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Y1 LSS Alimentary System > Alimentary mechanisms > Flashcards

Alimentary mechanisms Flashcards

Membrane transport; Absorption; Hydration; Appetite

1
Q

What is appetite?

A

Intrinsic desire to consume food

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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

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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

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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

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5
Q

What are the two neuronal populations in the arcuate nucleus?

A

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

POMC (proopiomelanocortin)

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6
Q

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

A

Stimulate food intake

Located medially in the arcuate nucleus

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7
Q

What do POMC neurones do and where are they located?

A

Inhibit food intake

Located more laterally in the arcuate nucleus

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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

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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

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10
Q

How do NPY/Agrp neurones increase food intake?

A

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

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11
Q

What does MC4R stand for and where is it located?

A

Melanocortin 4 receptor in the paraventricular nucleus

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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

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13
Q

What are the 3 hormones that regulate food intake?

A

Leptin
Ghrelin
PeptideYY₃-₃₆

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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

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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

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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

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17
Q

Why is ghrelin the hunger hormone?

A

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

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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

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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

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20
Q

Why is the osmolarity of the blood tightly regulated?

A

Maintain :

  • solute gradients
  • Suitable hematocrit
  • Ideal viscosity
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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

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22
Q

What are baroreceptors?

A

Respond to changes in blood volume and pressure

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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

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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

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25
Q

How are osmoreceptors available to sensitise and equilibrate with their local environment?

A

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)

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26
Q

What are the two ways in which thirst can be satisfied?

A

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

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27
Q

What are the 5 primary affects of Angiotensin II?

A

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

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28
Q

Give a brief overview of where angiotensin II comes from.

A

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

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29
Q

What is the enteric nervous system?

A

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

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30
Q

What is a plexus?

A

Dense local network of nerves and supporting cells

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31
Q

What is ganglia?

A

Nerve cells which carry signals, and glial cells which provide insulative, protective, nutritional and structural support

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32
Q

Why is the enteric nervous system referred to as the 2nd brain?

A

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

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33
Q

What causes dysfunction of the enteric nervous system?

A

Inflammation
Invasive abdominal surgery (just after it)
IBS
Ageing - constipation

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34
Q

What are the two main plexuses in the enteric nervous system?

A

Myenteric plexus - Auerbach’s plexus

Submucosal plexus - Meissner’s plexus

35
Q

Where is the myenteric plexus located and what is its role?

A

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
Q

Where is the submucosal plexus located and what is its role?

A

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
Q

What are the 4 key efferent functions of the enteric nervous system?

A

Secretion
Perfusion
Absorption
Motility

38
Q

Secretion of what is controlled by the enteric nervous system and why?

A

Enzymes
Paracrine signals
Endocrine hormones
to regulate local and non-local gut functions

39
Q

Why is perfusion a key efferent function of the enteric nervous system?

A

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
Q

How is absorption controlled by the enteric nervous system?

A

Adjustment of expression of luminal transport proteins carefully controls absorption of nutrients, vitamines, minerals and ions

41
Q

Why is motility a key efferent function of the enteric nervous system?

A

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
Q

Describe the neuronal populations of the enteric nervous system?

A

Most neurones multipolar - many dendrites
Sensory
Motor
Interneurones

43
Q

What types of stimuli do the sensory neurons of the enteric nervous system respond to?

A

Mechanical
Chemical
Osmotic
Thermal

44
Q

Where do motor neurons of the enteric nervous system terminate?

A

Axons terminate on:

  • smooth muscle cells of the circular or longitudinal layers
  • Secretory cells of GI tract
  • GI blood vessels
45
Q

What are interneurons?

A

neurons between sensory and motor neurons that integrate the sensory input and effector output

46
Q

What are the two branches of the autonomic nervous system?

A

Sympathetic - associated with stress and fight or flight response
Parasympathetic - associated with sedate activities, rest repair and recuperation

47
Q

Can the ANS be consciously controlled?

A

No
Cannot be activated voluntarily
Regulates smooth muscle, cardiac muscle and glands

48
Q

Where are the preganglionic cell bodies of the autonomic nervous system located?

A

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
Q

Where are the postganglionic cell bodies of the autonomic nervous system located?

A

SNS - postganglionic cell bodies found in the pre and paravertebral ganglia
PNS - postganglionic cell bodies located very close to target organs

50
Q

How do the length of nerves of the autonomic nervous system to the ENS compare?

A

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
Q

How does innervation of the ENS by the autonomic nervous system differ?

A

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
Q

What are the different neurotransmitters involved in the ANS?

A

SNS - noradrenaline between SNS and ENS, but between SNS and SNS use ACh
PNS - ACh

53
Q

What is the general effect of the branches of the ANS on the ENS?

A

SNS - reduce activity

PNS- increase activity

54
Q

What are 3 key points regarding the integration of the nervous systems?

A

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
Q

What secretes gut hormones?

A

Enteroendocrine cells of the alimentary canal

-specialised large family of cells

56
Q

How is stomach acid secretion controlled by gut hormones?

A

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
Q

Where are endocrine hormones acting in the gut released from?

A

Enteroendocrine cells in mucosa/submucosa of the gut wall

Specialised cells in organs e.g. pancreas

58
Q

What 3 functions in particular are controlled by which endocrine hormones?

A

Glucose regulation - insulin and glucagon
Appetite regulation - ghrelin and peptide YY
Gut function regulation - somatostatin, secretin, cholecystokinin,gastrin, glucose-dependent insulinotropic peptide

59
Q

What are the key features of gastrin? (where secreted from, locations, stimului, effects)

A

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
Q

What are the key features of secretin? (where secreted from, locations, stimului, effects)

A

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
Q

What are the key features of somatostatin? (where secreted from, locations, stimului, effects)

A

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
Q

What are the key features of cholecystokinin? (where secreted from, locations, stimului, effects)

A

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
Q

What are the key features of Glucose dependent insuliotropic peptide? (where secreted from, locations, stimului, effects)

A

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
Q

What does trancellular mean?

A

Through epithelial cells

65
Q

What does paracellular mean?

A

through tight junctions and lateral intercellular spaces

66
Q

What are the different types of gating found in channel proteins?

A

Voltage gated
extra/intracellular ligand gated
mechanically gated e.g. stretch/pressure

67
Q

What is the main difference between primary and secondary active transport?

A

1° links directly to cellular metabolism - ATP

2° derives energy from concentration of another substance that is actively transported

68
Q

How are carbohydrates absorbed?

A

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
Q

How is water absorbed?

A

Standing gradient osmosis powered by ion uptake, specifically Na+
8L a day absorbed in small intestine, 1.4L in large intestine

70
Q

How is Na+ absorbed?

A

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
Q

How are Cl- ions absorbed?

A

co-transported with Na+ in the ileum and exchanged for bicarbonate in the colon 2° active transport

72
Q

How is K+ absorbed?

A

Diffuses via paracellular pathways in small intestine

Leaking between cells in colon - passive transport

73
Q

How is Ca2+ absorbed?

A

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
Q

How is vitamin D absorbed?

A

1,25-dihydroxyD3 taken up by enterocytes
Increases levels of calbindin
Enhances cytosolic calcium transport

75
Q

What is the purpose of Iron?

A

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
Q

How is iron absorbed?

A

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
Q

How is iron toxicity prevented?

A

iron/ferritin unavailable for transport and lost to lumen and faeces

78
Q

What are vitamins?

A

Organic compounds that cannot be manufactured by the body but are vital to metabolism

79
Q

How are vitamins absorbed?

A

Passive diffusion dominates

Fat soluble vitamins (ADEK) transported to the brush border in micelles and are actively absorbed

80
Q

Where is vitamin b12 found?

A

Large store in liver

Most in food bound to proteins

81
Q

What is the purpose of R proteins?

A

Haptocorrin - R protein protects denaturation of b12 by HCl in the stomach after it is released from protein digestion
Binds to b12

82
Q

What is the purpose of intrinsic factors in vitamin B12 absorption?

A

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
Q

What happens to the B12-IF complex after it is absorbed into the distal ileum?

A

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

Y1 LSS Alimentary System (7 decks)

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