Synthetic Functions

Hepatocytes synthesize:
 plasma proteins except immunoglobulins

 most coagulation factors such as fibrinogen

& factorII,V,VII,IX,X XI, XII)
 lipoproteins,VLDL,HDL

 primary bile acids

General Metabolic Functions
Carbohydrate metabolism

Maintainence of the blood glucose level:

 Glycogenesis (glycogen synthesis), storage

 Glygenolysis (glycogen breakdown)

 Gluconeogenesis
Protein Metabolism
 Synthesis of most palsma proteins such as
albumin & transport proteins
 Deamiation of amino acids & formation of
urea
Lipid metabolism
 Oxidation of fatty acid to ketone bodies

 Synthesis of cholesterol & cholesterol

esters
 Synthesis of
lipoproteins,triglycerides,phospholipids
 synthesis of bile acids
Detoxification and Excretion
Substances that are inactivated & excreted by
the liver include:
Bilirubin

Bile acids

Steroid hormones

Many drugs

Toxins
 Formation & Excretion of bilirubin

Aged & Damaged

RBCs
RETICULOENDOTHELIAL
SYSTEM
Haemoglobin

Globin Haem

Unconjucated
Bilirubinn(UB)

BLOOD Albumin.UB
BLOOD Albumin.UB
LIVER
LIVER LIVER CELL UPTAKE by ligandin
Conjugation with Glucuronyl transferase

Bilirubin glucuronide
KIDNEY
Excretion into the bile

Common Bile Duct GUT

Conjugated Bilirubin Urinary

bacterial flora Urobilinogen
Enterohepatic circulation
Faecal Urobilinogen
Efficient excretion of bilirubin
depend on:
Normal functioning liver cells
Patent biliary duct
Normal blood flow through liver
In the routine laboratory
include
all or some of the following plasma
analytes
bilirubin
 transaminases(ALT, AST)
alkalinephosphatase,
gamma glutamyl transferases
totalproteins,albumin
Promthrombin time
Urinary bilirubin & urobilinogen may also be
considered as liver function tests
 Normally there is no bilirubin in the urine
 Bilirubinuria is always pathological it means
that conjugated hyperbilrubinaemia
 Urinary Urobilinogen is detectable in normal
people & in haemolysis, liver damage

(no great use in I/v of liver disease)

Plasma bililrubin
Plasma total bilirubin level is around
5 – 20 μmol/l
Clinical expression of
hyerbilirubinaemia (jaundice)
occur when the plasma level
rises above 40 μmol/l
Hyperbilirubinaemia may be due to:
 Increased production (prehepatic jaundice)
as in haemolysis

 Decreased excretion due to

- Congenital Disorder(Gilbert' s disease,Crigler Najar
syndrome, Dubin-Johnson syndrome)
- Hepatocellular disorder (hepatitis, cirrhosis,drugs )
- Obstruction in the biliary flow (obstructive
jaundice)
Plasma transaminases
 The transaminases are enzymes inolved
in transfer of an amino group from2 -

amino to 2 - oxalacid

 Rise in these plasma enzymes activities

indicate liver cell membrane damage
rather than function
Alanine transaminase (ALT)
(Glutamate pyruvate transaminase
(GPT))

ALT is present high concentration in liver

& lessr extent in muscle, kidney & heart

Normal value men - <40u/l

women - <31u/l
CAUSES OF RAISED PLASMA ALT LEVEL
Marked increase (10 to 100 times )
• Circulatory failure with shock and hypoxia
• Acute viral or toxic hepatitis
Moderate increase
• Cirrhosis
• Infectious mononucleosis
• Liver congestion secondary to CCF
• Cholestatic jaundices
• surgery or extensive trauma & skeletal muscle
disease
 Aspartate Transaminase( AST)
AST (glutamate oxaloacetate
transaminaseGOT) is present in high
concentration in cells of cardiac and
skeletal muscle,liver,kidney &
erytherocytes.
Damage to any of these tissue may increase
plasma AST level

Normal value men - <37u/l

women - <31u/l
CAUSES OF RAISED PLASMA LEVEL
Artefactual:
• In vitro release from RBCs in haemlysis
• Physiological:
• Neonate (1.5 times )
Marked Increase (10 to 100 times)
• circulatory failure with shock & hypoxia
• myocardial Infarction
• acute viral or toxic hepatitis
Moderate increase:
• cirrhosis
• infectious mononucleosis
• cholestatic jaundice
• malignant infarction of the liver
• skeletal muscle disease
(dystrophy,trauma)
• severe haemolytic episodes
Gamma – glutamyltransferase
(GGT)
GGT catalyses the transfer of gamma
glutamyl groups from one peptide to
another
GGT occur in liver, kidney, pancreas &
prostate
CAUSES OF RAISED PLASMA GGT
 Liver diseases :all types

 Induction of microsomal enzymes

by alcohol or drugs

Normal value men – 11 - 43u/l

women – 9 - 37u/l
Alkaline phosphatase (ALP)
ALP catalyses hydrolysis of phosphoric acid
mono-ester
ALP is found mainly in bone,liver (bile
canaliculi) , intestine, kidney &placenta
CAUSES OF RAISED PLASMA ALP
Physiological
 Age: neonate/children/ young adult
 Pregnancy: 3rd trimester

Liver d/s :
 Cholstasis
 space occupying lesion
 hepatocellular d/s
Bone d/s:
 Paget‘s d/s

 malignancy

 Hyperparathyroidism

 CRF

 Rickets/osteomalacia
Malignancy:
 Bone : primary, secondary
 liver : primary, secondary
 Ectopic production (Regan isoenzyme)

Miscellaneous
 Transient hyperphosphatasaemiaof
infancy
 Familial benign hyperphosphatsaemia
The liver has enormous functional
reserve
Deficiencies in synthetic function
(impaired albumin & promthrombin
synthesis) can only be detected if liver
disease is prolonged & extensive
 Gross pathology

The measurement of albumin &

promthrombin time may be used to
asses function in certained conditions
The measurement of total protein
estimates both albumin &globulin
Albumin is wholly synthesized in the liver
& low levels suggest severe liver cell
dysfuntion
The globulin fraction which includes the
immunoglobulins are usually increased in
chronic liver disease
CAUSES OF HYPOALBUMINAEMIA
Haemodilution
• Water overload, sample from infusion arm,
pregnancy
Decreased synthesis
• Deficient precursor: malnutrition malabsorption
• Severe liver disease: chronic hepatitis
• Cirrhosis
Loss from thebody
• Skin: burns, exudative lesion
• Gut protein losing enteropathy
• Renal: nephrotic syndrome
CAUSES OF PROLONG PT
 Oral anticoagulant drugs

 Chronic liver diseases

 Vitamin K deficiency

 Disseminated intavascular coagulation

 Factor II,V, VII,X,deficiency or defect

The prolonged promthrombin time in
liver disease may be due to
cholestasis
(vitamin K deficiency in impaired fat
absorption due to intestinal bile salt
deficiency ) in such case it is
corrected by parenteral adminstration
of vitamin K
A prolonged PT may also result from
severe impairment of synthetic
ability if liver cell mass is greatly
reduced which is not corrected by
parenteral adminstration of vitamin K
Liver cell damage is characterized y
release of enzymes (AST,ALT)from
damage hepatocytes
Cholesatsis is characterized by retension
of conjucated bilirubin and of alkaline
phosphatase(ALP)
Reduced mass of functioning cells is
characterized by reduction in
prothrombin & albumin synthesis