Physiology Flashcards
Swallowing
Swallowing centre in medulla coordinates contraction of skeletal muscle (30-40 cm/s) causing rapid pharyngeal swallow of less than 1 second
Resting UOS pressure
30-200 mmHg
Decreases entry of air into oesophagus during tonic contraction
UOS relaxation
Only for 0.5 - 1 second
Occurs during swallowing, burping and vomiting
Peristalsis of oesophagus
Contraction above bolus and relaxation below bolus
Primary and secondary peristalsis
Primary peristalsis
Initiated by swallowing Continuation of pharyngeal contraction 3-5 cm/s Lasts about 5 seconds Pressure between 30-80 mmHg
Secondary peristalsis
Not induced by swallowing
Involuntary
Sensory receptors in oesophagus by retained bolus or gastric acid cause stimulation and contraction
Innervation of oesophageal peristalsis
Autonomic nervous system
Enteric nervous system: both submucosal and myenteric plexuses for reflex coordination
Systems communicate with each other
Lower oesophageal sphincter
Specialised segment of smooth muscle 2-4 cm long
Relaxes 1-2 s after swallowing. Relaxation lasts 5-10 s then hypercontracts
Can also relax transiently without swallowing when standing up to release air from stomach
Resting pressure of LOS
20-35 mmHg
3 phases of swallowing
Oral phase - voluntary
Pharyngeal phase - involuntary
Oesophageal phase - involuntary
Control of swallowing
Controlled by both cortex and brainstem
Swallowing centre in brainstem receives sensory input from receptors in posterior mouth and upper pharynx. Innervates swallowing muscles via cranial nerves
Oral phase of swallowing
Mastication
Saliva secretion
Transfer of bolus into pharynx
Tongue connects with hard palate, closes off anterior oral cavity to push bolus into back of mouth
Pharyngeal phase of swallowing
Lasts less than 1 second
Bolus enters pharynx from back of mouth and descends through pharynx by peristalsis at 30-40 cm/s
Tongue pushes against palate, sealing off the oropharynx. Soft palate elevates, sealing off nasopharynx. Epiglottis swings down, sealing off lower airway
Oesophageal phase of swallowing
UOS relaxes
Bolus enters oesophagus
Oesophageal peristalsis initiated
GORD
Gastro-oesophageal reflux disease
Gastric contents enter oesophagus which irritates stratified squamous epithelium
Most reflux episodes occur during transient relaxations of LOS
GORD risk factors
Disordered gastric motility
Hiatus hernia
Impaired oesophageal peristalsis
Hypotensive LOS (doesn’t contract enough)
Caffeine, alcohol, chocolate, fats, medications
Hiatus hernia
Oesophagus protrudes through hiatus, an opening in the diaphragm
GORD complications
Reflux oesophagitis (ulceration) Oesophageal structure (scarring leading to dysphagia) Barretts oesophagus (metaplasia, potentially leading to cancer)
2 types of oesophageal cancer
Adenocarcinoma (likely to be in distal oesophagus/GO junction)
Squamous cell carcinoma (likely to be in proximal oesophagus)
Squamocolumnar junction
Junction between oesophagus and stomach forming a visible transition between stratified squamous and columnar epithelium
Causes of oesophageal ulceration
HSV
Cytomegalovirus
Doxycycline
Bisophosphonates
Eosinophilic oesophagitis
Eosinophils infiltrate the epithelium of oesophagus
Allergy mediated
Oesophageal ring/web
Used interchangeably
Thin mucosal membrane often associated with hiatus hernia
Adenocarcinoma likely causes
GORD, Barretts
Squamous cell carcinoma likely causes
Smoking, alcohol, diet
Oesophageal stricture
Narrowing of oesophagus
Can be peptic (due to stomach acid causing scarring)
Or caustic (due to ingestion of chemical agents)
Often occurs after radiotherapy and some surgeries
Malignant
Zenkers diverticulum
Pharyngeal pouch
UOS fails to relax
Excessive pressure causes weakest portion of pharynx to balloon out
Common in elderly
Diffuse oesophageal spasm (corkscrew oesophagus)
Non-peristaltic or simultaneous onset of contractions in the oesophagus
Chest pain, dysphagia, bolus obstruction
Achalasia
Degeneration of oesophageal nerves including ganglionic cells in myenteric plexus and inhibitory neurons in LOS that switch off tonic contraction
Prevents LOS relaxation and loss of peistalsis
Scleroderma
Connective tissue disorder causing fibrosis of submucosa and muscle layers
Absent peristalsis, weak contractions and loss of LOS tone
Dysphagia and reflux
Functions of stomach
Food reservoir Adjusts osmolarity of contents Grinding mill (fundus) Particle size regulation (pylorus) Acid secretion (among others)
Gastric motility steps
Relaxation of fundus
Contraction of body and antrum
Pylorus contracts
Mixing by retropulsion
Vagovagal reflex
Fundus relaxation
Dumping syndrome
Food moves too quickly from stomach into duodenum, not completely digested
Hyperosmolar chyme
Rapid fluid shift into gut
Causes diarrhoea, pain, nausea, vomiting and cramping
Prokinetics
Drugs that speed up gastric emptying e.g. metoclopramide which releases ACh at myenteric plexus
Diabetic gastroparesis
Due to autonomic neuropathy
Variable rate of glucose absorption
Upper abdominal discomfort
Gastric acid roles
Sterilisation
Protein denaturation
B12 and iron absorption
Achlorydia (absent or low gastric acid)
Gastric pH
HCl produced at 160 nm = pH 0.8
pH in stomach lumen = 1.5 - 2
Buffers with meals to 5-6
Gradually falls during night
Neurotransmitter
Molecule that transmits a signal from one neuron to another
Autocrine
Molecule released by a cell that targets itself
Paracrine
Molecule released by a cell that targets adjacent cells
Endocrine
Molecule released by a cell that targets distant cells via bloodstream circulation
ACh
Neurotransmitter
Released by vagus nerve and enteric neurons
Stimulates parietal cells to release HCl, ECL cells to release histamine (which stimulates parietal cells) and G cells to release gastrin (which stimulates parietal cells and ECL cells)
ECL cells
Located in stomach body
Secrete histamine (molecule with paracrine activity)
Stimulates acid secretion directly by acting on adjacent parietal cells
G cells
Located in stomach antrum
Secrete gastrin (hormone with endocrine activity)
Stimulates acid secretion indirectly via ECL cells which release histamine which stimulate parietal cells to secrete HCl
D cells
Located in stomach antrum
Secrete somatostatin (hormone with endocrine and paracrine activity)
Inhibits acid secretion by inhibiting gastrin from adjacent G cells
Cephalic phase mediation
Vagus nerve releases ACh which stimulates parietal cells
Gastric phase mediation
Distension of body and antrum causes acid secretion by vagus nerve
Protein in antrum stimulates G cells which release gastrin
Intestinal phase mediation
HCl in antrum causes somatostatin release from D cells. Gastrin inhibited.
HCl in duodenum stimulates secretin which inhibits gastric acid and stimulates bicarbonate secretion from pancreas
Partially digested fat and protein in duodenum stimulate CCK which inhibits gastric acid and emptying, also stimulating release of pancreatic enzymes and gallbladder contraction for bile release
Causes of increased gastric acid secretion
H. pylori gastritis
Gastrinoma
Causes of decreased gastric acid secretion
Loss of parietal cells e.g. pernicious anaemia
Vagotomy leading to less ACh
Drugs e.g. proton pump inhibitors and histamine 2 receptor antagonists
Gastric surgery
Pepsinogen
Secreted from chief cells
Pro-enzymes of pepsin - cleaved in acid
Pepsin
Degrades/hydrolyses proteins at aspartic amino acids
If pH less than 4 pepsin is inavtive
Pepsinogen role in digestion
Cleaves to pepsin which hydrolyses proteins which are a stimulus for gastrin release
Prostaglandins
Lipid molecules that protect and repair gastric mucosa
Peptic ulcer disease
Pain, bleeding, perforation and obstruction
Can cause swelling and stricture
Treatment includes triple therapy antibiotics and in severe cases, gastrectomy, vagotomy and pyloroplasty
H. pylori
Gastritis, ulcers, cancer, MALToma
MALToma
Mucosa-associated lymphoid tissue lymphoma
Triple therapy
Omeprazole Clarithromycin Amoxycillin 14 day treatment Low recurrence rate
Other causes of peptic ulcer disease
Aspirin and NSAIDS
Gastric adeocarcinoma
Intestinal: well-differentiated, cells arranged in a tubular/glandular pattern
Diffuse: poorly differentiated, lack glandular formation, linitis plastica
Linitis plastica
Metastatic infiltration of the stomach
H. pylori and gastric cancer link
Strong association for intestinal type adenocarcinoma
Widespread inflammation and destruction of parietal cells to reduce gastric acid secretion leading to achlorydia, bacterial overgrowth and carcinogens
Osmotic diarrhoea
Macronutrient malabsorption retains osmotic pressure in lumen of intestines. Water also retained, increasing water content in stools
Secretory diarrhoea
Increased second messengers increases anion secretion. To maintain charge balance in the cell cations stay or move in, bringing water along. No impact on sodium/glucose transporters.
Solvent drag
Responsible for increased sodium and increased urea absorption in jejunum
Transporters in intestinal epithelial cells
NaKATPases - mediate transcellular Na+ movement on the basolateral membrane
NaH exchanges
Na/glucose symporters on the apical membrane
NK2Cl channel
K+, Na+ and 2 x Cl- transported into cell
2 x Cl- then transported out of cell through CFTR channel
Mediated by second messengers
Absorption and secretion hormones
Enteric: ACh and secretagogues
Endocrine: Aldosterone
Paracrine: Serotonin
Small intestine net absorption and secretion
Absorption of water, Na+, Cl-, K+
Secretor of HCO3-
Hypovolemic shock
Decreased blood pressure due to water loss, heart rate rises to compensate BP and maintain cardiac output
Cholera toxin
Activates CFTR channel which increases Cl- secretion
Na+ and water follow
Oral rehydration therapy
Water and key ions to compensate extracellular fluid loss
During loss, body becomes acidotic. Oral rehydration therapy includes HCO3- to neutralise this effect
