Disorders of the Liver I - Exam 4 Flashcards
What makes up the porta hepatis?
hepatic portal vein
hepatic artery
common hepatic duct
What are 4 jobs of a hepatocyte?
-detoxify harmful substances
-help maintain normal blood glucose levels
-break down glycogen
-store vitamins A, D, E, K, B12, iron and copper
What are the roles of the liver with regards to glucose?
glycogenesis and glycogenolysis
Glycogenesis: Converting glucose to glycogen
Glycogenolysis: Converting glycogen, fats & proteins to glucose
What is the role of the liver with regards to testosterone?
Synthesis of cholesterol for use as bile salts and steroid hormones (testosterone)
What is the role of the synthesis of the plasma proteins?
Synthesis of plasma proteins (albumin) and clotting factors
What is bile composed of? Where is is made? Where is it stored?
bile salts
phosholipids
cholesterol
bilirubin
made in the liver and stored in the gallbladder
What are common manifestations of liver dz?
hyperbilirubinemia and jaundice
Where does bilirubin come from? How does it become conjugated?
from the breakdown of RBC, specifically heme that breaks down into protporphyrin and unconjugated bilirubin
Unconugated bilirubin gets picked up by albumin and taken to the liver, once it reaches the liver, UCB and the enzyme (UGT) combine to form conjugated bilirubin that is then taken to the gallbladder for storage
______ gives poop its brown color. If poop is NOT a brown color, what does it make you think?
stercobilin
problem with the liver
What is it called when the pt’s eye is jaundice?
scleral icterus
What is normal total serum bilirubin? What is normal total direct bilirubin? What should you order?
Total Serum bilirubin is normally
.2-1.2 mg/dL
Total Direct Bilirubin
Less than .3 mg/dL
typically order BOTH total and direct bilirubin
What body part tends to get jaundice first? What level does bilirubin have to be in order for it to show up in the skin?
Eyes show jaundice first, then skin
greater or equal to 2.5 for the skin to show jaundice
Would pre-hepatic jaundice have higher unconjugated or conjugated bilirubin?
pre-hepatic would have higher UNconjugated levels
What is pre-hepatic jaundice caused by? What is the MC cause?
increased RBC hemolysis or impaired uptake in certain illnesses
causes an increase in unconjugated bilirubin in serum
RBC hemolysis is MC cause
What effect does hepatic jaundice have on unconjugated and conjugated bilirubin levels?
Increased Unconjugated bilirubin in serum due to impaired function of hepatocytes
Increased Conjugated bilirubin in serum due to hepatocellular inflammation obstructs flow to hepatic ducts - blocking excretion
Post Hepatic Jaundice will show increased _____ bilirubin in serum and ________ in gut. What is the MC cause?
increase conjugated in serum
decreased bilirubin in gut (pale stools) and no urobilinogen in urine
Obstruction in biliary tract blocking excretion
will NOT have an effect on unconjuated bilirubin
UCB or CB?
Unconjugated Hyperbilirubinemia
UCB or CB?
Conjugated Hyperbilirubinemia
**if a pt complains of itching, is it pre, intra, or post- hepatic?
itching is POST-hepatic
What is this? Where is it commonly found?
acholic stool
post-hepatic jaundice
What are 6 common manifestations of liver dz? Give a brief description of each
Coagulopathy: Decreased production of clotting factors
Thrombocytopenia: decreased Thrombocytes produced in bone marrow due to decrease TPO which is needed to stimulate thrombopoiesis that is also made in the liver
Leukopenia/ Anemia: decrease in TPO and erythropoietin, bone marrow suppression, diminished filtering of blood and absorption from GI (iron malabsorption)
Hypoalbuminemia: albumin is synthesized by the liver
Hyperbilirubinemia: due to abnormalities
Portal Hypertension: increase in pressure
What is the job of the portal vein? What does portal hypertension manifest as?
Vein that carries blood from digestive organs to liver
Increased pressure causes large veins/varices to develop across the esophagus and stomach to get around blockage
What is the MC cause of portal hypertension?
cirrhosis of the liver, scar tissue blocks blood flow through the liver
**What is the gold standard for dx portal hypertension?
obtaining a hepatic venous pressure gradient measurement
Catheter is inserted inside the inferior vena cava (U/S can also be used), and then inside the portal vein (endoscopically) to measure the difference between both pressures
What are the 4 ways portal hypertension manifests?
Splenomegaly
Esophageal Varices
Hemorrhoids
Caput Medusae
What 6 veins commonly get engorged as a result of portal hypertension?
esophageal veins
paraumbilical veins
inferior mesenteric vein
superior mesenteric vein
middle rectal vein
inferior rectal veins
What are the ABCDE of portal hypertension?
Ascites
Bleeding
Caput medusae
Diminished liver function
Enlarged spleen
What is the “underfil” pathogenesis associated with ascites?
Hypoalbuminemia
Decreased serum albumin allows shift of fluid out of blood and into peritoneal cavity
What is the “overflow” pathogenesis associated with ascites?
Increased pressure in portal venous system and liver lymphatics
ascites also impairs _______. What does it result in?
RAAS system
increase in Na retention which increases water retention in the belly
______ is the pathogen most strongly associated with infected ascites/ Spontaneous bacterial peritonitis?
e. coli
What is hepatorenal syndrome? What does it result in?
Arterial vasodilation in splanchnic circulation triggered by portal hypertension. Increased production of vasodilators (nitric oxide) in splanchnic circulation. As hepatic disease becomes more severe, progressive rise in cardiac output and fall in SVR in splanchnic circulation.
kidneys become poorly perfused and it causes renal failure
Why does liver disease commonly cause pruritus?
Bile salts that enter blood and tissue as a result of bile backing up from liver impairment.
Bile salts deposit under skin, trigger receptors
Why can you see Testicular atrophy, gynecomastia (males); Menstrual irregularities (females) as a result of liver disease?
Impaired cholesterol synthesis for testosterone
Impaired inactivation of estrogen = excess estrogen
What are spider nevi and palmar erythema a result from? Where are spider nevi commonly found?
excess estrogen
on the belly and face
_____ is a result of build-up of ammonia and other toxic chemicals in bloodstream because the liver cannot remove waste from your body. What are the s/s?
Hepatic Encephalopathy
confusion, tremors, coma
What is important to note about LFTs?
they can only suggest a category of liver illness and are used to help point the provider in the right direction and give hints as to the underlying cause
What is included in the hepatic panel (LFTs)?
Total Protein
Albumin
Total Bilirubin
Direct Bilirubin
Aspartate Aminotransferase (AST) (SGOT)
Alanine Aminotransferase (ALT) (SGPT)
Alkaline Phosphatase (ALP)
Name 5 additional liver function tests that are not included in the standard LFTs.
Gamma glutamyl transferase (GGT)
PT/PTT
Cholesterol
BUN
Hepatitis Panel
which LFTs are found in serum?
ALT
AST
ALP
GGT
LDH
5’-nucleotidase
What 3 LFT are used to measure damage to hepatocytes?
AST
ALT
LDH
** Which LFT is most specific to the liver? Where is AST also found?
ALT is most specific for the liver
AST is also found in the heart and skeletal muscles
** in general terms, what are the values for ALT and AST for acute and chronic dz?
**________ = MOST suggestive of CHRONIC alcoholic liver disease
AST > ALT (ratio > 2)
**________ = NASH/nonalcoholic cirrhosis
AST > ALT (ratio > 1) but less than 2
What is important to remember about LDH?
it is present in most tissues and NOT specific enough to give information about liver damage
**What are the 2 enzymes that measure cholestasis (biliary obstruction)? Where is ____ found?
Alkaline phosphatase
Gamma-glutamyl transpeptidase (GGT)
GGT found in liver and biliary tract
Where is ALP commonly found? What is the typical normal range?
Enzyme found in liver, biliary tract, and bone
Typical normal range: 45-135 IU/L (lab specific)
**What are the general guidelines with regards to ALP levels?
Elevations > 4x upper limit = Hepatic cholestasis
aka think liver is the problem
Elevations < 4x upper limit = Nonhepatic/non cholestatic cause
aka not likely a hepatic cause
____ is one of the first enzymes to increase due to obstructive disease. ** ______ + ______ = hepatobiliary obstruction
Alkaline phosphatase
increased ALP + GGT = hepatobiliary obstruction
What 4 organs is GGT found in? Where is it NOT found?
LIVER, pancreas, spleen, brain
NOT found in bone disease
**An ____ plus and _____ = cholestatic (obstructive) hepatobiliary disease
elevated ALP
elevated GGT
An isolated elevated GGT WITHOUT elevated ALP = _______ or _______
alcohol or certain medications
What 3 tests indicate hepatocellular damage (intrinsic hepatic disease)?
Marked elevation of AST/ALT as compared to ALP
Elevated total bilirubin
Elevated direct bilirubin
What 4 tests indicate an obstructive disease?
Marked elevation of ALP as compared to AST/ALT
Elevated GGT
Elevated or normal total bilirubin
Elevated direct bilirubin
What is the clinical significance of overproduction of bilirubin?
prehapatic
What is the clinical significance of Impaired uptake, conjugation, or excretion of bilirubin?
intrahepatic
What is the clinical significance of backward leakage from damaged hepatocytes or bile ducts due to blockage?
Posthepatic
Elevated _____ = hepatobiliary disease
Conjugated/Direct bilirubin
What are the 2 tests of hepatic synthetic function?
albumin and Prothrombin Time
albumin is synthesized by the _____. Hypoalbuminemia in the setting of other liver test abnormalities = ?????
liver
liver damage resulting in diminished liver function
Hypoalbuminemia when other liver tests are normal = ????? What should you look at next?
not a result of liver damage
could be poor nutrition/ increased excretion by the kidneys
Liver is major site for synthesis of ______. A prolonged PT can result from _______ or _______.
11 coagulation proteins
lack of synthesis of clotting factors
consumption/damage to clotting factors
A prolonged PT in the absence of other abnormal liver tests = ????
not due to diminished liver function
aka look for another non-liver cause
What is the MC symptoms for common liver disorders?
fatigue
What is the MC pt type in autoimmune hepatitis? What is the underlying cause?
young to middle age women, has a genetic component
Continuing hepatocellular inflammation and necrosis and has a tendency to progress to cirrhosis. Will have circulating auto-antibodies and elevated serum globulin level
-insidious onset to sudden attack of fulminant hepatitis
-Mild, asymptomatic presentation to acute liver failure
-Often precipitated by a viral illness/drug exposure
-Exacerbations may occur postpartum
What am I?
What will the AST/ALT levels look like?
autoimmune hepatitis
AST/ALT elevations - greater than 1.5-50x normal
What other lab findings will be positive in autoimmune hepatitis? ____ is needed for definitive dx
Elevated total bilirubin
Positive ANA (Anti-nuclear antibody)
atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA)
Antibodies to soluble liver antigen (anti-SLA)
liver bx
What is the tx for Autoimmune hepatitis?
Prednisone 30-60 mg qd: need to start high and taper weekly
+/- azathioprine
liver transplant if pt fails corticosteroid therapy
What are the 4 major drug/toxin causes that induce hepatitis?
Acetaminophen (especially with alcohol)
Isoniazid (especially with rifampin)
Antibiotics: tetracyclines
“herbal supplements”
What will the ALT, AST levels look like in drug/toxin induced hepatitis? What is the tx?
Elevated transaminases (ALT > AST)
stop offending agent!! may require liver transplant
**What are the daily max doses for acetaminophen in adults and children? Why does acetaminophen overdose commonly happen?
More than 4g (4000 mg) adults or 80 mg/kg kids
Failure to recognize that acetaminophen is found in more than one medication
What stage of Tylenol induced hepatitis? What is the associated timeframe?
Stage I
(.5-24 hours)
What stage of Tylenol induced hepatitis? What is the associated timeframe?
Stage II
(24-72 hours)
What stage of Tylenol induced hepatitis? What is the associated timeframe?
Stage III (72-96 hours)
What stage of Tylenol induced hepatitis? What is the associated timeframe?
Stage IV
(4 days to 2 weeks)
What stage is death MC in for acetaminophen induced hepatitis? Why?
stage III
Death generally occurs in this stage d/t multiorgan system failure
How do you determine if a pt needs to be treated for Tylenol induced hepatitis?
Based on measurement of acetaminophen level
Plot the serum level versus time since ingestion on an acetaminophen nomogram
Treat “above the line”
What is the tx for Tylenol induced hepatitis?
Activated charcoal if possible within 1-2 hours of ingestion
Also treat with N-acetylcysteine oral or IV
Acts as a hepatoprotective agent
Loading dose for 60 minutes, then infusion over 20 hours
Are men or women at higher risk of developing alcoholic hepatitis?
women
**What are the 3 stages of alcoholic liver disease?
- Fatty Liver (Steatohepatitis)
- Alcoholic Hepatitis
- Cirrhosis
**____ is the symptoms of fatty liver if any are present at all. Is it reversible?
Hepatomegaly
Asymptomatic, Reversible
**What characterizes alcoholic hepatitis? What are some s/s? Is it reversible?
Characterized by acute/chronic inflammation and parenchymal damage
Symptomatic, RUQ pain, tender hepatomegaly, typically reversible
Fatigue, fever, nausea, anorexia, recurrent infections (aspergillosis), bouts of jaundice
often reversible but is an important precursor to cirrhosis
**What are s/s of cirrhosis? Is it reversible?
Ascites, abdominal pain, splenomegaly, fever
NOT reversible
alcohol is broken down into _______. Why does it cause damage?
acetaldehyde
Toxic to your body and liver
Can cause damage at the cellular level
Damages cellular DNA and prevents body from repairing
What is consider higher frequency alcohol intake?
Higher frequency in patient who consume over 50g alcohol daily for 10 years
4 oz 100 proof whiskey
15oz wine
4 12oz beer cans
What are the lab finding in fatty liver?
Mild AST, ALT elevations
Anemia (macrocytic)
What are the lab findings in alcoholic hepatitis?
See a greater increase in ALT, AST
AST > ALT, usually by a factor of 2 or more
Elevations in ALP, not more than 3x normal
Elevated total bilirubin
Leukopenia, Thrombocytopenia d/t direct toxic effect of alcohol on megakaryocyte production
What lab findings are common in alcoholic cirrhosis?
______ provides definitive dx for alcoholic liver dz? What will it show?
Liver biopsy
Demonstrates macrovesicular fat and PMN infiltration with hepatic necrosis
What is the non-pharm tx for alcoholic liver dz?
abstinence from Alcohol - Most Important
-Fatty Liver reverses with abstinence from alcohol
Nutritional support
Folic Acid, Zinc, Thiamine supplementation
What is the pharm tx for alcoholic liver dz?
Methylprednisolone
Pentoxifylline
_______ Increases blood flow and tissue oxygenation, decreases blood viscosity
Pentoxifylline
What is the alcoholic screening tool? What does each letter stand for? A “YES” to _____ questions is considered clinically significant and patient may have a problem with their alcohol usage
CAGE questionnaire
2 or more
What is Non-Alcoholic Fatty Liver Disease? What is a very common underlying factor?
Presence of liver fat (steatosis) when no other causes for secondary hepatic fat accumulation are present, may or may not have inflammation and can progress to cirrhosis
OBESITY!
What are the 2 different categories of Non-Alcoholic Fatty Liver Disease? Give a brief description of each
Non-alcoholic Fatty Liver (NAFL): Hepatic fat/steatosis without evidence of inflammation
Non-Alcoholic Steatohepatitis: Hepatic fat/steatosis with evidence of inflammation
When are Non-Alcoholic Fatty Liver Disease pts most commonly dx, what age? What are some common s/s?
Most patients diagnosed in 40s or 50s
RUQ discomfort, hepatomegaly
Signs of chronic liver disease uncommon
Asymptomatic or mild, vague symptoms
What do the labs commonly look like in NASH? _____ is needed for definitive dx
Mildly elevated AST/ALT
AST/ALT ratio with NASH is usually <2
liver bx
What is the spectrum of non-alcoholic fatty liver disease? Which ones are reversible?
What is the tx for Non-Alcoholic Fatty Liver Disease?
What are the 2 MC causes of cirrhosis? What significantly increases your likelihood of developing cirrhosis?
alcohol and chronic hep C
having MULTIPLE liver conditions
What is the pathophy behind cirrhosis?
Fibrosis and nodular regeneration throughout the liver
Replaces functional hepatocytes with nonfunctioning fibrotic nodules
_____ is often the first sign of cirrhosis
Hematemesis from esophageal varices often first sign
_____ is the first line dx study in cirrhosis. What is it assessing?
US
Assessing liver size, nodularity, blood flow, and confirming presence of ascites
**______ is needed for the definitive dx in cirrhosis. Need _____ to evaluate for esophageal varices
Liver biopsy
EGD
What is the tx for cirrhosis? what diet is recommended?
liver transplant, there is no cure!!
Getting enough protein, low carbs, low sodium
Reduce protein intake if hepatic encephalopathy
What are the 5 complications of cirrhosis?
What is the tx for ascites/edema?
-sodium restrict
-Spironolactone (Aldactone) and Furosemide (Lasix)
-paracentesis
-Transjugular Intrahepatic Portosystemic Shunt (TIPS)
What is the tx for Spontaneous Bacterial Peritonitis? What pathogen is MC?
Cefotaxime (Claforan) -> can also use augmentin or ceftriaxone
e. coli
What is the prophylaxis for recurrent Spontaneous Bacterial Peritonitis?
Oral fluoroquinolones
What are the 2 types of hepatorenal syndrome? What is the tx?
Type I = Sudden doubling of Cr to a level > 2.5
Type II = Slowly progressive
tx:
Stop diuretics
Increase blood flow to kidneys
IV Albumin
Dialysis
TIPS
Liver transplant
How do you dx hepatic encephalopathy? What is the tx?
clinical suspicion, confirmed with serum ammonia level. No imaging required.
-Reduce protein intake
-Lactulose = limits ammonia forming organisms produced in the gut
-Antibiotics (Rifaximin, Metronidazole) minimize gut ammonia producing bacteria
What is the tx for esophageal varices?
IV fluids
Transfusion with PRBC’s
FFP (d/t coagulopathy often associated)
Octreotide - vasoactive drug/slows bleeding
EGD once hemodynamically stable
IV antibiotic prophylaxis
Increased risk for infection
banding/sclerotherapy/balloon tamponade
How do you PREVENT a rebleed in esophageal varices?
Repeat Band ligation plus Beta blockers (Propranolol)
TIPS
Liver Transplant
What is your MELD score based on? Must have a MELD score of _____ to qualify for liver transplant.
Based on bilirubin, creatinine, and INR
14 or higher
_____, ______ and ______ can help reduce the risk of rapid cirrhosis decompensation
Coffee, tea, and statins
What is primary biliary cirrhosis? Who is the MC pt? What is it associated with?
Chronic, autoimmune destruction of intrahepatic bile ducts and cholestasis
Most common in women ages 40-60, genetic component
Often associated with other autoimmune disorders
____ and _____ are the most common early sx of Primary Biliary Cirrhosis. What are some later s/s?
Fatigue and pruritus
Hepatomegaly
Xanthomatous lesions
Jaundice
Steatorrhea
Portal Hypertension
Other manifestations of cirrhosis
What is this? What dz is it associated with?
Xanthomatous lesions
Primary Biliary Cirrhosis
What are the lab findings in Primary Biliary Cirrhosis? Do you need a liver bx?
Baseline Ultrasound completed, liver biopsy NOT necessary
_______ is the only DA approved treatment for Primary Biliary Cirrhosis. ______ provide symptomatic relief of pruritus. What is the definitive tx?
Ursodeoxycholic acid
Cholestyramine
definitive tx: liver transplant
What does Ursodeoxycholic acid help with in primary biliary cirrhosis?
Slows progression of disease
Reduces toxicity of cholestasis
Can delay or prevent need for liver transplant
