GI Physiology, the Oesophagus and Stomach

Gastroenterology FRACP Lecture Series

GI Physiology,

the Oesophagus and Stomach

Tony Catto-Smith

GI tract development

•Folding forms tube – closed at cranial and caudal ends (also forms respiratory tube)

•3 regions – Fore, Mid and Hind gut

•Midgut open but progressively reduced

•Digestive tube constricts to form oesophagus, stomach, small and large intestine

•Lining endodermal cells surrounded by mesodermal mesenchyme providing muscles

Anthony G Catto-Smith

Endoderm-mesoderm interactions direct development

•Endodermal tube induces regional specificity of splanchnic mesoderm via Sonic Hedgehog (Shh)

•Mesodermal receptor is “Patched” protein

•Induces nested expression of “Hox” genes in mesoderm, allowing regional specification – oesophagus to anus


Hepato-Pancreatic Development


Mid-gut rotation (7-11 weeks)


Normal intestinal rotation wk 5-12

Non-rotation

Incomplete

rotation

Malrotation without volvulus

Abnormalities of midgut rotation


Non-rotation

Mix rotation/volvulus

Reversed rotation

Sub hep cecum/appendix

Internal hernia

Midgut volvulus

Operative correction of malrotation

with volvulus by Ladd’s procedure

Intestinal malrotation with volvulus

– proximal jejunal “corkscrew”

Clinical Conditions Associated With Intestinal Malrotation

Asplenia/polysplenia/heterotaxy syndrome

Atrial isomerism

Congenital diaphragmatic hernia

Duodenal, jejunoileal atresia

Esophageal atresia/tracheoesophageal fistula

Gastroschisis/omphalocele

Hirschsprung’s disease, intestinal pseudo-obstruction

Intussusception

What is this?


Residual abnormalities from embryonic yolk sac





Intestinal mucosa


Enterocytes continually produced from stem cells







The Oesophagus

• MOTOR function – TWO types of peristalsis

• Primary – continuation of pharyrngeal contraction (5-8 sec)

• Secondary – results from distension – continues till relieved

– TWO types of muscle • Striated in pharynx and upper third

• Smooth in lower 2/3rds. Vagal control for both but myenteric plexus can still operate independently

• ACHALASIA – TWO requirements

• Aperistalsis AND

• Impaired LOS relaxation with swallow.


Achalasia

• Inhibitory myenteric ganglion degeneration

• Likely due to autoimmune process with latent infection of HSV-1 in genetically susceptible individuals

• Partial preservation of post-ganglionic cholinergic pathway basis for Botox effect


Achalasia - progression

• Earliest? – Diffuse oesophageal spasm

• Early stage – High amplitude contractions – often repetitive

– Lacks orderly relaxation/contraction of LOS

– Chest pain associated

– “Vigorous achalasia”

– Preservation of myenteric ganglia

– Responds well to treatment

• Classic achalasia – Negligible oesophageal contraction (big and baggy)


Progression of radiological

changes in achalasia


Achalasia – associations

• Triple A syndrome – ACTH insensitivity low BSL from age 5 yr alacrima from

birth

– Can be delayed dx till adults

– 12q13

• Rozycki syndrome – AR deafness, short stature, vitiligo, muscle wasting

• Others – Chagas, sarcoid, Hirschsprung, Downs, pyloric stenosis etc

Oesophageal Manometry



High Resolution Manometry


Early Late

Poor response Anthony G Catto-Smith

GOR: regurgitation


GOR: consequences

• “Reflux” is only a disease if it causes harm

• Most reflux and reflux “disease” usually resolves in infants by 1-2 years

• About half of older children and adults with GORD experience a chronic relapsing course


GOR: protective

mechanisms


Gravity, saliva, bicarbonate

peristalsis

GOR: destinations

and consequences


GORD in infants and children

• Oesophagitis – chest pain, dysphagia, blood

loss – asymptomatic oesophagitis – complicated oesophagitis

• peptic stricture • Barrett’s metaplasia

• Neurobehavioural – Sandifer’s – rumination

• Malnutrition

• Respiratory – pneumonia – asthma – apnoea (lary obstruction) – stridor – apnoea, bradycardia

(central) – BPD, CF – Oes atresia – Other

• belching, hiccups, cough, hoarseness, pharyngo-nasal, dental, sinusitis, otitis, subglottic stenosis


GOR: Sandifer’s syndrome


Oesophageal

acid cleared

by peristalsis

and saliva.

Helm JF. N Engl J Med

1984;310:284.



Natural evolution of physiological regurgitation

% children

with >3/day regurg

GOR: oesophagitis



Barrett esophagus


“Typical” Barrett's mucosa, with intestinal metaplasia and goblet cells adjacent to

squamous epithelium


GOR: apnoea


Differential diagnosis

• Extra GI

– otitis media

– pneumonia

– pyelonephritis

– meningitis

• GI infections

– gastroenteritis


Anatomical Atresia/stenosis/web

meconium ileus

hernia

malrotation

Motility disorders

Others metabolic, endocrine etc

Therapeutic approach to GOR

• Phase 1 Parental reassurance. Observation. Lifestyle changes. Exclude overfeeding.

• Phase 2 Dietary treatment (decrease regurgitation) Thickened formula, thickening agents, extensive hydrolysates or amino acid based formula in CMPI Positional treatment

• Phase 3 For immediate symptom relief: alginates (some efficacy in moderate GERD); antacids only in older children

• Phase 4 Proton pump inhibitors (drug of choice in severe GERD; more safety data needed) H 2 receptor antagonists less effective than PPIs

• Phase 5 Prokinetics (but not one product available on the market in 2009 has been shown to be effective) Would treat pathophysiologic mechanism of GERD

• Phase 6 Laparoscopic surgery

Nissen fundoplication


GOR: surgical therapy

• Fundoplication – indications

• unresponsive to medical therapy

• neurological disease

• peptic strictures

• Barrett’s

• G-tube feeds

• respiratory disease

– success • 90% (but depends on choice)


complications herniation

adhesions

gas bloat

inability to burp

dysphagia

dumping

Eosinophilic oesophagitis

Gonsalves et al. Gastroenterology 2012;142:1451


Effect of six food elimination diet


The stomach


3 gastric functions

• Motor • Secretory

• Endocrine

• Motor – reservoir

• compliance of wall • digestion (saliva/lingual)

– mixing of food, fluid and gastric enzymes

– kneading of food particles to <1mm diameter

– metered emptying in response to duodenal feedback





Modulation of gastric emptying

Meal factors Effect

Volume Rate proportional

Acidity Slows

Osmolarity Hypertonic slower

Nutrient density Rate inverse to density

Fat Slows

Other factors

Ileal fat Slows

Rectal/colonic distension Slows

Pregnancy Slows





3 gastric functions

• Motor

• Secretory • Endocrine

• Secretory – Hydrogen ion

• converts pepsinogen to pepsin

• kills microbes

• denatures protein

– Pepsinogens • partly digest proteins

– Mucus • lubricates/protects mucosa

– Bicarbonate • protects mucosa

– Intrinsic factor • nec for B12 absorption

– Water (2.5 L/d) • solvation and dilution


Stimulation of acid secretion is divided into four phases

PHASE STIMULUS % TOTAL

Interdigestive Basal 15

Cephalic Food, smell, taste, sight 30

Gastric Food in stomach 50

Intestinal Digestion products in

intestine

5


Meal Meal Meal

stomach oesophagus Anthony G Catto-Smith

3 gastric functions

• Motor

• Secretory

• Endocrine

• Endocrine

– Gastrin • stimulates acid secretion

• regulates mucosal growth

• stimulates pepsinogen sec’n

– Somatostatin • inhibits gastrin release


Intestinal mucosal structure


Carbohydrates


Conditions assoc with CHO malabsorption

• Primary or genetic – primary lactase non-persistence (adult) – sucrase-isomaltase deficiency – glucose-galactose malabsorption – congenital lactase deficiency

• Ontogenic – lactase deficiency of the premature infant – deficiency of pancreatic amylase in infancy

• Secondary or acquired – rotavirus infection, giardiasis – small bowel bacterial overgrowth – short gut syndrome, cow milk and soy protein hypersensitivity – AIDS

• Physiologic – fructose, sorbitol – fibre, vegetable oligosaccharides (beans)











SGLT-1


Glucose-galactose malabsorption

• SLC5A1 (solute carrier) encodes SGLT1

• Over 40 mutations in SLC5A1

• Defects give rise to glucose-galactose malabsorption

– Severe osmotic diarrhoea

– Stools acidic and contain sugar

– Normal fructose absorption and bowel structure

– Also have glycosuria (same defect in kidney)

– Diagnosis by reduced dose glucose breath test













Fermentation products - outcome Metabolic Product Target Organ Utilization / Function

Acetate Muscles, kidneys, heart and brain Energy production

Propionate Liver Potential precursor of gluconeogenesis; suppresses cholesterol synthesis

Butyrate Colonic epithelia Main energy supplier

Ethanol, succinate, lactate, pyruvate Intestines Fermentation to short chain fatty acids

Hydrogen Excretion (exhaled air or flatulence)

Methane Excretion (exhaled air or flatulence)

Carbon dioxide Excretion (exhaled air or flatulence)

Hydrogen sulfide Intestines Metabolized by bacteria

Ammonia Liver Conversion to urea

Branched chain fatty acids (BCFA) Liver Degradation

Amines Intestines Reaction partner during N-nitrosation reactions (possibly toxic if accumulated)

Phenolic compounds Excretion in urine (toxic potential)/Liver Detoxification Anthony G Catto-Smith





Mechanisms for antibiotic diarrhoea

– reduced Na-SCFA water salvage

– some antibiotics directly stimulate secretion

– induce overgrowth of opportunistic pathogens

Bacterial overgrowth in upper intestine

– Normal small intestine 103 to 106

– Predisposed by: • achlorhydria, blind loop,

dysmotility, stricture, inflammation, ileocaecal valve, PEM

– Causes • steatorrhoea

(deconjugated bile salts) • Normal histology, but

decreased disaccharidases • Hypoproteinaemia, • B12 def, d-lactic acidosis

– Diagnosis • lactulose breath test



Hydrogen

Methane



H. pylori


H pylori • Most common chronic bacterial infection

– at least 50% of world population infected

• Prevalence is higher in developing countries and in older age groups

• Inverse relationship to socioeconomic status – crowded living conditions

– suboptimal sanitation

• Person to person transmission – faeco-oral

– oro-oral


Clustering of H. pylori in families


H. pylori

• Epidemiology: children

– 10% adolescents in developed world

– 80% adolescents in developing countries

– neonatal infection very rare

– colonization may be reversible



H. pylori • Clinical

– asymptomatic in absence of ulceration

– commonest paed cause of chronic gastritis

– gastritis always present, but microscopic

– assoc with gastritis, GU and DU

– role in Rec Abdo Pain uncertain - prob not

– cancer / atrophic gastritis (declining)



H. pylori

• diagnosis

– endoscopy

• involves antrum, occ body

• antral nodularity (specific, not in adults)

• gram-neg spiral rods in surface mucus layer

– 13C-urea breath test (children)

– serology IgG, no use for 6 mo after therapy

• therapy

– 2-3 drugs for 2 or more weeks


H pylori: breath testing



Test Sens/Spec Confirms

eradication Serology 93%/90% No

Urea BT 96%/98% After >4 weeks

Biopsy urease 92%/98% After >4 weeks

Histology 98%/98% After >4 weeks

Culture 90%/100% After >4 weeks

H pylori: diagnostic tests


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GI Physiology, the Oesophagus and Stomach