Case 12- physiology

Question 1

What controls motility is the small intestine fasting stage

Answer 1

Motility in this state is rhythmically produced by the ENS and is governed by the migrating myoelectric complex (MMC)

Question 2

4 phase of motility in the SI fasting stage

Answer 2

• 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

Question 3

Why is there motility in the SI during a fasting stage

Answer 3

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

Question 4

Stages of motility in the SI during the fed state

Answer 4

1) Segmentation

2) Peristalsis

Question 5

Motility in the SI during the fed state- Segmentation

Answer 5

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.

Question 6

Motility in the SI during the fed state- Peristalsis

Answer 6

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.

Question 7

Types of motility in the large intestine

Answer 7

Churning

Mass peristalsis

Question 8

Motility in the LI- Churning

Answer 8

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).

Question 9

Motility in the LI- Mass peristalsis

Answer 9

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.

Question 10

Control of intestinal motility- slow waves

Answer 10

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.

Question 11

Effect of excitatory and inhibitory stimulation on motility

Answer 11

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.

Question 12

Control of intestinal motility- Extrinsic factors

Answer 12

1) PNS
2) SNS
3) Sphincters
4) Presynaptic interneuron

Question 13

Control of intestinal motility- PNS

Answer 13

Ach (muscarinic receptors), excitatory. Cholinergic drugs tend to cause diarrhoea as stool moves more quickly through the intestine and less water is reabsorbed.

Question 14

Control of intestinal motility- CNS

Answer 14

NE (β receptors), inhibitory. Beta blockers cause diarrhoea by inhibiting the inhibitory response.

Question 15

Control of intestinal motility- Sphincters

Answer 15

α adrenergic receptor= contraction, sympathetic stimulation is inhibitory

Question 16

Control of intestinal motility- Presynaptic interneuron

Answer 16

α adrenergic receptors= inhibits Ach release, sympathetic stimulation is inhibitory

Question 17

Control of intestinal motility- Intrinsic factors

Answer 17

Motorneurons of the ENS
• Excitatory: Ach, Substance P, contraction
• Inhibitory: Nitric oxide, Vasoactive intestinal polypeptide, ATP. Muscle relaxation

Question 18

Why do we need inhibitory and excitatory factors in intestinal motility

Answer 18

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.

Question 19

What muscles are primarily involved in movement in the intestine

Answer 19

The circular muscles

Question 20

How the ENS controls motility

Answer 20

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.

Question 21

What controls defecation

Answer 21

The Enteric NS, autonomic control and conscious control. It is initiated by distention of the rectum

Question 22

What causes defecation

Answer 22

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

Question 23

Conscious control of defecation

Answer 23

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.

Question 24

What anal sphincter do we have conscious control over

Answer 24

The external anal sphincter- relaxed during defecation

Question 25

Act of defecation

Answer 25

Mass peristalsis → distension of rectum → ↑ pressure & initiates the retco-sphincter reflex and relaxation of internal anal sphincter. Reflex is initiated through enteric NS.

Question 26

What happens if you dont defecate

Answer 26

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

Question 27

Pressure of defecation

Answer 27

Urge to defecate first appears when rectal pressure is about 18mmHg. At about 55mmHg the external as well as internal anal sphincters relax.

Question 28

Psychological causes of impaired defecation reflex (constipation)

Answer 28

Voluntary withholding stool because of fear of pain .

Question 29

Congenital causes of impaired defecation reflex (constipation)

Answer 29

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.

Question 30

Acquired causes of impaired defecation reflex (constipation)

Answer 30

Chaga’s disease. Trypanosome infection that destroys neural networks in the colon. Breakdown of reflex control and excessive retention of stool.

Question 31

Absorptive epithelium in the small intestine

Answer 31

Within the upper portion of the villi, which are finger or leaf like protrusions in the gut lumen

Question 32

Absorptive epithelium in the colon

Answer 32

No villi and the absorptive epithelia are found in the mucosal surface i.e. surface epithelia.

Question 33

Secretory and absorptive roles of the intestine

Answer 33

There is both fluid secretion and absorption across the luminal wall of the small and large intestines. Overall, there is net fluid absorption

Question 34

Secretion in the intestine

Answer 34

The epithelial cells responsible for secretion line the crypts (crypts of Lieberkühn) which are indentations into the lamina propria of the muscoa.

Question 35

Crypt-villus axis

Answer 35

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-

Question 36

MOA of Secretion in the small and large intestine

Answer 36

• 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.

Question 37

Absorption in the SI

Answer 37

• 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.

Question 38

Absorption in the LI

Answer 38

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

Question 39

Where does chloride secretion take place in the intestine

Answer 39

The epithelia of the crypts in the small and large intestine

Question 40

Chloride secretion in the intestine

Answer 40

• 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.

Question 41

Location of chloride absorption in the intestine

Answer 41

Takes place in the villi of the small intestine and the surface mucosa of the large intestine

Question 42

Chloride absorption in the Jejenum, Ileum and distal colon

Answer 42

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.

Question 43

Chloride absorption in just the Ileum and colon

Answer 43

• 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.

Question 44

Cl- absorption along the GI tract

Answer 44

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

Question 45

Sodium secretion in the GI tract

Answer 45

Fluid secretion is driven by the movement of Cl- across the luminal membrane and into the GI tract. Na+ and water follow. Covered earlier.

Question 46

What favours Na+ absorption in the GI tract

Answer 46

Intracellular Na+ concentration is low relative to extracellular fluid, so there is a concentration gradient that favours Na+ movement into the cell.

Question 47

Na+ reabsorption in the Duodenum and Jejenum

Answer 47

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.

Question 48

Na+ reabsorption in the Ileum and proximal colon

Answer 48

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.

Question 49

Na+ reabsorption in the Jejenum and Ileum

Answer 49

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.

Question 50

Na+ reabsorption in the distal colon

Answer 50

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.

Question 51

K+ secretion

Answer 51

Only the colon secretes K+, increased transport causes the loss of K+ in diarrhoea

Question 52

Primary mechanism of K+ secretion

Answer 52

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.

Question 53

K+ secretion- active transport

Answer 53

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+.

Question 54

K+ absorption in the small intestine

Answer 54

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

Question 55

K+ absorption in the colon

Answer 55

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.

Question 56

Where does the majority of nutrient absorption take place

Answer 56

The epithelia lining the upper third of the villi express the digestive enzymes and transport proteins that facilitate nutrient transport.

Question 57

Regulating absorption and secretion- the ENS (physiological regulation)

Answer 57

• 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.

Question 58

Regulation for absorption and secretion- Endocrine (physiological regulation)

Answer 58

• 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.

Question 59

Regulation of absorption and secretion- Immune/inflammatory system (pathological regulation)

Answer 59

• 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

Question 60

Regulation of absorption and secretion- Bacterial toxins (pathological regulations)

Answer 60

• 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.

Question 61

How cholera causes excess secretions

Answer 61

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.

Question 62

Ways to stimulate Cl- secretion

Answer 62

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.