Intestines, Liver, Gallbladder and Pancreas Secretions

Question 1

Describe the structure of the small intestine and the function 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

Question 2

What is the overall function of the small intestine

Answer 2

Completion of the chemical digestion of ingested food and subsequent nutrient absorption.

Question 3

What secretions does the small intestine receive and secrete?

Answer 3

It produces succus entericus and receives secretions from the liver/gall bladder and exocrine pancreas.

Question 4

What is the function of secretions in the small intestine?

Answer 4

Secretions facilitate the chemical digestion of ingested food in the SI.

Question 5

What is chemical digestion?

Answer 5

Chemical digestion is the complex series of enzymatic reactions that convert dietary macromolecules into their corresponding sub units that can then be absorbed by enterocytes primarily in the jejunum.

Question 6

What increases the surface area of the small intestine?

Answer 6

Circular folds, Villi, and Microvilli

Question 7

What are villi?

Answer 7

Contain blood vessels and lymphatics (lacteal)

nutrient absorption

Question 8

What are microvilli?

Answer 8

Cover surface
Brush border on cells
Brush border enzymes for final stages of digestion

Question 9

What is the crypt villus unit?

Answer 9

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

Question 10

Describe the enterocytes at the villus tip

Answer 10

At the villus tip, enterocytes are fully differentiated and undertake the absorption of nutrients, electrolytes, and fluid. After 3–4 days, the cells are sloughed off the villus tip as a defense mechanism against insults from the luminal contents

Question 11

What is the maturation zone?

Answer 11

The maturation zone is an intermediate zone where cells are moving toward the tip of the villus and are beginning to expresses enzymes and absorptive membrane transport proteins.

Question 12

Describe crypt cells

Answer 12

The crypt contains rapidly dividing stem cells that force migration of cells up the side of a villus. The cells initially produced in the intestinal crypts are immature and do not express enzymes or membrane transporters for nutrient absorption. Crypt cells are the source of intestinal fluid secretion.

Question 13

What is the function of columnar epithelium cells in both villi and crypts?

Answer 13

In villi - nutrient and electrolyte absorption

In crypts – secretion

Question 14

What is found in the crypts of lieberkuhn between villi?

Answer 14

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

Question 15

What cells are found in the villi?

Answer 15

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

Question 16

Where are brunner glands found and what do they do?

Answer 16

Brunner glands, which empty into the intestinal glands, secrete an alkaline fluid(i.e. bicarbonate mucus) which exerts a physiologic anti-acid function by coating the duodenal epithelium, therefore protecting it from the acid chyme of the stomach. Brunner’s glands in submucosa

Question 17

What is celiac sprue?

Answer 17

A malabsorption syndrome caused by hypersensitivity to wheat gluten and gliadin, resulting in immune-mediated destruction and denudation of the small intestinal villi. 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. Removal of gluten from the diet will resolve the condition. However, resolution of the malabsorption will not occur immediately upon dietary change because the crypt cells require a few days to mature and rebuild the absorptive intestinal villi

Question 18

What do the pancreatic duct and bile duct unite into? Name the sphincter controlling the duct

Answer 18

Pancreatic duct and Bile duct unite into hepatopancreatic duct, which enters the duodenum.
The entrance of this common duct into duodenum is controlled by the Sphincter of Odi.

Question 19

Describe the function of the pancreas in digestion

Answer 19

• secretes about 1.5l of juices
• 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.
• Has highest digestive power
• The pancreas has a separate endocrine function to secrete the hormones (e.g. insulin and glucagon) involved in metabolic regulation

Question 20

Describe the functional anatomy of the pancreas

Answer 20

Pancreas is basically 2 organs in one structure:

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)
secretions delivered to the duodenum via the large pancreatic duct)
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)
- secretions delivered to blood stream

Question 21

Give an example of dysfunction of the endocrine pancreas

Answer 21

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.

In type 1 diabetes, the beta cells of the pancreas no longer make insulin because the body’s immune system has attacked and destroyed them.
Type 2 diabetes usually begins with a condition called insulin resistance, in which the body has trouble using insulin effectively. Over time, insulin production declines as well, so many people with type 2 diabetes eventually need to take insulin.

Question 22

Give an example of a theoretical treatment currently being researched for diabetes

Answer 22

Pancreatic islet transplantation

Question 23

List the composition of pancreatic juices

Answer 23

Water, electrolytes and enzymes
Secreted enzymes are essential for digestion and absorption of ingested nutrients

Proteolytic enzymes make up the majority of proteins that are secreted by pancreatic acinar cells

Question 24

Describe the cellular origins of pancreatic secretions

Answer 24

Exocrine functions - The exocrine glands deliver digestive enzymes and an isotonic HCO3- ion rich secretion into the intestinal lumen.
Lobules
Blind-ended acini
Acinar cells make up 80% of all pancreas cells
secrete enzymes and Cl- rich secretion
Duct cells secrete HCO3-

Question 25

Describe the regulation of enzyme secretions in acinus and duct

Answer 25

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

Question 26

Describe the regulation of the alkaline secretions in acinus and ducts

Answer 26

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 27

Describe the mechanism of enzyme sections by acinar cells

Answer 27

Enzymes made on ribosomes attached to rough ER. 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]i
Appropriate signal leads to fusion and exocytosis of zymogen granules. After an appropriate neural or hormonal stimulus, zymogen granules move to apical membrane, fuse with plasma membrane and discharge their content into luminal space by the process of exocytosis

Question 28

How does the pancreas prevent self digestion?

Answer 28

• Most enzymes are produced as inactive precursors called zymogens.
• Enzymes are sequestered in membrane-limited vesicles throughout synthesis to the point of exocytosis, avoiding contact with the acinar cell cytoplasm.
• Activation of zymogens occurs in the small intestine. 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. Once trypsin is activated, it cleaves and activates all other zymogens.
  The pancreas produces a trypsin inhibitor to prevent activation of zymogens within the pancreas if trypsin is inappropriately activated inside the gland.

Question 29

What is pancreatitis?

Answer 29

Pancreatitis occurs when pancreatic enzymes are activated within the pancreas, resulting in autodigestion of the tissues. The most common causes of pancreatitis are gender specific and include gallstones in women and alcohol use in men. Pancreatitis is a painful condition, and is classically described as an epigastric pain radiating from the epigastrium to the back and is often relieved by leaning forward.

Question 30

What is the function of the secretions of pancreatic duct cells

Answer 30

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

Question 31

Describe the mechanism of Na+ and HCO3- secretions by ductal cells

Answer 31

HCO3− secretion from the cell cytoplasm into the lumen occurs via the Cl−/HCO3− exchange in the luminal cell membrane.

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.

Na+ is secreted into the duct lumen following HCO3− secretion; water follows by osmosis to produce fluid secretion.

Question 32

How does the ionic concentration of pancreatic juice depend on the rate of secretion?

Answer 32

The greater the rate of secretion, the higher the HCO3- levels and the lower Cl- levels

The ionic composition of panreatic juice depends on the rate of secretion.

In the unstimulated state - flow is low & electrolyte composition is similar to that of plasma.

In the stimulated state - flow rate increases and the rise in [HCO3-] ion in the secondary secretion is matched by reciprocal decline in [Cl-] ion.

Question 33

Give an example of dysfunction of the CL- channel

Answer 33

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. Blocked ducts impair secretion of needed pancreatic enzymes for digestion of nutrients, resulting in malabsorption. Treatment of this type of malabsorption includes oral pancreatic enzyme supplements taken with each meal.

Question 34

How does the cephalic phase regulate the secretion of pancreatic juice?

Answer 34

The sight, smell, thought of food trigger action potentials in higher brain centres – stimulate preganglionic vagal fibres to transmit AP to postganglionic fibres:
Ach increases 1˚ secretion from the acinar cells
Ach increases HCO3- ion secretion from the duct cells into intercalated ducts

Question 35

How does the gastric phase regulate the secretion of pancreatic juice?

Answer 35

Peptones in the stomach antrum stimulate gastrin release from G cells – increases acinar secretion as in the cephalic phase.

Increase in gastrin release from G cells via vagal peptidergic, postganglionic efferents (GRP) that stimulate pancreatic acinar cells to increase secretion of enzymes via cholecystokinin (CCK)A receptor

Gastric distension – vago-vagal reflex

Question 36

How does the intestinal phase regulate the secretion of pancreatic juice?

Answer 36

Accounts for about 70% of pancreatic juice secretion during a digestive period, stimulated by chyme entry into the duodenum

Protons (from stomach gastric acid) stimulate duodenal S cells to increase secretion of secretin – secretin increases HCO3- ion secretion from the duct cells.

Monoglycerides, fatty acids and amino acids induce CCK release from duodenal I cells – CCK promotes 1˚ enzyme rich secretion from the acinar cells.

Lipids and proteins trigger a vago-vagal (enteropancreatic) reflex that increases pancreatic juice secretion.

Question 37

List some functions of bile

Answer 37

Provides alkali to neutralise acid
Provides bile salts to facilitate absorption of fats
Acts a vehicle for the excretion of breakdown of blood cell components

Question 38

Give the composition of bile

Answer 38

Water
Ions
Bilirubin & biliverdin
Bile salts

Question 39

State the production and function of bile salts

Answer 39

Synthesized from cholesterol

Required for emulsification of and absorption of lipids, cholesterol and phospholipids.

Question 40

Where is bile secreted from in the liver?

Answer 40

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

Question 41

What is bilirubin formed from?

Answer 41

hemoglobin breakdown

Question 42

Describe the biliary tree

Answer 42

Hepatocytes secrete bile into the canaliculi, which are small 1-µm spaces bounded by neighboring hepatocytes.

Canaliculi join together and convey hepatic bile toward small terminal ductules at the periphery of the liver lobules.

Bile moves through a sequence of progressively larger ducts in each lobe of the liver and emerges in a hepatic duct.

The hepatic ducts from each lobe join outside the liver to form the common hepatic duct.

The cystic duct from the gallbladder joins the common hepatic duct to form the common bile duct.

Question 43

Describe the movement of bile from the liver to the duodenum

Answer 43

Bile is secreted by the hepatocyte canaliculus, undergoes modification in the bile ducts, is concentrated and stored in the gallbladder, and is ultimately excreted into the duodenum

Question 44

What is found in hepatic bile?

Answer 44

Bile salts (acids)
Bile pigments
Cholesterol
Lecithin
Mucus
Electrolytes

Question 45

Give the pH of hepatic bile

Answer 45

Isotonic 7.0-8.0

Question 46

How does the composition of hepatic bile change in the gallbladder?

Answer 46

Concentrates bile salts

Question 47

Describe the 2 distinct mechanisms which make the fractions of bile secretion

Answer 47

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 48

Describe primary and secondary secretions of bile salts

Answer 48

Hepatic cells secrete primary bile salts -
From cholesterol metabolism - generates cholic acid and chenodeoxycholic acid
These conjugated with taurine or glycine and Na+ to make water soluble (bile salts) and then secreted from hepatocytes
In intestine, small amount of secondary bile acids formed by bacteria converting small amount of primary acids

Question 49

Describe the process of enterohepatic circulation

Answer 49

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
Process is 94% efficient – use 20X ! 
Thus rate of acid-dependent secretion depends on rate returned via enterohepatic circulation

Question 50

What causes hepatic jaundice?

Answer 50

Hepatic jaundice (hyperbilirubinea) accumulation of bilirubin in blood
Impaired uptake by hepatocytes
Failure to conjugate bilirubin
As seen in hepatitis and cirrhosis

Question 51

What controls bile release?

Answer 51

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 52

List some common dysfunctions of the gallbladder

Answer 52

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