Gastrointestinal Anatomy

and Physiology

Part 4: Liver, Pancreas and Gall

Bladder

Feb 2009
Anatomy reminder
 Objectives
• Understand that the liver is a specialized
organ involved in processing of food,
protein synthesis, toxicology and immune
functions.
• Understand the role of the gallbladder and
bile in the process of digestion and nutrient
absorption.
• Understand that the pancreas has both
endocrine and exocrine functions.
 The liver has a dual blood supply

Hepatic

(branches from
the celiac trunk)
 The liver has specialized cells

• Hepatocytes
– Synthesis, storage, detoxification and metabolism
• Kupffer cells (hepatic macrophages)
– Eat bacteria, dying neutrophils, make cytokines
• Hepatic stellate cells
– Vitamin A storage (?collagen, nervous)
• Sinusoid endothelial cells
– Fenestrated
– No basement membrane
Visceral surface of the liver
The liver lobule
Liver -the histology
The hepatic sinusoids
Electron micrograph of hepatocytes
The sinusoidal endothelium is
fenestrated
 The liver is a food processor

• The liver processes sugar

• The liver processes amino

acids

• The liver processes fats

• The liver processes vitamins

 The liver processes sugar

• The liver stores glucose from dietary sources as glycogen.

– Monosaccharide converted to polysaccharide
– This can provide a 2 day source of glucose

• Glucose can also be used to synthesize new fatty acids and

amino acids (non-essential)

• The liver can also make new glucose;

– during fasting pyruvate and lactate are converted to glucose by
gluconeogenesis
– glycogenolysis

• The liver converts galactose and fructose to glucose.

 The liver processes
amino acids

• The liver will use essential amino acids for

protein synthesis (eg. Albumin)

• Non-essential amino acids are transaminated

to keto acid to be used in the Krebs cycle

• Oxidative deamination results in the formation

of urea (later excreted by the kidney).
Processing of amino acids
 The liver processes fats

• The liver packages fatty acids into forms that

can be transported or stored

• The liver packages triglycerides primarily as

VLDL to be delivered to adipocytes

• LDL is used to transport cholesterol to

peripheral tissues

• HDL brings excess cholesterol back to the liver

where is catabolized and secreted in bile salts.
 Review of transport from GI
from lumen of alimentary tract:
 Micelles
 epithelial absorptive cell of mucosal layer
 endoplasmic reticulum (+lipoprotein)
 As chylomicrons to lacteal
 left thoracic duct
 blood
 Liver (receptor-mediated endocytosis)
 The liver processes fats

• The liver packages fatty acids into forms that

can be transported or stored

• The liver packages triglycerides primarily as

VLDL to be delivered to adipocytes

• LDL is used to transport cholesterol to

peripheral tissues

• HDL brings excess cholesterol back to the liver

where is catabolized and secreted in bile salts.
Processing of fats
 The liver processes vitamins

• Vitamin A is absorbed in the micelle, converted to

retinyl esters and stored in the hepatic stellate cell.
• Vitamin D absorption requires bile salts. The liver
hydroxylates vitamin D for use in bone metabolism.
• Vitamin E absorption also requires bile salts. Some
forms of vitamin E are transported with lipids.
• Vitamin K1 (phylloquinone) is taken up in micelles
incorporated into chylomicrons and used by the
hepatocyte for the final processing of the
coagulation factors (II, VII, IX, X, Prot C and Prot S)
 The liver is a protein factory

• The liver makes albumin, the major serum protein

• The liver makes antitrypsin
– Deficiency of this protein associated with
emphysema in young people
• The liver makes coagulation factors
• The liver makes acute phase proteins such as
haptoglobin, C-reactive protein and acid
glycoprotein.
• The liver makes apolipoproteins used to transport
fatty acids and cholesterol.
 The liver is a hazardous
waste plant
• Most drugs must pass through the liver.
• The liver has a well equipped system of
enzymes to alter drugs and toxins
– Phase 1: Cytochrome P450 system allows for
hydroxylation. Products are more soluble
– Phase 2: Conjugation reactions (e.g.
glutathione S-transferase)
– Phase 3: ATP-binding cassette proteins (e.g.
mdr-1 transports anticancer drugs into bile)
…And perioxisomal conversion of free radicals to H2O2
 Detoxification and
antioxidants
Glutathione (L-gamma-glutamyl-L-cysteine-glycine) :

• The most important antioxidant in the liver.

• In acetominophen overdose this is depleted
(increased CytP450 metabolism with toxic
intermediate that require glutathione), leading
to hepatocyte damage.
• Glutathione levels can be restored by giving
N-acetylcysteine.
 The liver stores iron

• The liver stores approximately 10% of the

body’s iron bound to ferritin (a protein
made by the liver).
• The iron is transferred to transferrin to be
transported in the circulation.
• Heme from dead erythrocytes returns to
the liver where the iron is separated from
the heme molecule is disposed of as
bilirubin.
 The liver is an immune organ

• The liver contains 80% of the body’s

macrophages (Kupffer cells).
– The Kupffer cells phagocytose circulating
bacteria/toxins.
– The Kupffer cells elaborate cytokines.
• The liver also contains Natural Killer cells.
– This is important in controlling viral infections
and atypical cells.
Kupffer cell
 White Blood Cell Production

Pluripotent stem cell

Myeloid stem cell Lymphoid stem cell

Eosinophilic Basophilic Neutrophilic Monoblast Lymphoblast

myeloblast myeloblast myeloblast

Eosinophil Basophil Neutrophil Monocyte Lymphocyte

Granular Agranular
 The liver can regenerate

• If the insult is stopped the liver can heal

• Growth factors such as hepatocyte growth

factors, in conjunction with cytokines tell the
liver to make new cells

• This is why parents can donate a portion of

their liver to children with liver failure.
 The liver produces bile
• Bile is essential for normal lipid digestion
and absorption, cholesterol metabolism
and the excretion of lipid soluble drugs
• Bile is composed of bile acids (salts)
such as phosphatidylcholine,
cholesterol, bilirubin (from old red blood
cells) and electrolytes
• Bile is stored in the gall bladder, and
released via the common bile duct.
• Reabsorbed from the ileum and recycled
 Why do we have a gallbladder?
• The gallbladder is a thin, green sac that is
mostly muscle
• The bile is concentrated (water absorbed)
and stored until needed
• Release triggered by parasympathetic
nervous system and by CCK from
enteroendocrine cells lining the duodenum
• When the gallbladder is the removed the
extrahepatic bile duct expands.
Anatomy reminder
Fats in the duodenum stimulate bile
release
 Why do some people get gallstones?

• More common in obese, females over the age of 40

• In North America the most common gallstones

contain crystallized cholesterol due to increase
dietary cholesterol

• Pain often occurs after eating due to stones

impacting on the cystic duct and associated
gallbladder inflammation.
 Where does the pancreas come in?

• The pancreas contains the ductal system that

drains not only the pancreatic enzymes but also
the bile
– So gallstones can also cause pancreatitis

• The pancreas contains both an exocrine

component but also the endocrine component

• The hormone CCK regulates both the gallbladder

and the exocrine pancreas.
The exocrine pancreas
Acid in the duodenum stimulates the
pancreas

• In response to fatty
acids in the duodenum
the enteroendocrine
cells secrete the
hormone CCK.
• In response to acidic
chyme these other
enteroendocrine cells
secrete the hormone
secretin.
The pancreas tells the liver when to
make glucose available
 The ancients thought ...

the liver was the most important

organ in the body.