Physiology - Odes Flashcards
Endocrine regulators of the GIT
gastrin, motlin, secretin, peptide YY (PYY, peptide tyrosine tyrosine), cholecystokinin (CCK), glucagon and related gene products
Neuroendocrine regulators of the GIT
Acetylcholine, vasoactive intestinal polypeptide (VIP), substance P, CCK, somatostatin (SST-secreted by D cells in the body and antrum), calcitonin gene-related peptide (CGRP), serotonin (5-hydroxytryptamine))
Paracrine regulators of the GIT
Histamine, prostaglandins, somatostatin (released from D cells in the Body and antrum), serotonin (5-hydroxytryptamine)
Hormones in the antrum
Gastrin 17 (more active), 34 (less active except in tumors): protein, amino acids. Stimulated by an unknown mechanism involving protein in the stomach. Secreted by G cells.
Somatostatin: neural (stimulated by the enteric NS). Controls gastin secretion. Secreted from D cells, also in the
Hormones secreted in the duodenum and jejunum
Secretin: stimulated by free fatty acids and HCl and acid in the duodenum in general.
CCK (cholecystokinin) stimulated by FFAs >12C and amino acids
Somatostatin
Motilin (ENS)
PYY (FFA, CCK, vagus)
Pathway of Gastrin 17 and 34
Seecreted by G-cells
Receptor: CCK-B (produced in islet cells of the pancreas, stronger effect than CCK)
Intracellular action through G-proteins and calcium
Pathway of CCK
Secreted by I-cells in the intestines, not the stomach
Receptor: CCK-A (mainly in pancreas) and CCK-B (weaker)
Intracellular action through T-proteins and calcium
Pathway of somatostatin
Secreted by D cells in the body and antrum
Mechanism through G-proteins and cAMP intracellularly
Pathway of Secretin
Produced only in intestines, secreted by S-cells
Mechanism through G-proteins and cAMP
PYY pathway
Candidate hormone secreted by L-cells only in the intestines (duodenum and jejunum in response to FFAs, CCK and vagal stimulation, not stomach) including the colon stimulated by fat.
Decreases gastric acid secretion, decreases gastric emptying, decreases pancreatic secretion, decreases transit rate, decreases colonic motility.
Pathways of candidate hormones (that are not completely understood)
Pancreatic polypeptide released by protein, fat and glucose. Reduces all pancreatic secretion.
Peptide YY released y fat. Reduces gastric secretion and emptying.
Enteroglucagon released by fat and hexose. Reduces gastric secretion, stimulates insulin release.
Which hormones control eating behavior? Which decrease appetite and which increase?
Leptin (produced in gastric chief cells), PYY (from L-cells), CCK (from small intestine) decreases appetite, secreted when well fed.
Ghrelin (secreted by endocrine cells in stomach) increase appetite, secreted when hungry and decrease after meal.
What are the differences between secretions of different salivary glands?
parotid glands produce a purely serous
(protein-rich, enzymes), watery secretion- 75%
submaxillary (submandibular) glands
produce a mixed serous and mucous
secretion (25%)
sublingual glands secrete a saliva that is
predominantly mucous in character (5%)
Properties of salivary secretion (contents, hormonal control, etc.)
Composed of:
Bicarbonate secretion from ducts (alkaline)
Enzymes from acinus - Amylase, Lipase
Neural Stimulants:
Parasympathetic (salivary nucleus in medulla oblongata, otic, glossopharyngeal nerves and other ganglia, acetylcholine)
Sympathetic (superior cervical ganglion, norepinephrine)
Pharmacological control:
Stimulants: bethanechol
Inhibitors: Atropine (anticholinergic), Smoking (maybe by neural)
NO GI hormonal control, no neural inhibition
Electrolyte concentrations variation by flow rate
Salivary cells: Hypoospmotic at basal conditions. At max stimulatory state still less lower levels than in blood. Peristalsis always continues even between meals and in sleep.
When acid increases (in parietal cells), Na drops and the secretion is hyperosmotic at max flow rate.
Non-parietal (mucus): Flow rate 1/10 of normal. HCO3 increases.
Acid secretion in parietal cells, H+/K+ ATPase: mechanisms, treatment
Microtubules are organized during secretion at the apical portion of the cell, the side at which H+ is secreted through the H+/K+ ATPase (blocked by PPIs). Carbonic anhydrase needed to make HCO3 on the basal side (not a functional therapy to block with acetozolamide).
H+/K+ ATPase: Alpha portion on the cytoplasmic side, blocked by omeprazole (Losec), Lansoprazole, Pantoprazole. Medications must be taken before a meal so they are active before the enzyme secretes acid. Catalytic and transport functions.
Beta section in the cytoplasm. Protects against degradation. Enables trafficking to/from luminal membrane.
H2 blockers block the H2 receptors for cAMP (which comes from ECL cells). Blocking calcium through anticholinergices is not successful. Blocking gastrin isn’t either.
3 exocrine secretory zones
Cardia: Mucus, Bicarbonate, Trefoil peptides into mucous layer.
Fundus and body: Mucus, bicarbonate and trefoil peptides into mucous layer. H+, intrinsic factor (from parietal cells), enzymes: pepsin and lipase (by chief cells) into lumen
Antrum: Mucus, bicarbonate and trefoil peptides into mucous layer. Enzymes: pensin and lipase into lumen.
What happens at pH 3 that makes it so magical?
Pepsin is active at pH < 3
Gastric somatostatin is secreted (D-cells stimulated) at pH < 3
Duodenal bicarbonate is secreted (through the pyloris) at pH < 3
Duodenal secretin is released (from the proximal duodenum) at pH < 3
Overlapping phases of acid and pepsin secretion in different places in the GI tract
Cephalic
Neural
50% of acid secretion (in the mouth, before swallowed). Within the first hour.
Gastric
Hormonal
Neural
Food in stomach. Peaks a bit after an hour.
Intestinal
Hormonal
Neural
Not including colon. Complication because secretin release inhibits acid secretion. Peaks at 2 hours.
Circulatory
Chemical
Amino acid absorption causes acid secretion surge.
What does the duodenum secrete? Plus details of secretion.
Intrinsic: mucosal bicarbonate (from villi and crypt goblet and columnar cells, active transport against a concentration gradient, more proximal than distal) and mucus
Extrinsic: bile and pancreatic secretion
In a single meal the bicarbonate from the duodenum, bile and pancreas neutralizes the total gastric acid secretion (unless there is pancreatitis or cirrhotic liver).
Stimulants of bicarbonate secretion: HCl (most potent), prostaglandins, parasympathetic.
Inhibitors of secretion: NSAIDs, verapamil and other Ca channel blockers, histamine, smoking.
How does the release of bicarbonate in the stomach, duodenum and pancreas affect the PCO2 and pH?
PCO2 in the duodenal lumen is about 40x that of the blood. During a meal blood pH thus becomes more basic.
Because the stomach is releasing acid, blood around it is more basic. Because the pancreas secretes basic products, the venous pancreatic blood is more acidic.
Regulation of the pancreas
Acinus:
Endocrine-secreted by stimulated duodenum: CCK-modifies acinus to produce enzymes by exocytosis and secretin-water and bicarbonate from duct.
Neurocine: ACh, GRP, VIP, Substance P stimulate enzymes, ACh also acts on ducts to secrete water and bicarbonate.
Ductular system modifies electrolyte composition by bicarbonate secretion.
Takes 20 minutes to secrete.
CCK:
Stimulates pancreateic enzyme secretion by: neural pathway: vagal afferent–>dorsal vagal complex–>vagal efferent–>ACh, GRP, VIP–>enzyme secretion in acinus, break down and produce peptides, AA, FA–> I cell in wall of duodenum to produce CCK. When no more protein or fat the I cell is inactive, CCK not released, pancreas not stimulated.
Secretin
Stimulates cAMP which stimulates the CFTR to release HCO3 and Cl. Carbonic anhydrase produces HCO3 and H+. HCO3 goes into the lumen.
Synthesis of primary bile acids
Primary bile acids are synthesized by hepatocytes
from cholesterol
Daily synthesis = 200–400 mg
Rate-limiting step in synthesis is 7α–hydroxylase
enzyme which hydroxylates cholesterol at the 7
position of the steroid nucleus
Synthesis of bile acids can increase 10-fold after
resection of the terminal ileum (because no recycling being sent back through portal system)
Bile acids in aqueous solution are present as sodium
salts
Composition of Human Bile
Primary (Cholate and chenodeoxycholate)- 80%
Secondary (deoxycholate and lithocholate). Hydrolyzed by colonic bacteria.
75% of both is glycine, 25% taurine
Biliary lipids: Bile acids (54%), Phospholipids(18%-abundant in electrolytes), Cholesterol (8%). Bilirubin (<2%) makes color.
Concentrated by absorption of water in gall bladder, Na and bile acid anions become hyperosmotic. HCO3 and Cl are resorbed so their concentration decrea
What is Ursodeoxycholic acid and how does it work?
For primary biliary cirrhosis with too much bile being produced for the liver to uptake, causes itchiness
Competes with physiological conjugated bile
acids for active transport uptake in the
terminal ileum
In a steady dose of 15 mg/kg/day
ursodeoxycholic acid will account for 40% of
bile acid pool
Useful treatment in primary biliary cirrhosis
Not to be given together with cholestyramine
Digestion and absorption of proteins in the small intestine: what enzymes get released where and with which products? (3 sites)
Trypsin and pancreatic enzymes excreted into lumen to break down proteins. Mixes with pepsins pancreatic proteases
Products: 40% free AA and 60% oligopeptides
Peptidases (enterokinase) in the brush border break down tetra (3-5) peptides into free AA, dipeptides and tripeptides.
Inside the cell there is cytoplasmic peptidase which changes dipeptides and tripeptides into amino acids.
Lipase digestion (what are they, where do they act and where are they secreted)
Digestion of medium chain triglyceride (MCT)
Acid lipase secreted in lingual glands and gastric peptic cells act on the stomach and require pH of 4. Cleave in one place to make FA and diglyceride.
Pancreatic lipase (with colipase) is secreted in the acinus of the pancreas and acts in the small intestine. Requires a pH of 7. Can cleave 2 sites to create 2- monoglyceride and FA.
MCT–>pancreatic lipase–>MCFA (soluble) –>diffusion into mucosa, absorbed via portal blood
Digestino of carbohydrates (what is secreted from where into where and producing what?)
In the lumen of the stomach and small intestine amylose (start), amylopectin and glycogen are broken down via amylase (salivary and pancreatic) into maltose, maltotriose, alpha limit dextrins).
In the brush border:
Glucose oligomers are broken down by maltase to produce glucose.
Sucrase breaks down sucrose to produce glucose and fructose
Lactose is broken down by lactase to produce glucose and calactose.
SGLUT-1 transports sodium and glucose into cytoplasm from lumen, must be together.
Adsorption of sodium and water in the small and large intestines
Osmolality reaches isotonicity in the duodenum (regardless if meal is hypertonic or hypotonic) and stays at about 280 mOsm/L. Sodium is absorbed into cell by cotransport with glucose and amino acids and water follows.
