GI physiology Flashcards
Steps in smooth muscle contraction
voltage-gated Ca entry, SR Ca release –> increased intracellular Ca –> binds calmodulin –> activates MLCK –> myosin phosphorylation by ATP –> crossbridge cycling –> contraction
resting membrane potential of circular smooth muscle cells
-60 mV
slow waves/ basic electric rhythm
spontaneous rhythmic waves of depolarization. magnitude = 10-15 mV
Does not cause contraction
Effect of Ach on smooth muscle
causes action potentials to fire at each slow wave peak –> voltage-gated channel opening –> contraction at the frequency of BER (12/min)
more action potentials –> greater force of contraction
predominant motor activity in the intestines
segmentation = isolated, uncoordinated smooth muscle contraction/relaxation –> mixing without net propulsion –> ensures proper digestion and absorption
coordinated (via vagal input) contractions of adjacent segments in a proximal to distal manner
peristalsis
intestinal relaxation distal to food bolus, produced by pressure of the proximal bolus
receptive relaxation
effect of cutting the vagus nerve
BERs remain, but are disorganized –> abolished peristalsis
phases of swallowing
voluntary = tongue moves food back to pharynx –> soft palate pushed upward, closed nasopharynx via upper constrictor muscle contraction
pharyngeal = respiration inhibited for 1-2 seconds, larynx raises and glottis closes
esophageal = UES relaxation, peristalsis –> food descends esophagus –> LES relaxation
Phases of gastric motility
after eating, contractions start in mid-stomach at frequency of 3/min –> stronger, faster contractions in antrum –> transient opening of pylorus –> smaller particles and chyme leave the stomach, most content reflected back (retropulsion)
what increases rate of gastric emptying?
combination of gastric distension and gastrin
control of gastric emptying
duodenal distention and irritation (acidity and high osmolarity) –> reflex inhibition of gastric peristalsis, increased pyloric tone
fats in duodenum –> CCK secreted by enteric endocrine cells –> decreased gastric motility
transit time of chyme in intestines
3-5h
Purpose of myoelectric motor complexes
every 90 minutes –> removes bacteria and indigestible material
only occurs during fasting
Normal fecal fluid loss
100-200ml
mass movements
colonic forward propulsion. giant migrating contractions
primary stimulator of colonic contractions
distention
gastrocolic reflex
stimulates mass movements, pushing feces into the rectum
defecation reflex
spinal reflex, mediated by the pelvic nerves –> relaxation of internal anal sphincter
sufficient to empty lower bowel in babies and pts with damaged spinal cords
Parietal cells
secrete HCl via ATP consumption –> luminal pH of 2
secrete intrinsic factor –> B12 absorption
Mechanism of acid secretion by parietal cells
CO2 diffuses into the cell from blood –> combines with OH- from H2O (produces H+, which is pumped to lumen via H/K ATPase) –> HCO3-, via carbonic anhydrase –> exchanged for Cl- in blood via Cl/HCO3 exchanger –> Cl to lumen via luminal Cl channel
Stimulation of acid secretion
Direct path: Ach from vagus nerve –> M3 receptors –> parietal cell acid secretion
Gastrin –> increased intracellular Ca –> direct and/or indirect path –> H+ secretion
Indirect path: Ach from vagus nerve –> ECL M3 receptors –> Histamine release –> parietal cell H2 receptor binding –> Gs –> adenylate cyclase –> Ca and cAMP –> kinase activation –> phosphorylation of H/K ATPase
4 phases of gastric acid secretion
basal (inter-digestive) phase,
3 phases associated with eating: cephalic phase, gastric phase, intestinal phase
Circadian rhythm –> rate of acid secretion in lowest in the morning before awakening and highest in the evening. resting pH = 3-7
basal (inter-digestive) phase
initiated by smell, sight, taste and swallowing of food
cephalic phase
Vagal mediation of cephalic phase
stimulation of vagus –> release of Ach, triggering of histamine release from ECL cells, release of gastrin-releasing peptide (GRP) from the vagal and enteric neurons, and inhibition of somatostatin release from delta cells in the stomach
How much acid secretion is accounted for by the cephalic phase?
30% of total acid secretion
initiated by entry of food into the stomach
gastric phase
components of the gastric phase
food distends the gastric mucosa –> vagovagal and ENS reflexes
partially digested proteins –> antral gastrin (G) cell stimulation –> gastrin secretion
How much acid secretion is accounted for by the gastric phase?
50-60%
stimulation of the intestinal phase
presence of amino acid and partially digested peptides in the proximal portion of the small intestine –> duodenal gastrin (G) cell stimulation –> gastrin secretion –> acid secretion in stomach
Function of mucosal barrier
protect mucosa from acid, prevent diffusional dissipation of the pH gradient
fat absorption
fat digestive products –> lacteal –> –> thoracic duct –> blood stream
total absorptive area of the intestinal surface
200-400 square meters
secreted by the salivary glands, digests starch, in the mouth
product = polysaccharides
Amylase
secreted by serous glands of the tongue, digests fat, in mouth and stomach
Products: monoglycerides, fatty acids
lingual lipase
secreted by the stomach, digests protein
product: polypeptides
pepsin
secreted by the pancreas, digests proteins and polypeptides, located in the duodenum and jejunum
Product: small peptides and amino acids
trypsin, chymotrypsin, elastase, carboxypeptidases
secreted by the pancreas, digests starch, located in the duodenum and jejunum
Product = maltose, maltotriose, and alpha-limit dextran
amylase
Secreted by the pancreas, digests fat, located in the duodenum and jejunum
products = monoglycerides, fatty acids, cholesterol
lipase and colipase, phospholipase A2, cholesterol ester hydrolase (non-specific lipase)
Secreted by the liver, emulsify and dissolve fats, located in the duodenum and jejunum
bile salts
secreted by the stomach, kills bacteria and denatures proteins, located in the stomach
HCl
Ubiquitous secretion, buffers pH
NaHCO3
Ubiquitous secretion, lubricates and protects mucosal surfaces
mucus
Specificity of amylase digestion
catalyzes the hydrolysis of a-1,4 linkages (amylopectins)
will never digest cellulose (dietary fiber, a-1,6 linkages), will NEVER PRODUCE free glucose (products converted to glucose by brush-border enzymes)
transports glucose and galactose from intestinal lumen into the cytosol
Na-dependent glucose transporter (SGLT1) in the brush border or apical membrane of enterocytes
transports fructose from the lumen into the cytosol
GLUT5 (Na-independent fructose transporter)
transports fructose, glucose and galactose from cytosol to the blood
GLUT2 (Na-independent fructose transporter)
causes lactose intolerance
absence of lactase (brush-border enzyme)
lactose intolerance
unabsorbed lactose –> osmotic diarrhea; gut bacteria metabolize lactose –> gas
causes glucose-galactose intolerance
genetic absence of SGLT1 (Na/glucose cotransporter) –> potentially fatal in neonates
lack of Na and glucose absorption, –> lack of fluid absorption, osmotic fluid secretion –> diarrhea
treatment associated with glucose-galactose malabsorption
replace dietary glucose with fructose (uses different transporter)
two classes of peptidases
endopeptidases (hydrolyze interior peptide bonds) and exopeptidases (hydrolyze one amino acid at a time from the C terminus of proteins and peptides)
Pepsin, trypsin, chymotrypsin, elastase
endopeptidases
Carboxypeptidases A and B
exopeptidases
converts dipeptides to amino acids
Dipeptidase
removes dipeptides from the N terminus
Dipeptidyl aminopeptidase
removes one amino acid at a time from the N terminus
Aminopeptidase
What is the status of pepsinogen at pH 1-3
activated to pepsin
What is the status of pepsinogen at a pH above 5
inactive; remains pepsinogen
Patients with their stomach removed can’t secrete HCl or pepsin. Does this mean that they can’t digest protein?
No! neither pepsin, nor HCl are essential for protein digestion
Steps of small intestinal protein digestion
activation of trypsinogen to trypsin by enterokinase (brush border) –> activation of all other precursors by trypsin –> hydrolysis of proteins to amino acids and di-, tri-, oligopeptides via trypsin, chymotrypsin, elastase, carboxypeptidase A and B –> brush border proteases hydrolyze oligopeptides to amino acids –> pancreatic proteases digest themselves and each other
Which two amino acids require a specialized carrier for efficient absorption?
proline and glycine
patients lack the Na-amino acid transporters (genetic) –> lack capacity for renal or intestinal absorption of cysteine, lysine, arginine and ornithine
excretion of amino acid in the feces/urine
Cysteinuria
genetic absence/defect of the neutral amino acid transporter
Hartnup disease
genetic absence/defect in the Cl channel CFTR
Cystic fibrosis
digests triglycerides –> 2-monoglyceride and two free fatty acids, which can be absorbed
pancreatic lipase
solubilizes 2’-monoglycerides and fatty acids
bile-salt micelles
process of triglyceride absorption
pancreatic lipase digestion –> bile salt micelle solubilization –> entry into enterocyte –> triglycerides resynthesized –> packaged into chylomicrons with cholesterol and apolipoproteins –> golgi –> incorporated into secretory vesicles –> exocytosis to interstitial space –> lacteals (too large for capillaries)
What other nutrients are absorbed via the same route as fats and cholesterol?
Vitamin A, D, E, and K. All are fat-soluble
fat malabsorption disorders
Liver disease c bile salt deficiency
Pancreatic insufficiency (lack pancreatic lipase)
Weight loss medication use –| lipase activity –> anal leakage
Two important principles for water absorption
water readily moves across the intestinal epithelium –> chyme in duodenum rapidly brought to isotonic equilibrium with the blood
water absorption follows the absorption of solutes (absorbed isotonically)
important mechanism for colonic absorption of Na
epithelial sodium channels (ENaC)
Significance of K secretion in colon
increased Na absorption –> increased K secretion
net K secretion when lumenal [Na] drops below 25 mM
severe diarrhea –> significant fluid loss –> hypokalemia
How is B12 absorbed?
in complex with intrinsic factor in the distal ileum
Result of impaired absorption of B12
pernicious anemia
