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SUGER > Distal Convoluted Tubule And Collecting Duct > Flashcards

Distal Convoluted Tubule And Collecting Duct Flashcards

1
Q

A 19 year old man is diagnosed with diabetes insipidus which is a disease of the vasopressin system. Which serum osmolyte is likely to be the most important in controlling the release of vasopressin in this man?

A

Sodium

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2
Q

Aldosterone is a mineralocorticoid produced by the adrenal cortex. Which of the following statements about aldosterone is correct?

A

reduces sodium and water loss through the urine

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3
Q

Aldosterone is a key hormone involved in salt and water homeostasis. Which effect does aldosterone have on transporter proteins in the distal convoluted tubule?

A

Increase in Sodium - Potassium exchange transporters

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4
Q

Function of DCT

A

Fine tuning and regulation of Na+, K+, Ca2+ and Pi
Separation of Na+ from H2O
Continues active dilution of urine by reabsorption of Na+ in a water impermeable setting

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5
Q

What transporter aids reabsorption of Na+ and Cl- in DCT

A

NCC (sodium chloride cotransporter)

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6
Q

2 cell types of DCT

A

Principle cells
Intercalated cells

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7
Q

What do principle cells respond to

A

Aldosterone and vasopressin

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8
Q

Effect of aldosterone on principle cells

A

Increased expression of ENaC, ROMK, Na/K ATPase and H ATPase

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9
Q

Effect of vasopressin on principle cells

A

Insertion of AQP 2 on apical membrane - water reabsorption

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10
Q

Function of intercalated cells

A

Exchanging acids and bases

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11
Q

What do alpha intercalated cells secrete

A

Acid

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12
Q

What do beta intercalated cells secrete

A

Bicarbonate

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13
Q

Sodium reabsorption in distal tubule

A

Active transport of Na+ via basolateral Na/K ATPase pump out of proximal tubule cell into interstitial fluid- low intracellular concentration of Na+ compared to tubular lumen so Na+ moves down gradient into tubular epithelial cells
Secondary active transport of glucose and phosphate into cells
H+ exchanged for Na+ = lumen becomes acidic

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14
Q

What promotes sodium reabsorption in DCT

A

Aldosterone

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15
Q

Mechanism of aldosterone

A

Diffuses through membrane (steroid)
Binds to mineralocorticoid receptor complex intracellularly
Complex binds to MRE in the nucleus and increases protein synthesis for ENaC, ROMK, Na/K ATPase and H ATPase

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16
Q

What type of hormone is aldosterone

A

Steroid

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17
Q

What are co-transported with Na+ in the DCT

A

Glucose
Phosphate

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18
Q

How does DCT maintain acid-base balance

A

Secretes H+ (derived from intracellular carbonic anhydrase) by H ATPase H/K counter transporter - K+ brought into the cell

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19
Q

Effect of aldosterone

A

Increases Na+ reabsorption in DCT and subsequent H2O reabsorption
More K+ lost in collecting duct due to Na/K ATPase
Increases H+ secretion in collecting duct
Promotes Na+ reabsorption in gut and sweat gladns

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20
Q

What causes the release of aldosterone

A

RAAS
Sympathetic
Afferent arterioles wall tension
Paracrine factors
Hyperkalaemia
Hyponatraemia

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21
Q

Why does hyperkalaemia causes the release of aldosterone

A

Causes secretion of K+ via Na/K ATPase

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22
Q

Why does hyponatraemia causes the release of aldosterone

A

Retention of Na+

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23
Q

What is ANP

A

Atrial natriuretic peptide
28 amino acid peptide cleaved from a precursors

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24
Q

What causes the release of ANP

A

Stretch of atria due to:
Large circulating volume
High venous return
Increase in plasma Na+

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25
Q

Where is ANP synthesised and secreted from

A

Cardiac atrial cells - especially right atrium

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26
Q

Effects of ANP

A

Inhibits Na+ reabsorption by blocking ENac and Na/K ATPase
Renal vasodilator of afferent arterioles
Inhibits aldosterone secretion
Blocks renin secretion
Blocks effects of angiotensin

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27
Q

How does ANP inhibit Na+ reabsorption

A

Blocks ENaC and Na/K ATPase

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28
Q

ANP as a renal vasodilator

A

Afferent arterioles dilation
Increases GFR
increases Na+ excretion (natriuresis)

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29
Q

ANP and aldosterone

A

Inhibits secretion from Zona glomerulosa
Increases Na+ secretion

30
Q

ANP and renin

A

Blocks renin secretion in afferent arterioles
Causes dilation, increases pressure in glomerular capillaries increasing GFR, increases tubular flow rate so increases Na+ loss

31
Q

How does ANP block the effects of angiotensin

A

Blocks the H/Na exchange and Na/K ATPase

32
Q

When is parathyroid hormone released

A

In response to low plasma Ca2+ concentration

33
Q

Effect of parathyroid hormone

A

Reduces phosphate uptake
Stimulates formation of vitamin D

34
Q

Where is vitamin D formed

A

Kidneys

35
Q

How does parathyroid hormone work

A

Binging with a receptor causes an increases in Ca2+ uptake from the tubule which is carried across the basolateral membrane by Ca/H ATPase and Ca/H counter transporter

36
Q

Function of collecting duct

A

Acid-base balance
Regulation of salt
H2O reabsorption

37
Q

What percentage of glomerular filtrate reaches the collecting duct

A

15%

38
Q

What volume of glomerular filtrate reaches the collecting duct

A

20-25 L

39
Q

Concentration of fluid entering collecting duct

A

100 mOsm

40
Q

Why is the collecting duct impermeable to water

A

Cells have very tight junctions

41
Q

What urine concentration can it reach in the collecting duct if vasopressin active

A

1000-1200 mOsm

42
Q

What is vasopressin

A

9 amino acid peptide (nonapeptide)
Cleaved from a larger precursor

43
Q

Where is vasopressin synthesised

A

Magnocellular cells in the supraoptic and paraventricular nuclei of hypothalamus

44
Q

Where is vasopressin stored

A

Granules with neurophysin

45
Q

Where is vasopressin secreted from

A

Posterior pituitary

46
Q

How is vasopressin transported from the hypothalamus to pituitary

A

Neurohypophysis in neurones

47
Q

What controls the release of vasopressin

A

Hypothalamic osmoreceptors

48
Q

How sensitive are osmoreceptors

A

Very
Can detect changes as small as 1-2% in osmolarity

49
Q

What substances affect vasopressin secretion

A

Alcohol
MDMA (ecstasy)
Nicotine

50
Q

How does alcohol effect vasopressin secretion

A

Decreases
Results in hydration

51
Q

How does MDMA effect vasopressin secretion

A

Inhibits
Results in dilute blood which leads to seizures and fits

52
Q

How does nicotine effect vasopressin secretion

A

Increased

53
Q

Half life of vasopressin

A

15 mins- allows for quick adaptations to osmolarity changes

54
Q

Mechanism of vasopressin

A

Binds to V2R receptors (Gs GPCR)
Protein kinase A phosphorylates serine 256 sites on tetrameter of vesicle
If 3 out of 4 sites arephosphorylated the vesicle is shuttled to apical surface where AQP2 is inserted

55
Q

What channel protein transports water out of colllecting ducts

A

AQP2

56
Q

What receptor does vasopressin bind to in kidneys

A

V2R receptors

57
Q

What does binding of vasopressin to V2R receptors trigger

A

Protein kinase A to phosphorylate serine 256 sites on tetrameter of vesicle

58
Q

How many serine 256 sites must be phosphorylated for vesicle to fuse with apical membrane in collecting duct

A

3 out of 4

59
Q

How many times can shuttling back of the AQP2 occur before the protein is degraded

A

3/e

60
Q

What happens once water is reabsorbed via AQP2 on apical membranes

A

Escapes through AQP3 and AQP4 channels on basolateral membrane

61
Q

How does vasopressin affect arterioles

A

Constriction which helps restore arterial blood pressure to normal

62
Q

What stimulates thirst

A

Increase in plasma osmolarity
Decrease in extracellular fluid

63
Q

Vasopressin and urea

A

Causes insertion of urea transporters (UTA) onto the membrane
Vasa recta contain UTB
Try and keep the interstitium high in urea so we can excrete urine at a high concentration - stops osmotic effect
Vasopressin helps maintain the hyperosmolarity of medulla by increasing urea permeability of collecting duct

64
Q

Where are baroreceptors that control vasopressin secretion located

A

CVS eg aortic arch and carotid sinus

65
Q

What causes baroreceptors to decrease their firing

A

CV pressures decrease eg reduced blood pressure

66
Q

Baroreceptors and vasopressin secretion

A

Decrease firing when CV pressures decrease
Baroreceptors transmit fewer impulses via afferent neurones and ascending pathways to hypothalamus—> vasopressin secretion

67
Q

Baroreceptors and vasopressin decrease

A

Increase CV pressures
Increased baroreceptors firing
Decrease vasopressin secretion

68
Q

Sensitivity of baroreceptor reflex of vasopressin

A

High threshold = sizeable reduction in CV pressure required to trigger it
Les sensitive than osmoreceptors reflex

69
Q

Transporters on apical membrane of DCT

A

NCC (na and Cl)
Ca2+

70
Q

Aldosterone action

A

Increases transcription (steroid receptor) of ENaC (and NaKATPase)
This increases apical Na influx
This charge movement facilitates K efflux
Thus aldosterone drives both Na reabsorption and K secretion

SUGER (17 decks)

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