1. Option D3: Functions of the liver

2. Essential Idea: The chemical composition of the blood is regulated by the liver.

3. Understandings
U.D.3.1: the liver removes toxins from the blood and detoxifies them.
U.D.3.2: components of red blood cells are recycled by the liver.
U.D.3.3: the breakdown of erythrocytes starts with phagocytosis of red blood cells by Kupffer cells.
U.D.3.4: iron is carried to the bone marrow to produce hemoglobin in new red blood cells.
U.D.3.5: surplus cholesterol is converted to bile salts.
U.D.3.6: endoplasmic reticulum and Golgi apparatus in hepatocytes produce plasma proteins.
U.D.3.7: the liver intercepts blood from the gut to regulate nutrient levels.
U.D.3.8: some nutrients in excess can be stored in the liver.

4. Applications A.D.3.1: causes and consequences of jaundice.
A.D.3.2: dual blood supply to the liver and differences between sinusoids and capillaries.

5. Circulation of blood to and from the liver
The liver receives blood from two major blood vessels, and is drained by one vessel.
Hepatic artery: branch of the aorta; carries oxygenated blood to the liver tissue.
Hepatic portal vein: brings blood to the liver from the capillaries of the villi of the small intestine.
Both the hepatic artery and hepatic portal vein drain into special capillaries of the liver, called sinusoids.
All sinusoids will then drain into the hepatic vein, which takes blood from the liver to the heart.

6. Liver blood schematic Absorbed nutrients from the intestine
Hepatic portal vein
Liver (sinusoids)
Hepatic vein
To vena cava
Hepatic artery
Oxygenated blood

8. Hepatic portal vein and hepatic vein
The hepatic portal vein differs in two ways from other blood vessels that come to organs:
The blood from the hepatic portal vein is low in oxygen and under low pressure, because it has come from the capillaries of the villi
The concentration of nutrients varies considerably, and is dependent on what was consumed and the timing of digestion
The hepatic vein is also under low pressure and is deoxygenated, but the nutrient concentration is usually fairly consistent, as one of the main roles of the liver is to remove and store nutrients from the blood.

9. Sinusoids (A.D.3.2)
The role of the liver is to remove substances from the blood, as well as occasionally add substances. This is the role of the liver’s cells, called hepatocytes.
As blood comes into the liver from the hepatic artery and hepatic portal vein, it flows into the capillaries of the liver, known as sinusoids. Sinusoids are where the exchanges between hepatocytes and the blood occur.
Sinusoids are different from normal capillaries in several ways:
Sinusoids are wider
Sinusoids are lined with epithelial cells with gaps between them, which allows large molecules to be exchanged between the bloodstream and the hepatocytes
Hepatocytes have direct contact with blood, increasing efficiency
Kupffer cells are found in sinusoids. These cells break down hemoglobin from old red blood cells.
Sinusoids receive both oxygen-rich and oxygen-poor blood

10. Sinusoid structure

11. Detoxification (U.D.3.1 and U.D.3.3)
One of the main roles of the liver is detoxification of the blood.
Two types of cells are responsible for detoxification:
Kupffer cells – specialized leukocytes that line the interior of the sinusoids. Kupffer cells remove old erythrocytes (RBCs) and bacteria through phagocytosis. Contain many lysosomes for intracellular digestion.
Hepatocytes – most numerous cells in the liver; most active in removing and processing chemical toxins from the blood.
Hepatocytes are continually bathed by the liquid component of blood (plasma), and works on toxins in two steps.
The toxins are modified chemically to make them less destructive
Chemical components are added to the toxins to make them water soluble, which allows them to be removed by the kidneys.

12. Kupffer cells and hepatocytes

13. Alcohol vs. the liver
Alcohol can damage the liver when abused in high volumes and/or over long periods.
This is because unlike other substances, alcohol visits the liver twice.
First, alcohol comes to the liver from the hepatic portal vein. Then, any alcohol that was not absorbed in the first trip comes back to the liver through the hepatic artery.
Every time alcohol comes through the liver, the hepatocytes attempt to remove it, and thus alcohol has a magnified effect on the liver.

14. Long-term alcohol abuse
Long-term alcohol abuse can damage the liver in three ways:
Cirrhosis – a disease in which healthy liver tissue is destroyed by alcohol exposure is replaced with scar tissue with no function
Fat exposure – areas that are damaged replace normal tissue with fatty deposits
Inflammation – swelling of damaged liver tissue

15. Cirrhosis

16. Regulation of nutrients in the blood (U.D.3.7)
Recall that the body has a set homeostatic range for a variety of nutrients in the body (ex. glucose).
Whenever the concentration of nutrients exceeds the homeostatic set level, hormones will stimulate the liver to store the excess in the hepatocytes. This helps lower the nutrient concentration of the blood.
Conversely, when nutrient concentration decreases below the set homeostatic level, hormones will stimulate the release of the stored nutrients, and the hepatocytes will release the nutrients into the blood flowing through the sinusoids.

17. Nutrients stored by the liver
Relevant information
Glycogen
Polysaccharide of glucose; stored energy
Iron
Removed from hemoglobin, later sent to the bone marrow
Vitamin A
Provides retinal function and vision
Vitamin D
Promotes healthy bone growth

18. Recycling of erythrocytes and hemoglobin (U.D.3.2 and U.D.3.4)
Erythrocytes (RBCs) are anucleate (they have no nucleus). This means they are unable to reproduce by mitosis, and must be created by the bone marrow.
As erythrocytes begin to break down at the end of their cell cycle, their membrane becomes weak and will eventually rupture. When ruptured, the erythrocyte will release millions of hemoglobin molecules into the blood.
It is the responsibility of the Kupffer cells in the sinusoids to collect these hemoglobin molecules by phagocytosis (hemoglobin is large, and so must be brought in by way of active transport).

19. Recycling of erythrocytes and hemoglobin cont.
Hemoglobin is made up of four polypeptides, four heme groups (a non-polypeptide molecule) and four iron atoms.
As hemoglobin comes into the Kupffer cells, it is disassembled.
First the polypeptides are hydrolyzed into amino acids. These are released back into the blood stream.
Next, the iron is removed from the heme group; some is stored in the liver, while the rest goes to the bone marrow for erythrocyte production.
Lastly, what’s left of the heme group becomes bilirubin, which is a key component of bile.

20. Production of bile and plasma proteins (U.D.3.5 and U.D.3.6)
Recall that bile is added to the duodenum and is used to emulsify fats.
The way that bile works is by breaking apart fat globules, exposing more surface area for lipase to break down the fat molecules.
Bile is produced by the hepatocytes of the liver.
First, excess cholesterol is converted into bile salts by the hepatocytes.
Next, the bile salts are combined with bilirubin to create bile.
It is the bile salts that are responsible for the emulsification of lipids.
Hepatocytes are also responsible for the production of plasma proteins. Plasma proteins are found in the plasma of blood. Two plasma proteins are albumin and fibrinogen.
Albumin – regulates osmotic potential and carries bile salts and other fat soluble substances
Fibrinogen – converted to fibrin to create blood clots
Review the process of exocytosis of proteins from section 1.4.

21. Causes and effects of jaundice (A.D.3.1)
Jaundice is a condition in which too much bilirubin circulates in the blood and body tissues. Since bilirubin has a yellowish color, people with jaundice have a yellow tint to their skin and eyes.
There are two types of jaundice:
Infant jaundice – most commonly found in premature babies. The liver is not yet capable of processing bilirubin into bile. Excessive bilirubin levels are toxic to the brain. Treatment typically includes exposure to blue-green light, which stimulates a shape and structural change in the bilirubin, allowing it to be eliminated from the baby until the liver begins functioning.
Adult jaundice – there is not one cause of adult jaundice, aside from improper liver function. The jaundice is a symptom of some other liver issue. It has the effects on the body as infant jaundice.

22. Jaundice

23. More jaundice