Neuroscience

Front 1

Functions of digestive system (6)

Back 1

Ingestion, movement of food, Digestion, Absorption (main), Defecation, Other (pleasure, barrier integrity, medicinal)

Front 2

Function of the mouth in digestion

Back 2

Chewing through the use of pattern generators mechanically breaks up food. It helps mix food with saliva (lipase and amylase) to start the digestion process. When ready the body initiates a swallowing action to push the food bolus into the oesophagus.

Front 3

Function of the stomach in digestion

Back 3

A container for food, acts as a grinder for the food, initialises proteolysis and continues lipolysis. This mix is then under regulation emptied into the SI depending on the neural and hormonal feedback from the SI.

Front 4

Function of the SI

Back 4

Peristalsis (movement), segmentation (mixing of contents to allow everything to be absorbed)

Front 5

Function fo LI

Back 5

Most of H2O absorption occurs here. Flora within the LI can break down foods we cannot (cellulose). Retropulsion pushed food back up LI for more digestion. Haustration is a more vigerous version of segmentation to increase SA contact. Peristalsis still occurs.

Front 6

What is eliminated during defication. What controls defecation?

Back 6

Bacteria, exfoliated cells, secretions, bile breakdown products, undigested foods. The ENS controls defecation but it hands over to voluntary control once faeces arrives at the rectum.

Front 7

Describe the inputs that allow for the rhythmic peristalsis to occur.

Back 7

Pacemaker cells (called interstitial cells of Cajal) in the stomach (near greater curvature) and SI (near common bile duct) produce constant slow waves that propagate through the smooth muscle cells. But this AP is not enough to cause contraction. However, Vagal and enteric neurons can release ACh onto M2 and M3 receptors, which increases cytosolic Ca2+ allow contraction. So therefore, contraction only occurs where ACh is. Also the summation of APs can occur to cause larger contractions.

Front 8

Where are the GIT PSNS and SNS efferents coming from.

Back 8

PSNS

- Upper efferents are from Vagus n (CN X)

- Lower from S2/3/4 to pelvic splanchnic nn

SNS

- T5-9 via greater splanchnic

- T9,10 via lesser splanchnic

- T12 via least splanchnic

- L1-2 via lumbar splanchnic

Front 9

What are the plexuses of the GI

Back 9

Myenteric Plexus

- Motility

Submucosal plexus

- secretions and sensory

Front 10

What do the ENS inhibitory neurons release, Excitability release?

Back 10

ACh from M receptors causes excitation. VIP and NO inhibit.

Front 11

What are the 5 endocrine molecules and functions

Back 11

Gastrin - Stomach acid secretion and GO growh.

Cholecystokinin - pancreatic contraction and bile secretion

Secretin - controls pH via bicarbonate secretion.

Gastric inhibitory peptide - insulin release and suppression of Acid production.

Motilin - fasting state

Front 12

What are the paracrine factors

Back 12

Histamine and somastatin

Front 13

What are the 3 phases of digestions

Back 13

1. Cephalic - feeling hungry, tastebuds send a quick message to stomach to get reading for food.

2. Gastric phase - food is mixed with stomach acids

3. Intestinal phase - the mix the then regulated and pushed out by bit into the SI

Front 14

Describe the cephalic phase

Back 14

Smell, taste or thought of food triggers the CNS to send an impulse through the PSNS via the vagus nerve to the submucosal plexus. This plexus innervates mucous cells (mucous), chief cells (pepsinogen), parietal cells (HCl) and G cells (stimulate the release of gastrin into the blood). This all happens in preparation for food to arrive.

Front 15

Describe salivation and its reflexes.

Back 15

Simple reflex: Pressure receptors and chemoreceptors in the mouth detect information such as a dry mouth and send afferent info to the salivary centre in the medulla where it is integrated by salivatory nuclei -> then efferents are sent through the ANS visceral motor nerves to the salivary glands to begin secretion.

Nerve afferents:

touch - Trigeminal (CN V)

Taste - facial (Vll), Glossopharyngeal (lX), Vagus (X)

Nerve efferents (PSNS via CNS)

- submandibular, sublingual: facial (Vll)

- Parotid: glossopharyngeal (lX)

Front 16

Deglutition (Swallowing)

Back 16

It is initiated voluntarily by the pharyngeal constrictor muscles for the first 1/3 of oesophagus. Then the ENS takes over for the lower 1/3 with peristaltic waves. Upper and lower oesophageal sphincters coordinate.

So swallowing can be concious and voluntary but it is also a reflex. tactile receptor at the entrance of the pharynx send sensory info to the swallowing centre in the medulla and lower pons -> motor outputs go through:

- cranial nerve to pharynx and upper oesophagus

- vagus to the rest of oesophagus

- also the centre pauses pontine respiratory centre

The sequence

1. soft palate elevates to close entry to nose

2. vocal cords close and larynx elevates

3. epiglottis closes

4. pause in breathing

5. briefly relax UES

6. contract upper oesophagus

7 peristaltic waves to the rest.

If the food bolus is not moved by the 1st wave, then continued oesophageal distension triggers a secondary peristaltic wave (ENS reflex).

Front 17

vomiting

Back 17

Triggers in the medulla - SNS, PSNS activity includes:

- sweating, pallor

- Tachycardia, tachypnoea

- salivation

- increased gastric tone.

The abs contract to make a pressure gradient and the LES/UES relax to allow contents to pass. Nasopharynx is closed off by palate.

Front 18

The Gastric phase

Back 18

Distention in the stomach, increased pH, protein detection and peptide detection stimulated the gastric phase. ENS stimulates parietal and chief cells (ACh) and G cells (GRP) and increases motility for mixing waves

Endocrine actions:

peptides and AAs in the pyloric antrum are detected and stimulte G cells to release gastrin which increase parietal and chief cell secretion and also increases motility.

Paracrine actions: distention + vagus stimulates ECL (enterochromaffin-like) cells to release histamine -> which stimulates parietal acid production.

Front 19

what are the cells in the gastric pits and what do they secrete?

Back 19

Front 20

What is intrinsic factor?

Back 20

It is secreted from parietal cells along with HCl. Its job is to seek out Vit B12 and form a dimer complex. This complex is resistant to pepsin digestion. The B 12 can survive through the stomach, until it binds to a certain receptor in the iluem which allos the B 12 to be internalised. If you are defiecient in intrinsic factor => pernicious anaemia.

Front 21

How do parietal cells secrete HCl

Back 21

Acid from CO2 crossed the parietal cell membrane. Proton pump pushes H+ out and K+ in. Cl- ions go from blood to cytosol through exchange channel with HCO3- (which goes into blood) then to gastric lumen through channel, it is balanced by the K+ leak channels.

Front 22

What are the ways the proton pumps are activated?

Back 22

Front 23

What is the function of mucous in the stomach

Back 23

Acts as a protective barrier for the cells. Pepsin constantly degrades the mucus. But mucus is constantly replaced. The epithelial cells secrete HCO3- which increases pH to ~ 7 under the mucous. This way the stomach can stay at ~pH 2 without destroying the cells.

Front 24

Basal electric rhythm

Back 24

BER pacemaker are different to other pacemaker cells, the waves are lower frequency and amplitude and are longer in duration. produced by the interstitial cells of cajal and propagated between cells through gap junctions. Different GI sections have different rhythms governed by separate clusters of ICC cells.

Middle corpus - slow BER

towards antrum - amplitude increases, at the pylorus the amplitude is high enough to break the AP threshold and a massively stronger contraction (as Ca++ can enter from extraceullar stores) squeezes food up against the pyloric sphincter

The wave amplitude and plateau can be changed

- ACh and gastrin increase

- NE decreases (SNS decreases digestion)

Front 25

Regulated filling of duodenum and duodenal feedback

Back 25

stomach emptying into the duodenum is constant regardless of irregular food intake. This is important to prevent injury to the duodenum by acid. Low duodenal pH stimulates duodenal motility and decreases antrum contraction to stop acid stomach contents from entering. Also the SI digests different foods at different rates. Reflexes regulate gastric emptying depending on food composition. (the alcohol + fatty food timebomb)

Duodenal feedback

ENS and ANS reflexes regulate pyloric sphincter. Hormones are produced when undigested food remains in the duodenum. It is released by duodenum to compete with gastrin to decrease gastrin effect.

Front 26

What happens most at the duodenum, jejunum and ileum?

Back 26

Front 27

Intestinal phase of digestion

Back 27

Chyme released from the stomach into the duodenum has a negative feedback on gastric activity and stimulates antacid and chemical digestion.

Processes of inhibition:

- Neural: enterogastric reflex reduces gastrin production and stomach motility.

- Endocrine: secretin (in response to low pH), CCK (Cholecystokinin) and GIP (in response to Lipid and Carbohydrates in Duodenum) inhibit stomach activity and stimulate pancreas to release pancreatic juice. Gastrin, CCK and insulin stimulate peristalsis. But this can be inhibited by the SNS (danger/stress)

Front 28

Cholecystokinin (CCK)

Back 28

In response to Lipid and Carbohydrates in the Duodenum -> i cells release CCK -> stimulates the gallbladder to contract and pancreatic enzyme secretion to occur. It also inhibits gastric emptying (by occupying the gastrin receptor) and Reduced appetite (CNS receptors)

Front 29

Secretin

Back 29

Low duodenal pH stimulates S cells to release secretin. This retrieves HCO3- from the pancreas, liver and brunner's glands of the duodenum to neutralise the acidic chyme. Also secretin inhibits gastric acid and pepsin secretion via VIP receptors (vasoactive intestinal polypeptide).

Front 30

GIP

Back 30

sugars/fats in the duodenum/jejunum stimulates K cells to release GIP (gastric inhibitory peptide) -> GIP stimulates pancreatic beta cells to release insulin which inhibits gastric acid secretion, gastric motility and inhibits liver glycolysis.

Front 31

Where are the hormones in the gut found?

Back 31

Front 32

control of pancreatic/biliary secretions

Back 32

chyme entering the duodenum stimulates the following.

- slow neural Enterogastric reflex

- increase in CCK (activates pancreatic enzyme secretion) and secretin (elicits alkaline pancreatic juice)

- decrease in gastrin

- CCK and secretin also activate gallbladder contraction and relaxes the hepatopancreatic sphincter to release bile.

Pancreatic juice

- aqueous component which raises duodenal pH (by secreting HCO3- and dumping H+ into ECF) is released from duct cells in response to secretin.

- enzyme components lipase (TGs -> FFAs) and amylase (carbohydrates -> disaccharides) are released from acini of pancreas.

Front 33

purpose of microvilli

Back 33

maximises SA

Front 34

Ileum emptying into colon

Back 34

Front 35

Main functions of the LI

Back 35

- water and ion absorption

- Bioreactor and maintenance of complex flora

- absorption of short chain fatty acids fro bacterial breakdown of undigested food.

- storage of post digestion/faecal matter for 16-20 hours.

Front 36

Reflexes of LI

Back 36

Front 37

Rectum

Back 37

the rectum is usually empty due to retrograd contractions returning faeces to the sigmoid colon. Just before defecation there is a mass movement of faeces to the rectum from the sigmoid c. Visceral stretch receptors detect increase in pressure. This causes relaxation of the inner sphincter and contraction of outer sphincter.

Front 38

Defecation, whats in faeces

Back 38

- bacteria

- exfoliated cells

- secretions of intestinal linings like mucous

- bile breakdown products

- undiested or un-absorbed food intake.

Delivery to rectum controlled by ENS and voiding of rectum is voluntary through relaxation of external anal sphincter (this sphincter has atypical striated muscles which are continuously contracted. The reflex for defecation is located within the sacral spinal cord, which is then voluntarily modulated. Sigmoid colon undergoes propulsive contraction. Also expiratory, lungs and abdominal muscles act to create a pressure gradient compared to the outside.

Efferents: PSNS fibres located in the pelvic nerves.

Front 39

Fasting state

Back 39

Migrating myoelectic complex (MMC) removes large undigested remnants from the stomach. It is wave that occurs every 70-90 mins regardless of food input. BER frequency is similar after a meal, but amplitude is below contraction/AP threshold.

Front 40

Motilin

Back 40

Front 41

Enterohepatic circulation of bile salts

Back 41

Hepatocytes release bile acids, then these deconjugate into bile salts in the alkaline environment of duodenum. These bile salts are reabsorbed into portal circulation back to the liver to repeat cycle.

If there is failure to reabsorb this causes insufficient lipid digestion and osmotic problems later on in the colon

Front 42

regulation of body water

Back 42

Intake of water is regulated by the hypthalamus. The kidney regulate via hormones excretion of water. this balance can be upset by hyperventilation, vomiting, diarrhoea, perspiration, burns etc.

water intake

- metabolic (fat)

- ingestion

Water loss

- GI tract

- Lungs

- skin

- kidneys

Front 43

How is water absorbed in the intestines

Back 43

The intestines have large SA and are ideal for absorption. Solutes (salts) are moved mostly paracellularly (and 1/3 intracellularly) in across the intestine wall. Then water follows via osmosis paracellularly mostly (some transcellularly across lipid membrane).

In the jejunum - sodium transport through uniports (for salts) and co-transporters (eith aid of glucose, AAs)

In ileum and colon - sodium transport via H+ exchangers.

Front 44

Na balance

Back 44

average intake is variable:30-250 mmol/day

another 250 mmol/day enters from:

- salivary

- gastric

- biliary

- intestinal secretions

Pancreatic juice puts out lots of sodium but most of it is reabsorbed. Mostly by jejunum (50%), ileum (25%) and colon (variable)

Front 45

Sodium absorption in upper SI

Back 45

SI absorbs 95% of Na via Na+/glucose co transporter. The intracellular pH is maintained by the H+/Na+ exchanger.

Front 46

Water absorption on lower SI

Back 46

Most H2O absorption occurs from lumen across apical membrane of epithelial cells via Na+/H+ and Cl-/HCO3- exchangers

In the lumen H + HCO3 -> H20 + CO2 which then diffuses back in to cells.

Active secretion of Na into paracellular space occurs via osmotic absorption.

Front 47

Sodium and water absorption in LI

and Diarrhoea

Back 47

Na+/H+ and Cl-/HCO3- exchanger pumps in the apical membrane of epithelial cells.

In the lumen H + HCO3 -> H2O + CO2

A pH gradient running cytosol 5.5 : Lumen 7.5 affects Na+ uptake rate. If this is decreased e.g. by lactic acid from later lactose breakdown it impairs Na+ and H2O absorption -> Diarrhoea.

Diarrhoea

failure of water reclamation from gut lumen -> increased stool frequency, fluidity, volume. As a protective function it clear the intestine when distended, or invaded/poisoned by organisms or toxins. But negatively is is the worlds leading cause of death and disability -> hypocolaemia and CVS collapse, hypokalaemia and acid-base imbalance.

Front 48

The bristol stool scale

Back 48

Constipated: passing type 1 or 2, infrequently

Diarrhoea: passing type 6 or 7, very frequently

'Normal': passing type 3 or 4 every 1-3 days, depending on the normal patterns of the individual.

Front 49

Diarrhoea and solutes

Back 49

As water follows solute, the amount of solute in the lumen is important. Release of salts by gut wall

- inflammation

- stimulated secretion (e.g. cholera toxin)

Excess of solutes in the lumen

- un-absorbable solutes (e.g. Mg2+, SO42-, sorbitol)

- failure of absorption mechanisms (alcohol, coeliacs)

- overwhelming of absorption (e.g lactose intolerance; bile acids in colon; coeliac)

- overwhelming of absorption

Front 50

E. Coli and diarrhoea

Back 50

The E. Coli attaches to the enterocytes of the GIT via the cells own proteins -> once attached the E. Coli send signals into the cells, causing breakdown of the tight juctions between cells -> this increases permeability and allows water to seep out.

Front 51

Types of diarrhoea

Physiological

aetiological

Back 51

Secretory - toxins (e.g. V. Cholera) increase intracellular cAMP in crypt cells -> stims oversecretion of chloride. (cholera treated with combined glucose & Na+ rehydration)

Osmotic - osmolarity of lumen contents > normal (e.g. lactase deficiency leaves lactose in lumen). This keeps water in lumen

Defective ion transport

- bile acids present in the colon

- inflammation, decrease in Na+ absorption

- congenital lack of Na+/H+ exchanger

Hypermotility

- bacterial toxins

- transit too fast (e.g IBD)

Aetiological types

tumours - release secretagogues (upset normal GI secretions)

Infection - if infection lingers in the small bowel, damage to mucosa can leave patients with post-enteric diarrhoea

Traveller's diarrhoea - bacterial infections causing secretory diarrhoea

Front 52

Osmotic vs secretory diarrhoea

Back 52

Front 53

Laxatives

Back 53

same principle as diarrhoea

Secretory laxatives (e.g. castor oil, fig syrup) - broken down by bacteria into stimulatory factors for the ENS -> Cl- oversecretion

Osmotic laxatives (sorbitol, epsom salts - MgSO4)

Fibre (indigestible cellulose) -physically retains water in colon to bulk up and plasticise faeces (thus making it easier to move)

Front 54

visceral afferents to the CNS

Back 54

The visceral afferents are 1/10 the amount of somatic afferents.

Mechanical stimuli (both innocious and noxious) make up 50% of afferents

Mechanically insensitive information makes up 40-50% of afferents.

There is high and low threshold afferents.

- low threshold (responds to distension at innocuous and noxious pressures)

- High threshold aka silent fibres (responds to distension only within noxious pressures)

Front 55

visceral nociceptive pathways

Back 55

Visceral nociceptor afferents travel with ANS motor nerves and enter spinal cord via dorsal root.

primary afferents make local synapses with relay neurons (These neurons share afferents from somative nociceptors)

secondary visceral and secondary somatic nociceptor axons travel to thalamus and cerebrum to give sensation and experience of pain.

Front 56

nociception and pain (generally)

Back 56

nociception (noxious reception)

- senses tissue damage

- can cause withdrawal reflex

- the information detected is quantifiable and and objective

Pain sensation is the subjective interpretation of nociception + other factors

emotions (distress, anxiety, fear) are significant in relation to visceral pain.

Front 57

Somatic nociception and pain

Back 57

Cutaneous

- detects damage of free nerve ending in skin and near structures

- produces sharp and localised pain, this pain is influenced by experience.

Deep somatic

- detects pressure, ischaemia, tissue damage at periosteum, muscles and tendons

- resultant pain is diffuse and radiates.

There is hyperalgesia on compression of site

Note: there are also somatic nociceptors in the parietal structure which gives a localised pain ontop of the visceral responses.

Front 58

visceral nociception and pain

Back 58

distension, spasm, inflam or ischaemia (not necessarily related to tissue damage) of visceral organs sends info via visceral and/or vagal afferents to produce visceral responses: nausea, vomiting, sweating (all reflexes to slow the person down)

Note: there are also somatic nociceptors in the parietal structure which gives a localised pain ontop of the visceral responses.

Viseral pain is poorly localised, dull, felt at midline (mostly). There is no hyperalgesia on compression of site

Emotional reactions: anxiousness, anguish

Front 59

visceral peripheral sensitisation

Back 59

This refers to when the nociceptor thresh hold (point at which stimuli makes AP to stim pain) is lowered. this can be caused by pro-inflammatory substances (e.g. LPS in an inflammed bladder causes greater pain response for low thresh and also turns on silent fibre (high thesh) sensation)

Pro-inflammatry mediators

- bradykinin

- prostaglandins

- substance P

- serotonin

- Acid (H+)

"Silent" visceral C-fibres (acount for 40-50% of total afferent info)

- normall unresponsive to noxious and innocuous mechanical simuli but are 'switched on' when organ is inflamed

- found in bladder, bowel

Front 60

Central sensitization

Back 60

refers to the decrease of activation threshold fro the CNS nociceptive relay. It is caused by an abnormal increase in signalling from peripheral nociceptors. Thus it is more likely after peripheral sensitisation.

It persists after sensitising stimulus has finished. This is because local interaction caused by the original stimulus can increase the excitability of second order nociceptor neurons. These neurons can be driven without primary input. This whole process is mediated by neuronal plasticity and glial responses to the abnormal activity levels.

Inflammatory mechanisms of increased nociceptive transmission

- irritation to microglia in the spinal cord can enhance nociceptive transmission across the synapse. Acitvated microglia allow the post-synaptic NMDA receptor to be open. This receptor acts as a positive feedback loop allowing more Neuron transmitters to send pain info.

- Nerve damage can sensitise intact fibres and make them more responsive.

Front 61

progression of visceral pain.

Back 61

prolonged visceral nociception can create an abnormal (sensitised) sensory states. At first there is hyperalgesia from sensitisation of peripheral and central mechanisms. If extreme prolonging -> results in neuropathic pain where the system drives itself.

Front 62

visceral vs somatic pain

Back 62

Front 63

Convergence and referred visceral pain

Back 63

Because the viscera, skin and other structures originate from the same embryological layer, afferents from all these areas converge together and travel as one to be interpreted, even though organs may be far away from the other structures.

Referred pain occurs due to confusion of where the afferents are coming from. So you may feel pain on your skin even though an internal organ tissue is actually what is damaged. Normally there is parietal localised somatic pain on the organ + referred visceral pain somewhere else on a part of skin.

Segments

parietal pleura, pericardium - C3-5

Heart T1-T5

Foregut T6-T9

Midgut T9-T11

Hindgut T11-L1

Kidneys T10-L1

Ureter L2

Classic example is appendicitis

- visceral referred pain to the umbilical region

- parietal peritoneum somatic pain at the overlying location of the appendix (RIF)