liver function tests - shms-prod.s3.amazonaws.com · •alp •ldh •5 ... high sgot(ast) and...

TtáxÜ À TuwxÄté|Å? c{WTtáxÜ À TuwxÄté|Å? c{WTtáxÜ À TuwxÄté|Å? c{WTtáxÜ À TuwxÄté|Å? c{W

LIVER FUNCTION TESTSLIVER FUNCTION TESTSLIVER FUNCTION TESTSLIVER FUNCTION TESTS

3/20/2018

Dr/ Aaser Abdelazim ----assistant professor

of Clinical Medical Biochemistry and

Molecular Biology

24

TtáxÜ À TuwxÄté|Å? c{WTtáxÜ À TuwxÄté|Å? c{WTtáxÜ À TuwxÄté|Å? c{WTtáxÜ À TuwxÄté|Å? c{WAssistant professor of Medical Biochemistry

Zagazig University, Egypt

University of Bisha, KSA

[email protected]

Liver Functions Tests

1.Functions of human liver.

2.Major tests used in diagnosis of liver

disorders.

3.Major changes in plasma enzymes and their

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Molecular Biology

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3.Major changes in plasma enzymes and their

indication in liver diseases.

4.Major pathological changes in liver.

5.Hepatic coma.

6.Jaundice.

Functions of liver:

1. Metabolism (Lipid, Proteins,

Carbohydrates)

2. Storage (Glycogen, Vitamins,

Vitamin B12)

3. Excretory function (Bilirubin,

Cholesterol).

Liver is the master organ in the body, it serve all other organs

Cholesterol).

4. Detoxification (Phenbarbiton,

Amonia, Steroid Hormones,

Benzoic)

5. Hematological function (Blood

formation, Blood volume, Blood

coagulation).

CAH: chronic active hepatitis

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Anatomical over view

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Figure (1): liver Lobule

Major tests used to diagnose Major tests used to diagnose Major tests used to diagnose Major tests used to diagnose

liver functionsliver functionsliver functionsliver functions

Major tests used to diagnose Major tests used to diagnose Major tests used to diagnose Major tests used to diagnose

liver functionsliver functionsliver functionsliver functions

•ALT 1. Albumin (cirrhosis) 1. Anti mitochondrial .

Plasma enzymes Plasma proteins Serology

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•ALT

•AST

•GGT

•ALP

•LDH•5` nucleosidase

1. Albumin (cirrhosis)

2. (α, ᵦ, ɣ) globulins

(Cholestasis)

3. Immunoglobulins(IGs)

- IgG: chronic active

hepatitis

- IgA: portal cirrhosis

- IgM: biliray cirrhosis, viral

hepatitis

1. Anti mitochondrial .

Ab.(CAH, Biliray

cirrhosis

2. Anti nuclear:

autoimmune

hepatitis

3. Anti smooth muscle: CAH

CAH: Chronic active hepatitis

(1) Serum ALT (sGPT)(N= up to 35 U/ml)

It presents in high concentration In:

1. Liver2. Skeletal muscles 3. Kidneys

4. Heart

Major changes in plasma enzymes and its indication in liver diseases

Causes of ALT increase 4. Heart

Marked increase(10- 100

times)

1. Viral hepatitis

2. Toxic liver hepatitis 3. Circulatory failure

Moderate increase

1. Liver cirrhosis

2. Cholestatic jaundice

3. Liver congestion

4. Secondary to cardiac failure 5. Extensive trauma

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Causes of ALT increase

It present in high concentration In:

1. Heart 2. Liver 3. Muscle 4. Kidenys

(2) Serum AST (sGOT)(N= up to 40 U/ ml)

Causes of AST increase

Physiological increase

In newborn its increase= 1.5 of normal level

Marked increase (10-

100 times )

1. Myocardial infraction

2. Viral hepatitis

3. Toxic liver cirrhosis

4. Circulatory failure

due to

- Shock - Hypoxia

Artefacual increase

Due to hemolysis of

blood in lab. Led to its release

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Moderate increase

1. Liver cirrhosis

2. Cholestatic jaundice

3. Liver infiltration

4. Skeletal muscle

disease

5. After trauma or surgery

Presents in high concentration In:

1. Bone 2. Liver 3. Kidneys

4. Lactating mammary glands

5. Intestinal wall 6. Placenta

(3) Serum Alkaline Phosphatase (ALP) N= (50-190 U/L)

Causes of ALP increase

Physiological

1. Children until

puberty 2.5 times

of adult level 2. Pregnancy

Bone diseases

1. Osteomalcia

2. Rickets

3. Bone carcinoma

4. Healing stage of bone fractures

Liver diseases

1. Cholestatic jaundice*

2. Hepatitis

3. Cirrhosis

4. Tumors * *5. Infiltration * *

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Presents in

1. Heart

2. Skeletal muscles

3. Liver

4. Kidneys

5. Brain 6. Malignant tissues

LDH isoenzymes1. LDH1:heart, erythrocytes, blast, kidneys

2. LDH2: heart

3. LDH3:intermediate

4. LDH4:liver 5. LDH5:liver

(4) Serum Lactate Dehydrogenase (LDH) N= (60-250

IU/L)

Causes of serum LDH increase

Marked increase

1. Myocardial infarction

2. Hematological diseases

- Leukemia

- Shock - Pernicious anemia

Moderate increase

1. Viral hepatitis

2. Skeletal muscle

diseases

3. Pulmonary

embolism 4. Infections

Artefacual increase Hemolysis of samples

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Causes of serum LDH increase

Presents in:

1. Liver 2. Kidneys 3. Pancreas

(5) Gamma Glutamyle transpeptidase (γ-GT) N= up

to 38 U/L

Causes of GGT increase

Liver diseases

1. Cirrhosis

2. Metastatic cancer

3. Hepatic infiltration

4. Cholestasis

Chronic alcoholism Patient with anticonvulsant therapy

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Major pathological changes in liver Major pathological changes in liver Major pathological changes in liver Major pathological changes in liver

Liver cell damage Cholestasis Infiltration of liver

Impaired the secretion of bile

Then accumulated in the

1. Secondary to a disease

2. Abscess

Destruction of cell

plasma 3. Parasitic emboli

As bilhariziasis cause

destruction of cells

Acute: as viral infection Chronic : Loss of function

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((((1111) Liver cell damage ) Liver cell damage ) Liver cell damage ) Liver cell damage

Causes:

•Viral infection

•Toxins (alcohol, paracetamol, acetaminophen)

•Hypoxia and congestion in chronic heart failure (CHF).•Secondary to biliray obstruction.

Biochemical effect:

1. Release of intracellular constituents into blood.1. Release of intracellular constituents into blood.

2. High sGOT (AST) and sGPT(ALT).

- Massive destruction: sudden fall after high elevation

- Chronic destruction: high level for long time

ALT than AST Means liver viral hepatitis

AST than ALTMeans excess damage,cirrhosis, hypoxia and tumors

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Liver diseases and AST-to-ALT ratio

Disease Ratio

EtOH 1.5

Drugs 2.0

Cirrhosis 1.4-2.0

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Hepatocellular carcinoma (HCC) > 1.5

Intra hepatic cholestasis > 1.5

Extra hepatic cholestasis 0.7-0.8

Acute viral hepatitis < 0.65

Acute myocardial infraction (MI) > 3.0

With jaundice (Cholestatic jaundice) With out jaundice

1. Obstruction to only part of biliary

system

2. Cholengitis3. Primary biliary cirrhosis

((((2222) Cholestasis ) Cholestasis ) Cholestasis ) Cholestasis

1. Gall stones

2. Carcinoma (obstruction of bile duct)

1. Some forms of Viral hepatitis

2. Biliary cirrhosis 3. Drugs : phenothiazine.

1. Plasma Bilirubin increased to be 50 mg/dl

2. ALP increases

3. ALT, AST increases

4. Increase GGT 5. Increase 5` nucleotidase

3. Primary biliary cirrhosis

Biochemical changes

3/20/2018 38Dr/ Aaser Abdelazim ----assistant professor of Clinical Medical Biochemistry and Molecular Biology

Intra hepatic Extra hepatic

Biochemical changes:Biochemical changes:

Abscess (1)

Amyloidosis(2)

Tuberculosis (3)

((((3333) Liver infiltration ) Liver infiltration ) Liver infiltration ) Liver infiltration

(5) Carcinoma from lung or stomach

Parasitism(4)

CAUSES

1. Increase synthesis in

sinusoids

2. Regarded to circulation 3. But it highest in Cholestasis

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High serum ALP

High serum GGT

Normal bilirubin

ALT and AST normal or slight raised

Why?

Case study (1):

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17.1 µmol/l bilirubin=1 mg/dl

0.41 mg/dl

Casestudy (1):

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1. Liver function tests indicate mild cell damage; this appeared from

normal levels of AST and Bilirubin and slight increase of ALT (38/N =

<35).

2. High serum ALP indicates one of the following:

a) Bone metastasis tumor; and this not excluded by normal level

of Ca as ALP is very high (bone scan is very important here)

Comments on case 1

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of Ca as ALP is very high (bone scan is very important here)

b) Metastatic breast carcinoma

c) Hepatic metastatic carcinoma from breast

3. Further investigations are required

a) Bone scan

b) Tumor markers

c) Histopathological examinations

Aaser Aaser Aaser Aaser

Hepatic coma

Definition: is the occurrence of confusion, altered level of consciousness as a

result of liver failure.

Biochemical findings

High blood ammonia

3/20/2018Dr/ Aaser Abdelazim ---- lecturer of Medical

Biochemistry and Molecular Biology 43

High blood ammonia

�Serum ammonia levels are

elevated in 90% of patients.

�Not all hyperammonemia

(high ammonia levels) is

associated with coma.

Abnormal liver function tests

indicating liver failure

Causes: other causes with hepatic faliure may predispose coma like:

Type Cause

Excessive

nitrogen

load

1. Consumption of large amounts of protein

2. Gastrointestinal bleeding e.g. from esophageal varices (blood is high in protein, which

is reabsorbed from the bowel),

3. Renal failure (inability to excrete nitrogen-containing waste products such as urea),

4. Constipation

Electrolyte

or

metabolic

1. Hyponatraemia (low sodium level in the blood) and hypokalaemia (low potassium

levels)—these are both common in those taking diuretics, often used for the treatment of

ascites

2. Alkalosis (decreased acid level),



metabolic

disturbance2. Alkalosis (decreased acid level),

3. Hypoxia (insufficient oxygen levels),

4. Dehydration

Drugs and

medications

1. Sedatives: such as benzodiazepines (often used to suppress alcohol withdrawal or

anxiety disorder),

2. Narcotics: (used as painkillers or drugs of abuse) and sedative antipsychotics, alcohol

intoxication

Infection Pneumonia, urinary tract infection, spontaneous bacterial peritonitis, other infections

OthersSurgery, progression of the liver disease, additional cause for liver damage (e.g. alcoholic

hepatitis, hepatitis A)

Unknown In 20–30% of cases, no clear cause for an attack can be found

Hepatic failure

(NH3)

Crosses the blood-brain barrier

(NH3)

Glutamate Glutamine

Ammonia (NH3) accumulates in the systemic circulation



The energy to brain cells is decreasedDue to depletion of α-ketoglutarate

Excess Glutamine lead to increase the osmotic pressure in brain cells (become swollen) Increase the activity of GABA in brain due to

conversion of α-ketoglutarate in to glutamate(inhibitory neurotransmitter)

Brain edema (cytotoxic type)

1. Definition of jaundice

2. Bilirubin metabolism

3. Causes of jaundice

4. Differential diagnosis of jaundice

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4. Differential diagnosis of jaundice

1) Is a yellow discoloration of skin or/and sclera due to high

concentration of plasma Bilirubin over 40 µmol/l2) Normal plasma total bilirubin is less than 22 µmol/l (3-15

µmol/l OR 0.3 -1 mg/dl )3) Normal conjugated = 0.1 mg/dl

1. See bilirubin metabolism figure (3) Jaundice

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1. See bilirubin metabolism figure (3)2. Main causes of high bilirubin are three

figure (4)• Hemolysis • Failure of conjugation mechanism in

liver • Obstruction in biliary system

17.1 µmol/l bilirubin=1 mg/dl

Jaundice

�Indicates an elevated level of

serum bilirubin .

�In neonates it is important to

determine the concentration of

Unconjugated bilirubin in order to

decide the treatment required

�In adults most common type isdue obstruction.

Water soluble

•Non water soluble (not secreted

from kidneys)

•It is neurotoxic

•Can cause permanent brain damage in neonates

Bacteria

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Figure (2) Bilirubin metabolism

•Brown coloration of feces

•If not present lead to pale colored feces

Bacteria

Orange color of urine on long standing

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Figure (3): Causes of jaundice

Hemolysis

Plasma Unconjugated bilirubin

Main in neonates

Extra hepatic obstruction

Both Plasma bilirubin and ALP

Partial Complete

ALP with bilirubin within reference range

Hepatocellular damage

Obstruction occurs

here secondary to

hepatic cell

damage by toxinsor infection

conjugated

Little or no

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>> 200 µmol/l (12

mg/dl); need

phototherapy

>> 300 µmol/l(17

mg/dl); need exchange transfusion

Little or no urobilinogen in urine

Pale stool

Level of ALP indicate the degree of obstruction

Both Plasma bilirubin and ALP with ALT and AST

Indicates

damage of liver cells

Little or no Stercobilinogen in intestine

Laboratory differential diagnosis of jaundice

Feature Hemolytic Cholestatic Hepatocellular

Serum Bilirubin >75 µmol/l (4.38 mg/dl)

(Unconjugated)(Indirect)

Over 3 times than in

hemolytic (Conjugated) (Direct)

>75 µmol/l but later

(Unconjugated/conjugated)

Conjugated increased when obstruction occurs later on

Bilirubin in urine

Not present(Unconjugated is not water

soluble and bound to albumin and not filtered )

Present Present(high level of conjugated bilirubin)

Urine Urobilinogen

Increased Decreased /absent Decreased/absent

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Stool Normal Clay/pale in color

(no bilirubin reaches the intestine)

Normal

Reticulocytosis + - -

Hemoglobin /Haptoglobin Decrease Normal Normal

Plasma enzymes LDH may increased

1. ALP over 3 times the

reference range it act

as a mirror for the

degree of obstruction.

2. High AST, ALT, GGT

and LDH

High ALP but appear later

High ALT and ASTDue to hepatocytes damage

Neonatal jaundice

Causes:

1. Inability of immature liver of neonates to produce UDPG- transferase2. Higher turnover of neonatal erythrocytes shortly after birth to replace fetal HbF

with normal HbA

Neonatal jaundice

Transient Sustained

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Physiological jaundice of the newborn (PJN)

1. Hemolytic diseases

2. Biliray artesia (post hepatic type)

3. Idiopathic neonatal

hepatitis (rare) (hepatic jaundice)

1. Blood groups

incompatibility

between mother and

fetus (+ direct anti-

globulin)

2. Absorption of large

hematoma.

Blood cells of mother Blood cells of fetus

Mechanism of neonatal jaundice

Group (O) orRH-

Group (A/B) orRh+

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Both come in contact

1. Through transfusion2. Or during pregnancy

Immune system of

mother recognizedthem as foreigners

Produce antibodiesagainst them

RBCs destruction

This usually not affects the 1st

child but affects the second oneAaser

1. High amounts of IgM (anti-A, anti-B)

2. Small amounts of IgG (anti-A, anti-B)

Consequence of neonatal jaundice

Treatment

Phototherapy if the level exceed 10 mg/dl

Source of light emitted light of 450 nm

Kernicterus

Brain cell nuclei stained yellow

Damaged due to high

bilirubin can cross blood

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Unconjugated

bilirubin (insoluble)

Soluble bilirubin

bilirubin can cross blood

brain barrier (not occurs in adults

why?! Here type of bilirubin is unconjugatedwhich is water insoluble).

Usually brain is damaged if

the level reaches > 20mg/dl

cerebral palsy, deafness,mental retradation


Transient condition/ phenomena in whichbilirubin subsides within few weeks

Other factors affecting neonatal hyperbilirubinemia

1. Increase total and Unconjugated bilirubin

2. Near-normal conjugated bilirubin 3. Normal hepatic enzymes if there is no iflammation


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Other factors affecting neonatal hyperbilirubinemia

1. Decrease binding of Unconjugated bilirubin to albumin

2. reabsorption of intestinal meconium

3. constituents in mother’s milk. Progesterone and other hormones in

breast milk as well as beta-glucuronidase may suppress neonatal

conjugation of bilirubin

Case study (2):

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Case study (2):

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