Physiology

Question 1

Regulation of gastric emptying

Answer 1

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

Question 2

Mediators of intestinal contractions

Answer 2

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

Question 3

Defecation reflex

Answer 3

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.

Question 4

2 functional areas of stomach

Answer 4

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)

Question 5

3 phases of gastric acid secretion

Answer 5

• 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.

Question 6

Mechanisms that stimulate parietal cell acid release

Answer 6

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

Question 7

Ghrelin production site and function

Answer 7

secreted from stomach

Triggers growth hormone release
–> stimulates appetite, body growth
(GI-hypothalamic-pituitary axis)

Antagonises leptin

Question 8

Gastric mucosal defences

Answer 8

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.

Question 9

Digestion of carbs, protein and lipid

Answer 9

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

Question 10

CCK site of production and function

Answer 10

Duodenum and jejunum
Triggered by acid, protein and fat content of lumen

Stimulates: BG contraction, pancreatic enzyme release

Inhibits gastric emptying of liquids

Question 11

Secretin site of production and function

Answer 11

S cells in duodenum
Response to lumen acidification

Stimulates HCO3 release from pancreatic ductal cells

Inhibits gastrin release (and thus acid release)

Question 12

Somatostatin site of production and function

Answer 12

Gastric D cells
Release in response to protein/lipid and bile

Inhibits gastric acid secretion by inhibiting EC cell Histamine production
inhibits pepsin secretion

Question 13

Gastric inhibitory peptide site of production and function

Answer 13

Proximal SI cells
Response to FAs, glucose, peptides

Stimulate pancreatic islet insulin release

Inhibits gastric motility

Question 14

Glucagon site of production and function

Answer 14

Enteric and pancreatic
In response to FAs or glucose

Inhibits gastric emptying and H+ release
Reduces gut permeability

Question 15

Motilin site of production and function

Answer 15

All GI cells
Stimulated by acid and fasting

initiates migrating motility complexes during fasted state

Coordinates secretions during feeding

Question 16

Vasoactive intestinal polypeptide site of production and function

Answer 16

Vagal stimulation

Increases blood flow, stimulates fluid secretions
relaxes smooth muscle

Question 17

Normal B12 absorption

Answer 17

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

Question 18

Function of B12 and result of deficiency

Answer 18

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

Question 19

Causes of B12 deficiency

Answer 19

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

Question 20

Tests to assess B12 status and their pros/cons

Answer 20

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

Question 21

Source of folate and its absorption

Answer 21

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

Question 22

Different areas involved in vomiting and receptors found there

Answer 22

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

Question 23

Differences between cat and dog vomiting receptors

Answer 23

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.

Question 24

Impact of protein on GI motility and secretion.
Causes of maldigestion

Answer 24

• 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

Question 25

Impact of fat on GI motility and secretion.

Answer 25

• slow gastric emptying in dogs but not cats
• reduce LES tone (increase reflux risk)

Question 26

What is food intolerance and what are the mechanistic classifications (JSAP 2019)

Answer 26

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)

Question 27

What are food toxicities

Answer 27

infection, microbial or added toxin, plant derived toxins, metals,
Nutrient excess (eg vit D or A)
? Food additives
Microbial spoilage

Question 28

What are pharmacological adverse food reactions

Answer 28

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

Question 29

Dietary factors contributing to dysmotility

Answer 29

high in fat, highly viscous (e.g. soluble fibre), or contain poorly digestible starch, may prolong gastric retention and promote vomiting in some dogs

Question 30

Why are cats more prone to B12 deficiency

Answer 30

Lack transcobalamin 1 so more readily lose B12 through enterohepatic recycling

Question 31

How does the colon reabsorb water

Answer 31

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

Question 32

Substances involved in normal control of colonic motility

Answer 32

Somatostatin - produced locally and rest of GIT
CCK
ACh from vagus n and pelvic n
Substance P
SNS via lumbar splanchnic n.

Question 33

Nerves involved in defecation

Answer 33

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)

Question 34

What is the recto-anal inhibitory reflex

Answer 34

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

Question 35

Benefits and complications of Enteral nutrition

Answer 35

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.

Question 36

When is parenteral nutrition indicated and what should it consist of

Answer 36

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

Question 37

Definitions of sarcopaenia and cachexia

Answer 37

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

Question 38

Normal structure of peritoneum and formation of peritoneal fluid

Answer 38

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

Question 39

Define sarcopaenia and cachexia

Answer 39

Sarcopaenia = age related loss of lean body mass

Cachexia = loss of lean body mass secondary to disease