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Clinical diagnostic biochemistry - 9
Dr. Maha Al-Sedik2015
CLS 334
1-Excretory function• Bilirubin.• Bile acids.2-synthetic function• Protein (mainly albumin and coagulation factors).• Lipids and lipoprotein.• Urea. 3- metabolic function• Ammonia.• Carbohydrate.4- storage function
LIVER FUNCTIONS
Bilirubin synthesis
RBCs life span is 120 days and are destructed and this releases
hemoglobin, which is broken down to heme and globin which
turned to amino acids cycle.
The heam is then turned into unconjugated bilirubin.
This unconjugated bilirubin is not soluble in water and it can cross
blood brain barrier , it is carried by albumin to liver.
Each gram of albumin can carry 6 – 8 mg of indirect bilrubin.
In the liver, bilirubin is conjugated with glucuronic acid making it
soluble in water.
In the intestinal tract, conjugated bilirubin are hydrolyzed and
reduced by bacteria to form colorless urobilinogens, which
undergo an enterohepatic circulation.
A small fraction (2% to 5%) escapes the liver and is excreted in
urine.
In the colon, urobilinogens spontaneously oxidize to
stercobilinogen then stool pigments stercobilin.
(i)Protein Synthesis:
The liver is the primary site of the synthesis of plasma proteins.
Although disturbances of protein synthesis occur as a consequence
of impaired hepatic function:
Other factors affect plasma protein concentrations include:
Decreased availability of amino acids (malnutrition, maldigestion,
and malabsorption).
Catabolic states (hyperthyroidism, burns, postsurgery recovery).
Protein losing states (nephrotic syndrome )
Hepatic Synthetic Function:
Albumin:
Albumin is the most commonly measured serum protein and is
synthesized exclusively by the liver. The rate of synthesis varies,
depending on the colloidal osmotic pressure of the blood.
These proteins interact to produce a fibrin clot.
Inhibitors of the coagulation system, including antithrombin,
protein C, and protein S, are also synthesized in the liver.
Activated protein C in plasma inhibits coagulation by inactivating
factors V and VIII.
Parenchymal liver disease of sufficient severity to impair protein
synthesis or obstructive liver disease sufficient to impair
intestinal absorption of vitamin K is there fore a potential cause
of bleeding disorders.
Coagulation Proteins:
The prothrombin time (PT):
Measures activity of fibrino gen (factor I), prothrombin (factor II),
and factors V, VII, and X ( extrinsic pathway ).
Normally from 10 – 15 seconds.
Since all of these factors are made in the liver and several are
vitamin K dependent, a prolonged PT often indicates the presence
of significant liver disease.
In cholestasis, vitamin K deficiency may also cause an increase
in PT. In this case, the coagulation abnormality is corrected
within a few days by parenteral injection of l0mg of vitamin K.
In con trast, if PT is prolonged because of hepatocellular
disease, factor synthesis is decreased and administration of
vitamin K does not typically correct the problem.
Patients with severe hepatocellular disease have decreased
synthesis of the vitamin K-dependent clotting factors, especially
factor VII.
Patients with cholestatic disease have decreased bile salt
secretion, which is necessary for the absorption of vitamin K,
leading to failure of activation of factors II, VII, IX, and X. In these
patients, unlike those with hepatocellular disease, the
prothrombin time can be cor rected with an injection of vitamin K.
Prothrombin time:
A sample of the patient's blood is obtained by venipuncture. The blood is decalcified (by collecting it into a tube with oxalate or citrate ions) to prevent the clotting process from starting before the test. The blood cells are separated from the liquid part of blood (plasma) by centrifugation. The PT test is performed by adding the patient's plasma to some source of Tissue Factor (e.g.: a protein, thromboplastin, from homogenized brain tissue) that converts prothrombin to thrombin. The mixture is then kept in a warm water bath at 37°C for one to two minutes. Calcium chloride (excess quantities of ionized calcium) is added to the mixture in order to counteract the sodium citrate and allow clotting to start. The test is timed from the addition of the calcium chloride until the plasma clots. This time is called the Prothrombin Time.
Catabolism of proteins and amino acids results in
the formation of ammonia then in the liver urea is
formed from ammonia, which is predominantly
cleared from the body by the kidneys.
Urea Synthesis:
Protein
Proteolysis, principally enzymatic
Amino acids
Transamination and oxidative deamination
Ammonia
Enzymatic synthesis in the “urea cycle”
Urea
Patients with end-stage liver disease may have low concentrations
of urea in plasma.
In addition, plasma concentrations are elevated for ammonia.
These findings suggest that patients with liver disease have an
impaired ability to metabolize protein nitrogen and to synthesize
urea.
Inflammation of the liver which causes damage of liver cells
with reduced the liver’s ability to perform life preserving
functions.
What is Hepatitis ?
Infection Non-Infection
• Autoimmune
• Toxic: (drug, Alcohol)
• Traumatic
• Bacterial leptospira (Weil's disease) mycoplasma - rickettsia (typhus fever)
• Parasitic Amoeba and schistosome
• Viral: A, B, C, D, E.• chickenpox, Rubella &• cytomegalovirus
Individuals infected with a hepatitis virus tend to have
generalized symptoms, which in the early stages are
similar to the flu:
• Fatigue• Loss of appetite
• Nausea• Fever
Jaundice.
Ascites.
Esophageal varies.
Hepatic encephalopathy.
Bleeding tendency.
Hepatitis Viruses are Highly Infectious, Particularly HBV 50-100
times More than HIV.
A E B D C
EntericallyTransmitted
Parenterally
Transmitted
Acute hepatitis
May range from asymptomatic (without any signs or
symp.) to severe fatigue, jaundice, nausea, vomiting or
diarrhea. The acute infection cleared within 6 months.
Symptoms often subside without treatment within a few
weeks or months.
Chronic hepatitis
About 5 % of cases develop into an incurable form of the
disease > 6 months, called chronic hepatitis, which may last for years
causing slowly progressive liver damage that lead to cirrhosis, a
condition in which healthy liver tissue is replaced with dead,
nonfunctional fibrous tissue. In some cases, cancer develops.
A and E(feco-oral) through:• Ingestion of contaminated water supplies or food (most common)• Close contact.
B C DBlood: Drug abuse, tattoo, Stick injury, Hemodialysis, Blood transfusion, transplantation.Sexual: sexual Contact with infected household objects . It is not sure about virus C .Placental: Mother to neonate.
Routes of transmission
Chronicity
E D C B ANo Yes Yes Yes No
Hepatocellular Carcinoma
E D C B ANone Yes Yes Yes None
Reference: Burtis and Ashwood Saunders, Teitz fundamentals of Clinical Chemistry, 4th edition, 2000.
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