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2.7 liver disease
Terms in this set (71)
which disease state is classified by simple fatty liver w additional evidence of hepatocyte injury (ballooning degeneration, mallory-denk bodies, necroinflammation)?
which cells, when activated, cause damage to hepatocytes, reactive oxygen species, and propogation of inflammatory cascade?
which cells, when activated, become fibrogenic and cause secretion of fibrin and collagen in the space of Disse?
which area, when enlarged, separates the hepatocytes from sinusoid (and thus oxygen/nutrients) and leads to hepatocyte apoptosis?
what is needed in order to establish the severity/classification of alcoholic liver disease?
which stages may be present simultaneously in alcoholic liver disease?
simple steatosis, steatohepatitis, fibrosis/cirrhosis
what are the 3 pathways of alcohol metabolism?
alcohol dehydrogenase, MEOS(CYP450 2E1), catalase
what does alcohol dehydrogenase reduce NAD to?
what does excess NADH promote?
decreased beta oxidation of FAs
what does excess acetaldehyde promote?
glutathione depletion, blocks PPARa (FA oxidation), formation of adducts, oxidative stress, lipid peroxidation
what type of medical therapy is recommended for ppl with mild/moderate alcohol liver disease and no encephalopathy?
medical therapy is NOT recommended
what tyoe of treatment is used for alcoholic hepatitis?
abstinence(most critical), nutrition, anti-inflammatory agents
which drug is shown to reduce alcohol withdrawl symptoms and has structural similarities to GABA?
which drug blocks EtOH induced DA release and is a pure opioid antagonist?
which vitamins do alcoholics tend to show impaired storage of?
A, D, B12, Folate
what MDF score defines severe AH?
greater than or equal to 32
when should corticosteroids be used in alcoholic liver disease?
in severe AH (prednisolone 40mg)
which drug, used for alcoholic liver disease, is a TNF-a inhibitor and should be used in severe AH patients when there is a CI to steroids(variceal bleed)?
which liver disease is characterized by steatosis + necroinflammation (ballooning, mallory bodies, megamitochondria)?
non-alcoholic steatohepatitis (NASH)
which liver disease is primarily caused by an over supply of FAs and is linked to insulin resistance(leads to incr lipolysis of periph adipose tissue)?
non-alcoholic fatty liver disease (NAFLD)
which class of drugs are used for NAFLD to improve insulin resistance?
TZDs (pioglitazone 30mg)
which drugs used for NAFLD is an anti-oxidant to reduce oxidative stress?
Vitamin E (800 IU/day)
what are the cirrhotic manifestations?
(FA HAIR) fatigue, anorexia, hepatomegaly, AMS, itching, right quadrant pain
what are cirrhotic complications?
(AVPP HHHH) ascites, variceal bleeding, portal HTN, pulm/cardiac manifestations, hepatic encephalopathy, hepatorenal syndrome, hematologic manifestation, hepatocellular carcinoma
which cirrhotic complication is defined as the elevation of hepatic venous pressure gradient: >12mmHg (norm 5-10)?
which cirrhotic complication is characterized by an accumulation of free fluid within the peritoneal cavity (abdominal distention when collections > 1L)?
what is the max weight loss goal in the treatment of ascites?
what do you want to limit sodium restriction to in the treatment of ascites?
1.5 -2 g/day
which vasopressin antagonists are NOT recommended in the treatment of ascites?
what types of diuretics are used in the treatment of ascites?
aldo-antags, loops, k-sparing
what is the most effective pharmacological treatment of ascites and what is the ratio?
spironolactone + furosemide
how often should patients with ascites be monitored?
every 2-4 weeks acutely
which SE should be monitored for in the Tx of ascites with diuretics?
gynecomastia, hyperkalemia (K>6), hyponatremia (Na<120), encephalopathy, inc Scr, dehydration
what are the pharmacologic treatment options for refractory ascites?
midodrine and beta blockers
which treatment of ascites carries the risk of shunt occlusion and severe encephalopathy?
which treatment of ascites is a safe method of fluid removal which also removes 5-10g of albumin for every liter of fluid removed?
which treatments of ascites are used when plasma renin is elevated?
albumin infusion (large vol paracentesis), midodrine, terlipressin
what is a diagnostic factor for SBP (spontaneous bacterial pertinitis)?
ascitic fluid PMN count > 250
what are the common sx of SBP?
fever, abdominal pain, peritoneal irritation, AMS, abdominal tenderness
empiric abx should cover wich 3 most commonly encountered SBP pathogens?
e. coli, klebsiella pneumoniae, streptococcus pneumoniae
what is the treatment of choice for suspected SBP?
cefotaxime (similar 3rd gen cephalosporin may be substituted)
which empiric tx of SBP is as effective as IV cefotaxime?
what should be given in addition to cefotaxime in the tx of SBP when meeting the following criteria: ascitic fluid PMN > 250, clinical suspision of SBP, Scr > 1, BUN > 30, total bilirubin > 4?
pt who survived previous episode of SBP and meet certain requirements can use what drugs for long-term prophylaxis SBP?
norfloxacin(400 qday) or DS bactrim (qday)
what complication is a result of angeogenisis leading to formation of collateral vessels and creates a hyper dynamic circulatory state?
varisces (commonly formed in esophagus, stomach, rectum)
what are the 3 steps in treating esophageal varisces?
1) prevention by reducing portal HTN
2) treatment during acute variceal hemorrhage
3) secondary prophylaxis after variceal bleeding episode(via portal HTN reduction)
which drugs should be used in variceal hemmorhage prevention to reduce portal pressure by reducing portal venous flow?
non-selective BBs: propranolol and nadolol or EVL(only for pt's who have not bled)
what is the first priority in a variceal bleed?
volume resucitation (NG tube or blood transfusion)
what type of prophylaxis should be instituted in a pt with an upper GI bleed and risk for severe bacterial infection?
short term abx prophylaxis: norfloxacin, IV cipro, or ceftriaxone
which pharmacologic agents are used to stop acute bleeding in variceal hemorrhage?
vasopressin/NTG, terlipressin, somatostatin/ocreotide
which drug is a synthetic analog of vasopressin and is used in acute variceal bleeds?
terlipressin (used with NTG)
which drug used for acute variceal bleeds causes splanchnic vasoconstriction and inhibit the release of glucagon?
what is used in combination with drugs for prolonged therapy of variceal bleeds?
what is used as rescue therapy for variceal bleeds by direct compression of the varix?
which variceal rescue therapy is used when hepatic portal vein gradient is >20 mmHg?
what is the best option for secondary prophylaxis of vericeal bleeds?
nonselective BB + EVL
what is used as initial tx of hepatixc encephalopathy and is a non-absorbable disaccharide?
what is used as an alt therapy to lactulose in the tx of HE and has CNS-related(including ototoxicity) SE from long-term use?
metronidazole (SHORT TERM ONLY!!)
which drug used in the tx of HE by inhibiting intestinal glutaminase(leads to dec ammonia), and can lead to nephro/ototoxicity from long-term use?
which drugs are used in the secondary prevention of HE?
lactulose and rifaximin
which drug used as secondary prevention of HE is used as add-on therapy to lactulose and lowers ammonia plasma levels by eliminating ammonia producing bacteria in the gut?
what are the mechanisms of drug-induced liver disease?
disruption of Ca homeostasis, binding of drug to CYP-P450, oxidative stress, affects transport proteins of canalicular membrane
which drug leads to the direct activation of stellate cells leading to DILD?
which drug leads to increased collagen/fibrinmatrix deposition leading to DILD?
Vitamin A toxicity
which child-pugh score indicates class A?
which child-pugh score indicates class B?
which child-pugh score indicates class C?
what type of dose reduction should be initiated in drugs that are primarily(>60%) metabolized in liver with a child-pugh score of 8-9?
what type of dose reduction should be initiated in drugs that are mostly metabolized in liver with a child-pugh score of >10?
what are the evaluated components of the detoxification/excretory fxns of the liver?
1) conjugated/unconjugated serum bilirubin
2) plasma ammonia levels
3) transaminases (ALT/AST)
what are the evaluated components of the biosynthetic fxns of the liver?
1) serum albumin(dec production)
2) clotting factors(dec production)
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