BHS 116.2: Physiology II
Notetaker: Stephanie Cullen
Date: 1/23/13
Page: 1
Anatomy of the Liver
- Largest organ in the body (besides skin)
o 1/50th of body weight (2%)
- Composed of a right and a left lobe
- Most abused since it detoxifies everything put into the body
- Functions:
o Filtration and storage of blood
o Metabolism of carbohydrates, proteins, fats, and hormones
o Detoxification of foreign chemicals
o Bile formation
o Storage of vitamins and iron
o Formation of coagulation factors (clotting cascade)
o Removal of bacteria and old erythrocytes from the blood
Objective: Describe the circulation (portal and systemic).
-
Circulation
o Approximately 1400 ml of blood flows into the liver every minute
(tremendous blood supply)
 28% of the cardiac output is in the liver at a given time
o The liver receives both portal blood and systemic blood
 Very vascular
o Very low resistance to blood flow through the liver
 No muscular arterioles
 Very compliant
o Systemic blood (25%)
 Enters the liver via the hepatic artery
 Supplies the liver cells with oxygen (oxygenated blood)
 Merges w/ portal blood in the liver sinusoids (hepatic portal vein)
o Portal system (75%)
 Enters the liver via the hepatic portal vein
 Contains the nutrient-rich blood from the GI tract
 This blood can contain bacteria and other impurities (toxins) and needs to be
processed before being sent to the systemic system
 Except fats (central lacteal in lymphatic system)
o After processing, the blood is sent to the systemic circulation via the hepatic vein
 Get a pool of blood that flows into the liver through the hepatic artery, processed
by the liver, leaves through hepatic vein
BHS 116.2: Physiology II
Notetaker: Stephanie Cullen
Date: 1/23/13
Page: 2
Objective: Describe the anatomy of the liver (portal triad, sinusoids, cells, Space of Disse).
o
o
o
o
o
o
o
Portal triad
 Comprised of the hepatic a., hepatic portal v., and bile duct (carries bile to gall
bladder)
 All run together so that all the main branches enter the liver then branch
at the same time within the liver
 Consistent throughout the liver
 Artery and vein carry fluid in and bile duct carries fluid out to SI or gall
bladder
The hepatic a. and hepatic portal v. drain into sinusoids after they merge
 Like a major capillary bed
The sinusoids are lined by hepatocytes (main cell type, outside), endothelial cell, and
Kupffer cells (phagocytic, inside)
All of the sinusoids drain into central veins
Central veins come together to form the hepatic vein
 Leaves the liver to take blood to the vena cava
Hepatocytes
 Main cell type of the liver
 Perform all of the functions of the liver except phagocytosis of bacteria and
foreign material
 Continuously make and secrete bile into the bile canaliculi
 Carry bile into the bile duct
 In contact w/ the sinusoid on 1 side and a bile canaliculus on the other
 One in contact w/ the sinusoid (usually a basal-lateral surface because it
doesn’t secrete bile)
Endothelial cells
 Thin layer of cells that form the sinusoids
 Have very large pores so that everything except large particles and bacteria are
filtered through via diffusion and bulk flow
 Filtered blood enters the Space of Disse between endothelial cells and
hepatocytes
 Contact allows hepatocytes to take up glucose
 The Space of Disse connects to the lymphatic vessels and excess fluid or
unabsorbed nutrients in these spaces is removed via the lymphatics
 Goes to the circulatory system
BHS 116.2: Physiology II
Notetaker: Stephanie Cullen
o
o
Date: 1/23/13
Page: 3
Space of Disse
 There is a cell called the Stellate cell that is found here (so it is not empty) and it
is basically a fat storage cell for overflow
 Usually quiescent
 There is also a delicate collagen framework
 Structure and support needed since the blood in the sinusoids exerts
pressure
 W/o support, the blood would push the sinusoid against the hepatocytes
Kupffer cells
 Macrophage-like cells capable of phagocytozing bacteria, foreign matter, and
other large particles (including dying RBCs) flowing through the sinusoids
Objective: Describe the structure and function of the liver lobule.
o
o
Liver lobules (hundreds of thousands)
 The liver is broken up into functional units called lobules that are comprised of
hepatocytes, the portal triad, sinusoids, bile canaliculi, and the central vein
 Hexagonal shape w/ the portal triad at the end of each side (corners)
 The center is the central vein for sinusoid drainage
The hepatocytes are arranged (organized) in cords (2 cells thick)
 Parallel the sinusoids and bile canaliculi
 Radiate from the central vein like spokes on a bicycle wheel
 Each central v. is responsible for the blood in that hexagon
BHS 116.2: Physiology II
Notetaker: Stephanie Cullen
o
o
o
Date: 1/23/13
Page: 4
The portal and systemic blood flow to the central vein via the sinusoids
The blood is processed via the hepatocytes (metabolism and secretion of nutrients and
proteins, detoxification) and the Kupffer cells (phagocytosis of bacteria and foreign
particles
The bile synthesized in the heptaocytes is secreted into the bile canaliculi and carried to
the bile duct then gall bladder
 Opposite direction of blood flow
Objective: Describe the functions of the liver (filtration and storage, metabolism, bile and protein
synthesis and secretion, detoxification).
Metabolic Functions
- Filtration and storage of blood
o Due to large numbers of sinusoids and the Spaces of Disse, excess blood volume can
actually be stored in the liver
 The liver can act as a blood reservoir
 Usually occurs during right-sided hypertension
 Back up through the venous system
 Sinusoids can expand to hold more blood
 Very compliant
- Metabolism of carbohydrates
o Storage of large amounts of glycogen (major store of glycogen outside the skeletal
muscle)
 Excess glucose is removed from the blood (insulin independent)
 Processed (insulin dependent), stored, and returned to the blood when glucose
levels decline (via glucagon action)
 Glucagon: triggers breakdown to glucose
o Gluconeogenesis
 Stimulated by glucagon and cortisol
 Occurs when the glucose levels fall below normal
 Conversion of amino acids and glycerol to glucose
o Conversion of galactose and fructose to glucose
 Absorbed w/ Na+ in enterocytes
o All of these processes are involved in maintaining a normal blood glucose level
- Metabolism of proteins
o Deamination of amino acids
 Required before they can be used for energy
o Formation of urea for removal of ammonia from the body fluids
 Ammonia is formed during deamination process and by GI bacteria and can be
toxic leading to hepatic coma and death
o Formation of plasma proteins
 90% of plasma proteins are made in the liver (albumin being the most abundant,
but hormone binding proteins are included, as well as coagulation factors and γglobulins)
o Interconversions of the various amino acids and synthesis of other compounds from
amino acids
- Metabolism of hormones
o Several of the hormones secreted by the endocrine glands are either chemically altered or
metabolized in the liver (including thyroxine and all of the steroid hormones) if they are
not taken up by the target cell
BHS 116.2: Physiology II
Notetaker: Stephanie Cullen
-
-
Date: 1/23/13
Page: 5
Metabolism of fats
o Oxidation of fatty acids to supply energy for other functions
 Splits fats into glycerol and free FAs and the FAs into acetyl CoA (Krebs cycle)
o Synthesis of large quantities of cholesterol, phospholipids, and lipoproteins
 80% of the cholesterol synthesized in the liver is converted to bile salts (used in
fat digestion)
 Remainder is packaged into lipoproteins which are transported in the blood to
other tissues
o Synthesis of fat from proteins and carbohydrates
 Liver is primary tissue where this occurs
 Synthesized fat is transported in lipoprotein particles
o Lipids and cholesterol are absorbed in the intestinal epithelium and repackaged as
chylomicrons (main lipid particle in the blood after a meal)
 86% triglycerides
 10% phospholipids
 3% cholesterol
 1% protein
o After a meal, chylomicrons enter the circulation via the lymph and are taken up and
processed by the liver hepatocytes and endothelial cells
 Circulation to the hepatic artery to the liver
 Avoid the hepatic system via the lymph to get to the liver
o In the absence of chylomicrons (between meals), 95% of the lipid in the blood is in the
form of lipoproteins (smaller particles that contain triglycerides, phospholipids,
cholesterol, and protein)
 Primarily LDL
 Source of lipids in the blood for tissues if needed between meals
3 main types of lipoproteins
o Very low density lipoprotein (VLDL)
 High concentration of triglyceride, moderate concentration of phospholipid, and
protein
 Can be quickly converted to LDL because cells use the TG
 Have lipases on their surface to chop out TG from the lipoprotein particle
 Left with a more cholesterol-rich particle: LDL
o Low density lipoprotein (LDL) “Bad cholesterol”
 Most triglyceride removed, high concentration of cholesterol, moderate
concentration of phospholipid
 Predominant lipoprotein in the plasma between meals
o High density lipoprotein (HDL)
 High concentration of protein (50%) and much smaller concentration of
cholesterol and phospholipid
Objective: Describe the circulation of bile salts.
-
Synthesis and Secretion of Bile Salts
o 80% of cholesterol made in the liver is converted into bile salts
 Cholesterol is converted into cholic acid which combines w/ glycine to form
glycocholic acid or glycocholate (the major bile acid)
 Glycocholate then combines w/ sodium to form sodium glycocholate (the major
bile salt)
 When made from cholesterol (not water soluble) so the Na is added to
make it water soluble
BHS 116.2: Physiology II
Notetaker: Stephanie Cullen
o
Bile salts are secreted w/ other components to form bile

-
-
-
Date: 1/23/13
Page: 6
Gall bladder has more concentrated bile
 Main components are in much higher concentrations in the gall bladder
than when first released from the liver
 Stronger bile is released from the gall bladder
Enterohepatic Circulation of Bile Salts
o The bile salts are synthesized in the liver and stored in the gall bladder
o During digestion they are secreted into the small intestine and emulsify the fats
o They are reabsorbed into the portal circulation w/ nutrients from digestion process (in the
ileum)
 Go into the hepatic portal vein
 Taken back up by liver
o The bile salts are recycled into the pool of bile for
another round
 Reused
o Most is recycled
 Very small amount is made from new
cholesterol
o Bile sequestering drug: binds bile in intestine to
prevent it from being absorbed
 Excreted in feces
 Reduce cholesterol levels by forcing the
body to make more bile instead of recycling
Detoxification
o The liver processes every drug, chemical, pesticide,
and toxin that enters the blood
o There are 2 major pathways
 Phase 1 (cytochrome P450 enzyme system)
 Toxin is processed via a series of oxidation, reduction, hydrolysis or
hydroxylation reactions which makes it a less harmful substance
 Phase 2 (conjugation pathway)
 A glycine or sulphate is added to the toxin to make it water soluble
which can then be excreted in the urine or bile
o A lot of times, a portion of the bile is these detoxified
compounds that are not reabsorbed with the bile salts
Storage of Vitamins and Iron
o The liver stores many vitamins w/ the largest amount being vit A (up to 10 months)
 Also large quantities of vit D (3 months) and vit B12 (1 year)
 Remember: intrinsic factor from the parietal cells is needed to take up B12
 When we take up the B12, the liver stores it because we might not be able
to take up a lot of it
 Role in stimulation of coagulation factors
BHS 116.2: Physiology II
Notetaker: Stephanie Cullen
o
-
Date: 1/23/13
Page: 7
The liver is the largest store of iron in the body w/ the exception of iron bound to
hemoglobin in the blood
 Free iron will bind to the liver protein apoferritin and be stored in the liver as
ferritin
Synthesis and Secretion of Proteins
o Proteins involved in the coagulation process in the blood are synthesized and secreted by
the liver (fibrinogen, prothrombin, Factor VII)
 Vit K is essential for the synthesis of many of these proteins
Clicker Question: Which cell type performs the majority of the liver’s functions?
a. Hepatocyte
b. Endothelial cell
c. Stellate cell
d. Kupffer cell