Liver Functions

The liver1
The liver is the largest organ in the human body, its weight 1.2-1.5 kg in adult and it accounts for
about 3% of body weight in early life (children), and about 2% in the adult life. It has a great
reserve capacity; nearly 4/5 of the liver can be removed without seriously affecting its function,
but mild diffuse lesion can alter the result of liver functions.
Liver functions:
1. Metabolism & synthesis: of carbohydrates, lipids & proteins.
2. Uptake & transport: Binding and conjugation function.
3. Formation of bile.
4. Detoxication & conjugation.
Circulation:
1. The portal vein: carries blood from the capillary bed of alimentary tract, thus blood is rich
of nutrients absorbed from GIT; it supplies about 75% of the blood volume of the liver.
2. The hepatic artery: hepatobiliary branch of celiac trunk carries well oxygenated blood to
liver
3. The venous drainage from liver is via right &left hepatic veins
4. Portal triad = portal veins + hepatic artery + common bile duct
Liver cells:
- Hepatocytes (parenchymal cells): 60-80 %: metabolic differences noted between
hepatocytes in different zones may be either intrinsic or due to their location within the
lobule (exposure to different levels of oxygen tension, substrate concentration gradient &
other factors)
- RES cells (kupffer cells) (phagocytic macrophages): 16-30%
- Supporting tissues, capillary (vascular) & biliary canaliculi.
Liver Profile:
1. Bilirubin:
Total: 0.2-1.2 mg/dl
Conjugated: 0.0-0.2
Non-conjugated Calculated (= Total - conjugated)
2. Total protein: 6-8 g/dl
3. Albumin: 3.5-5 g/dl
4. Globulin: Calculated (= Total - Albumin)
5. Enzymes:
ALT (SGPT): ≤ 42 More specific.
AST (SGOT): ≤ 40 Present in heart & RBCs. Has short half life.
ALP: Age dependent Non specific, present in bone, liver, placenta,
intestine, heart
γGT: very specific & sensitive, so don't account on
it, as any patient taking chronic medication
will found high. Used alone to follow up
alcoholism & severe fatty liver.
5 Nucleutidase (5'NT)
6. Prothrombin time (PT)

‫ سوسن سعيد‬.‫د‬.‫ أ‬1

1
 Liver Functions

7. Total cholesterol
Laboratory assessment of liver function
a. Tests of the liver capacity to transport  S. bilirubin
organic anion and metabolized drugs:  S. bile acid
 S. caffine
 Breathe test (obsolete)
Each of these test measure the liver ability to clean
endogenous substances from the circulation.
b. Tests that detect injury to  ALT, AST & ALP: are the most useful
hepatocytes: include all enzymes:  GGT, 5'NT & Glutathion S transeferase: are less
useful 2.
c. Tests of the liver's biosynthetic 1. S. Albumin: a marker for synthetic function of
activity: These substances are the liver; it is valuable guide to the severity of
synthesized in liver for transport in the chronic liver disorders. Low S. albumin is bad
circulation: prognostic sign.
2. Ceruloplasmin
3. Ferritin
4. α1-antitrypsin
5. Lipoproteins
6. Blood clotting factors except VIII & vWF: PT
(INR) is a marker of synthetic function but
because of its short half life it is a sensitive
indicator of both acute and chronic liver
disease3.
d. Tests to detect chronic inflammation  Immunoglobulins
in liver altering immunoregulation:  Hepatitis markers.
They are not truly LFTs because most  Specific auto-antibodies.
of these substances are proteins made
by B-lymphocytes not by hepatocytes;
however they are quite specific for
certain liver diseases.

2
MCQ: GGT is very sensitive to drugs.
3
MCQ: PT is the best indicator of recovery from liver failure.

2
 Liver Functions

UDP glucoronyl transferase: very important transferase formed 7month IU life.

Obsolete names: (never say in front of Dr Sawsan)
Direct: soluble in water  measured directly,
Indirect: fat soluble, measured after adding solvent (ether)
MCQ: What are urobilinogens? Stercobilinogen, urobilinogen and mesobilinogen
Absence of urobilinogen in urine = obstruction

3
 Jaundice

Jaundice
It is yellow pigment of skin & sclera of the eye caused directly by increase in bilirubin in the
serum.
Reference value Hyperbilirubinaemia Manifested
hyperbilirubinaemia (jaundice)
- Total: 0.1-1.0 mg/dl. Increase of S. bilirubin >RV (1- Bilirubin >3mg/dl or >51 μmol/l
- Conjugated: 0.0-0.2 mg/dl. 3mg/dl)
Metabolism of bilirubin:
15% of bile come from catabolism of other haem containing protein such as myoglobin,
cytochrome and 250-300 mg bilirubin produced daily. The intestinal bacterial enzymes
hydrolyze the bilirubin then reduce it to urobilinogen 4.
Presence of urobilinogen in urin is best and early indicator of recovery from acute hepatitis.
Clinical manifestation of hyperbilirubinaemia:
Jaundice, nausea, vomiting, abdominal pain, general malaise & fatigue.

Types of Hyperbilirubinaemia:
1. Prehepatic hyperbilirubinaemia:
- Due to increased breakdown of hemoglobin (usually there is no active liver disease).
- Increased unconjugated (lipid soluble, water insoluble bilirubin).
- Causes: - Hemolytic anaemia - Pernicious anaemia
- ABO &RH incompatibility - G6PD deficiency
- Sport injury
- Chemical agents e.g insecticides, drugs (novocaine, NSAID)
2. Hepatocellular:
Problem in liver parenchyma affecting:
a) Hepatic uptake: increase unconjugated
i. Gilbert syndrome ii. Hepatitis. iii. Cirrhosis.
b) Conjugation failure: increase unconjugated due to:
i. Premature infant: UDP gluourenyltranseferase is not formed well before 7 months.
ii. Congenital defeciency of conjugation enzyme: Gilbert syndrome, Crigler-Najjar
syndrome.
iii. Competitive inhibition of conjugating enzyme: Novobiocin.
c) Transport (release): 75% conjugated bilirubin, 25% unconjugated bilirubin.
- Causes: Roter & Dobin-Johnson syndromes.
3. Post hepatic:
Increased conjugated bilirubin
a. Intra-hepatic (medical):
i. Hepatitis. ii. Cirrhosis. iii. Intrahepatic carcinoma.
iv. Primary biliary cirrhosis.
v. Drugs: methyltestosterone, phenothiazide
b. Extra-hepatic (surgical):
i. Gall stones in CBD.
ii. Cancer head of pancreas.
iii. Cancer of biliary tree.

4
MCQ: so, no urobilinogen in massive dose of antibiotics

4
 Jaundice

Jaundice with special condition:

1. Jaundice with pregnancy: rare (1/1500) with rare indication to interrupt pregnancy
Causes:
a. All causes of jaundice (general)
b. ‫ هام‬Unusual response to estrogen causing intra hepatic cholestasis or jaundice of late
pregnancy: uncomfortable yet it is generally not serious. Usually last for a week (usually
the last week of pregnancy) and release after labour.
c. Acute fatty metamorphesis (acute fatty liver of pregnancy): more serious condition.
Occurs in the first pregnancy and it is difficult to differentiate between it and acute viral
hepatitis, mortality rate for mother and baby are high, most of them develop renal failure
– ‫هام‬
2. Jaundice with anaesthesia: within 8 hours from surgery, especially with halothan.
3. Jaundice with surgery: especially with cholecystectomy (accidental closure of CBD)
4. Jaundice after blood transfusion:
a- Old stored RBCs
b- ABO & Rh incompatibility
5. Jaundice after drugs: phenothiazide, anabolic steroids, novobiocin.

Congenital hyperbilirubinaemia
Gilbert syndrome: (congenital not neonatal)
Incidence:
- 2-5% of population.
- Predominant in males (2-7 times more common in male).
Clinical Presentation:
- Usually detected in adolescence
- Coincidently with other disease (stress). The other disease may not be a liver disease.
- Asymptomatic unconjugated hyperbilirubinemia: Total bilirubin 2-3 mg/dl & may be more
with the degree of the other illness.
Causes:
1. Defect of hepatic uptake of bilirubin from plasma.
2. Mild deficiency of UDP-glucuronyle transferase 5.
Significance: Patient with Gilbert's syndrome are unable to metabolize some drugs. So, most
care for those patients on medications.
Laboratory diagnosis: All liver functions are OK except high total and unconjugated bilirubin.
Differential Diagnosis:
To differentiate between Gilbert & Haemolytic anemia: ‫هاااااام جدا‬
Gilbert's Hemolytic anemia
a. Reduced energy intake up to bilirubin elevates to no change
400 cal/day for 3 days (to be in double
stress):
b. Nicotinic acid test (obsolete): elevation occurs after 2-3 elevation occurs before
IV injection of 50 mg, normally hrs, (up to twice the basal 90 min, due to fragile
elevates unconjugated bilirubin level) (higher), RBCs
within 90 min.

5
Uridine Di-Phospho glucuronyle transferase.

5
 Jaundice

Crigler-Najjar syndrome: (neonatal)

Incidence: Rare
Cause: UDP-GT
Type I (severe form) Type II (moderate form)
Complete absence of UDP-GT Moderate reduction in the level of UDP-GT
Severe, hyperbilirubinaemia in neonate  Total bilirubin < 20 mg/dl
total bilirubin 20-50 mg/dl
Causes Kernicterus The condition depends on the level of enzyme
Early death reduction.

Dubin Johnson & Rotor syndromes:

Incidence: Rare, benign conjugated hyperbilirubinaemia and bilirubinuria.
Cause: Genetic (autosomal recessive) defect in the transfer of conjugated bilirubin into the
biliary canaliculi (defect in bilirubin excretion) due to deficiency of transport globulins.
Clinical presentation: Total bilirubin 2-5 mg/dl, the majority (75%) is conjugated. ‫هاااام جدا‬
Dubin Johnson Rotor
Urinary corpoporphyrin Normal ↑
Histology of the liver Black or very dark pigment Normal
Gall bladder x-ray Cannot be visualized Can be visualized
Treatment Both need gene therapy

Reye's syndrome
Definition: Acute encephalopathy in combination with fatty degeneration of the viscera.
N.B: Aspirin is fat soluble, thus it increases the diameter of pores of the brain barriers. So, it is
forbidden in extremes of age.
Incidence: It frequently affects children aged 6-11 years (in rural areas).
Cause: The etiology is unknown; however there is generalized mitochondrial dysfunction.
Clinical picture:
- Prodromal phase: Febrile viral illness caused by either varicella or influenza B for one weak as
a prodromal phase
- Followed by abrupt onset of:
Protracted (projectile) vomiting,
Neurological changes e.g. lethargy, confusion deteriorate rapidly into stupor & coma.
At the same time liver is enlarged, marked abnormalities in functions become evident.
- Cerebral oedema is the major factor contributing to the mortality rate.
Lab finding:
AST & ALT ↑ (especially ALT).
Total bilirubin N or slight ↑
Ammonia (encephalopathy). ↑
AAs & FFAs Hyper-aminoacidemia
UA Hyperuracemia
PT  (Hypoprothrombinemia unresponsive to vitamin k)
Glucose Tendancy to hypoglycemia in young age
- Liver biopsy is diagnostic.
Manegment: Consists of judicious treatment of increased intracerebral pressure secondary to
cerebral oedema with osmotic diuretics such as mannitol.

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 Liver Diseases

Liver Diseases
A. Hepatitis

Hepatitis

Non infectious Infections

Idiopathic
Chemical
Drugs Parasitic Viral
Metabolic ToxoplasmaGondii
disorders E. histolytica
E. granulosus Secondary Primary
Schistosoma CMV HAV
EBV HBV
HSV HCV
VZV HDV
HEV
HFV
HGV
Laboratory diagnosis of hepatitis:
A. Serological diagnosis
Acute Panel

HBs-Ag HAV-Ab HCV-Ab

HBc-IgM  
If HAV-Ab +ve: If HCV-Ab +ve:
 
If If If Ac. hepatitis A HCV heapatitis
HBs Ag -ve HBs-Ag +ve HBs-Ag +ve
HBc IgM +ve HBc-IgM +ve: HBc-IgM -ve:
  
Acute viral hepatitis Acute phase
Do
very early (10%) = B heapatitis
HBe-Ag
Window Gap

HBsAg to be
repeated (+ve) +ve -ve
 
Ch. Persistent B hepatitis
Ch. active B hepatitis
(Carrier)
(Multiplication)
Or D on top of Hepatitis B
If all are negative  consider other causes of hepatitis
B. Chemical diagnosis of hepatitis:
1. AST & ALT:
 Typically elevated during the final weeks of the incubation period in viral hepatitis
 Usually the first abnormal biochemical tests regardless of the causative agent.
 10- 100 times of normal values  Probably viral hepatitis.
 < 10 times of normal may suggest a non viral etiology.
2. ALP: increase by twice normal (2x).
LDH: increase by twice normal (2x).

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 Liver Diseases

3. Urine bilirubin: detected before appearance of jaundice.

4. Serum bilirubin: start to elevate during prodromal phase.
5. GGT: elevated by 5 folds (5x)
6. PT: Prolonged.
7. ESR: Increased.
N.B: Hypoalbuminemia is present only in chronic hepatitis as the half life of albumin is 21
days.
B. Steatohepatitis
Non Alcoholic Steatohepatitis (NASH):
Definition:
 A disease of unknown origin, characterized by changes similar to that noticed in alcoholic
liver injury with absence of significant alcoholic intake.
 A type of chronic hepatitis
 A severe form of a spectrum called non alcoholic fatty liver disease (NAFLD).
Course:
 The condition usually runs through an indolent course,
 50% of patients progress to liver fibrosis,
 15% develop cirrhosis
 3% may progress to terminal liver failure.
Types:
1. Primary NASH:
Incidence: It is the predominant form of NASH, affecting individuals at least as many as
chronic hepatitis C.
Characteristic: Associated with dysmetabloic syndromes (e.g. obesity, type 2 DM,
dyslipidemia).
2. Secondary NASH:
Characteristic: Accompanies other syndromes or caused by certain drugs.
Pathogenesis:
Hepatic fat accumulation (steatosis),
Abnormal cytokines production
Abnormal peroxidation and oxidative stress.
Laboratory diagnosis:
1. Serum AST & ALT:
Mildly to moderately elevated (up to 5 times).
AST/ALT ratio > 1 (of < 1 normally) as NASH progress to cirrhosis.
2. Serum ALP & bilirubin: usually within 2 times the normal range
3. GGT: increases, but more with alcoholic steatosis.
New markers include: ‫مش مهم‬
1. Microsomal AST (mAST).
2. Carbohydrate deficient transferrin (CDT)
3. Serum 5- hydroxytryptophol.
4. β- hexosaminidase.

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 Liver Diseases

C. Cholestasis
Definition: Not a disease per se, but a clinical & biochemical syndrome that occurs whenever
adequate amounts of both bile salts & bilirubin have failed to reach the intestinal tract & have
accumulated instead in blood.
The impairment of bile flow or blockage may occur at any point from liver cell canaliculus to the
entrance of CBD at the duodenum (ampulla of Vater).
Etiology & pathophysiology: ‫مش مهم‬
I. Intrahepatic:
1. Viral hepatitis
2. Drugs or alcohol induced liver diseases.
II. Extrahepatic:
1. CBD stones (acute pain & acute relief)
2. Cancer head of pancreas.
3. Biliary atresia & strictures.
4. Biliary tract carcinoma
Pathogenesis:
- As bile canaliculus becomes congested with bile they tend to be enlarged & even to rupture.
This leads to escape of bile & bile salts directly into blood stream.
- The case starts by conjugated, and then unconjugated hyperbilirubinemia i.e. mixed
hyperbilirubinemia.
- If obstruction is complete, the stool will be grey (clay) colored, which is the result of lack of
bile & increased fat content of stool.
- Lack of emulsifying action of bile in intestine causes malabsorption of fat (i.e. decrease of fat
to half of the normal amount) which means that a big amount of fat would not be absorbed
leading to steatorrhea & interference in absorption of fat soluble vitamins & calcium. When
vitamin D & calcium decrease, that means osteoprosis & bone pain. Also, vitamin K deficiency
causes defect in synthesis of various clotting factors leading to prolongation of PT & bleeding
tendency. Vitamins A & E also decrease.
Clinical picture:
Jaundice, pruritis, light colored stool, -ve urobilinogen.
Characterestics of prolonged cholestasis:
1. Jaundice: 75% conjugated.
2. Pruritis: often severe itching. It is due to movement of bile salts to peripheral tissues.
3. Malabsorption: due to lack of bile in intestine  fat soluble vitamins
4. Hypercholestrolemia: increased synthesis may result in fatty tumor like masses in the skin
called Xanthomas (mostly in back, shoulders).
Laboratory diagnosis:
1. GGT6:
- Usually most significantly elevated by obstructive disease.
- It has good specificity for liver diseases & not in bone diseases, pregnancy (as in ALP) or
skeletal muscles diseases (as in AST).
- In mechanical & viral cholestasis GGT & ALP are equally elevated (x equal), while in drug
induced cholestasis GGT is elevated much more significantly than ALP.

6
.‫الزم يتكتب أول واحد فيهم‬

9
 Liver Diseases

- N.B: Patients with drug history must be considered in evaluation of abnormal GGT levels
especially Phenobarbital & phenytoin (anti-epileptics) on long term basis, as these drugs
induce liver microsomes to increase protein synthesis & produce certain enzymes
especially GGT.
2. ALP: is elevated to around 2x the upper reference range limits for adults in parynchemal
damage (e.g. hepatitis with cholestasis).
It is increased to 2x – 4x the normal reference range for adults in diseases or damage of the
ducts with cholestasis.
3. Urine bilirubin: +ve, due to presence of conjugated bilirubin.
4. Urine urobilinogen: -ve in obstructive disease with cholestasis.
N.B: urine dipsticks do not measure –ve urobilinogen levels & only measure normal or
elevated amounts. It is only measured by quantitative test.7
5. PT: prolonged, & the patient will exhibit bleeding tendency if cholestasis is prolonged. This is
mainly due to malabsorption of fats & vitamin K.
6. Serum transaminases (AST & ALT): elevate with both intra- & extra- hepatic cholestasis.
7. Serum amylase: its elevation usually indicates extrahepatic obstruction from head of
pancreas.
8. Liver biopsy: Usually not needed (imaging replaces it) but may also help to clarify diagnosis.

‫ مهم‬MCQ ‫ سؤال‬7

10
 Liver Diseases

Liver cirrhosis
N.B:
Diffuse liver cell death is the precursor of cirrhosis whatever the cause is.
Cirrhosis is a disease in which there is permanent structure damage of liver cells.
Morphologically, cirrhosis presents with two features:
1. Increased fibrous tissue.
2. Nodular regeneration.
Clinical manifestations:
 Jaundice, fluid accumulation in the peritoneal cavity (ascitis), CNS dysfunction, increased
interstitial fluid (edema), then finally; the distorted intra-hepatic vasculature by fibrosis
leading to portal venous hypertension, splenomegaly & esophageal varices.
 With alcoholic cirrhosis: weakness, fatigue, anorexia, weight loss, muscle wasting,
gynecomastia & testicular atrophy or amenorrhea. The liver may be firm & enlarged. These
features are generally secondary to the large intake of ethanol. The cause of death is usually
hepatic coma or hemorrhage from ruptured esophageal varices.
 With post-necrotic cirrhosis: more jaundice, but signs of wasting <alcoholic cirrhosis.
 With biliary cirrhosis: patient typically female with biliary cirrhosis may complaint of itching,
pale stool, jaundice, dark urine, steatorrhea, diarrhea, osteomalacia, backache, bone pain &
yellowish plaques and nodules.
Laboratory analysis & diagnosis:
N.B: The most definite mean for diagnosing cirrhosis is liver biopsy, it is 3 times more definite
than any other manipulation.
Due to alteration in liver metabolism: 1. Reduced albumin synthesis.
2. Prolonged PT.
3. Reduced cholesterol synthesis.
4. Insulin resistance (metabolic disturbance).
If cirrhosis on top of cholestasis:\ 5. Elevated ALP & GGT.
6. Elevated total & conjugated bilirubin.
If cirrhosis is post-necrotic (either mild 7. Elevated AST & ALT (1 – 5 times).
or severe) 8. Elevated LDH (4 & 5 isoenzymes).
If primary biliary cirrhosis (autoimmune 9. Variable level of increased bilirubin with
disease): hyperpigmented skin.
10. Early, there is rise in serum triglycerides &
cholesterol leading to xanthomas (on skin),
also xanthelesma (on upper eye led)
develops.
11. ALP increases 2 – 10 folds.
12. AST & ALT elevates moderately
13. 85–90% of patients have +ve anti-
mitochondrial antibodies. ANA & ASMA
may be +ve.
The reliable poor prognostic indicators:
1. High level of bilirubin
2. Low level of albumin with prolonged PT.
- In late stages:
3. Elevated serum copper 10 – 100 times reference range.
4. Elevated serum ceruloplasmin
5. High susceptibility to UTI.

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 Liver Diseases

Liver carcinoma
Primary cancer liver:
 Hepatocellular carcinoma: in liver cells.
 Cholangiocellular carcinoma: in liver cells & bile ducts.
Secondary cancer liver:
Almost all types of cancer have the potential to metastasize to the liver. This is because the liver
participates in many metabolic functions & is highly vascular.
Etiology & pathophysiology:
Predisposing factors:
a. Chemical carcinogens: e.g. aflatoxin B which originates from the fungus asprigillus flavus.
b. Cirrhosis on top of hepatitis B: 80 – 90% of all patients with primary cancer are previously
infected with HBV, & 40 -50% of patient carriers for HBsAg will develop cancer liver in their
lifetimes.
c. Inflammation: either after post-necrotic liver cirrhosis, alcoholic liver cirrhosis, biliary
cirrhosis, or diseases caused by metabolic deficiency.
No single laboratory test is useful for early detection, diagnosis or monitoring of cancer liver.
I. Oncofetal tumor markers:
1. AFP: it is an oncofetal antigen that is highly glycoselated & produced in utero, first by yolk
sac, and later by fetal liver. It is similar in molecular weight to albumin. As the liver
develops it shifts from AFP to albumin production.
Reference Range: in sera of non-pregnant adults: 0–3 μg/dl. In pregnancy: 5–35 μg/dl.
- Gray Zone: Levels of 4–100 μg/dl are associated with benign liver diseases (cirrhosis &
acute hepatitis), early primary cancer liver, & other tumors (e.g. GIT tumors such as colon,
pancreas, & stomach).
NB: Persistent AFP elevation for 6-12 months is associated with liver cancer, whereas
transient elevation is associated with benign liver diseases.
- Diagnostic levels of AFP > 100 μg/dl are almost always associated with advanced
hepatocellular carcinoma. Patints in this group are often beyond treatment.
2. CEA: it is a glycoprotein increases in cancer colon, liver diseases (primary & secondary
cancer) in alcoholic liver disease
Can be used in assessment of patients in conjunction with AFP:
a. Large increase of AFP (>100) is suggestive of primary liver cancer
b. If CEA is increased with normal AFP, this is extrahepatic malignancy
c. If both are increased: In 1ry liver cancer where a mild eleveation of AFP coupled with 
CEA is suggestive of secondary liver carcinoma.
d. Increased CEA without increased AFP is suggestive of cancer colon without liver
malignancy (RR < 2.5 ng/ml)
NB: In heavy smokers level is accepted up to 12.5ng/mL
II. Hepatic enzymes markers: Little role in cancer liver, only in follow up
1. ALP: total ALP is only useful as screen test for malignant disease because it is elevated
much with obstructive bone disease, liver metastasis (even when bilirubin is still normal)
- Regan isoenzyme
- α1 isoenzyme.

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 Liver Diseases

2. GGT & 5NT: are elevated x20 together with clinical sensitivity 75-85% (good markers for
metastasis).
Other Laboratory Findings:
1. Hypoglycemia
2. Hyper calcemia (produced by cancer cells  bad sign)
3. Dysfibrinogenemia
4. LDH x10
5.  Vit B12 (by tumor cells  bad sign)

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13
 Hepatic Failure

Hepatic failure
It can be defined as the condition in which the liver cells fail to function adequately. The degree
& duration of failure will determine the prognosis of survival.
Failure occurs because the liver either: Cannot receive the necessary substances for metabolism,
or there are undergoing necrosis.
Etiology & pathogenesis:
It may be the result of chronic liver disease (e.g. HCV, or HDV on top of HBV, which is serious), or
it may be of sudden onset caused by massive liver cell destruction (acute of drug or blood, which
may be controlled).
Predisposing conditions:
1. Viral hepatitis.
2. Drug toxicity: e.g. halothane anesthesia, industrial poisons, chemotherapy, or OCPs.
3. Metabolic diseases e.g. Wilson's disease, galactosemia, fructosemia, tyrosinemia or α-1
antitrypsin deficiency.
Clinical manifestations & complications:
Hypoglycemia, jaundice, hyponatremia, hypokalemia, then edema & ascitis (both are reflection
of fluid & electrolyte imbalance) these may predispose to infection & septicemia, hypertension,
bleeding which may occur from any site (nose, anus, veinipuncture sites). Death is often caused
by GI hemorrhage.
Also, hepatorenal syndrome may develop. This is a condition in which renal failure occurs as a
sequel of hepatic failure.
The accumulation of toxic substances may result in encephalopathy (from I to V) whch may
progress to coma. Pancreatitis will be a further complication.
N.B: the degree of lab results abnormality will reflect the degree of liver failure
Lab analysis & diagnosis: ‫الترتيب هام جدا‬
1. Serum bilirubin; Increases, it may be the first presenting feature.
2. Urine bilirubin: becomes detectable before the appearance of jaundice. N.B: an elevated
bilirubin level is not in itself diagnostic of hepatic failure, but it is strong evidence that the
hepatocytes is not functioning normally.
3. Urine urobilinogen: decreases, normalizes, and then starts to increase.
4. ALP: will show a greater degree of elevation in obstruction & liver metastasis.
5. AST & ALT: will show a greater degree of elevation in hepatocyte injury.
N.B: In the presence of hepatic failure, all three (ALP, AST & ALT) will be moderately elevated
in the serum during the early course of the disease, then all will eventually return to normal
levels or low normal either as the condition improves or the liver cell injury becomes massive
& virtually complete.
6. LDH isoenzymes 4 & 5: will be elevated.
7. GGT: will be elevated.
8. PT: It is the single most important diagnostic hematological test, which can be used to
judge the progress of hepatic failure. The degree of hepatic failure is parallel to the degree of
prolongation in PT (thus result is not given as >60, but actual seconds whatever it is).
Prognosis: Acute hepatic failure has a mortality rate of 75% in the presence of severe hepatic
necrosis & 85% in persons who reach encephalopathy.
Score for bad prognosis:
 Low normal ALT and AST (3,4)
 PT>120 seconds
 Cholesterol <100
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14