Dr Gihan Gawish

Liver - Anatomy and Physiology

Largest organ in the body

Three basic functions• Metabolic• Secretory• Vascular

Major function• Excretion of waste products from

bloodstream by excretion into bileDr Gihan Gawish

Liver - Anatomy and Physiology

Location• Upper right quadrant• Four lobes made up of hepatocytes• phagocytic cells

Blood supply• One major vein - portal vein• One major artery - hepatic

Dr Gihan Gawish

Liver - Anatomy and Physiology

Functions of liver• Blood glucose concentration• Protein metabolism• Fat metabolism• Storage functions• Drug metabolism• Ammonia conversion

Dr Gihan Gawish

Metabolic Profile of the Liver

The primary function of the liver is to regulate the metabolism.

It metabolizes the intake of carbohydrates, fats, and proteins.

It accomplishes this function by working closely with other systems such as lymphatic system, circulatory system, as and endocrine

system.

In order for the liver to metabolize the fats, carbohydrates, and proteins, it must be

healthy and free of any diseases.Dr Gihan Gawish

Bile Production Liver produces and secretes a product called

bile.

This is what makes it possible for metabolize the intake of fats, proteins, and carbohydrates.

This fluid is a very important presence in the body due to the fact that it aids in the

elimination of contaminants in the body, such as drugs.

The bile system is also responsible for re-circulating red blood cells.

Dr Gihan Gawish

BILIRUBIN PRODUCTION

Heme(250 to 400 mg/day)

Heme oxygenase

Biliverdin reductase

Hemoglobin(70 to 80%)

Erythroid cellsHeme proteinsmyoglobin, cytochromes

(20 to 25%)

Biliverdin

Bilirubin

NADPH + H+

NADP+

3 [O]

Fe3+ + CO

apoferritinferritin

indirectunconjugatedpre-hepatic

albumin

Dr Gihan Gawish

Dr Gihan Gawish

BILIRUBIN PROCESSING

albumin-Bilirubin

ligandin

Bilirubin diglucuronide

ER

hepatocyte

UDP-Glucuronyl transferase

albumin

ligandin-Bilirubin

bile (gall bladder)

directconjugatedpost-hepatic

2 UDP-glucuronate

2 UDP

Dr Gihan Gawish

BILIRUBIN EXCRETION

Bilirubin diglucuronide

Intrahepatic urobilinogen

cycle

Stercobilinogen

Bacterial enzymes

Bilirubin

Bacterial enzyme2 glucuronate

Bacterial enzyme

Urobilinogen

8H

liver

Urobilinkidneys

urine

Stercobilin feces

kidneys

intestines

DEGRADATION OF HEME TO BILIRUBIN

P450 cytochrome

75% is derived from RBCs

In normal adults this results in a daily load of 250-300 mg of bilirubin

Normal plasma concentrations are less then 1 mg/dL

Hydrophobic – transported by albumin to the liver for further metabolism prior to its excretion

“unconjugated” bilirubin

NORMAL BILIRUBIN METABOLISM

Uptake of bilirubin by the liver is mediated by a carrier protein (receptor)

Uptake may be competitively inhibited by other organic anions

On the smooth ER, bilirubin is conjugated with glucoronic acid, xylose, or ribose

Glucoronic acid is the major conjugate - catalyzed by UDP glucuronyl tranferase

“Conjugated” bilirubin is water soluble and is secreted by the hepatocytes into the biliary canaliculi

Converted to stercobilinogen (urobilinogen) (colorless) by bacteria in the gut

Oxidized to stercobilin which is colored

Excreted in feces

Some stercobilin may be re-adsorbed by the gut and re-excreted by either the liver or kidney

Dr Gihan GawishDr Gihan Gawish

Failure to Produce Bile It is possible for a type of liver disease to cause

the liver to stop the secretion of bile.

When this happens, the liver loses the capability to metabolize the fats, carbohydrate, and

proteins.

The only way fats can be absorbed into your blood system is if bile is present.

This is why it would be impossible for the body to absorb the fat-soluble vitamins without bile.

HYPERBILIRUBINEMIA

Increased plasma concentrations of bilirubin (> 3 mg/dL) occurs when there is an imbalance between its production

and excretion

Recognized clinically as jaundice

Dr Gihan GawishDr Gihan Gawish

Diagnoses of Jaundice

Red Blood Cell System

Another important function the liver performs is that it cleanses the body from

the damaged, or old, red blood cells.

The liver will also store iron in your body, as well as breakdown hemoglobin.

This is the reason why many people who suffer from liver disease may suffer from

anemia. Dr Gihan Gawish

Hepatitis Inflammation of the liver

Viral hepatitis is the most common type A, B, C, D and E

Noninfectious hepatitis may be caused by drugs and chemicals

Dr Gihan Gawish

Hepatitis – Clinical Manifestations

Preicteric or Prodromal phase• Precedes jaundice• Lasts 1 – 21 days

• Maximal infectivity for hepatitis A• Symptoms

Anorexia, right upper quadrant pain, constipation or diarrhea, malaise, fever,

headache, arthralgias, weight loss

Dr Gihan Gawish

Lab Tests Elevated Alkaline

phosphatase

Elevated with bone and liver disorders

Elevated SGOT/AST

Elevated SGPT/ALT

Elevated serum globulin

Elevated LDH

Decreased albumin

Increased prothrombin time

Blood ammonia level • Increased due to

decreased metabolism of

ammonia to urea by the liver

Dr Gihan Gawish