3 B: Physiology of Liver Flashcards
What are functions of the liver?
1) Glycogenolysis & Glycogenesis
2) Protein metabolism/urea synthesis
3) lipid metabolism
4) hormone metabolism
5) iron metabolism and storage
6) vitamin storage
7) drug detoxification
8) Vit D activation pathway
9) plasma protein syntheis
10) synthesis of blood clotting factors
11) bile synthesis
What does storage of glycogen allow?
Allows the liver to remove excess glucose from the blood, store it, and then return it to the blood when the blood glucose concentration falls
How much glycogen can the liver store?
8% of their weight (100-120 g in an adult)
How much is found in the muscles?
1-3% of muscle mass; but total amount exceeds that in liver!
More muscles
Where does amino acid degradation occur?
Mostly in the LIVER, and begins with deamination.
What is deamination?
The removal of amine (NH2) groups from the amino acids
What do deamination reactions require?
Set of enzymes; aminotransferases or transaminases
What is AST ?
SGOT (serum glutamate-oxaloacetate transaminase) also called aspartate transaminase
What is ALT?
SGPT( serum glutamate-pyruvate transaminase) also called alaine transaminase
What other purpose do AST & ALT have?
They are also used to synthesize non-essential amino acids within liver hepatocytes
What are high levels of ALT and AST indicative of?
Liver disease
What happens to the amine groups cleaves form the amino acids ?
They are converted into ammonia (NH3) or ammonium ions (NH4+), which are then converted into urea
Where is al urea synthesized?
The liver
What is hepatic coma or hepatic encephalopathy?
In serious liver disease, ammonia that accumulates in the blood and lead to this state
How is urea excreted by the kidneys?
Urea diffuses from liver hepatocytes into the body fluids
What is azotemia or uremia?
A build-up of urea in the blood which high levels of urea become toxic to a variety of tissues
**Note: This is often a symptom of renal disease or failure!!
What is the normal range of BUN in an adult?
5-26 mg/dL
Elevated Blood Urea Nitrogen (BUN) can occur with?
1) **impaired renal function
2) increased protein intake or catabolism
3) GI bleeding (due to intestinal flora creating nitrogenous waste)
4) dehydration
What is HMG-COA reductase required for?
An important enzyme in liver hepatocytes required for endogenous cholesterol synthesis
What is the only way the body can eliminate excess cholesterol ?
Via bile
Why does Ketogenesis occur?
Occurs in fasting states or poorly controlled type I diabetes mellitus
The steroid hormones, as well as T3 and T4 are degraded by what?
The liver
What form is iron stored as in the liver?
Ferritin
Describe iron metabolism and storage
1) Mixture of Fe2+ and Fe3+ are ingested
2) Stomach acid converts Fe3+–>Fe2+
3) Fe2+ binds to gastroferritin
4) Gastroferritin transports Fe2+ to s. intestines & releases it for absorption
5) In blood plasma Fe2+ binds to transferrin
6) In liver, some transferrin releases Fe2+ for storage
7) Fe2+ binds to apoferritin to be stored as ferritin
8) Remaining transferrin is distributed to other organs where Fe2+ is used to make hemoglobin, myoglobin, etc
Large quantities of vit A, B12, and D are stored where?
Liver
What is the most important organ involved in drug metabolism? Why?
The LIVER;
Because it has many enzymes systems
( The MOST important = Cytochrome P450 System)
What is the basic purpose of drug metabolisms in the body ?
To make drugs less active and more water soluble and thus more readily excreted in the urine or bile
Where can Cytochrome P450 Enzymes be most predominantly found?
Predominantly in the LIVER but also in the intestines, lungs and other organs!
How are the cytochrome P450 enzymes designated by?
By the letter “CYP” followed by a Arabic numeral, a letter and another Arabic numeral (e.g, CYP2D6).
**EACH enzyme is termed an isoform since each derives form a different gene
What does phase I and phase 2 enzymes consist of?
Phase I= Cytochrome P450 enzymes
Phase 2= Conjugative enzymes
What are conjugation reactions designed to do?
To make metabolites more polar or hydrophilic, sometimes after they’ve been created by P450 enzymes
What do conjugation reactions involve?
Endogenous substrate (Glucuronic acid, glutathione, acetyl-CoA or an amino acid), being added to a metabolite)
What is Glucuronidation?
The most common and the most important conjugation reaction
What does CP450 Inhibition involve?
In the decreed metabolic activity of CP450 enzymes leading to decreased metabolism of drugs
What does CP450 Induction involve?
Results in increased activity of CP450 enzymes leading to increased metabolism of drugs
What are the major types of plasma proteins?
1) Albumin
2) Globulin
3) Fibrinogen
Where is the albumin, fibrinogen, and 50-80% of the globulin formed?
In the LIVER
Where are the remainder of the globulins formed?
OIn the lymphoid tissues
What constitutes the antibodies used in the immune system?
Gamma globulins
What represents a smaller fraction of proteins found in the blood?
Hormones (e.g insulin, GH, ADH, PTH, etc.), angiotensinogen, etc.
What are the function of the major classes of plans proteins ?
1) excretion of obconic pressure across capillary walls, which prevents EDEMA (albumin)
2) supplying approx. 15% of the buffering capacity of the blood (albumin)
3) transport of thyroid, adrenocortical, gonadal, and other hormones (albumin & globulin)
4) acting as carriers for metals, ions, fatty acids, amino acids, bilirubin, enzymes and drugs (albumin & globulin)
5) Participating in blood clotting (fibrinogen)
6) Participating in immune responses (gamma-globulin)
Which Blood Clotting Factors are synthesized by the liver?
1, 2, 5, 7, 8, 9, 10, 11 and 12
What are the organic constituents of bile?
Bile salts (50%), phospholipids (40%), cholesterol (4%), and bile pigments such as bilirubin (2%)
What is secreted by cells lining the bile ducts?
Bile containing electrolytes and water
What are the 2 primarily bile acids synthesized by the Hepatocytes?
1) cholic acid
2) chenodeoxycholic acid
A portion of the primary bile acids is converted by intestinal bacteria into what 2 secondary bile acids?
1) deoxycholic acid
2) lithocholic acid
What helps make the bile acids AMPHIPATHIC at duodenal pH?
The liver conjugates the bile acids w/ amino acid glycine or taurine to form bile salts–>making them amphipathic
What is the most common variety of phospholipids found in bile?
LECITHIN
Phospholipids are ___________
Amphipathic
What accounts for most of the cholesterol breakdown in the body?
Hepatic synthesis of bile acids
In humans how much of cholesterol is converted to bile acids and eliminated in bile everyday?
500 mg
***Some cholesterol is also eliminated in the bile as a WASTE PRODUCT
What is Bilirubin?
A waste product of hemoglobin degradation
What are the types of bilirubin?
Free bilirubin OR unconjugated bilirubin OR Indirect bilirubin. Conjugated bilirubin OR direct bilirubin
How is free bilirubin transported into the blood?
By attaching to albumin
As free bilirubin passes thru the liver, it is release from?
Where is it moved?
Release from albumin & moved into hepatocytes
What functions do free bilirubin passing thru liver in hepatocytes preform?
- Uptake of bilirubin from the circulation
- Conjugation of bilirubin
- Excretion of bilirubin into the bile
What does conjugation involve?
The attaching of glucuronic acid to bilirubin in a reaction catalyzed by the enzyme glucuronyl transferase
Which type of bilirubin iix more water soluble?
Conjugated is more then free or unconjugated bilirubin
What are other bile constituents?
Ions ( Na+, K+, Cl-, HCO3-) and water are secreted into bile by epithelial cells lining the bile ducts
What are other waste products with bile?
lipophilic drugs and metabolites, antigen-antibody complexes, etc.
Describe the 3 steps of bile formation
1) Hepatocytes actively secrete bile into bile canals (canaliculi)
2) Intrahepatic and extra hepatic ducts not only transport this bile, but the cells that line these duct (cholangiocytes) also secrete a watery, HCO3- rich fluid
3) Between meals approx. 1/2 the hepatic bile is diverted to the gallbladder, stores and removes salts & water.
What is hepatic bile?
The first 2 steps producing 900 ml/day
What is the result of removing salts and water?
The gall bladder concentrates the key remaining solutes-bile salts, bilirubin, cholesterol and lecithin by 10-20 fold
During meals, bile that reaches the duodenum is what?
A mixture of relatively DILUTE hepatic bile & CONCENTRATED gall bladder bile.
What are the 2 important functions of Bile?
1) Provides the sole excretory rout for many solutes that are not excreted by the kidneys.
2) Secreted bile salts and lecithin are required for normal lipid digestion & absorption in the s. intestine
