Alimentary mechanisms Flashcards

Membrane transport; Absorption; Hydration; Appetite

1
Q

What is appetite?

A

Intrinsic desire to consume food

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How is circulating gut and appetite hormones detected by the brain?

A

Hypothalamus has an incomplete blood brain barrier so it can detect increasing and decreasing concentrations in the blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are features of the arcuate nucleus?

A

Has an incomplete blood brain barrier which allows peripheral signals to directly activate its circuitry
Two neuronal populations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where is the arcuate nucleus?

A

Located at the base of the brain
Adjacent to 3rd ventricle and median eminence
Part of the hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the two neuronal populations in the arcuate nucleus?

A

NPY/Agrp(Neuropeptide Y/Agouti-related peptide)

POMC (proopiomelanocortin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What do NPY/Agrp neurones do and where are they located?

A

Stimulate food intake

Located medially in the arcuate nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What do POMC neurones do and where are they located?

A

Inhibit food intake

Located more laterally in the arcuate nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where do the axons from NPY/Agrp neurones project for appetite?

A

Project to many locations in the brain

Key site is the paraventricular nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How do POMC neurones reduce food intake?

A

α-MSH (alpha melanocyte stimulating hormone) from POMC neurones binds to MC4R of paraventricular nucleus
Agonises the receptor and reduces food intake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do NPY/Agrp neurones increase food intake?

A

Agrp binds to MC4R of paraventricular nucleus
Antagonises receptor
Maintains food intake behaviours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does MC4R stand for and where is it located?

A

Melanocortin 4 receptor in the paraventricular nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What mutations in the hypothalamic appetite circuit influence energy balance?

A

No known mutations in NPY/Agrp that effect appetite

POMC deficiency and MC4R mutation caues morbid obesity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the 3 hormones that regulate food intake?

A

Leptin
Ghrelin
PeptideYY₃-₃₆

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the purpose of leptin and where is it secreted?

A

Long term appetite regulation
Stimulates anorexigenic behaviours
Secreted by cells in white adipose tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the leptin feedback mechanism and how could it be disrupted?

A

well nourished adult will accumulate body fat
Increases leptin secretion ∴ suppresses appetite
Leptin resistance is associated with obesity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is ghrelin and where is it secreted?

A

Peptide hormone that regulates short term appetite control by promoting eating behaviours
Secreted from stomach in increasingly higher quantities in the build up to a meal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Why is ghrelin the hunger hormone?

A

Binds to hypothalamic receptors and increases the perception of hunger and the urge to eat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is PeptideYY₃-₃₆ and where is it secreted?

A

Peptide hormone that regulates short term appetite control by suppressing eating behaviours
Satiety hormone
Secreted from cells in ileum and colon in response to a meal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why is PeptideYY₃-₃₆ the satiety hormone?

A

Binds to hypothalamic receptors and reduces the perception of hunger and the urge to eat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why is the osmolarity of the blood tightly regulated?

A

Maintain :

  • solute gradients
  • Suitable hematocrit
  • Ideal viscosity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the sensing organs for solute concentration and where are they found?

A

Osmoreceptors

Found in brain adjacent to structures with an incomplete blood brain barrier - hypothalamus within OVLT and SFO regions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are baroreceptors?

A

Respond to changes in blood volume and pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the thresholds for responsive action by the hypothalamus and why are they useful?

A

2-3% increase in osmolarity
10-15% decrease in volume and/or pressure
Corrective action can be initiated without any critical risk to the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is vasopressin and what are its primary functions?

A

Antidiuretic hormone produced in the hypothalamus and released from the posterior pituitary gland
Insert aquaporin-2 channels into the collecting duct of renal nephrons to increase water absorption
Stimulate vasoconstriction
Stimulate thirst to lead to increased fluid intake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
How are osmoreceptors available to sensitise and equilibrate with their local environment?
Osmoreceptive cells have cell bodies outside the blood brain barrier that are bathed in ECF If ECP varies from 290 mOsm/kg the cells will proportionately grow (↓osmolarity) or shrink by osmosis(↑osmolarity) These changes affect firing rate of the cells Adjusts the basal level of ADH being secreted (↑ ADH, more water retained, ↓ osmolarity)
26
What are the two ways in which thirst can be satisfied?
Presence of water in GI tract: -can quench thirst for a short period of time -Thought to result from receptors in upper GI tract -short term feedback Once original stimulus (osmolarity or BP) corrected, perception of thirst no longer felt: -long term feedback mechanisms not fully understood
27
What are the 5 primary affects of Angiotensin II?
1) binds to receptors on vascular smooth muscle cells to stimulate vasoconstriction 2) Upregulates activity of sympathetic nervous system which promotes vasoconstriction 3) Stimulates aldosterone secretion ∴ increasing sodium reabsorption in nephron ∴creating an osmotic gradient for water reabsorption 4) Direct influence on sodium reabsorption, causing water reabsorption 5) stimulates ADH release and thirst
28
Give a brief overview of where angiotensin II comes from.
Renin from kidney (secreted in response to low BP) converts angiotensinogen from the liver into angiotensin I Converted to angiotensin II by ACE (angiotensin converting enzyme) which is expressed on vascular endothelial cells of the pulmonary and renal microvessels
29
What is the enteric nervous system?
Intrinsic second brain capable of independence Consists of neurones arranged in two main plexuses of ganglia interconnected by fine tracts of unmyelinated nerve fibres Acts as an integrating centre for coordinating function
30
What is a plexus?
Dense local network of nerves and supporting cells
31
What is ganglia?
Nerve cells which carry signals, and glial cells which provide insulative, protective, nutritional and structural support
32
Why is the enteric nervous system referred to as the 2nd brain?
It can integrate function like the brain receives signals from different parts of the body, integrates them and produces a response It can produce a coordinated response to specific stimuli independent of the CNS
33
What causes dysfunction of the enteric nervous system?
Inflammation Invasive abdominal surgery (just after it) IBS Ageing - constipation
34
What are the two main plexuses in the enteric nervous system?
Myenteric plexus - Auerbach's plexus | Submucosal plexus - Meissner's plexus
35
Where is the myenteric plexus located and what is its role?
Between circular and longitudinal smooth muscle layers Has efferent innervation of both smooth muscle layers Allows for coordinated control of motor function ∴motility of the muscularis externa
36
Where is the submucosal plexus located and what is its role?
Located in the submucosa Has afferent and efferent functions: Afferent - sense environment within lumen via mechanoreceptors, chemoreceptors and osmoreceptors Efferent - Fine tune local blood flow, epithelial transport and secretory/paracrine/endocrine cell function
37
What are the 4 key efferent functions of the enteric nervous system?
Secretion Perfusion Absorption Motility
38
Secretion of what is controlled by the enteric nervous system and why?
Enzymes Paracrine signals Endocrine hormones to regulate local and non-local gut functions
39
Why is perfusion a key efferent function of the enteric nervous system?
Blood flow needs to be carefully controlled to ensure high perfusion in regions of gut that are working and/or absorbing (VSMC, submucosal glands, enterocytes)
40
How is absorption controlled by the enteric nervous system?
Adjustment of expression of luminal transport proteins carefully controls absorption of nutrients, vitamines, minerals and ions
41
Why is motility a key efferent function of the enteric nervous system?
Smooth muscle cells in the circular and longitudinal muscle layers can contract and relax to cause effective gut transit May be desirable to accelerate or stop this e.g. after large meal or after exercise
42
Describe the neuronal populations of the enteric nervous system?
Most neurones multipolar - many dendrites Sensory Motor Interneurones
43
What types of stimuli do the sensory neurons of the enteric nervous system respond to?
Mechanical Chemical Osmotic Thermal
44
Where do motor neurons of the enteric nervous system terminate?
Axons terminate on: - smooth muscle cells of the circular or longitudinal layers - Secretory cells of GI tract - GI blood vessels
45
What are interneurons?
neurons between sensory and motor neurons that integrate the sensory input and effector output
46
What are the two branches of the autonomic nervous system?
Sympathetic - associated with stress and fight or flight response Parasympathetic - associated with sedate activities, rest repair and recuperation
47
Can the ANS be consciously controlled?
No Cannot be activated voluntarily Regulates smooth muscle, cardiac muscle and glands
48
Where are the preganglionic cell bodies of the autonomic nervous system located?
SNS - preganglionic cell bodies located in the spinal cord in the lower thoracic and upper lumbar spinal cord PNS - preganglionic cell bodies located in the brainstem and sacral spinal cord
49
Where are the postganglionic cell bodies of the autonomic nervous system located?
SNS - postganglionic cell bodies found in the pre and paravertebral ganglia PNS - postganglionic cell bodies located very close to target organs
50
How do the length of nerves of the autonomic nervous system to the ENS compare?
SNS - preganglionic terminate close to spine ∴ short, postganglionic extend from sympathetic chain to target organ ∴ long PNS - preganglionic nerves synapse close to target organs ∴ relatively long, postganglionic relatively short (most cases pre ganglionic synapse directly with ENS neurons)
51
How does innervation of the ENS by the autonomic nervous system differ?
SNS - splanchnic nerves carry preganglionic neurons - arise from thoracic (foregut) and lumbar (hindgut) regions PNS - innervation arises from vagus nerve, colon onwards innervation from pelvic splanchnic nerves
52
What are the different neurotransmitters involved in the ANS?
SNS - noradrenaline between SNS and ENS, but between SNS and SNS use ACh PNS - ACh
53
What is the general effect of the branches of the ANS on the ENS?
SNS - reduce activity | PNS- increase activity
54
What are 3 key points regarding the integration of the nervous systems?
Myenteric and submucosal plexuses communicate directly to make local decisions based on local signals ANS typically inputs to the ENS to integrate with local afferent signals for a coordinated response (exception is sympathetic innervation of vascular smooth muscle which allows ANS to shut down gut perfusion in high stress situations) Disruption of ANS would only minimally decrease gut functionality
55
What secretes gut hormones?
Enteroendocrine cells of the alimentary canal | -specialised large family of cells
56
How is stomach acid secretion controlled by gut hormones?
Paracrine action D cells secrete somatostatin which inhibits secretion of acid from parietal cells in gastric pits ECL cells secrete histamine which binds to H2 receptors on pariteal cells to stimulate acid secretion
57
Where are endocrine hormones acting in the gut released from?
Enteroendocrine cells in mucosa/submucosa of the gut wall | Specialised cells in organs e.g. pancreas
58
What 3 functions in particular are controlled by which endocrine hormones?
Glucose regulation - insulin and glucagon Appetite regulation - ghrelin and peptide YY Gut function regulation - somatostatin, secretin, cholecystokinin,gastrin, glucose-dependent insulinotropic peptide
59
What are the key features of gastrin? (where secreted from, locations, stimului, effects)
Secreted from G cells in gastric antrum, upper duodenum Stimulated by: -single amino acids and small peptides -stomach distension & mechanoreceptors that detect presence of a meal -PNS Causes increased acid secretion, gastric emptying and pepsinogen secretion Release inhibited if pH below 3 (protect duodenal mucosa)
60
What are the key features of secretin? (where secreted from, locations, stimului, effects)
Secreted from S cells in duodenum and jejunum Stimulated by reduced pH in duodenal lumen Causes secretion of pancreatic HCO3- If secretin in excess, inhibits acids secretion in stomach and inhibits gastric emptying
61
What are the key features of somatostatin? (where secreted from, locations, stimului, effects)
D cells in stomach, gut mucosa and pancreas Stimulated by reduced pH/in response to a mixed meal Has a number of inhibitory effects: -Reduces gastric acid secretion by inhibiting G cells and ECL cells -Decreases motility of the gut -Decreases gastric emptying UNIVERSAL INHIBITOR Inhibited by vagus nerve
62
What are the key features of cholecystokinin? (where secreted from, locations, stimului, effects)
CCK secreted by I cells in small intestine Stimulated by detection of small peptides and fats Causes: -Increased secretion of pancreatic enzymes -Reduced gastric emptying -Gall bladder contraction -Reduced appetite Can act independently of the vagus nerve
63
What are the key features of Glucose dependent insuliotropic peptide? (where secreted from, locations, stimului, effects)
GIP secreted from K cells in duodenum and jejunum Stimulated by mixed meal nutrients, specifically glucose Causes increased insulin secretion, and at high concentration reduces acid secretion and gastric emptying also called gastric inhibitory peptide
64
What does trancellular mean?
Through epithelial cells
65
What does paracellular mean?
through tight junctions and lateral intercellular spaces
66
What are the different types of gating found in channel proteins?
Voltage gated extra/intracellular ligand gated mechanically gated e.g. stretch/pressure
67
What is the main difference between primary and secondary active transport?
1° links directly to cellular metabolism - ATP | 2° derives energy from concentration of another substance that is actively transported
68
How are carbohydrates absorbed?
Glucose/galctose uses 2° active transport using SGLT-1 on apical membrane, against concentration gradient Fructose uses GLUT-5 facilitated diffusion GLUT-2 carries glucose over basolateral membrane to equilibriate
69
How is water absorbed?
Standing gradient osmosis powered by ion uptake, specifically Na+ 8L a day absorbed in small intestine, 1.4L in large intestine
70
How is Na+ absorbed?
Proximal bowel - counter transport in exchange for H+ Jejunum - co-transport with amino acids, monosaccharides Ileum - co-transport with Cl- Colon - restricted movement through ion channels Actively transported into lateral intercellular spaces by Na+K+ ATPase into the lateral plasma membrane
71
How are Cl- ions absorbed?
co-transported with Na+ in the ileum and exchanged for bicarbonate in the colon 2° active transport
72
How is K+ absorbed?
Diffuses via paracellular pathways in small intestine | Leaking between cells in colon - passive transport
73
How is Ca2+ absorbed?
Largely in the small intestine (duodenum and ileum) A Ca2+ deficient diet increases gut's ability to absorb Vitamin D and PTH stimulate absorption Ion channels and intestinal calcium binding proteins Calbindin binds to calcium in cytosol to stop it acting as a signal when it as absorbed Ca2+ ATPase has high affinity for Ca2+ but is slow Na+/Ca2+ ATPase exchanger has low affinity but is rapid, requires high concentration of Ca2+ to be effective
74
How is vitamin D absorbed?
1,25-dihydroxyD3 taken up by enterocytes Increases levels of calbindin Enhances cytosolic calcium transport
75
What is the purpose of Iron?
can act as electron donor and acceptor Needed for oxygen transport and oxidative phosphorylation In excess is toxic and body has no mechanism to excrete it Need to absorb it quickly but also absorption needs to be limited
76
How is iron absorbed?
Duodenal cytochrome B catalyses reduction of Fe3+ to Fe2+ Fe2+ transported by divalent metal transporter 1 Fe2+ binds to cytosolic factors and is carried to basolateral membrane, moves via ferroportin ion channels to blood - can be suppressed by hepcidin
77
How is iron toxicity prevented?
iron/ferritin unavailable for transport and lost to lumen and faeces
78
What are vitamins?
Organic compounds that cannot be manufactured by the body but are vital to metabolism
79
How are vitamins absorbed?
Passive diffusion dominates | Fat soluble vitamins (ADEK) transported to the brush border in micelles and are actively absorbed
80
Where is vitamin b12 found?
Large store in liver | Most in food bound to proteins
81
What is the purpose of R proteins?
Haptocorrin - R protein protects denaturation of b12 by HCl in the stomach after it is released from protein digestion Binds to b12
82
What is the purpose of intrinsic factors in vitamin B12 absorption?
Produced by parietal cells Protects the R protein-B12 complex as it moves towards the distal ileum Cubulin then detects B12-IF complex and absorbs it
83
What happens to the B12-IF complex after it is absorbed into the distal ileum?
Complex broken down B12 binds to transcobalamin II Then crosses basolateral membrane and travels to the liver Receptors on liver take up the complex and proteolysis releases transcobalamin II