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95 Cards in this Set
- Front
- Back
What is another name for vasopressin?
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Antidiuretic hormone
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What is the first step to the pathophysiology in cirrhosis?
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Injury to hepatocellular elements (alcohol, infection, etc)
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What is the second step to the pathophysiology in cirrhosis?
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Inflammatory response with cytokine release
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What is the third step in the pathophysiology in cirrhosis?
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Fat storing cells in the liver, or stellate cells, begin to resemble fibroblasts and actively engage in extracellular matrix production depositing fibrous material within the sinusoids disrupting the normal blood flow through the hepatic lobule.
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What is the fourth step in the pathophysiology in cirrhosis?
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Destruction of hepatocytes, bile duct cells, vascular endothelial cells
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What is the normal function of hepatic stellate cells?
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Storage of retinoids like vitamin A
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Where do hepatic stellate cells normally reside?
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In the sinusoidal space (special blood vessel)
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What does cirrhosis of the liver do to the flow of nutrients and vascular blood flow?
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Prevents the normal flow of nutrients to hepatocytes and increase vascular resistance
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Is fibrosis of the liver in cirrhosis reversible?
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yes, if inciting events are removed during the initial stage of injury
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What occurs with the progressive deposition of fibrous material within the sinusoids during cirrhosis of the liver?
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Disruption occurs with the normal blood flow leading to elevations in porktal blood pressure or portal hypertension
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What are the common etiologies of hepatic cirrhosis?
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Alcohol, biliary obstruction (biliary atresia / neonatal hepatitis, congenital biliary cysts, cystic fibrosis), primary or secondary biliary cirrhosis, chronic hepatitis B or C, hemochromatosis, NAFLD (usually secondary to obesity, also can occur after jejunoileal bypass)
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What are the drug and toxin induced causes of hepatic cirrhosis?
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Methyldopa, amiodarone, INH, MTX, Vitamin A
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What are the immune-mediated induced causes of hepatic cirrhosis?
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Autoimmune chronic hepatitis
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What are the genetic metabolic disease induced causes of hepatic cirrhosis?
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alpha1-antitrypsin deficiency, amino acid disorders, bile acid disorders, lipid disorders, Porphyria (A rare hereditary disease in which the blood pigment hemoglobin is abnormally metabolized)
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What are the infectious causes of hepatic cirrhosis?
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Brucellosis, Congenital or tertiary syphyllis, Schistosomiasis
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What are the vascular abnormalities that cause hepatic cirrhosis?
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Rt-sided heart failure, pericarditis
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What are the idiopathic causes of hepatic cirrhosis?
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Sarcoidosis, Idipathic portal fibrosis
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What are the important epidemiologic notes about cirrhosis?
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Affects 3.6/1k persons in the US, 12th leading cause of death in US in 2000 (>27k deaths annually), 4th leading cause of death among 45-54 year olds; american indian, alaskan native and hispanic populations more affected than others
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What are the clinical presentations of early and well-compensated cirrhosis?
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anorexia, weight loss, weakness/fatigue, osteoporosis (Vit D deficiency)
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What are the clinical presentations of decompensated cirrhosis?
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ascites, SBP (spontaneous bacterial peritonitis), hepatic encephalopathy, variceal bleeding, jaundice of eyes or skin, pruritis, coagulaopathy
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What are the physical findings of cirrhotic patients in relation to the effects of portal hypertension?
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Esophageal varices (lead to melena and hematemesis), splenomegaly, dilated abdominal viens (caput medusae), ascites, rectal varies (hemorrhoids)
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What are the physical findings of cirrhotic patients in relation to the effects of liver cell failure?
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Coma, fetor hepaticus (death breath), spider nevi, gynecomastia, jaundice, ascites, loss of sexual hair, testicular atrophy, liver 'flap' (coarse hand tremor), bleeding tendency (decreased PT), anemia macrocytic iron deficiency (blood loss), ankle edema
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What is another term for coarse hand flap associated with liver cirrhosis?
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Asterixis
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What causes fector hepaticus?
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increase in dimethylsulfide concentrations
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What physical findings in liver cirrhosis are related to altered sex hormone metabolism?
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Spider angiomata, gyneocomastia, testicular atrophy
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What are the labs typically done for liver cirrhosis?
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Liver panel (ALT, AST, GGT), CBC with platelets, prothrombin time
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What is AST?
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Aspartate aminotransferase
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What is ALT?
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Alanine aminotransferase
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Do normal aminotransferases preclude rirrhosis dx?
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No
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What is the ration of AST to ALT in acute liver injury?
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2 AST : 1 ALT
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What is MELD?
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Mayo End-Stage Liver Disease or Model for End-Stage Liver Disease
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Are alkaline phosphatase and GGT (gamma-glutamyl transpeptidase) found solely in the liver?
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No
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What is the cobination of an elevation in alkaline phosphatase level with a concomitant elevation in GGT level a marker of?
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Considered to be both a sensitive and specific marker of cholestatic liver disease
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What is the significance of an increase in the level of bilirubin in liver cirrhosis?
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Elevations are common in end stage liver disease, degree of elevation has prognostic significance; can also be elevated in common bile duct obstruction, gallstones, and malignancy
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What is the significance of a decrease in Albumin?
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Levels decline as liver function declines, decrease is not specific to cirrhosis (can occur in CHF, nephrotic syndrome, malnutrition)
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Where is albumin synthesized?
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exclusively in the liver
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What is the significance of an increase in PT?
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An increase in prothrombin time reflects the degree of hepatic dysfunction
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What is the significance of a decrease in serum sodium in liver cirrhosis?
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Common in cirrhosis and ascites; related to an inability to excrete free water
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What is the significance of anemia?
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Multifactorial in origin (GI losses, direct toxicity secondary to alcohol, hypersplenism, bone marrow suppression)
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What is the significance of lowered platelets?
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Mainly caused by portal hypertension with attendant congestive splenomegaly
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What is the significance of leukopenia and neutropenia in liver cirrhosis?
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due to hypersplenism
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What is the the significance of coagulation defects in liver cirrhosis?
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most of the proteins involved in the coagulation process are produced in the liver; can also develop varying degrees of DIC, fibrinolysis, vitamin K deficiency, dysfibrinogenemia, and thromobocytopenia resulting in increased bleeding
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What is the gold standard of diagnosis of cirrhosis?
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biopsy
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What are the diagnostic imaging tests for liver cirrhosis?
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ultrasound, computed tomography, magnetic resonance imaging
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What are the advantages and uses of ultrasound in diagnosing liver cirrhosis?
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Non-invasive, well tolerated, widely available. Can be used as a screening test for hepatocellular carcinoma and portal hypertension
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What are the advantages and disadvantages of computed tomography?
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provides similar information as ultrasound but with added exposure to radiation, contrast, and cost
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Why is magnetic resonance imaging not routinely used for diagnosing liver cirrhosis?
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$$$$$
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What are the two types of liver disease scoring systems?
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Child-Pugh Classification and Model for End-Stage Liver Disease Scoring (MELD)
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What are the two type of manifestations that Child-Pugh Classification quantifies in cirrhotic process?
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laboratory and clinical manifestations
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What are the potential problems of the Child-Pugh Classification?
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the classification is subjective due to the measurements in ascites and encephalopathy
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In the Child-Pugh Scoring of liver disease, what is the score of Grade A?
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<7 points
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In the Child-Pugh Scoring of liver disease, what is the score of Grade B?
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7-9 points
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In the Child-Pugh Scoring of liver disease, what is the score of Grade C?
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10-15 points
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In the Child-Pugh Scoring of liver disease, what is the score if bilirubin is < 2 mg/dl?
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1
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In the Child-Pugh Scoring of liver disease, what is the score if bilirubin is 2-3 mg/dl?
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2
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In the Child-Pugh Scoring of liver disease, what is the score if bilirubin is > 3 mg/dl?
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3
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In the Child-Pugh Scoring of liver disease, what is the score if Albumin is > 3.5 g/dl?
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1
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In the Child-Pugh Scoring of liver disease, what is the score if Albumin is 2.8-3.5 g/dl?
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2
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In the Child-Pugh Scoring of liver disease, what is the score if Albumin is < 2.8 g/dl?
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3
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In the Child-Pugh Scoring of liver disease, what is the score if there are no ascites?
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1
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In the Child-Pugh Scoring of liver disease, what is the score if there are mild ascites?
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2
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In the Child-Pugh Scoring of liver disease, what is the score if there are moderate ascites?
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3
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In the Child-Pugh Scoring of liver disease, what is the score if there is no encephalopathy?
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1
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In the Child-Pugh Scoring of liver disease, what is the score if there is grade 1-2 encephalopathy?
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2
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In the Child-Pugh Scoring of liver disease, what is the score if there is grade 3-4 encephalopathy?
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3
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In the Child-Pugh Scoring of liver disease, what is the score if there is a PT of < 4 sec or an INR of <1.7?
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1
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In the Child-Pugh Scoring of liver disease, what is the score if there is a PT of 4-6 sec or an INR of 1.7-2.3?
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2
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In the Child-Pugh Scoring of liver disease, what is the score if there is a PT of > 6 sec or an INR of > 2.3?
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3
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What is the equation for MELD score?
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0.957 x Loge(SCr)
+ 0.378 x Loge(Bilirubin) + 1.120 x Loge(INR) + 0.643 |
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What is the estimate of 3 month mortality for a MELD score of 40 or more?
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71.3%
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What is the estimate of 3 month mortality for a MELD score of 30-39?
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52.6%
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What is the estimate of 3 month mortality for a MELD score of 20-29?
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19.6%
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What is the estimate of 3 month mortality for a MELD score of 10-19?
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6.0%
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What is the estimate of 3 month mortality for a MELD score of < 9?
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1.9%
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What is UNOS?
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United Network for Organ Sharing (evaluate the need of pt for liver based off of MELD score)
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What are the pharmacodynamic changes in liver failure?
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changes in volume of distribution, increased sensitivity (opiates, bzds, nsaids)
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What happens to Phase I metabolism in liver failure?
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Phase I metabolism (hydrolysis, oxidation, dealkylation, reduction) tends to be significantly impaired
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What happens to Phase II metabolism in liver failure?
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Phase II metabolism (conjugation) remains relatively unaffected
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How is lorazepam metabolized and does it have any active metabolites?
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metabolized by conjugation and has no active metabolite
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How is diazepam metabolized and does it have any active metabolites?
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Metabolized by oxidation and has active metabolites
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What is the reduction in dose of Tigecycline in Child Pugh Class C?
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50% dose reduction
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What drugs mentioned in lecture should have a dose reduction in liver cirrhosis?
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Tigecycline, clindamycin, caspofungin
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What are the 5 non-pharmacologic supportive strategies in hepatic failure?
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Osteoporosis screening, vaccinations, nutrition, alcohol abstinence, tobacco abstinence
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What are the treatments for osteoporosis?
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bisphosphonates, Calcium 1500mg/d, selective estrogen receptor modulator (wm), calcitonin, testosterone in men
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What vaccinations should a liver cirrhosis receive?
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Hep A&B, Pneu, Flu
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How does cirrhosis impair nutritional metabolism?
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Cirrhosis impairs hepatic function and causes decreased glucose, protein, and lipid metabolism
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What is PCM?
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protein calorie malnutrition; is common in advanced liver disease with weight loss, nausea, and anorexia
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What complications in liver cirrhosis is PCM associated with?
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increased risk for infections, esophageal variceal bleeding, and both renal and pulmonary complications
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Why should raw seafood be avoided in pts with cirrhosis?
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risk of septicemia with Vibrio vulnificus
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Can alcohol abstinence offer improvement to a pt with decompensated liver disease?
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yes, can improve survival
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What are the benefits of tobacco abstinence for a liver cirrhosis pt?
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liver is a target of many carcinogens in tobacco, many liver transplant programs will not offer tranplant to patients that smoke, smoking is associated with hepatic artery thrombosis if the patient continues to smoke post transplant
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What are the non-pharmacologic treatments for liver cirrhosis?
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slowing/reversing liver disease progression(treat underlying cause), prevent superimposed insults (avoid hepatotoxic substances, do not exceed 2g apap/d), prevent complications, determine appropriate liver transplant timing, proper nutrition (take a multivitamin)
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What are the indications for liver transplant?
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fulminant hepatic failure, decompensated cirrhosis (incl hepatorenal syndrome), hepatocellular carcinoma
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What are the contraindications for liver transplant?
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Multisystem organ failure, extrahepatic or extrabiliary malignancy or infection, advanced cardiac or pulmonary disease, HIV, active alcohol or illicit substance abuse
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What are the relative contraindications for liver transplant?
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renal insufficiency, hemochromatosis, sponateous bacterial peritonitis, age greater than 65, inability to comply with immunosuppression regimen
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