages
  40. 40. Spider angioma
  41. 41. • Serum albumin (or prealbumin levels): – multipurpose serum protein synthesized in the liver. – It is decreased when disease is prolonged enough to deplete the blood levels. – Albumin is the protein of the highest concentration in plasma. Tests of liver function
  42. 42. –Albumin transports many small molecules in the blood (for example, bilirubin, calcium, progesterone, and drugs). – It is also of prime importance in maintaining the oncotic pressure of the blood (that is, keeping the fluid from leaking out into the tissues).
  43. 43. –This is because, unlike small molecules such as sodium and chloride, the concentration of albumin in the blood is much greater than it is in the extracellular fluid. –Because albumin is synthesized by the liver, decreased serum albumin may result from liver disease.
  44. 44. – It can also result from kidney disease, which allows albumin to escape into the urine. – Decreased albumin may also be explained by malnutrition or a low protein diet. – The normal range is 3.4 to 5.4 g/dL.
  45. 45. –Prothrombin time (PT)- • Prolongation of the PT is one of the most sensitive prognosticators of severe liver disease. • Tests capacity for protein synthesis • It measures the function of the livers clotting ability of factors I (fibrinogen), II (prothrombin), V, VII, and X. Tests of Liver Function
  46. 46. • When any of these factors is deficient, the PT is prolonged. • Coumadin or vitamin K deficiency impair the function
  47. 47. Plasmalogen
  48. 48. • The normal PT range is 11 to 15 seconds – ("normal" varies somewhat in different labs). • The normal value for the INR is 1.0 • Also used for oral anticoagulant monitoring following venous thromboembolism, myocardial infarction, atrial fibrillation or rheumatic heart disease PT (prothrombin time) & INR (international normalized ratio)
  49. 49. • For a person on full anticoagulant therapy, the PT should be 2 to 3 times the laboratory "control" value. INR 2.0-3.0 • For oral anticoagulant monitoring for those with mechanical heart valves: INR 2.5-3.5
  50. 50. • Transaminases Aspartate-AST (SGOT) & Alanine-ALT (SGPT): LFT’s/Transaminases
  51. 51. – AST (SGOT) • is normally found in a diversity of tissues including liver, heart, muscle, kidney, and brain. It is released into serum when any one of these tissues is damaged. –For example, its level in serum rises with heart attacks and with muscle disorders. • It is therefore not a highly specific indicator of liver injury.
  52. 52. – ALT (SGPT) • is, by contrast, normally found largely in the liver. • This is not to say that it is exclusively located in liver but that is where it is most concentrated. • It is released into the bloodstream as the result of liver injury. • It therefore serves as a fairly specific indicator of liver
  53. 53. – status.released into the circulation following hepatocyte injury or death. • The ratio of AST:ALT can be helpful – AST:ALT > 2:1 suggesting alcoholic liver disease – AST:ALT < 1:1 suggesting viral hepatitis. AST/ALT
  54. 54. – They are sensitive, but non-specific for liver damage. – Need isoenzymes – The normal range of values for AST (SGOT) is from 5 to 40 units per liter of serum (the liquid part of the blood). – The normal range of values for ALT (SGPT) is from 7 to 56 units per liter of serum. • Normal range can vary according to a number of factors, including age and gender.
  55. 55. • The highest levels of AST and ALT are found with disorders that cause the death of numerous liver cells (extensive hepatic necrosis). – Although, the precise levels of these enzymes do not correlate well with the extent of liver damage or the prognosis AST/ALT
  56. 56. • This occurs in such conditions as acute viral hepatitis A or B, pronounced liver damage inflicted by toxins as from an overdose of acetaminophen (Tylenol), and prolonged collapse of the circulatory system (shock) when the liver is deprived of fresh blood bringing oxygen and nutrients
  57. 57. • Derived from liver, intestines, bones & placenta. • Released causing high levels during – liver damage, particularly necrosis, – cholestasis/ bile duct obstruction, – neoplastic, – infiltrative & granulomatous liver disease. • Need isoenzymes Serum Alkaline Phosphatase- (Alk Phos)
  58. 58. Alk Phos
  59. 59. Alk Phos
  60. 60. Alk Phos
  61. 61.   Property Examined Significance of Abnormal Result Tests of Hepatic Function (Normal Values) Serum albumin  (3.5-5.5 mg/dl) Protein  synthetic  capacity (over  days to weeks) Decreased synthetic capacity Protein malnutrition Increased protein loss (nephritic  syndrome, protein-losing  enteropathy) Increased extracellular fluid  volume Prothrombin  time (10.5-13  sec) Protein  synthetic  capacity (hours  to days) Decreased synthetic capacity  (especially factors II and VII) Vitamin K deficiency  Consumptive coagulopathy 
  62. 62.   Property Examined Significance of Abnormal Result Screening Tests of Hepatobiliary Disease Tests of Biliary  Obstruction or  Impaired Bile Flow     Serum bilirubin  (0.2-1.0 mg/dl) (3.4-17.1 mol/L Extraction of  bilirubin from blood  conjugation and  excretion into bile  Hemolysis  Diffuse liver disease  Cholestasis Extrahepatic bi,e  duct obstruction Congenital disorders  of bilirubin  metabolism 
  63. 63.   Property Examined Significance of Abnormal Results Serum alkaline  phosphatase (also 5’- nucleotidase and γ- glutamyl  transpeptidase) (56- 176 U/L) Increased enzyme  synthesis and  release  Bile duct obstruction Cholestasis Infiltrative liver  disease (neoplasms,  granulomas)Bone  destruction/remodeling    Pregnancy 
  64. 64.   Property Examined Significance of Abnormal Results Tests of Hepatocellular Damage Aspartate  Aminotransferase (AST, SGOT)  (10-30 U/L) Release of  intracellular  Enzyme Hepatocellular  necrosis Cardiac or skeletal  muscle necrosis Alanine  aminotransferase  (ALT, SGPT)  (5-30 U/L) Release of  intracellular  enzyme  Same as AST;  however, more  specific for liver cell  damage 
  65. 65. Characteristic Patterns of Liver Function Tests Disorder  Bilirubin Alkaline  Phosphatas e Aspartate  Aminotransferas e Alanine  Aminotransfera se Prothromb in Time Albumi n Gilbert’s syndrome  (abnormal bilirubin  metabolism) ↑ NL NL NL NL NL Bile duct  obstruction  (pancreatic cancer) ↑↑↑ ↑↑↑ ↑ ↑ ↑-↑↑ NL Acute  hepatocellular  damage (toxic, viral  hepatitis) ↑-↑↑↑ ↑-↑↑ ↑↑↑ ↑↑↑ NL-↑↑↑ NL-↓↓ Cirrhosis  NL-↑ NL-↑ NL-↑ NL-↑ NL-↑↑ NL-↓↓ NL = normal;  ↑ = increased; ↓ = decreased (arrows indicate extent of change; ↑-↑↑↑=slight to large)
  66. 66. • Liver biopsy- U/S or CT guided. – Valuable in the histological differential, diagnosis & treatment of diffuse or localized parenchymal disease. – Generally safe. – Must check coagulation values and platelets before procedure secondary to risk of severe hemorrhage. LFT’s/ Diagnostic Tests
  67. 67. • Serum bilirubin- Balance between bilirubin  production and its conjugation & excretion into  bile by the liver.   • Elevated level is not specific for any etiology of  liver disease Tests for biliary obstruction/cholestasis   &/or  hepatocellular damage
  68. 68. – Direct bilirubin (already conjugated by the  liver): elevated in intra- or extra hepatic  obstruction. – Indirect bilirubin (Unconjugated, insoluble):  elevated when hemolysis releases it from red  blood cells (RBC’s) or in rare genetic  deficiencies in conjugating enzymes.
  69. 69. • Jaundice- yellow/green appearance to the skin &  eyes (Icterus) produced by increased serum  bilirubin.  • Usually given in a direct/total relationship • Normal Bilirubin ranges 0.5 to 1.0 mg/dl.   • Levels >3.0 mg/dl to be clinically  jaundiced.   – Newborn period is the exception Approach to Jaundice
  70. 70. • Red cells (Heme) break down forming  biliverdin (bile pigment).   • This is unconjugated (indirect bilirubin).   • It is transported by albumin & is not soluble.   – (No Bilirubin in the urine).  Bilirubin Metabolism
  71. 71. • (i.e., Binding Bilirubin ("indirect", unconjugated) to plasma albumin.) • The bile pigment is converted to conjugated (Direct bilirubin) by the Kupffer cells of the liver.
  72. 72. • In the liver, the bilirubin is conjugated  – with UDPglucuronate, making it water- soluble Bilirubin diglucuronide,  • i.e. ("direct" conjugated bilirubin).    • This is soluble & only shows up in blood &  urine with obstruction in the system.
  73. 73. • In the terminal ileum the bilirubin is converted to  stercobilinogen & urobilinogen by natural  bacteria.   • Conjugated bilirubin is excreted into the bile and  passed into the intestine where it is further  metabolised: urobilinogen ->urobilin->  stercobilin, which colors the feces brown.  Bilirubin conjugation
  74. 74. • Some is reabsorbed and returned to the liver. • Some urobilinogen is found in the urine. • If excretion of conjugated bilirubin is hindered, it is excreted by the kidney.
  75. 75. A. Normal process of conjugation of bilirubin by the liver, which promotes  excretion through the bile. B. With increased destruction of red blood cells,  large amounts of unconjugated bilirubin are released and the liver is unable to  conjugate all that comes to it. Increased bilirubin in the blood results, which  leads to bilirubinemia and jaundice.
  76. 76. • Pre-hepatic jaundice – Hemolytic disease • Post hepatic jaundice – Hepatitis – Drug induced hepatitis – Cirrhosis Bilirubin Metabolism
  77. 77. • Notes: – Obstruction of biliary system prevents production of urobiligen & stercobilinogen • Stool is light and urine is dark showing bilirubin
  78. 78. • Diseases that elevate blood levels of bilirubin fall  into one of these four categories of disorder: – 1. Increased bilirubin production – 2. Decreased bilirubin uptake by the liver – 3. Impaired conjugation in the liver – 4. Decreased excretion of bilirubin into the bile  (cholestasis) Hyperbilirubinemia
  79. 79. • The first 3 types listed are unconjugated (indirect)= normal stool and urine color. • The 4th (decreased excretion/ cholestasis) shows increased conjugated bilirubin (direct) with dark urine and light stool color.
  80. 80. Due to overproduction, decreased hepatic uptake or decreased conjugation of bilirubin Unconjugated (Indirect)  hyperbilirubinemia
  81. 81. – 1. Overproduction 20  hemolysis  (autoimmune), ineffective erythropoiesis  (megablastic anemia), increase RBC  fragility/turnover (2,3 DPG deficiency) – 2. Impaired hepatic uptake: Gilbert’s  syndrome & certain drugs such as rifampin,  anesthetics & radiographic dyes 
  82. 82. • 3. Impaired conjugation: Hepatocellular  disease, drug inhibition such as  chloramphenicol, anabolic steroids, genetic  disorders such as Gilbert’s syndrome or  Crigler- Najjar syndrome (decreased UDP- glucuronyl transferases). Unconjugated (Indirect) hyperbilirubinemia
  83. 83. • The most common cause of jaundice is neonatal jaundice – They do not have a significant quantity of  glucouronyl transferase (the enzyme used for  conjugation), due to enzyme immaturity, but  kicks in within a few weeks. Unconjugated (Indirect) hyperbilirubinemia
  84. 84. • Bilirubin is very toxic to the neonatal brain  (kernicterus), UV light is used to isomerize  the bilirubin, which prevents it from crossing  the blood-brain barrier.
  85. 85. – Common causes of neonatal jaundice Rh  disease/ABO incompatibility is hemolytic  and also impaired hepatic intake. – Kernicterus: is a type of brain damage that  causes athetoid cerebral palsy and hearing  loss. It also causes problems with vision and  teeth and sometimes can cause mental  retardation. 
  86. 86. 4. Due to Altered biliary drainage, impaired hepatic excretion of bile, or extra hepatic obstructions: – A. Altered biliary drainage of bile (TPN,  cholestasis, drugs), hepatocellular disease,  cirrhosis.  Conjugated (Direct) hyperbilirubinemia
  87. 87. • May occur in setting of cholestasis with  impaired formation or excretion of all  components of bile or hepatocellular injury  independent of cholestasis.  • May indirectly cause increase in unconjugated  also if severe enough  **You will have change in color of stool and urine**
  88. 88. – B. Impaired hepatic excretion: intrahepatic cholestasis- Dubin-Johnson syndrome & all  disorders in the transport of conjugated bile  from the hepatocytes to intrahepatic bile  ducts. • Drug-induced cholestasis-phenothiazines, OCP’s &  methyltestosterone.   Conjugated (Direct) hyperbilirubinemia
  89. 89. – C. Extra hepatic: Gallstones,  pancreatic/biliary obstructive tumors,  strictures & biliary atresia  **Dark brown or green urine implies conjugated hyperbilirubinemia
  90. 90. • Cholestatic jaundice--Increased alk phos to  3-4 times normal.   – Hypercholesterolemia, pruritus, malabsorption of  fat & fat-soluble vitamins.   – Minimal or marked evidence of liver cell damage. Causes of Conjugated (Direct)  hyperbilirubinemia
  91. 91. Determine mechanism involved: • Hx: pale stools & pruritus--> cholestasis.  – & nausea--> gallstones = biliary obstruction.   – Inquire about drugs & alcohol use, risks for viral  hepatitis & pre-existing liver disease.   Diagnosis of conjugated  hyperbilirubinemia
  92. 92. • Laboratory:  – biliary obstruction: <5-10 fold increase in  transaminases & >2-3x normal alk phos.   – Hepatocellular disease: >10-15 fold increase  in transaminases & < 2-3x normal alk phos.  
  93. 93. • Sepsis- – mainly gram-negative organisms. – Mildly elevated serum alk phos Disorders of the Biliary System
  94. 94. • Post-op jaundice-- 1-10 days post-op.   – 15% incidence following heart/ 1% elective  abdominal surgery.   – Increased alk phos & minimally elevated levels of  transaminases.  – Secondary to anesthesia side effects
  95. 95. • Hepatocellular disease (hepatitis, cirrhosis) – elevated transaminases, prolonged PT,  hypoalbuminemia & clinical features of hepatic  dysfunction. • Extrahepatic biliary obstruction– – obstruction of extra hepatic bile ducts--gallstones,  neoplasias, bile duct strictures, chronic  pancreatitis.   – Clay-colored stools.
  96. 96. • Extra hepatic obstruction:  CT or U/S to  determine stone or bile duct dilation. • Bile duct dilation: endoscopic retrograde  cholangiography (ERCP) for management &  treatment. • Liver biopsy: for determining cause of  intrahepatic cholestasis. Special diagnostic procedures in  cholestatic jaundice
  97. 97. • "HOT Liver": Hemolysis Obstruction Tumor Liver disease  Hyperbilirubin Mneumonic
  98. 98. Prehepatic (Excessive Red Blood Cell Destruction) Hemolytic blood transfusion reaction Hereditary disorders of the red blood cell Sickle cell anemia Thalassemia  Spherocytosis  Causes of Jaundice
  99. 99. Acquired hemolytic disorders  Hemolytic disease of the newborn Autoimmune hemolytic anemias 
  100. 100. Intrahepatic Decreased bilirubin uptake by the liver  Gilbert’s disease  Decreased conjugation of bilirubin  Hepatocellular liver damage Hepatitis  Cirrhosis  Cancer of the liver  Drug-induced cholestasis 
  101. 101. Posthepatic (Obstruction of Bile Flow) Structural disorders of the bile duct  Cholelithiasis  Congenital atresia of the extrahepatic bile ducts  Bile duct obstruction caused by tumors 
  102. 102. Predominantly Unconjugated Hyperbilirubinemia  Overproduction  Hemolysis (e.g., spherocytosis, autoimmune disorders) Ineffective erythropoiesis (e.g., megaloblastic anemias)  Decreased hepatic uptake  Gilbert’s syndrome  Drugs (e.g., rifampin, radiographic contrast agents) Neonatal jaundice  Classification of Jaundice 
  103. 103. Decreased conjugation  Gilbert’s syndrome Crigler-Najjar syndrome types I and II Neonatal jaundice  Hepatocellular disease  Drug inhibition (e.g., chloramphenicol) 
  104. 104. Predominantly Conjugated Hyperbilirubinemia  Impaired hepatic excretion  Familial disorders (Dubin-Johnson syndrome, Rotor  syndrome, benign recurrent cholestasis, cholestasis of  pregnancy) Hepatocellular disease  Drug-induced cholestasis  Primary biliary cirrhosis  Sepsis  Postoperative 
  105. 105. Extrahepatic (“mechanical”) biliary obstruction  Gallstones  Tumors of the head of the pancreas Tumors of bile ducts  Tunors of the ampulla of Vater  Biliary strictures (postcholecystectomy, primary  sclerosing cholangitis) Congenital disorders (biliary atresia)
  106. 106. OBSTRUCTIVE JAUNDICE VERSUS CHOLESTATIC LIVER DISEASE  SUGGESTS OBSTRUCTIVE JAUNDICE SUGGESTS CHOLESTATIC LIVER DISEASE History Abdominal pain Fever, rigors Prior biliary surgery Older age Anorexia, malaise, myalgias,  suggestive of viral prodrome Known infectious exposure Receipt of blood products, use  of intravenous drugs Exposure to known hepatotoxin Family history of jaundice
  107. 107. Physical examination High fever Abdominal  tenderness Palpable abdominal  mass Abdominal scar  Ascites Stigmata of liver disease  (e.g., prominent  abdominal veins,  gynecomastia, spider  angiomata, Kayser- Fleischer rings) Asterixis, encephalopathy
  108. 108. Laboratory Studies Predominant elevation  of serum bilirubin and  alkaline phosphatase Elevated serum  amylase Prothrombin time  which is normal or  normalizes with  vitamin K  administration Predominant elevation of  serum transaminases Prolonged prothrombin  time which does not  correct with vitamin K  administration Blood tests indicative of  specific liver disease 
  109. 109. Approach to the patient with cholestatic jaundice
  110. 110. The word "hepatitis" means inflammation of the  liver.  It can be caused by a number of agents, including  bacteria, drugs, toxins and excess alcohol, but of  serious concern is hepatitis that results when any  one of several hepatitis viruses infect the liver.  Hepatitis
  111. 111. 1. Virus A. Hepatitis A (HAV) B. Hepatitis B (HBV) C. Hepatitis C (HCV) D. Hepatitis D (HDV) E. Hepatitis E (HEV) F. Cytomegalic (CMV) G. Epstein-Barr (EBV) Hepatitis Causes
  112. 112. 2. Toxins 3. Alcohol 4. Other diseases a. Wilson’s disease b. Leukemia c. Lymphoma
  113. 113. • **Hepatitis E & A are fecal-oral • (f E c A l –oral) • **While Hep B,C,D are blood borne (parenteral) • “Coming in the Back Door”
  114. 114. • Viral Hepatitis • Hepatitis A virus • Hepatitis B virus • Hepatitis C virus • Hepatitis D virus (“delta agent”) • Hepatitis E virus • Epstein-Barr virus
  115. 115. • Cytomegalovirus • Alcohol • Toxins • Amanita phalloides mushroom poisoning • Carbon tetrachloride • Drugs • Acetaminophen
  116. 116. • Isoniazid • Halothane • Chlorpromazine • Erythromycin • Other • Wilson’s disease • Herbs
  117. 117. • Hepatitis A virus • Hepatitis B virus • Hepatitis C virus • Hepatitis E virus • Yellow fever virus • Epstein-Barr virus (infectious mononucleosis)
  118. 118. • Lassa, Marburg, and Ebola viruses • Rubella virus • Herpes simplex virus • Cytomegalovirus • Enteroviruses other than hepatitis A virus • Leptospires (leptospirosis) • Entamoeba histolytica (amebic hepatitis)
  119. 119. • Hepatitis can be defined as a constellation of  signs & symptoms resulting from inflammation  & hepatic cell necrosis • In a previously asymptomatic individual the  term “acute” is applied Acute Hepatitis
  120. 120. • Virus is the most common cause of hepatitis. – Only occasionally can bacterial infections  like syphilis or TB be considered • Most cases of acute hepatitis are sub- clinical & usually undiagnosed
  121. 121. • The different types of hepatitis cannot be  distinguished clinically & their distinction  depends upon serological testing Acute Hepatitis
  122. 122. Histologically they are all the same: • Classically the histological appearance of  acute hepatitis is liver damage & necrosis in  the centrilobular area • Mild edema occurs in the portal tracts with  some degree of cholestasis causing jaundice,  depending on the degree of obstruction
  123. 123. • The hepatic cells undergo degeneration with  some scarring • Most cases only have minimal damage & go on  to complete recovery • Some cases progress to liver failure and death Acute Hepatitis
  124. 124. Symptoms of Hepatitis •Malaise •Vomiting •Nausea  •Diarrhea •Anorexia •Low grade fever •Fatigue •Rash •Arthralgias
  125. 125. • Tenderness of the liver • Hepatomegally on occasion • Dark urine • Jaundice Clinical findings of Hepatitis
  126. 126. • Bilirubin elevated • SGPT (ALT) (very specific for liver) • SGOT ( AST) (not as specific) • Alkaline phosphatase (alk phos) – Nonspecific- represents obstruction of liver • Can be elevated in bone ds. or child growth • PT,PTT (elevated c ~55% liver destruction) • Hypoglycemia Laboratory Tests (LFT’s)
  127. 127. Serum markers for viral hepatitis  Anti-HAV (IgM-IgG) HBsAg   HBeAg Anti-HBc (IgM-IgG)   Anti-HBe Anti-HBs   Anti-HCV Anti-HDV   Monospot, Heterophile   (also do Urinalysis)   
  128. 128. • 1. Massive hepatic necrosis (1%) – Usually in B,C,D,E • 2. Chronic Hepatitis • 3. Cholestatic Hepatitis Syndrome – Pruritis – Dark urine – Light stools – Hyperbilirubinemia – Alk phos elevation Complications of Hepatitis
  129. 129. Don’t complain about the seating arrangements
  130. 130. Age: 15-25 yo “ Kissing Disease” Symptoms: Fever Hepatosplenomegally Malaise** Lymphadenopathy* Loss of appetite Sore throat** Nausea/Vomiting Rash (maculopapular) Fatigue Abd pain Jaundice Headache** **Most common symptoms Mononucleosis Epstein-Barr Virus (EBV) 
  131. 131. • Maculopapular rash: • NEVER GIVE AMPICILLIN FOR SORE THROAT TO MONO PATIENT causes rash Mononucleosis (EBV) 
  132. 132. • Key Signs: – Fever – Exudative Pharyngitis – Lymphadenopathy – Splenomegaly Mononucleosis (EBV)
  133. 133. • Labs – 1. CBC  • shows a relative lymphocytosis – Atypical lymphocytes • Reduction in platelet count – 2. Mono spot test  Heterophile – 3. EBV specific serology • IgM specific IgG confirms prior illness – 4. Transaminase elevated slightly (AST/ALT) Mononucleosis Epstein-Barr virus
  134. 134. • Complications- – Bacterial pharyngitis – Upper airway obstruction – Bells palsy – Ruptured spleen Mononucleosis (EBV)
  135. 135. • Treatment- – Supportive therapy – Tylenol for fever and malaise – Antibiotic if bacterial pharyngitis is present • Avoid ampicillin (RASH) – Steroids for severe pharyngitis & fever • 40-60 mg of prednisone/day – Activities reduced- no contact sports for 6 weeks Mononucleosis (EBV)
  136. 136. • Similar to EBV in many ways • No pharyngitis or respiratory symptoms • Atypical lymphocytes • Abnormal liver function studies • Diagnosis made by CMV titers • Transmitted in same manner as mono  • more common in transplant and AIDS patients. **If mono test neg due CMV titer Cytomegalic Virus
  137. 137. • Approximately 25% of all cases of hepatitis • Less morbidity & mortality • Contact by fecAl-oral route • Incubation period 2-6 weeks (shortest) Hepatitis A
  138. 138. • Symptoms: (more severe sx than mono) Malaise Abd pain Fever Jaundice Hepatosplenomegally(25%) Diarrhea Anorexia ** h/o eating clams, out of country travel, etc.
  139. 139. • Duration: 4 weeks • Complications: rare (no chronic type) • Lab:  – SGOT  , SGPT   , Bilirubin   ,  – HAV IgM, HAV IgG • Treatment: – Good nutrition – No alcohol Hepatitis A (cont)
  140. 140. • Prophylaxis: – Administration of Gamaglobulin  • effective in prevention (prior to exposure) – Post exposure: is recommended for household &  sexual contacts within two weeks, plus Hepatitis A  vaccine Hepatitis A (cont)
  141. 141. – Travelers: recommended in normal dose for  2 mo stay, and triple dose for 4-6 mo stay – Hepatitis A vaccine given 15 days prior to  travel, followed by 6 mo later
  142. 142. • Incubation: 1-6 months • Symptoms: same as Hep A, but even more  severe • Contact: Parenteral inoculation, sexual (blood or mucus membrane) Hepatitis B
  143. 143. • Course: – 90% recover – 10% develop chronic hepatitis (with HBsAg carrier state) – A small amount go onto chronic progressive hepatitis which goes on to cirrhosis – 1% develop a fulminate course Hepatitis B
  144. 144. • Lab tests: – SGPT (ALT) & SGOT (AST) rise with symptoms – Bilirubin & alk phos – PT, PTT **(all these labs are higher than in HAV)
  145. 145. • Serological tests: – HBcAg: disappears soon after the peak of ALT – HBeAg: Positive in acute HBV – HBsAg: positive in acute & chronic Hepatitis B (Lab continued)
  146. 146. – Anti-HBs: + in late acute HBV and immunized (protective) – HBeAb: appears when antigen decreased – HBcAb: • IgM marker for acute infection. • IgG chronic HBV & carrier
  147. 147. • HBsAg: First virologic marker detectable in serum in acute HBV infection; • precedes elevations of liver enzymes and clinical symptoms. Serologic Markers:
  148. 148. • Usually detectable 4 weeks after infection and typically disappears at 6 months after active infection. • Persistence of HBsAg beyond 6 months implies chronic HBV infection.
  149. 149. • Anti-HBs: Appears shortly after HBsAg disappears from serum and persists indefinitely in patients who have recovered from acute infection. Serologic Markers:
  150. 150. • Anti-HBs is felt to be the protective antibody against HBV infection; thus, vaccine consists of nonglycosylated HbsAg particles that are safe and highly immunogenic, thereby inducing active immunity.
  151. 151. • HBcAg: Not detectable in serum Serologic Markers: (cont)
  152. 152. • Anti-HBc: – IgM • appears at 1 to 2 weeks after the appearance of HBsAg; • its detection in serum is indicative of acute HBV infection. • It is the only marker of acute HBV during the window period between the disappearance of HBsAg and the appearance of anti-HBs in serum. Serologic Markers: (cont)
  153. 153. • IgM predominates for the first 6 months following acute infection but may persist up to 2 years.
  154. 154. –IgG • predominates after 6 months and generally persists indefinitely in patients who have recovered from HBV infection. • Present in virtually all patients who have ever been exposed to HBV
  155. 155. • HBeAg: – Considered to be a marker of active virus replication and infectivity; – also correlates with detection of HBV DNA in serum. – Usually appears with or after the appearance of HBsAg in serum and disappears shortly after peak elevations in serum aminotransferase activity in acute infection.
  156. 156. – In chronic infection, HBeAg may persist for years prior to seroconversion to anti- HBe; – its presence is indicative of the replicative stage of HBV infection, which represents a time of maximal infectivity and liver injury.
  157. 157. – Likelihood of perinatal transmission correlates with presence of HBeAg: ~90% of HBeAg-positive mothers transmit HBV to their offspring but only 10-15% of anti- HBe positive mothers do so.
  158. 158. – In a small subset of patients with acute HBV infection, HBeAg is not detected because of a viral mutation; in such patients, HBV DNA levels are elevated, representing the replicative stage of the virus.
  159. 159. • Anti-HBe: – Appears after seroconversion of HBeAg to anti-HBe. – Its presence in chronic HBV infection signals the onset of the nonreplicative phase, where HBV DNA becomes undetectable in serum and liver injury tends to subside. Serologic Markers: (cont)
  160. 160. – Generally exists in serum indefinitely unless seroconversion back to HBeAg occurs.
  161. 161. • HBV DNA: – Probably the most reliable indicator of active viral replication. – Can be detected by hybridization methods or PCR. – Recovery from acute HBV infection is accompanied by the disappearance of HBV DNA from serum; however, very low levels may remain detectable by PCR. Serologic Markers: (cont)
  162. 162. – Persistence of HBV DNA implies chronic infection. – Useful in predicting response to interferon therapy; • high pretreatment HBV DNA levels > 200 pg/ml by hybridization assay are predictive of poor response to interferon. • Also, clearance of HBV DNA is used as an endpoint in assessing response to treatment.
  163. 163. HBs Ag Anti- HBs Anti- HBc HBe Ag Anti- HBe Interpretation + – IgM + – Acute HBV, high infectivity + – IgG + – Chronic HBV, high infectivity + – IgG – + Late-acute or chronic HBV infection, low infectivity + + + +/– +/– Heterotypic anti-HBs with HBsAg; usually indicates chronic HBV carrier state
  164. 164. HBs Ag Anti- HBs Anti- HBc HBe Ag Anti- HBe Interpretation – – IgM +/– +/– Acute HBV (anti-HBc window) – + IgG – +/– Recovery from HBV infection – – IgG – +/– Low-level HBsAg carrier or remote past infection – + – – – Immunization for HBV (HBsAg)
  165. 165. • Screening for acute viral hepatitis: – anti-HAV IgM – HBsAg – anti-HBc IgM – anti-HCV Screening
  166. 166. • Screening for chronic viral hepatitis: – HBsAg – anti-HCV – if + HBsAg then check HBeAg – +/- HBV DNA.
  167. 167. • Chronic hepatitis B is characterized by the persistent presence of HBV DNA and usually HBeAg in the serum; • remissions are characterized by the disappearance of HBV DNA and HBeAg from serum despite the persistence of HBsAg.
  168. 168. • Treatment: – After exposure: • give hepatitis B immunoglobulin (IG) + • active immunization with HBV vaccine (Combivax) in any patient who is: – Stuck by a needle – Within 14 days of sexual exposure – An infant born to a mother HBsAg positive Hepatitis B
  169. 169. – Preventative to: • Health care workers • Homosexual men • Household & sexual contacts of HBsAg carriers
  170. 170. • Follow up: – Recheck in 3 months if tests are normal – A liver biopsy if patient appears to have chronic hepatitis – Keep in mind patients with chronic hepatitis B can develop hepatocellular carcinoma Hepatitis B
  171. 171. • (Blood) Parenteral – Associated with transfusion in 85% of the time – inoculation from drug abuse • 50-70% go onto chronic hepatitis which can lead to cirrhosis of the liver 20% of the time • Incubation is 5-10 weeks • Anti-HCV (antibody to the C virus) is 70% accurate • Hepatitis C account for 80-90% of the Non A, Non B hepatitis Hepatitis C
  172. 172. • New serologic test for Hep C – Anti-HCV if present indicates the presence of viremia (80%) – + HCV plus ALT (SGPT) is confirmatory – A second generation recombinant immunoblot assay (RIBA) is used for confirmation. – Polymerase chain reaction (PCR) is used in equivocal cases, but is not + for at least 6-8 weeks (this is a test to specifically find the HCV RNA virus) Hepatitis C
  173. 173. • Treatment: –The patient is given alpha interferon for the chronic infection 3 x’s/ wk for 6 months –What is interferon: • 30% of circulating lymphocytes are B cells & 70% are T cells Hepatitis C
  174. 174. –B cells produce immunoglobulins that produce antibodies –T cells produce cytokines (hormone like proteins) that bind to the target cells. There are many kinds, one of which is interferon which limit viral replication.
  175. 175. • The latest treatment is 6-12 mo of combination therapy using a-2b interferon plus ribavirin • The cure rate varies around 40% with no HCV detectable 6 mo after cessation of treatment • Do not use if the patient is depressed or on alcohol (must be off ETOH x 6 mo) Hepatitis C treatment (cont)
  176. 176. • Recommendations: – Treatment is worth considering on selective basis on some patients with mild liver disease – Patients with geno type 2 or 3; treatment is stopped at 6 mo. Cure rate 50-70% to 90% – Patients with geno type 1 is less responsive with overall cure rate of 27% Hepatitis C
  177. 177. • Toxicity: – Ribavirin can cause hemolytic anemia – Interferon causes depression
  178. 178. • Requires HBV for its replication • Incubation 4-6 weeks • Can accelerate chronic hepatitis B to cirrhosis • Anti-HDV become positive in 12-15 weeks • Hepatitis B vaccine is preventative • Treatment poor. Interferon can be tried **Must have B to get D** Hepatitis D
  179. 179. • Found mostly in India, Asia, Mexico, Africa • Usually water borne (fEcal- oral) • Incubation 2-9 weeks • All cases in US have been imported by immigrants • HEV antibodies found in blood Hepatitis E
  180. 180. Comparative Features of the Common Forms of Viral Hepatitis Hepatitis A Hepatitis B Hepatitis C Genome RNA DNA RNA Incubation period 3-6 weeks 6 weeks to 6 months 7-8 weeks Transmission Oral Parenteral Parenteral Blood No Yes Yes Feces Yes No No
  181. 181. Hepatitis A Hepatitis B Hepatitis C Vertical No Yes ? Fulminant hepatic necrosis Very rare Yes Yes Chronic hepatitis No 10% 50% Carrier state No Yes Yes Liver cancer No Yes Yes
  182. 182. Characteristics of Common Causative Agents of Acute Viral Hepatitis Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Hepatitis G Causative agent 27-nm RDA virus 42-nm DNA virus; core and surgace components Flavivirus- like RNA agent 36-nm hybrid particle with HBsAg coat 27-34 nm non enveloped RNA virus Single strand RNA virus Trans mission Fecal-oral; waterborne or foodborne Parenteral inoculation or equivalent; direct contact Similar to HBV Similar to HBV Similar to HAV Parenteral
  183. 183. Hepatiti s A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Hepatitis G Incubation period 2-6 wk 4 wk-6 mo 5-10 wk Similar to HBV 2-9 wk 2-4 wk Period of infectivity 2-3 wk in late incubation and early clinical phase During HBsAg positivity (occasionally only with anti-HBc positivity) During anti- HCV positivity During HDV RNA or anti HDV positivity Similar to HCV Unknown Massive hepatic necrosis Rare Uncommon Uncommon Yes Yes Unclear
  184. 184. Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Hepatitis G Carrier state No Yes Yes Yes No Unknown Chronic hepatitis No Yes Yes Yes No Possible; viremia per- sistent but hepatitis uncertain
  185. 185. Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Hepatitis G Prophylaxis Hygiene, immune serum globulin, vaccine Hygiene, hepatitis B immune globulin, vaccine Hygiene Hydiene, HBV vaccine Hygiene, sanitation Hygiene
  186. 186. Agent Marker Definition Significance Hepatitis A virus (HAV) Anti-HAV IgM type IgG type Antibody to HAV Current or recent infection or convalescence Current or previous infection; conferring immunity Hepatitis B virus (HBV) HBsAg HBeAg HBV surface antigen e antigen; a component of the HBV core Positive in most cases of acute or chronic infection Transiently positive in acute hepatitis B May persist in chronic infection Reflection of presence of viral replication, whole Dane particles in serum, and high infectivity
  187. 187. Agent Marker Definition Significance Anti-HBe Antibody to e antigen Transiently positive in convalescence Possibly persistently present in chronic cases Usually a reflection of low infectivity Anti-HBc (IgM or IgG) Antibody to HBV core antigen Positive in all acute and chronic cases Reliable marker of infection, past or current IgM anti-HBc a reflection of active viral replication Not protective
  188. 188. Agent Marker Definition Significance Anti-HBs Antibody to HBV surface antigen Positive in late convalescence in most acute cases Conferring immunity Hepatitis C virus (HCV) Anti-HCV Antibodies to a group of recombinant HCV peptides (C22-3, C200) Positive on average 15 wk after exposure; not protective Persistent in chronic infection Hepatitis D virus (HDV) Anti-HDV (IgM or IgG) Antibody to HDV antigen Acute or chronic infection; not protective
  189. 189. • An acute or chronic illness involving the liver with necrosis, inflammation & scarring • 95% develop a fatty liver which is a reversible process • Encephalopathy & death 20% • 30% go on to cirrhosis within 6 mo • 50% of those abstaining for 6 mo recover completely Alcoholic Hepatitis
  190. 190. • Most patients are symptomatic. The most common complaints are: – Anorexia, nausea, vomiting – Abdominal pain (RUQ) – Fever (due to infection or inflammation of liver) – Weight loss due to anorexia – Jaundice is usually mild – Diarrhea which is due to portal hypertension Alcoholic Hepatitis Symptoms
  191. 191. • Jaundice • Spider angiomas • Palmar erythema • Clubbing of fingers • Gynecomastia • Hepatomegaly Alcoholic Hepatitis Physical Findings
  192. 192. • Splenomegaly • Pruritis • Ascites • Edema • Caput medusa • Testicle atrophy • Dark urine, light stool
  193. 193. • Hepatic insufficiency: which is responsible for the following: – Coma – Jaundice – Ascites – Anemia – Hemorrhagic tendency – Ankle edema Alcoholic Hepatitis Damage to liver causes
  194. 194. • Hyperestrinism: which is responsible for: – Spider nevi – Alopecia – Gynecomastia – Palmar erythema – Testicle atrophy Alcoholic Hepatitis Damage to liver causes
  195. 195. • Portal Hypertension: causes the following: – Esophageal varices – Splenomegaly – Caput medusa – Ascites Alcoholic Hepatitis Damage to the Portal System
  196. 196. • Hypersplenism: causes the following: – Anemia – Leukopenia – Thrombocytopenia Alcoholic Hepatitis Damage to the Portal System
  197. 197. • A. Laboratory Test: – The SGOT (AST) 2-10x’s normal – SGPT (ALT) is less elevated – Bilirubin mild to moderate – Alk phos is usually 2-3x’s normal Alcoholic Hepatitis Diagnostic Studies
  198. 198. – Globulins elevated with reverse A/G ratio – Prothrombin time elevated (poor prognosis) – Leukocytosis – Blood NH3 (Ammonia) level
  199. 199. • B. Ultrasound • C. Liver Biopsy – To be done early, but not to be done if PT/PTT are elevated – Microscopic exam confirms the diagnosis Alcoholic Hepatitis Diagnostic Studies
  200. 200. – Findings of biopsy • Hepatocellular necrosis • Inflammatory exudates • Fibrosis • Fatty infiltration • Cholestasis • Hemosiderosis (iron accumulation in the lungs)
  201. 201. • 1. Mortality of 10-15% • 2. Worsening of symptoms in early recovery program • 3. Complication: Varices gastritis Peptic ulcer coagulopathy Kidney infection lung infection Peritonitis Acute Hepatitis Course
  202. 202. • 4. Seizures with withdrawal – Use of benzodiazepines are helpful – Can also cause encephalopathy
  203. 203. • 5. Hepato-renal syndrome – Development of Acute Renal Failure – Renal functions are excluded – There is an intense intra-renal vasoconstriction and distribution of blood flow, causing oliguria
  204. 204. • A. Supportive therapy with bed rest – Stop the BOOZE • B. Diet – Multiple vitamins: folic acid & thiamine • Magnesium, calcium, phosphate, & glucose are carefully monitored – 2500 calories at least. • Low protein if encephalopathy is present. • Vegetable protein & milk are acceptable. Acute hepatitis Therapy
  205. 205. • C. Benzodiazepines if – Alcohol withdrawal • Seizures- delerium tremons • Encephalopathy may occur • D. Steroids: – Used with encephalopathy – Minimal value in less severely ill patients Acute Hepatitis Therapy (cont)
  206. 206. • Wernicke Encephalopathy • Ophthalmoplegia • Ataxia • Nystagmus Acute Hepatitis Nutritional Complications
  207. 207. • Korsakoff Syndrome • Loss of new memory • Disorientation to time & place • Confabulation **Treatment: large doses of thiamine Hcl
  208. 208. • 1. Pathology: – hepatocellular necrosis similar to virus (cholestatic reaction) • 2. Diagnosis: – usually established by history of drug use • 3. Lab: – similar to viral disease Drug Related Hepatitis
  209. 209. • 4. Cholestatic reaction: – impairment of bile secretion by hepatocytes (BC pills) • 5. Hepatocellular reaction: – very similar to viral hepatitis (acetominophen, isoniazid, methyldopa)
  210. 210. Drug Related Hepatitis • 6. Symptoms: – Arthralgias – Fever – Rash – Eosinophilia • Treatment: – Removal of offending agent
  211. 211. Classification of Drug-Induced Liver Disease Category Examples Predictable hepatotoxins with zonal necrosis Acetaminophen Carbon tetrachloride Nonspecific hepatitis Aspirin Oxacillin Herbs (chaparral, germander) Viral hepatitis-like Reactions Halothane Isoniazid Phenytoin Cholestasis Estrogens Noninflammatory 17 α-Substituted steroids Chlorpromazine Antithyroid agents
  212. 212. Category Examples Fatty liver Large droplet Ethanol Corticosteroids Small droplet Amiodarone Allopurinol Chronic hepatitis Methyldopa Nitrofurantion Tumors Estrogens Vinyl chloride Vascular lesions 6-Thioguanine Anabolic steroids Herbs (senna, comfrey) Methotrexate Fibrosis Methotrexate Granulomas Allopurinol Sulfonamides
  213. 213. Chronic Hepatitis
  214. 214. • Refers to inflammation, necrosis & fibrosis for at least 6 months. • Varying from benign process to death. • Groups: – Viral – Autoimmune Chronic Hepatitis
  215. 215. – Alcoholic – Primary biliary cirrhosis – Drug induced liver disease – Wilson’s disease – Anti-trypsin deficiency – Hemochromatosis – Sclerosing cholangitis
  216. 216. • Viral • Hepatitis B • Hepatitis B with superimposed hepatitis D • Hepatitis C • Drugs and Toxins • Methyldopa • Nitrofurantoin Causes of Chronic Hepatitis
  217. 217. • Amiodarone • Isoniazid • Autoimmune • Genetic and Metabolic Disorders • Wilson’s disease • α1- Antitrypsin deficiency • Nonalcoholic steatohepatitis
  218. 218. • Forms: –A. Chronic Active Hepatitis: • Refers to the form of CH were the liver test & histology are compatible with active & progressive inflammation & necrosis Chronic Hepatitis
  219. 219. –B. Chronic Persistent Hepatitis: • Refers to the mild & histological non progressive CH where the inflammation is confirmed only to the portal tracts. The enzymes are normal or only moderately elevated.
  220. 220. • Mainly a disease of young women • Most have hypergamaglobulinemia & ANA positive Chronic Hepatitis Autoimmune Hepatitis
  221. 221. • Patients have multisystem disease which include: Arthritis kidney involvement Colitis heart Thyroiditis portal hypertension Pulmonary fibrosis
  222. 222. • Diagnosis: – Consider any young female with elevated liver function studies without course with hepatitis for greater than 6 months – Positive ANA – Elevated GG =means chronic – Liver biopsy showing chronic inflammation Chronic Hepatitis Autoimmune Hepatitis
  223. 223. • Treatment: –Steroids • Decrease in symptoms –Prognosis: is good. About 50% live more than 15 years from the time of diagnosis
  224. 224. • Inherited Chronic Liver Disorders – A. Wilson’s disease – B. Hemachromatosis – C. Alpha 1-antitrypsin deficiency – D. Reye syndrome Other causes of Chronic Hepatitis
  225. 225. • Pathogenesis: – a rare treatable genetic disorder of copper metabolism. – There is an abnormal accumulation of copper in the hepatocytes. – This is a metabolic disorder affecting basal ganglia, eyes, & kidney. Wilson’s Disease
  226. 226. – The defect is in the ceruloplasm which carries the copper. – The serum ceruloplasm & copper are both low (copper low b/c it can’t be carried)
  227. 227. • Diagnosis: – Made by seeing neurological, psychiatric, hepatitis, cirrhosis in a young person. – Liver disease with the Kayser-Fleischer ring in the eyes in the young is characteristic Wilson’s disease (cont)
  228. 228. Kayser – Fleischer Ring
  229. 229. • Pathogenisis: A group of disorders with excessive absorption of iron. • The iron is layed down in liver, heart, pancrease, kidney, & skin (bronze diabetes) – Primary cause unknown Haemochromatosis
  230. 230. – Secondary- Iron overload : • anemias • cirrhosis • Dietary – Diagnosis: • Lethargy, weakness in men 40-60 yo • Skin hyperpigmentation • Diabetes 30-60% of pt’s • arthopathy
  231. 231. • In children associated liver disease • In teenagers & adults, a progressive liver disease with pulmonary manifestations • Pathogenesis: Alpha 1-trypsin is a potent protease inhibitor found in the serum, body fluids, & tissues Alpha 1-Antitrypsin Deficiency
  232. 232. • It is synthesized by the liver to protect from tissue injury resulting from protease like trypsin
  233. 233. • An illness seen in the pediatric age group associated with the flu • Symptoms: Nausea, vomiting, hyperactivity, confusion, seizures, & coma, Increasing drowsiness, Belly Pains Reye’s Syndrome
  234. 234. • On liver biopsy there are fatty infiltration • Chemistry: elevated liver enzymes, NH3 ***NEVER give Aspirin to children with varicella infection (chicken pox), or during flu sx.***
  235. 235. • only happens in kids less than 15 years old. • The cause is unknown, but it is strongly associated with Aspirin use during flu's. • The liver becomes inflamed and destroyed for unknown reasons. REYE'S SYNDROME
  236. 236. • It is important because Reye's syndrome kills about half of kids who get it. • NEVER give aspirin containing medications to your kids under 15 years old for fever control. • Use Acetaminophen/ Ibuprofen instead.
  237. 237. • May result from: – A. Slow deterioration as part of a chronic progress – B. Rapid worsening after repeated injuries – C. catastrophic event such as massive necrosis Hepatic (Liver) Failure
  238. 238. • Causes: – 1. Functional liver failure without overt necrosis • Reye’s syndrome, tetracycline toxicity – 2. Chronic liver disease • Chronic active hepatitis • Cirrhosis
  239. 239. – 3. Fulminate failure: refers to acute severe impairment of liver function with encephalopathy & coma in patients who have had liver disease for less than 8 weeks
  240. 240. Management of Selected Problems in Fulminant Hepatic Failure Complications Pathogenesis Management Hepatic encephalopathy Liver failure Search for treatable causes, i.e., hypoglycemia, drugs used for sedation, sepsis, gastrointestinal bleeding, electrolyte imbalance, decreased PO2, increased PCO2 ; lactulose Cerebral edema Unknown Elevate head of bed 20-30 degrees; hyperventilate (PCO2 25-30 mm Hg); mannitol, 0.5-1 g/kg IV bolus over 5 min; pentobarbital infusion; urgent liver transplantation
  241. 241. Complications Pathogenesis Management Coagulopathy and gastrointestinal hemorrhage Decreased synthesis of clotting factors Gastric erosions Vitamin K; fresh-frozen plasma if actively bleeding and for prevention of bleeding; IV H2- antagonist prophylaxis Hypoglycemia ↓ Gluconeogenesis Insulin degradation IV 10% dextrose, monitor every 2 hours; 30%-50% dextrose may be needed Agitation May be due to: Encephalopathy ↑ Intracranial pressure Hypoxemia Search for treatable causes (i.e., ↓ PO2, skin ulcersl lacerations, or abscesses); soft restrains; if severely agitated and a concern of injury, consider sedation along with mechanical ventilation to protect airway
  242. 242. • Clinical features: – Jaundice – Hypoalbuminemia – Hyperestrogenism which causes • Testicular atrophy • Gynecomastia • Palmar erythema • Spider angiomas Hepatic Failure (cont)
  243. 243. – Hepatorenal Syndrome – Fetor odor – Coagulopathy
  244. 244. • CLAPS: Clubbing Leukonychia Asterixis Palmar erythema Scratch marks Liver failure (chronic): signs of found on the arms Mneumonic
  245. 245. Complications of hepatic failure
  246. 246. • Hepatic encephalopathy: – A metabolic disorder of the CNS system & neuromuscular system with slight changes in the brain (edema) Hepatic Failure (cont)
  247. 247. – Clinical Features: • Confusion • Flapping tremor (asterixis) • Drowsiness • Coma death Caused by elevated levels of NH3 (ammonia)
  248. 248. • HEPATICS: Hemorrhage in GIT/ Hyperkalemia Excess protein in diet Paracentesis Acidosis/ Anemia Trauma Infection Colon surgery Sedatives Hepatic encephalopathy: precipitating factors Mneumonic
  249. 249. • Treatment: – Remove precipitating causes (drugs/ETOH) – Decrease enteric toxins (BUN-NH3) – Gut enema – Low protein diet – Neomycin 1-2 gms Q 2 hrs PO Hepatic failure (cont). Hepatic Encephalopathy
  250. 250. –Lactulose 50 ml orally Q 2hrs until diarrhea ensues. Then reduce dosage until there are two stools per day – Transplantation: • Any young patient with progressive disease • Metabolic disease: wilson’s, alpha antitrypsin def.
  251. 251. • Etiology: triad – 1. necrosis – 2. regenerating nodules – 3. fibrosis • Categories: – Major • Alcoholic (#1 cause in western world) • Post necrotic Cirrhosis
  252. 252. –Minor • Wilson’s disease • Haemochromatosis • Biliary • Chronic hepatic congestion
  253. 253. –Budd-Chiari syndrome »uncommon condition induced by thrombotic or nonthrombotic obstruction to hepatic venous outflow –Cardiac »Right sided heart failure »Tricuspid insufficiency
  254. 254. • HEPATIC: Hemochromatosis (primary) Enzyme deficiency (alpha-1-anti-trypsin) Post hepatic (infection + drug induced) Alcoholic Tyrosinosis Indian childhood (galactosemia) Cardiac/ Cholestatic (biliary)/ Cancer/ Copper (Wilson's) Causes of hepatic cirrhosis Mneumonic
  255. 255. • Common causes are ABC: Alcohol B (Hepatitis) C (Hepatitis) Cirrhosis: differential: common and rarer Mnoumonic
  256. 256. • · Rarer are also ABC: Autoimmune Biliary cirrhosis Copper (Wilson's)
  257. 257. Cirrhosis
  258. 258. Cirrhosis resulting from chronic viral hepatitis
  259. 259. Budd-Chiari syndrome. Therombosis of the major hepatic veins has caused extreme blood retention in the liver.
  260. 260. • Biliary Cirrhosis: – One of the more common causes of nonalcoholic liver disease – Pathology is destruction of the intrahepatic bile ducts – 90% are found in middle age females – Most common symptoms are fatigue & pruritis – Antimitochondrial antibodies (90%) • Order after all hepatitis profile excluded Cirrhosis (cont)
  261. 261. • Complications of cirrhosis: – Spontaneous bacterial peritonitis (SBP) which occurs in 10% of alcoholic cirrhosis (E. coli) Cirrhosis (cont)
  262. 262. –Ascites: • Refers to the accumulation of excessive volumes of fluid within the peritoneal cavity • Always a poor prognostic sign • Ultrasound & CT scans are best method of detection of small amounts of fluid. Flat plate has ground glass look.
  263. 263. • Ascites (cont) – Diagnosis of ascites: • Bulging flanks • Umbilical hernia • Shifting dullness • Scrotal edema • Right sided pleural effusion Cirrhosis (cont)
  264. 264. –Paracentesis: • 50cc of fluid removed, look at color • CBC, WBC, protein, LDH, glucose, amylase, albumin • Gram stain, AFB, fungus cultures, cytology
  265. 265. Clinical and Laboratory Features of Cirrhosis Clinical Laboratory Hepatocellular Dysfunction Jaundice Hyperbilirubinemia Spider angiomas Edema Palmar erythema Low serum blood urea nitrogen Gynecomastia Prolonged prothrombin time Loss of body hair Hyperammonemia Testicular atrophy Thrombocytopenia Dupuytren’s contracture Leucopenia Muscle wasting ─
  266. 266. Clinical and Laboratory Features of Cirrhosis Clinical Laboratory Hypoalbuminemia Low serum albumin Bruising ─ Signs of hepatic encepha-lopathy ─ Fetor Hypertension Splenomegaly ─ Ascites ─ Caput medusae ─ Variceal bleeding ─
  267. 267. • Pathophysiology: – Alteration of hepatic blood flow causing portal hypertension. – Reduction in liver function: • Reduction in synthesis of albumin & coagulation proteins • Reduction in detoxification of bilirubin, ammonia, & drugs Ascites (cont)
  268. 268. Ascites
  269. 269. • Complications of ascites: Dyspnea vomiting Decreased cardiac output hydrothorax Anorexia scrotal edema Reflux esophagitis Ascites (cont)
  270. 270. • Treatment: – Improve hepatic function – Restrict sodium & fluid intake – Aldactone which inhibits aldosterone – Paracentesis (removal of fluid with addition of IV albumin)
  271. 271. –Shunts –Abstain from alcohol –Diuretics • Aldactone • Lasix
  272. 272. • Treatment (cont): – Supportive • Nutrition high calories, low protein with encephalopathy • Minerals & vitamins • Sodium restriction • Copper restriction if wilson’s disease Ascites treatment (cont)
  273. 273. – Neomycin & Lactulose if NH3 elevated – Liver Transplants
  274. 274. • Classification: – Portal vein (prehepatic) – Intrahepatic (sinusoids) – Hepatic (posthepatic) (Budd Chiari- usually due to tumor) Portal Hypertension
  275. 275. • Findings: – Ascites – Varices • Gastric, esophageal, hemorrhoids • Caput medusa – Encephalopathy – Splenomegaly which causes: • Sequestration & destruction of RBC’s • Neutropenia • thrombocytopenia
  276. 276. Presinusoidal Portal or splenic vein occlusion (thrombosis, tumor) Schistosomiasis Congenital hepatic fibrosis Causes of Portal Hypertension
  277. 277. Sarcoidosis Sinusoidal Cirrhosis (all causes) Alcoholic hepatitis Postsinusoidal Veno-occlusive disease Budd-Chiari syndrome Constrictive pericarditis
  278. 278. Increased portal blood flow Splenomegaly not due to liver disease Arterioportal fistula
  279. 279. • Diagnosis: – Barium swallow for varices of esophagus – Angiography – Endoscopy Portal Hypertension (cont)
  280. 280. • Treatment: – Transfusion of platelets – Vasopressin decrease splanchnic blood flow – Balloon tamponade – Endoscopic sclerotherapy – Portal shunts
  281. 281. Manifestations of Portal Cirrhosis Primary Alteration in Function Manifestation Hepatocellular Dysfunction Impaired metabolism of sex hormones Female: menstrual disorders Male: testicular atrophy, gynecomastia, decrease in secondary sex characteristicsSkin disorders: vascular spiders and palmar erythema Impaired synthesis of plasma proteins Decreased levels of serum albumin with development of edema and ascites Decreased synthesis of carrier proteins for hormones and drugs
  282. 282. Decreased synthesis of blood- clotting factors Bleeding tendencies Failure to remove and conjugate bilirubin from the blood Jaundice Impaired bile synthesis Malabsorption of fats and fat- soluble vitamins Impaired metabolism of drugs cleared by the liver Risk of drug reactions and toxicities Impaired gluconeogenesis Abnormal glucose tolerance Decreased ability to convert ammonia to urea Elevated blood ammonia levels, encephalopathy
  283. 283. • Signs of liver disease & causes – Jaundice- diminished bilirubin secretion – Fetor hepaticus- sulfur compounds produced by intestinal bacteria, not cleared by liver Liver Review
  284. 284. – Spider angiomas, palmar erythema, & gynecomastia- elevated estrogen levels – Ecchymoses- decreased synthesis of clotting factors – Xanthomas- elevated cholesterol levels
  285. 285. • Hypoglycemia- decreased glycogen stores • Hypersplenism- portal hypertension • Encephalopathy, asterixis- portosystemic shunt, NH3 Liver Review
  286. 286. • Hepatorenal syndrome (rapid decline of GFR)- renal failure of unknown pathogenesis, kidneys are normal (may be transplanted), assoc c ascites, almost always fatal
  287. 287. • Liver cell damage= AST, ALT • Bile duct obstruction= alk phos • Cholestasis= bilirubin • Hep A: IgG antibodies= previous exposure IgM antibodies= recent infection Liver review
  288. 288. • Hep B: HBsAg-acute or chronic inf. (used for blood bank screening HBeAg- high degree of infectivity Anti-HBc- earliest indicator of acute infection Anti-HBe- resolution of acute infection Anti-HBs- indicates immunity (post infection or vaccine)
  289. 289. • The liver is the largest internal organ • The liver has a right lobe and a left lobe. • The liver holds about 13 percent of the body's blood supply at any given moment. • The liver is visible on plain abdominal film • Ultrasound exam of the liver shows size and consistency • The liver has the ability to regenerate Liver Jeopardy Facts

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