10 Flashcards
It is a transient, physiologic jaundice,
because
the activity of hepatic bilirubin
UDP-glucuronyl transferase (UGT) is low at
birth. UGT reaches adult levels in about 4
weeks.
Elevated unconjugated bilirubin, in excess of
the binding capacity of albumin (20–25
mg/dl), can cause?
can penetrate blood-brain barrier and
diffuse into the basal ganglia.
• If left untreated → toxic encephalopathy, or
kernicterus → can causes mental retardation.
Neonatal; Physiologic Jaundice:
They are treated with
blue fluorescent light (phototherapy) that converts bilirubin to
more water-soluble photo-isomers → can be
excreted into bile without conjugation.
Crigler-Najjar Syndrome Types I & II:
• Both types are due to defects in
UDP- glucuronyl transferase activity.
the severe form of Crigler-Najjar Syndrome?
Type I is the severe form → serum bilirubin over 20 mg/dL → brain damage that reflects the complete absence of the enzyme activity.
Phototherapy ↓ plasma bilirubin levels somewhat, but phenobarbital has no beneficial effect.
• The disease is often fatal within the first 15 months of life.
In type II, some of the enzyme activity is retained→ more benign course.
Serum bilirubin tends not to exceed 20 mg/dL and the patients respond to treatment with large doses of phenobarbital.
Gilbert’s Syndrome:
It is due to
• Benign unconjugated hyperbilirubinemia with normal liver
chemistries.
• It is due to low activity of bilirubin UDP-glucuronyl transferase
Common Liver Chemistry Tests
Synthetic Functions of the Liver:
o Albumin: 3.4 - 4.7mg/dL, 40% of albumin is present in plasma & 60% is present in extracellular spaces ,, essential for maintenance of osmotic blood pressure Important for transport of many substances
oTotal Plasma Proteins: 7.0 - 7.5 g/dL The major plasma proteins: albumin, globulins & fibrinogen.
oProthrombin Time: One of coagulation factors that is synthesized in liver in the presence of vitamin K. Prothrombin is transformed into thrombin by clotting factor X. Thrombin then transforms fibrinogen → fibrin. Fibrin in combination with platelets → forms a clot.
The most common tests used as prognostic factors are:
PT, albumin & bilirubin
Cause of Prolonged Prothrombin Time:
§ Liver disease. § Vitamin K deficiency: malabsorption, malnutrition, antibiotics. § Congenital disease. § Warfarin. §
Massive transfusion.
Causes of Low Serum Albumin Levels:
§ The most common reason is chronic liver failure caused by liver cirrhosis.
§ ↓ Serum albumin levels are NOT seen in acute liver failure. It takes several weeks of impaired albumin production before serum albumin level ↓.
§ ↓ Serum albumin due to some other conditions than liver disease:
- Sever malnutrition.
- Some kidney diseases:→ extensive albumin loss in urine.
- Severe burns: → damage capillaries & blood vessels → huge loss of serum
proteins.
Importance of Liver Enzymes in Clinical Diagnosis:
Liver transaminases; ALT & AST; are NOT true liver function but they are biomarkers of “liver injury”.
Other tests to assess liver functions include: GGT, ALP & its
hepatic isoenzyme and 5’-nucleotidase.
ALT catalyzes the following reaction:
Alanine + α-Ketoglutarate → Pyruvate + Glutamate
AST catalyzes the following reaction:
Aspartate + α-Ketoglutarate → Oxaloacetate + Glutamate
§ AST is found in many tissues.
§ Not very specific for liver disease. § Often follows ALT to a degree.
AST , ALT in
AST : Cytosol (20%) and in mitochondria ,,, liver, cardiac muscle, skeletal muscle, kidneys, brain, pancreas, lungs, leucocytes, and RBC.
ALT: Cytosol more specific to the liver.
ALT AST: Reference range
AST: Reference range (0 up to 35 IU/L). ALT: Reference range (0 up to 45 IU/L).
Cholestasis
o ALP,
o GGT,
o 5’-nucleotidase, (Bilirubin & bile acids)