LIVER FUNCTIONS

Liver

a very large and complex organ that is responsible for performing vital task that can impact all the body system.

Liver

It can regenerate the cells that have been destroyed by either short term injuries, disease or if it has been removed

Liver

if this organ becomes completely nonfunctional, death can occur within approximately within 24 hours because of Hypoglycemia.

1.2-1.5kg

weight of liver

Liver

located Beneath and attached to the diaphragm, is protected by the lower rib cage

hepatic artery and the portal vein

sources of blood supply of liver

hepatic artery

supplies oxygen rich blood which is 25%

portal vein

supplies nutrient rich blood which is 75%.

1500 mL

blood pumped in the liver per minute

Lobules

are responsible for all the metabolic and excretory functions performed by the liver.

Lobules

Structural unit of Liver

Hepatocytes, Kupffer cells

2 types of cells in the liver

Hepatocytes

responsible for the major functions and regeneration

Kupffer cells

active phagocytes that are capable of engulfing bacteria, debris, toxins and other substances that are flowing through the sinusoids.

• Hepatocytic system

• Biliary system

• Reticuloendothelial System

3 systems present in a normal liver function

Hepatocytic System

Concerned with the Metabolic reactions, macromolecular synthesis especially Proteins and also degradation and metabolism of Synbiotics (drugs)

Biliary System

Metabolism of Bilirubin, Bile salts

Reticuloendothelial System

Concerned with the immune system and the production of Heme and Globin metabolites.

Bilirubin

principal pigment in Bile and is derived from the breakdown of RBC.

3L

Bile Production per day

1L

Bile excretion per day

126 days

days that the RBCs will be phagocytized and the Hemoglobin will be released.

Hemoglobin

will be degraded into Heme, Globin and Iron.

Iron

Will bind to Transferrin and it will be returned to Iron storage in the liver and bone marrow for reuse.

Globin

It will be degraded to its constituent amino acid which will also be reused by the body.

Heme

Converted to bilirubin within 2-3 hours.

Feces

oxidized to bilirubin/stercobilin (80%)

Urine

Absorbed in the circulation and filtered by kidney

200-300 mg

Production of bilirubin per day

Bilirubin 1

Unconjugated Bilirubin

Bilirubin 1/ Unconjugated bilirubin

water insoluble

B1 / Unconjugated Bilirubin

Non-polar bilirubin

Unconjugated Bilirubin

Indirect Bilirubin

Unconjugated bilirubin

Hemobilirubin

B1 / Unconjugated Bilirubin

Slow reacting

B1 / Unconjugated Bilirubin

Prehepatic Bilirubin

Bilirubin 2

Conjugated bilirubin

B2 / Conjugated Bilirubin

water soluble

B2 / Conjugated Bilirubin

Polar Bilirubin

B2 / Conjugated Bilirubin

Direct Bilirubin

B2 / Conjugated Bilirubin

Cholebilirubin

B2 / Conjugated Bilirubin

One minute / Prompt Bilirubin

B2 / Conjugated Bilirubin

Posthepatic / Obstructive and Regurgitative Bilirubin

Regurgitative Bilirubin

Condition characterized by the presence of Bilirubin in the urine and there is also significant elevation of Bilirubin in the blood

0 – 0.2 mg/dL

Ref value of conjugated bilirubin

0.2-0.8 mg/dL

Ref value of unconjugated Bilirubin

0.2- 1 mg/dL

Ref value of total bilirubin

17.1 mmol/L

Conversion factor of Bilirubin

Chief Metabolic organ

The liver is regarded to as the ___ of our body because it includes the metabolism of Carbohydrates, Lipids, Proteins etc.

Carbohydrates

Uses glucose for own cellular energy requirements.

Carbohydrates

Circulates the glucose for use at the peripheral tissues and store glucose as glycogen.

Fatty acids / Lipids

will be broken down into Acetyl CoEnzyme A which will be used in several pathways forming the Triglycerides, Cholesterol and Phospholipids

Immunoglobulin and adult Hemoglobin

Almost all proteins are synthesized by the liver except for the

Transamination and Deamination of Amino Acids

most critical aspect of metabolism

Transamination

results in the exchange of one amino group in one acid, replacing the ketone group in another acid.

Deamination

process will degrade the amino group after the transamination to produce ammonium ions that are later on consumed in the synthesis of urea and the urea will be excreted by the kidneys.

Liver

Every substance that is absorbed by our gastrointestinal tract must first pass through this organ

Liver

The “gatekeeper”

Liver

it can allow important substances to reach our systemic circulation, but it can also serve as a barrier to prevent toxic / harmful substances from reaching the systemic circulation.

• Bind to the material to inactivate it.

• Modify the compound chemically.

2 mechanisms of detoxification

Oxidation, reduction, hydrolysis, hydroxylation, carboxylation, and demethylation.

Detoxification process

Cytochrome P-450 isoenzymes

Most of the detoxification processes happens in the liver, specifically in the Microsomes, via the ___?

1.0 - 1.5 mg/dL

Normal Upper Limit of Bilirubin

Jaundice / Icterus

It is used to describe the yellow discoloration of the skin, the eyes and the mucous membrane because of the retention and elevation of Bilirubin.

3-5mg/dL

Usually, Jaundice is not seen by the naked eye until it reaches the value of

Icterus

is more commonly used in the laboratory describing a serum or plasma that is yellowish in color

Jaundice

can be classified based on the site of the disorder. It is important for us to classify the ___ because from that we will know what would be the proper treatment or the treatment plan.

Prehepatic Jaundice

Usually caused by erroneous error prior to liver metabolism leading to the elevation of the Unconjugated Bilirubin.

Prehepatic Bilirubin

will not be filtered by the kidney since it is water insoluble and will not be evident in the urine.

Prehepatic Jaundice

Acute and Chronic Hemolytic Anemia, Unconjugated Hyperbilirubinemia

Hemolytic Anemia

leads to continuous destruction of RBC and there is subsequent release of increased amount of Bilirubin presented in the liver for processing.

Hepatic Jaundice

• The problem is inside the liver itself

• Disorder of metabolism and transport

Gilbert’s Syndrome

Genetic mutation in the gene (UGT1A1) that produces UPDGT.

Gilbert’s Syndrome

• Bilirubin transport deficit (impaired cellular uptake of bilirubin).

• Increased Unconjugated bilirubin

Gilbert’s Syndrome

• Most common

• No morbidity, No mortality, No hemolysis

• The liver will still work at 20% norm

Conjugation Deficit

prone to Kernicterus which is a rare neurological disorder characterized by having excessive levels of bilirubin in blood during pregnancy.

Type 1 Crigler-Najjar Syndrome

where there is a complete absence of enzymatic bilirubin conjugation (bile is colorless).

Type 2 Crigler-Najjar Syndrome

where there is a mutation causing a severe deficiency of enzyme responsible for bilirubin conjugation.

- More severe and dangerous.

Dubin Johnson

• Bilirubin excretion deficit

• Rare autosomal recessive disorder that is caused by the Deficiency of MDR2 (Multidrug resistance 2) or the cMOAT (canalicular multispecific organic anionic transporter).

- Defective removal of conjugated bilirubin from the liver cell and the excretion into the bile

Dubin Johnson

- Increased delta bilirubin

- Bilirubin concentration is at 2-5 mg/dL

Dubin Johnson

Appearance of dark-stained granules on a liver biopsy sample.

Delta Bilirubin

Conjugated bilirubin bound to albumin

Delta Bilirubin

With longer half-life than other types of bilirubin

Delta Bilirubin

• Formed due to prolonged elevation of bilirubin

• It reacts with diazo reagent.

Rotor Syndrome

Clinically similar to Dubin-Johnson syndrome but the defect causing the Rotor syndrome is unknown.

Rotor Syndrome

Liver biopsy does not show dark pigmented granules.

Lucey Driscoll Syndrome

Unconjugated hyperbilirubinemia caused by circulating inhibitor of bilirubin conjugation.

Physiologic Jaundice of the Newborn

• Deficiency in the enzyme UDPGT, resulting in rapid build-up of unconjugated bilirubin.

• Could lead to Kernicterus

Physiologic Jaundice of the Newborn

Treated with ultraviolet radiation

• Some require exchange transfusion (severe cases, done when Phototherapy fails). It removes aliquot of blood from the blood bag and replace it to remove abnormal blood components circulating in the body.

Phototherapy (UV radiation)

Infants having Physiologic Jaundice is treated using _______. It will help destroy the bilirubin through the capillaries of the skin.

Posthepatic Jaundice

Abnormalities that lies outside the liver.

Posthepatic Jaundice

Caused by biliary obstructive disease (Gallstones or tumors) that prevent the flow of conjugated bilirubin into the bile canaliculi. The bile will not go to the intestines, causing the loss of fecal color.

Posthepatic Jaundice

Clay-colored stool.

• All levels of Bilirubin (B1, B2, Total Bilirubin) is increased.

Cholelithiasis

The most common cause of Hyperbilirubinemia in adults under Post hepatic jaundice is ____?

1. Jaundice

2. Cirrhosis

3. Cancers of the Liver

4. Reye’s Syndrome

Liver diseases

Cirrhosis

Scarring of the liver

Cirrhosis

Signs and Symptoms

• Fatigue, Nausea, unintended weight loss, jaundice, bleeding from the gastrointestinal tract, intense itching, and swelling in the legs and abdomen.

• Usually when these symptoms appear, the disease is already chronic or severe.

Interferron

If Virus such as HEP C, you can use _____ as treatment

Corticosteroids

if Cirrhosis is caused by autoimmune hepatitis, it is treated with?