GI Secretions Part 2: Intestine, Pancreas, Liver, Gallbladder

Question 1

the SI is comprised of 3 sections: what are they and give a brief description of each

Answer 1

Duodenum -receives stomach contents, pancreatic juice and bile, neutralizes stomach acids, emulsifies fats, pepsin inactivated by pH increase, pancreatic enzymes

• Jejunum -most nutrient absorption occurs here

Ileum- has peyer’s patches – aggregated lymphoid nodules
( form an important part of the immune system by monitoring intestinal bacteria populations and preventing the growth of pathogenic bacteria in the intestine)

Question 2

What are the 3 features that contribute to increasing the SA of the SI? and give a brief description of each
look at slide 5

Answer 2

Villi- are finger like projections
contain blood vessels and lymphatics (lacteal)
nutrient absorption

Microvilli- 1 micron tall
cover surface
brush border enzymes for final stages of digestion

The crypt-villus unit- is the functional unit of the small intestine. Stem cell division produces immature cells in crypts of Lieberkühn which secrete intestinal fluid; mature cells at the villus tip absorb nutrients, electrolytes, and fluid.

Question 3

what types of cells are in the villi-divide into crypt and tips zone

Answer 3

Intestinal glands, intestinal crypts
Paneth cells (lysozyme)
Enterocytes (secrete 1.5L water and electrolyte, isotonic with plasma)
Enteroendocrine cells:
I (CCK-Cholecystokinin- stimulates gallblader to release bile)
D (somatostatin)
S (secretin –stimulates pancreas to release acid neutralizer bicarbonate

Tip- Goblet cells (mucus- lubricates and protects intestinal surface)
Enterocytes with brush border - enzymes (disaccharidases and polypeptidases) including

Progenitor cell – differentiates into specialized cells (e.g. Paneth or goblet cell

Question 4

what is the villi divided into

Answer 4

Submucosa and mucosa
sub-mainly vessels-VAN
mucosa-muscles, crypts,blood cappilaries

Question 5

Dysfunction in small intestine absorption?

Answer 5

Celiac sprue:The denuded small intestine results in malabsorption of nutrients, causing diarrhea (excess fecal fluid) and steatorrhea (excess fecal fat), with associated abdominal bloating and flatulence.

Question 6

function of pancreas in digestion

Answer 6

secretes an alkaline fluid (pH ~8-8.3) that neutralizes the acidic chyme that enters the small intestine from the stomach. This fluid is necessary because pancreatic enzymes have a neutral pH optimum

to secrete the enzymes that break down the macromolecules in food and to produce smaller nutrient molecules for intestinal absorption

• The pancreas has a separate endocrine function to secrete the hormones (e.g. insulin and glucagon) involved in metabolic regulation

Question 7

Pancreas has 2 types of function: Please explain each

Answer 7

Exocrine glands (digestive function, 80% of pancreas volume, structure is similar to that of the salivary glands)
Made up of acinus (secrete digestive enzymes) and duct cells (secrete bicarbonate)
The exocrine glands deliver  digestive enzymes and an isotonic HCO3- ion rich secretion into the intestinal lumen.

Endocrine glands (metabolic function)
     -  consist of ~ 4 types of islet cells that releases hormones (e.g. insulin and glucagon to control blood sugar levels)

Question 8

Dysfunction of endocrine pancreas

Answer 8

Diabetes develops when the pancreas does not make enough insulin, the body’s cells do not use insulin effectively, or both. As a result, glucose builds up in the blood instead of being absorbed by cells in the body.

T1- immune-Beta cells
T2-Insulin resistance

Question 9

Composition of pancreatic juices

Answer 9

Proteolytic enzymes-80%

Amylolytic Enzymes

Nucleases

Lipolytic Enzymes

Question 10

How are enzymes and alkali of pancreatic secretions regulated ?

Answer 10

Enzyme secretions:
Ach (Acetylcholine) - binds muscarinic receptor on acinar cells, Ach/Vasoactive Intestinal Peptide (VIP) increase blood flow, and gastrin (gastric phase)
CCK (Cholecystokynin) - the major agonist - released from duodenal I cells when food enters duodenum in response to
Fats, monoglycerides, Fatty Acids
AAs phenylalanine, tryptophan

lkaline secretions:
Secretin - released by S cells in duodenum. S cells stimulated by low pH as food enters, secretin enters blood - duct cells
pH rarely low enough to stimulate high levels of secretin. Duct cells become “hypersensitive” to low levels of hormone - CCK (and Ach in early phases) potentiate action of secretin

Question 11

Acinar cells are rich in

Duct cells are rich in secretions

Answer 11

enzymes and CL- secretions

HCO3-

Question 12

Biochemical mechanisms to secretions by acinar cells

Answer 12

Pancreatic enzymes are synthesised as inactive proenzymes on ribosomes and transferred into rER – Golgi complex – acidic condensing vacuoles and zymogen granules.

Upon stimulation by agonists (such as CCK Ach, or secretin), Release of content into the lumen via
intracellular 2nd messengers: [Ca2+]i and [cAMP]

leads to fusion and exocytosis of zymogen granules.

, zymogen granules move to apical membrane, fuse with plsma membrane and sicharge their content into luminal space

Question 13

What prevents auto digestion

Answer 13

1. Zymogens are made in an inactive form
2. Cellular sequestration of zymogen granules
3. Co-packaging of trypsin inhibitor, prevents following process from occurring in the pancreas:The process depends on the conversion of the proenzyme trypsinogen to the active proteolytic enzyme trypsin. Trypsinogen is cleaved by the enzyme enterokinase, which is bound to the apical cell membranes of enterocytes lining the small intestine.
4. Geographical separation of sites of zymogen release and activation

Question 14

Dysfunction of enzyme activation

Answer 14

Pancreatitis occurs when pancreatic enzymes are activated within the pancreas (and surrounding tissues), resulting in autodigestion of the tissues

Question 15

secretions of pancreatic duct cells

Answer 15

Neutralize acidic chymes entering duodenum
Provide optimum pH for pancreatic enzyme function
Protects the mucosa from erosion by acid

Question 16

Mechanism of HCO3- secretion by ductal cells

Answer 16

1. HCO3− secretion from the cell cytoplasm into the lumen occurs via the Cl−/HCO3− exchange in the luminal cell membrane.
2. To supply enough intracellular Cl− to sustain the rate of Cl−/HCO3− exchange, Cl− is recycled from the lumen into the cell via the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel.
3. Na+ is secreted into the duct lumen following HCO3− secretion; water follows by osmosis to produce fluid secretion.

Question 17

IONIC COMPOSITION of pancreatic juice during secretion

Answer 17

The greater the rate of secretion, the higher the HCO3- levels (& Na+ constantly highest) and the lower Cl- levels (& K+ constantly lowest)

Question 18

Dysfunction in ductal Cl- channel

Answer 18

Patients with cystic fibrosis lack a functional Cl− channel in the luminal membrane, which results in defective ductal fluid secretion. The ducts become blocked with precipitated enzymes and mucus and the pancreas undergoes fibrosis - resulting in malabsorption

Question 19

Dysfunction in ductal Cl- channel

Answer 19

Patients with cystic fibrosis lack a functional Cl− channel in the luminal membrane, which results in defective ductal fluid secretion. The ducts become blocked with precipitated enzymes and mucus and the pancreas undergoes fibrosis - resulting in malabsorption

Question 20

regulation of pancreatic secretions-

Answer 20

Slide 29

Question 21

Functions of bile (exocrine secretion of liver stored in gall bladder)

Answer 21

• Provides alkali to neutralise acid (It assists in neutralizing gastric acid because it is an alkaline solution)
• Provides bile salts to facilitate absorption of fats
• Acts a vehicle for the excretion of breakdown of blood cell components

Question 22

what is the composition of bile

Answer 22

Water
Ions
Bilirubin & biliverdin
Bile salts

Question 23

Hepatocytes secrete hepatic bile into

Answer 23

the blind ended canaliculi - drain into bile ducts, then stored in gall bladder

Question 24

In the gall bladder

Answer 24

bilirubin pigment from hemoglobin breakdown
intestinal bacteria convert to urobilinogen = brown color
bile acid (salts) emulsify fats and aid in their digestion
enterohepatic circulation - recycling of bile acids from ileum

Question 25

What is the Biliary tree

Answer 25

From,- Hepatocytes secrete bile into the canaliculi-Canaliculi join together and convey hepatic bile toward small terminal ductules at the periphery of the liver lobules.

• emerges in a hepatic duct.
• The hepatic ducts from each lobe join outside the liver to form the common hepatic duct
• cystic duct from the gallbladder joins the common hepatic duct to form the common bile duct.

Question 26

As hepatic bile travels along ducts

Answer 26

, HCO3- secreted by duct epithelium

Question 27

Bile made of 2 distinct fractions through different mechanisms

Answer 27

Bile acid-dependent fraction (hepatic bile) made by hepatocytes when sufficient bile acids available

Bile acid-independent fraction produced by duct epithelium - by secretion of water and electrolytes (HCO3- rich)

Question 28

Describe enterohepatic circulation

Answer 28

After functioning (fat absorption), 25% bile deconjugated by bacteria during length of ileum.  
Conjugated bile acids (solid line) completely reabsorbed by terminal ileum and returned by hepatic portal vein in entero-hepatic circulation.
Deconjugated acids also returned (dotted line), but fraction converted into lithocholic acid by bacteria lost to faeces

Question 29

rate of acid-dependent secretion depends on …

Answer 29

rate returned via enterohepatic circulation

Question 30

Control of bile release

Answer 30

Minor role of vagus

Major - CCK is released from duodenum on presence of fatty and acidic chyme

CCK stimulates emptying of gall bladder and relaxation of sphincter of Oddi

Question 31

Dysfunction of gallbladder

Answer 31

Cholecystitis :is blockage of the cystic duct with associated infection of the gallbladder.

Choledocholithiasis: is blockage of the common bile duct.

Ascending cholangitis: is blockage of the common bile duct with associated infection of the bile duct