ENI - Gastrointestinal hormones Flashcards
What is GIT function regulated by?
- Enteric nervous system
- Enteric endorine system, which controls secretions, motility and appetite
- Some CNS control via the nervous and endocrine system
Compare the endo and exocrine function of the GIT
- Mainly based on location of secretory granules within the cell
- Exocrine: on apical side
- Endocrine: on basolateral side
List the GI hormones
- Insulin
- Glucagon
- Gastrin
- Secretin
- Cholecystokinin
- Incretins (Gastric Inhibiting Peptide and Glucagon-Like Peptide-1)
- Motilin
- Ghrelin
Where is gastrin produced?
G cells in stomach (fundus and corpus)
What are the stimuli for gastrin release?
- Presence of peptides and AAs in gastric lumen
- Stomach distension
- Vagal stimulation i.e. sight, smell, taste, chewing of food
- Hypercalcaemia
What are the major effects fo gastrin?
- Stimulates release of gastric acid from parietal cells
- Stimulates release of pepsinogen from chief cells
Describe the inhibition of gastrin
- Once pH ~3 secretion inhibited
- Negative feedback to prevent dropping pH too far as would damage tissues
Describe gastrinomas
- TUmour of gastrin secreting cells
- Dogs and cats
- Excessive gastrin and thus excessive HCl and pepsinogen
- Can lead to ulcers, vomiting (may contain blood), poor appetite, dark blood in faeces
Describe secretin (production site, stimulus and major effect)
- Produced in duodenum
- Stimulus for release if H+ in small intestine
- Stimulates release of bicarb rich pancreatic and biliary fluid i.e. reverse action of gastrin
Describe cholecystokinin (production site, stimulus and effects)
- Produced in duodenum
- Stimulated by fatty acids, monoglycoerides and AAs in small intestine (products of digestion)
- Stimulates secretion of pancreatic enzymes and contraction and emptying of gall bladder
Describe Gastric Inhibitory Polypeptide (production site, stimulus, effects)
- Producedi in proximal small intestine
- Stimulus for release is fat, glycose and AAs in small intestine (products of digestion)
- Stops digestion, signals “overload” of digestive products
- Inhibits gastric secretion of motility
- Potentiates release of insulin in reponse to elevated blood glucose
- Stimulates lipoprotin lipase activity in adipocytes
Describe motilin (production site, stimulus, effects)
- Produced by Mo cells of small intestine
- Release stimuli unclear, secretion associated with fasting
- Maintains motility in stomach and small intestine
- Stimulates production of pepsin
List the factors involved in appetite regulation
- Incretins
- Hypothalamic inputs
- 4 theories: lipostat, gut peptides, glucostat and thermostat
Describe the role of GLP-1 in appetite regulation
- Promotes insulin secretion
- Suppresses glucagon drive of gluconeogenesis
- Slowed gastric emptying (fuller for longer)
- Promotes satiety (hypothalamus by decreasing pleasure of food, motivation to eat and quantity and frequency of food consumption)
What are the hypothalamic inputs into appetite regulation?
- Neurons in arcuate nucleus
- Satiety centre
- Appetite
centre - Biological clock
- Processes from other cerebral loci
What is the effect of hormones at the level of the hypothalamus in appetite regulation?
- Leptin causes satiety (anorexigenic)
- Ghrelin stimulates appetite (orexigenic)
Outline the satiety centre within the hypothalamus
- Responds to high glucose levels
- Inhibits eating
Outline the appetite centre within the hypothalamus
- Responds to low glucose levels
- Stimulates eating
Outline the effect of other cerebral loci in appetite regulation
- Processses from other loci project into hypothalamus and modify appete
- e.g. limbic system (linked to emotions)
What are the 4 theories of appetite?
- Lipostat (fat deposits and leptin)
- Gut peptides (CCK, PYY, Ghrelin)
- Glucostat (glucose, VFAs, AAs)
- Thermostat
Describe the lipostat theory of appetite
- Adipose tissue producing leptin proportional to fat
- Acts on membrane bound receptors in hypothalamus to decrease food intake and increase energy output
- In general related to fat mass, but also increased in night (suppress appetite) and during starvation (even if have lots of stores, want to maintain these and use other energy)
What is the effect of starvation and leptin?
- HPA axis stimulated
- Suppresses reproductive functions, thyroid axis and immune functions
What is the result of genetic lack of leptin?
- Obesity
- Hyperphagia, hypothermia and infertile
Expalin the importance of varying leptin resistance in seasonal reproduction
- Leptin varies with season
- Allows building of fat stores coming up to breeding in order to sustain pregnancy (also occurs with hibernation)
Explain the role of cholecystokinin in satiety
- Acts on G-protein coupeld receptors
- Released rapidly in response to meal
- Leads to gall bladder contraction, secretion of pancreatic enzymes and bicarbonates, slow gastric emptying, inhibits gastric acid secretion, reduces food intale
- Also found in some cells in brain and expansion of stomach after meal causes release of CCK from these
Explain the role of peptide YY (PYY) in satiety
- Secreted by L cells in GIT
- Released after meal in proportion to calories ingested and meal composition (higher after high fat meal, even if calories are the same)
- Stimulates satiety and decreases food intake
Explain the role of Ghrelin in satiety
- produced by stomach motly but also intestine and hypothalamic nuclei
- Increased before a meal but decreases after
- Stimulates appetite and removal then stimulates satiey
Explain the role of ghrelin in hedonic pleasure of food
- Receptors found in hippocampus and regions in vovled in reward systems, as well as hypothalamus
- May activate reward links that communicate pleasure and reinforcing aspects of natural rewards e.g.food
(As well as addictive drugs such as ethanol)
Outline the glucostat theory of satiety
- High glucose stimulates satiety centre
- Requires insulin
- VFAs in ruminants
- AAs do the same
Outline the thermostat theory of satiety
- Fall in body temp below set point stimulates appetite
- Increase above normal inhibits appetite
What are the hormonal responses to negative energy balance?
- Insulin decrease
- Thyroxine decrease
- Glucagon increase
- Growth hormone increase
- Cortisol increase
- Catecholamine increase
What are the metabolic responses to negative energy balance?
- Initially use up carbohydrate stores e.g glycogen found in liver and muscle
- Then use fat and protein (muscle mass will decrease)
What are some reasons for negative energy balance in the dairy cow?
- Energy demands of foetus in late gestation
- Energy demands of milk production
- Transient anorexia at time of parturition
- Periparturient diseases
- Low dry matter intake combined with increased energy demands
Which of the volatile fatty acids are glucogenic and which are ketogenic?
- Glucogenic: proprionate
- Ketogenic: acetate, butyrate
- Ketogenic:glucogenic ratio 4:1
Outline the use of proprionate in gluconeogenesis
- Converted to oxaloacete
- Converted to glucose
What is the fate of the ketogenic VFAs?
- Converted to acetyl CoA
- Enters TCA cycle
- ATP produced
- Or stored as fats
- Or converted to ketones
What hormones stimulate HSL?
- Low insulin and high glucagon
- Catecholamines
- Growth hormone
- Cortisol
What inhibits HSL?
High insulin and low glucagon
What are the 2 key risk factors for lipid metabolism disorders with negative energy balance?
- Obesity
- Insulin resistance
Outline the effect of obesity on lipid metabolism
- Larger TAG present for mobilisation
- No negative feedback/fine control of this
- Amount released if proportional to what is available
- More fat present, more released
- Accumulation of lipid in adipocytes alters density of insulin receptors on membranes and insulin signalling
Outline the pathophysiology of lipids in negative energy balance
- Excessive mobilisation of fatty acids from adipose tissue
- Increase in blood non-esterified fatty acids
- Increased fatty acid uptake by liver
- Attempt to increase energy production via beta oxidation
- Pathways overwhelmed as oxaloacetate is deficient
- Excess fatty acids converted back to TAG
- Accumulation interferes with liver function
Outline the link between periparturient events and negative energy balance
- NEB in late pregnancy
- Increased energy demand of foetus but decreased intake
- Shift in blood hormones at parturition: insulin, IGF-1, thyroid hormones decrease
- GH, prolactin and cortisol increase
- More lipid mobilisation, less intake of food
- Increased insulin resistance in late gestation as cortisol more present
What is the common presentation for hepatic lipidosis in dairy cows?
- Periparturient cow
- Non-specific complaints: lower milk production, loss of appetite and mild depression
What are the common findings of hepatic lipidosis on physical examination?
- Decreased rumen motility
- Ketosis
- Concurrent disease e.g. dystocia, LDA, retained placenta
- Metritis or mastitis
What are common risk factors for hepatic lipidosis
- Obesity (high BCS, older cow)
- Insulin resistance (obesity induced, stress, pregnancy related, parturition peak in cortisol)
- Concurrent disease e.g. metritis (stress, inflammatory mediators)
- Improper housing (stress)
- Poor nutrition
Outline secondary ketosis in obesity
- Fatty acids converted to acetyl CoAto make ATP
- Propionate precursor for oxaloacetate, acetate and butyrate aare precursors for acetyl CoA
- Low proprionate if eating less, acetyl CoA into TCA inhibited = bottleneck
- Mobilised fat nowhere to go
- Converted back to TAG and stored in hepatocytes, or back to ciruclation in horse
- Excess acetyle CoA diverted to ketones
What are the effects of secondary ketosis?
- Fruity smell to breath (acetone)
- Ketones weak acids, excess amounts induce ketoacidosis
- Lower PH of blood affecting enzymatic actions
- CNS depression
- Lower appetute
Describe the temporary export pathway for TAGs
- TAGs exported from liver in VLDLs
- Serve as TAG overflow system for liver, not very responsive in cows
- TAG levels in blood reflect VLDL
- VLDL levels do not increase
- Plasma TAG levels fo not rise in cows, but in horses lots of TAG in blood and tissues end up filled leading to organ dysfunction
Describe the pathology within a fatty liver
- Cell swelling
- Disrupted cell metabolism
- Elevated liver enzyme levels (leak from damaged cells)
- Loss of hepatic function
- Capsule rupte
Describe feline hepatic lipidosis
- Obesity and NEB main risk factors
- Fat and then suddenly off food for other reason e.g. illness such as pancreatitis
- Friable fatty liver
Describe hyperlipidaemia in horses and ponies
- Following choke or anorexia due to pain (laminitis)
- Stop eating leading to NEB
- Repackage fat out of liver as VLDL
- Organ dysfunction due to systemic hyperlipidaemia
