Hepatic & Coagulation Laboratory Parameters

_____ Injury - damage to liver cells

Hepatocellular

Aminotransferases (ALT and AST) shows _____ injury

Hepatocellular

_______ Injury – biliary system, slowing of bile flow

from the liver

Cholestatic

– Mixed pattern - _____ – both liver and biliary system

hepatobiliary

Comprehensive Metabolic Panel (CMP)

– ____, Albumin/Globulin Ratio (calculated), _____, ____, _____, BUN/Creatinine Ratio (calculated),

Calcium, Carbon Dioxide, Chloride, Creatinine with GFR

Estimated, Globulin (calculated), Glucose, Potassium,

Sodium, ____, _____, Urea Nitrogen


fill in blank: evaluation = related to liver

Albumin, Alkaline Phosphatase, ALT, AST, Total Bilirubin, Total Protein

Aminotransferases lab values that are commonly associated with liver injury

AST (Aspartate aminotransferase), ALT (Alanine aminotransferase)

AST = Aspartate aminotransferase ALT = Alanine aminotransferase

reference values are ____

Intracellular Enzymes: Convenient/easy to measure

• Not specific to the liver

  • AST: liver, muscle, heart, brain, kidney, red cells

  • ALT: liver, muscle, kidney

< 35 units/L

_____ Aminotransferases = irritation to live

Elevated

Aminotransferases elevation is mild if ____xULN (upper limit of normal)

<5

Aminotransferases is moderate if ____xULN (upper limit of normal)

5-15

Aminotransferases is severe if ____xULN (upper limit of normal)

>15

In most types of liver disease, ____

ALT is higher than AST

in alcoholic hepatitis, AST to ALT Ratio ____ suggests alcoholic liver disease:

>2

Lactate Dehydrogenase (LDH)

• Reference value: _____

• Not specific to the liver

• Elevations reflect tissue injury

• Released by the heart, liver, RBCs, kidneys, skeletal muscle, brain, and lungs

• Possible marker for hypoxic liver injury due to decreased perfusion (reduction in blood flow)

60-100 Units/L

lactate dehydrogenase (LDH) shows ____ injury 

Hepatocellular

Alkaline Phosphatase (ALP) shows _____ injury

Cholestatic

Alkaline Phosphatase (ALP)

• Reference value: 36-92Units/L

• Not specific to liver

• Present in liver especially ____, bone, intestinal tract, and placenta

biliary tract

Alkaline Phosphatase (ALP)

• ______ stimulates synthesis and release of ALP

  • Sensitive, easily measured

Cholestasis 

Alkaline Phosphatase (ALP)

• Used to detect and monitor

diseases of liver or bone

• Elevated: extrahepatic and intrahepatic obstructive biliary disease and cirrhosis obstruction, stones, or tumors

• Use _____ to confirm origin of ALP

GGT (Gamma-Glutamyl Transferase)

Reference value: 0-30 Units/L

• Present mainly in the liver, biliary tract, and pancreas (not in bone)

• Sensitive indicator for hepatobiliary disease

• NOT very specific – not a routine test

• Clinical value

  • Differentiate source of ALP elevation

  • Evaluate heavy or chronic alcohol use

• Increased by enzyme inducing drugs and other medications

Gamma-Glutamyl Transferase (GGT)

Hepatocellular and/or Cholestatic Injury is aka

hepatobiliary

Bilirubin → Unconjugated bilirubin is conjugated in the liver and excreted in bile

• Unconjugated: indirect, insoluble

• Conjugated: direct, soluble

• Total = indirect + direct

Hyperbilirubinemia

• Total bilirubin > 2mg/dl

  • Jaundice, Icterus, Pruritis

Any bilirubin found in the urine is conjugated and implies _____

disease – dark urine

hepatobiliary

Bilirubin (Levels of direct bilirubin increase when the liver loses ~____ of its excretory function.)

Reference value 0.2 - 1 mg/dl total

• 0 - 0.2 mg/dl conjugated (direct) 

• 0.2 - 0.9 mg/dl unconjugated (indirect)

50%

Isolated elevation of indirect bilirubin (unconjugated), Rarely reflects liver disease; commonly found in _____

• Overproduction, large volume blood transfusion, genetic disorders

hemolytic disease

Elevations of direct bilirubin indirect means

NOT Liver

– Almost always reflects _____ - decreased excretion

hepatobiliary disease

Both can be elevated in hepatitis, cirrhosis, post hepatic obstruction, drug induced cholestasis (slowing of bile flow

• Jaundice can be ____ to resolve

slow 

Liver Function: Synthetic and Detoxifying

To measure_____, measure what the liver produces.

If you do not have enough cells, you cannot make albumin or prothrombin.

liver function

Albumin:

• Reference value: 3.5-5.0g/dL

• Manufactured by the liver, 60% of total protein

– Maintains oncotic pressure, binds drugs, and hormones

• Measure of _____(synthetic ability) and measure of nutrition

• Albumin is slow to fall after hepatic dysfunction

– Reflects _____

– Half-life: approximately 20 days

• Decreased - Liver disease, malnutrition, burns, over hydration, nephrotic syndrome

• Increased - Anabolic steroids, dehydration

liver function, long-term liver dysfunction

Coagulation: Monitors rapid changes in liver function, can reflect _____

• Measures the time it takes for blood to clot

• PT = Prothrombin Time

- > v= Liver not make CF

– Measures the function of the extrinsic and common pathways of coagulation

N (measure Heparin hepaceflicy)

• aPTT = Activated Partial Thromboplastin Time

– Measures the function of the intrinsic and common pathways of coagulation

– Factors I (fibrinogen), II (prothrombin), V, VIII, IX, X, XI, XII, prekallikrein (PK), and

high molecular weight kininogen (HK)

– Used to measure efficacy of heparin

• PT = Prothrombin Time (if decreased means liver not make coagulation factors

either short term or long term dysfunction

Coagulation: ____ tells us acute liver dysfunction

Liver is the sole source of vit K dependent clotting factors Decreased

produc on of clo ng factors = ↑PT = bleeding risk

• Reference Value 11.0-12.5 seconds (lab dependent)

• PT measures clotting ability of Factors I (fibrinogen), II (prothrombin), V,

VII, X

• Significantly diminished liver function (> ~80%) may prolong PT

• Insensitive marker for liver dysfunction, but will rapidly reflect changes

in liver function – high prognostic value

Prothrombin Time (PT)

Coagulation: International Normalization Ratio (INR)

• _______ from lab to lab

• Number (no units) calibrated based on the characteristics of

the reagent used for the test

• Normal INR = 1

• Elevated INR = increased risk of bleeding

• Used to evaluate efficacy of warfarin

Standardizes results of PT

Ammonia: _____

• Reference value: 40-80 mcg/dL

• Product of amino acid metabolism

• Metabolized by the liver to urea to be excreted by the kidneys

• Decreased metabolism of ammonia = increased ammonia

levels

– Leads to Hepatic Encephalopathy (TOXIC)

– Levels do not correlate with severity

– Not indicated for routine monitoring in chronic disease

Detoxifying Liver Function

Ammonia

• Hepatic Encephalopathy Symptoms:

– Mood and personality changes

– Cognitive impairment

– Balance problems

– Coma

• Treatment includes medications directed at lowering the gut

____ and thus the serum ammonia levels.

nitrogen load

laboratory parameters used primarily to monitor Hepatocellular Injury

ALT, AST, LDH

laboratory parameters used primarily to monitor Cholestatic Injury

Alkaline Phosphatase, Gamma-glutamyl transferase (GGT)

laboratory parameters used primarily to monitor Hepatobiliary Injury (both)

bilirubin

laboratory parameters used primarily to monitor Synthetic Liver function

albumin, PT/INR

laboratory parameters used primarily to monitor Detoxifying Liver function

ammonia 

What indicates acute liver injury?

normal lab values, elevated AST/ALT (hepatocellular), elevated Alkaline Phosphatase (cholestatic), elevated total and direct bilirubin, elevated PT/INR   

what indicates chronic liver injury/disease?

increase/decreased AST/ALT, elevated Alkaline Phosphatase (cholestatic), elevated total and direct bilirubin, elevated PT/INR, decreased albumin, increased ammonia

____ is elevated when urine is dark because its water soluble 

Conjugated (Direct) Bilirubin

BB is a 45 yo obese male with elevated transaminases. What injury does he have?

Increased AST and ALT = hepatocellular

increased PT/INR means ____ in liver function

decline

While a decreased albumin level suggests ______, an increased albumin level is related to non-hepatic physiological state

liver disease or long-term liver dysfunction

LDH is a possible marker for ____ due to decreased perfusion

hypoxic liver injury

Increased ammonia is listed as a feature of ____

Chronic Liver Injury/Disease

Which of the follow lab value abnormalities would indicated cholestatic injury?
Decreased albumin, Increased LDH, Decreased unconjugated bilirubin, Increased conjugated bilirubin

increase conjugated bilirubin= hepatobiliary disease