Case 12- physiology Flashcards
What controls motility is the small intestine fasting stage
Motility in this state is rhythmically produced by the ENS and is governed by the migrating myoelectric complex (MMC)
4 phase of motility in the SI fasting stage
- Prolonged quiescent period, little activity
- Period of increasing action potentials in the muscles of the SI
- Period of maximal action potentials and contractions (peristalsis)
- Period of declining actions potentials
Why is there motility in the SI during a fasting stage
Helps move large particles which did not move through the tract during the fed state. Helps move secretions, dead cells and colonic bacteria. Colonic bacteria tends to migrate to the SI. MMC’s suppressed by feeding through vago-vagal reflexes and GI hormones e.g. gastrin, secretin, CCK1
Stages of motility in the SI during the fed state
1) Segmentation
2) Peristalsis
Motility in the SI during the fed state- Segmentation
Predominant form of motility in fed state. Non-propulsive, contents don’t move in any direction. Contraction of smooth muscles. Churning of luminal contents, mixes chyme with digestive enzymes. Reduces unstirred layer adjacent to luminal surface. Allows contents to have contact with epithelial lining for reabsorption of water as well. Allows time for absorption to take place.
Motility in the SI during the fed state- Peristalsis
Propulsive, sequential contraction of smooth muscle. Generally, promotes caudal movement of intestinal content. The content is moved to a more distal site for further absorption or elimination in the stool. After peristalsis you can get segmentation again, to allow absorption to take place. There is contraction behind the bolus and relaxation in front.
Types of motility in the large intestine
Churning
Mass peristalsis
Motility in the LI- Churning
Non-propulsive. Predominant form of motility in the colon. Prolonged exposure for absorption and digestion. Contents gets shuffled back and forth to assist with absorption of fatty acids and electrolytes and fermentation of dietary fibres. Water is reabsorbed in order to create faeces. Faecal matter is shuffled within the Haustra (segments of the large intestine).
Motility in the LI- Mass peristalsis
Propulsive, sequential haustration. Mass movement (20cm) towards rectum 1-3 times per day. The contents being moved into the rectum will initiate the defecation reflex. Then returns back to the churning pattern.
Control of intestinal motility- slow waves
Interstitial cells of Cajal (ICC) have an unstable membrane potential that spreads to intestinal wall muscle through gap junctions. There is an Oscillating pacesetter potential. There will be different frequencies in different parts of the gut. When it reaches the contraction threshold there will be muscle tension. Contraction may need excitatory stimuli (tone). However, at certain frequencies with a certain amount of muscle tension, the muscle will contract even without an external stimulus.
Effect of excitatory and inhibitory stimulation on motility
Inhibitory stimulation decreases the membrane potential, less likely to breach the contraction threshold, so there will be less contractions. Excitory stimulations raise the membrane potential, contractions will be stronger and more frequent.
Control of intestinal motility- Extrinsic factors
1) PNS
2) SNS
3) Sphincters
4) Presynaptic interneuron
Control of intestinal motility- PNS
Ach (muscarinic receptors), excitatory. Cholinergic drugs tend to cause diarrhoea as stool moves more quickly through the intestine and less water is reabsorbed.
Control of intestinal motility- CNS
NE (β receptors), inhibitory. Beta blockers cause diarrhoea by inhibiting the inhibitory response.
Control of intestinal motility- Sphincters
α adrenergic receptor= contraction, sympathetic stimulation is inhibitory
Control of intestinal motility- Presynaptic interneuron
α adrenergic receptors= inhibits Ach release, sympathetic stimulation is inhibitory
Control of intestinal motility- Intrinsic factors
Motorneurons of the ENS
• Excitatory: Ach, Substance P, contraction
• Inhibitory: Nitric oxide, Vasoactive intestinal polypeptide, ATP. Muscle relaxation
Why do we need inhibitory and excitatory factors in intestinal motility
Inhibitory neurons are released in front of the bolus so there is relaxation. There will be triggering of excitatory neurons before the bolus, to push it towards the anus. All controlled within the enteric NS.
What muscles are primarily involved in movement in the intestine
The circular muscles
How the ENS controls motility
The enteric nervous system coordinates the cyclical patter of motility during the inter-digestive (fasting) state through the migrating myoelectric complex in the small intestine. The intrinsic motility of the intestine is controlled entirely within the intestine itself, via the ENS, without an external influence.
What controls defecation
The Enteric NS, autonomic control and conscious control. It is initiated by distention of the rectum
What causes defecation
1) Presence of chyme in the duodenum causes activation of duodeno-colic reflux
2) Presence of food in the stomach activates the gastro-colic reflex
3) All this causes mass peristaltic movement of the colon.
4) Stretch of rectum causes Parasympathetic defecation reflex
Conscious control of defecation
Defecation is a spinal reflex that can be voluntarily inhibited by keeping the external anal sphincter contracted or facilitated by relaxation coupled with contraction of the abdominal muscles.
What anal sphincter do we have conscious control over
The external anal sphincter- relaxed during defecation
Act of defecation
Mass peristalsis → distension of rectum → ↑ pressure & initiates the retco-sphincter reflex and relaxation of internal anal sphincter. Reflex is initiated through enteric NS.
What happens if you dont defecate
If you do not defecate the faeces will move back in the colon for further drying out, it will then move to the rectum with the next peristaltic wave
Pressure of defecation
Urge to defecate first appears when rectal pressure is about 18mmHg. At about 55mmHg the external as well as internal anal sphincters relax.
Psychological causes of impaired defecation reflex (constipation)
Voluntary withholding stool because of fear of pain .
Congenital causes of impaired defecation reflex (constipation)
Hirschsprung’s disease. Congenital absence of ENS ganglia. Internal anal sphincter does not relax after rectal distension. Retention of colonic material. The colon can be blocked.
Acquired causes of impaired defecation reflex (constipation)
Chaga’s disease. Trypanosome infection that destroys neural networks in the colon. Breakdown of reflex control and excessive retention of stool.
Absorptive epithelium in the small intestine
Within the upper portion of the villi, which are finger or leaf like protrusions in the gut lumen
Absorptive epithelium in the colon
No villi and the absorptive epithelia are found in the mucosal surface i.e. surface epithelia.
Secretory and absorptive roles of the intestine
There is both fluid secretion and absorption across the luminal wall of the small and large intestines. Overall, there is net fluid absorption
Secretion in the intestine
The epithelial cells responsible for secretion line the crypts (crypts of Lieberkühn) which are indentations into the lamina propria of the muscoa.
Crypt-villus axis
In the small intestine, you have the crypt-villus axis. The relatively immature cells of the crypts express transport proteins that facilitate fluid secretion. As the epithelial cells migrate up the crypt-villus axis (over 2-4 days) they differentiate and the mature cells of the upper villus express the transport proteins that facilitate fluid absorption. The cells near the bottom secrete more Cl-
MOA of Secretion in the small and large intestine
- The small intestine secretes about 1L of fluid per day from crypt epithelia.
- The large intestine secretes a small volume of mucin rich fluid from crypt epithelia. This lubricates the passage of the drying faeces through the colon in order to limit damage caused by rubbing of the mucosal surface.
Absorption in the SI
• The small intestine is presented with around 8-10L of fluid and will absorb around 6.5-8L per day. The maximal capacity for absorption by the small intestine is around twice that of “normal” daily absorption.
Absorption in the LI
The large intestine is presented with around 1.5-2L of fluid and reabsorbs all but around 100ml per day (that which is lost in the stool). The maximum absorptive capacity is twice the normal daily amount
Where does chloride secretion take place in the intestine
The epithelia of the crypts in the small and large intestine
Chloride secretion in the intestine
- Cl- crosses the basolateral membrane from the interstitial fluid via the Na+/K+/2Cl- co-transporter. Most of the K+ is recycled across the basolateral membrane via a K+ channel and Na+ can move back out via the Na+/K+ ATPase.
- Cl- will move down its electrochemical gradient into the lumen via Cl- channels, CFTR.
- This Cl- movement results in a slightly more negatively charged luminal side which will pull along cations, primarily Na+, between the cells (the paracellular route) to maintain electro-neutrality.
- Water follows the movement of the ions.
Location of chloride absorption in the intestine
Takes place in the villi of the small intestine and the surface mucosa of the large intestine
Chloride absorption in the Jejenum, Ileum and distal colon
Na/K+ ATPase channel on the basolateral membrane absorbs Na+. Chlorine then follows through chloride channel on the luminal and basolateral membrane. This is how the majority of Cl- is reabsorbed. Cl- can also move through paracellular transport.
Chloride absorption in just the Ileum and colon
- A Cl-/HCO3- (anion) exchanger is expressed in the luminal membrane of the absorptive epithelia. It moves Cl- into the cell and moves bicarbonate out. It is responsible for the net HCO3- secretion.
- The HCO3- that is secreted is created from intracellular production using carbonic anhydrase (CA) which converts H2O and CO2 into H+ and HCO3-. The H+ produced can exit the cell into the intestinal lumen or interstitial via Na+/H+ exchangers on the luminal and basolateral membranes, respectively.
- The Cl- that is now within the cell can exit via a Cl- channel found in the basolateral membrane.
Cl- absorption along the GI tract
Cl- crosses the basolateral membrane on the Na+/K+/2Cl- transporter. When in the cell Cl- can then exit across the apical membrane. Na+ follows through paracellular transport
Sodium secretion in the GI tract
Fluid secretion is driven by the movement of Cl- across the luminal membrane and into the GI tract. Na+ and water follow. Covered earlier.
What favours Na+ absorption in the GI tract
Intracellular Na+ concentration is low relative to extracellular fluid, so there is a concentration gradient that favours Na+ movement into the cell.
Na+ reabsorption in the Duodenum and Jejenum
Na+/H+ exchangers (NHE3) on the luminal membrane enables Na+ to move into the cell which then exits across the basolateral membrane via Na+/K+ ATPase. The acid (H+) that is moved out by the Na+/H+ exchangers creates an acidic microclimate adjacent to the luminal membrane that is important in facilitating peptide and amino acid transport/absorption. The movement of Na+ results in an electrical gradient that will promote Cl- absorption (as per previous section) and water will follow. This is the primary mechanism for fluid absorption in the inter-digestive period.
Na+ reabsorption in the Ileum and proximal colon
Na+ absorption is facilitated by Na+/H+ exchangers (NHE2 and NHE3) in the luminal membrane. In these regions the movement of Na+ is linked to Cl- absorption and HCO3- secretion as described in the chloride movement section.
Na+ reabsorption in the Jejenum and Ileum
Na+/glucose transporters and Na+/amino acid transporters use the concentration gradient of Na+ moving into the cell to provide the energy to move amino acids and glucose. Na+ can exit across the basolateral membrane via the Na+/K+ ATPase. This nutrient coupled Na+ absorption is the primary mechanism for Na+ (and thus anion and water) absorption in the digestive period.
Na+ reabsorption in the distal colon
The absorptive epithelia express epithelial Na+ channel (ENaC) in the luminal membrane. The absorption of Na+ creates a relative negatively charged lumen which will promote anion (e.g. Cl-) absorption, and cation (e.g. K+) . Absorption of fluid in this region can be regulated. For example, aldosterone increases expression and activity of ENaC and the basolateral Na+/K+ ATPase resulting in increased fluid absorption.
K+ secretion
Only the colon secretes K+, increased transport causes the loss of K+ in diarrhoea
Primary mechanism of K+ secretion
Through passive movement. K+ moves down the electrochemical gradient into the lumen via paracellular transport. The electrochemical gradient is generated by the absorption of Na+ and/or the secretion of Cl- which effectively creates a relatively negative charged lumen side which attracts and draws the K+ through the paracellular route.
K+ secretion- active transport
K+ enters the cells via the Na+/K+ ATPase (energy dependent). K+ can then be secretes through K+ channels on the luminal membrane or reabsorbed through K+ channels on the basolateral membrane. K+ secretion can be regulated by controlling the activity of the K+ channels on the luminal membrane relative to the activity of the K+ channels in the basolateral membrane. We can therefore increase or decrease the amount of K+ lost in the faeces and how much is recycled across the basolateral membrane. Helps get rid of excess K+.
K+ absorption in the small intestine
Solvent drag- K+ in the lumen is dragged along with the bulk absorption of Na+, Cl- and water via the paracellular route. The SI is where the bulk of water, nutrient, Na+ and Cl- absorption takes place
K+ absorption in the colon
The absorptive epithelia in the colon also express a K+/H+ ATPase. This active process facilitates the movement of K+ across the luminal membrane into the cell in exchange for H+ secretion. K+ can then leave the cell via a channel in the basolateral membrane. This contributes to acid/base balance and K+ concentrations in the blood.
Where does the majority of nutrient absorption take place
The epithelia lining the upper third of the villi express the digestive enzymes and transport proteins that facilitate nutrient transport.
Regulating absorption and secretion- the ENS (physiological regulation)
- Secretagogues (e.g. Ach, 5-HT & VIP) increase intracellular Ca2+ or cAMP in secretory epithelia to increase Cl- secretion. They also act on absorptive epithelia to slow down Na+ transport and inhibit absorption.
- Enkephalins (ligand for opioid receptors) & norepinephrine decrease intracellular Ca2+ in epithelia to increase NaCl absorption.
- Local reflex response to intestinal distension involves the release of 5-HT (serotonin) which increases fluid and electrolyte secretion.
Regulation for absorption and secretion- Endocrine (physiological regulation)
- Angiotensin II increases Na+ absorption via an increase activity of apical Na+/H+ exchange.
- Aldosterone increases Na+ absorption via increased activity of ENaC and the Na+/K+ ATPase.
- Guanylin is a gastrointestinal hormone the regulates fluid movement in the intestine by stimulating Cl- secretion. It is the `ligand for the gualylin receptor which binds many pathogens, stimulating secretion in an attempt to flush the pathogen away, which results in diarrhoea.
Regulation of absorption and secretion- Immune/inflammatory system (pathological regulation)
- Inflammatory mediators such NF-KB make the paracellular route more permeable increasing fluid secretion
- White blood cell activation leads to secretion of inflammatory mediators that stimulate secretion.
- Prostaglandin secretion by the intestinal mucosa increases in IBD. Prostaglandins stimulates Cl- secretion (via increasing cAMP) causing diarrhoea.
- Antigens act cause mast cells to release histamine which acts via the enteric nervous system, to increase Cl- secretion
Regulation of absorption and secretion- Bacterial toxins (pathological regulations)
- GI infections- Bacterial toxins bind to receptors in the epithelia which up-regulate secretion and down-regulate absorption of fluid (salt and water) causing diarrhoea without damaging the mucosa.
- Some bacteria act via adenylate cyclase, e.g. Cholera toxin; E. coli heat-labile toxin. Others cause their effect through activation of guanylate cyclase, e.g. E. coli heat-stable toxin (STa)
- Some bacteria open tight junctions making the epithelia more permeable causing excessive secretion, e.g. ZOT – V. cholerae zonula occludens toxin.
How cholera causes excess secretions
The Cholera toxin binds to a monosialoganglioside (Gm1) receptors on the apical/luminal membrane of enterocytes (intestinal epithelia). This results in endocytosis of the receptor/toxin complex. The toxin is then able to activate adenylate cyclase and stimulate the increased production of cyclic AMP which activates protein kinase A (PKA). PKA activity results in increased opening of chloride channels (CFTR) which increases Cl- secretion (accompanied by water), causing diarrhoea.
Ways to stimulate Cl- secretion
Endocrine and inflammatory mediators. Histamine release by mast cells can act directly to increase Cl- secretion or indirectly through the enteric nervous system which releases Ach to stimulate secretory cells as well as increasing motility in an effort to rid the body of the antigen.
