liver function 1 Flashcards
what is the second largest organ in the human body
liver
functions of the liver
Metabolic Circulatory Storage Protective/Detoxification Excretory
The liver is so important that if it becomes nonfunctional, death will
occur within 24 hours due to hypoglycemia.
Remember: glucose is stored as glycogen in the liver. If breakdown
of glycogen is impaired, hypoglycemia occurs
gross anatomy of liver
Located in upper right side of abdominal cavity
Below diaphragm
Divided in 2 lobes (left & right)
Supplied by a portal vein & hepatic artery
Unique, 2 circulations
Hepatic artery - carries oxygenated blood to the liver
- vein takes it away
- hepatic artery is a branch of the aorta
Portal vein – carries blood from GI tract to liver
how much blood passes through the liver per minute
1.5 liters/ min
hepatic circulation
Hepatic artery carries oxygenated blood to right and left
lobes; it is a branch of the aorta
The right and left hepatic veins carry blood away from the
liver and join the inferior vena cava near the right atrium
Hepatic Circulation includes:
Hepatic artery
Hepatic veins
Portal Circulation
Portal vein carries blood (nutrients) from the GI tract to the liver.
Portal circulation ends in capillaries called sinusoids.
All nutrients except fat are brought to the liver first (First pass)
Liver metabolizes as needed and sinusoids drain into hepatic vein
Liver Excretory System
Excretory Products via bile (e.g. bilirubin)
Canaliculis
Hepatic Duct
Bile Duct
Small Intestine (Duodenum)
internal anatomy of liver
•The liver is divided into lobules - functional units responsible for all
metabolic and excretory functions in the liver
◦ ~ 100,000 lobules in the liver
•Lobules are six-sided structures each containing a central vein with portal
triads at each of the corners.
•Portal triads contain:
◦ Hepatic artery
◦ Portal vein
◦ Bile duct
•Blood moves around lobule and is filtered inwards
2 major types of cells in liver
1) Hepatocytes
- Large parenchymal (functional) cells which radiate out from the central vein
- perform metabolic functions
- Responsible for regenerative properties of the liver
- Make up 80% of the volume of the liver
2) Kupffer cells
- line the sinusoids
- fixed phagocytic macrophages
- engulf bacteria, debris, toxins, and other substances that flow through the sinusoids.
Space of Disse
◦ Lies between kupffer cells and hepatocytes
◦ Permits transfer of nutrients and wastes between
livers cells and circulatory blood
Biliary Canaliculi
◦ Formed by membranes of adjoining parenchymal cells
◦ Carry bile to the larger bile ducts
◦ The bile ducts then carry bile to the gall bladder
1st pass
Nutrients and toxins enter via portal vein to the liver. (1st pass is
through the liver)
In the sinusoids, nutrients are absorbed and toxins are removed by kupffer cells.
Purified blood enters the central hepatic vein, on the way to the inferior vena cava (brings deoxygenated blood to the heart)
Metabolic Functions
• Carbohydrate Metabolism
◦ Maintains blood glucose concentrations
◦ Glucogenesis (stores glucose as glycogen)
◦ Glycogenolysis (breaks down glycogen to glucose)
◦ Gluconeogenesis (glucose formed from non-carbohydrates: pyruvate, lactate, and amino acids)
• Protein Metabolism
◦ Most proteins are synthesized by the liver
◦ Exceptions are immunoglobulins (by plasma cells) and adult hemoglobin (in developing RBCs)
• Lipid Metabolism
◦ Metabolize lipids and lipoproteins
◦ Gather free fatty acids and break them down into acetyl-CoA
◦ ~70% of daily cholesterol production occurs in liver
Circulatory Functions
- Haematopoiesis (formation of blood cells)◦ Occurs in liver of embryo and fetus until bone marrow develops
- Removal of aged RBCs◦ Mainly occurs in spleen, but some removed by liver
• Production of coagulation factors◦ Hepatocytes synthesize fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S and antithrombin
◦ Liver sinusoidal endothelial cells produce factor VIII and Von Willebrand
factor
Storage Function
Stores Metabolites:
◦ Iron
◦ Glycogen (stabilizes blood glucose)
◦ Some lipids (temporary storage)
- Most lipids are stored in adipose tissue but the liver can temporarily
store some
◦ Some vitamins
- Vitamin A (Retinol - vitamin A1)
- Vitamin D
- B12Protective Function
• Phagocytosis by Kupffer cells
◦ Kupffer cells line the sinusoids and are the largest group of fixed phagocytes in the body
• Detoxification
◦ Liver acts as a gatekeeper between toxic substances absorbed by GI tract and the blood (1st pass)
◦ Toxic metabolites → non-toxic (eg. ammonia → urea)
◦ Active drugs → inactive forms
• Alter solubility so substances can be excreted (eg. bilirubin in bile)
Excretory Function
• Only organ that has the capacity to remove heme waste
products from the body. (very important function!)
◦ Bilirubin is the major heme waste product
• Liver processes and excretes substances into bile or urine.
Bile
• 95-97% water
• Contains bile acids or salts, bile pigments, cholesterol and other substances
from blood
- Soap-like (bile salts emulsify lipids in the intestine)
- 3L made daily
• Stored in the gall bladder and released into the intestine
Liver excretory function can be assessed by measuring serum bilirubin
concentrations.
• Bilirubin is the main pigment in bile and gives it the yellow or orange color
Bilirubin Metabolism
Bilirubin
• Orange-yellow pigment found in bile
• Derived from the breakdown of red blood cells
- 85% from breakdown of aged RBCs
- 15% from breakdown of immature RBCs in marrow or breakdown of other
heme containing proteins (myoglobin, etc)
Bilirubin = waste product from breakdown of hemoglobin
Structure of Hemoglobin
• Protein portion called globin containing 4 chains
- e.g. HbA contains 2 α chains and 2 β chains
• 4 heme groups attached to the globin
- Cyclic with 4 pyrrole rings
- Rings joined by methane bridge
- Each ring = porphyrin ring
- Ferrous (Fe2+) iron bound inside each ring
Normal Breakdown of Hemoglobin
After 120 days: RBC’s broken down biliverdin bilirubin
How?
Phagocytes (liver, spleen, BM) act on RBC’s .
Porphyrin ring opens,
Iron is released & 1 methene group lost Biliverdin (green)
Biliverdin is reduced to bilirubin (yellow-orange)
2 bile pigments which end up in bile:
- Biliverdin
- Bilirubin
Normal Breakdown of Hemoglobin
1) Unconjugated Bilirubin + Albumin → liver(unconjugated bilirubin is not water soluble and must be carried by albumin)
2) [Bilirubin-Albumin] + Glucoronic Acid Bilirubin Glucoronide(Albumin releases bilirubin and gets conjugated with glucuronic acid)
3) Bilirubin Glucoronide → Bile → Gall Bladder → Small Intestine(This is conjugated bilirubin and is water soluble)
4) In small intestine:
Bilirubin Glucoronide + Bacteria → Mesobilinogen, Stercobilinogen & Urobilinogen(Bacteria reduce bilirubin to urobilinogens - colorless)
5) Some Urobilinogen → Portal Blood → Liver → General Circulation → Kidney → Urine(Up to 20% of urobilinogen enters portal blood to go to liver for re-excretion in bile)
(2-5% enters general circulation to go to kidneys and be excreted in urine)
6) Other Urobilinogen → Colon → Urobilin, Stercobilin(Most urobilinogen stays in colon and gets oxidized to pigments - yellow-brown color)
unconjuageted vs conjugated bilirubin
Conjugated Bilirubin• AKA Direct Bilirubin
• Polar (esterfied with glucoronic acid → bilirubin glucuronide)
• Water Soluble
• If elevated levels in the serum, it will be filtered to the urine
- polar
- H2O soluble
Unconjugated Bilirubin• AKA Indirect Bilirubin
• Non-polar (binds to albumin)
• Not water soluble
• Not in urine (because it isn’t H2O soluble)
- non-polar
- not H2O soluble
Daily Bilirubin
• 250-300 mg produced in healthy adults
• Bilirubin eliminated via:
- Feces (urobilinogens, urobilin, stercobilin)
- Urine (urobilinogen)
• Concentration of bilirubin in plasma is low (mostly unconjugated)
Blood
- both bilirubins ( unconjugated + conjugated)
Urine
- urobilinogen
- should be negative for bilirubin in healthy adults
Diazo Reaction
- Most methods are based on the Diazo Reaction
- First described by Ehrlich
• Bilirubin + Diazo Reagent → Azobilirubin—–> Red/Purple @ neutral pH
Blue @ alkaline pH
diazo reagent: Diazotized Sulfanilic Acid
Diazo = 2 linked N atoms at a terminal end
diazo reaction accelerators
Without an accelerator, the diazo reagent only reacts with conjugated
bilirubin (and not unconjugated bilirubin)
Accelerators
• Make unconjugated bilirubin soluble so that it can react with the diazo
reagent
• Alcohol, caffeine
Species of Bilirubin
• Direct Reacting (react directly with Diazo Reagent):
• Bilirubin monoglucuronide (10%)
• Bilirubin diglucuronide (90%)
• Delta bilirubin
- Conjugated bilirubin that is covalently bound to albumin, tightly and
irreversibly
- Only seen when there is a significant hepatic obstruction
• Indirect Reacting: (reacts only in presence of accelerator)
. Unconjugated bilirubin (non-covalently bound to albumin)
- Main form found in blood
