Physiology Flashcards
Regulation of gastric emptying
Pyloric resistance and pressure differential
Water content of ingesta
Nutrient composition
(Carbohydrates faster than proteins which are faster than lipids
High fat content in the duodenum/ileum initiates a neuroendocrine mechanism that impedes gastric emptying)
Nutrient acidity
Nutrient osmolality
Hot or cold temperatures
GE is inhibited by nutrients entering the small intestine (feedback control) through enterogastric reflexes and secretin from the intestinal epithelium
GI motility is coordinated so that the main priority is the protection of the duodenum: excessive distension of the stomach leads to constriction of the pylorus, which prevents large volumes of solid ingesta from being rapidly emptied into the duodenum
Mediators of intestinal contractions
Contraction is stimulated by ACh and SP; relaxation is induced by VIP and NO
If an area of bowel is distended contractile activity in the rest of the bowel is inhibited to prevent the movement of ingesta into a segment of intestine that is already dilated.
Mediated by the extrinsic autonomic NS
Defecation reflex
stimulated by fecal accumulation in the anorectal canal stimulating smooth muscle contraction of the rectal wall and reflex inhibition of the internal anal sphincter
The external anal sphincter is under somatic (voluntary) control and is tonically contracted
The relaxation of the internal sphincter is transient as the rectal wall accommodates the stimulus of distension → regaining tone and stimulus to defecate subsiding
If rectosphincteric reflex is triggered when defecation is appropriate the external sphincter will be relaxed and evacuation will occur.
2 functional areas of stomach
Oxyntic gland contains parietal cells and comprises 80% of the stomach
The pyloric gland area comprises the remaining 20% and is made up of gastrin (G cells)
3 phases of gastric acid secretion
- Basal occurs in absence of stimulation to maintain gastric flora
- Cephalic phase is caused by anticipation of food, mediated by vagal postganglionic neurons
- Gastric phase accounts for the majority of acid secretion and is mediated by the direct and indirect effects of gastric distension and amino acids on parietal cells and antral G cells.
- Intestinal phase is mediated by effects of intraduodenal amino acids.
Mechanisms that stimulate parietal cell acid release
Neural: ACh binds M3 (IP3/DAG path)
Paracrine: histamine, from enterochromaffin cells, binding H2R (cAMP path)
Endocrine: gastrin from G cells in response to ACh, binds R (IP3/DAG)
Feedback: Somatostatin (from gastric D cells), PGs and adenosine have paracrine effects of inhibiting acid secretion through blocking cAMP production
Ghrelin production site and function
secreted from stomach
Triggers growth hormone release
–> stimulates appetite, body growth
(GI-hypothalamic-pituitary axis)
Antagonises leptin
Gastric mucosal defences
mucus-bicarbonate phospholipid barrier;
continuous cell renewal (proliferation of progenitor cells);
continuous blood flow through mucosal microvessels;
sensory innervation and
generation of PGs and nitric oxide.
Digestion of carbs, protein and lipid
Carbs - b/d by stomach acid –> pancreatic amylases then brush border enzymes
Glucose/calactose absorbed via GLUT cotransporters
Protein - pepsin in stomach and pancreatic proteases (released in response to CCK) in SI. Some brush border peptidases also expressed. amino acids absorbed by specific carriers
Ammonia (a/a digestion byproduct) - diffuses into circulation transported to liver for urea cycle
Lipid - gastric lipases and pancreatic lipases in SI then solubilised by bile salts into micelles (also have fat soluble vitamins present) –> diffuse into enterocytes and form lipoproteins –> lymphatics
Colonic bacterial fermentation of lipids –> SCFAs which are absorbed by colonic mucosa and utilised locally
CCK site of production and function
Duodenum and jejunum
Triggered by acid, protein and fat content of lumen
Stimulates: BG contraction, pancreatic enzyme release
Inhibits gastric emptying of liquids
Secretin site of production and function
S cells in duodenum
Response to lumen acidification
Stimulates HCO3 release from pancreatic ductal cells
Inhibits gastrin release (and thus acid release)
Somatostatin site of production and function
Gastric D cells
Release in response to protein/lipid and bile
Inhibits gastric acid secretion by inhibiting EC cell Histamine production
inhibits pepsin secretion
Gastric inhibitory peptide site of production and function
Proximal SI cells
Response to FAs, glucose, peptides
Stimulate pancreatic islet insulin release
Inhibits gastric motility
Glucagon site of production and function
Enteric and pancreatic
In response to FAs or glucose
Inhibits gastric emptying and H+ release
Reduces gut permeability
Motilin site of production and function
All GI cells
Stimulated by acid and fasting
initiates migrating motility complexes during fasted state
Coordinates secretions during feeding
Vasoactive intestinal polypeptide site of production and function
Vagal stimulation
Increases blood flow, stimulates fluid secretions
relaxes smooth muscle
Normal B12 absorption
Bound to dietary protein, cobalamin reaches the stomach where it is released by activated pepsinogen and gastric acid
Binds to haptocorrin (R protein) - to protect it from bacterial utilization in the proximal GI tract
In the duodenum, pancreatic proteases separate cobalamin from haptocorrin, and free cobalamin is bound to intrinsic factor (IF).
In dogs IF is produced primarily by the exocrine pancreas and to a lesser extent in the stomach
The cobalamin-IF-complex is then absorbed by receptor-mediated endocytosis.
The receptor, known as cubam, is localized at the brush border of the ileum
Function of B12 and result of deficiency
Acts as an essential cofactor for the intracellular enzymes methionine synthase and methylmalonyl-CoA mutase
Methionine synthase - converts homocysteine to methionine and tetrahydrofolate. B12 deficiency results in functional folate deficit (needed for purine synthesis) and increased HCY
Methylmalonic CoA mutase - produces succinyl-CoA for citric acid cycle from proprionyl CoA
In B12 deficit - increase methylmalonic acid (MMA)
MMA - inhibits urea cycle enzymes thus increasing ammonia which can result in neurological symptoms
Causes of B12 deficiency
Hereditary selective malabsorption (beagles, Borderr collie, giant schnauzer, Greyhound (US)) - defect/mutation in IF-receptor
GI Dz - reduced IF-receptor expression or altered function
EPI - reduced IF production and possibly reduced release of B12 from protein
Dysbiosis - ?Bacteroides can compete for use of IF bound B12
Tests to assess B12 status and their pros/cons
serum B12 - readily avialable, does not reflect intracellular B12 status
Serum HCY - increase is a reflection of reduced methionine synthase function, more sensitive than serum B12 for detection of intracellular deficiency. But not specific for B12 deficiency as affect by folic acid and B6 levels.
Serum/urine MMA - increased due to reduced MM-CoA mutase enzyme defect. Indicates B12 intracellular deficit.
Most sensitive test but not widely available and can be affected by renal dz or LUTI if measuring in urine
Source of folate and its absorption
Water soluble B9 in diet
Ingested form is deconjugated in proximal SI by brush border enzymes and absorbed via carrier mediated process or by passive diffusion.
SI disease can reduce folate carriers and deconjugase resulting in decrease in serum levels (reduced in 14% of dogs with CIE)
May be increased in some dysbiosis
Different areas involved in vomiting and receptors found there
Peripheral (Duodenum > gastric stretch> peritoneum, biliary pnacreatic, urinary and repro)
5HT3, D2 and NK1 receptors
–> sends vagal and sympathetic afferents to the vomiting centre
Vestibular centre - ACh M1, H2, NK1
–> input to vomiting centre and CRTZ
CRTZ - no BBB so exposed to any toxins/inflam in blood. Also affected by CSF pressure
Opioid, NK1, D2, alpa2, 5HT3. H1 and 2, ACh M1
Vomiting centre (brainstem) - alpha 2, NK1, 5HT1
Differences between cat and dog vomiting receptors
Cats do not express as much dopamine2 R as dogs and as such metoclopramide has less efficacy.
Cats express more alpha2 R than dogs which is why xylazine and other alpha antags cause nausea/vomiting.
Impact of protein on GI motility and secretion.
Causes of maldigestion
- increases LES tone
- slows SI transit
- increases secretion of gastrin and pancreatic hormones
Maldigestion may be due to poor quality,
lack of digestive enzymes or
↓ resorptive function →
↓ protein availability, impaired GI function, impaired GI mucosal repair, ↑ bacterial ammonia production in the distal SI and colon, altered bacterial flora
Impact of fat on GI motility and secretion.
- slow gastric emptying in dogs but not cats
- reduce LES tone (increase reflux risk)
What is food intolerance and what are the mechanistic classifications (JSAP 2019)
Food intolerance refers to any abnormal physiological response to a food or food additive, believed not to be immunological in nature
Food toxicity
Pharmacological reactions
Metabolic reactions eg lactose intolerance in older animals (brush border lactase deficiency)
Dysmotility
Dysbiosis
Physical Effects (eg dietary indiscretion)
What are food toxicities
infection, microbial or added toxin, plant derived toxins, metals,
Nutrient excess (eg vit D or A)
? Food additives
Microbial spoilage
What are pharmacological adverse food reactions
Defined as adverse reactions to biologically active food chemicals, both natural and added
- Histamine in food at non-toxic doses may be a casue of variety of symptoms. Unknown significance in vet med.
- Salicylates
- Methylxanthines: such as theobromine due to slow excretion
- Grapes, Macadamia, Hops
- Onions
- Xylitol
Dietary factors contributing to dysmotility
high in fat, highly viscous (e.g. soluble fibre), or contain poorly digestible starch, may prolong gastric retention and promote vomiting in some dogs
Why are cats more prone to B12 deficiency
Lack transcobalamin 1 so more readily lose B12 through enterohepatic recycling
How does the colon reabsorb water
occurs passively across osmotic gradient by coabsoprtion of sodium.
Neutrality is maintained by the exchange of Na and K against Cl and bicarbonate
Aldosterone and glucocorticoids affect colonic transport by enhancing the activity of Na/K ATPase pump
Substances involved in normal control of colonic motility
Somatostatin - produced locally and rest of GIT
CCK
ACh from vagus n and pelvic n
Substance P
SNS via lumbar splanchnic n.
Nerves involved in defecation
Pudendal - conscious control of external sphincter and coccygeus/levator ani muscles that form pelvic diaphragm
Pelvic - from sacral spinal cord carries vagal innervation to distal colon and generates giant migrating contractions
Hypogastric - carris sympathetic input from paravertebral ganglion to the distal colon (where it inhibits contractions) and to the int/ext sphincters (where it causes contractions)
What is the recto-anal inhibitory reflex
relaxation of the internal sphincter and contraction of the external sphincter to maintain continence and allow slow filling of the rectum
If there is minimal feces or the external sphincter remains contracted then the internal sphincter contracts pushing faeces back into the colon.
This back and forth continues until the volume of feces is sufficient to contact the anal mucosa resulting in a stronger urge to defecate
Benefits and complications of Enteral nutrition
Safer than parenteral
Prevents starvation associated villus atrophy and altered intestinal permeability
Provides nutrients to enterocytes/coloncytes which rely on lumen
Facilitates biome function
Demonstrated benefits in improving recovery of dogs/cats with pancreatitis or GI dz including PLE, and suggestive evidence in pupies with Parvo
Complications: intolerance, aspiration, tube associated infections/dehiscence.
When is parenteral nutrition indicated and what should it consist of
intractable vomiting/regurgitation or inability to protect airway.
Basically critical care
5% Dextrose as main energy source; 8% amino acids, 10-20% lipid
Ready to use preparations are only 30-50% of RER.
STRICT ASEPSIS
Risk of phlebitis
Definitions of sarcopaenia and cachexia
Cachexia = weight loss due to severe illness
Sarcopaenia = muscle mass loss due to aging or illness. rapid loss of skeletal muscle often occurs at same time as cachexia
Normal structure of peritoneum and formation of peritoneal fluid
Single layer of mesothelial cells on basement membrane. with deeper connective tissues, adipose, immune cells and elastic collagen fibres.
Mesothelial cells produce small amount of surfactant to lubricate organs and reduce friction.
TP <2.5g/dL; TNCC <3000/ul
Vol <1ml/kg
Highly permeable to water and has fenestrated basement membrane which allows bidirectional movement of low MW solutes and water
Define sarcopaenia and cachexia
Sarcopaenia = age related loss of lean body mass
Cachexia = loss of lean body mass secondary to disease
