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ESA3 > Urinary 6 - Plasma osmolarity (disorders + diuretics) > Flashcards

Urinary 6 - Plasma osmolarity (disorders + diuretics) Flashcards

1
Q

What are the main receptors in the body that detect changes in plasma osmolarity, and where are they located?

A

Hypothalamic osmoreceptors

Organum Vasculosum of Lamina Terminalis (OVLT)

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2
Q

How do the hypothalamic osmoreceptors respond if they detect increased osmolarity?

A
  • Increase thirst stimulus

- Increase ADH secretion

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3
Q

For the hypothalamic osmoreceptors to increase the thirst response, what change in osmolarity must be detected?

A

Increased osmolarity by 10%

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4
Q

For the hypothalamic osmoreceptors to change ADH secretion rate, what change in osmolarity must be detected?

A

Increased or decreased osmolarity by 1%

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5
Q

How does an increase in ADH secretion cause reduction of plasma osmolarity?

A

ADH increases the insertion of AQP2 into the apical membrane of principal cells of collecting ducts = increased water reabsorption

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6
Q

Which aquaporin channels are controlled by ADH?

A

AQP2 in the principle cells of the collecting duct

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7
Q

ADH mediates aquaporin insertion in what part of the kidney tubule?

A

Collecting ducts (principle cells)

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8
Q

Which aquaporin channels are present in the apical membrane of the PCT?

A

AQP1

AQP7

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9
Q

Which aquaporin channels are present in the apical membrane of the descending LoH?

A

AQP1

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10
Q

Which aquaporin channels are present in the basolateral membranes of the PCT and descending LoH?

A

AQP1

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11
Q

Which aquaporin channels are present in the basolateral membrane of the collecting ducts?

A

AQP3

AQP4

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12
Q

List some causes of Central Diabetes Insipidus:

A

Damage to hypothalamus and/or pituitary gland:

  • Brain injury (particularly fracture of base of skull)
  • Meningitis
  • Brain tumour
  • Sarcoidosis
  • TB
  • Encephalitis
  • Aneurysm
  • Langerhans cells histiocytosis
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13
Q

What is the pathophysiology of central diabetes insipidus?

A

Damage to hypothalamus and/or pituitary gland
= lack of circulating ADH
= inadequate reabsorption of H2O from collecting ducts

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14
Q

What are the symptoms of central diabetes insipidus?

A

Polyuria

Polydipsia

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15
Q

What is the treatment of central diabetes insipidus?

A

ADH nasal spray

ADH injections

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16
Q

List some causes of Nephrogenic Diabetes Insipidus:

A
  • Hereditary
  • Acquired (Lithium, hypercalcaemia, hypokalaemia, polycystic kidney disease, sickle cell anaemia, severe pyelonephritis)
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17
Q

What is the inheritance pattern of hereditary nephrogenic diabetes insipidus?

A

X-Linked Recessive

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18
Q

What is the pathophysiology of nephrogenic diabetes insipidus?

A

Kidney is less sensitive to ADH

= Inadequate reabsorption of H2O from collecting ducts

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19
Q

What are the symptoms of Nephrogenic Diabetes Insipidus?

A

Polydipsia

Polyuria

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20
Q

What are the treatments for Nephrogenic Diabetes Insipidus?

A 
Mild:
- Reduced intake of salt and protein
- Adequate water intake
More severe:
- NSAIDs
- Thiazide diuretics
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21
Q

What does SIADH stand for?

A

Syndrome of Inappropriate ADH secretion

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22
Q

List some causes of SIADH:

A
  • Nervous system disorders (MS, encephalitis, infection, epilepsy)
  • Brain injury
  • Drug induced (Lithium, antidepressants, opiates)
  • Pulmonary disorders (Infection, asthma, CF)
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23
Q

Describe the pathophysiology of SIADH:

A

Excessive release of ADH
= Massive volume expansion
= Hyponatraemia

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24
Q

List some symptoms of SIADH:

A

Nausea/Vomiting
Cramps/Tremors/Seizures
Depressed mood/Irritability/Confusion

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25
Q

What is the treatment for SIADH?

A
  • Treat underlying cause
  • Fluid restriction
  • Na+ replacement (IV hypertonic saline)
  • ADH receptor antagonists
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26
Q

Define diuretic:

A

Substance which promotes diuresis by increasing renal excretion of H2O and Na+, to decrease ECF volume

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27
Q

List the 5 classes of diuretic:

A

1) Loop
2) Thiazide
3) K+ Sparing
4) Carbonic Anhydrase inhibitors
5) Osmotic

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28
Q

What is the mechanism of action of Loop diuretics?

A

Block NKCC2 in TAL (Thick ascending limb of LoH)

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29
Q

What class of diuretic does Furesomide belong in?

A

Loop diuretic

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30
Q

What type of diuretic is the most powerful?

A

Loop diuretics

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31
Q

What conditions are Loop diuretics used to treat?

A
  • Heart failure
  • Fluid retention and oedema in Nephrotic syndrome, Liver cirrhosis and renal failure
  • Hypercalcaemia
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32
Q

What are the main complications of Loop diuretics?

A
  • Hypokalaemia
  • Dehydration
  • Hyperuricaemia = Gout attack
  • Hyponatraemia (less common)
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33
Q

Give an example of a diuretic that acts on the TAL (Thick ascending limb of LoH):

A

Furosemide

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34
Q

What class of diuretics block NKCC2 channels?

A

Loop diuretics

35
Q

What is the mechanism of action of Thiazide diuretics?

A

Block Na+/Cl- symporter in the DCT

36
Q

What class of diuretic does Metolazone belong to?

A

Thiazide diuretics

37
Q

What is the preferred diuretic used in patients with osteoporosis, and why?

A

Thiazide diuretics

Increase Ca2+ reabsorption

38
Q

What condition is commonly treated with Thiazide diuretics?

A

Hypertension

39
Q

Which diuretic is most commonly used to treat hypertension?

A

Thiazide diuretics

40
Q

What are the main complications of Thiazide diuretics?

A
  • Hypokalaemia
  • Hyponatraemia
  • Hyperuricaemia = Gout attack
  • Hyperglycaemia
  • Hyperlipidaemia
  • Erectile dysfunction
41
Q

Give an example of a diuretic that acts on the DCT:

A

Metolazone (Thiazide)

Amiloride (K+ sparing ENaC blocker)

42
Q

Which class of diuretics block the Na+/Cl- symporter?

A

Thiazide diuretics

43
Q

What is the mechanism of action of K+ sparing diuretics?

A

EITHER:
1 - Inhibition of ENaC in DCT and collecting duct
2 - Aldosterone antagonist

44
Q

What class of diuretic does Amiloride belong to?

A

K+ Sparing (ENaC inhibition)

45
Q

What class of diuretics does Spironalactone belong to?

A

K+ sparing (Aldosterone antagonist)

46
Q

What are ENaC blockers used for?

A

Used alongside K+ losing diuretics, to minimise K+ loss

47
Q

What conditions are commonly treated with Aldosterone antagonists?

A
  • Hypertension (if caused by Conn’s syndrome)
  • Ascites and Oedema in Cirrhosis
  • Heart failure (with loop diuretics)
48
Q

What is the main complication of K+ sparing diuretics?

A
  • Hyperkalaemia
49
Q

What may increase the risk of hyperkalaemia occurring when taking K+ sparing diuretics?

A
  • ACEi
  • K+ supplements
  • Renal impairment
50
Q

To which class of diuretics do ENaC blockers belong?

A

K+ Sparing diuretics

51
Q

Give an example of a diuretic that acts on the collecting ducts:

A

Amiloride (K+ sparing ENaC blocker)

Spironolactone (K+ Sparing aldosterone antagonist)

52
Q

To which class of diuretics do Aldosterone antagonists belong?

A

K+ sparing

53
Q

What class of diuretic does Acetazolamide belong to?

A

Carbonic Anhydrase inhibitor

54
Q

What condition are Carbonic Anhydrase inhibitors used for?

55
Q

What is the main complication caused by Carbonic Anhydrase Inhibitors?

A

Metabolic acidosis (increases HCO3- loss)

56
Q

What is the mechanism of action of osmotic inhibitor diuretics?

A

Small inert molecules increase the osmolarity of blood and filtrate
= Increased driving force for H2O loss

57
Q

What class of diuretics does Mannitol belong to?

A

Osmotic Inhibitor diuretics

58
Q

What condition can be treated with osmotic inhibitor diuretics?

A

Cerebral oedema

59
Q

By what mechanisms can Loop and Thiazide diuretics cause hypokalaemia?

A

1 - Increased Na+ delivery to late DT/collecting ducts
= Increased Na+ reabsorption (ENaC)
= Increased K+ secretion (ROMK down favourable electrical gradient)
2 - Increased flow rate in lumen
= Secreted K+ is washed away faster (reduced local conc.)
= Increased K+ secretion (ROMK down favourable concentration gradient)
3 - Decreased ECF
= RAAS activation
= Increased Aldosterone activation
= Increased Na+ absorption and K+ secretion

60
Q

Which diuretics can cause hypokalaemia?

A

Loop diuretics

Thiazide diuretics

61
Q

Which diuretics can cause hyperkalaemia?

A

K+ Sparing diuretics

62
Q

Which diuretics can cause hyponatraemia?

A 
Thiazide diuretics
Loop diuretics (less likely)
63
Q

Which diuretics can cause hyperuricaemia?

A

Loop diuretics

Thiazide diuretics

64
Q

Which diuretics can cause hyperglycaemia and hyperlipidaemia?

A

Thiazide diuretics

65
Q

Which diuretics can cause erectile dysfunction?

A

Thiazide diuretics

66
Q

What is a complication of Spironolactone diuretics?

A

Gynaecomastia

67
Q

Which diuretics can cause gynaecomastia?

A

Spironolactone

68
Q

How do Spironolactone diuretics cause gynaecomastia?

A

Decreased testosterone production and Increased peripheral conversion of Testosterone to Estradiol

69
Q

How does Alcohol cause diuresis?

A

Inhibits ADH release

70
Q

How does coffee cause diuresis?

A
  • Increased GFR

- Decreased tubular reabsorption of Na+

71
Q

How does Lithium cause diuresis?

A

Inhibits ADH action on collecting ducts

72
Q

How does hyperglycaemia cause diuresis?

A

Increased osmolarity of plasma and filtrate

73
Q

How does psychogenic polydipsia cause diuresis?

A

Increased fluid intake = increased fluid loss

74
Q

Which nephrons have a vertical osmotic gradient?

A

Juxtamedullary nephrons only

75
Q

What is the concentration of the filtrate when it reaches the distal tubule of juxtamedullary nephrons?

A

100 mosm/L

76
Q

Describe the relationship between the vasa recta and a juxtamedullary nephron:

A

Flow of the vasa recta is in opposite direction to the tubule:

  • Desc. limb of vasa recta accompanies the asc. limb of LoH
  • Asc. limb of vasa recta accompanies the desc. limb of the LoH
77
Q

Na+, Cl- and Urea diffuse into which limb of the vasa recta?

A

Descending limb

78
Q

H2O diffuses into which limb of the vasa recta?

A

Ascending limb

79
Q

What type of nephrons can produce hyper/hypotonic urine?

A

Juxtamedullary nephrons

80
Q

What is the maximum concentration of urine?

A

1200 mosm/L

81
Q

What is the average concentration of urine?

A

300 mosm/L

82
Q

ADH binds to which cells in the kidney?

A

Principal cells in the collecting duct

83
Q

Where is ADH produced and secreted from?

A

Produced - hypothalamus

Secreted from - posterior pituitary

84
Q

How does ADH cause increased water reabsorption across the principle cells of the collecting duct?

A

ADH induces the relocation of AQP2 into the apical membrane

ESA3 (48 decks)

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