Lecture 8 Flashcards
What is the structure and function of the small intestine
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
( peyer’s patches are small masses of lymphatic tissue found throughout the ileum region of the small intestine; form an important part of the immune system by monitoring intestinal bacteria populations and preventing the growth of pathogenic bacteria in the intestine)
Collectively, the SI is responsible for the completion of the chemical digestion of ingested food and subsequent nutrient absorption.
It produces succus entericus and receives secretions from the liver/gall bladder and exocrine pancreas.
Secretions facilitate the chemical digestion of ingested food in the SI.
Define the crypt-villus unit
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.
Define the maturation zone
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.
Explain the crypt
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.
Discuss the different intestinal secretions
Crypts of Lieberkuhn between villi
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 )
Villi Goblet cells (mucus- lubricates and protects intestinal surface)
Enterocytes with brush border - enzymes (disaccharidases and polypeptidases) including enteropeptidase
What are the histological differences between the duodenum, jejunum and ileum
Duodenum
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
Jejenum
extensive intestinal folds
- main site of absorption
Ileum
contains peyer’s patches - intestinal immune system
State and explain a dysfunction in small intestine absorption
Celiac sprue is 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.
Describe the function of pancreas in digestion
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
Describe the functional anatomy of pancreas
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)
consisting of a mixture of secretions from the acini and ducts,
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) (islets of Langerhans- discovered in 1869 by German pathological anatomist Paul Langerhans. ) -secretions delivered to blood stream
State and describe a dysfunction of endocrine pancreas
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. The immune system protects people from infection by identifying and destroying bacteria, viruses, and other potentially harmful foreign substances. A person who has type 1 diabetes must take insulin daily to live. 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.
Possible treatment currently in clinical stage trial is
Pancreatic islet transplantation
Describe the composition of pancreatic juices
Proteolytic enzymes make up the majority of proteins that are secreted by pancreatic acinar cells
Lipolytic enzymes, amykikytic enzymes, nucleases, procolipase, trypsin inhibitor
Describe the cellular origin of pancreatic secretions
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-
Explain how pancreatic secretions are regulated in the acinus and duct
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
Alkaline 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
Describe the mechanism of enzyme secretion by acinar cells
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 release their content into luminal space by the process of exocytosis
Describe the prevention of pancreatic auto digestion
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.
State and describe a dysfunction in pancreatic enzyme activation
Pancreatitis occurs when pancreatic enzymes are activated within the pancreas (and surrounding tissues), 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.
Describe the mechanism of isotonic NaCl primary secretion by acing cells
- The Na-K pump creates the inwardly directed Na+ gradient across the basolateral membrane.
- The Na/K/Cl cotransporter produces the net CL- uptake, driven by the Na+ gradient, which is generated by the Na-K pump
- The rise in intracellular [K+] that results from the activity of the pump and cotransporter is shunted by basolateral K+ channels that provide an exit pathway for K+.
- The intracellular accumulation of Cl- establishes the electrochemical gradient that drives Cl- secretion into the acinar lumen through apical membrane Cl- channels.
- Movement of Cl- into the lumen makes the transepithelial voltage more lumen negative, driving Na+ into the lumen via the tight junctions.
Explain the role of the secretions of the pancreatic duct cells
Neutralize acidic chymes entering duodenum
Provide optimum pH for pancreatic enzyme function
Protects the mucosa from erosion by acid
Explain the mechanism of HCO3- secretion by ductal cells
- 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.
How does the ionic composition of pancreatic juice depends on rate of secretion
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 2 secretion is matched by reciprocal decline in [Cl-] ion.
State and describe a dysfunction in ductal Cl- channel
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 (hence the name of the disease). 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.
Explain the regulation of pancreatic juice secretions
Cephalic Phase (accounts for 20% of total)
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
Gastric Phase (accounts for 10% of total)
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
Intestinal Phase
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.
What are the bile functions?
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
(It facilitates the assimilation of dietary lipid; approximately 50% of dietary lipid appears in feces if bile is excluded from the small intestine. Bile facilitates fat digestion by promoting its emulsification and solubilization. This is achieved through the formation of mixed micelles, which enhance lipase action and then assist in the delivery of the digestive products to be absorbed by the enterocytes.)
Acts a vehicle for the excretion of breakdown of blood cell components (It provides a pathway to excrete hydrophobic molecules that may not be readily excreted by the kidney.
Describe the composition of bile
Bile composition: Water Ions Bilirubin & biliverdin Bile salts
Production and functions of bile salts:
Synthesized from cholesterol
Required for emulsification of and absorption of lipids, cholesterol
and phospholipids.
