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CLM exam 2
what is the largest solid organ in the body
liver
where is the liver located
right upper quadrant of the abdomen
what are the functions of the liver
process and synthesize amino acids into circulating proteins
breaks down excess amino acids and make byproducts
store carbohydrates from the gut in the form of glycogen and helps prevent hypoglycemia
cholesterol synthesis
primary location of detoxification
what are lab tests to check protein synthesis in the liver
albumin
prealbumin
prothrombin time/INR
what lab tests check excretion into bile ducts and drainage into duodenum
bilirubin
alkaline phosphatase (ALP)
4’-nucleotidase
gamme-glutamyl transpeptidase (GGT)
what disease state is the impairment of excretion into bile ducts and drainage into the duodenum
cholestasis
what lab tests check for hepatocellular injury
aspartate aminotransferase (AST)
alanine aminotransferase (ALT)
what lab tests check for detoxification in the liver
ammonia
what lab tests check for lipid metabolism/synthesis
cholesterol
what lab tests are used to check for liver damage
albumin
INR/PT
ALP
AST/ALT
bilirubin
ammonia
what lab tests are used to check for alcohol intake
GGT
AST — usually 2x ALT
ALT
what is a normal range for albumin
3.5-4.8 g/dL
what happens when there are low concentrations of albumin in the body
drop oncotic pressure → fluid leaks into interstitial space → edema
does prealbumin or albumin have a shorter half life
prealbumin
what protein is less affected by liver disease and hydration status
prealbumin
what is a normal INR/PT
0.9-1.2/12.7-15.4 seconds
where are most clotting factors made
in the liver
what, besides liver dysfunction, can elevate INR/PT
vitamin K deficiency
where is alkaline phosphatase found
in liver, bone, small intestine, kidneys, placenta, and leukocytes
what level of alkaline phosphatase indicates cholestasis
concentration 4x greater than normal
what is the normal range of total bilirubin
0.2-1.3 mg/dL
what type of bilirubin is not water soluble
total bilirubin
what type of bilirubin is bound to albumin in the blood
total bilirubin
what is the normal range of direct bilirubin
0-0.3 mg/dL
what type of bilirubin is water soluble
direct bilirubin
what type of bilirubin is excreted by the kidneys
direct bilirubin
what causes yellowing of the skin and sclera of the eyes (jaundice)
elevated bilirubin
what is the total bilirubin range that presents with visible jaundice
2-4 mg/dL
how is indirect (unconjugated) bilirubin produced
breaking down erythrocytes from circulation
how is indirect bilirubin removed from circulation
by converting direct bilirubin via the liver
what can cause elevated indirect bilirubin
increased breakdown of red blood cells
reduced hepatic conversion to direct bilirubin
how is direct (conjugated) bilirubin synthesized
by conjugating indirect bilirubin in hepatocytes
what does elevated direct bilirubin suggest
hepatic or biliary tract disease — interferes with secretion of bilirubin from hepatocytes or clearance of bile from liver
what is direct hyperbilirubinemia classified as
positive cholestatic liver test
how much ammonia does the liver remove during first pass metabolism
>90%
what does elevation in ammonia correlate with
severity of encephalopathy and likelihood of death
what is the current treatment of encephalopathy targeted towards
reducing ammonia levels
what is the normal AST range
14-36 units/L
what is the normal ALT range
9-52 units/L
what is a child-pugh score
score to assess prognosis of chronic liver disease (usually cirrhosis)
provides prediction of increasing severity of liver disease and survival rate
what child-pugh score is indicative of a better survival rate
A
what child-pugh score is indicative of the worst survival rate
C
what is included in a child-pugh score
total bilirubin, albumin, INR, ascites, encephalopathy
what is a MELD score
prognostic system used to predict 3 month mortality due to liver disease
what does a higher MELD score mean
higher 3-month mortality related to liver disease
what is included in a MELD score
dialysis, creatinine, bilirubin, INR, sodium levels
what lab tests are related to hepatitis A
anti-HAV IgM
total anti-HAV
what lab tests are related to hepatitis B
HBeAg
HBsAg
Anti-HBc IGM
Anti-HBc
Anti-HBe
Anti-HBs
what lab tests are related to hepatitis C
HCV PCR
Anti-HCV
what lab tests are related to hepatitis D
Anti-HDV
HDV PCR
what lab tests are related to primary biliary cirrhosis
antimitochondrial antibody
what are the three diagnostic criteria for pancreatitis
characteristic symptoms
elevation of amylase or lipase to at least 3x ULN
characteristic findings on imaging (CT or MRI)
must have at least 2 of the 3
what is lipase
enzymes secreted by the pancreas that aids in fat digestion
what is the serum half-life of lipase
7-14 hours
what is amylase
enzyme that breaks down starch into individual sugar molecules
what is the serum half-life of amylase
1-2 hours
how do we detect noninvasive H. pylori
serology (most common)
urea breath test
fecal antigen test
how do we detect invasive H pylori
histology
culture
rapid urea test
what does serology detect for H pylori testing
circulating IgG against bacteria proteins
what does urea breath test detect
ability of bacteria to produce urease
what are clinical symptoms of clostridioides difficile
asymptomatic OR chronic diarrhea + acute colitis
what are tests for C. diff
enzyme immunoassays for toxin A + B
enzyme immunoassays for glutamate dehydrogenase (GDH)
nucleic acid amplification test (NAAT)
cell culture
C. diff antigen
cell cytotoxicity assay
stool culture
what are the characteristics of immunoassays for toxins A + B
rapid
low sensitivity
what are the characteristics for immunoassay for glutamate dehydrogenase
low specificity
detects nontoxigenic strains
what are characteristics of nucleic acid amplification tests (NAAT)
rapid and accurate diagnosis
becoming a standard test for initial eval
being used if initial test result is negative
detects asymptomatic carriers
what is the first test used when C diff is suspected
immunoassay for GDH and toxin A + B
what happens when the stool sample is positive for GDH and toxin A/B
testing is consistent with C diff infection
what happens if the stool sample is positive for GDH but negative for toxin A/B
indeterminant result → use PCR to detect C diff toxin
what happens if the stool sample is negative for GDH but positive for toxin A/B
indeterminant result → use PCR to detect C diff toxin
what happens if the stool sample is negative for GDH and toxin A/B
testing is not consistent with C diff infection
what are the primary causes of dyslipidemia
genetic mutations
overproduction or defective clearance of TG and LDL
under production or excessive clearance of HDL
what are the secondary causes of dyslipidemia
disease states
medications
lifestyle choices
what conditions can cause secondary dislypidemia
diabetes mellitus
obesity
sedentary lifestyle
hypothyroidism
cigarette use
pregnancy
cholestasis
liver failure
what drugs or diets can cause secondary dyslipidemia
alcohol
beta blockers
thiazides
contraceptives
high carb diet
high saturated fats diet
corticosteroids
atypical antipsychotics
what conditions usually have high LDL, low HDL, high TG
diabetes
hypothyroidism
obesity/sedentary lifestyle
nephrotic syndrome
what conditions usually have high TG
acute hepatitis
pregnancy
systemic lupus erythrematosis
uremia
alcohol
amiodarone
oral contraceptives
what conditions usually have high LDL and high TG
corticosteroids
diet
thiazides
what are the major plasma lipids
cholesterol
triglycerides
phospholipids
what is cholesterol
component of cell wall membranes
precursor to steroid hormones and bile acids
either dietary or synthesized in the liver
what are triglycerides
fat found in blood that the body uses for energy
exogenous and endogenous
what are phospholipids
lipid molecules that contain a phosphate group
not absorbed through the diet
intracellular metabolism and blood coagulation
what are apolipoproteins
proteins embedded in the surface of lipoproteins
what is the role of apolipoproteins
assembly and secretion of lipoproteins
major structural of lipoproteins
act as ligands for LDL receptors on cell surfaces
cofactors for activation of enzymes
what are the largest but least dense lipoproteins
chylomicrons
what are the smallest but most dense lipoproteins
HDLs
what is included in a fasting lipid panel
total cholesterol (TC)
high-density lipoprotein (HDL)
low-density lipoprotein (LDL) — calculated value
triglycerides (TG)
what is included in a non-fasting lipid profile
total cholesterol (TC)
high density lipoprotein (HDL)
what is the equation for total cholesterol
TC = LDL + HDL + TG/5 (used if TG <400)
when must a measured LDL be obtained
when TG >400
what is non-HDL
TC - HDL
secondary target when TG >200
what is an optimal LDL
<70 mg/dL
what is a high LDL
>160 mg/dL
what is calculated LDL
TC - HDL - TG/5
do not use if TG >400
what are the instructions for the lipid panel profile
no food for 9-12 hours
water and meds ok
black coffee ok
soda not ok
what are interfering factors for a lipid panel
pregnancy
recent weight loss
vigorous exercise
acute myocardial infarction
low in severe liver disease or malnutirition
optimal lipid panel levels
LDL — <70 mg/dL
HDL — 40-60 mg/dL
triglycerides — <150 mg/dL
what is atherosclerosis
deposits of fatty plaques on the inner walls of the arteries
what are the criteria for classification of ASCVD
MI or acute coronary syndrome
coronary or other revascularization procedure
transient ischemic attack
ischemic stroke
atherosclerotic peripheral artery disease
what are CVD risk factors
age — >45 for men, >55 for women
family Hx of premature CHD — male <55, female <65
cigarette smoking
HTN or HTN meds
HDL <40 mg/dL
adult treatment therapy III summary
patient treatment therapies based on CHD, CV risk factors, 10-year risk assessment, targeted LDL levels
therapeutic lifestyle changes
drug therapy