Physiology Flashcards
Gastro-intestinal motility is mostly due to the activity of what kind of muscle?
Smooth muscle
Circular, longitudinal and muscular mucosae
Where in the GI tract is there skeletal muscle?
Mouth, pharynx, upper third of oesophagus.
External anal sphincter
What skeletal muscle is not under voluntary control in the GI tract?
Upper oesophageal skeletal muscle.
Contraction of circular muscle does what to the lumen>
Narrower and longer
Longitudinal muscle makes the intestine
shorter and fatter
Adjacent smooth muscle cells are coupled by?
forming a functional…?
Gap junctions.
Forming a functional syncytium
How does electrical activity in the small and large intestine occur?
As slow waves
Synchronous muscle cell contractions
What are the slow waves driven by (pacemaker)?
Interstitial cells of Cajal
When does contraction occur? (in terms of slow waves)
Contraction only occurs if the slow wave amplitude is sufficient to trigger SMC action potentials
A threshold must be reached
Up- stroke of GI AP?
Voltage activated Ca2+ channels
Downstroke by?
Voltage activated K+ channels.
Where are the interstitial cells of cajal located?
Between the longitudinal and circular muscle layers
More action potentials =
stronger contraction
Enteric Nervous system
Intrinsic to GI tissue
Can operate independently
Hormones and extrinsic nerves exert a strong influence
Basal electric rhythm of stomach, S.I. and L.I.
Stomach = 3 slow waves/min
S.I. = 12 waves/min in duodenum
8/min in terminal ileum
L.I. = 8/min in proximal colon
16/min in sigmoid colon
favouring retention of luminal contents
Myenteric Plexus (Auerbach’s)
Regulates motility and sphincters.
Submucous (Meissner’s) plexus
Modulates epithelia and blood vessels
How is muscular, secretive and absorptive activities coordinated?
> Sensory neurones
Interneurones
Effector neurones
What do the pelvic splanchnic nerves innervate?
The distal 1/3rd of the transverse colon
Sigmoid colon
Rectum
S2,3,4 keeps the shit of the floor
PARASYMPATHETIC
What does the vagus nerve innervate?
The proximal 2/3 of the transverse colon and the rest of the proximal GI tract (stomach, S.I.)
PARASYMPATHETIC
What does the parasympathetic nerves in GI do?
Excitatory - increase gastric, pancreatic and S.I. secretion, blood flow and SM contraction
Inhibitory - relaxation of some sphincters
Sympathetic innervation of the GI tract
Superior cervical ganglion - oesophagus
- Celiac
- Superior mesenteric
- Inferior mesenteric
correspond to their arterial counterparts
Function of sympathetic innervation
Increased sphincter tone.
Decreased motility, secretion and blood flow.
Nerve reflexes in GI tract
- 3 types
- Intrinsic and extrinsic reflexes
Local reflex - peristalsis (intrinsic reflex)
Short reflex - intestino-intesitnal inhibitory reflex (extrinsic reflex)
Long reflex - gastroileal reflex (extrinsic reflex) – these go to the medulla oblongata
Short reflexes bring about
local distension activates sensory neurones exciting sympathetic pre-ganglionic fibres that cause inhibition of muscle activity in adjacent areas)
Long reflex
increase in gastric activity causes increased propulsive activity in the terminal ileum)
Peristalsis
Wave of relaxation followed by contraction
Contraction behind food
Relaxation in front
Contraction of circular muscle and longitudinal muscle…
Release of ACh and substance P from excitatory motorneurone
Relaxation of circular muscle and longitudinal muscle
Due to release of vasoactive intestinal peptide (VIP) and NO from inhibitory motorneurone
Segmentation
what is it
where does it occur?
Mixing, churning movements
Rhythmic contraction of circular muscle layer that mix and divide luminal contents
Occurs in small intestine
Colonic mass movement
sweeping contraction that forces faeces into the rectum
Migrating motor complex
sweeping contraction from stomach to terminal ileum
Tonic contractions
sustained contractions
Low pressure - stomach (storage function)
High pressure - sphincters
Sphincters of GI tract
6 (excluding the sphincter of Oddi)
One way valves
UOS (skeletal, not voluntary) LOS Pyloric sphincter Ileocaecal valve Internal anal (smooth) External anal (skeletal)
Swallowing
phases
i) Oral/voluntary phase
ii) Pharyngeal
iii) Oesophageal
- Close lips (orbicularis oris and CNVII)
- The tongue (CN XII) pushes the blousy posteriorly towards oropharynx
- Contract pharyngeal constrictor muscles (CNX) to push bolus inferiorly towards oesophagus
- inner longitudinal layer of pharyngeal muscles (CN IX & X) contracts to raise the larynx, shortening the pharynx and closing off laryngeal inlet
- Bolus reaches oesophagus
Alpha amylase
Breaks down linear INTERNAL alpha-1,4 linkages but NOT terminal linkages
Products are linear glucose oligomers (maltose, maltotriose)
Oligosaccharides
Integral membrane proteins
Lactose Intolerance
Caused by lactase insufficiency
Primary lactase deficiency (primary hypolactasia) — most common
Secondary lactase deficiency - caused by damage/infection to proximal S.I.
Congenital lactase deficiency - rare autosomal recessive disease
Overall process of digestion and absorption is known as?
Assimilation
Where are the final products of carbohydrate digested?
Duodenum and jejunum
What are glucose and galactose absorbed by?
Fructose
Secondary active transport - SGLT1
Fructose - facilitated diffusion mediated by GLUT5
EXIT for ALL monosaccharides?
Facilitated diffusion by GLUT2
SGLT1 operation
Sodium and glucose symport
- 2 Na bind
- Affinity for glucose increases and glucose binds
- Na+ and glucose translocate
- 2 Na+ dissociate
- Glucose dissociates
- repeat
All dietary carbohydrate must be converted to?
Monosaccharides in order to be absorbed
How many pathways of protein digestion?
4
End product is amino acid in the blood.
Pepsin is an…
Endopeptidase
Enzymes in duodenum
Endopeptidases//
Trypsin
Chymotrypsin
Elastase
Exopeptidases//
Procarboxypeptidase A
Procarboxypeptidase B
All of these enzymes are secreted as proenzymes and are converted to active form in duodenum.
Amino acid absorption
7 different mechanisms at brush border//
5 Na+ dependent co transporters
2 Na+ independent
5 different mechanisms on basolateral membrane//
3 mediate efflux, Na+ independent
2 mediate influx, Na+ dependent
BIDIRECTIONAL
How are Di-, tri- and tetra-peptides transported?
Via H+ dependent mechanisms (PepT1) at brush border
What does PepT1 do?
Transports Oligopeptides
Satiation
Sensatiion of fullness generated during a meal
Satiety
Period of time between termination of one meal and initiation of the next
Satiation signals
CCK (cholecystokinin)
Peptide YY
Glucagon-like peptide 1
Oxyntomodulin
Obestatin
Ghrelin
“Hunger signal”
Secreted by oxyntic cells
Increase before meals
Decrease after meals
Stimulates food intake (hypothalamus)
Help control fat metabolism
CCK (Cholecystokinin)
Satiation signal
Secreted from enteroendocrine cells in duodenum and jejunum.
Stimulates hindbrain directly
Nucleus tractus solitarus
Peptide YY
Satiation signal
Secreted from endocrine mucosal L cells
Signals travel to hypothalamus
Glucagon-like peptide
Satiation signal
Released from L cells
Inhibits gastric emptying
reduces food intake
acts upon Hypothalamus and Nucleus Tractus Solitarus
Oxyntomodulin
Suppresses appetite
Obestatin
Satiation signal
Reduce food intake
Which hormones report fat status back to the brain?
“ADIPOSITY SIGNALS”
Leptin - made and released from fat cells
Insulin - made and released from pancreatic cells
Inform brain to alter energy balance - eat less and increase energy burn
MALFUNCTIONS in obese state
Leptin roles
Food intake/energy expenditure/fat deposition
Peripheral glucose homeostasis/insulin sensitivity
Maintenance of immune system
Maintenance of reproductive system
Angiogenesis
Tumourigenesis
Bone formation
Insulin
Circulates in proportion to body adiposity
High levels of insulin receptors in hypothalamus
Dopamine
Hedonistic pathway
Food addiction
Chocolate, sugar & fat
Human obesity
High levels of leptin levels
Corresponds to High fat level
Diet induced obesity leads to
Leptin resistance
1) Defective leptin transport
2) Altered signal transduction following leptin binding to its receptor
Therapy for obesity
Bariatric surgery
Gastric by pass surgery
Induces high level of complete resolution of TIIDM
Restricts calorie intake.
Adaptive thermogenesis
> Adult humans have brown adipose tissue
> Brown adipose tissue dissipates energy as heat
Increase energy expenditure uncoupling of oxidative metabolism from ATP production
Uncoupling protein 1 (UCP1) - fatty acid activated protein
short circuits proton gradient in mitochondria -
Produce heat
What 3 glands is saliva secreted from?
which nerves innervate them?
Parotid - CN IX
Submandibular - CN VII
Sublingual - CNVII
Parotid duct of Stensen (opposite second maxillary molar teeth)
Submandibular - duct of Wharton –> sublingual caruncula
Sublingual - medial to submandibular glands. Ducts of Rivinus –> connect with whartons
Largest saliva gland?
Parotid
What are the functional units of the salivary gland?
Salivons
Serous cells (within salivon)
Watery secretion rich in α-amylase; contain small, dense, secretory granules
Mucous cells (within salivon)
Produce a thick mucous rich secretion.
What pH is salvia normally?
What does this help with?
Alkaline, hypotonic
Helps buffer acids in foods
Which electrolytes are found in HIGHER concentrations than that in the plasma?
K+ & HCO3-
Secretions of glands.
Composition
Parotid - watery, alpha-amylase rich
Submandibular - mixed serous and mucous cells, more viscous
Sublingual - thick solution rich in mucous
HCO3- concentration… with increased flow rate of saliva?
Increases
as does pH
K+ concentration… with rate?
Decreases
Formation of saliva - stages
- Primary secretion by acinus cells
2. Secondary modification by duct cells -
Secondary modification of saliva
By striated, intercalated and excretory ducts.
Removes Na+ and Cl-
Adds K+ and HCO3-
Diluting effect.
Saliva becomes alkaline
Salivary control
Simple (unconditioned)//
Receptors in mouth activated in presence of food
Acquired (conditioned, pavlov’s dog)//
- think about, see, smell, hear prep of food
Impulses via afferent nerves.
Normal salvia production is dominated by what kind of stimulation?
Parasympathetic
Glossopharyngeal (CNIX)
Facial (CNVII)
Muscarinic ACh receptors
More blood to glands
Increased synthesis and secretion of alpha amylase
Increased fluid flow
Contraction of myoepithelial cells
Large volume, watery saliva
What do muscarinic receptor antagonists cause/ antidepressants cause?
Dry mouth
Sympathetic stimulation of saliva glands
Dominant at stressful times.
Dry mouth
Increased secretion of alpha amylase, K+ and HCO3-
Increased contraction of myoepithelal cells
Decreased blood flow to glands
Thick mucous rich saliva
What causes relaxation in the stomach (nerve)?
Vagus CNX
Emptying of stomach.
Rate of emptying proportional to:
Peristaltic action in direction of pylorus
Contractions become stronger due to presence of food
Supra-threshold gastric slow waves
Pyloric sphincter open just enough to allow a wee squirt of chyme into duodenum
Rate of emptying proportional to VOLUME and consistency of chyme in stomach.
Duodenum has to be ready to receive chyme. Can delay emptying of stomach by:
Enterogastric reflex (neuronal)//
decreases astral peristaltic activity
Hormonal response//
release of enterogastrones (secretin and CCK) - inhibits stomach contraction
What stimuli in the duodenum drive the neuronal and hormonal responses?
FAT - delay required to digest and absorb in S.I.
ACID - time required for neutralisation
HYPERTONICITY - products of carbs are osmotically active and draw water into S.I.. Need for slowing down of digestion
DISTENSION
What cells are present in the funds and body of the stomach?
Oxyntic mucosa
> Chief cells - pepsinogen
Enterochromaffin - histamine
Parietal cell - HCL, Intrinsic factor
What cells are present tin the antrum?
pyloric gland area
D cells - somatostatin
G cells - gastrin
What does intrinsic factor do?
Binds vitamin B12
allows absorption in terminal ileum.
What does histamine do?
Stimulates HCl secretion
Gastrin - function in stomach
Stimulates HCl secretion
Somatostatin - function in stomach
INHIBITS HCL secretion
HCl - function in stomach
Activates pepsinogen –> pepsin
Denatures proteins
Kills many micr organisms
Pepsinogen
Inactive precursor
Pepsin, once formed (by HCl), activates pepsinogen
POSITIVE FEEDBACK LOOP
What enzyme does H+ and Cl- secretion depend on?
Carbonic anhydrase
HCO3- ions exchanged for Cl- ions
Proton (H+) pump with K+
What receptor does gastrin bind to?
CCK2 receptors
What is the STRONGEST agonist of hydrogeen ion secretion?
HISTAMINE
Secratagogues (histamine, gastrin, ACh) cause…
Trafficking of H+/K+ ATPase
Moves the ATPase from cytoplasm to apical membrane/ extended microvilli.
What do D cells do?
Secrete somatostatin
What are the 3 phases of gastric secretion?
Cephalic phase
Gastric phase
Intestinal phase
Half the acid produced during cephalic stage
Cephalic stage
Prepares stomach to receive food.
Gastric phase
Mechanical and chemical factors augment secretion.
Distension –> increased HCl via ACh receptor
Protein digestion products –> stimulate G cels –> Gastrin –> HCl release
G cells secrete?
Gastrin
Enterochromaffin-like cells secrete?
Histamine
Intestinal Phase - factors originating from S.I. that switch off acid secretion.
↓ gastric motility –> ↓ gastric secretion
As stomach empties, the stimuli for secretion become less intense.
Secretion of somatostatin resumes
large inhibitory
What do PPIs block?
K+/H+ ATPase membrane inserted
do not bock tubulovesicles
NSAIDs block?
COX
thereby reducing Prostaglandins whihc inhibit secretion
leading to increased acid secretion.
–> Peptic ulcers & bleeding
What protects the mucosa?
Locally produced prostaglandins (PGE2 and PGI2)
> Reduce acid secretion
Increase mucous and bicarb secretion
Increase mucosal blood flow
H. pylori
Protected in mucous gel.
Secretes agents causing a persistent inflammation
Wekanes mucosal barrier
Breakdown of mucosal barrier damages the mucosal cell layer and leaves the submucosa subject to attack by HCl and Pepsin.
Zollinger-Ellison syndrome
Rare
gastrin-producing tumour
Salivary gland composition
External capsule
Septa separating lobes and lobules
Lobules composed of salivons
Each salivon consists of
Secretory acinus
Intercalated duct
striated duct
Striated ducts unite to form
Interlobular ducts
Excretory cells
Salivon
• ACINUS
Formed from pyramidal shaped secretory acinar cells around a central lumen that are either
- – serous cells
- – mucous cells
- Contractile myoepithelial cells that surround the acinus
- Serous demesnes
- Intercalated duct (cuboidal)
- A striated duct (columnar)
Functions of saliva (4)
> Lubrication
Protection
— against bacteria and their metabolic products
> Digestion
— alpha amylase
> Other
What pH is saliva?
Alkaline so to buffer foods
Why is the overall effect of the secondary modification of saliva diluting?
Because H20 cannot pass through the duct walls (intercalated, excretory and striated)
What exchanges Cl- for HCO3- across the apical membrane?
What is it regulated by?
HCO3-/CL- antiporter
Regulated by the cystic fibrosis transmembrane conductance regulator (CFTR)
What empties from the stomach more quickly?
Liquids
Stomach distension increases… what?
Motility due to stretch of smooth muscle
Activity of intrinsic nerve plexuses
Vagus nerve activity
Gastrin release
Roll of mucous in oxyntic mucosa?
Protective
What do parietal cells do in the stomach?
Secrete HCl
Intrinsic factor
What occurs in pernicious anaemia?
Autoimmune disease
Targets parietal cells and intrinsic factor
Does not allow absorption of vitamin b12
–> b12 deficiency
How can gastric damage die to long term NSAID treatment be prevented?
By using a stable PGE1 analogue
— inhibits basal and food stimulated gastric acid production
— maintains (or increases) secretion and mucous and bicarbonate
Cushing’s ulcer
Heightened vagal tone leading to acid hypersecretion
Sucralfate
Mucosal strengthener
Aluminium
Binds to ulcer base ionically (aluminium is negative and ulcer base is positive) and forms a mucosal barrier against acid and pepsin
Bismuth chealate
Mucosal strengthener
aluminium
toxic towards H pylori
