Acute and Chronic Liver Disease Lectures Flashcards
Where does the majority of blood in the liver come from?
port vein –from intestines (60%)
What is the portal triad?
hepatic artery
portal vein
bile duct
entering into the liver
Kupffer cell
a macrophage in the portal space that works to remove endotoxins to prevent it from going into the systemic circulation
Stellate cells
within the space of disse (space between sinusoid and hepatocytes)
normally these cells are benign –simply storing vitamin A
however when they get activated or damaged they form COLLAGEN
in between the endothelial lining and the hepatocytes —this is where these cells are and where scaring occurs
What are the functions of the liver?
detox
synthesizes plasma proteins —clotting factors
synthesize lipids, lipoproteins, glucose
synthesize and metabolize endocrine hormones
Ag-Ab complex removal (Kupffer cells)
LFTs
hepatic panel
- bilirubin - total and direct
- AST - asparate aminotransferase
- ALT - alanine aminotransferase
- AlkP or AP (alkaline phosphatase)
- Albumin
the real “function” tests of the liver are bilirubin, albumin, and PT
the others are only measures of enzymes released from injured cells
How is bilirubin carried to the liver?
by albumin
carries UGB to the liver to become CB
How does the liver metabolize bilirubin?
conjugate it to diglucuronide with UDPG
What happens to diglucuronide?
it gets stored in the bile where it slowly gets sent into the intestine where bacteria break it down further into urobilinogen and sterobolinogen (which makes your stool brown)
urobilinogen has two fates —one is to be converted to sterobolinogen which becomes feces
the other is to get absorbed into the blood where it becomes urobilin which gets filtered in the kidney and makes urine yellow
Direct vs indirect bilirubin?
direct is conjugated bilirubin (water soluble) –most commonly diglucuronide
indirect is unconjugated (not water- soluble) –only form in normal plasma –increase by hemolysis —always bound to albumin
When you see an increased indirect bilirubin, what does that mean?
higher unconjugated bilirubin
always bound to albumin
increased d/t hemolysis
If you see a decrease in albumin what does this mean?
This decrease has to be d/t a chronic liver disease because it takes 20 days before you will see a decrease in albumin d/t its half life of 20 days
remember that the liver is the ONLY source of albumin
What does a prolonged PT in a normal pt mean?
The liver is not making the necessary clotting factors
the first thing you want to try is give vitamin K —it the PT corrects then the problem is probably not in the liver but in the absorption of vitamin K
you need vitamin K for clotting factors to work
Which tests on the liver panel tell you about cell injury/inflammation?
AST
ALT
Which test is more liver specific, AST or ALT?
ALT
What does elevated AST mean?
it could mean many things because it is found in high concentrations in the heart, kidney, muscle, and liver
so it could be elevated due to running a marathon, etc.
In most cases of liver injury, what do you expect to see with AST and ALT?
ALT > AST
What if you see AST > ALT?
could be:
- sudden acute liver necrosis
- EtOH-related liver injury
- cirrhosis and/or malnutrition
What does a rise in AlkP mean?
a possible obstruction in the biliary tree or the parenchyma of the liver
this is because alkaline phosphatase is release from the cell membrane of hepatocytes in the canalicular membrane when bile is blocked up and resting on the membrane too long
What tests are used to detect cholestasis?
bilirubin
AlkP
GGT
At what level will you start to see jaundice?
when the bilirubin is 2X the normal level
If you have a higher indirect bilirubin compared to direct bilirubin, what might this mean?
That the problem is with hemolysis
What sxs might you see in chronic cholestasis?
The bile can’t get out so it accumulates in the blood (pruritic rash) and in the skin (xanthelasma and xanthomata)
Pts with steatorrhea might have deficiency in vitamin A, D, E and K, why?
because if they aren’t able to absorb fats they aren’t absorbing fat-soluble vitamins
remember with the prolonged PT you should first try and see if the pt responds to vitamin K
What sxs might you see in chronic liver disease?
palmar erythema clubbing spider angiomata (blanching) gynecomastia testicular atrophy
Why do we want to keep the pressure down in pts with cirrhosis?
put them on prophylaxis BB (propranolol) to try and precent the formation of varices
What annual screening should be done with cirrhosis pts?
do endoscopy looking for esophageal varices (and treat if they have them)
these are under such high pressure that if they rupture they will bleed like an artery and have a 40% chance of killing the pt
What is the management of ascites?
d/c NSAIDs avoid renal toxic drugs (aminoglycosides) 2g sodium diet do not restrict water spironolactone or furosemide
monitor treatment with daily weights (goal weight loss 1-2 lb/day)
Refractory ascites
ascites that doesn’t respond to our treatment
poor prognosis
What is the treatment for hepatic encephalopathy?
restrict dietary protein in diet
lactulose (nonabsorbable sugar)
Rifaxamin or neomycin (nonabsorbale ABX)
Lactulose
non-absorbable sugar used in hepatic enchpalopathy
maintains regular bowel movements
favors growth of lactobacilli in gut that compete with more amminogenic bacteria and tend to produce a more acidic environment
may contribute to acidification of gut
Hepatorenal syndrome
NOT DONE HERE
What is primary biliary cirrhosis?
PBC
idiopathic autoimmune of INTRAhepatic small bile ducts thus decrease bile salt excretion
Who gets PBC?
middle aged (40-60) age WOMEN
I GET SMASHED
causes of acute pancreatitis:
I- idiopathic G- gallstones E- EtOH T - trauma S - steroids M - mumps virus A - autoimmune dz S - scorpion sting H - hyperTG + hypercalcemia E - ERCP D - drugs
What is the difference between zone 1 and zone 3 of the liver?
Based on oxygenation
Zone 1 - around the portal veins –most oxygenated blood
Zone 3 - around the central vein –least oxygenated blood
Where is albumin made?
liver
liver is the ONLY source of albumin
What is happening to bilirubin in the liver?
after UCB (indirect) has been transferred to the liver via albumin, it is digested via UDPG or UGT to form direct bilirubin aka diglucuronide
this will then get stored in the bile where it eventually will be released into the gut and broken down by bacteria into urobilinogen (reabsorbed into blood and excreted in urine) and then broken down into stercobilin which gets excreted in poop
Will you see higher conjugated or unconjugated bilirubin in cholestasis?
higher conjugated bilirubin
the liver is still turning UCB to CB
the gallbladder is just having a build up of CB
Will you see higher conjugated or unconjugated bilirubin in hepatitis?
higher UCB
problem at the site of the liver
the UCB is getting to the liver just not getting formed into CB
What are major causes of jaundice in adults?
Prehepatic - inherited disorders like Gilberts
Hepatic - cirrhosis
hepatitis
Biliary tree - obstruction
What is the initial test of choice for bile duct obstruction like cholestasis?
US
What is the difference between collagen types in a normal liver vs a cirrhotic liver?
Normal liver is mainly collagen type 3
Cirrhotic liver is mainly collagen type 1 (best seen with reticulin stain)
Why do some pts experience a pruritic rash with cholestasis?
more commonly in chronic cholestasis
this is because bile acid cant get out and accumulates in the blood
What might steatorrhea tell you?
that the pt is not digesting or absorbing fats
this can be caused by decrease cholesterol since cholesterol is needed to make bile acids and bile acids are needed to break down fat
Prehepatic causes of portal HTN
portal vein thrombosis
Hepatic causes of portal HTN
Sinusoidal -cirrhosis
Posthepatic causes of portal HTN
outflow obstruction like cor pulmonale
What is normal HVWP?
Hepatic venous wedge pressure
HVWP - IVC = < 4mmHg
cirrhosis >4mmHg
really bad if its >12mmHg
What is a major and potentially life threatening complication of portal HTN?
esophageal varices
under such high pressure that if they rupture they could bleed out
GO TO THE ER if you see blood in your vomit or if you cough blood
How can you prophylactically treat pts with risk of esophageal varices?
BB - propranolol
How do you treat a bleeding esophageal varices?
variceal band ligation (standard of care)
What heme problems might a pt with cirrhosis have?
Splenomegaly (d/t portal HTN)
thrombocytopenia as a result of splenomegaly
impaired synthesis of clotting factors d/t liver fibrosis
assess PT –prolonged indicates a large portion of the liver is not functioning (in the absence of vit K deficiency)
tx: vit K, FFP or platelets, as indicated
How do you manage ascites?
d/c meds that adversely effect the kidney such as NSAIDS (decrease PG with decrease renal circulation which leads to N+ retention)
avoid renal toxic drugs (aminoglycosides)
2g Na diet
do not restrict water unless hyponatremia
spironolactone
furosemide
daily weights –goal: lose 1-2 lb per day
urine sodium levels
What must you do for a pt with new-onset ascites?
get a sample of the fluid via tapping to confirm transudate and r/o bacterial peritonitis
SBP
spontaneous bacterial peritonitis
frequent complication of ascites –occurs in 20% of cases
dx: low grade fever, abdominal tenderness, increase WBC, decrease in pH
increase BUN/Cr
encephalopathy
What suggests infection of SBP?
peritoneal tap WBC >500
culture at beside of peritoneal fluid
positive urine dipstick for leukocyte esterase
What is the treatment for SBP?
IV broad spectrum ABX
+/- albumin infusion
PO ABX for at risk pts (rifaxamin or norfloxacin)
What are common pathogens causing SBP?
E. coli
K. pn
S. pn
What are signs of hepatic encephalopathy? What might you see on EEG?
triphasic slow waves on EEG
asterixis
mental confusion
constructional apraxia
fetor (odor of mercaptans)
How do you treat hepatic encephalopathy?
Underlying condition
Consider restricting dietary PROTEIN (protein broken down by bacteria in gut can release NH3)
lactulose - a nonabsorbable sugar –maintains regular bowel movement
consider a non-absorbable ABX -rifaxamin or neomycin
avoid sedation
OLT
orthoptic liver transplantation
survival after OLT >80% at 5 years
What are the indications of OLT?
evidence of end-stage liver disease
expected survival < 1 year
clinical decompensation of liver disease
What are contraindications of OLT?
systemic infections of AIDS (HIV alone is not an absolute contraindication)
Severe cardiopulmonary disease
Metastatic malignancy
