Liver Diseases

Liver
Diseases
Lecture 3
Outline
• Functions of the liver
• Biochemical tests for liver disease
• Bilirubin metabolism and jaundice
• Bile and gallstones
• Diseases of the liver (cholestasis, hepatitis,
cirrhosis, liver failure, malignancy, metabolic,
NAFLD)
Functions of the liver
1- Metabolic functions: glucose storage as glycogen,
gluconeogenesis from aa, VLDL, ketogenesis
2- Synthetic function: plasma proteins, coagulation
factors, bile acids, lipoproteins
3- Excretion and detoxification: cholesterol, ammonia,
drugs, and toxins
4- Formation and excretion of bilirubin
1-The liver can lose three-
quarters of its cells before it
stops functioning.
2-The liver is the only organ in

the body that can regenerate
itself.
Diagnosis of Liver Disease
1. Patient's symptoms
2. Physical examination
3. Liver function tests
4. Ultrasound, computed tomography (CT)
scan, and magnetic resonance imaging (MRI)
scan
5. Liver biopsy
What is Portal Hypertension?
• high blood pressure in the portal vein.

• Causes: increased blood pressure in the portal blood
vessels, or resistance to blood flow through the liver.
• can lead to the growth of new blood vessels (called
collaterals) that connect blood flow from the intestine to
the general circulation, bypassing the liver.
• When this occurs, substances that are normally removed
by the liver pass into the general circulation.
• Symptoms:
1-Ascites
2-Bleeding of the varicose veins at the lower end of the
esophagus and in the stomach lining
What is Ascites?
• fluid build-up in the abdominal cavity caused by fluid leaking from
the surface of the liver and intestine.
• usually accompanies portal hypertension
• Symptoms: distended abdominal cavity, which causes discomfort
and shortness of breath
• Causes: liver cirrhosis (especially cirrhosis caused by alcoholism)
• alcoholic hepatitis
• chronic hepatitis
Biochemical tests for liver diseases
• Hepatocyte damage: aminotransferases (ALT & AST)
• Hepatocellular synthetic function: albumin,
prothrombin time
• Hepatic excretory function: bilirubin, ALP, GGT
Aminotransferases
• A rise in plasma aminotransferase activities is a

sensitive indicator of damage to cytoplasmic and/or
mitochondrial membranes.
• Plasma enzyme activities rise when the membranes
of only very few cells are damaged. Liver cells contain
more AST than ALT, but ALT is confined to the
cytoplasm, in which its concentration is higher than
that of AST.
• Albumin
A plasma albumin concentration below the lower reference limit
may imply hepatic disease chronicity. However, there are many
other causes of a low plasma albumin concentration that are not
due to hepatic disease.
• Prothrombin time
The prothrombin time may be prolonged by cholestasis.
Fat-soluble vitamin K cannot be absorbed normally if fat
absorption is impaired due to intestinal bile salt deficiency. The
abnormality is then corrected by parenteral administration of
the vitamin.
A prolonged prothrombin time may also result from severe
impairment of synthetic ability if the liver cell mass is greatly
reduced; in such cases it is not corrected by parenteral
administration of vitamin K.
• Alkaline phosphatase (ALP)
• Alkaline phosphatase is derived from different tissues, including the
liver, the osteoblasts in bone and the placenta.
• Plasma activities rise in cholestatsis because ALP is within the biliary
tract is regurgitated into plasma.
• A raised ALP + raised GGT = implies that ALP is of hepatic origin.
• Gamma-Glutamyl transferase (GGT)
• GGT is derived from the endoplasmic reticulum ( microsomal
enzyme) of the cells of the hepatobiliary tract.
• As this reticulum proliferates, for example in response to the
prolonged intake of alcohol and of drugs such as phenobarbital and
phenytoin, synthesis of the enzyme is induced.
• LDH
• Platelet count:
• Individuals with liver disease develop splenomegaly so
platelets are trapped within the spleen in an exaggerated
way causing decreased platelet count.
Bilirubin metabolism and jaundice
Bilirubin metabolism and jaundice
• Jaundice usually becomes clinically apparent when the plasma
bilirubin concentration reaches about twice the upper
reference Limit 50 umol/L (hyperbilirubinaemia). It occurs
when bilirubin production exceeds the hepatic capacity to
excrete it. This may be because:
• An increased rate of bilirubin production exceeds normal
excretory capacity of the liver (prehepatic jaundice).
• The normal load of bilirubin cannot be conjugated and/or
excreted by damaged liver cells (hepatic jaundice).
• The biliary flow is obstructed, so that conjugated bilirubin
cannot be excreted into the intestine and is regurgitated into
the systemic circulation (posthepatic jaundice).
Jaundice
Physiological Pathological Congenital
Pre-hepatic hepatocellular Post-hepatic

(hemolytic) (Obstructive)
Patients with liver disease often
present with characteristic
symptoms and signs,
particularly jaundice, the
yellow-orange discoloration of
the skin due to a high plasma
concentration of bilirubin.
Bilirubinuria reflects an increase
in the plasma concentration of
conjugated bilirubin, and is
always pathological.
Pathological Jaundice
Pre-hepatic hepatic Post-hepatic
Plasma bilirubin Increased Increased Increased
unconjugated unconjugated & conjugated
conjugated
Plasma enzymes ↑ LD1 & LD2 ↑↑AST&ALT ↑↑ALP&GGT

↑↑↑AST ↑ALP&GGT ↑AST&ALT
↑ LD5
Urobilinogen and Increased Highly increased Tea- Absent

urine colour Deep yellow like? Pepsi-like?
Urinary bilirubin ------- high Very high
Stercobilin and Increased Decreased Decreased

colour of feces Dark brown Clay pale
Neonatal jaundice
• Red cell destruction, together with immature hepatic
• processing of bilirubin: increase unconjugated bilirubin
(physiological jaundice).
• Normal full-term babies may show jaundice between days 2-8
of life.
• Physiological jaundice rarely exceeds 100 μmol/L. As a result
of hemolytic disease, the plasma concentration of
unconjugated bilirubin may be as high as 500 μmol/L and may
exceed the plasma protein-binding capacity; free
unconjugated bilirubin may be deposited in the brain, causing
kernicterus.
• Treatment: Phototherapy, glucose and phenobarbital
Inherited hyperbilirubinemia
• Unconjugated hyperbilirubinemia:
1- Gilbert’s syndrome
2- Crigler–Najjar syndrome
• Conjugated hyperbilirubinemia:
1- Dubin Johnson’s syndrome
2- Rotor’s syndrome
Inherited hyperbilirubinemia
Unconjugated hyperbilirubinemia:
Gilbert’s syndrome Crigler Najar’s syndrome

conjugated hyperbilirubinemia:
Dubin-Johnson Rotor’s syndrome

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Liver Diseases

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Liver

2-The liver is the only organ in

• high blood pressure in the portal vein.

• A rise in plasma aminotransferase activities is a

Physiological Pathological Congenital

Pre-hepatic hepatocellular Post-hepatic

Plasma enzymes ↑ LD1 & LD2 ↑↑AST&ALT ↑↑ALP&GGT

Urobilinogen and Increased Highly increased Tea- Absent

Urinary bilirubin ------- high Very high

Stercobilin and Increased Decreased Decreased

Gilbert’s syndrome Crigler Najar’s syndrome

Dubin-Johnson Rotor’s syndrome

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