Disorders of the Liver Part 1 Flashcards
What are the 4 lobes of the liver and what separates them?
- Anteriorly: Right lobe and left lobe by falciform ligament.
- Posteriorly: Anterior and posterior caudate via porta hepatis
What are the 3 components of the porta hepatis?
- Hepatic portal vein
- Hepatic artery
- Common Hepatic duct
Not the same as a portal triad
What are the two vessels that supply hepatocytes?
- Venous blood via portal vein
- Oxygenated blood via hepatic arteries
What is the flow of blood beginning at a portal vein?
- Portal veins
- Sinusoids
- Central Veins
- Hepatic Veins
- IVC
What two lipoproteins are made by hepatocytes?
- VLDL
- HDL
What is bilirubin from?
End product of the breakdown of an RBC, created as unconjugated/indirect/lipid soluble bilirubin
Breakdown of heme to protoporphyrin to bilirubin
UCB = unconjugated bilirubin
What binds to UCB and takes it to the liver?
Albumin
What enzyme is used to conjugate bilirubin?
Uridine glucuronyl transferase = UGT
What happens to bilirubin once it is conjugated?
- Transported down bile canaliculi to bile ducts
- Deposited within the gallbladder at direct/conjugated bilirubin
It is now water soluble.
What converts CB to urobilinogen and what happens to it?
- Microbes convert it to UBG.
- UBG can either become stercobilin into your poop (giving it color)
- It can also become urobilin and get excreted via the kidneys or goes back to the liver
What is jaundice?
- Product of heme metabolism
- Accumulation of bilirubin
How elevated is serum total bilirubin to give skin a yellow discoloration?
Usually greater than 2.5mg/dL
Would pre-hepatic jaundice present with higher UCB or CB?
UCB
How do bilirubin levels look in pre-hepatic jaundice?
Increased UCB in serum due to RBC hemolysis
aka hemolytic anemias
How can bilirubin levels vary in hepatic jaundice?
- Increased UCB in serum due to hepatocyte impairment
- Increased CB in serum due to hepatic duct obstruction
How do bilirubin levels look in post-hepatic jaundice?
- Increased CB in serum due to biliary tract obstruction
- Decreased bilirubin in gut = pale/acholic stool and no UB in urine
What clinical findings are most suggestive of elevated UCB?
- Normal stool and urine color
- Mild jaundice
- No bilirubin in urine
- Splenomegaly (Except in SCD)
What clinical findings are most suggestive of elevated CB?
- Pruritis and jaundice
- Light colored stools
- Malaise, anorexia, low-grade fever, RUQ, Dark urine
- Hepatomegaly, spider telangiectasias, palmar erythema, ascites, gynecomastia, sparse body hair
- Varies based on liver dysfunction
What is the term for light colored stool?
Acholic stool
What clotting factors are NOT affected in liver disease?
- III
- IV
- VIII
What does Vit K require to be absorbed from the GI tract?
Bile
What CBC count will be lower in liver disease?
Thrombocytopenia
TPO is made in the liver
What are the 3 common CBC abnormalities seen in liver disease?
- Thrombocytopenia
- Leukopenia
- Anemia
EPO is made in both the kidneys and liver
What carrier protein does the liver make?
Albumin
What is the underlying mechanism behind portal HTN?
Blockkage in blood flow through the liver, resulting in cirrhosis most commonly.
What is the gold standard to diagnose portal HTN?
IVC catheter to measure hepatic venous pressure
What are the clinical manifestations of portal HTN?
- Splenomegaly
- Esophageal varices
- Hemorrhoids
- Caput Medusae
What are the main veins implicated in portal HTN?
- Esophageal veins
- Paraumbilical veins
- Superior mesenteric veins
- Inferior mesenteric veins
- Middle rectal veins
- Inferior rectal veins
What are the ABCDEs of Portal HTN?
- Ascites
- Bleeding
- Caput Medusae
- Diminished liver function
- Enlarged spleen
What is the MCC of ascites?
Cirrhosis
What are the underlying mechanisms of ascites?
- Underfill due to lack of albumin and shift of fluid
- Overflow due to increased pressure
- Impairment of RAAS
What is the MC organism that causes spontaneous bacterial peritonitis?
E. Coli
Why does hepatorenal syndrome occur?
- Arterial vasodilation in splanchnic circulation due to Portal HTN
- More NO is made, vasodilating more and causes a fall in CO
- Kidneys become poorly perfused
- Acute renal failure ensures
What causes pruritis in liver disease?
Bile salts
What are spider nevi and palmar erythema due to?
Excess estrogen
What can happen specifically to males with liver disease? Females?
- Males: testicular atrophy & gynecomastia due to impaired cholesterol synthesis
- Females: Menstrual irregularities due to excess estrogen
What is the severe manifestation of liver disease?
Hepatic encephalopathy due to buildup of ammonia
Confusions, tremors, coma
What are the components of a LFT/hepatic panel?
- Total protein
- Albumin
- Total bilirubin
- Direct bilirubin
- AST/SGOT
- ALT/SGPT
- ALP
- GGT
- PT/PTT
- Cholesterol
- BUN
- Hepatitis Panel
Bolded are addons
What are the two serum aminotransferases?
- Alanine aminotransferase (ALT/SGPT)
- Aspartate aminotransferase (AST/SGOT)
What liver enzymes measure hepatocyte damage?
- AST/ALT
- LDH
Which liver enzyme is most specific for hepatocellular damage if markedly elevated?
ALT
AST is found in heart and skeletal muscle too.
ALT has a L, so its the most Liver specific
Acute Liver Trouble
What do significant elevations of ALT and AST associate the most with?
Hepatocellular damage
8-25x = acute damage
In general, what does an acute liver damage present as in terms of the aminotransferases enzymes? Chronic?
- Acute: ALT > AST (8-25x ULN)
- Chronic: AST > ALT (< 8x ULN)
ALT = Acute Liver Trouble
What does a moderate elevation of AST > ALT of around 2 or more suggest?
Chronic alcoholic liver disease
What does a moderate elevation of AST > ALT of around 1-1.99 suggest?
Chronic NASH/non alcoholic cirrhosis
What elevates LDH?
Any cellular damage in general. Non-specific test.
What liver enzymes are used to measure cholestasis?
- ALP
- GGT (both)
- 5’-nucleotidase (liver specific)
What does a elevation of ALP > 4x ULN suggest? < 4x ULN?
- More than 4x ULN = hepatic cholestasis
- Less than 4x ULN = non-hepatic/non-cholestatic cause
What might elevated ALP and GGT suggest?
Hepatobiliary obstruction
What is one of the first enzymes to increase in an obstructive disease of the biliary tract?
ALP
What might elevated GGT without elevated ALP suggest?
Alcohol or medications
What is GGT not elevated in?
Bone disease
What LFTs suggest hepatocellular damage?
- Marked elevation of AST/ALT compared to ALP
- Elevated total and direct bilirubin
What LFTs suggest obstructive disease of the liver?
- Elevated ALP compared to AST/ALT
- Elevated GGT
- Elevated/normal total bilirubin
- Elevated direct bilirubin
In summary, what does elevated direct bilirubin suggest?
Hepatobiliary disease
What are the tests for hepatic synthetic function?
- Albumin
- PT
What affects albumin level?
- Liver damage
- Poor nutrition
- Kidney disease causing increased excretion(Nephrotic)
If PT is prolonged but LFTs remain normal, what does this suggest?
Liver function is fine and not the cause
What characterizes autoimmune hepatitis?
Circulating auto-antibodies and elevated serum globulin levels
What demographic is autoimmune hepatitis MC in?
Young to middle aged women
How does autoimmune hepatitis present?
- Insidious onset
- Often precipitated by a viral illness/drug exposure or postpartum
- Otherwise healthy with multiple spider nevi, cutaneous striae, acne
- Extrahepatic features like arthritis or thyroiditis
What lab findings are associated with autoimmune hepatitis?
- AST/ALT elevations of 1.5x-50x ULN
- Elevated total bilirubin
- Positive ANA
- pANCA
- Anti-SLA (soluble liver antigen)
How is autoimmune hepatitis definitively diagnosed?
Liver biopsy
What conditions are autoimmune hepatitis co-existing with sometimes?
- Primary biliary cirrhosis
- Sclerosing cholangitis
How do we treat autoimmune hepatitis?
- Prednisone
- May add azathioprine
- Liver transplant last resort
What medications can induce hepatitis?
- Acetaminophen with alcohol
- Isoniazid with rifampin
- ABX (tetracyclines)
- Herbal supplements
How does drug/toxin induced hepatitis present?
- Hepatomegaly
- Jaundice
- Fatigue
- N/V
How do the transaminases present in drug/toxin induced hepatitis?
ALT > AST
Acute Liver Trouble
How much acetaminophen can cause hepatitis?
4g in adults or 80mg/kg in kids
Found in more than just tylenol!!!!!!
When does stage 1 of acetaminophen induced hepatitis occur and what happens?
- Timing: 30 minutes - 24 hours
- N/V, diaphoresis, pallor, lethargy, malaise
- Normal labs
- Could be asymptomatic
When does stage 2 of acetaminophen induced hepatitis occur and what happens?
- Timing: 24-72 hours
- Stage 1 symptoms resolve, but then the patient worsens
- AST/ALT elevations occur
- RUQ pain with hepatomegaly and tenderness
- PT and bilirubin elevations
When does stage 3 of acetaminophen induced hepatitis occur and what happens?
- Timing: 72-96 hours
- Stage 1 symptoms reappear + hepatic encephalopathy
- AST/ALT > 10k
- Prolong PT/INR
- Hyperammonemia
- Hypoglycemia
- Acute renal failure
- Death usually occurs d/t multi organ failure
When does stage 4 of acetaminophen induced hepatitis occur and what happens?
- Timing: 4 days to 2 weeks
- Only occurs if you survive stage 3
- If you do recover, complete recovery is seen
How do you diagnose acetaminophen induced hepatitis?
- Serum level of acetaminophen
- treat above the line for the graph
How do you treat acetaminophen induced hepatitis?
N-acetylcysteine
Activated charcoal also helps
What is considered excessive alcohol intake and how long do you have to do it for have high risk?
- Males: 2+ drinks a day
- Females: 1+ drinks a day
- 10 years of this
What are the stages of alcoholic liver disease?
- Fatty liver/steatohepatitis (hepatomegaly)
- Alcoholic hepatitis (acute/chronic inflammation and parenchyymal damage)
- Cirrhosis (Non-reversible)
How much do you have to drink to have a higher frequency of alcoholic liver disease?
50g of alcohol daily for 10 years
Why does alcohol cause damage?
Acetaldehyde is a metabolite of ethanol that causes cellular damage
In steatohepatitis, how do labs look?
- Mild AST/ALT elevations
- Macrocytic anemia
In alcoholic cirrhosis, how do labs look?
- AST/ALT elevations
- Elevated total bilirubin > 10mg
- Hypoalbuminemia
- PT/INR prolongation
- Anemia (iron and folate)
- Later: Lyte abnormalities and elevated BUN/Cr
In alcoholic hepatitis, how do labs look?
- AST > ALT by 2x or more
- ALP elevated up to 3x
- Elevated total bilirubin
- Leukopenia and thrombocytopenia
Not an acute process, so AST elevates more
How do you definitively diagnose alcoholic liver disease?
Biopsy showing macrovesicular fat and PMN infiltration with hepatic necrosis
How do alcoholic steatohepatitis and NASH present?
Identical
What is the #1 treatment for alcoholic steatohepatitis?
Not drinking
Reversible at steatohepatitis stage.
What are the pharmacotherapy options for alcoholic hepatitis?
- Methylprednisolone x1 month
- Pentoxifylline if severe (vasodilator) x1 month
What are the unfavorable prognostic factors for alcoholic hepatitis?
- Prolonged PT/PTT
- Bilirubin > 10mg
- Hepatic encephalopathy
- Azotemia
What is the MC risk factor for NA fatty liver disease?
Obesity
What is the difference between Non-alcoholic fatty liver and non-alcoholic steatohepatitis?
- NAFL has NO inflammation
- NASH has inflammation
When is NAFLD typically diagnosed?
40s-50s
How do AST/ALT appear for NASH?
< 2
ETOH would make it higher
How do you definitively diagnose NASH?
Liver biopsy
NAFLD Spectrum Image
What medications can help treat NAFLD?
- Vit E
- TZDs
- Metformin
- Wt loss agents
Insulin sensitizing agents
What are the poor risk factors for NASH to become cirrhosis?
- Old
- Male
- Obesity
- DM
What is seen throughout the liver in cirrhosis?
- Fibrosis
- Nodular regeneration replacing functional hepatocytes with nonfunctioning fibrotic nodules
How does cirrhosis typically present?
- N/V
- Abd pain
- S/S of Portal HTN
- Spider angiomas, palmary erythema
- Menstrual abnormalities, ED, gynecomastia
- Anemia
- Glossitis
- Jaundice (later)
- Ascites (later)
- Encephalopathy (later)
How do labs appear early in cirrhosis?
Minimal changes
What is the first-line test for cirrhosis?
US to assess size and ascites and other stuff
How is cirrhosis definitively diagnosed?
Liver biopsy
What other imaging is highly useful in cirrhosis evaluation?
EGD to check for esophageal varices
Since Portal HTN is v common w/ cirrhosis
How do we treat ascites/edema?
- Na restriction
- Spironolactone
- Lasix
- Paracentesis (new onset, unable to tolerate diuretics, or respiratory issues)
- TIPS placement for variceal bleeding, but also treats ascites
What suggests bacterial peritonitis from ascites?
- Worsening abd pain
- Fever
- Leukocytosis
What is the MCC of bacterial peritonitis and the treatment and prophylaxis?
- MC organism: E. coli
- Tx: Cefotaxime 2g IV q8-12h x 5-7d
- Prophylaxis: Oral FQ
How do you treat hepatic encephalopathy?
- Less protein
- Lactulose to get rid of ammonia organisms
- ABX (Rifamixin or metro)
What infusions may help with anemia and coagulopathies due to cirrhosis?
- Ferrous sulfate
- Folic acid
- Vit K
- FFP
- Oral thrombopoietin (maybe)
What are the components of a MELD score and what is it?
- Model for End Stage Liver Dz
- Bilirubin, creatinine, and INR
- 14 or higher needed to qualify for transplant
What everyday things can help reduce the risk of rapid decompensation from cirrhosis?
- Coffee
- Tea
- Statins
What is primary biliary cirrhosis/cholangitis?
Chronic, autoimmune destruction of intrahepatic bile ducts and cholestasis
Who is primary biliary cholangitis MC in?
Women aged 40-60
Often with other autoimmune conditions
What lab finding is incidentally found that suggests primary biliary cholangitis?
Elevated ALP
What are the MC early s/s of primary biliary cholangitis?
Fatigue and pruritis
What labs are elevated in primary biliary cholangitis?
- Early: ALP and cholesterol
- Later: Bilirubin
- Antimitochondrial Ab in 95% of pts
- Positive ANA and IgM
How is primary biliary cirrhosis diagnosed?
US and labs only
What is the treatment for Primary biliary cholangitis?
- Ursodeoxycholic acid (FDA approved)
- For itchin: Cholestyramine (bile salt binder)
What does primary biliary cirrhosis increase your risk of?
Hepatobiliary carcinoma
