D.3 Functions of the liver Flashcards
1
Q
Diagram of the liver and gall bladder showing the most important functions of the liver
A
2
Q
How is the liver supplied with oxygenated blood from the heart?
A
- Through the hepatic artery.
- The blood then leaves the liver through the hepatic vein, which carries deoxygenated blood.
- This vein joins the vena cava, which returns the blood to the heart.
3
Q
What is the hepatic artery?
A
A branch of the aorta
4
Q
Diagram showing blood supply to the liver
A
5
Q
How is the liver supplied with deoxygenated blood?
A
- The liver also receives deoxygenated blood coming from the spleen, stomach, pancreas, gall bladder and intestines through the hepatic portal vein.
- This vein carries foods absorbed mainly in the small intestine.
- The blood supplied by this blood vessel represents the majority of the blood received by the liver (around 75% of the total blood supplied to the liver).
6
Q
What nutrients does the hepatic portal vein contain?
A
It is rich in amino acids, glucose, vitamins, minerals and other foods.
7
Q
Why is it said that the liver has a dual blood supply?
A
- Because it receives oxygenated blood from the hepatic artery and deoxygenated blood from the hepatic portal vein.
- Because the blood from these two sources is mixed before entering the liver, its cells never receive fully oxygenated blood.
8
Q
What structures does blood from the hepatic artery and the hepatic portal vein supply?
A
- It supplies the sinusoids that bathe the hepatocytes and Kupffer cells.
- As blood passes through the liver, the hepatocytes monitor the contents of the blood and remove many toxic substances such as alcohol and drugs before they can reach the rest of the body.
- Enzymes metabolize these toxins to render them harmless.
9
Q
What is the effect of the many metabolic reactions that take place in the liver?
A
- These reactions liberate heat, so when blood passes through the liver it is warmed up.
- This helps to maintain the body temperature in warm-blooded organisms.
10
Q
Which artery carries blood from the heart to the liver?
A
Hepatic
11
Q
What is the main function of the hepatic portal vein?
A
Carry nutrients from the small intestine to the liver.
The liver receives deoxygenated blood coming from the spleen, stomach, pancreas, gall bladder and intestines through the hepatic portal vein. This vein enters the liver carrying foods absorbed mainly in the small intestine (amino acids, glucose, vitamins, minerals and other foods).
12
Q
Describe the structure of the liver and its lobes
A
- The liver is a triangular-shaped organ consisting of four lobes.
- The internal structure of each lobe has around 100,000 lobules, each consisting of a central venule coming from the hepatic vein surrounded by six venules coming from the hepatic portal vein and six arterioles from the hepatic artery.
- These blood vessels are connected by sinusoids.
13
Q
Diagram showing the structure of a lobule in the liver
A
14
Q
What are sinusoids?
A
Tubes that resemble capillaries but have a discontinuous endothelium.
15
Q
Diagram of capillaries and sinusoids
A
16
Q
Pores in capillaries vs. sinusoids
A
Capillaries: Very small pores (intracellular clefts)
Sinusoids: Fenestrated (with pores of approximately 175 nm diameter)
17
Q
Membrane in capillaries vs. sinusoids
A
Capillaries: Continuous basement membrane
Sinusoids: Discontinuous basement membrane
18
Q
Shape of capillaries vs. sinusoids
A
Capillaries: cylindrical shape
Sinusoids: no definite shape
19
Q
Size of capillaries vs. sinusoids
A
Capillaries: smaller
Sinusoids: larger
20
Q
Intracellular space in capillaries vs. sinusoids:
A
Capillaries: little intracellular space
Sinusoids: large intracellular space
21
Q
What can pass through in capillaries vs. sinusoids
A
Capillaries: only small molecules can pass
Sinusoids: leaky
22
Q
What are the two main types of cells that the lobules have?
A
Hepatocytes and Kupffer cells
23
Q
What is the function of hepatocytes?
A
They perform most of the liver functions, especially storage and metabolism.
24
Q
Describe the size of hepatocytes
A
These cells are large (around 25 μm) and constitute around 80% of the total liver cells.
25
Describe the structure of hepatocytes
Their nucleus is round and found in the centre of the cell.
26
What are hepatocytes capable of doing?
Regenerating when exposed to toxic substances.
27
Explain liver regeneration
- Liver regeneration involves the replication of hepatocytes followed by the replication of other liver cells.
- Once cell proliferation is completed, the newly divided cells undergo restructuring and reformation of the extracellular matrix to complete the process.
- During regeneration, liver function is only partially affected.
28
How does the ability of the liver to regenerate make it useful for transplants?
Because human liver cells regenerate it has become possible to use partial livers from living donors for transplantation, thereby increasing the number of organs that are available for transplantation.
29
What organelles and other structures are hepatocytes rich in and why?
They are rich in mitochondria, Golgi complexes, rER, ribosomes, glycogen granules, and lipid droplets because they are involved in many metabolic processes.
30
Role of rER and sER in hepatocytes
- Plasma proteins are synthesized in hepatocytes mainly in the rough endoplasmic reticulum (rER) and processed in Golgi complexes.
- Hepatocytes are also involved in the degradation of toxins, such as the detoxification of alcohol.
- Many of the detoxification reactions occur in the smooth endoplasmic reticulum (sER).
- Hepatocytes also have an exocrine function in the secretion of bile.
31
How many mitochondria and Golgi complexes can hepatocytes have per cell?
Up to 1000 mitochondria and 50 Golgi complexes per cell.
32
What are Kupffer cells?
White blood cells (macrophages) that break down red blood cells.
33
What is the function of Kupffer cells?
They are involved in the recycling of erythrocytes.
34
Bile ducts in the lobules
In the lobules there are also canals (bile canaliculi) that carry bile to the bile duct that leads to the gall bladder where bile is stored until it is used in the small intestine.
35
How can temporary mounts of liver cells be prepared from fresh liver tissue and observed under a light microscope?
- This can be done by mashing pieces of liver tissue in a mortar together with a 10 ml salt solution.
- Cells can be stained with a drop of methylene blue before placing the coverslip on the slide.
36
(Mouse) liver seen under light microscope ×100
37
(Mouse) liver cells ×400
38
Give an overview of how the liver processes and stores nutrients
- The liver is in charge of the processing and storage of many nutrients.
- Blood enters the liver through the hepatic portal vein.
- This vein carries most of the food digested and absorbed in the digestive tract.
39
What happens to glucose in the liver?
- Hepatocytes in the liver absorb most of the glucose and store it as glycogen.
- When the body requires energy, this glycogen is broken down into glucose.
40
Lipid metabolism in the liver
- Fatty acids in the blood passing through the liver are absorbed by hepatocytes and metabolized to produce energy in the form of ATP.
- The liver is also responsible for the synthesis of large quantities of phospholipids and cholesterol
- These compounds are then stored by the liver or exported to cells by different types of lipoproteins
- Low density lipoprotein (LDL) transports cholesterol to cells, for use in the cell membrane and in steroid synthesis
- High density lipoprotein (HDL) transports excess cholesterol from cells back to the liver (for storage or conversion)
- LDL is considered ‘bad’ as it raises blood cholesterol levels, while HDL lowers cholesterol levels and is therefore ‘good’
- Surplus cholesterol is converted by the liver into bile salts, which can be eliminated from the body via the bowels
41
What happens to protein in the liver?
- Amino acids entering the liver are transformed into other amino acids or used to synthesize new proteins.
- Endoplasmic reticulum and Golgi apparatus in hepatocytes produce plasma proteins.
- These plasma proteins include fibrinogen used in blood clotting and albumin that transports hormones and maintains the blood pH.
42
What happens to amino acids when they are no longer necessary?
- The body can not store amino acids, meaning they must be broken down when in excess
- Hepatocytes remove the amine group from the acid group (deamination).
- The acid group of the amino acid is used to produce energy or new glucose molecules while the amine group is converted into ammonia.
- As ammonia is toxic, it is transformed into urea, which is then eliminated by the kidneys in urine.
43
What happens to ammonia in the liver?
Because is toxic, it is transformed into urea, which is then eliminated by the kidneys in urine.
44
Diagram showing metabolism of nutrients in the liver
45
Explain how the liver carries out detoxification
- The liver gets rid of drugs, hormones, and other toxins.
- In some cases, it breaks down the substances into harmless compounds.
- If it cannot break them down, it attaches these substances to other organic groups (such as glycine), which allows the kidneys to recognize them as unwanted waste material and are therefore excreted.
46
How does the liver metabolize alcohol?
- Ethanol is oxidized into acetaldehyde, a toxic substance, by the hepatic enzyme alcohol dehydrogenase.
- Acetylaldehyde is converted into a less toxic substance, acetate, by aldehyde dehydrogenase.
- Acetate is then broken down to acetyl-CoA that can enter fatty acid metabolism or be used in the Krebs cycle.
- If acetaldehyde is not broken down immediately, it can combine with proteins that induce liver injury.
- Excess of alcohol can damage the liver, causing cirrhosis.
47
What can an excess of alcohol do to the liver?
It can damage it, causing cirrhosis
48
Diagram showing the chemical reactions involved in alcohol detoxification
49
What functions does the liver have other than storing and processing nutrients?
Recycling of red blood cells and formation of bile.
50
In which form is glucose mainly stored in the liver?
Glycogen
51
What are red blood cells also known as?
Erythrocytes
52
How is the structure of red blood cells or erythrocytes linked to their function?
- Red blood cells or erythrocytes are cells modified to increase their capacity in the transport of oxygen.
- In order to do this, they have a biconcave shape and have lost their nucleus and organelles.
- These cells are rich in hemoglobin, a protein that binds oxygen.
53
What effect does the biconcave shape of red blood cells have?
It increases their surface area: volume ratio, thus increasing the absorption of oxygen.
54
Lack of nucleus in a red blood cell
- The lack of a nucleus increases the amount of hemoglobin in each cell.
- But at the same time, this means that they cannot reproduce, therefore they must be produced in the bone marrow from undifferentiated cells.
55
Where are erythrocytes produced and released to?
They are produced in the bone marrow and are liberated into the bloodstream.
56
After how long do red blood cells die?
After approximately 120 days circulating in blood.
57
What happens to dead erythrocytes?
- They are engulfed by macrophages in the liver, spleen, or bone marrow by phagocytosis.
- In the liver, these macrophages are Kupffer cells.
58
How do Kupffer cells recycle dead erythrocytes?
By phagocytosis
59
Explain how dead erythrocytes are recycled by Kupffer cells
- In the Kupffer cells, the hemoglobin is split into globin chains and heme groups.
- Globin is re-used in protein synthesis.
- The heme group is transformed into iron and bilirubin.
- Iron is carried back to the bone marrow where it is used to produce new red blood cells.
- Bilirubin is secreted into bile that will be used in the emulsification of fats.
60
What happens to the globin from red blood cells recycled by Kupffer cells?
It is re-used in protein synthesis.
61
What happens to the heme group from red blood cells recycled by Kupffer cells?
It is transformed into iron and bilirubin.
62
What happens to the iron from red blood cells recycled by Kupffer cells?
It is carried back to the bone marrow where it is used to produce new red blood cells.
63
What happens to the bilirubin from red blood cells recycled by Kupffer cells?
It is secreted into bile that will be used in the emulsification of fats.
64
Diagram of how the liver recycles erythrocytes and iron
65
What is the product of the heme group after the breakdown of hemoglobin?
Iron and bilirubin.
66
Synthesis of cholesterol in the liver
- You ingest cholesterol in your diet, but it is not essential, as most cholesterol molecules are synthesized in the liver.
- As most animal cells require cholesterol for membrane synthesis, a small portion is added to the membranes of hepatocytes, and the rest is exported as lipoproteins or bile salts.
67
What important molecules in cholesterol a precursor for?
Bile salts, steroid hormones (such as estrogen and progesterone), and vitamin D.
68
How is cholesterol synthesis regulated?
- According to its concentration in cells.
- This depends on the amount ingested in the diet, and the regulation is performed by the hormones glucagon (inactivating its synthesis) and insulin (activating its synthesis).
69
Diagram showing the structure of a cholesterol molecule
70
How are cholesterol molecules carried in the blood?
- Cholesterol molecules, like triglycerides and phospholipids are insoluble in water.
- Therefore, to be carried in the blood to other tissues, they need to be carried as plasma lipoproteins.
- Different combinations of lipids and proteins produce particles of different densities.
71
What is the difference between high-density lipoproteins (HDLs) and low-density lipoproteins (LDLs)?
High-density lipoproteins (HDL) contain more protein, while low-density lipoproteins (LDL) contain more lipids.
72
Where are LDLs and HDLs produced?
They are both produced in the plasma; however, a small amount is synthesized in the liver.
73
What is the function of LDLs?
To transport cholesterol from the liver to other organs.
74
What is the function of HDLs?
To transport cholesterol from tissues to the liver.
75
Formation of an atheroma or plaque (cholesterol)
- Fats can deposit in arteries causing an atheroma or plaque.
- This is mainly caused by white blood cells (foam cells) and LDL.
- Molecules of LDL deposit in the blood vessels and can become oxidized.
- This will cause atherosclerosis of the walls of the arteries/
76
Diagram showing the effect of LDL on blood vessels
77
What is the difference between atherosclerosis and arteriosclerosis?
Atherosclerosis is the narrowing of arteries due to plaque, while arteriosclerosis is the hardening of arteries.
78
Explain how coronary heart disease can happen and what this can lead to
- If the artery leading to the heart (coronary artery) is clogged, the cells of the heart will not receive enough oxygen and can therefore die.
- These cells are replaced by fibers causing coronary heart disease (CHD).
- If the artery leading to the head (carotid artery) is affected, this can lead to a brain stroke.
79
Why is HDL considered "good cholesterol"?
Because it removes LDL from blood by transporting it to the liver and helps to maintain the endothelium of the blood vessels, thus avoiding coronary heart problems.
80
What is the role of bile salts?
- They have a crucial role in digestion as they emulsify fats.
- This means they break fats down into smaller droplets to increase their surface area.
- This allows enzymes (for example pancreatic lipase) to work better.
- Bile salts aid in the digestion and absorption of dietary lipids and fat-soluble vitamins.
81
How are bile salts made?
They are synthesized by the liver from surplus cholesterol and may be modified by bacteria in the intestines.
82
How are bile salts lost from the body? (reword?)
- Bile salts are reabsorbed from the intestines into the liver, but lots are lost in feces.
- Approximately 600 mg of bile salts are synthesized daily to replace bile acids lost in egestion.
83
How much bile is produced by the liver per day?
About one liter.
84
How is bile carried throughout the body?
By the bile canaliculi to the bile duct, which carries it to the gall bladder to be stored.
85
Describe the composition of bile
Mainly water (97%), bile salts, cholesterol and fatty acids, bilirubin (from the breakdown of erythrocytes) and inorganic salts.
86
How is cholesterol carried in blood plasma?
As lipoproteins.
As cholesterol is not soluble in water, it combines with proteins in order to be transported in blood.
87
What is jaundice a sign of?
Liver malfunction
88
What can the diseases that affect the function of the liver be caused by?
Pathogens, for example hepatitis virus; metabolic problems; or toxins such as drugs and alcohol
89
What is jaundice?
A condition where the skin and white of the eyes turn yellow.
90
What is jaundice caused by?
By the presence of bilirubin in extracellular fluid.
91
Jaundice
Jaundice is a condition caused by an excess of bile pigment – bilirubin – within the body
- Bilirubin is produced as part of the natural breakdown of hemoglobin by the liver
- Normally, the liver conjugates this bilirubin to other chemicals and then secretes it in bile
- When there is an excess of bilirubin, it may leak out into surrounding tissue fluids
Jaundice may be caused by any condition which impairs the natural breakdown of red blood cells, including:
- Liver disease – impaired removal of bilirubin by the liver may cause levels to build within the body
- Obstruction of the gall bladder – preventing the secretion of bile will cause bilirubin levels to accumulate
- Damage to red blood cells – increased destruction of erythrocytes (e.g. anemia) will cause bilirubin levels to rise
92
Under what circumstances can jaundice appear?
- Increased destruction of red blood cells.
- Immaturity in the conjugation of bilirubin (greater in premature babies).
- Genetic diseases (e.g. Gilbert syndrome).
- Defects in the secretion of conjugated bilirubin from hepatocytes (in liver damage).
- Defects in transit of bilirubin to intestines (e.g. with bile duct obstruction).
93
What is a high level of bilirubin in the blood a sign of?
Liver malfunction
94
What can the effects of a high level of bilirubin in the blood range from?
Depending on the level of exposure, the effects range from clinically unnoticeable to severe brain damage and even death.
95
What is jaundice usually a symptom of?
- Hepatitis or liver cancer.
- It can also be caused by the use of drugs, genetic factors, malaria, or anemia.
96
Jaundice in babies
It is common for a baby's bilirubin level to be a bit high after birth as it might take some time for the liver to function properly.
97
What are the causes of high bilirubin levels in babies?
A mismatch between the blood type of the mother and the child, lack of certain enzymes, or excess or abnormal blood cells
98
How is jaundice cured in babies?
Special blue lights are used on infants whose bilirubin levels are very high.
99
What is cirrhosis?
A disease where the damaged liver tissue is replaced by scar tissue.
100
What effects does cirrhosis have?
Not only does this affect the functioning of liver cells, but also interferes with the blood supply to these cells.
101
What are the effects of cirrhosis?
Weakness, fatigue, jaundice and bruising.
102
How can cirrhosis be detected?
A liver biopsy will confirm the presence of scars.
103
Can cirrhosis be cured?
- There is no cure for this disease.
- A liver transplant can be the solution in extreme cases.
104
Diagram of a normal and cirrhotic liver
105
What are the causes of cirrhosis?
- Excessive alcohol or drug consumption may cause liver cirrhosis.
- Other causes of cirrhosis include chronic viral hepatitis B or C, chronic bile duct obstruction, fatty liver disease, excess iron, cystic fibrosis, and Wilson’s disease.
106
Map showing the deaths due to liver cirrhosis per 100,000 people in 2010.
107
Relationship between the amount of alcohol consumed and the probability of liver cirrhosis
- The amount of alcohol consumed affects the possibility of liver cirrhosis in a direct manner: the greater the consumption, the greater the chances of dying of liver cirrhosis.
- The probability of dying of cirrhosis is greater in women than men at lower alcohol consumption but higher for men at greater alcohol consumption.
108
Graphs showing increasing amounts of average daily alcohol consumption and relative risk of death from cirrhosis
109
Arguments in favor of alcoholics receiving liver transplants
- Everybody has the right to live.
- They can change their lifestyle and stop drinking.
- They might be the only support for a family.
- Many people care for them.
110
Arguments against alcoholics receiving liver transplants
- They caused the liver damage by their own choice of drinking.
- They must put up with the consequence of their own reckless attitude.
- Other people deserve the transplant more.
- They can relapse back into drinking and damage the new liver.
111
Outline the synthesis of plasma proteins by hepatocytes
- Hepatocytes are the major synthesizers of blood plasma proteins, such as albumin and fibrinogen
- Plasma proteins are synthesized by ribosomes associated with the rER
- These proteins are transported from the rER to the Golgi apparatus (in vesicles) for processing
- Once processed, the proteins are once again packaged in vesicles and transported to the plasma membrane, where exocytosis occurs
- Plasma proteins can pass through large fenestrations in the sinusoids, entering the bloodstream
