The Liver

What are some of the major functions of the liver?

1) Metabolism

2) Detoxification

3) Storage

4) Phagocytosis

5) Heat production

6) Synthesis

Anatomy of the Liver

• It is the largest organ (approx 1.5kg)

• Located in upper right quadrant of abdomen

• Protected by the ribs

How many lobes does the Liver have

Can be 4 or 2 depending on how you’re viewing it.

Anteriorly, the liver has two lobes, left and right. Posteriorly, there are two lobes, the caudate and quadrate lobes which are technically still part of the right lobe.

How is the liver anchored to the anterior abdominal wall?

By the falciform ligament, which is a thin fold of peritoneum.

What are the “dips” and “creases” in the posterior of the liver?

The impressions of the surrounding organs

Porta Hepatis

Main site where structures enter and leave the liver, including the portal triad which consists of the hepatic artery, portal vein, and bile duct.

What are the two blood supplies of the liver?

1) Hepatic artery (from coelic trunk [first branch of the aorta] of aorta) provides oxygen rich blood

2) Hepatic portal vein (convergence of veins draining the GI tract). MOST of blood supply and brings any ingested toxins up to the liver

How is blood drained from the liver?

by 3 hepatic veins into the inferior vena cava

What is different about the blood in the portal vein?

It is partially deoxygenated

What is a portal system?

connects one organ to the other without going to the heart first. This is essential for processing, hormones, and delivery of nutrients and toxins

Hepatocytes

Liver cells. Make up 70-80% of all liver cells are hepatocytes. They are considered being the chemical transformation factories (have a higher concentration fo ER and mitochondria compared to other cells)

Space of Disse

The area between hepatocytes and the liver sinusoid, important for the exchange of substances. Bathes hepatocytes in plasma

Canuliculus

“Channel”

Stellate cells

Sit in space of disse. In healthy conditions, remain inactive. In diseased states, they produce collagen to cause fibrosis

Kupffer Cells

located in sinusoids. Specilized macrophages and break dwon RBCs

Lobules

Hepatocytes and vessels of the liver are arranged into hexagonal units with branches of the portal triad at each corner and a central vein

Sinusoids

Speciallized capillaries that have a fenestrated endothelial layer that allow for passage of metabolites.

They are low pressure vessels that drain blood from the portal vein into the central vein of each lobule.

Phases of drug detoxification

Phase I: Modification→ Transforming the drug into a metabolite, by adding a polar group which prevents its diffusion across membranes

Phase II: Conjugation → Attachment of ionised group which makes it more water soluble and allows it to pass into the liver

Phase III Excretion → Small metabolites are exreted in kidneys/urine. Large metabolites are excreted in bile through the intestines.

What enzyme facillitates the modification phase of drug detoxification?

Cytochrome P450 enzymes

WHere does the modification phase take place?

In the endoplasmic reticulum of hepatocytes

What is added during modification in the drug detoxification process?

Either oxygen (O) or Hydroxyl (OH)

What is one downside to modification?

Some resulting metabolites can be toxic

What are some ionized groups added during the conjugation phase?

Sulfate, Glycine, Glutathione

Where does the conjugation phase take place?

Cytoplasm of the hepatocytes

How do orally administered drugs differ from those administered through an IV in terms of how they get into the liver?

Orally administered drugs pass through the stomach and then get abrobed into a vein that brings the drug to the liver. IV administered drugs do not pass through the digestive system and enter the bloodstream directly.

Enterohepatic Cycling

When metabolites that are absrobed from GI tract are take up into the liver and the result gets secreted back into the GI track by bile.

In the excretion phase, where would a large metabolite go? What about a smaller metabolite?

Large metabolites are secreted back into the GI tract in bile and excreted as feacal waste while smaller metabolites go to the kidneys and are excreted as urinary waste.

Bilirubin

A pigment formed by the broken down RBCs. Gives feacal matter its pigment

Why is free bilirubin potentially dangerous?

It can pass through the blood brain barrier and the placenta

How is bilirubin excreted?

Conjugated to glucuronic acid to from bilirubin diglucuronide, making it more soluble before being excreted by bile.

What disease is caused by excess plasma bilirubin?

Jaundice

How common is neonatal jaundice

about 60% of all full term births

What is the treatment for neonatal jaundice?

Phototherapy. The light oxidizes the bilirubin into a more soluble form

What role does the liver play in lipid metabolism?

Synthesis of triglycerides and cholesterol

What role does the liver play in carbohydrate metabolism?

It regulates blood glucose levels, converting excess glucose into glycogen for storage and releasing glucose when needed.

What role does the liver play in protein metabolism?

Sythesis of all non-essential amino acids, of almost all plasma membranes, removal of amino groups from amino acid, Urea cycle

How can the liver regenerate?

Severe injury to the liver will lead to the activation of liver prognitor stem cells which can differentiate into other cell types. Chronic disease however impairs that regenerative ability.