Weeks 3 & 4: Liver Function Flashcards
metabolic function of liver
detoxification/breakdown: toxins, hormones, drugs
synthesis: bile - for emulsification of fats in the lumen of the GI tract
protein: production - including amino acids, clotting factors, vitamins, albumin and various other hormones. Activation.
carbohydrate: including glyconeogenesis.
lipid: including cholesterol and triglyceride production
red blood cells: normal in the fetus but pathological in adults
storage: nutrients - glucose. vitamins & minerals: Vitamin A/D/B12, iron & copper
Immunological: kupffer cells lining sinusoids acts as antigen presenting cells
liver (hepatocyte) function and revelation after resection
removing metabolic waste production, hormones, drugs & toxins
producing bile to aid in digestion
processing nutrients absorbed from the digestive tract
storing glycogen, certain vitamins and minerals
Maintaining normal blood sugar
Synthesizing plasma proteins, albumin, and clotting factors
Producing immune factors & removing bacteria
Removing senescent red blood cells from the circulation
Excreting bilirubin
common lab liver tests
Bilirubin AST ALT GGTP Alkaline phosphate LDH PT
what has recently happened to normal values
ALT
AST, normal range
<40
ALT normal range
19-35 for women, 29-33 for men
GGT normal range
< 60
alkaline phosphate normal range
< 112
what are the liver enzymes
ast, alt, ggt, alkaline phosphate
what are liver function tests?
bilirubin, albumin, prothrombin time
normal range for bilirubin
< 1.2
albumin normal range
3.5-4.5
prothrombin time normal range
< 14 seconds
WBC normal?
4000-11000
hematocrit normal?
> 40
platelet normal
> 150000
what should you say instead of liver function tests?
liver tests b/c more tests aren’t a function of liver function
what does ALT (alanine transaminase) do?
Produce in hepatocytes
Very specific marker of hepatocellular injury
Relatively low concentrations in other tissues so more specific than AST
Levels fluctuate during the day
Rise may occur with the use of certain drugs or during periods of strenuous exercise
what does AST aspartate transaminase do?
Occurs in two isoenzymes, indistinguishable on standard AST assays
The mitochondrial isoenzyme is produced in hepatocytes and reacts to membrane stresses in a similar way to ALT
The cytosolic isoenzyme is present in skeletal muscle, heart muscle and kidney tissue
Caution must be exercise in its use to evaluate hepatocellular damage
Usually rises in conjunction with ALT to indicate hepatocellular injury: a hepatitis picture
what does alkaline phosphatase (ALP) do
A group of isoenzymes that act to dephosphorylate a variety of molecules throughout the body
Produced in the membranes of cells lining bile ducts and canaliculi
Released in response to the accumulation of bile sales or cholestasis
Non-hepatic production in the kidney, intestine, leukocytes, placenta & bone
Physiological rise in pregnancy or in growing children
Pathologic rise in Paget’s disease, renal disease, and with bone metastases
what does GGT do (gamma glutamyl transferase)?
Present in liver, kidney, pancreas & intestine
It is found in the microsomes of hepatocytes and biliary epithelial cells
Elevation of GGT in association with a rise in ALP is highly suggestive of a biliary tract obstruction and is known as a cholestatic picture
Subject to rise with hepatic enzyme induction d/t chronic alcohol use or drugs such as rifampicin and phenytoin
what test is liver specific?
GGTP - an isolate elevation of just one of the other test values should raise suspicion that a source other than the liver is the cause, when several liver test results are simultaneously out of normal range consideration of non-hepatic sources becomes irrelevant
GGTP level is too sensitive, frequently elevated when no liver disease is apparent. A GGTP is useful in only two instances
- it confers liver specificity to an elevated alkaline phosphate level
- in aminotransferase level elevations with AST/ALT ratio > 2, elevation of GGTP further supports alcoholic liver disease
in addition it can be used to monitor abstinence from alcohol
an isolated elevation of the GGTP level does not need to be further evaluated unless there are additional clinical risk factors for liver disease
differential diagnosis of increased AST
primary liver disease acute myocardial infarction muscle trauma/diseases pancreatitis intestinal surgery burns renal infarction pulmonary embolism
differential diagnosis of increased ALT
primary liver disease biliary obstruction pancreatitits ALT>AST viral hepatitis AST>ALT alcoholic liver disease
differential diagnosis of increased ALP
biliary obstruction primary liver disease (changes parallel GGT) infiltrative liver disease bone diseases hyperparathyroidism
differential diagnosis of increased GGT
biliary obstruction
primary liver disease (changes parallel ALP)
alcohol consumption
pancreatitis
differential diagnosis of increase bilirubin
biliary obstruction
primary liver disease
hemolytic anemias
hypothyroidism
medications & liver
may cause increases in one or more liver chemistry tests because of direct hepatotoxicity or cholestasis
ALT & AST?
are abundant liver enzymes
AST is also present in heart & muslce
where is ALP present?
in nearly all tissues, primarily bone & liver.
where is GGT?
abundant in liver, kidney, pancreas & intestine
do ALT & AST vary on lab?
yes, generally < 40
mild ALT & AST elevations?
- less than 5 times upper normal limit - they should be rechecked prior to extensive workup
possible causes: chronic hepatitis C or B, acute viral hepatitis, NAFLD, hemachromatosis, autoimmune hepatitis, medicaitons, alcohol-related liver injury, Wilson’s disease
moderately elevated ALT & AST?
- 5-15 times upper normal limit.
should be investigated w/o waiting to confirm the persistence of abnormal ALT,
possible causes - entire spectrum of liver diseases
severe ALT & AST elevations
> 15 times ULN
suggest severe acute liver cell injury
acute viral hepatits, ischemic hepatitis, or other vascular disorder, toxin mediated hepatitis, acute autoimmune hepatitis
what is bilirubin?
heme degradation product excreted in the bile, it requires conjugation in the liver before it is secreted
what should you do about hyperbilirubinemia?
investigate cause by direct (conjugated) or indirect (unconjugated) fraction of bilirubin
pre-hepatic causes (increased production, decreased liver uptake)
cause increase of indirect
intra-hepatic/post-hepatic causes
decreased hepatic excretion, increase of direct
increased production causes of hyperbiliirubinemia
hemolysis
decreased liver uptake causes of hyperbilirubinemia
Gilbert syndrome (5% of populatin - benign)
decreased hepatic excretion causes of hyperbilirubinemia
bile duct obstruction, primary biliar cirrhosis, primary sclerosing cholangitis, benign recurrent cholestasis, hepatitis, cirrhosis, medications, sepsis, total parenteral nutrition, Dublin-Johnson Syndrom,
what causes increased GGT?
alcohol consumption
what causes increased ALP & GGT
bile duct obstruction, primary biliary cirrhosis, primary sclerosing cholangitis, benign recurrent cholestasis, infiltrative disease of the liver (sarcoidosis, lymphoma, metastatasic disease)
causes of isolated elevated ALP (extra hepatic disease)
bone disease, pregnancy, chronic renal failure, lymphoma, congestive heart failure
causes of abnormal PT and albumin levels
indicate severe hepatic synthetic dysfunction & indicates progression to cirrhosis or impending hepatic failure
what is nonalcoholic fatty liver disease?
fatty infiltration (steatosis) of the liver, exceeding 5% of liver weight
requires exclusion of alcohol as potential cause. acceptable levels of alcohol consumption are controversial but in general < 20 grams/ day (2 drinks) in men & < 10 grams/day (1 drink) in women
what is primary NAFLD?
common term for typical NAFLD associated w/ central obesity and/or DM2 or insulin resistance w/o another specific etiology
what is secondary NAFLD?
used to defined as NAFLD in the absence of insulin resistance and associated w/ other causes such as :
polycystic ovary syndrome
hypothyroidism
hypogonadism
hypopituitarism
medicaiton use (glucocorticoids, tamoxifen, amiodarone, HAART, diltiazem)
disorders of lipid metabolism (abetalipoproteinemia, lipodystrophy, Weber-CHristian syndrome, Andersen’s disease)
total parenteral nutrition and jejunoileal bypass surgery
many cases of secondary NAFLD likley represent an exacerbation of often unrecognized “primary” NAFLD
what is non alcoholic steatohepatitis (NASH)?
the more seer form of NAFLD characterized by inflammation, hepatocyte injury (ballooned hepatocytes) with or without fibrosis. it can progress to cirrhosis & possibly liver cancer
what is NASH cirrhosis
the presence of cirrhosis w/ current or previous evidence of steatosis or NASH
what is cryptogenic cirrhosis
a term used to define the presence of cirrhosis w/ no obvious etiology, frequently there is a history of DM & obesity.
do DM2 have > or < risk for cirrhosis
DM2 higher risk for cirrhosis compared to the general population, possibly d/t NAFLD
also at higher risk of hepatocellular carcinoma compared to the general population, possibly d/t NAFLD
race groups at higher risk for NAFLD?
non hispanic whites and hispanics at higher risk
what are predictors of more severe disease of NAFLD?
age > 40-50 years female severe obesity hypertension DM hypertriglyceridemia elevated ALT, AST, GGT, AST/ALT ratio > 1
genetic predisposition for NAFLD?
single variant in an allele is strongly associated w/ liver fat & liver inflammation. allele is more common among Hispanics.
diagnosis of NAFLD requires?
presence of steatosis (by imaging or liver biopsy)
absence of significant alcohol consumption
competing cause of chronic liver disease
what are tests to rule out co-existing treatable conditions for NAFLD?
viral hepatitis C
autoantibodies
hemachromatosis
imaging methods to distinguish fatty liver and steatohepatitis?
no imaging methods to distinguish fatty liver & steatohepatitis
but imaging can help exclude biliary tract or focal liver disease
how to detect the presence of liver fat?
US is more sensitive than CT scan, less expensive & no radiation risk…
MRI primarily used in research settings to quantify the amount of fat in the liver
how to detect liver fibrosis
US based transient elastography measures tissue elasticity non invasively and correlates well w/ liver fibrosis in liver biopsy in patients with viral hepatitis. this method has been approved by FDA.
what is gold standard for NAFLD diagnosis
liver biopsy
staging (extent of injury)
& grading (degree of activity) of NAFLD
