GI secretions (Part 2) - Intestine, pancreas, liver and gallbladder Flashcards
Function of the duodenum
Receives stomach contents, pancreatic juice and bile, neutralises stomach acids, emulsifies fats, pepsin inactivated by ph increase, pancreatic enzymes
Function of the jejunum
Most nutrient absorption occurs here
What are pever’s patches?
Aggregated lymphoid nodules which are found throughout the ileum region of the small intestine
They also form an important part of the immune system by monitoring intestinal bacteria populations and preventing the growth of pathogenic bacteria in the intestine
What is the product of the SI called?
Succus entericus
What are villi?
Fingerlike projections 1mm tall which contain blood vessels and lymphatics(lacteal) nutrient absorption
What are microvilli?
1 micron tall; cover surface brush border on cells. Brush border enzymes for final stages of digestion
What is the crypt-villus unit?
The functional unit of the small intestine
Stem cell division produces immature cells in crypts of lieberkuhn which secrete fluid; mature cells at the villus tip absorb nutrients, electrolytes and fluid
What is there at the villus tip?
- 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
What is the maturation zone?
The maturation zone is an intermediate zone where cells are moving toward the tip of the villus and are beginning to express enzymes and absorptive membrane transport proteins
What is the crypt?
- Crypt contains rapidly dividing stem cells that force migration of cells up the side of the villus
- The cells initially produced in the intestinal crypts are immature and do not express enzymes or membrane transporters for nutrient absorption
How can you identify the duodenum in histology?
- Brunner glands, which empty into the intestinal glands, secrete an alkaline fluid which exerts a phsyiologic anti-acid function by coating the duodenal epithelium, therefore protecting it from the acid chyme of the stomach
- Brunner’s glands in submucosa
How can you identify the jejunum in histology?
- Extensive intestinal folds
- Main site of absorption
How can you identify the ileum in histology?
- Contains peyer’s patches (intestinal immune system)
What is celiac sprue
A malabsorption syndrome caused by hypersensitivity to wheat gluten and gliadin, resulting in immune-mediated destruction and denudation of the small intestinal villi
What are the effects of celiac sprue
- Malabsorption of nutrients causing diarrhoea and steatorrhoea(excess fecal fat) with associated abdominal bloating and flatulence
What is the function of pancreas in digestion?
- Secretes about 1.5l of juices
- Secretes an alkaline fluid that neutralises 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 a separate endocrine function to secrete insulin and glucagon involved in metabolic regulation
What do the exocrine glands of the pancreas secrete?
- Secretions delivered to the duodenum via the large pancreatic duct
- 1-2L of pancreatic juice is secreted per day
- 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
Describe the endocrine glands of the pancreas
- Consist of 4 types of islet cells that releases hormones
- Secretions delivered to blood stream
What is the composition of pancreatic juices?
- Proteolytic enzymes
- Amylolytic enzymes
- Nucleases
- Lipolytic enzymes
What are the enzyme secretions of the pancreas?
Ach - binds muscarinic receptor on acinar cells, Ach/vasoactive intestinal peptide increase blood flow, and gastrin
CCK - The major agonist released from duodenal I cells when food enters duodenum in response to fats, monoglycerides, fatty acids, AAs
What are the alkaline secretions of the pancreas?
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 actions of secretin
What is the mechanism of enzyme secretions by acinar cells?
- Appropriate signal leads to fusion and exocytosis of zymogen granules
- Zymogen granules move to apical membrane, fuse with plasma membrane and discharge their content into luminal space by the process of exocytosis
– Upon stimulation by agonists(such as CCK, Ach, or secretin), release of content into the lumen via intra
Prevention of pancreatic autodigestion
- Most enzymes are produces 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 , this process depends on the conversion of the proenzyme trypsinogen to the active protelytic enzyme trypsin
Which enzyme cleaves trypsinogen
Enterokinase, which is bound to the apical cell membranes of enterocytes lining the small intestine
What does trypsin do once activated?
It cleaves and activates all other zymogens
What is the trypsin inhibitor for?
The trypsin inhibitor is produced by the pancreas to prevent activation of zymogens within the pancreas if trypsin is inappropriately activated inside the gland
What is pancreatitis?
Occurs when pancreatic enzymes are activated within the pancreas, resulting in autodigestion of the tissues
What are the most causes of pancreatitis?
Gender specific and include gallstones in women and alcohol use in men
What is pain from pancreatitis like?
Classically described as epigastric pain radiating from the epigastrium to the back and is often relieved by leaning forward
Mechanism of isotonic NaCl primary secretion by acinar 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 provides 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
What are potent stimulators of Cl- secretion?
The hormone CCK and the cholinergic neurotransmitter acetylcholine
What are the secretions of the pancreatic duct cells?
- Duct cells secrete 1-2l of alkaline(HCO3- rich) fluid into the duodenum per day which
Provides optimum pH for pancreatic enzyme function
Protects the mucosa from erosion by acid
What is the mechanism of HCO3- secretion by pancreatic 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
Relation between rate of secretion and concentrations of HCO3- and Cl- levels
The greater the rate of secretion, the higher the HCO3- levels and the lower Cl- levels
What is the flow rate at an unstimulated state
Low and electrolyte composition is similar to that of plasma
What is the flow rate at a stimulated state
Flow rate increases and the rise in [HCO3-] ion in the secondary secretion is matched by reciproacal decline in Cl- ion
Purpose of bile
- Provides alkali to neutralise acid
- Provides bile salts to facilitates absorption of fats
- Acts as a vehicle for excretion of breakdown of blood cell components(provides a pathway to excrete hydrophobic molecules that may not be readily excreted by the kidney)
Composition of bile
- Water
- Ions
- Bilirubin and biliverdin
- Bile salts
Production and functions of bile salts
- Synthesized from cholesterol
- Required for emulsification of and absorption of lipids, cholesterol and phospholipids
What is enterohepatic circulation
Recycling of bile acids from ileum
What is urobilinogen?
Intestinal bacteria convert bilirubin pigment from haemoglobin breakdown
What does the gall bladder do to the bile?
Concentrates bile salts
What is bile acid-dependent fraction
Made by hepatocytes when sufficient bile acids available
What is bile acid-independent fraction
produced by duct epithelium - by secretion of water and electrolytes (HCO3- rich)
What acids are produced from primary bile salts
From cholesterol metabolism - generates cholic acid and chenodeoxycholic acid
Which acids are produced from secondary bile acids?
- Small amount of secondary bile acids formed by bacteria converting small amount of primary acids (deoxycholic and lithocholic acid)
