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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