How does Ascites develop?
- Backup in a portal vein causes an increase in pressure
- Decreased NO causes decreased vasodilation, adding to the pressure
- Increased endothelin causes increased vasoconstriction, adding to the pressure
- Fluid then starts to be forced into the abdominal cavity through leaky blood vessels
How does portal hypertension develop?
- Inflammation of the liver leads to fibrosis, which leads to cirrhosis
- Cirrhosis causes impaired blood flow, which leads to portal HTN
What is the vicious cycle of portal hypertension?
- Blocked flow, decreased NO, and increased endothelin add to pressure
- Increased pressure adds to ascites
- Ascites leads to a decrease in effective intravascular volume, CO, and renal perfusion
- RAAS is turned on by low volume and decreased renal perfusion
- Sodium and water are retained to increase volume
- This retention increases the pressure and around and around we go!
How does hepatic encephalopathy develop?
increase in ammonia, mercaptans, short-chain fatty acids, and phenol due to decreased ability of the cirrhotic liver to detoxify them
What are the sx of hepatic encephalopathy?
- asterixis ("liver flap" of the hands)
What is the nonpharmacologic tx for hepatic encephalopathy?
- Remove sedating drugs
- Treat infection
- Limit dietary protein to 1.5-2.2g/kg/d
- Fix GI bleed (breaks down to ammonia in the gut, adding to problem)
- Prevent overdiuresis (can cause alkoalosis which increases ammonia and other amines in the brain)
- Treat constipation
What is the tx for hepatic encephalopathy?
- Lactulose (DOC)
- Lactulose + Neomycin
What is the MOA of lactulose in hepatic encephalopathy?
- Metabolized to lactic, acetic, and formic acid
- Acid plus colonic NH3 = NH4+ which cannot get back into the blood so it passes with the stool
What is the MOA of Neomycin in hepatic encephalopathy?
- Kills urea splitting bacteria
- Can't make ammonia without splitting urea
What is the monitoring for Lactulose and Neomycin?
- Diarrhea (SE and therapeutic goal → these pts should have 2-4 loose stools/d)
- Mental status and connect the number test
- Renal function (Neomycin)
- Ototoxicity (Neomycin)
What is the tx for Esophageal varices?
- Octreotide (DOC): vasoconstriction
- Vasopressin: more vasoconstriction, but more SE (ischemia, ↓CO, gangrene)
- Balloon tamponade
- Portosystemic shunt
How can you prevent esophageal varices?
- Propranolol (DOC): low dose, titrate to pulse of 55-60 or 25% reduction
- Isosorbide mononitrate: vasodilation of veins
- Propranolol + Isosorbide mononitrate: better than either alone
- Variceal ligation (banding)
Why do we use potassium sparing diuretics to treat ascites?
Diuretics increase excretion of sodium which will help overcome the retention caused by the RAAS activation, but you don't want to get rid of all of your potassium and go hypokalemic
How do you treat ascites?
- Both are DOC, but spironolactone causes gynecomastia
- Furosemide (if impatient)
- Paracentesis + infusion of albumin
How do you monitor treatment for ascites?
- Aldosterone antagonist: aim for 1L/d urine output with peripheral edema; 0.5L/d if no edema (don't want to go too fast since you're already hypovolemic)
- Goal is urine sodium:potassium ratio is 1 or higher
- For furosemide: weight and BUN/creatine ratio (using baseline ratio, not 20:1 ratio since they are not producing urea very well d/t malnourishment)
What is the rationale for large volume paracentesis?
Adding the albumin will increase the oncotic pressure and draw fluid into the vasculature
How is Spontaneous Bacterial Peritonitis (SBP) diagnosed?
PMN ≥ 250/mm3
What is the tx for spontaneous bacterial peritonitis (SBP)?
AG, FQ, Metronidazole, or Pip-tazo for anaerobic and gram negative coverage
What is the prophylaxis for spontaneous bacterial peritonitis (SBP)?
Norfloxacin or Bactrim
How do you minimize risk of hepatorenal syndrome?
What are the functions of the pancreas?
- Islets produce insulin
- Acinar cells produce enzymes
- Bicarbonate protect intestine from low pH
What stimulates the production of enzymes in the pancreas?
- food in the duodenum stimulates CCK (cholecystokinin)
- CCK stimulates enzyme production
- Trypsinogen is cleaved by enterokinase to trypsin
- Trypsin activates pro-enzymes
What stimulates production of bicarbonate in the pancreas?
- food in the duodenum stimulates secretin
- Secretin stimulates production of bicarb and water secretion into the duodenum
What are the causes of pancreatitis?
- Gall stones
What are the key indicators of pancreatitis?
- Elevated amylase and lipase
- Lipase more indicative
What are the Ranson's criteria?
- At admission:
- Age > 55
- WBC > 16,000/mm3BG > 200mg/dL
- AST > 250 IU/L
- ALT > 350 IU/L
- At 48 hours:
- Ca < 8 mg/dL (very bad sign)
- Hematocrit drop > 10%
- Oxygen < 60mmHg
- BUN increased by ≥ 5mg/dL after IV hydration
- Base deficit > 4 mEq/L
- Sequestration of fluids > 6L
What is the tx for acute pancreatitis?
- Fluid resuscitation (#1 priority)
- Pain control (#2 priority)(Hydromorphone preferred)
- Parenteral nutrition or enteral feedings distal to the jejunum (to avoid further enzyme production)
What is the tx for severe acute pancreatitis?
- Octreotide (decreases secretions, but not very efficacious)
- Antibiotic prophylaxis (ceftazidime, metronidazole, amikacin, or imipenem-cilastatin)
What are the signs of chronic pancreatitis?
- Wt loss
- Abdominal pain after eating
- amylase and lipase levels are usually normal because there's not enough production to get it into the blood
What is the tx for malabsorption d/t chronic pancreatitis?
- Enteric coated pancreatic enzymes
- H2RA or PPI to keep pH around 5 and protect the enzymes