Transcript The Liver The Challenge: In 20 minutes, can we at least start to find out what the liver has to do with cholesterol levels.

The Liver
The Challenge: In 20 minutes,
can we at least start to find out
what the liver has to do with
cholesterol levels in our body?
To get there, we need to
1. Get it situated (ANATOMY)
2. Get it a blood supply with all the “stuff”
in the blood that it needs to do its work
(PHYSIOLOGY or organ-level
function)
3. See the micro-structure of the liver
(HISTOLOGY)
4. Marvel at the wonder of hepatocytes,
or liver cells—are they perhaps the
most ‘intelligent” entities on the planet?
(CELL BIOLOGY)
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Liver Brainstorm
• Largest “solid-mass”
organ of the body
• Perhaps least
understood, both
popularly and
scientifically?
• Brainstorm: 30 seconds
and three adjectives or
phrases (good to do in
previous class or on-line)
Liver Brainstorm—take
30 seconds to write
what comes out…top of
your head
Adjective/phrase 1:
Adjective/phrase 2:
Adjective/phrase 3:
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Locate your liver
• Upper right quadrant
deep to inferior ribs
• Dome of liver abuts
aganst inferior
diaphragm surface
• Left/right lobes
• Gall bladder is thin
muscular sac on inferior
surface where bile
collects (1 above)
1. ANATOMY
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Percuss your liver
• Easiest organ to
percuss
• Dense tissue gives
rock-solid sound/feel
on percussion
• Mid-clavicular line
moving inferiorly from
mid-chest to lower
right quadrant
Measuring liver span by percussion: variation in liver span
Variation in liver span according to the vertical plane of examination. Since there is
variability in where clinicians determine the mid-clavicular line to be, the inevitable
consequence is that liver span may also vary even if multiple observers are
perfectly accurate in measuring it.
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
What does the liver do?
Multi-function, blood-processing “factory”
• Temporary nutrient storage (glucoseglycogen)
• Remove toxins from blood
• Remove old/damaged RBC’s
• Regulate nutrient or metabolite levels
in blood—keep constant supply of
sugars, fats, amino acids, nucleotides
(including cholesterol)
• Secrete bile via bile ducts and gall
bladder into small intestines.
Needs blood supply laden with “stuff” to process
2. PHYSIOLOGY
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Dual blood supply to liver:
1. Hepatic portal system (review)
• Main drainage of
blood from gut—why
to liver?
• Why does liver need
another blood supply?
What does this blood
NOT have that liver
(and any organ)
needs?
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Dual blood supply to liver
2. Hepatic artery (review)
• Primary branch from celiac
artery which is one of the three
main visceral branches of aorta
(review from circulation)
• Brings oxygen-rich blood
• Within liver lobules, blood
mixes:
– Nutrient-rich, toxin-laden,
oxygen-poor blood from gut via
hepatic portal vein
– Oxygen-rich blood from hepatic
portal artery
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Where do the two blood supplies mix?
• Triads: Branches of three vessels: hepatic
portal vein, hepatic artery, along with bile
drainage ductiles all run together to infiltrate
all parts of liver.
• Sinusoids—special liver capillaries where
blood mixes and liver cells act…by-products
leave as bile in caniliculi which merge to form
bile ducts
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
3. HISTOLOGY
Hepatocytes at work
• Metabolic map of liver—PDF link
• Hepatocytes are incredible chemical transformation
factories
• Just deep to epithelial lining of sinusoids
• Able to convert from one type of organic substrate (sugar,
protein, fat, nucleotide) to another
• Produce bile
Kuppfer cell
immune function
4. CELL BIOLOGY
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
What is bile?
• Bile composed of water, ions, bile
acids, organic molecules (including
cholesterol, phospholipids, bilirubin)
• Gallstones are mostly cholesterol
• Acids and salts emulsify fats for
absorption across wall of small
intestines into lacteal lymph capillaries
(review)
• Contains waste products from RBC
breakdown and other metabolic
processing (color of feces from
bilirubin in bile)(review)
• Ions buffer chyme from stomach
(review)
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Bile processing and recycling
• Hepatocytes initially secrete
bile into canaliculi, carried to
gall bladder via hepatic ducts
• Gall bladder stores bile until
needed in gut when secreted
out cystic duct to common
bile duct to duodenum
• 95% of the bile produced by
the liver is “recycled”…often
2 or 3 times during the
digestion of a single meal
Great bile page with enterohepatic recirculation animation
(from Colorado State University)
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Cholesterol—one example of liver processing
• Our body needs cholesterol for
–
–
–
–
–
Cell membranes
Vitamin D
Hormones—progesterone and testosterone
Myelin (neuron axonal “wrapping”)
Component of bile salts
• 85% of cholesterol in our blood is “endogenous”
or manufactured by our own cells (mostly liver)
• 15% comes from the food we eat
• So, is zero-cholesterol good…or even healthy?
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Cholesterol in the liver:
Where’s it from? Where’s it go?
• Liver constantly manufactures cholesterol
using acetyl-CoA as substrate
• Some cholesterol to gut via bile for
emulsification of dietary fats
• Some cholesterol to blood for cell
membranes, myelin, hormones, vitamins
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
“Good” and “bad” cholesterol
• Two ways cholesterol is “packed”
– LDL—low density lipo-proteins (“bad”)
– HDL—high density lipo-proteins (“good”)
• LDL is component of arterial plaques that can lead to “blocked
arteries”
• HDL can help to clear LDL from arterial walls
• “Packing” of cholesterol and interactions with other dietary
and liver-produced fats maybe more important than
cholesterol levels alone
• Trans and saturated fats (especially artificially hydrogenated
fats) may be most culpable element of diet in raising LDL
levels
• Mono-unsaturated fats (such as olive oil, canola oil) along
with dietary fiber raise HDL levels Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Cholesterol processing in liver and relation to
cardio-vascular disease and arterial plaques
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Other liver cell functions
• Red blood cell decomposition and
recycling of components
• Toxin neutralization
• Conversion of “substrates:” altering amino
acids, amino acids to sugars, sugars to
amino acids, etc….to insure adequate
supply of necessary “molecules of life.”
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006
Summary
• ANATOMY: Locate liver by percussing upper right quadrant
of abdomen
• PHYSIOLOGY: Liver is blood processing organ with dual
blood supply.
• HISTOLOGY: Blood mixes in sinusoids where hepatocytes
“do their magic”
• CELL BIOLOGY: Multiple functions for hepatocytes.
Manufacture cholesterol for use and recycling in digestion
(via bile) and delivery to cells of body via circulatory system
(via central vein of liver lobules).
– Cholesterol is necessary for many normal metabolic processes
– High levels of LDL cholesterol may contribute to plaque formation in
arteries
– HDL cholesterol may help to break down plaques
Liver Physiology, Larry Frolich, Yavapai College, March 10, 2006