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Which of the following proteins is primarily synthesized by the liver? A.Insulin B.Hemoglobin C.Albumin D.Immunoglobulins ANSWERV ¥V C.Albumin Which of the following statements correctly describes the blood supply to the liver? A.The hepatic artery provides most of the liver's blood supply. B.The hepatic portal vein provides most of the liver's blood supply. C.AII of the blood supply to the liver comes from the hepatic artery. D.The hepatic artery and the hepatic portal vein each provide 50% of the liver's blood supply. ANSWERV ¥ B.The hepatic portal vein provides most of the liver's blood supply. Which of the following substances is primarily detoxified by the liver? A.Bilirubin B.Creatinine C.Ammonia D.Lactate ANSWERY V¥ C.Ammonia Blood Supply of Liver — 2 sourees ANSWERV ¥ Hepatic artery ¢500ml//min of oxygenated blood. 30% of liver's blood supply Hepatic portal vein ©1000ml/min of partly oxygenated blood °70% of liver's blood supply. plus rich supply of nutricnts, toxins, drugs from stomach, small and large intestines, pancreas and spleen Portal venous system -- define ANS WERY V¥ refers to a system of veins that come from the stomach, bowel, spleen and pancreas to the portal vein portal vein then breaks off into smaller blood vessels and travels through the liver 6 Main Functions of the Liver ANSWERV V 1. Blood filtration & detoxification Na . Metabolism (carbohydrate, lipid and protein) 3. Bile production » . Storage (vitamin, minerals, glycogen) wn . Synthesis (hormones, proteins) 6. Immune function Antigen-antibody complex initiates the immune response & activates the complement system Acute phase of Hepatitis (11 symptoms) ANS WER¥ ¥ can be symptomatic - anorexia - nausea - vomiting - malaise - fatigue - headache - low-grade fever - arthralgias - skin rash - RUQ discomfort - change to sense of taste Acute phase of Hepatitis -- possible physical exam findings (3) ANSWERV v 1. Hepatomegaly (RUQ) 2. lymphadenopathy 3. Jaundice Tcteric = present Anicteric or non-icteric = no jaundice Acute vs Chronic Hepatitis (16 acute, 8 chronic) ANSWERV V Acute - altered taste/smell - anorexia - arthralgia - dark urine - fatigue - low fever - headache - hepatomegaly - jaundice - clay colored stool - malaise ~ nausea/vomit - pruritis - RUQ tender - splenomegaly - weight loss Chronic 1. fatigue 2. hepatomegaly 3. malaise 4, myalgia (*) and arthralgia 3. Dark amber urine -- bilirubin is being excreted by the kidneys 4. Clay-coloured or white stool that is floating -- lack of bilirubin in stool, high fat content of stool Liver enzymes -- 2 for damage to liver cells ANS WERY V 1. aspartate aminotransferase (AST) -- found in other tissues 2. alanine aminotrans[crase (ALT) -- MOST SPECIFIC for liver damage Liver enzymes -- 2 for damage to bile ducts ANSWERV V 1. alkaline phosphatase (ALP) - - liver but also bone, ducts, kidneys, intestines, placenta 2. gamma-glutamyl transpeptidase (GGT) -- liver, bile ducts, and other organs **marker for alcohol use disorder 3 Measures of liver function ANS WERV V 1. Albumin -- will be low 2. Bilirubin -- will be high 3. Prothrombin time or INR -- will be prolonged Hepatitis A (cause, severity, route, symptoms) ANSWER¥ V Cause: Hepatitis A virus (HAV) Typically acute, self-limiting Route: oral-fecal route Most infectious during 2 weeks before symptoms develop - acute symps in adults NOT kids Hepatitis A -- viral serological tests (2) ANSWERV ¥ 1. Anti-HAV IgM = acute hepatitis 2. Anti-HAV IgG = past infection, or vaccination Ilepatitis A -- treatment, prevention ANS WERV V No specific treatment Management is focused on relief of symptoms Recovery gives lifelong immunity Vaccine is available (e.g. Havrix) Hepatitis B (cause, route, symptoms) ANS WERV V Cause: Hepatitis B virus (HBV) Main medication used -- nucleoside analogues (oral antivirals) Tlepatitis B pharmacotherapy -- Nucleoside analogues (work by, rare AE, 2 types and their notes) ANSWER¥V ¥ work by -- inhibiting viral DNA replication Rare AE of severe hepatomegaly & lactic acidosis Tenofovir = nephrotoxicity Entecavir = contraindicated in pregnancy Hepatitis B vaccine options (3 total, what do they contain?, given when) ANSWERV / Hep B ONLY -- Energix-B, Recombivax Hep A & B -- Twinrix Vaccines contains hepatitis B surface antigen (HBsAg) Usually given 3 doses: at 0, 1 and 6 months Hepatitis C (cause, route, symptoms) ANSWER V Cause: Hepatitis C virus (HCV) Route: exposure to blood or blood products (parenteral or mucosal), sexual contact, perinatal transmission (like hepatitis B) Infectious 1-2 weeks before symptoms appear, and can be asymptomatic Hepatitis C -- viral serological tests (2) & how many genotypes ANSWERV V Anti-HCV = past or current infection HCV RNA = viral load confirming active disease 6 different genotypes Hepatitis C -- pharmacotherapy (goal, recommended, indicated for) ANS WERV V Goal = to cure HCV infection 50% of acute ppl will clear spontaneously but early treatment recommended to prevent complications Indicated for -- people with acute and chronic IICV infection Hepatitis C -- pharmacotherapy (what drug used, 4 categories) ANS WERV V Direct-acting antiviral agents (DAAs) 4 Categories 1. Protease inhibitors 2. NSSA inhibitors 3. NSSB nucleoside polymerase inhibitors (NPIs) Common AE of all Direct-acting antiviral agents (DAAs) ANSWERV V headache & fatigue Direct-acting antiviral agents (DAAs) -- used in to ___, how long is course, what need to do at the end ANSWERV V¥ these are used in combination to decrease developing viral resistance 12-week course of therapy Need to check response to agents by checking HCV RNA (viral load) at 12 weeks after the end of therapy What may be used with DAAs for Iepatitis C? (5 side effects, 2 AE) ANSWERV 4 Ribavirin may be used with DAAs eCommon side effects include anemia, fatigue, headache, nausea, insomnia eAE include hemolytic anemia, teratogenic effects Hepatitis D (cause, route, treatment) ANS WERV V Cause: Hepatitis D virus (HDV) **Hepatitis D can only cause infection if hepatitis B is present** Route: same as hepatitis B Treatment - acute is supportive - chronic may necd treatment with pegylated interferon alpha Tlepatitis D -- symptoms (main, 7 other) ANS WERV ¥ °Flu-like symptoms occur in up to 90% of patients other side effects include fatigue. anorexia, nausea, diarrhea, weight loss, hair loss, bone marrow suppression Hepatitis E (cause, severity, route, associated with, treatment) ANSWERV V Cause: Hepatitis E virus (HEV) - disease usually mild and self-limiting Route: oral-fecal Zoonotic: may be transmitted from animals to humans Outbreaks typically associated with contaminated water supply Treatment is supportive, chronic is ribavirin (in immunocompromised pts) Which of the following clinical manifestations is most characteristic of chronic hepatitis? A.Dark urine B.Jaundice Results in an overgrowth of new, fibrous connective tissue which distorts the normal structure of the liver's lobules Causes of cirthosis (3) ANSWERV ¥ final state of liver discase 1. Chronic viral hepatitis -- Hepatitis B and C 2. Excessive Alcohol use — direct, hepatoxic effect that causes cell necrosis & fatty infiltration in the liver 3. Non-alcoholic fatty liver disease -- too much fat being stored in liver cells Pathophysiology of Cirthosis (6 steps) ANSWERV V 1 - Ischemia & ncerosis of hepatocytes 2 - Replacement of healthy cells with fibrous (scar) tissuc 3 - Fibrous tissue form nodules in liver «(liver appears lumpy) 4 - Growth of fibrosis leads to impaired blood flow 5 - Cells lack nutrition, Hypoxia in liver, Irregular cell growth 6 - Decreased functioning of liver Clinical manifestiations of Cirrhosis -- Compensated (3) ANS WERY V Liver is still able to function normally Often is undetected May have abdominal pain, non-specific signs & symptoms Clinical manifestiations of Cirrhosis -- Decompensated (3) ANS WERV V Liver is not functioning normally Illustrated by tests of liver function: albumin (Low), bilirubin (high), INR (high) Clinical signs & symptoms of liver disease Endocrine disturbance with Cirrhosis (estrogen) ANS WER¥ ¥ accumulate estrogen causing.. - gynecomastia (in males) - palmar erythema - spider angiomas - amenorrhea in younger women - vaginal bleeding in older women eHepatic encephalopathy e[Jepatorenal syndrome What is the most common varices formed duc to portal hypertension? ANSWERV 4 esophageal varices Esophageal & Gastric varices -- what, they can, may see (2), severity ANS WERV 4 varices are enlarged veins they can rupture and bleed may see - hematemesis - melena stool EMERGENCY Management of Varices -- avoid, meds to use for bleeding & hov ANSWERV J/ Avoidance of irritants: ASA, NSAIDs Non-selective beta-blocker agents --> used to prevent bleeding, such as propranolol Reduces portal venous pressure by decreasing the cardiac output Management of Varices -- treatment (initial, 2 meds) ANS WERV V Initial management: hemodynamic stabilization Medications: octreotide or vasopressin - used to reduce blood flow *Octreotide used more often, fewer adverse effects Management of Varices -- treatment (endoscopy, 3 types) ANSWERV V Sclerotherapy -- done with endoscopy injecting solution to cause clotting in varices Variceal ligation -- use of elastic bands to tie off the vessels that are bleeding Compression of the varices with an inflatable tube or balloon -- balloon tamponade Management of Varices -- treatment (shunting procedure) ANS WERY V Interventional radiology to create a shunt from the portal vein to the inferior vena cava (done as last step) called a transjugular intrahepatic portosystemic shunt (TIPS) What is connected in a transjugular intrahepatic portosystemic shunt (TIPS)? ANSWERV ¥ portal vein to a branch of the hepatic vein 
