[Liver Function Tests Information]
Introduction:
The liver is the largest organ (other than skin) in the body, making up about 2% of total body weight, or 1.5 kg, in the
average adult human.
Hepatocytes
www.procto-med.com/hepatocytes-the-liver-cells/
The Functions of the Liver:
Carbohydrate metabolism: important in maintaining
blood glucose homeostasis.
Fat metabolism: liver bears the main responsibility of
this, although most cells are capable of some fat
metabolism.
Protein metabolism: liver metabolism of proteins is
essential for life and no other part of the body can
undertake many of these responsibilities.
Vitamin/ Mineral Storage
Biotransformation Functions
 The main routes by which drugs and their
metabolites leave the body are: the kidneys, the
HEPATOBILIARY SYSTEM and the lungs.
Converts galactose and fructose to glucose.
Glucose buffer function; in response to hormonal
controls, stores and releases glucose to blood when
needed.
Gluconeogenesis: when glycogen stores are empty and
blood glucose levels are falling, converts amino acids and
glycerol to glucose.
Converts glucose to fats for storage.
Primary body site of beta oxidation (breakdown of fatty
acids to acetyl CoA).
Converts excess CoA to ketone bodies for release to
tissue cells.
Stores fats.
Forms lipoproteins for transport of fatty acids, fats and
cholesterol to and from tissues.
Synthesises cholesterol from acetyl CoA; catabolises
cholesterol to bile salts, which are secreted in bile.
Deaminates amino acids (required for their conversion to
glucose or use for ATP synthesis).
Forms urea for removal of ammonia from the body.
Forms most plasma proteins (exceptions are gamma
globulins and some hormones and enzymes).
Transamination: intraconversion of nonessential amino
acids.
Stores Vitamin A (1-2 yrs’ supply).
Stores large amounts of Vitamin D and B12 (1-4 months’
supply).
Stores iron as ferritin until needed on the bloodstream.
Metabolises alcohol and drugs by performing synthetic
reactions yielding inactive products for excretion by the
kidneys and non-synthetic reactions that may result in
products with a changed state of activity.
Processes bilirubin resulting from RBC breakdown and
excretes bile pigments in bile.
Metabolises bloodborne hormones to forms that can be
excreted in urine.
Liver Function Tests:
Test
Serum Enzymes
Alkaline phosphatase (ALP)
Gamma-glutamyl
transpeptidase (GGT)
Aspartate aminotransferase
(AST)
Alanine aminotransferase
(ALT)
Lactate dehydrogenase (LDH)
Normal value
Interpretation
13-39 units/L
Male: 12-38 units/L
Female: 9-31 units/L
5-40 units/L
Increases with biliary obstruction and cholestatic hepatitis
Increases with biliary obstruction and cholestatic hepatitis
5’-Nucleotidase
2-11 units/L
Bilirubin Metabolism
Serum Bilirubin: Unconjugated
Serum Bilirubin: Conjugated
Total
Urine bilirubin
Urine urobilinogen
Serum Proteins
Albumin
Globulin
Total
Alumbin/globulin (A/G) ratio
5-35 units/L
90-220 units/L
Increases with hepatocellular injury (and injury in other
tissues e.g. skeletal, cardiac muscle)
Increases with hepatocellular injury and necrosis
Isoenzyme LD5 is elevated with hypoxic and primary liver
injury
Increases with increase in alkaline phosphatise and
cholestatic disorders
<0.8 mg/dl
0.2-0.4 mg/dl
<1.0 mg/dl
0
0-4 mg/24 hr
Increases with hemolysis (lysis of red blood cells)
Increases with hepatocellular injury or obstruction
Increases with biliary obstruction
Increases with biliary obstruction
Increases with hemolysis or shunting of portal blood flow
3.5-5.5 g/dl
2.5-3.5 g/dl
6-7 g/dl
1.5:1 to 2.5:1
Reduced with hepatocellular injury
Increases with hepatitis
Transferrin
250-300 mcg/dl
Alpha fetoprotein (AFP)
Blood-clotting Functions
Prothrombin time (PT)
6-20 ng/ml
Ratio reverses with chronic hepatitis or other chronic liver
disease
Liver damage with decreased values, iron deficiency with
increased values
Elevated values in primary hepatocellular carcinoma
11.5-14 sec or 90%100% of control
25-40 sec
Increases with chronic liver disease (cirrhosis) or Vitamin K
deficiency
Increases with severe liver disease or heparin therapy
<6% retention in 45
min
Increased retention with hepatocellular injury
Partial thromboplastin time
(PTT)
Bromsulphalein (BSP) excretion
Enzymes:
ALP: is synthesised by biliary tract and bone, but these two tissues contain different ALP isoenzymes, so the enzyme
origin can be determined. GGT is also synthesised in the liver. An elevation of both ALP and GGT is required to
conclude that the problem is in the biliary tract. cholestasis (failure of normal amounts of bile to reach the
intestine, resulting in obstructive jaundice)
Essentially any hepatocellular insult produces a release of ALT, AST and LDH from the hepatic cytosol. 
hepatocellular injury
In liver disease, the ALT elevation is approx. double the AST elevation. LDH elevation is usually minor. *If AST
exceeds ALT, other tissues should be suspected of releasing the enzymes.
The degree of elevation can help diagnostically:
 With typical hepatitides (A, B, C), the ALT peaks in the 2000-5000 U/L range.
 With non-specific liver infections (e.g. Epstein-Barr virus, CMV, toxoplasmosis, leptospirosis, brucellosis, Q
fever), lesser degrees of elevation are seen; 300-1000 U/L is common.
 In any febrile illness, viraemia, dehydration, etc, trivial elevations of 2-3 times the reference range are
commonly seen.
Function tests:
Three major responsibilities of the liver provide markers for us to deduce how well the liver is functioning.
 Maintenance of glucose homeostasis
 Protein synthesis
 Detoxification
Glucose homeostasis generally only becomes a concern in end-stage liver failure.
However, serum albumin and bilirubin levels can indicate how well the liver is coping with protein synthesis and
detoxification.
Because the liver is the sole source of most of the circulating proteins, if there is a severe liver disturbance of
sufficient duration, we commonly see a fall of albumin. However, albumin has a half-life of 7-10 days, so the level is
unaffected by brief or acute illness.
“Dying erythrocytes [RBCs] are engulfed
and destroyed by macrophages. The haem
“When bilirubin is released from the reticuloendothelial tissues in
of their haemoglobin is split off from the
which effete red cells are broken down, it is in the form of waterglobin. Its core of iron is salvaged, bound
insoluble unconjugated bilirubin. It is carried bound to albumin to
to protein (as ferritin or hemosiderin) and
the liver where each bilirubin molecule is conjugated with two
stored for reuse. The balance of the haem
molecules of glucuronic acid. It thus becomes more water-soluble.
group is degraded to bilirubin, a yellow
Under normal circumstances, the conjugated bilirubin is secreted
pigment that is released to the blood and
directly into the bile from here. However, if biliary drainage is
binds to albumin for transport. Bilirubin is
obstructed, the conjugated bilirubin refluxes back into the circulation
picked up by liver cells, which in turn
and is excreted into the urine.” (Appleton) Elevated levels indicate
secrete it (in bile) to the intestine, where it
cholestasis first and foremost, as the process is less sensitive to
is metabolised into urobilinogen. Most of
hepatocellular damage.
this degraded pigment leaves the body in
faeces, as a brown pigment called
stercobilin.” (Marieb)
There are also
imaging techniques to view structure and function of the liver.
The Liver & Paracetamol Poisoning:
Paracetamol overdose causes a very acute form of liver failure; the patient may be extremely ill (perhaps beyond
treatment) before significant changes to the usual markers of function are detected. Different tests, testing
parameters and shorter response times are required.
Serum glucose and
Hypoglycaemia and lactic acidosis arise as a consequence of failure of glyconeogenesis.
lactic acid levels
Coagulation profile
This assesses protein synthesis effectively (several clotting factors have half-lives of 6-8
hours).
Plasma ammonia levels Allows accurate assessment of detoxification efficiency; ammonia rises rapidly with failure
of the hepatic urea cycle. NB: hyperammonaemia also contributes to vomiting, confusion
& coma of terminal live failure.
Note: If it has been less than 24 hours since ingestion of paracetamol, the paracetamol will show up in the blood. By
plotting plasma conc. against time on the Rumack-Matthew nomogram, the likely toxicity can be assessed.
 How does paracetamol poisoning cause liver failure?
“The liver metabolizes more than 90% of an acetaminophen dosage to sulfate and glucuronide conjugates, which
are water soluble and are then eliminated in the urine. Sulfation is the primary metabolic pathway in children aged
12 years and younger. Glucuronidation predominates in adolescents and adults. Two percent of an acetaminophen
dose is excreted unchanged by the kidneys. The remaining acetaminophen is metabolized by the hepatic
cytochrome P450 (CYP450) system to form a reactive, highly toxic metabolite known as N -acetyl-p-benzoquinone
imine (NAPQI). Glutathione binds NAPQI, enabling the excretion of nontoxic mercapturate conjugates in the urine.
Therapeutic doses of acetaminophen do not cause hepatic injury; however because hepatic glutathione stores are
depleted (by 70-80%) in an acetaminophen overdose, NAPQI cannot be detoxified and covalently binds to the lipid
bilayer of hepatocytes, causing hepatic centrilobular necrosis.”
“Furthermore, alcohol and certain medications such as phenobarbital, phenytoin (Dilantin), or carbamazepine
(Tegretol) (anti-seizure medications) or isoniazid (INH, Nydrazid, Laniazid) - (anti-tuberculosis drug) can significantly
increase the damage. They do this by making the cytochrome P-450 system in the liver more active. This increased P450 activity, as you might expect, results in an increased formation of NAPQI from the acetaminophen. Additionally,
chronic alcohol use, as well as the fasting state or poor nutrition, can each deplete the liver's glutathione. So, alcohol
both increases the toxic compound and decreases the detoxifying material.”
http://emedicine.medscape.com/article/1008683-overview
References:
Human Anatomy and Physiology, Marieb & Hoehn
Medical Biochemistry, Baynes & Dominiczak
Murtagh’s General Practice
Pharmacology, Rang & Dale
Pathophysiology, MCance, Huether et al
Textbook of Medical Physiology, Guyton & Hall
http://www.mdconsult.com
http://www.patient.co.uk/doctor/Paracetamol-Poisoning.htm
Additional Reading: QML Liver Function Tests, Appleton
Oxford Concise Medical Dictionary
http://www.medicinenet.com/tylenol_liver_damage/page3.htm
http://emedicine.medscape.com/article/1008683-overview