Lecture 6 - Secretions II Flashcards
How do bacterial infections of the GIT occur?
If a large enough amount of bacteria make it to the small intestine past the stomach, it provides a very favorable environment for the bacteria to reproduce because it is warm and contains many nutrients
Where are progenitor cells found in the GIT?
- Crypts of Lieberkühn in small intestine
2. Oxnytic glands of the stomach
Describe the pH in the stomach?
Above mucosa: 1.5
In mucous covering of epithelium with HCO3-: 2 to 7
What are the 3 phases of gastric secretions? Describe each.
- Cephalic: “anticipation”-chemo and mechanoreceptors on tongue and buccal canal, nasal mucosa => vagal effects: gastrin, acid, enzymes
- Gastric: food in stomach => vagal and ENS effects: gastrin, acid, enzymes, pH changes
- Intestinal: highly acidic chyme enters duodenum => composition of chyme important => feedback to HCl secretion + decrease gastric emptying
What are intestinal secretions made up of?
- Intestinal mucosal secretions from glands in the crypts of Leiberkuhn: mucus, hormones, enzymes, ions
- Secretions from the pancreas, liver and (indirectly) gallbladder, which travel down the hepatic duct and through the sphincter of Oddi to enter the duodenum
How are ions and water secreted in the intestine?
Via the CFTR (cystic fibrosis transmembrane regulator) which is an ion channel that secretes Cl- in lumen (with Na+ and H2O following via passive diffusion)
What are the 5 major cell types of the small intestine mucosa? Role for each? Where is each found?
- Paneth cells: probably host defense by secreting zinc and lysozymes that attack bacteria (bottom of Crypts of Lieberkuhn)
- Goblet cells: secrete mucus (Crypts of Lieberkuhn and surface of the intestinal villi)
- Endocrine cells: secrete gastrin, CCK, secretin, GIP, motilin, serotonin, etc (along lateral borders of Crypts of Lieberkuhn)
- Brunner’s glands: located in the first part of the duodenum before sphincter of Oddi, they secrete thick mucus and proteases (submucosa)
- Absorptive cells (Crypts of Lieberkuhn and surface of the intestinal villi)
What regulates the Brunner’s glands of the small intestine?
Stimulated by secretin, vagus and inhibited by sympathetic NS
Describe the neural regulation of intestinal secretions.
- Chyme contact and distention will increase secretions (by local, enteric reflexes)
- Parasympathetics will increase and sympathetics will decrease secretions
What determines the amount of hormones released by GIT cells?
Amount of stimulus
Which 2 hormones play an important role at the end of a meal? Why?
CCK and GIP because that is when the concentration of fats is highest (fat floats so it empties from stomach last) and that stimulates both of these: CCK needed because stimulates release of bile, GIP needed because stimulates the uptake of lipids by muscle/adipose
Type of receptors of GIT?
GPCRs
What 2 ions do the ileum and jejunum secrete? Explain how. Purpose?
- H+: Na+/H+ exchangers
- HCO3-: HCO3-/Cl- exchangers (from CO2 metabolism with carbonic anhydrase in cells)
=> help reclaim Na+, Cl-, and H2O
AND once H+ and HCO3- go in lumen they can convert back to H2O and CO2 and diffuse back in the cell to start all over again as many times as necessary to reclaim those molecules
What are the 2 types of pancreatic secretions? Describe each.
- Endocrine: insulin, glucagon, and somatostatin which can affect gastric secretion and motility, in addition to their other systemic effects
- Exocrine: ecbolic secretions, and hydrelatic secretions of acinar cells
What are ecbolic secretions?
Secretions of enzymes
What are hydrelatic secretions?
Secretions of electrolytes
Describe the pancreatic acinar cell types. Where do they empty?
- Acinar: on the outside and produce enzymes
- Centroacinar: on the inside and secrete an electrolyte solution rich in bicarbonate
Secrete through extralobular ducts into the main duct
Does further secretion/reabsorption happen in the ducts of the pancreas?
Yes in extralobular ducts, but not main duct
How are pancreatic proteases stored and secreted?
- Stored as zymogens
2. Secreted as zymogens or as precursors
Types of pancreatic enzymes?
- Proteases
- Amylase
- Lipases
- Pre co-lipase
- Nucleases
What are the major pancreatic proteases? What are they secreted as in the duodenum? What is each activated by?
- Trypsinogen => trypsin (enterokinase and trypsin by autoactivation)
- Chymotrypsinogen => chymotrypsin (trypsin)
- Proelastase => elastase (trypsin)
- Procarboxypeptidases A & B => carboxypeptidases A & B (trypsin)
Which is more active: salivary or pancreatic amylase?
Pancreatic
3 pancreatic lipases? 3 names for first one. What to note?
- Pancreatic lipase = glycerol ester hydrolase/lipase = triacylglycerol hydrolase
- Cholesterol esterase
- Phospholipase A2 (secreted as prophospholipase)
Role of pre co-lipase? How is it activated?
Co-factor for pancreatic lipase and activated by trypsin
Where does enterokinase come from?
Secreted by duodenal cells
Role of pancreatic trypsin inhibitor? Other name?
Fire extinguisher to keep trypsin from being activated in pancreas and its ducts (very small amount found in small intestine)
= monitor peptide
Consequence of loss of trypsin inhibitor?
Pancreatitis
Primary stimuli for pancreatic secretions? What does each stimulate?
- CCK and insulin: enzymes by acinar cells
2. Secretin/vagovagal reflexes: buffers by centroacinar cells
3 colonic secretions? Describe each and what stimulates it.
- Mucus: goblet cells on surface and in crypts; stimulated by contact, parasympathetic NS, and ENS
- Bicarbonate: secretion through a HCO3-/Cl- exchanger to buffer chyme made acid from luminal bacterial action
- Potassium: Na+ will be reabsorbed and K+ can be secreted (stimulated by aldosterone); this can accompany mucus secretion or also K+ secreted from lysed cells and dead bacteria
Why is it good that MMC pushes bacteria out of small intestine and into colon?
Dryer with fewer nutrients
Which GIT secretions are closest to being isosmotic at all secretion rates?
Pancreatic and bile juices
2 regions of in the small intestine mucosa? Main differences between the 2?
- Brush border villus cells
- Crypts of Lieberkuhn cells
Difference:
- Brush border villus cells have abundant expression of hydrolases on the glycocalyx for final digestion of proteins and carbs
- Brush border villus cells have high nutrient transport
- Brush border villus cells absorb vs crypts secrete
- Brush border villus cells have a low permeability
What happens during cystic fibrosis? Treatment?
CTFR is missing and mucus is not fluid enough => pancreatic juices cannot be diluted => damage to the pancreatic ducts (dilation + fibrosis)
Pancreatic enzyme supplements to relieve the symptoms of exocrine pancreatic insufficiency
What happens with celiac disease?
Reduced brush border with decreased absorption capacity of carbs and proteins because lack of brush border hydrolases => malabsorption => bacterial production of gases, diarrhea, cramps, and vitamin deficiencies
Do lipids need brush border enzymes for absorption in small intestine?
NOPE
Why is there a blood rise in insulin before a rise in glucose?
Because GIP secretion by duodenum and jejunum is stimulated by contents of food to prepare the body to receive glucose
What % of digestion happens pre-duodenally?
25-30%
What % of digestion happens due to pancreatic enzymes?
70-75%
Other name for enterokinase?
Enteropeptidase
What happens to pancreatic secretions at the end of the meal?
They cease when chyme is in lower GIT because of:
- Reduction in vagal stimulation/secretin since no chyme in upper GIT
- Somatostatin
- Glucagon
- Pancreatic polypeptide
- Peptide YY
What happens to electrolytes during diarrhea?
- Buffer secretion loss => acidemia
- Lack of Na+/H2O being reabsorbed => dehydration
- Loss of K+
Preferred pH of pancreatic enzymes?
Neutral
Role of pancreatic nucleases?
Break nucleic acids into purine and pyrimidine bases
How is phospholipase A2 activated?
Trypsin
Which is secreted first during digestion: GLP-1 or peptide YY?
GLP-1
What are the 5 duodenal hormones that are secreted in response to the presence of chyme?
- Gastrin
- Secretin
- CCK
- GIP
- Somatostatin
What are the 4 jejunal hormones that are secreted in response to the presence of chyme?
- CCK
- GIP
- GLP-1
- Peptide YY
What is the one ileal hormone that is secreted in response to the presence of chyme?
Peptide YY
In the SI can Na+ enter the lumenal membrane via the Na+/K+-ATPase?
NOPE, only on basolateral membrane
In the SI can Na+ enter the lumenal membrane via simple diffusion?
YUP