Liver Lab Tests Flashcards
What is a liver biochemical test called?
liver function test/hepatic panel
Why is the LFT not accurate at showing how well the liver is functioning?
- it can be ABNORMAL in non-liver diseases
- it can be NORMAL in patients with advanced liver DZ
What 3 things is tested in the liver tests?
Liver enzymes (ALT, AST, ALP)
- alanine, aspartate; alk phos [alkaline phosphatase
Protein (Total, albumin/Globulin ratio)
Bilirubin (total and direct)
What are other liver tests that are NOT on the CMP?
CGT, LDH, PT, AFP, urea/ammonia
What are the 4 liver function test CATEGORIES?
- injury to hepatocytes
- capacity to clear endogenous and exogenous substances from circulation
- biosynthetic capacity
- chronic inflammation
What are examples of the liver test for injury to hepatocytes?
Aminotransferases (AST, ALT) LDH
(These are only released from liver cells when there is injury)
What is an example of the liver function testing of capacity to clear end/ex-ogenous substances?
Bilirubin
What are examples of a liver function testing for biosynthetic capacity?
Albumin, prothrombin time (PT)
What are examples of liver function testing for chronic inflammation?
hepatitis serology, immunoglobulins, specific autoantibodies
What is the MOST SENSITIVE indicator for ACUTE hepatocyte injury?
What do they stand for?
AST (aspartate) and ALT (alanine aminotransferase) enzymes
ALT and AST increase ~ 1 week before serum _____?
Bilirubin
When are ALT and AST elevated?
Liver dz
Liver D/O (fatty liver, HF, infxn, metastic carcinoma)
Is ALT or AST related to alcohol associated hepatitis and Cirrhosis?
AST enzyme predominant (aspartate)
What serum amino transferase is highest in concentration in the liver and is the VERY sensitive AND specific for liver disease?
Alanine (ALT) enzyme
What serum amino transferase is highest in concentration in the liver; less specific for liver disease; but predominant in alcoholic hepatitis and cirrhosis?
Aspartate (AST) enzyme
Highest to least concentration of AST within the body?
Liver, Heart, Skeletal muscles, kidneys, brain, pancreas spleen, lungs, WBCs/RBCs
When would AST levels be DECREASED?
Acute renal DZ, beriberi, chronic renal dialysis, Diabetic ketoacidosis, pregnancy
Alk Phos (ALP) is increased highest in?
ALP is also increased in?
- Obstructive biliary dz, bone growth
New bone growth (adolescence, Healing, - osteoblastic metastatic dz)
ALP is the MOST sensitive test for what?
Metastatic Cancer of the Liver
What is measured in Total Protein?
Albumin, non-albumin proteins, and Globulins [antibodies]
What is the function of Albumin?
Why is it a measure of liver biosynthetic ability?
When is albumin markedly decreased?
- maintain intravascular osmotic pressure; transport blood constituents like drugs and hormones
- it is made in the liver
- albumin is markedly decreased in hepatocellular dysfunction
Globulins measured in total protein include what two things?
non-albumin proteins
Alpha, beta, gamma [antibodies]
When dz can total protein be normal but albumin is abnormally lower than globulins?
How?
- Chronic liver dz
- Liver damage = decreased albumin… reticuloendothelial system = more globulins
What is a proper albumin/globulin ratio?
What does an abnormal ration indicate?
- albumin > globulin… ration 1.0+
- decreased albumin suggests albumin targeted dz
A SPEP (serum protein electrophoresis) has a normal pattern of peaks showing what?
highest peak of albumin (+electrode)
other peaks > > > (- electrodes)
- alpha 1 and 2
- beta 1 and 2
- gamma
What should you do next if you have an abnormal SPEP?
Immunofixation electrophoresis (IFE)
SPEP and IFE: Polyclonal spike show what type of cell lines and what process?
Multiple cell lines
shows processes of infection/inflammatory process
SPEP and IFE monoclonal spike show what type of cell line and what process?
what is this abnormality called?
monoclonal spike shows ONE cell line REPLICATED (excessive amount
- monoclonal PRO (M)
shows the processes of a neoplasm (ex. multiple myeloma)
“monoclonal Gammopathy)
Review chart on slide 14
Where does Bilirubin come from?
bilirubin is the product of heme breakdown, primarily from Hgb (from RBCs)
Where is the 1st step of bilirubin metabolism?
What happened in this step?
Spleen
- RBC –> Hbg –> globulin and heme
- heme is metabolized = UNconjugated (INdirect) bilirubin (lipid soluble)
- bilirubin binds to albumin which CANNOT be filtered by the kidneys so this will not end up in the urine
Where is the 2nd step of bilirubin metabolism?
what are the 3 main steps?
Liver
a) uptake
b) conjugation
c) excretion
2a) of bilirubin metabolism
UPTAKE
[liver] bilirubin-albumin complex… bilirubin dissociated and will enter hepatocytes
2b) of bilirubin metabolism
CONJUGATION
[liver] UNconjugated bili + GLUCURONIC ACID (via hepatic glucuronosyltransferase) … becomes CONJUGATED (Direct) bili (water soluble)
2c) of bilirubin metabolism
EXCRETION
- hepatocytes excrete conjugated bilirubin = bile
Why is the 2c (excretion step) of bilirubin metabolism the rate limiting step?
if excretion is impaired, conjugated bilirubin enters hepatic sinusoids and then bloodstream
“conjugated Hyperbilirubinemia”
Where is the 3rd step of Bilirubin metabolism?
Bowel and Kidney
… Duodenum
What 2 things can happen to conjugated bilirubin in the 3rd step [bowel &kidney]
- excreted unchanged; filtered by the kidneys (conjugated bilirubin)
- converted to urobilinogen bacteria in the colon
Urobilinogen can be reabsorbed in ________ which then enters the ________ ____________.
Urobilinogen can be reabsorbed in INTESTINE which then enters the PORTAL CIRCULATION
Once in the portal circulation, the urobilinogen can do what 3 things?
- some is taken up by liver and re-excreted in bile
- some bypasses the liver and is excreted by KIDNEY
- some is converted to STERCOBILIN in bowel
- turns the stool brown
How does an Extrahepatic obstruction effect bilirubin metabolism?
conjugated bilirubin cannot be excreted into intestines… LIGHT STOOLS (lack of stercobilin) and conjugated hyperbilirubinemia
if conjugated bilirubin cannot be excreted into the intestine due to extrahepatic obstruction, how will conjugated hyperbilirubinemia effect the urine?
conjugated hyperbilirubinemia levels in the urine will increase turning the urine DARK, TEA COLORED
Total Bilirubin equation? What is it used for?
What type of bilirubin makes up the majority of total bili?
- direct + indirect bili
- used to differentiate whether hyperbilirubinemia is predominantly (>50%) due to direct or indirect
- INDIRECT makes up the MAJORITY (70-85%)
What does the Total Serum Bilirubin mean?
balance between production and clearance
What 3 things can increased serum bilirubin be due to?
which lead to increased Unconjugated/indirect?
Which lead to increased conjugated/direct?
- overproduction of bilirubin (UN)
- impaired uptake (UN), conjugation (UN), and excretion(C)
- backward leakage from damaged hepatocytes or bile ducts (C)
Describe the 3 ways that lead to Unconjugated (Indirect) hyperbilirubinemia?
Which are the most common causes?
Overproduction: from hemolysis/hemolytic anemia, ineffective erythropoiesis
Impaired hepatic
- uptake: HF, sepsis, certain drug effects
- conjugation: Gilbert DZ, Crigler Najjar syndrome, sepsis
MC causes: Hemolysis/hemolytic anemia, Drug effects, Gilbert DZ
Describe the 2 ways that lead to Conjugated (Direct) hyperbilirubinemia?
Decreased Hepatic excretion: (Dubin-Johnson Syndrome, Rotor syndrome)
Backward leakage of bilirubin: Biliary tract obstruction (intra or extra-hepatic)
What are examples of EXTRAhepatic biliary tract obstruction?
Gallstones, tumors, inflammation, scarring, or other obstruction
What are examples of INTRAhepatic biliary tract obstruction?
moderate-sever acute or chronic hepatocellular DZ/damage (Viral/alcoholic hepatitis)
What is more accurate than individual tests of the liver? give 2 examples?
What is common in both examples?
The pattern is more accurate?
1. Hepatocellular damage “pattern”
- AST, ALT disproportionately elevated compared to ALP
2. Cholestasis “pattern)
- ALP disproportionately elevated compared to aminotransferases (GGT can also be elevated
*BOTH will have elevated serum/conjugated hyperbili with synthetic function tests abnormal
What AST: ALT ratio suggests alcoholic hepatitis
> /= 2.1 ration suggests alcoholic hepatitis
What can gamma-Glutamyl Transferase (GGT/GGTP) be elevated in?
What does it VERY ACCURATELY detect even in small amounts?
What GGT helpful at detecting in relation to elevated ALP?
- Elevated in Cholestasis and chronic alcoholism, recent medication, or recent MI
- GGT very accurately detects Cholestasis
- When ALP is elevated, if GGT is NOT = implies skeletal DZ; if GGT IS ELEVATED = implies hepatobiliary DZ
Elevated Ammonia supports the DX of what?
What are the two hepatocellular dysfunctions?
Severe liver DZ (filminant hepatitis or cirrhosis)
1. liver DZ preventing conversion of ammonia to urea
2. altered blood flow preventing ammonia from reaching liver (portal hypertension/obstruction)
What can high levels of ammonia lead to?
Confusion, delirium, encephalopathy, and coma
What does PT/INR measure?
When is is prolonged?
PT/INR measures the clotting ability of factors 1 (fibrinogen), 2 (prothrombin), 5, 7, and 10
(extrinsic and common clotting pathway)
- prolonged when the factors are descreased
What can increase PT/INR? describe
What two things can the increase mean?
Liver DZ causing decrease in PROCOAGULANTS in which anticoagulants can overshoot in trying to balance out
1. tendency to bleed
2. hypercoagulable (recent warfarin)
What are the vitamin K dependent coagulation factors?
2, 7, 9, 10, Protein C and S
What are some examples of increased PT/INR?
- Deficiency in factors 1, 2, 5, 7, 10
- Disseminated Intravascular Coagulation (DIC)… uses up clotting factors
- liver DZ
- Vitamin K deficiency
- Warfarin (depletes vitamin K)
- Poor fat absorption (depletes vitamin k)… ex: sprue, celiac DZ, chronic diarrhea
- Biliary obstruction… poor fat absorption
A specific type of oncofetal protein, Alpha-fetoprotein (AFP) is produced by? Is abnormally seen in?
AFP is normally produced by the fetus during development
AFP is abnormal in adults and suggests cancer (hepatocellular carcinoma and sometime testicular/ovarian cancer)
When can AFP be detected in pregnancy?
When can AFP be decreased in pregnancy?
in the amniotic fluid at week 10
- Increased during NEURAL TUBE DEFECTS, multiple pregnancies, fetal/distress/congenital abnnormalities, abdominal wall defects, and itrauterine death
- Trisomy 21 and fetal wastage
When is AFP increased during pregnancy?
- Increased during NEURAL TUBE DEFECTS, multiple pregnancies, fetal/distress/congenital abnormalities, abdominal wall defects, and intrauterine death
What is Lactate Dehydrogenase (LDH)?
When condition leads to to be measured in the serum?
Cytoplasmic (intracellular) enzyme found in tissues throughout the body
LDH is leaked out of the cells when the cells die/lyse *hemolytic anemia
What are the LDH isoenzymes throughout the body (5)?
1- heart
2. reticuloendothelial system (macrophages, spleen)
3 - lungs
4 - kidneys, placenta, pancreas
5 - liver and striated muscle
Compare LDH to AST/ALT in relation to Liver DZ
LDH is NOT as sensitive as AST/ALT; LDH has poor specificity in liver DZ
