Dec 28, 2015
Smooth Muscle of the Gut
(1) General properties
– Low excitability
– High extensibility
– Tonic contraction
– Autorhythmicity
– High sensitivity to temperature, stretch & chemical stimulation
(2) Electrophysiological properties
(a) Resting potential: – between -50 and -60 Mv– Ionic basis
– Em (selective membrane permeability to K+)– Electrogenic Na+-K+ pump
(b) Slow wave (basic electrical rhythm,BER)
– The spontaneous rhythmic, subthreshold
depolarizations of the cell membrane (slow
wave) of the gastrointestinal tract
– Initiated in the interstitial cells of Cajal (ICC)
(pacemaker cell)
• Slow wave (basic electrical rhythm)
– Intensity: 5~15 mV
– Frequency: 3~12 cpm
– Ionic mechanism
• spontaneous rhythmic changes in Na+-K+ pump
activity
• Mechanisms
– BER might be due to spontaneous
rhythmic changes in Na+-K+ pump
activity
– BER not generated by nervous activity
• Features of slow waves
– always present but do not always cause contraction
– dictate frequency of contractions
– frequency and height modulated by
• body temp & metabolic activity
• intrinsic & extrinsic nerves
• circulating hormones
• Spike potential (Action potential)
–Duration: 10~20 ms
–Ionic mechanism:
• Depolarization: Ca2+ influx
• Repolarization: K+ efflux
(3) muscle contraction
• Ca2+ binds to calmodulin (intracellular
protein) activates myosin light chain
kinase phosphorylates myosin light
chain phosphorylated myosin then (in
the presence of ATP) binds to actin
• Function
– Myenteric plexus : control over GI motility
– Submucous plexus: regulate gastrointestinal
blood flow and control GI secretion
• Neurotransmitters secreted by enteric neurons
–Ach: Stimulatory
–NE: inhibitory
–Others: Substance P, Nitric oxide , Vasoactive intestinal polypeptide (VIP), Opioid peptide, serotonin, histamine, ATP…
Gastrointestinal Hormone
• The hormones synthesized by a large number of endocrine cells within the gastrointestinal tract
• Brain-gut peptides: a number of the classical GI hormones are also synthesized in the brain
• Physiological functions
– control of the digestive function
– the release of other hormones
– trophic action
Five major GI hormones• Gastrin• Cholecystokinin• Secretin• Gastric inhibitory polypeptide (GIP)• motilin
The abundant smooth muscle in the stomach is responsible for gastric motility.
Specialized cells in the stomachsynthesize andsecrete mucous fluid, enzyme precursors,hydrochloric acid,and hormones.
Gastric Secretion
Parietal cells synthesize and secrete the hydrochloric acid responsible for the acidic pH in the gastric lumen.
Chief cells synthesize and secrete the protease precursor known as pepsinogen.
(i)Composition and Function
• Properties– pH 0.9~1.5– 1~2.5 L/day
• Major components– Hydrochloric acid – Pepsinogen– Mucus– Intrinsic factor
(1) Hydrochloric acid
• Secreted by the parietal cells
• Output
– Basal: 0~5 mmol/h
– Maximal: 20~25 mmol/h
• Mechanism of HCl secretion
• HCl is actively secreted against a huge concentration gradient
• H+/K+ ATPase or "proton pump"
One inhibitory andthree stimulatory signals that alteracid secretion byparietal cellsin the stomach.
Four chemical messengers regulate HCl secretion
p595
• Role of HCl
– Acid sterilization
– Activation of pepsinogen
– Promotion of secretin secretion
– Assisted effect of iron and calcium absorption
(2) Pepsinogen
• Secreted by the chief cells as an inactive precursor of pepsin
• Activated in the stomach, initially by H+ ions and then by active pepsin, autocatalytic activation
• Active pepsin (MW: 35,000)
The acidity in the gastric lumen converts the protease precursor pepsinogen to pepsin; subsequent conversions occur quickly as a result of pepsin’s protease activity.
• Effect of pepsin
Pepsin is an endopeptidase, which attacks peptide bonds in the interior of large protein molecules
ProteinsProteosesPeptonesPolypeptides
Pepsin
(3) Mucus
• Secreted by the epithelial cells all over the mucosa and by the neck mucus cells in the upper portion of the gastric glands and pyloric glands
• a layer ~500 m thick • composed chiefly of mucins
•Role–Lubrication of the mucosal surface–Protection of the tissue from mechanical damage by food particles
Mucus-HCO3- barrier
•Epithelial cells and neck mucus cells secrete a bicarbonate-rich mucus that coats and lubricates the gastric surface
•Serves an important role in protecting the epithelium from acid and other chemical insults. The mucus layer also traps HCO3
- secreted by the mucosal cells and this
buffers, or chemically insulates, the mucosa from the acidic stomach contents.
(4) Intrinsic factor
• A high molecular weight glycoprotein,
synthesized and secreted by the parietal cells
• The intrinsic factor binds to Vit B12 and facilitates
its absorption
(ii) Regulation of Gastric Secretion
(1) Basic factors that stimulate gastric secretion
– Acetylcholine (+ all secretory cells)
– Gastrin (+ parietal cells)
– Histamine (+ parietal cells)
(2) Nervous regulation
– ‘Short’ reflex pathways
• ‘Short’ excitatory reflexes: mediated by cholinergic
neurons in the plexuses
• ‘Short’ inhibitory reflexes: mediated by non-
adrenergic non-cholinergic (NANC) neurons
(2) Nervous regulation
‘Long’ autonomic pathways
• ‘Long’ excitatory reflexes: parasympathetic
• ‘Long’ inhibitory pathways: sympathetic
(3) Humoral regulation
Excitatory
ACh
Histamine
Gastrin
Inhibitory
Somatostatin
Secretin
5-hydroxytryptamine (5-HT)
Prostaglandin
(5) Inhibition of gastric secretion
The functional purpose of the inhibition of gastric secretion by
intestinal factors is presumably to slow the release of chyme
from the stomach when the small intestine is already filled or
overactive
Gastric Motility
Proximal stomach
cardia
fundus
corpus (body)
Distal stomach
antrum
pylorus
pyloric sphincter
• Receptive relaxation
– Storage function (1.0~1.5 L)
– Vago-vagal reflex
• Peristalsis
– BER in the stomach
Waves of smooth muscle contraction mix and propel theingested contents of the gastric lumen, but only a small amount of the material enters the small intestine (duodenum) as a result of each wave cycle.
Emptying of the stomach
• Emptying rate
– Fluid > viscous
– Small particle > large particle
– Isosmotic > hyper- & hypo-osmotic
– Carbohydrates > Protein > Fat
– Regular meal 4 ~ 6 hrs
• Regulation of stomach emptying
– Gastric factors that promote emptying
• Gastric food volume
• Gastrin
– Duodenal factors that inhibit stomach emptying
• Enterogastric nervous reflexes
• Fat
• Cholecystokinin
The exocrine cells in the pancreas play a central role in the production of digestive enzymes; the endocrine functions of the pancreas will be discussed at length in Chapter 16.
(I) Pancreatic Secretion
• pH 7.8~8.4
• ~1500 ml/day
• Isosmotic
• Components:
– Pancreatic digestive enzymes: secreted by pancreatic acini
– Sodium bicarbonate: secreted by small ductules and larger ducts
Were digestive enzymes synthesized in their active form, they would digest the very cells that make them. Hence, inactive precursors (e.g., trypsinogen) become activated (trypsin).
• Secretion of bicarbonate ions
– Secreted by the epithelial cells of the ductules and ducts
that lead from acini
– Up to 145mmol/L in pancreatic juice (5 times that in the
plasma)
– Neutralizing acid entering the duodenum from the
stomach
• Secretion of pancreatic digestive enzymes
– Carbohydrates -- Pancreatic amylase
Pancreatic lipase (coplipase)
– Fat Cholesterol esterase
Phospholipase
Trypsinogen
– Proteins Chymotrypsinogen
Procarboxypolypeptidase
Proelastase
-RNAase
-DNAase
• Trypsin Inhibitor
– Inhibits the activity of trypsin and thus guards
against the possible activation of trypsin and
the subsequent autodigestion of the pancreas
(II) Regulation of pancreatic secretion
• Basic stimuli that cause pancreatic secretion– Ach– Cholecystokinin:
• Secreted by I cells• Stimulates the acinar cells to secrete large amounts of
enzymes
– Secretin: • Released by S cells• Acts primarily on the duct cells to stimulate the secretion of
a large volume of solution with a high HCO3- concentration
• Phases of pancreatic secretion
– Cephalic Phase: taste of food- ‘long’ parasympathetic pathways
– Gastric Phase: distension of stomach- ‘long’ parasympathetic
reflex pathways
– Intestinal Phase
• The most important regulators are CCK and secretin
• Acid, fats, amino acids, peptides and protein are the main stimulus
for pancreatic production and secretion
Function of bile
(1) Bile are critical for digestion and absorption of fats and fat-soluble vitamins
– Bile salts are facial amphipathic
(2) Eliminate many waste products
– Excrete bile pigments or drug metabolites
"Looking at you with a jaundiced
eye"
Bilirubin (useless and toxic breakdown product of hemoglobin)
(3) Prevent the precipitation of cholesterol in the
gallbladder and eliminate excess cholesterol
90% of gallstones are of cholesterol stones
Up to 95% of the cholesterol-based bile salts are “recycled” by reabsorption along the intestine. -------Enterohepatic circulation
(4) Increasing bile
synthesis & secretion
(5) neutralize the stomach acid
Regulation of bile secretion
Substances increasing bile production
1) Bile salts
2) Secretin
3) Cholecystokinin
4) parasympathetic input
1. Absorptive surface of small intestinal mucosa
• Total area of 250 m2:
– Folds: 3-fold– Villi: 10-fold– Microvilli: 20-fold