lecture 7-Profile test

Liver/Hepatic Function Test - (LFT)

designed to give information about the state of a patient's liver

Profile (test) for liver disease include:

◦ Bilirubin, ALP, AST, ALT, GGT, LD, TP,Alb., Hepatitis tests

◦ Markers increased in liver problem

• reference ranges controls are based on human trends/pools to determine the high risk values

Liver

A secretory and excretory organ

 Storage site for iron, glycogen, vitamins and many other substances

 Makes plasma proteins (albumin, lipoproteins, coagulation proteins)

 Remove toxins from the blood

 Secrete bile via bile ducts and gall bladder into the small intestine which helps in digestion

Functions even if onlyy 10% viable

Bilirubin

Waste product formed in the liver and excreted in bile

◦ Produced from broken down RBC; metabolism continues in the liver

◦ Test for liver or gall bladder dysfunction

◦ Increased in patients with jaundice

◦ Increased in babies with HDN

◦ Degraded by light - protect from light and test ASAP

Total serum bilirubin level

• Is the sum of the conjugated (direct) and unconjugated (indirect) bilirubin

• Reference Range (Total) 2 – 21 μmol/L

Direct bilirubin

is secreted as bile into the intestine and helps with digestion

Direct Reference Range 0 – 6 μmol/L

Icteric (jaundiced) serum

contains high amount of bilirubin – serum is dark yellow to amber

indicates liver damage (like from hepatitis)

ALP (AP) - Alkaline Phosphatase

◦ Increase levels in disorders of the bone, liver (including hepatitis) or the biliary tract

◦ Reference Range 20 – 130 U/L

If this and AST elevated indicate liver issues

AST - Aspartate Aminotransferase

Previously called GOT or SGOT

◦ Enzyme present in liver, skeletal and cardiac muscle

◦ Reflects damage to the liver, and muscles, including the heart

◦ Reference Range 10 – 37 U/L

If this and ALP elevated indicate liver issues

ALT - Alanine transaminase

◦ Enzyme high in hepatocytes (liver cells)

◦ Serum ALT rises dramatically in acute liver damage

◦ More specific than ALP

◦ Reference Range 3 – 30 U/L

GGT - Gamma glutamyl transpeptidase

◦ Found in liver, kidney, prostate tissue

◦ Used to monitor recovery from hepatitis and cirrhosis

◦ Reference Range 3 – 40 U/L

LD / LDH - Lactate dehydrogenase

◦ Found in many body tissues, including the liver – not specific

◦ Elevated levels of LDH may indicate liver damage

◦ Reference Range 110 – 230 U/L

acute liver damage will cause big spike

chronic liver damage/issues will cause not as big spikes

Two major groups of serum proteins are

albumins and globulin

Albumins

• make up about 60% of total serum protein

• are transport protein

• and maintin osmotic pressure

• is synthesized in the liver

  • and therefore is a measure of hepatic function

• help to maintain fluid balance in the body

• Decreased levels/ hypoalbunminemia can be seen in

  • liver disease, starvation, impaired absorption

• Reference range 38 - 50 g/L

Globulins

make up about 40% of serum/plasma proteins

Included are –

• antibodies,

• coagulation

• proteins and enzymes

 Measured according to specific globulin

Total Protein – TP (liver function test profile)

◦ Measure the total amount of protein,

• albumin,

• and globulin in the blood

◦ Low levels can suggest

• a liver or kidney disorder,

• malnutrition and malabsorption

◦ Increase levels may be seen with

• chronic inflammation

• or infections such as viral hepatitis or HIV,

• and multiple myeloma

◦ Reference range 60 - 80 g/L

Albumin/Globulin ratio – A/G ratio

◦ Provide a clue as to the cause of change in protein levels

◦ Total protein and albumin are used for the measurement/calculation

A low A/G ratio may reflect

 Overproduction of globulins

 Underproduction of albumin

A high A/G ratio suggests

Underproduction of immunoglobulins

Bence Jones Proteins/proteinuria

◦ Found in the blood or urine

◦ Finding this protein is often suggestive of multiple myeloma

◦ The proteins are immunoglobulin light chains

◦ Found in urine due to the kidneys' decreased filtration capabilities due to renal failure

Electrophoresis

is a technique used in laboratories in order to separate macromolecules based on size and charge

• Protein molecules can be separated and analyzed

• Applies a negative charge, so proteins move towards a positive charge and are separated

Hepatitis panel

• done by PHO

• done in chem department

 Blood test used to find markers of hepatitis infection

 Hepatitis causes inflammation of the liver

 Common panel include:

◦ Hepatitis A IgM antibodies (HA Ab-IgM)

◦ Hepatitis B surface antigen (HBsAg)

◦ Hepatitis B IgM core antibody (HBcAb-IgM)

◦ Hepatitis C antibodies (HC Ab)

 Reference Range – Negative

Cardiac Profile (Markers)

 Substances that are released into the blood when the heart is damaged

 Cardiac markers play important roles for diagnosis and therapy for myocardial infarction (MI) and ischemia

 Increased in MI

 Cardiac Markers Profile:

• Troponin I,

• CPK/CK,

• CK-MB,

• Myoglobin,

• AST, (Cholesterol)

 Specimen collection

• Green Top – Heparinized blood

• (Gold Top – SST)

Troponin I (cTnI)

◦ A cardiac muscle protein

◦ cTnI is a specific marker for the diagnosis of acute myocardial infarction (AMI)

◦ The most specific of all the cardiac markers

◦ cTnI is released rapidly into the blood after the onset of AMI

◦ Reference Range 0 - 0.4 ng/mL

Creatine Phosphokinase / Creatine Kinase (CPK/CK)

◦ Helps in the diagnosis of myocardial infarction (MI)

◦ Present in muscles (cardiac and skeletal) and the brain

◦ Increased after a heart attack – not specific to heart disease however (due to muscle stresss/death)

◦ Reference Range 30 - 170 U/L

Creatine kinase-MB (CK-MB)

◦ Isoenzyme of CK

◦ Highest percentage found in cardiac muscles– small % in skeletal muscles

◦ CK-MB is released in the circulation following a MI

◦ Reference Range < 6% of total (0 – 5 μ)

• not spun down, TAT is usually 1 hour

Myoglobin

◦ Protein found primarily in muscle tissues – cardiac and skeletal

◦ Present in the bloodstream following muscle injury

◦ Useful with the other cardiac markers to diagnose AMI

◦ Reference Range 20 - 90 ng/ml

Lipid Profile

 A group of tests ordered together to determine risk of cardiovascular disease (CVD) or stroke

◦ Caused by blockage of blood vessels or hardening of the arteries (atherosclerois)

 Most commonly measured lipids are:

◦ Cholesterol/fractions and triglycerides

 Fasting for 9 -12 hours before the sample is collected is required

◦ Only water is permitted

Cholesterol

• is a steroid, which is a type of fat, found in the blood

• produced by the body and also comes from the foods eaten (animal products)

• is needed in the

  • membrane of cells,

  • organs and tissues in the body

• oronary artery

  disease

Too much cholesterol leads

coronary artery disease

Blood cholesterol level

• is related to the foods eaten or

• to genetic conditions (passed down from other generations of family members)

Cholesterol: Endogenous Sources

70% synthesized in the body or stored in the liver

Cholesterol: Exogenous Sources

30% from food (animal source as meat, eggs and dairy products)

test ordered for Cholesterol/fractionst

• Total Cholesterol,

• LDL,

• HDL

• and Triglycerides

Cholesterol (Total)

Elevated levels can increase the risk of coronary artery disease, atherosclerosis

◦ Reference Range 3.6 - 6.5 mmol/L

LDL – Low Density Lipoprotein

◦ Often called “bad cholesterol”

◦ Carries cholesterol from the liver to the blood then to organs

High levels of LDL in blood is associated with

• atherosclerosis,

• heart disease

• and myocardial infraction

◦ Reference Range < 2.5 mmol/L

• higher # higher chance of blockage

HDL – High Density Lipoprotein

◦ Often called “good cholesterol”

◦ Transport cholesterol from organs and blood to the liver to get rid of it

◦ Removes excess cholesterol from tissues (it cleans the blood)

◦ High levels linked to a reduced risk of heart and atherosclerosis disease

◦ The higher your HDL level, the better

◦ Reference Range > 1.04 mmol/L

Triglycerides

◦ Main form of lipid (fat) storage

◦ Most found in adipose/fat tissue

◦ Provide energy in the absence of carbohydrates

◦ High levels of triglycerides have been linked

• to atherosclerosis,

• risk of heart disease

• and stroke

◦ Reference Range 0.11 - 2.15 mmol/L

Endocrine System

is a system of glands

Each gland secretes a type of hormone directly into the bloodstream to regulate body functions

• Cortisol

• Thyroid

Cortisol overview

• produced by the adrenal glands

  • but is controlled by the hypothalamus and pituitary gland

• the body’s main stress hormone

• works with the brain to control mood, motivation and fear

Cortisol Important role

◦ Helps the body respond to stress

◦ Regulates blood pressure

◦ Keep inflammation down

◦ Increase blood sugar

◦ Controls sleep and wake patterns

• essential for flight or fight response

  • but can be maladative

    • for example spikes during tests

Thyroid Profile/Function

• one of the largest endocrine glands in the body which synthesize hormones

• The two major thyroid hormones are

  • thyroxine(T4)

  • triiodothyronine (T3)

• Thyroid hormones control how quickly the body use energy and make proteins

Profiles for Thyroid test for

◦ Free or total T4, T3 and TSH (Thyroid stimulating hormone)

◦ TSH – Hormone that regulates thyroid gland activity

• – Stimulates T3 and T4 secretion

Hyperthyroidism

excessive secretion of thyroid hormones

– T4 & (T3

Graves disease

• A common cause of hyperthyroidism

• a chronic autoimmune disorder where antibodies cause the thyroid to overproduce hormones (hyperthyroidism), accelerating metabolism

Hypothyroidism

Decreased thyroid function/hormones – T4 & (T3)

• commonly caused by hashimoto diease

Reference Range for TSH, T3 T4 vary according to age

 Adult range

◦ TSH 0.35 - 5.0 μU/L

◦ T4 8.5 – 15.2 pmol/L

◦ T3 3.5 – 6.5 pmol/L

Therapeutic Drug Screening/Monitoring

• To determine the presence or absence of specified drugs or their metabolites

• Specimen in Biochemistry lab

  • – blood (serum) and/or urine

    • usually red top; and no anticoagulant

  • Could also include hair, sweat, saliva

  • urine can be used as well

  • meconium:

    • a newborn's first, thick, sticky, dark green-black stool, typically passed within 48 hours of birth.

• help determine optimum dosage of drug/treatment

• can be used for criminal case

  • if no metabilites of drugs in urine, cant say drug was taken

  • if whole drug in urine, indicates tamperin

referance range: 0

Example of drugs tested for Drug screening/monitoring

• ◦ Heart ailments - digoxin

• ◦ Antiepileptic/seizure- phenytoin (dilantin),

• carbamazepine,

• valproic acid,

• phenobarbital

Analgesic (pain meds) & Anti-inflammatory

(drug testing/monitoring for this conditon)

- acetaminophen, tylenol, salicylate (ASA, aspirin),

Reference Range – Negative

Anti-psychotic/anti-manic

lithium carbonate

Reference Range – Negative

Respiratory ailments (eg asthma)

theophylline

Reference Range – Negative

Antibiotics

gentamicin, amikacin

Reference Range – Negative