Term
| How do we know if the liver is working? |
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Definition
| Check Liver synthetic capability, hepatocellular injury, cholestatic disease and bilirubin metabolism |
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Term
| What markers are in the liver synthetic capability? |
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Definition
- Albumin
- Prealbumin
- Globulin
- Total protein
- Prothrombin time |
|
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Term
| What to check for hepatocellular injury? |
|
Definition
- Aminotransferases (ALT/AST)
- Lactate dehydrogenase |
|
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Term
| What to check for cholestatic disease? |
|
Definition
- Alkaline phosphatase
- 5'Nucleotidase
- Gamma-glutamyl transpeptidase (GGT) |
|
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Term
| What are markers for billirubin metabolism? |
|
Definition
- Total bilirubin
- Unconjugated/indirect bilirubin
- Conjugated/direct bilirubin |
|
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Term
| How much albumin is synthesized by the liver daily? |
|
Definition
12g/day
It maintains plasma oncotic pressure
Normal t1/2 is 20 days
Slowly falls in hepatic dysfunction
|
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Term
| What are other causes of low albumin? |
|
Definition
- Malnutrition
- Malabsorption
- Overhydration
- Nephrotic syndrome
- Burns
- Chronic illness |
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Term
| What do we use prealbumin for? |
|
Definition
To assess nutrition status
t1/2=2 days |
|
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Term
|
Definition
Total measurement of immunoglobulins in serum
Immunoglobulins synthesized by B-cell lymphocytes throughout body-not just liver
Not specific for liver disease
Elevation sign of iflammation-often in hepatitis (viral or autoimmune) |
|
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Term
| When do we see low globulin? |
|
Definition
In immunodeficiency symdromes
- Malabsorption
- Protein losing enteropathy
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Term
| Total protein= primarily sum of albumin and globulin |
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Definition
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Term
| What factors are synthesized by the liver? |
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Definition
| Factors: I, II (prothrombin), V, VII(7), VIII (8), IX (9), X (10), XII(12), XIII (13) |
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Term
| What causes decrease in factors? |
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Definition
Substantial liver damage will cause decrease in factors
Other causes of prolonged PT- inadequate vit K in diet or vit K malabsorption, use of drugs (warfarin)
PT=prothrombin time |
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Term
| When do AST, and ALT increase? |
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Definition
They are enzyme in cytoplasm of hepatocytes
They increase with hepatocellular injury:
>20* normal acute viral, drug induced, r/o ischemic events (cardiac arrest) |
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Term
|
Definition
| Found in liver, cardiac muscle, kidneys, brain, pancreas, lungs. Normal 8-42 IU/L |
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|
Term
|
Definition
| Found primarily in liver-more specific to liver disease. normal 3-30 IU/L |
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Term
| In alcoholic liver disease ALT and AST =? |
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Definition
| Both usually <300 and AST usually 2* ALT (specific to live) |
|
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Term
| Where do we find lactate dehydrogenase? |
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Definition
Primarly in myocardium, liver, skeletal muscle, brain, kidneys, and red blood cells
Elevated in many illness
Not specific to liver
Elevated in hepatitis, biliary obstruction, metastatic liver disease, cirrhosis |
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Term
| What is cholesteric disease? |
|
Definition
Primary interference with metabolism or secretion of bilirubin anywhere from its initial production in the hepatocytes to its secretion into deodenum
Accumulation of substances normally excreted by liver into bile
Jaundice(bilirubin), pruritus(bile salts), Xanthomas (lipid deposits in skin) |
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Term
| T/F: Intrahepatic cholestatic disease is problem in liver cells or bile ducts in liver? |
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Definition
| True, its seen in viral hepatitis, alcoholic hepatitis, AIDS, and cirrhosis |
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Term
|
Definition
RBCs taken up destroyed by spleen. Hgb released from RBCs broken down to bilirubin
- Unconjugated bilirubin (indirect) bound to albumin carried to liver
- In liver conjugated (direct) with glucuronic acid and excreted in bile
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Term
| T/F: Elevated bilirubin id sensitive indicator of hepatic dysfunction? |
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Definition
|
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Term
| When is bilirubin elevated? |
|
Definition
- In en stage liver disease---Prognostic
- Hemolysis and ineffective RBC production, anorexia
- Biliary obstruction associated with inc in bilirubin and alk phos out of proportion to aminotransferases |
|
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Term
Total bilirubin 2-4 mg/dl-jaundice, urine dark (xs conjugated excreated by kidneys
>15 mg/dl-intense itching |
|
Definition
|
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Term
| When is unconjugated/indirect bilirubin elevated? |
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Definition
- Hemolysis
- Gilbert's syndrome
- Crigler-Najjar syndrome
- Neonatal joundice
- can be elevated in Liver disease |
|
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Term
| When is conjugated/direct bilirubin elevated? |
|
Definition
Associated w/ elevation in other hepatic enzymes
- Inc w/ alk phos and GGTP suggests cholestatic disorder
Inc w/ ALT/AST suggests hepatitis or cirrhosis |
|
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Term
| In hepatocellular disease, what three majot steps of bilirubin metabolism are interfered? |
|
Definition
- Uptake
- Conjugation
- Excretion: usually impaired to greater extent (rate limiting step). Therefore, conjugated bilirubin predominated in serum |
|
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Term
|
}Unconjugated
◦Overproduction: Hemolysis
◦Dec hepatic uptake
◦Dec bilirubin conjugation: Hereditary, Neonates
Acquired à hepatitis, cirrhosis
◦Sepsis
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|
Definition
|
}Conjugated
◦Impaired excretion, Hereditary, Hepatocellular disease (hepatitis, cirrhosis), Drug induced cholestasis, Alcoholic liver disease
◦Extrahepatic biliary obstruction, Gallstones, malignancy
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Term
| When does elevation in alkaline phosphatase indicate hepatic disease? |
|
Definition
If elevated with elevated 5" nucleotidase or GGTP
5'-nucleotidade found in liver, brain, heart , blood vessels. Elevated only in hepatic disease |
|
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Term
| What marker is elevated markedly in alcoholic liver disease? |
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Definition
GGTP (gama-glutamyl transpeptidase)
GGTP/alk pgo ratio >2.5---alcohol abuse likely
GGTP decrease within 2 wks of abstinence |
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|
Term
|
Definition
|
}Low in acute and chronic liver disease, proportional to extent of disease
}Hypersplenism (overactive spleen) with pooling of plts, immune mediated destruction, inability of bone marrow to compensate
}Bone marrow depression- alcohol, drugs, nutritional deficiency
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Term
| What are causes of liver disease? |
|
Definition
- Drug & toxins: alcohol
- Infections: hepatitis
- Immune-mediated: primary biliary cirrhosis, autoimmune heaptitis, primary sclerosising cholangitix
- Metabolic: hemochromatosis, prophyria, wilson'd dz
- Bilary obstruction: cystic fibrosis, atresia, strictures, gallstones
CVD: chronic right HF, Veno occlusive dz |
|
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Term
| What are pathophysiology of liver disease? |
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Definition
|
◦Fibrosis (limits blood flow) and normal liver tissue to nodules (cirrhosis)
◦Reduced liver blood flow
◦Intra- and extrahepatic portal-systemic shunting
◦Reduction in number and in activity of the hepatocytes
◦Impaired production of proteins
◦Impaired secretion of bile acids, bilirubin, and other organic anions
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Term
| What are common complications of liver disease? |
|
Definition
- Prtal hypertension
- Varices
- Ascites
- Encephalopathy
- Coagulopathy |
|
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Term
| What are less common complications? |
|
Definition
- Hepatorenal syndrome
- Hepatopulmonary syndrome
- Endocrine dysfunction |
|
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Term
| What are abnormal lab test seen in liver disease? |
|
Definition
- Hypoalbuminemia
- Elevated prothrombin time
- Thrombocytopenia
- Elevated alkaline phosphatase
- Elevated AST, ALT and GGTP
|
|
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Term
| Sign and symptoms of liver disease? |
|
Definition
- Fatigue (65%), Pruritus (55%), Hyperpigmentation (25%), Jaundice , Hepatomegaly, Splenomegaly
- Palmar erythema, Spider angioma
- Gynecomastia, Ascites (fluid in peritoneal cavity)
- Edema, Pleural effusion, respiratory difficulty
- Malaise, anorexia, wt loss, encephalopathy |
|
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Term
| Clinically wignificant portal hypertension? |
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Definition
Portal venous inc >10mmHg greater than pressure in inferior vena cava
Risk for bleed if >12 mmHg greater than vena cava pressure |
|
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Term
| What are the most clinical significant varices? |
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Definition
Left gastric vein w/ development of esophageal varices
Hemorrhage from varices-25-40% of pts w/ cirrhosis
Each bleeding episode-5-50% risk death
Rebleding 60-70% w/in 1 yr |
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Term
| What signs indicates increase risk of varices hemorrhage? |
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Definition
| Child B/C or presence of red signs |
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Term
| What are primary prophylaxis for small varices? |
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Definition
If have increased risk of hemorrhage, give non-selective beta blocker
If Low risk--consider non-selective beta-blocker
Repeat EGD (esophagogastroduodenoscopy) in 2 yrs
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Term
| What are primary prophylaxis for large varices? |
|
Definition
If high risk of hemorrhage, give non-selective beta blockers or endoscopic variceal band ligation (EVL)
If low risk (child A and no red signs), give non-selective beta-blockers
EVL if beta-blocker intolerance or CI |
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Term
| What are dose, dosage form of non-selective beta-blockers? |
|
Definition
Initiate propranolol 10 mg tid or nadolol 20 mg QD
Titrate dose weekly to HR 55-60 bpm or HR 25% lower than baseline or development of ADE (hypotension, orthostatic)
Causes: significance reduction in incidence of 1st bleed with trend to lower mortality |
|
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Term
| How do we manage acute variceal hemorrhage? |
|
Definition
- Fluid resuscitation and hemodynamic stability (BP, low, HR high) give more fluid (NS, albumin...)
- Correct coagulopathy and thrombocytopenia (give platelets if low)
- Control bleeding w/ octreotide, endoscopy ( sclerotherapy, band ligation)
- Abx-if risk of preitonitis (SBP)
- Prevention of rebleeding, preservation of liver fct
No vit K-may kill pt |
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Term
| Which abx can be used as prophylaxis to decrease SBP? |
|
Definition
- Norfloxacin 400 mg po BID * 7 days
- Ciprofloxacin 400 mg IV BID * 7 days
- Ceftriaxone 1g IV daily * 7 days if have high resistance rate |
|
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Term
| When should we give octreotide or somatostatin in acute variceal hemorrhage? |
|
Definition
Following fluid resuscitation
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|
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Term
| Mechanism of action of octreotide? |
|
Definition
Inhibit vasodilatory peptides producing mesenteris vasoconstriction
Dec splanchnic blood flow, reduce portal and variceal pressure |
|
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Term
| What are dosing of sctreotide and somatostatin? |
|
Definition
Octreotide: 50 ug IV bolus, then 50 ug/hr IV * 5 days
somatostatin: 250 ug IV bolus, then 250-500 Ug/hr IV * 5 days
ADE: hypo or hyperglycemia, abd cramping |
|
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Term
| What are complications of sclerotherapy? |
|
Definition
- Perforation, ulceration, stricture, and bacteremia
injection of 1-4 ml of sclerosing agent into lumen of varices to tamponade blood flow
Rebleeding and mortality are less with slerotherapy than band ligation |
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Term
| When do we use secondary prophylaxis? |
|
Definition
| All pts with h/o variceal bleeding |
|
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Term
| What are secondary prophylaxis? |
|
Definition
- Band ligation- endoscopic tx of choice, repeated every 2 wks until no further varices identified. Then repeat exams at 3 and 6 months
band ligation + drug therapy-most effective
- Non-selective beta-blockers (20% dec in rebleeding, 7% dec in mortality, target HR)
Target: dec hepatic venous pressure <12 mmHg or > 20% from baseline |
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Term
| What are clinical presentation of ascites? |
|
Definition
Protuberant abdomen, shifting dullness, fluid wave, bulging flanks, abdominal pain/discomfort, leg swelling, resp difficulties, malaise, anorexia, wt loss
Even though water and Na retention will still get hyponatremic (more severe)-bc of fluid overload. symptoms are mental status changes |
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Term
| What are treatment for ascites? |
|
Definition
- Stop alcohol-assess for delirium T (give benzo)
-Sodium restriction (2g/d) (-Na balance)
- Fluid restriction <1.5 L/d in pats with serum Na<120 meq/L
Diuretics-spironolactone and furosemide
- Paracentesis |
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Term
| If fluid is that bad (bif belly) need to get rid of flui with paracentesis first before starting diuretics |
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Definition
|
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Term
| How do we dose diuretics? |
|
Definition
Spironolactone 100 mg + furosemide 40 mg daily in Am.
Max dose spironolactone=400 mg
furosemide=160 mg daily |
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Term
| What is the goal maximum wt loss with diuretics? |
|
Definition
0.5 kg/d unless massive edema then no limit.
Titrate to goal inc every 2-4 days (bc waiting for steady state of spironolactone (longt1/2))
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Term
| When do we D/C or don't give diuretics? |
|
Definition
If encephalopathy present (bc may cause renal failure), Na <120 meq/L, or scr >2mg/dl
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Term
| What do we monitor for diuretics? |
|
Definition
- Spironolactone- urine in and out
- Mesure belly
- Measure Na, K
- Watch Bp, serum creatinine |
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Term
| T/F: if > 5 L fluid removed with paracentesis, give albumin (dec mortality) 6-8 g/L for each liter of fluid removed (we can give the SBP dose and iand one time) |
|
Definition
True
Paracentecis: cell count, total protein and albumin, serum ascites albumin gradient (SAAG)
If infection suspected--culture |
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|
Term
| When do we perform paracentesis repeatedly? |
|
Definition
| When refractory (resist tx) disease |
|
|
Term
| When are incidence of SBP higher? |
|
Definition
| In patients with ascitic fluid protein levels <1g/dl and with serum bilirubin >2.5 mg/dl |
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|
Term
| What indicates the presence of SBP? |
|
Definition
- Hematogenous seeding from gut
- Fever
-Leukocytosis
- abd pain
- Hypoactive or absent bowel sounds |
|
|
Term
|
Definition
Ascitic fluid cell counts: absolute polymorphonuclear (PMN) leukocyte count >=250 cells/mm3
positive ascitic fluid culture
Cirrhotic ascites presenting with convincing signs and symptoms of infection |
|
|
Term
| What are treatment of choice of SBP? |
|
Definition
- Cefotaxime 2g IV q8-12 hr
- Ceftriaxone 2 g daily
Treat 5-10 days, 5=10 in efficacy
Options: fluoroquinolone-oflox 400 mg q 12h
Do not use if had it for prophylaxis
Aminoglycoside? liver dz want to avoid then u don't want to get pt into renal failure |
|
|
Term
| When to use albumin in SBP? |
|
Definition
If ascitic fluid PMN>250 cells/mm3 & either proven or suspected SBP, and
- Scr >1mg/dl or
- BUN >30 m/dl or
-Total bilirubin >4mg/dl
Give albumin 1.5 g/kg within 6 hours and then 1 g/kg on day 3 |
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|
Term
| Prophylaxis for SBP-chronic tx for life when to use? |
|
Definition
|
◦Prior episode of SBP or if have variceal hemorrhage
◦Acute GI bleed (7 day)
◦If ascitic fluid protein <1.5 g/dl and at least one of the following:
Scr≥1.2 mg/dl, BUN≥25 mg/dl, Serum Na ≤130 meq/L
Or Chlid Pugh score ≥9 points with bilirubin ≥3mg/dl
|
|
|
Term
| What regimen to use for prophylaxis SBP? |
|
Definition
- Norfloxacin 400 mg/d (preferred)
- Ciprofloxacin 750 mg/week
- Bactrim Ds 5* week (M-F) |
|
|
Term
| How does hepatic encephalopathy present? |
|
Definition
- ALtered mental status (minor--coma)
- Asterixis
- Fetor hepaticus (pungent odor to breath) |
|
|
Term
| What are precipitating factors for hepatic encephalopathy? |
|
Definition
- Constipation
- GI bleeding
- Infection
- Sedative ingestion
- Excess protein in diet
- Hypotension
- Dehydration
- Hypokalemia |
|
|
Term
| How to treat acute encephalopathy? |
|
Definition
Protein withheld or limited to 10-20 g/d while maintaining total calories, until situation improves
Then restart protein at 0.5-0.6 g/kg per day and advance by 0.25-0.5 g/kg per day every 3-5 days until target of 1-1.5 g/d pr progression of HE occurs |
|
|
Term
| Treatement of acute HE continue? |
|
Definition
Give lactulose (goal is to give diarrhea 2-4 per day) titrate to stool, not to ammonia level)
45 ml po every hour (retention enema 300 ml) latulose syrup in 700 ml water, held for 30-60 min)
dec dose to 15-45 ml po q 8-12 hr (enema q 6-8) and titrated to produce 2-4 soft stools a day
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|
|
Term
|
Definition
| Initiate lactulose at 30-60 ml/d titrate to 2-4 soft stools a day |
|
|
Term
| What are ADE of lactulose? |
|
Definition
- xs diarrhea
- Dehydration, hypokalemia
- Gaseous distention
- Flatulence belching
- Nausea-sweet taste dilute in water, juice, carnbonated bev |
|
|
Term
| What to monitor with lactulose? |
|
Definition
- Electrolytes
- Mental status
- Stool |
|
|
Term
Metronidazole-use after stopping lactulose unless patient doesn't stop drinking than can't use
250 mg BID |
|
Definition
Rifaximin: as effective as lactulose and may be better tolerated.
550 mg BID
but expensive (disadvantage) |
|
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Term
| When do we use gaba-aminobutyric acid antagonists? |
|
Definition
When HE and in coma
Use flumazenil (but is waste of time) 0.2-0.4 mg titrated to response, rapid effect, short duration
replace zinc if deficient |
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