Liver Disease Flashcards
What are some different functions of the liver?
Filtration of blood secretion of bile excretion of bilirubin metabolic functions conversion of sugar to glycogen glycogen storage protein and lipid synthesis production of clotting factors lipid and ammonia-urea cycle
What are some causes of liver disease?
viral infections drugs and toxins biliary obstruction inbonrn erros of metabolism CV Autoimmune cryptogenic
What are the different types of liver disease?
Acute vs chronic
focal vs diffused
mild vs severe
reversible vs irreversible
What are the most common causes of chronic liver siease and cirrhosis?
Alcohol and HCV
What are two immediate life-threatening complications?
Acute variceal bleeding and spontaneous bacterial peritonitis
The liver recieves blood from the _______ artery and the ______ vein.
hepatic artery and the portal vein
Where does the blood from the portal vein come from?
The mesenteric, gastric, splenic and pancreatic veins
What is the definition of cirrhosis?
chronic disease of the liver with widespread hepatic cell injury and hepatocyte destruction
Inflammation in hepatocytes causes what?
permanent hepatic scarring and deposition of fibrous material
Fibrosis ______ the normal blood flow through the liver
disrupts
resistance to portal blood flow results in what?
persistent and progressive elevations in portal blood pressure or portal hypertension
What are some sxs of cirrhosis?
pruritus, jaundice, hyperpigmentation
ascites, edema, malaise,anorexia, weight loss
What are some abnormal lab tests for cirrhosis?
hypoalbuminemia, elevated prothrombin time, thrombocytopenia, inc AP, inc LFTs
What are Liver Function tests?
AST, ALT, AP, GGT, glotting factors (abnormal), bilirubin
How long can GGT be elevated?
for up to 3 wks
At ESLD will you see abnormal LFTs?
No
What is the Child-Pugh classification of Liver Disease?
A way to classify liver disease based on life expectancy and 1-yr survival
What is another liver disease classification system?
The Model for End Stage Liver Disease (MELD)
What lab values does the MELD score use?
bilirubin, INR, SCr
What is the Meld equation?
3.8xLn(bilirubin) + 11.2xLn(INR) + 9.6xLn(Scr) + 6.4
What does the MELd score tell you?
Risk of dying while waiting for a transplant
What are some clinical manifestations ofl iver disease?
portal hypertension gastroesophagel varices and bleeding acites spontaneious bacterial peritonitis hepatic encephalopathy hepatorenal syndrome coagulopathy
What causes portal hypertension?
inc portal pressure from:
1) structural resistnace to blood flow
2) intrahepatic vasoconstriction
Hepatic venous pressure gradient (normally 3-5) - its 10-12 in cirrhosis with varices
How do you diagnose gastroesophageal varices?
esophagogastroduodenoscopy (EGD)
What is given to prophylaxis of portal hypertension and variceal bleeding?
nonselective beta blockers (Propranolol 20mg BID or nadolol 20-40mg QD) or carvidolol
How is the dose escalated in propranolol or nadolol?
dec HR 20-25% or 55beats/min
How long do you need to use propranolol for prophylaxis of portal hypertension or variceal bleeding?
indefinitely unless not tolerated
What are some CI of propranolol?
Asthma/COPD Insulin-dependent diabetes - blocks side effects of diabetes peripheral vascular disease Heart block, bradycardia uncompensated CHF
What are some side effects of Propranolol?
Fatigue, SOb, lightheadedness
Do you prophylax on the formation of variceal polyps or just on them popping and bleeding?
on them popping and bleeding
AASLD guidelines recommend against prophylaxis use of:
Nitrate monotherapy
nitrate + nonselective beta blockers
carvedilol (not first line)
What are some risk factors of acute variceal bleeding?
Alcohol and NSAIDs
If the HVPG is greater than ___ you have difficulty controling bleeding, higher risk of early rebleeding and a higher 1yr mortality riate
> 30mmHg
For an acute variceal bleed what should you give to prevent infection?
Prophylactive antibiotics for a max of 7 days:
Norfloxacin
Ciprofloxacin
IV ceftriaxone
What is Octreotide used for?
acute variceal bleed
iv bolus and then continuous infuction;
continued for 3-5 days after diagnosis confirmed
what is Endoscopic varceal ligation?
Tie off nodules to slough them off
Should beta blockers be used in the acute variceal bleed?
No
What type of surgical options are there for portal hypertension and varceal bleeding?
transjugular intrahepatic portosystemic shunt, dec vascular resistance,
What is the TIPS procedure?
putting a connection between the portal vein and hepatic vein and using stent to open up a new vein formation to dec pressure
Ascites is a complication of _______
cirrhosis
What is ascites?
accumulation of fluid in peritoneal cavity
Portal hypertension leads to peripheral vasodilation which leads to _____________–
compensatory Na and water retention
How do you tx Ascites?
Underlying cause
alcoholic hepatitis - abstinenece and time
HBV cirrhosis - antiviral therapy
Dietary salt restriction (2g/day)
fluid restriction
diuretics (spironolactone 100mg and Furosemid 40mg)
Consider holding diuretics if what?
Uncontrolled/recurrent hepatic encephalopathy
serum Na 2 mg/dL
Should liver transplantation be considered in patients with cirrhosis and ascites?
Yes
For Refractory ascites what are the tx options?
Paracentesis + albumin
TIPS procedure
What is SBP?
Spontaneous Bacterial Peritonitis
Infection of abdominal cavity due to ascites and portal hypertension
What are some sxs for SBP?
abdominal pain/tendernes fever/chills tachycardia hepatic encephalopathy altered WBC
How do you diagnose SBP?
positive ascitic fluid bacterial culture
elevated ascitic fluid absolute PMN count
abdominal paracentesis
What are the three most common isolates of SBP?
E.coli, K. pneumoniae, S. pneumonia
How do you tx SBP?
Cefotaxime 2gm IV q8h
Ceftriaxone 1gm Q24h
Could you consider Flouroquinolone in pts w/o prior quinolone exposure?
Yes
Should you give albumin infusions with antimicrobial therapy for SBP?
Yes
how do you prophylax SBP for pts with previous episodes?
Norfloxacin 400mg QD
Trimethoprim-Sulfamethoxazole DS QD
Ciprofloxacin 750mg PO qwk
What is Hepatic encephalopathy?
spectrum of neurological to psychosocial symptoms in the setting of liver disease
- alterend level of consciouness, intellectual functioninong and behavior
-altered skeletal muscle and motor skills
Elevated ammonia level
What is the tx for HE?
avoid Benzos and narcotic analgesics (consider reversal with flumazenil/naloxone limit daily protein lactulose neomycin or metronidazole Rifaximin Zinc
How does lactulose work?
It is a nonabsorbable disaccharide that undergoes fermenation by gut flora and produces organic acids which lower colonic pH; the acidification of colon lowers ammonia levels in the blood by reducing protein degradation and ammonia absorption
What is the dose of Lactulose for management of HE?
20g/30mL PO TID, titrate to 3-4 bowel movements per day
Can you give Lactulose as an enema?
300mL mixed with 700mL water/saline
What are some adverse effects of Lactulose?
Diarrhea, Cramping, Flatulence, Dyspepsia
Can you use Neomycin or Metronidazole for HE?
Yes
What does neomycin do to bacteria?
kills them; inhibits activity of urease-producing bacteria
what is the Dose of neomycin for NE acute episodes and maintenance?
1g PO TID up to 6g daily for acute epidodes
1-2 g PO daily for maintenance
when taking Neomycin what should you monitor for?
aminoglycoside so monitor renal function, ototoxicity and nephrotoxixicty with chronic use.
Can you use Neomycin with lactulose?
Yes
Can Metronidazole be used for HE? Why?
Yes; dec ammonia production by gut flora
What is the dose of metronidazole for HE?
250mg PO q6-12 hours
What must you be careful with when dosing metronidazole?
Neurotoxicity (peripheral neuropathy) with chronic use due to impaired hepatic clearance
Can Rifaximin be used for HE? What is the MoA for HE?
Yes; dec urease producing bacteria in the GI tract; <1% absorbed after oral administration
What is the prophylaxis dose of Rifaximin for HE?
550mg PO BID
What is the tx dose of Rifaximin for HE?
400mg PO TID
What is the efficacy of Rifaximin when compared to Neomycin?
Similar
What are some ADRs of Rifaximin?
HA, Abdominal pain, constipation, N/V
Can Zinc be used for HE?
Yes; cofactor of urea cycle enzyme
Can you send pts home on zinc and can it be used as monotherapy?
Yes, but no not monotherpay, must be on lactulose and an antibiotic
What is the dose of zinc for HE?
500mg daily can inc urea formation and lower ammonia levels
Can renal failure happen in pts with liver disease? How?
Yes, liver cirrhosis that leads to vasoconstriction in renal vasculature
What is the difference between type 1 and type 2 hepatorenal syndrome
Type 1 is rapidly progessive dec in renal function
Type 2 is steady moderate impairment in renal function
How do you manage hepatorenal syndrome?
avoid all nephrotoxic drugs avoid overaggressive diuretic use hemodialysis albumin infusions midodrine combined with octreotide expedited referral for liver transplantation
Impaired drug metabolism clinially significant only in severe liver disease with a Child-Pugh class of __
C
Which phase of metabolism is effected more by liver damage?
Phase 1 (oxidation)
Clearance of _____ extraction drugs is decreased in patients with chronic liver disease. So can you predict dosage reduction?
High; No you still cannot predict due to highly variable degree of hepatic blood flow reduction
There are three categories of drug extraction, what are they?
High (>60%)
Intermediate (30-60)
Low (<30%)
What are some high extraction drugs?
morphine, sertraline, fluvastatin, lovastatin, sumatriptan, labetalol, metoprolol, midazolam
Do we need a dosage reduction for renally eliminated drugs?
Yes
The volume of distribution of _______ drugs may be increased in patients with _____ and ______.
Hydrophilic
ascites
edema
If the drug causes the following things you have to consider dose adjusting in liver disease:
High extraction ratio drugs Inc Na and water retention Drugs that precipitate HE Drugs that inc risk of ADRs Highly protein bound drugs APAP
