1. Option D: Human Physiology D.3 Functions of the Liver

2. D.3
Essential idea: The chemical composition of the blood is regulated by the liver.

4. Blood arrives at the liver from two sources:
D.3.A2 Dual blood supply to the liver and differences between sinusoids and capillaries.
Hepatic vein carries blood from the liver on to the heart with levels of food adjusted
How much oxygen would be in the blood coming in from the portal vein?
Very little since it has already delivered oxygen the stomach and intestines
Liver
Blood arrives at the liver from two sources: 2
Hepatic artery brings oxygenated blood to the liver 1
Hepatic portal vein carries blood containing digested food from the intestines to the liver

6. Continuously Spaces between lined with cells cells
D.3.A2 Dual blood supply to the liver and differences between sinusoids and capillaries.
Capillary vs Sinusoid
Narrow Wide
Continuously Spaces between
lined with cells cells
*fenestrated epithelium = an endothelium that is full of holes
Note: Artery branches into arterioles and vein branches into venules before reaching the sinusoids. When blood leaves the sinusoid it enters venules before reaching hepatic vein.
No basement membrane which along with fenestrations permits blood plasma to wash freely over the exposed surfaces of the hepatocytes in the space of Disse. Siumed.edu (basement membrane = a thin, delicate membrane of protein fibers and glycosaminoglycans separating an epithelium from underlying tissue)

7. (space between hepatocyte and a sinusoid)1 3 7 6
(store Vitamin A) 2 4 5
(space between hepatocyte and a sinusoid)

8. D.3.U1 The liver removes toxins from the blood and detoxifies them.
Every day you ingest many toxic substances. The liver functions to remove toxins and detoxify (convert into non-toxic or less toxic substances) them.
Examples:
Alcohol is converted into a less toxic substance by the enzyme ethanol dehydrogenase
Ammonia is converted into urea and transported to the kidneys where it is filtered out of the blood and released in the urine
Other toxic substances include pesticides, herbicides, preservatives, medications, etc.
Note: Artery branches into arterioles and vein branches into venules before reaching the sinusoids. When blood leaves the sinusoid it enters venules before reaching hepatic vein.
No basement membrane which along with fenestrations permits blood plasma to wash freely over the exposed surfaces of the hepatocytes in the space of Disse. Siumed.edu

9. D.3.U7 The liver intercepts blood from the gut to regulate nutrient levels. AND D.3.U8 Some nutrients in excess can be stored in the liver.
Note: Artery branches into arterioles and vein branches into venules before reaching the sinusoids. When blood leaves the sinusoid it enters venules before reaching hepatic vein.
No basement membrane which along with fenestrations permits blood plasma to wash freely over the exposed surfaces of the hepatocytes in the space of Disse. Siumed.edu

10. D.3.U7 The liver intercepts blood from the gut to regulate nutrient levels. AND D.3.U8 Some nutrients in excess can be stored in the liver.
Stored in liver when in excess and released when there is a deficit in the blood.

12. (bilirubin) D.3.U5 Surplus cholesterol is converted to bile salts.
Hepatocytes break down surplus cholesterol into bile salts and use it to make bile.
(carry bile from hepatocytes to bile duct)
(bilirubin)

13. Captures erythrocytes
D.3.U6 Endoplasmic reticulum and Golgi apparatus in hepatocytes produce plasma proteins.
In addition to producing bile, the hepatocytes also produce plasma proteins.
90% of plasma proteins are produced here, but two well documented proteins include:
Albumin – helps regulate blood osmotic pressure and is a carrier for bilirubin (bile salts from blood to liver) and some other fat-soluble substances
Fibrinogen – gets converted to fibrin to form the mesh component of a blood clot
Platelet/Cell Damage
clotting factors
Thrombin
REVIEW: 6.3.U4 The cascade results in the rapid conversion of fibrinogen to fibrin by thrombin.
Fibrinogen Fibrin
(soluble) (fibrous)
Captures erythrocytes
Clot
High levels of protein synthesis!

14. Review of protein synthesis and secretion:
D.3.U6 Endoplasmic reticulum and Golgi apparatus in hepatocytes produce plasma proteins.
In addition to producing bile, the hepatocytes also produce plasma proteins.
Review of protein synthesis and secretion:
DNA within the nucleus of the hepatocyte synthesizes mRNA for a particular protein (transcription)
mRNA exits nucleus through a nuclear pore
mRNA finds a ribosome located on rough ER
Plasma protein is synthesized (translation)
Plasma protein is transported by vesicle to Golgi apparatus
The Golgi apparatus may modify the protein and then it is surrounded with another vesicle
Vesicle goes to plasma membrane for exocytosis (secretion)
Plasma protein enters blood
High levels of protein synthesis!

15. The liver also functions to breakdown and recycle erythrocytes.
D.3.U3 The breakdown of erythrocytes starts with phagocytosis of red blood cells by Kupffer cells.
The liver also functions to breakdown and recycle erythrocytes.
The life span of a erythrocyte (red blood cell) is about 4 months, or 120 days.
The do not contain a nucleus (anucleate) and must be made by the bone marrow and not mitosis.
When they are at the end of their lifespan, the cell membrane becomes weak and the cell bursts open. This results in hemoglobin being released into the blood. (There is about 280 million hemoglobin molecules in each RBC!)

16. D.3.U3 The breakdown of erythrocytes starts with phagocytosis of red blood cells by Kupffer cells.
The liver also functions to breakdown and recycle erythrocytes.
As they age and swell, erythrocytes may also be taken in by Kupffer cells through phagocytosis. Here they are broken down.
Kupffer cells are a type of macrophage (type of leucocyte – WBC)

17. The liver also functions to breakdown and recycle erythrocytes.
D.3.U2 Components of red blood cells are recycled by the liver. AND D.3.U4 Iron is carried to the bone marrow to produce hemoglobin in new red blood cells.
The liver also functions to breakdown and recycle erythrocytes.
Hemoglobin in the blood is also ingested through phagocytosis by Kupffer cells in the sinusoids:
Four globin proteins (alpha & beta chains) are hydrolyzed into amino acids
Amino acids are released into bloodstream & can be used for protein synthesis
Iron atom is removed from each of the 4 heme groups. Some is stored in the liver & some is sent to bone marrow to produce hemoglobin in new RBCs
Bilirubin remains & is absorbed by hepatocytes to make bile

18. D.3.U2 Components of red blood cells are recycled by the liver. AND D.3.U4 Iron is carried to the bone marrow to produce hemoglobin in new red blood cells.

19. Iron is transported in the blood by a protein called transferrin.
D.3.U2 Components of red blood cells are recycled by the liver. AND D.3.U4 Iron is carried to the bone marrow to produce hemoglobin in new red blood cells.
Iron is essential but can be toxic if concentrations are too high. Therefore, maintaining homeostasis of iron levels in the blood is important.
Iron is transported in the blood by a protein called transferrin.
Iron can be stored in hepatocytes or transported to the bone marrow where RBCs are made from stem cells.
Hemoglobin is synthesized in RBCs. When iron is bound to transferrin it can bind to receptors on the surface of developing RBCs and enter the cell. There the iron can be incorporated into the heme groups or stored in a storage molecule called ferritin.

20. Overview of iron homeostasis.
D.3.U2 Components of red blood cells are recycled by the liver. AND D.3.U4 Iron is carried to the bone marrow to produce hemoglobin in new red blood cells.
Overview of iron homeostasis.
Overview of iron homeostasis. The central portion of the figure depicts the flow of iron into the body (through the small intestine), to transferrin (Tf), to the major site of utilization (the erythroid bone marrow), to circulating erythrocytes, to tissue macrophages that phagocytose senescent erythrocytes and recycle iron (spleen), to storage in hepatocytes, and back to TF through mobilization of iron stores. Cellular iron transport is described in detail in the text and shown in schematic form on the outside edges of this figure. (A) Nonheme iron transport across an intestinal enterocyte. (B) Erythrophagocytosis and iron recycling in a tissue macrophage. The aqua oval in the cytoplasm represents a storage depot for ferroportin protein within the cell. (C) Hepatocyte iron transport, with arrows indicating that neither import nor export is well understood. (D) Iron uptake through the transferrin cycle in the erythoblast. Illustration by Kenneth Probst.
Nancy C. Andrews Blood 2008;112:
©2008 by American Society of Hematology

21. Detailed summary:
Erythropoietin = a hormone secreted by the kidneys that increases the rate of production of red blood cells in response to falling levels of oxygen in the tissues.
Erythropoiesis = to make red blood cells
Transferrin = iron-binding blood plasma glycoprotein; transport protein
Ferritin = Ferritin is a protein with a capacity of about 4500 iron (III) ions per protein molecule

22. There are two main types of jaundice: Infant jaundice & Adult jaundice
D.3.A1 Causes and consequences of jaundice.
Jaundice is a condition characterized by having too much bilirubin in the blood and within the tissues.
Bilirubin is a yellow pigment which causes individuals with jaundice to have a yellow tinge to their skin and yellowing of the whites of their eyes.
There are two main types of jaundice: Infant jaundice & Adult jaundice

23. D.3.A1 Causes and consequences of jaundice.
1. Infant Jaundice
Causes: Typically occurs in premature babies because their liver is not yet capable of fully processing bilirubin to bile. Another cause is that some newborns do not feed properly and the lack of intestinal contents means the bilirubin can be reabsorbed.
Consequences: A brain condition called acute bilirubin encephalopathy – excessive levels of bilirubin are toxic to brain cells
Treatment: Exposure to sunlight or the use of a “bili” lamp which uses UV light – blue and green portion of the light spectrum changes the shape of bilirubin allowing it to be excreted
Encephalopathy = A broad term for any brain disease that alters brain function or structure.

24. D.3.A1 Causes and consequences of jaundice.
2. Adult Jaundice
Causes: Many causes: liver diseases such as hepatitis or liver cancer; Obstruction of bile duct by gallstones or pancreatic cancer
Consequences: A brain condition called acute bilirubin encephalopathy – excessive levels of bilirubin are toxic to brain cells; Itching; other consequences associated with the underlying cause
Treatment: Depends on the underlying cause