12- Control

Question 1

How does the hypothalamus sense substances levels in the blood

Answer 1

many regions of the hypothalamus have an incomplete blood brain barrier, which allows sensing organs in hypothalamus to detect increasing and decreasing concentration of circulating gut and appetite regulation hormones.

Question 2

What is the arcuate nucleus

Answer 2

Arcuate nucleus: At base of the brain, and has an incomplete bbb, which allows peripheral signals (nutrients, hormones, concentrations, temperature etc.) to directly activate its circuitry.
has two neuronal populations: NPY/Agrp (Neuropeptide Y/Agouti-related peptide) neurons stimulate food intake and are located medially. POMC neurons inhibit food intake and are located more laterally. POMC is a long peptide that can be cleaved many ways for many different purposes.
The axons from these neurons (whose cell bodies lie in the arcuate nucelus) project to many locations in the brain, but for appetite, a key site is the paraventricular nucelus.

Question 3

2 mutations causing obesity

Answer 3

However POMC deficiency and MC4R mutation is known to cause morbid obesity.

Question 4

Paraventricular nucleus

Answer 4

Paraventricular nucleus: Axons from the arcuate nucleus secrete neuropeptides (Agrp; POMC forms α-MSH) that bind to receptors in the paraventricular nucleus. Specifically, the melanocortin 4 receptor (MC4R), which is highly involved in the regulation of food intake. When activated, this receptor decreases food intake behaviours.

α-MSH binds to MC4R, which responds by reducing food intake behaviours
Agrp binds to MC4R and competitively blocks the satieting signal (i.e. I’m full and I don’t need to eat) from α-MSH. This causes an increase in food intake behaviours

Question 5

Leptin

Answer 5

Leptin is a hormone that provides long term appetite regulation. It is secreted by cells in white adipose tissue. Leptin binds to receptors in the hypothalamic circuits and suppresses appetite).

leptin resistance is associated with obesity.

Question 6

Grehlin

Answer 6

Ghrelin is the ‘hunger hormone’ and is secreted from cells in the stomach in increaisngly higher quantities in the build up to a meal. This is because ghrelin binds to hypothalamic receptors and increases the perception of hunger and the urge to eat.

Ghrelin is a peptide hormone that regulates short-term appetite control by promoting eating behaviours.

Question 7

Peptide YY3-36

Answer 7

Peptitde YY3-36 is the ‘satiety hormone’ and is secreted from cells in the ileum and colon in response to a meal. PYY3-36 binds to hypothalamic receptors and reduces the perception of hunger and the urge to eat.

PYY3-36 is a peptide hormone that regulates short-term appetite control by suppressing eating behaviours.

Question 8

What are the thresholds for a hypothalamic response

Answer 8

A 2-3% increase in osmolality

A 10-15% decrease in volume and/or pressure

Question 9

3 functions of ADH

Answer 9

To insert aquaporin-2 channels into the collecting duct of renal nephrons to increase water reabsorption
To stimulate vasoconstriction
Stimulate thirst

Question 10

How do osmoreceptors work

Answer 10

Osmoreceptive cells have cell bodies outside of the blood brain barrier that are bathed in the extracellular fluid (ECF). These cells are very sensitive to their local environment and quickly equilibrate with it. If the ECF varies from about 290 mOsm/kg, the cells will proportionately grow (in response to reduced osmolality) or shrink (in response to increased osmolality) by osmosis.

These changes will affect the firing rate of these cells, which will adjust the basal level of ADH being secreted. Increased ADH secretion will lead to water retention (and a decreased osmolality).

Question 11

2 ways of quenching thirst

Answer 11

Firstly, even the presence of water in the GI tract can quench thirst, for a short period of time at least. This is thought to results from receptors in the upper GI tract (mouth to oesophagus) - short term feedback
Secondly, once the original stimulus (osmolality or blood pressure) has been corrected, then the perception of thirst is no longer felt - long term feedback

Question 12

5 effects of AT II

Answer 12

It binds to receptors on vascular smooth muscle cells to stimulate vasoconstriction
It upregulates activity of the sympathetic nervous system, which largely promotes vasoconstriction
It stimulates aldosterone secretion, which increases sodium reabsorption in the nephron, which creates an osmotic gradient for water reabsorption
It directly influences sodium reabsorption, causing water reabsorption
It stimulates ADH release and stimulates thirst

Question 13

What is the enteric NS

Answer 13

can produce a coordinated response to specific stimuli independent of the central nervous system.
Consists of rich plexuses of ganglia
Unmyelinated
Intrinsic 
It integrates function

Question 14

4 things causing disfunction of enteric NS

Answer 14

Inflammation (ulcerative colitis; Crohn’s disease)
Following invasive abdominal surgery
Irritable bowel syndrome
Ageing (constipation)

Question 15

2 main plexuses of the gut

Answer 15

myenteric plexus and the submucosal plexus.

Question 16

Afferent and efferent function of the submucosal plexus

Answer 16

Afferent: Senses the environment within lumen using mechanoreceptors, chemoreceptors and osmoreceptors.

Efferent: Can fine tune local blood flow, epithelial transport and secretory/paracrine/endocrine cell function.

Question 17

Function of the myenteric plexus

Answer 17

This plexus is located between the circular and longitudinal smooth muscle layers, and has efferent innervation of both. This careful control of the entire activity of muscularis externa allows for coordinated control of motor function, and hence, motility.

Question 18

Functions of the enteric NS (spam)

Answer 18

Secretion - controlling the secretion of enzymes, paracrine signals and endocrine hormones to regulate local and non-local gut functions.
Perfusion - blood flow needs to be carefully controlled to ensure high perfusion in regions of the gut that are working (vascular smooth muscle cells [VSMC], submucosal glands) and/or absorbing (enterocytes)
Absorption - carefully controlling the absorption of nutrients, vitamins, minerals and ions by adjusting expression of luminal transport proteins
Motility - smooth muscle cells [SMCs] in the circular and longitudinal muscle layers can contract and relax to cause effective gut transit. It may be desirable to accelerate this (e.g. following a large meal) or stop it completely (e.g. during exercise)

Question 19

Summarise the SNS in the gut

Answer 19

From thoracolumbar nerves 
Short pre ganglionic, long post ganglionic
Noradrenaline 
Decreases gut activity 
Thoracic splancnic: mid/ foregut
Lumbar splancnic: hindgut

Question 20

Summarise the PNS in the gut

Answer 20

Increases activity
Cranialsarcal spinal nerves
Ach
Long preganglionic, short post ganglionic
Mostly vagus nerve, after descending colon then pelvic splancnic nerves

Question 21

Structure of an enteroendocrine cell

Answer 21

typically has a small apical membrane with a lot of sensory apparatus (receptors and intracellular signalling techniques) that can sense changes in the gut contents (or activation by neurotransmitters). Conversely, they have a broad basolateral surface, close to blood vessels for rapid distribution. Near the basolateral membrane they have vesicles with their secretory products ready for exocytosis.

Question 22

2 paracrine signalling molecules in the stomach

Answer 22

Firstly, D-cells in the stomach secrete the gut hormone somatostatin, which inhibits the secretion of acid from parietal cells in the gastric pits.

Secondly, enterochromaffin-like (ECL) cells in the gastric mucosa secrete histamine. Which binds to H2 receptors on the parietal cells, stimulating acid secretion.

Question 23

Where is gastrin secreted

Answer 23

G-cells in the distal end of the stomach (gastric antrum), the proximal duodenum

Question 24

Stimuli and effects of gastrin

Answer 24

Secretion of gastrin is stimulated by the presence of single amino acids and small peptides in the stomach.
Stretching of mechanoreceptors in the stomach wall after a meal
the parasympathetic nervous system can stimulate gastrin release by releasing gastrin-releasing peptide from vagal efferents.

Gastrin causes an increase in gastric acid secretion from parietal cells in the stomach.

Question 25

Where is secretin synthesised

Answer 25

Synthesised by S-cells in the proximal small intestine (duodenum and the jejunum).

Question 26

Stimuli and effects of secretin

Answer 26

Secretion of secretin is stimulated by a drop in pH in the duodenal lumen (usually following acid chyme leaving the stomach through the pyloric sphincter).

Secretin stimulates the secretion of bicarbonate rich juice from the exocrine pancreas (to neutralise the acid). Excessive levels of secretin actually inhibit the secretion of acid by the stomach and inhibit gastric emptying

Question 27

Where is somatostatin secreted

Answer 27

Synthesised by D (delta) cells in stomach, pancreas and small intestine

Question 28

Stimuli and effects of somatostatin

Answer 28

Reduced Ph
It decreases secretion of gastric acid via two mechanisms. It inhibits G-cells form secreting gastrin (which promotes acid secretion), and it inhibits ECL cells from secreting histamine. It also decreases motility of the gut and decreases gastric emptying.

Question 29

Cholecytokinin: where secreted, stimuli + effects

Answer 29

CCK is secreted by I-cells in the small intestine following detection of small peptides and fats (i.e. a mixed meal) in the lumen. This triggers a number of effects, including:

increased secretion of pancreatic enzymes
reduced gastric emptying
gall bladder contraction
reduced appetite

Question 30

Gastric inhibitory peptide: secreted, stimuli and effects

Answer 30

GIP is secreted from K cells in the duodenum and jejunum. This peptide hormone is involved with glucose storage, with its main physiological effect being the upregulation of insulin secretion in response to glucose concentration in the small intestine. In high concentrations it does have inhibitory effects on stomach function.