Liver Function Tests

Liver Function

takes up amino acids from the intestines, processes them, & synthesizes them into circulating proteins

By products of amino acids

urea & ammonia

The liver absorbs _____ & stores them as glycogen & releases them to prevent hypoglycemia

carbohydrates

What type of metabolism occurs in the liver?

lipid & lipoprotein metabolism

The liver is the primary location for what processes?

detoxification and excretion of a wide variety of endogenous substances (sex hormones) as well as bile acids & bilirubin

Components of liver function tests

- ALT

- AST

- ALP

- Bilirubin

- Albumin

- PT/INR

ALT

- alanine aminotransferase

-

AST

- aspartate aminotransferase

-

ALP

- alkaline phosphatase

- 35-104 U/L

PT/INR

- protime/international normalized ratio

- 6.1-8.2 g/d

CMP

usually made up of a BMP + liver function tests excluding the PT/INR

How to evaluate the liver:

- 1. injury

- 2. cholestasis

- 3. excretion

- 4. synthesis

1. Injury

- ALT

- AST

- cells are leaking enzymes; this is not the same as liver failure

2. Cholestasis

- ALP

- GTT

- 5'-nucleotidase

- bile flow or biliary epithelium

3. Excretion

- total/direct bilirubin

- urine bilirubin

- urobilinogen

- pigment traffic

4. Synthesis

- albumin

- PT/INR

- true function of the liver; use this for determining liver failure

Tests used for synthetic liver function

- albumin

- PT/INR

- prealbumin

Inadequate protein synthetic function is mainly limited to:

severe liver damage (cirrhosis)

What do we use protein synthesis tests for?

to determine the severity of liver damage

Albumin

major plasma protein (transport protein) synthesized by hepatocytes that helps maintain plasma oncotic pressure

Albumin Half Life

long half-life of 20 days and levels are slow to fall after hepatic injury so it can take days to see a decline in acute injury

Albumin is a negative acute phase reactant, meaning that the liver produces less ablumin in the setting of:

- systemic inflammation

- infection

- malignancy

Because albumin changes slowly it is less helpful for what?

acute hepatocellular injury

Low albumin (hypoalbuminemia) occurs with:

- inflammation

- malnutrition

- nephrotic loss

- protein-losing enteropathy

- burns

- dilution from volume overload

How should albumin be interpreted?

alongside history, exam, urinalysis/proteinuria, nutrition status, & signs of chronic liver disease

Albumin is a marker of _______ and _______ not a rapid damage meter

chronic physiology; inflammation

Hypoalbuminemia

when albumin is

Low albumin can affect:

interpretation of calcium & drug concentrations

Hyperalbuminemia

seen with dehydration or in patients on anabolic steroids

Prealbumin

similar to albumin except half-life is 2 days only; generally used to assess protein calorie nutrition

What do we use prealbumin for?

to monitor patients on IV or tube feedings

Liver is required for the synthesis of what?

several clotting factors, many of which require vit. K as a cofactor for their activation

Prolongation of PT/INR can be from:

- synthetic liver failure

- vit. K deficiency

INR prolongation can reflect:

- impaired hepatic synthesis

- vit. K deficiency

- warfarin/DOAC effect

- DIC

- malabsorption

INR elevation + encephalopathy can reflect:

acute liver failure physiology

Increased bilirubin + INR distinguishes:

mild injury from impaired liver reserve

Cholestasis

deficiency of the exretory function of the liver

Intrahepatic Cholestasis

problem occuring within the liver itself that is preventing excretory function

Extrahepatic Cholestasis

problem occuring outside of the liver such as obstruction of large bile ducts that is preventing excretory function

What is needed to determine intra vs extra hepatic cholestasis?

lab tests do not distinguish so radiographs are needed

Alkaline Phosphatase (ALP)

group of enzymes with unknown function but appear to have active role in down-regulating the secretory activities of the intrahepatic biliary epithelium

ALP in bone

involved in calcification

ALP in other sites

participates in transport processes

Which tissues of the body is ALP present in?

- liver

- bone

- intestine

- other (kidneys/placenta/leukocytes)

80% of ALP is found in the:

liver & bone

Bile accumulation increases hepatocyte synthesis of _____

ALP which then leaks into the blood stream

ALP > than 4 times normal rate is suggestive of:

cholestatic disorder

What do we order to determine the cause of elevated ALP?

- ALP isoenzymes (to see if it is bone or liver)

- fractionated ALP (to see what fraction is from bone or liver)

Alkaline Phosphatase Isoenzymes

idenfication of different types of isoenzymes in the blood by electrophoresis

Alkaline Phosphatase Isoenzymes can rise normally in situations such as:

3rd trimester of pregnancy or in adolescence when bone is forming

5'-Nucleotidase

found in the liver, intestines, brain, heart, blood vessels, and pancreas with a physiological function that is unknown

5'-Nucleotidase is located in the ______

hepatocytes

Elevation 5'-Nucleotidase

seen in the same tupes of hepatobiliary diseases as ALP

5'-nucelotidase as specificity for ______

hepatobiliary disease

If 5'-nucleotidase & ALP are both elevated, then ALP is of ______ origin

hepatic

Gamma-Glutamyl Transpeptidase (GGT)

biliary exretory enzyme

Sensitivity of GGT

cholestasis & ETOH

Specificity of GGT

very low because it is related to issues other than just the liver

Non-Liver Causes of increased GGT

- pancreatic disease

- MI

- renal failure

- COPD

- DM

Sensitivity of GGT in alcoholism

52-94%

What do we use GGT for?

use it in evaluating other serum enzyme levels (ALP) and to support ETOH disease

If GGT & ALP is elevated, then ALP is of ______ origin

hepatic

Normal Bilirubin Metabolism

- 1. red blood cells from the spleen or bone marrow & are broken down into hemoglobin, then heme, and then bilirubin

- 2. nonconjugated bilirubin travels to the liver where bilirubin is conjugated

- 3. conjugated bilirubin then either travels into intestine where intestinal bacteria breaks it down into urobilinogen & it is excreted in feces or it is recycled into the plasma as urobilinogen

- 4. urobilinogen in plasma then travels either to the kidneys and is excreted in urine or is recycled back into the liver where it will continue this cycle until excreted

Total Serum Bilirubin

0.3-1.2 mg/dL in adults & 2.0-12.0 mg/dL in neonates

Direct/Conjugated Serum Bilirubin

0-0.2 mg/dL; there should be none in the blood

Pre-Hepatic Jaundice

unconjucated hyperbilirubinemia (indirect)

Hepatic or Post-Hepatic Jaundice

conjugated hyperbilirubinemia (direct)

Unconjugated Hyperbilirubinemia is caused by:

- physiologic jaundice

- hemolysis

Physiologic Jaundice

caused by underdeveloped liver in neonates & can last 1-5 days; phototherapy breaks down bilirubin in the skin

Kernicterus

rare neurological condition that occurs in some newborns with severe jaundice where they can't breakdown unconjugated bilirubin because their liver isn't converting so it builds up

Hemolysis

excess bilirubin presented in the liver & overload is usually handled well by the liver

Process of Hemolysis

increased Hgb -> increased unconjugated bilirubin -> increased conjugated bilirubin -> increased urobilirubin -> increased urobilirubin in the urine due to amounts being filtered through the kidney

Overview of Hemolysis

- increased total bilirubin

- normal conjugated bilirubin

- negative urine bilirubin

- increased urine urobilinogen

Overview of Physiologic Jaundice

- increased total bilirubin

- normal conjugated bilirubin

- negative urine bilirubin

- normal urine urobilinogen (not truely normal, its high but not in the blood because it never gets processed by the liver to enter the blood)

Causes of Conjugated Hyperbilirubinemia

- biliary stasis

- mechanical obstruction

- hepatocellular damage (drugs, ETOH, virus)

- rare conditions such as dubin-johnson syndrome or rotor's syndrome

Process of Hepatocellular Damage

Hgb -> unconjugated bilirubin -> damaged liver -> increased unconjugated bilirubin (due to inability to break it down) & conjugated bilirubin -> conjugated bilirubin leakage into circulation (increased bilirubinuria) and to the intestine -> urobilinogen -> increased urobilinogen in the urine because the damaged liver doesn't allow it to pass back through

Overview of Hepatocellular Damage

- increased total bilirubin

- increased conjugated bilirubin

- increased urine bilirubin

- increased urine urobilinogen

Obstruction Process

Hgb -> unconjugated bilirubin -> liver -> conjugated bilirubin -> blockage causes leakage of conjugated bilirubin into circulation -> increased bilirubinuria & decreased urobilinogin because it never gets converted in the intestine

Obstruction Overview

- increased total bilirubin

- increased conjugated bilirubin

- increased urine bilirubin

- decreased urine urobilinogen