CMP and LFTs

Liver

- largest organ of the body

- receives dual blood supply (20% from hepatic artery, 80% from portal vein)

_______________ are the primary cells of the liver

hepatocytes (2/3 liver mass)

- Blood enters liver via the ______________ and drains through the _______________ of the hepatic ____________.

- Bile flows in the _______________ direction

- enters via the portal triad

- drains through the sinusoidal space

- hepatic lobule

- opposite direction

Function of hepatocytes

- synthesis of serum proteins

- production of bile

- regulation of nutrients

- metabolism & conjugation of lipophilic compounds for excretion in bile or urine

What serum proteins do hepatocytes synthesize? (3)

- albumin

- coagulation factors (Protein C and S)

- growth factors

What do hepatocytes produce? (3)

- bile acids

- cholesterol

- phospholipids

What processes do hepatocytes do to regulate nutrients?

- gluconeogenesis

- glycolysis

- lipogenesis

What kind of compounds undergo metabolism and conjugating for excretion in bile or urine

- bilirubin

- urea

What are markers of hepatocellular function?

- serum bilirubin

- serum albumin

- coagulation factors-prothrombin time (INR)

Normal serum values of total bilirubin

0.3-1 mg/dL- comprised of direct and indirect bilirubin

Unconjugated (indirect) bilirubin

- insoluble in water, bound to albumin

- byproduct of heme degradation

What is elevation in indirect bilirubin typically due to?

other causes, such as hemolysis

Conjugated (direct) bilirubin

- water-soluble, excreted by kidney

- ULN= 0.3 mg/dL

The liver is responsible for the metabolism (conjugation) of bilirubin to a...

water-soluble form that can be eliminated from body

What can an elevation in direct bilirubin indicate?

an obstruction or liver injury

Normal serum albumin value

3.5-5 g/dL

Serum albumin is exclusively synthesized by....

hepatocytes

What is the half-life (t1/2) of serum albumin?

18-20 days

Serum albumin < _______ g/dL is indicative of chronic liver disease

<3 g/dL

T/F: Hypoalbuminemia is often seen in acute liver condition (viral hepatitis drug-related hepatotoxicity)

FALSE

not often seen

T/F: Hypoalbuminemia is not specific for liver disease

TRUE

- can also see hypoalbuminemia in malnutrition, nephrotic syndrome, chronic infections

With the exception of ________, clotting factors are synthesized exclusively by hepatocytes

factor VIII

What is the t1/2 of factor VII?

6 hrs

What is the t1/2 of fibrinogen?

5 days

Prothrombin time (INR) normal value

0.8-1.2

Prothrombin time is measured in _______________ and reported as a ratio compared to an __________________________

- seconds

- average reference group

Can see an increase in clotting time with.......

acute injury and chronic liver disease

Markers of liver injury

- aminotransferases- AST, ALT

- alkaline phosphatase ALP

- GGT

Normal ranges for AST and ALT are typically between...

10-40 units/L

Normal levels of AST and ALT should be...

low

AST and ALT are released into the blood in response to....

hepatocyte injury and death

Where is AST found? (5)

- liver

- cardiac tissue

- skeletal muscle

- kidney

- brain

AST:ALT ratio > ______ is indicative of alcoholic liver disease etiology

>2:1

Where is ALT found?

primarily in liver

Typically ______ is higher than or equal to _______ in most hepatocellular disorders

- ALT

- AST

Acute or chronic liver injury will cause ____________ in serum concentrations of AST and ALT

increases

Elevations of AST and ALT are associated with hepatocellular injury such as:

- viral hepatitis

- ischemic liver injury

- toxin- or drug-induced liver injury

Normal serum value for alkaline phosphatase (ALP)

30-120 units/L

Where is alkaline phosphatase (ALP) found?

- liver

- bone

- placenta

- small intestine

Alkaline phosphatase (ALP) can be elevated due to.....

- cholestatic liver disease

- increased amount of bone turnover

Normal serum value of GGT

8-61 units/L

GGT is specific for...

liver

GGT is often tested if ____ is elevated to rule in or out liver disease

ALP

Is GGT increased or decreased in the setting of liver disease?

increased in liver disease

Liver is responsible for converting ammonia into....

urea for excretion by the kidneys

Normal serum value of ammonia

11-35 micromoles/L

Ammonia may be ____________ in the setting of chronic liver disease & hepatic encephalopathy

elevated

T/F: There is a clinical correlation between the degree of elevation of blood ammonia and severity of acute encephalopathy

FALSE

there is NO correlation

What is the gold standard for determining the presence of cirrhosis (fibrotic liver tissue)?

Liver biopsy

In practice, ____________ is often used, which can detect the presence of fibrosis

- ultrasound

- used in combination with clinical picture (presence of portal hypertension, ascites)

The 14 different tests contained in a metabolic panel

- glucose

- calcium

- sodium, potassium, carbon dioxide, and chloride

- albumin

- total protein

- ALP, AST, and ALT

- total bilirubin

- BUN and creatinine

Fishbone diagram for CMP

Normal range for ALT

<35 units/L

Normal range for AST

<35 units/L

Normal range for ALP

30-120 units/L

Normal range for albumin

3.5 - 5 g/dL

Normal range for total protein

6.3 - 7.9 g/dL

Normal range for total bilirubin T. bili

0.3 - 1.0 mg/dL

Normal range for direct (conjugated/water soluble) bilirubin

0.1 - 0.3 mg/dL

Normal range for indirect (unconjugated/insoluble) bilirubin

0.2 - 0.7 mg/dL

Normal range for GGT (Gamma-glutamyl transferase)

8 - 61 units/L

Normal range for INR

0.8 - 1.2

Normal range for ammonia

11-35 mcmol/L

Which of the following would be considered markers of liver injury?

a. Serum albumin

b. Serum bilirubin

c. ALT

d. Prothrombin time

c. ALT

Which of the following lab values would you expect to be DECREASED in the setting of chronic liver disease?

a. Albumin

b. Total bilirubin

c. GGT

d. INR

a. Albumin

Child-Pugh - staging/severity classification system

Child-Pugh - staging/severity classification system

Grade A < ____________, considered mild

Grade B = ___________

Grade C = ___________, considered severe

Grade A < 7 points

Grade B = 7-9 points

Grade C = 10-15 points

Model for End-Stage Liver Disease (MELD)

prognostic indicator, used for staging of liver transplantation patients

4 variables in the MELD

1. INR

2. Serum bilirubin

3. Serum creatinine

4. Serum sodium

- MELD score ranges from ____ to ____

- What are higher scores correlated with?

- 6 to 40

- with increased severity and higher 3-month mortality

MELD score of 30-39 associated with a....

3-month mortality rate of 52.6%