1. Functions of the Liver

2. Overview of major functions of the liver
Acts as main biochemical synthesizer
Removes toxins from the blood and detoxifies them
Recycles components of red blood cells
Converts surplus cholesterol to bile salts
Endoplasmic reticulum and Golgi apparatus in hepatocytes produce plasma proteins
Regulates nutrient levels by intercepting blood from the gut
Stores some excess nutrients
…And around 500 other functions

3. Liver and surrounding organs anatomy
Portal vein: vein conveying blood to the liver from the spleen, stomach, pancreas, and intestines

4. Overview of the circulation of blood

5. A closer look at liver anatomy
Sinusoids: microscopic blood channels, receive blood from the hepatic artery and portal vein and deliver it into central veins
Are a type of capillary. Sinusoids in general replace capillaries in certain organs (liver, spleen, bone marrow, etc.)
Hepatic artery: oxygenated blood
Portal vein: nutrient-rich blood

6. A closer look at liver anatomy cont.

7. Biochemical synthesis
The liver is the body’s biggest factory.
Converts amino acids into proteins to build muscle, enzymes, etc.
Produces cholesterol and converts it to bile (to cover later)
Converts ammonia released from the body’s digestion of protein into urea

8. Detoxification
Filters blood coming from the intestines (after digestion) before allowing the blood to be pumped to the rest of the body from the heart
Microorganisms, drugs, food additives, preservatives, sweeteners, chemicals used in agriculture, alcohols, air pollutants
Harmful substances from internal sources such as burning sugars, fats, or protein

9. Detoxification cont.
The liver adds groups, removes groups, activates things, deactivates things, as needed
Because cell membranes are primarily lipid-based and the transport of water-soluble compounds would then need specialized transport proteins, converting lipid-soluble compounds to water-soluble compounds can deactivate the compound in question
(“conjugation pathway”: add another substance, such as cysteine, glycine, or an S molecule to make it less harmful and more water-soluble)
But the reverse can happen too, so don’t generalize the liver as only deactivating
Chemotherapy drug Xeloda is activated in the liver

10. Detoxification cont. Alcohol detoxification
Alcohol can only be oxidized in the liver, because that’s where the necessary enzymes are found
Oxidation of ethanol to acetaldehyde, then further oxidized to acetic acid, and finally CO2 and water through the citric acid cycle
The NADH formed from the previous reaction converts pyruvic acid to lactic acid
The consumption of pyruvic acid originally meant to be converted into glucose causes hypoglycemia (low blood sugar) from lack of glucose synthesis
Excess lactic acid causes acidosis

11. Recycling components of red blood cells
Red blood cell recycling happens in the liver, lymph nodes, and spleen
RBCs generally last about 120 days
2.5 mil red blood cells destroyed per second; 25 trillion RBC circulating in body
Generally, specialized white blood cells known as macrophages engulf the RBC, and the macrophage’s lysosomes break them down
Broken down into constituent amino acids (“globin”), iron ion (Fe2+) and heme groups. Amino acids and iron ions enter the bloodstream and are picked up and used by the bone marrow to form new RBCs; heme is transformed into bilirubin and will be excreted either through kidneys or intestines.

12. Recycling components of red blood cells cont.
Kupffer cells (Kupffer-Browicz cells): star-shaped cells that line the liver sinusoids. A macrophage found specifically in the liver.

13. Bile acid synthesis and excretion
Bile is a fluid containing water, electrolytes, and a variety of organic molecules including bile acids, cholesterol, phospholipids, and bilirubin. (bilirubin: substance produced when liver breaks down old red blood cells)
Synthesis of bile
Mainly occurs in the liver; the liver is the only place where the whole synthesis process occurs
One of the main mechanisms for the catabolism (breakdown) of cholesterol and excretion of excess cholesterol

14. Bile acid synthesis and excretion cont.
Cholesterol and lipoproteins
A note about cholesterol: there is only one cholesterol.
However, cholesterol is mostly nonpolar, and therefore water-insoluble. To be transported effectively, then, it is carried by lipoproteins, and the interaction of these different lipoprotein with blood vessels is what makes the HDL or LDL “good” or “bad”.
Studies have shown that HDLs are healthier for us than LDLs – HDLs can even be considered “good”
LDLs carry cholesterol molecules to cells where they’re needed; HDLs transport cholesterol back to the liver, which decides whether to recycle or dispose of it
LDLs are harmful because after LDLs have distributed their cholesterol, they become small enough to burrow into linings of arteries and oxidize, resulting in damaging inflammation

15. https://pacbio.com/news-media/white-paper/bile-acids/

16. Bile acid synthesis and excretion cont.
Functions of bile include:
Aiding in digestion and absorption of fats and fat-soluble vitamins in the small intestine (A, D, E, K)
Eliminating waste products from the body by secretion into bile and elimination in feces
Fun fact: Bilirubin gives stool its normal color

17. Synthesis of plasma proteins
Plasma proteins: aka blood proteins or serum proteins; are the proteins present in blood plasma
Functions include transport of lipids, hormones, vitamins, and minerals; functioning of the immune system; acting as enzymes, and more.
The endoplasmic reticulum and Golgi apparatus in functional liver cells (hepatocytes) are important in protein synthesis (modify the proteins after they are synthesized by the rest of the cell)

18. Synthesis of plasma proteins cont.
Albumin, the major plasma protein, is synthesized almost exclusively by the liver.
Maintains osmotic pressure of plasma to assist in transport of lipids and steroid hormones
The liver also synthesizes many of the clotting factors (proteins in the blood that control bleeding) necessary for blood coagulation
Work on the surface of activated platelets in case of an injury and cause a series of chemical reactions (known as the coagulation cascade) to form a fibrin clot (the final “mesh”)

19. Role in regulating nutrient levels
The liver regulates nutrient levels in the blood, most notably glucose
Converts excess blood glucose into glycogen
Low blood glucose levels:
Glycogenesis: hepatic cells reconvert glycogen into glucose
Gluconeogenesis: after a fast, the liver and kidneys use amino acids, lactic acid and glycerol to produce glucose
Also regulates

20. Storage of excess nutrients and other things
Glucose (glycogen – around 400 calories worth)
Iron (ferritin)
Vitamins (especially A, D, and B-12)
Salt
Amino acids
Stores extra blood that can be quickly released when needed

21. Hepatocytes
Hepatocytes make up the main parenchymal (functional, instead of structural) tissue of the liver, which is about 70-85% of the liver’s mass.
Hepatocyte nuclei are round, with one or two prominent nucleoli. They also have particularly large quantities of both rough and smooth ER, and more Golgi membranes than other cells.
Lifespan of a hepatocyte is ~ days

22. Diseases related to the liver
Jaundice
Condition in which too much bilirubin is circulating in the blood
May indicate damage to the liver in adults; is common in babies (more cells to break down soon after birth, and liver is often slower)
Doesn’t cause problems in itself; rather, indicates the possibility of other conditions that will hurt you

23. Diseases related to the liver cont.
Cirrhosis
Scar tissue replaces normal, healthy tissue as a result of cells getting damaged over a long period of time (years)
The liver becomes lumpy and hard, and the scar tissue makes it hard for blood to get through the portal vein. After a while, the organ will start to fail.
There is no cure for cirrhosis except for a liver transplant. You can, however, slow it down by treating whatever is causing it
Common causes:
Alcohol. Causes fat and inflammation in the liver.
Hepatitis: inflammation of the liver. Can be caused by heavy alcohol use, medications, viruses, or coming into contact with infected blood.
Nonalcoholic fatty liver disease: fat build up. Being overweight, diabetes, high cholesterol & triglycerides in blood, and high blood pressure can contribute to this.

24. Some things to think about
Excessive alcohol consumption may cause liver cirrhosis. Are attitudes to drugs and alcohol an example of something that is relative to culture? Is all knowledge dependent on culture?
Given the pressure on health resources, especially the availability of organs for transplant, should an alcoholic be allowed a liver transplant?

25. References http://themedicalbiochemistrypage.org/bileacids.php

26. References cont. http://www.mananatomy.com/basic-anatomy/sinusoids
liver.html