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Renal Week 1 > Lecture 11: Disorders of Water Balance, HYPOnatremia > Flashcards

Lecture 11: Disorders of Water Balance, HYPOnatremia Flashcards

1
Q

What is hyponatremia? Significance?

A

An electrolyte abnormality in which the serum sodium level is <280 mOsm/kg or functional osmolarity)
Tonicity influences cell volume and therefore cell health

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2
Q

What causes hyponatremia?

A

When water intake exceeds body’s ability to excrete the water

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3
Q

What is the renal water clearance?

A

Known as the free water clearance

Not necessarily equal to urine volume

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4
Q

What is osmolarity?

A

Osmolarity = 2*Na + glucose/18 + BUN/2.8
Number of ALL particles per volume
Nature of particles are irrelevant

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5
Q

What is tonicity?

A

Effective osmolarity
Only particles that do NOT freely cross cell membranes contribute to tonicity
Tonicity = 2*Na + Glucose/18
You drop BUN because urea is freely mobile across cell membranes

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6
Q

What is the difference between osmolarity and tonicity?

A

In osmolarity, the nature of the particles are irrelevant as long as they are there
In tonicity, only particles that don’t cross the cell membrane matter

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7
Q

How does one determine osmolarity?

A

By measuring the freezing point of the solution
The more particles in a solution = lower the freezing point
Freezing depression at its finest!
This is what an osmometer does

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8
Q

What does equilibrium mean in tonicity?

A

Water movement into the cell equal water movement out of the cell

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9
Q

What happens when you add more fluid into the ECF?

A

Both the ECF and ICF become more hypotonic and less concentrated
-so mOsm in both compartments drop
ICF volume increases, thereby expanding the cell

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10
Q

If fluid is added to the ECF, and the ICF volume expands to compensate, what are the compensatory mechanisms for ICF volume expansion?

A

Extrusion of intracellular osmolytes such as K+ and amino acids, thereby causing water to flow out

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11
Q

Why does hypotonicity develop? Key Point 1

A

Because there is more water intake than water excretion

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12
Q

What are major factors controlling water excretion? Significance?

A
  1. EABV (effective arterial blood volume)
    -a measure of renal perfusion
  2. ADH
    Low EABV and High ADH impairs kidney’s water excretory capabilities

When somebody has hypotonicity or hyponatremia, that means you either have a low EABV or a high ADH level

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13
Q

What is renal water clearance a function of? Key Point 2

A

Renal water clearance is a function of the volume and concentration of the urine

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14
Q

What does normal water excretion depend on?

A

Normal water excretion depends largely on kidney’s ability to produce urine that is HYPOtonic to the plasma

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15
Q

What is the impact of a low EABV on kidney’s ability to excrete H2O?

A

90% of filtered load reabsorbed at proximal tubule vs 65% normally
90% of delivered load reabsorbed at thin descending limb vs 65% normally
Thus max water excretion is only 1.5 L/D when it is usually 18L/D
Thus, low EABV = low excretion of water

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16
Q

What is distal delivery? What determines it? Key Point 3

A

Distal delivery = amount of filtrate not reabsorbed by proximal tubule and thin descending limb
Distal delivery = GFR-proximal reabsorption
Distal delivery is thus determined by proximal reabsorption
The more proximal reabsorption, the less distal delivery and the less water excreted

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17
Q

What is the significance of determining the distal delivery? Key Point 4?

A

The volume delivered distally is the maximum volume of dilute urine (water) that kidney can secrete
Low EABV = less renal perfusion = secretion of renin

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18
Q

What are the effects of angiotensin II on the proximal tubules and peritubular capillaries?

A

Proximal tubules, angiotensin II binds to AT1 receptors leading to activation of
i. Na/H exchanger
ii. Na/HCO3 cotransporter
iii. Na/K ATPase
iv. insertion of H/ATPase into the apical membrane
So on the whole leads to greater reabsorption of sodium and bicarb
Angio 2 produced in proximal tubules
Peritubular capillaries
Increases the oncotic pressure which increases water reabsorption

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19
Q

What is the MoA of ADH on kidney?

A

ADH, a peptide hormone, binds to a GProteinCR called V2 located on the basolateral membrane of collecting duct epithelial cell
V2, which is a Gstimulating receptor, activates adenylcyclase which upregulates cAMP
Increased cAMP levels trigger insertion of aquaporin 2 into apical membrane by exocytosis
Increased cAMP also upregulates transcription of aquaporin 2 gene
Can also increase permeability of urea in collecting duct, thereby increasing gradient
ADH also has actions on CV system (vasoconstriction) and CNS (mechanisms unknown)

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20
Q

What receptor does ADH bind to?

A

V2 receptors on basolateral membrane of collecting duct

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21
Q

What are V2 receptors?

A

Aka AVPR2 (or arginine vasopressin recetor 2)
The receptors that ADH binds to in the collecting duct
V2 = Gstimulating Protein Couple Receptors or Gs
Located on basolateral membrane of collecting duct

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22
Q

What does AVP stand for?

A

Arginine vasopressin

Aka ADH aka vasopressin

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23
Q

What are Weibel-Palade bodies?

A 
Storage granules of endothelial cells
Located in the inner lining of blood vessels and the heart
Release following two molecules:
	i. vWF
	ii. P-selectin
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24
Q

What cells secrete ADH?

A

Magnocellular neurosecretory neurons in the
1. Paraventricular nucleus of hypothalamus (PVN)
2. Supraoptic nucleus (SON)
Which secrete ADH to posterior pituitary gland
AND
Parvocellulary neurosecretory neurons in the PVN
Released at median eminence, travels to anterior pituitary, stimulates corticotropic cells synergistically with CRH to produce ACTH
ADH  upregulation of ACTH

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25
Q

What is the role of ADH in the kidney?

A

Upregulates aquaporin II receptors on collecting tubule to make water permeable
WITHOUT ADH, collecting ducts are impermeable to water
With ADH…water content goes from 18L to 0.5L
Without ADH…water content stays at 18L at the start of collecting tubule

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26
Q

How does one calculate the free H2O clearance?

A

Total urine volume = volume of free H2O + volume of urine with electrolyte content of serum
Free H2O clearance = urine volume x (1- urineNa+K/SerumNa+K)

27
Q

What is free water content of 1000 mL of urine with a UNa = 40 mEq/L and UK = 50 mEq/L in a patient with a SNa = 115 mEq/L & SK = 5 mEq/L?

A

Free water content = 1000 ml * [1-(40+50)/(115+5) = 1000 * (1-3/4) = 250 mL
Free water content = 250 mL

28
Q

Why can you remove potassium from the calculation sometimes?

A

Because potassium is always 5 and if it fluctuates too much, patient is dead
That’s why sometimes you can just ignore serum and urine K and focus just on Na

29
Q

What decreases ADH secretion?

A

Hypotonicity

30
Q

V

A
  1. Hypertonicity
  2. Low BP (via baroreceptors)
  3. Low EABV (via volume receptors)
  4. Pain
  5. Nausea
  6. Hypoxia
  7. Drugs (morphine)
31
Q

Is water an effective intravascular volume expander?

A

No it is not, but it is still upregulated because during hypovolemia because it is better than nothing
Na is the most effective volume expander

32
Q

What does one need to consider when the serum sodium is low?

A
  1. Determine the tonicity!
  2. Why is the kidney not getting rid of excess water
  3. What needs to be done for the patient?
33
Q

How does one work through a case of low serum Na?

A
  1. Is sodium low? If yes,
  2. Calculate tonicity of URINE
    2a. 100 mOsm/kg of urine = physical exam
    2bi. Reason one for hyponatremia is volume overload
    - edema, rales
    - CHF
    - cirrhosis
    2bii. Reason two for hyponatremia is volume depletion
    - orthostasis
    - renal Na loss
    - extrarenal Na loss
    2biii. Euvolemic
    - SIADH
    - Thiazides
    - Endocrinopathies
34
Q

Why did the hypotonicity develop in someone who lost blood and was given water?

A
  1. volume depletion causing a low EABV
  2. water intake
  3. Volume depletion causing a high ADH
    All of the above were causes
35
Q

What is orthostasis?

A

Blood pressure falls and heart rate rises when person stands up

36
Q

What are the three types of hypotonic hyponatremias?

A
  1. Hypovolemic
  2. Hypervolemic
  3. Euvolemic
37
Q

What is the clinical sign of hypovolemic hyponatremia?

A

Orthostasis

38
Q

When patient presents with orthostasis and hyponatremia, what are the probably causes?

A 
Abnormal Sodium loss due to
Renal Na Loss
1. Diuretics
2. renal failure
3. adrenal insufficiency (not enough aldosterone)
4. vomiting
5. NG suction
Extra-Renal Na Loss
6. diarrhea
7. profuse sweating
8. excessive burns
39
Q

What are the causes for impaired water excretion physiologically in hypovolemic hyponatremia?

A 
Decreased EABV (because of Na loss)
High ADH
40
Q

What are the clinical symptoms of euvolemic hypotonic hyponatremia?

A

No orthostasis or edema
But it does not mean EABV is necessarily normal
Small cell lung cancer
-because small cell of lung can lead to a tumor that makes ADH
Diagnosis made because urine concentration >100 mOsm/kg
So even though patient doesn’t have any symptoms, they have the laboratory measure of hyponatremia

41
Q

What are the causes of euvolemic hypotonic hyponatremia?

A
  1. thiazides = subclinical hypovolemia (decreased EABV and increased ADH)
  2. Glucocorticoid deficiency = increased ADH
  3. Hypothyroid = poor EABV due to poor pump function and increased ADH
  4. SIADH = too much ADH or ADH activity (drugs, tumors, CNS processes)
42
Q

What is SIADH?

A

Syndrome of Inappropriate Antidiuretic Hormone Secretion
A subset of euvolemic hypotonic hyponatremia
Suspect when Urine Osm > 100, urine Na > 40 and SERUM uric acid is low (because it is excreted into urine as a result of too much ADH)
Caused by
i. tumors that make ADH (small cell of lung cancer)
ii. drugs that can stimulate ADH release
a. chlorpropamide
b. cyclophosphamide
c. Haldol
iii. Pulmonary processes like pneumonia
iv. Genetic (mutation of V2 receptor that makes it perpetually activated)

43
Q

What is Haldol?

A

Haloperidol
Antipsychotic
MoA is that it SILENTLY antagonizes D1, D5, 5HT2A, 5HT2C, 5HT6/7, H1, M1, Alpha adrenergic 1a, 2a, 2b, 2c
And is an agonist for D2, D3, D4, Sigma 2, and 5HT1A

44
Q

How do you treat SIADH?

A
  1. Restrict water intake

2. correct cause if possible (eg stop offending drug)

45
Q

Why is SIADH a sublinical volume EXPANDED state?

A

Because while body has held onto water, water is not effective at expanding EABV although it still does to a certain extent

46
Q

What is the difference in findings between thiazides and SIADH patients?

A

Both cause euvolemic hypotonic hyponatremia
However, a key difference is that SIADH causes subclinical volume OVERLOAD whereas thiazide causes sublinical volume DEPLETION
SIADH = subclinical hyperVOLEMIA
Thiazide = subclinical hypoVOLEMIA

47
Q

If patient had intake of 2500 ml water in 12 hours and a urine output of 200 ml/hr (adds up to 2400 ml/12 hr)…therefore the net ins and outs are 100 ml
What is his net water balance?

A

2500 mL because no water is being peed out!
SNa = 127, SK = 5, UNa = 70 and Uk = 62…so 132/132 = 1
1000 *(1-1) = o
Net water balance is 0
Net water balance = free water clearance = 1000 * (1-Una+Uk/Sna + Sk)

48
Q

Does water balance of 2500 ml explain drop of SNa from 130 to 127 meQ?

A 
130*36L = 4680
127*42L = 4572
Difference = 130 mEq of Na or 2500 ml of 3% saline
49
Q

What are the symptoms of hypervolemic hypotonic hyponatremia?

A

Edema (with or without CHF) as well as rales, S3

>100 mOsm/kg of urine

50
Q

What is the cause of hypervolemic hyponatremia?

A

Total body volume is increased BUT renal perfusion is poor
Etiologies
i. CHF (poor pump function so poor renal perfusion)
ii. Liver disease (AV shunting so poor renal perfusion)
iii. Nephrosis (low intravascular oncotic pressure due to loss of albumin in urine…loss of albumin = less renal perfusion)

51
Q

What is the physiological conditions that lead to hypervolemic hyponatremia?

A

This is caused by impaired water secretion
Decreased EABV = limited distal delivery since there is poor renal perfusion
High ADH which leads to less water excretion

52
Q

What are the clinical manifestations of hypotonic hyponatremia?

A 
Symptoms are mostly CNS
1. Headache
2. Muscle Twitching
3. Seizures
4. Comas
There are two types of hyponatremia
i. Acute
ii. chronic
53
Q

What are the characteristics of acute hyponatremia?

A

<115 mEq/L

54
Q

What are the characteristics of chronic hyponatremia?

A

Asymptomatic until Na <115 mEq/L

55
Q

How do you treat hyponatremic patients?

A

Treat for SYMPTOMS and not for the Na numbers

56
Q

What are strategies for correction of hyponatremia?

A
  1. correct osmolality of plasma at a rate that matches the rate of creation of hyponatremia
    • Do not exceed 0.5 mEq/L/hr
    • Do not correct to greater than 130 mEq/L
  2. For hypovolemic hyponatremia
    • give volume (NaCl + H2O)
  3. For euvolemic hyponatremia
    • correct underlying disorder (like removing the drug, treating endocrinopathy)
    • restrict water intake and liberalize solute
    • drugs that block ADH effect (for SIADH)
  4. For hypervolemic hyponatremia
    • treat underlying disorders (inotrope for CHF)
    • water restrict
    • diuretics; drugs that block ADH effect
57
Q

What is the danger of rapid correction?

A

Central Pontine Myelinolysis

58
Q

What is central pontine myelinolysis?

A

A danger of rapid correction of hyponatremia
Severe damage to myelin sheath of the pons
Characterized by dysphagia, paralysis and dysarthria
By adding too much hypertonic fluid into the ECF, too much fluid rushes out of neurons at the pons, thereby causing region of brain to shrink and myelin to break apart

59
Q

What are Vaptans?

A

Vasopressin antagonists
Correct serum Na in patients with cinically significant euvolemic and hypervolemic hyponatremia (Na <125 mEq/L)
Example: Tolvaptan
However, although serum Na was corrected, symptoms were not

60
Q

How do you treat a patient with Na = 110 mEq/L who is having seizures?

A

High mortality

Administer hypertonic 3% saline (Na = 513 meQ/L) to get serum into 120 mEq/L safe range

61
Q

Why do you give someone with 513 mEq saline rather than 140 mEq?

A

Because if it was isotonic, kidneys would just excrete all the saline
However, if it is more concentrated, you can correct the hyponatremia

62
Q

How much 3% saline do you give 70kg man who has 110 mEq of sodium content (and you want to raise it to 120 mEq)?

A

Amt of Na in 70kg man = 42L * 110mEq/L = 4620 mEq of total sodium content
Amt of Na in 70kg man with 120 mEq/L of Na = 42L * 120 mEq/L = 5040 mEq of total sodium content

5040 – 4620 = 420 mEq of salt is the amount of salt needed in order to bridge the gap of what’s needed
Thus, since there is 513 mEq of Na in 1 L of 3% saline, you need to give the patient 813 mL of 3% saline in order to deliver 420 mEq of salt and get his concentration from 120 mEq/L to 120 mEq/L

63
Q

What are two potential concerns for adding saline?

A
  1. after you add 813 mL of 3% saline, water content = 42.82 L so the volume has changed. Thus repeat labs after therapy is given
  2. The above calculation for total content assumes Na is in all body water, however 66% of body water is intracellular with low Na levels. For theses cases, potassium is used in place of sodium, so TBW still can be used (fellowship point of interest so no need to worry)

Renal Week 1 (15 decks)

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