Case 6 - Physiology of upper GI tract

Question 1

what are the 3 distinct phases to eating?

Answer 1

the cephalic phase, gastric phase and
intestinal phase.

Question 2

what is the cephalic phase

Answer 2

Thought, Sight, Smell, Taste (learned responses)
Prepares GI tract: Saliva, gastric acid, pancreatic secretion

Question 3

what is the gastric phase

Answer 3

Satiation, Early Digestion, Gastric emptying
Triggered by mechanical distension

Question 4

what is the intestinal phase

Answer 4

Feedback & Satiety (Fullness)
Triggered mainly by chemoreceptor activation in small bowel

Question 5

primary function of the Gastrointestinal tract
is to?

Answer 5

to provide the body with a continual supply of
water, electrolytes and nutrients. [The small
intestine is the location of the most water and
nutrient reabsorption]

Question 6

function of stomach

Answer 6

The stomach is a bag-like organ that is for STORAGE and MIXING NOT really
ABSORPTION (although alcohol, some drugs and a very small amount of water can
be absorbed here)

stomach mixes food with acid and enzymes to form chyme

The stomach also has a number of other
secretions which are released from
specialised regions called gastric pits.

Question 7

what is the pyloris of the stomach and what does it do?

Answer 7

The pylorus, which roughly translates as gatekeeper, is an opening between the
stomach and small intestine, guarded by the pyloric sphincter. This thickened band
of smooth muscle relaxes to allow only a small amount of chyme into the small
intestine at any one time.

Question 8

the gastric glands are what kind of structures?

Answer 8

simple tubular structures.

Question 9

Hydrochloric acid is released from [what cells in the body]?

Answer 9

Parietal cells.
[HCL is not simply manufactured by one cell type and released]

Question 10

Lipase and Pepsinogen is released from [what cells in the body]?

Answer 10

chief cells
[Pepsinogen converts into pepsin (pH3)]

Question 11

Bicarbonate is released from [what cells in the body]?

Answer 11

Mucous neck cells

Question 12

Gastric juice is a variable mixture of?

Answer 12

water, hydrochloric acid (HCl), electrolytes and
organic substances.

Question 13

what happens in the cephalic phase

Answer 13

Parasympathetic activity of the vagus nerve influences gastric acid and salivary gland secretion. These fibres stimulate the myenteric plexus, which secretes acetylcholine.

Activity of the vagus nerve also promotes the secretion of gastrin from G-Cells and Histamine from enterochromaffin-like cells.

Acetylcholine, Histamine and Gastrin act on the gastric cells to increase the secretion of
hydrochloric acid (and increase motility of the GI tract).

Question 14

what are parietal cells stimulated by and what happens as a response to this?

Answer 14

Parietal cells (also called oxyntic cells) are stimulated by acetylcholine, gastrin and histamine. In response to these triggers, there is insertion of H+-ATPase into membrane (apical surface).
Stimulation triggers dramatic morphological changes in the parietal cell from the resting state to the stimulated state

Question 15

how is Hydrochloric acid formed

Answer 15

It is formed by the diffusion of CO2 into parietal cells and its dissociation by carbonic
anhydrase.

Question 16

regarding hydrochloric acid secretion, what occurs in regards to chloride ions?

Answer 16

Chloride ions move through a co-transporter on the latero-basal surface of the parietal cell in exchange for bicarbonate. Chloride then moves into the lumen through the CFTR
channel.
{HCO3- moves out of parietal cell into interstitial space and Cl- moves into parietal cell from the interstitial space]

Question 17

Mucus in acid control

Answer 17

Mucous surface and neck cells secrete mucous and bicarbonate to prevent the local low pH from damaging stomach lining.

The mucus that is produced is specialised to allow one way movement of the HCl.

Question 18

clinically what can the function of
mucous cells be disrupted by?

Answer 18

NSAIDs and alcohol

Question 19

The gastric phase is triggered by? and what does this stimulate?

Answer 19

triggered by the arrival of food in the stomach. This stimulates
acid, pepsinogen and mucous release. Distention of the stomach activates
mechanoreceptors and both local (myenteric) and long-loop (vagus nerve)
reflexes.

Question 20

what happens in gastric phase?

Answer 20

Gastrin is also released further enhancing the release of hydrochloric acid from parietal
cells.

Gastrin secretion is inhibited when
the pH of gastric contents falls to
between 2 and 3.

The inhibition of hydrochloric acid secretion in mediated by somatostatin (a peptide) from
cells in the gastric mucosa. Somatostatin also slows gastric emptying, reduces blood flow,
and inhibits secretion of digestive enzymes.

Question 21

As chyme distends the duodenum, what happens?

Answer 21

there is a reflex that suppresses secretary activity (effectively stopping chemical digestion) and gastrointestinal motility. Several hormones contribute to this reflex: secretin, cholecystokinin and gastric inhibitory
polypeptide.
They inhibit the release of hydrochloric acid
and intrinsic factor from parietal cells and pepsinogen and gastric lipase from chief cells.

Question 22

what is CCK?

Answer 22

cholecystokinin

Question 23

what is the feedback control of gastric emptying?

Answer 23

When food is in the duodenum, the
content is sensed releasing the hormone cholecystokinin which reduces opening of
the pyloric sphincter, reducing stomach contractions and increasing accommodation
so that food can be stored for longer. Fats that get to the ilium will also slow gastric
motility and produce satiety.

Question 24

what kind of bacteria is Helicobacter pylori

Answer 24

A gram-negative helical bacteria lying
dormant in the antrum of the stomach

Question 25

how can Helicobacter pylori damage the antrum and duodenum producing cellular erosions and inflammation?

Answer 25

4 stages: * Tunnels through mucus layer * H. pylori produces urease enzymes which convert urea into ammonia to neutralise the gastric acid * Recruits more H pylori * Mucosal damage - inflammation by gastric acid, proteases and effector molecules & mucosal cell death by cytotoxins and ammonia

Question 26

what bacteria is a major cause of peptic ulcer

Answer 26

Helicobacter pylori, Combined with: stress, smoking, alcohol, NSAIDs

Question 27

how is H. Pylori transmitted

Answer 27

H.Pylori lies dormant in the antrum of the stomach (commensal bacteria; microflora) but it can also be transmitted through infection (from saliva, vomit or stool)

Question 28

diagnosis of H.Pylori - name 4

Answer 28

* Urea breath test: urea C14 is given to patient and H. Pylori converts urea C14 to ammonia (NH3) + C^14 O2 * CLO test: biopsy placed in media with urea and pH indicator. Conversion of urea to ammonia raises pH ( if H. pylori present), which changes the colour of pH indicator. * blood antibody test: antibodies to H. Pylori * stool antigen test (H. Pylori proteins)

Question 29

Treatment of H.Pylori infection

Answer 29

Vagotomy (surgery): truncal/highly selective Histamine (H2) antagonists: cimetidine famotidine Proton pump inhibitors: omeprazole or lansoprazole Antibiotics: e.g. Amoxycillin + Clarithomycin Treatment: Triple therapy: 2 antibiotics + 1 Proton pump inhibitor → can combine the above 2 treatment methods

Question 30

purpose of treating H. Pylori with Vagotomy (surgery): truncal/highly selective

Answer 30

Reduces ACh secretion from entericneurones Reduce acid secretion

Question 31

purpose of treating H. Pylori with Histamine (H2) antagonists: cimetidine famotidine

Answer 31

Block H2 receptors on parietal cell Reduce acid secretion

Question 32

purpose of treating H. Pylori with Proton pump inhibitors: omeprazole or lansoprazole

Answer 32

Prevent H+/K+ ATPase on parietal cell Reduce acid secretion

Question 33

purpose of treating H. Pylori with Antibiotics: e.g. Amoxycillin + Clarithomycin

Answer 33

Kill H Pylori bacteria Eradicate infection

Question 34

Vitamin B12 absorption

Answer 34

Vitamin B12 is usually bound to protein in foods and is released by stomach acid. Following its release, B12 is absorbed by the body in the ileum after binding to a protein known as intrinsic factor (IF). Intrinsic factor is produced by parietal cells* of the gastric mucosa. The intrinsic factor-B12 complex is absorbed by receptors on the ileum epithelial cells. *the same cells that secrete hydrochloric acid

Question 35

what is Pernicious anaemia characterised by?

Answer 35

B12 deficiency, which is often caused by the absence or reduction of intrinsic factor (due to autoimmune reduction of parietal cells).

Question 36

what enzyme uses B12?

Answer 36

Methionine synthase is an enzyme that uses B12. It converts homocysteine to methionine and tetrahydrofolate (DNA synthesis).

Question 37

Vitamin B12 (cobalamin) and Folate (vitamin B9) are what type of vitamins?

Answer 37

Water soluble vitamin

Question 38

what is Vitamin B12 (cobalamin) found in?

Answer 38

Found in Meat, eggs, cheese animal protein

Question 39

is Vitamin B12 (cobalamin) destroyed by cooking?

Answer 39

no

Question 40

is a deficiency in Vitamin B12 (cobalamin) distinguishable from a folate deficiency?

Answer 40

Deficiency initially indistinguishable from folate deficiency

Question 41

the storage and absorption of vitamin B12 (cobalamin)

Answer 41

storage: 3 years Absorption: Bound to IF → ileum

Question 42

what is folate (vitamin B9) found in

Answer 42

Liver, greens, yeast, grains, nuts.

Question 43

is folate (vitamin B9) destroyed by cooking?

Answer 43

yes, Prolonged boiling or deep frying (brief cooking eg stir-frying ok)

Question 44

is a deficiency in folate (vitamin B9) distinguishable from a vitamin B12 (cobalamin) deficiency?

Answer 44

Deficiency mostly indistinguishable from B12 deficiency

Question 45

storage and absorption of Folate (vitamin B9)

Answer 45

storage: 4 months only Absorption: duodenum & jejunum

Question 46

Main Causes of B12 deficiency

Answer 46

Nutritional - diet, e.g vegan diet Malabsorption Gastric - Pernicious anaemia, Surgical gastrectomy (Parietal cells removed and Gastroferrin for iron absorption reduced) Intestinal - Ileum disease, e.g.Crohn’s

Question 47

Causes of folate deficiency

Answer 47

Nutritional - Old age, poverty, alcoholism Malabsorption - Coeliac, Crohn’s Excess utilization - Pregnancy, lactation, Haemolytic anaemias, Psoriasis Anticonvulsants

Question 48

Folate deficiency clinical features are same as for pernicous anaemia but without

Answer 48

neurological symptoms. Treatment: oral folic acid

Question 49

Pernicious anaemia is a what kind of disorder?

Answer 49

Autoimmune disorder

Question 50

incidence of Pernicious anaemia

Answer 50

Incidence is 1-2% in population > 60 years with more Females than males being affected. Associated with fair hair, blue eyes, blood group A

Question 51

pernicious anemia is due to what?

Answer 51

Due to an Autoantibody against parietal cells, that can target the H+/K+ transporter. Absence of HCL secretion is called achlorhydria. Leads to gastric atrophy, ↓ HCl acid & ↓ IF secretion

Question 52

Pernicious anaemia: clinical features

Answer 52

* Insidious (gradual onset but fatal if untreated) * Anaemia * Glossitis (inflammation of tongue) * Mild jaundice * Neurological Symptoms – Peripheral neuropathy – Damage to Sensory and Motor tracts – Dementia – Optic atrophy

Question 53

treatment of Pernicious anaemia

Answer 53

intramuscular injection of B12 every 3 months. for life

Question 54

Lab investigations of Pernicious anaemia

Answer 54

Lab investigations show Macrocytic anaemia, Hypersegmented neutrophils Decreased Serum B12

Question 55

what is vomiting?

Answer 55

a forceful contraction resulting in expulsion of contents from the mouth. It is caused by sustained contraction of abdominal muscles, descent of diaphragm, opening of gastric cardia and gastric retropulsion.

Question 56

vomiting is associated with?

Answer 56

It is associated with autonomic signs, cold sweat, pallor

Question 57

vomiting is followed by?

Answer 57

followed by tiredness attesting to metabolic requirements during the action. It can be repetitive and go on for hours, days or weeks and might not go away. This can be associated with dehydration, anorexia, broken ribs, torn blood vessels, refusal to take medications.

Question 58

There are connections between the CTZ (chemoreceptor trigger zone) and?

Answer 58

vomiting centre.

Question 59

There are also incoming signals to the vomiting centre from the? and what does this relay?

Answer 59

There are also incoming signals to the vomiting centre from the nucleus of the solitary tract, relaying vagal afferents from the gastrointestinal tract, and sensory information from visual, vestibular (inner ear), smell (olfactory), and higher level cortical areas [nucleus tract solitaris - NTS]

Question 60

roles of organs in vomiting

Answer 60

glottis closes oesophageal sphincters relax stomach relaxes abdominal muscles and diaphragm contract duodenum contracts

Question 61

Antiemetics include?

Answer 61

cinnarizine, prochlorperazine and metoclopramide.

Question 62

Cinnarizine mechanism of action?

Answer 62

Antihistamine (H1 receptor antagonist) and calcium channel blocker

Question 63

Prochlorperazine mechanism of action?

Answer 63

Anti-nausea effect is mainly due to D2 blockade. At higher doses, it can also affect other receptors (like histamine and acetylcholine).

Question 64

Metoclopramide mechanism of action?

Answer 64

Dopamine D2 receptor antagonist. Can also act on 5-HT3 receptors, especially at higher dose.

Question 65

A post hepatic blockage is serious. when does this condition occur

Answer 65

occurs most often in people with serious liver disease, including cirrhosis from alcoholism

Question 66

when do Oesophageal varices develop

Answer 66

develop when normal blood flow to the liver is blocked by a clot or scar tissue. To go around the blockages, blood flows into smaller blood vessels that aren't designed to carry large volumes of blood. These veins can rupture causing bleeding in the stomach which is vomited or released in the stool.