SM 199a - IVF and Diuretics Flashcards
What fraction of total body water is plasma?
1/12
ECF = 1/3 of total body water
Plasma = 1/4 of ECF = 1/4 of 1/3 = 1/12
The proximal convoluted tubule reabsorbs 60% of the sodium in the filtrate.
Why aren’t PCT diuretics very powerful?
Inhibiting Na+ reabsorption in the PCT increases the Na+ in the filtrate.
The transport mechanisms distal to the PCT can compensate and reabsorb more Na+ than usual, resulting in only a small decrease in total Na+ reabsorbed
How do potassium-sparing diuretics spare potassium?
Decreaed Na+ reabsorption in the distal convluted tubule and collecting duct leads to decreased electrostatic force pushing K+ into the urinary space
-> Decreased K+ secretion
Which IVF if best if you’re not sure if a patient is hypovolemic or dehydrated?
Normal saline
It is best to replace volume first, then let kidneys deal with balancing electrolytes
Can also give 1/2 normal saline
What kind of diuretic is amiloride?
Where does it act?
What is the mechanism of action?
Amiloride, like other K+ sparing diuretics, acts in the distal convoluted tubule
- Directly inhibts (closes) renal epithelial Na+ channels
Triemterene also acts by this mechansim
How do loop diuretics lead to hypocalcemia?
Loop duretics (ex: furosemide) block the Na+/K+/2Cl- cotransporter
- -> Decreased Na+/K+ ATPase activity on the basolateral membrane
- Less Na+ reabsorption = less drive to pump it into the interstititum = less K+ into the cell
- -> Less intracellular K+
- -> Less K+ pumped out into the tubular lumen (less recycling)
- -> Decreased lumen positivity
- -> Decreased electric gradient driving paracellular Ca2+ reabsorption through claudin 16
- -> hypocalcemia
Note: This is the same mechanism by which loop diuretics may cause hypomagnesemia
What kind of diuretic is spironolactone?
Where does it act?
What is the mechanism of action?
Spironolactone, like other K+ sparing diuretics, acts in the distal convluted tubule
- Blocks the aldosterone receptor
- Aldosterone cannot act to increase Na+ reabsorption
Eplerenone also acts by this mechansim
What are the side effects of K+ sparing diuretics?
- Amiloride and triemterene
- Hyperkalemia
- Nausea
- Vomiting
- Spironolactone
- Hyperkalemia
- Gynecomastia
Describe the mechanism of action of proximal tubule diuretics
PCT Diuretic = Acetazolamide
Inhibits carbonic anhydrase
- Normally carbonic anhydrase promotes the absorption of Na+ with bicarbonate
- Inhibiting carbonic anhydrase causes less Na+ reabsorption, less bicarbonate reabsorption, and less H+ secretion
Note: not often used because not very effective - distal Na+ reabsorption mechanisms compensate
Why would you give a patient D5W?
(What does it fix?)
D5W is given to fix dehyration and/or hypertonicity
It is not great for increasing plasma volume, since only 1/12 of the fluid you give will go to the plasma
(D5W = dextrose + water; the dextrose is metabolized and the water is distributed proportionally to the body water compartments)
If a patient is euvolemic and hyperosmotic, which IVF would you give?
D5W
The patient is dehydrated. D5W will distribuit proportionally to body fluid compartments
How fast should you give fluid to volume resuscitate a patient who has lost 5L via diarrhea?
- If hemodynamically unstable
- Give a 1-2 L bolus in 1 hour or so
- If hemodynamically stable
- Replete in 1-2 days
- 200 cc/h of normal saline would relpace 4.8 L in 1 day
Which IVF is best for treating volume depletion?
Normal saline or lactated ringers
Describe the composition of 5% D5W.
What happens to a patient’s fluid compartments when you give D5W?
50 gm dextrose per 1 L of water
Sugar is metabolized, and the water is distributed according to body water. It is basically like giving pure water, but will not lyse the RBCs
Best used to fix dehyration or hypertonicity
(Not great at fixing plasma volume, since only 1/12 of the fluid given will go to the plasma)
What are the side effects of loop diuretics?
- Volume depletion
-
Electrolyte imbalances
- Hypocalcemia
- Hypomagnesmia
- Hypokalemia
- Ototoxicity, hyperuricemia, hyperglycemia, increased LDL and triglycerides
Use primarily for volume overload. Only used for HTN in patients with CKD
Give some examples of loop diuretics.
What is their mechanism of action?
The -semide and -tanide diuretics
- Furosemide
- Torsemide
- Bumetanide
Mechanism:
- Block the Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Henle
- Major side effects = hypokalemia, hypocalcemia
Which cells would lyse if you gave a patient pure water?
Red blood cells
Usualy, you would give something with at least some solutes, even to treat pure dehydration
How does body fluid compartment volume change upon administration of 1 L of ½ normal saline?
Like giving 1/2 L pure water and 1/2 L normal saline
- 1/2 L (500 mL) pure water
- 167 mL -> ECF
- 42 mL -> Plasma
- 125 mL -> Interstitium
- 333 mL -> ICF
- 167 mL -> ECF
- 1/2 L (500 mL) normal saline
- 500 mL -> ECF
- 125 mL -> Plasma
- 375 mL -> Interstitium
- 0 mL -> ICF
- 500 mL -> ECF
-
Total
-
667 mL -> ECF
- 42 + 125 = 167 mL -> PLasma
- 125 + 375 = 500 mL -> Interstitium
- 333 mL -> ICF
-
667 mL -> ECF
Normal saline contains ______ grams of NaCl in 1 liter
Normal saline contains 9 grams of NaCl in 1 liter
(also called 0.9% saline)
It is basically isotonic (slightly hyper), so all of the infused fluid will stay in the ECF
(1/4 to plasma, 3/4 to interstitium)
How does acetazolamide cause acidosis?
Acetazolamide inhibits carbonic anhydrase in the PCT
This results in:
- -> Decreased Na+ reabsorption
- -> Decreased HCO3- reabsorption
- -> Decreased H+ secretion
Decreased HCO3- = Acidosis
(Non-anion gap, implying that the decereased reabsorption of HCO3- plays a larger role than the retention of H+)
A 20 yo man is admitted after returning from Mexico and having profound diarrhea. He is hypotensive, and his weight is down 5 kg from his usual.
What IVF would you administer?
Normal saline or lactated ringers
What is the difference between diuresis and natriuresis?
Diuresis = producing more urine
Natriuresis = promoting salt excretion
Where in the kidney tubule does furosemide act?
What is the mechanism of action?
Thick ascending limb of the loop of Henle
Blocks the Na+/K+/2Cl- cotransporter
Which diuretics are first-line treatment for hypertension?
Thiazide diuretics
(but use loop diuretics in patients with renal failure)
Which IVF is best for dehydration?
D5W
What is the recommended daily sodium intake?
1500 mg = recommended adequate intake
<2300 mg = recommended upper limit
What kind of diuretic inhibits carbonic anhydrase?
Where does it act?
What is the effect on Na+, HCO3-, and H+?
Acetazolamide
Inhibits carbonic anhydrase in the proximal convoluted tubule
- > Decreased Na+ reabsorption
- > Decreased HCO3- reabsorption
- > Decreased H+ secretion
This can lead to acidosis
Note: not often used because not very effective - distal Na+ reabsorption mechanisms compensate
When would you prescribe loop diuretics?
Rapid diuresis in patients with volume overload
Only use for HTN in patients with kidney disease
(Normally use thiazides, but these are less effective in patients with CKD)
Holding onto or excreting ________ generally controls the volume of the vascular space
Holding onto or excreting sodium generally controls the volume of the vascular space
Which fluid compartment do we measure when we sample blood?
Plasma compartment
(1/12 of total body water)
What is the mechanism of action of potassium-sparing diuretics?
Where do they act?
List some examples
Potassium sparing diuretics decrease flow through Na+ channels in the act in the late distal tubules and collecting duct
-
Triamterene, Amiloride
- Directly inhibt renal epithelial Na+ channels
- They close the channels
- Directly inhibt renal epithelial Na+ channels
-
Spironolactone, Eplerenone (MRAs)
- Block the aldosterone receptor on epithelial cells in the late distal tubule
- Aldosterone can no longer increase Na+ reabsorption
Which diuretics are likely to cause hypercalcemia?
Which diuretics are likely to cause hypocalcemia?
Hypercalcemia = Thiazide diuretics
- Block the Na+/Cl- cotransporter
- -> Less Na+ in the cell
- -> Increased Ca2+/3Na+ exchanger (Basolateral)
- Na+ into the cell, Ca2+ into the interstitium
Hypocalcemia = Loop diuretics
- Block the Na+/K+/2Cl- contranporter
- -> Decreased Na+/K+ ATPase
- -> Decreased K+ pumped back out into the lumen
- -> Decreased positive charge in the lumen to drive Ca2+ reabsorption
Describe the changes to body fluid compartments when you give 1 L of D5W
- 2/3 of the water (667 mL) goes to the ICF
- 1/3 of the water (333 mL) goest to the ECF
- ~83 mL to the plasma
- ~250 mL to the interstitium
In general, D5W is given to fix dehydration or hypertonicity.
It is not great at fixing hypovolemia
What do lactated ringers contain?
Na, Cl, K, Ca, lactate (converted to bicarb in the liver)
It resembles plasma more closely than just saline
You can give it whenever you would give normal saline (acts similarly, except a small amount is moved to the ICF)
What are the effects on body fluid compartments upon administration of 1 L of lactated ringers?
- 900 mL -> ECF
- 225 mL -> Plasma
- 675 mL -> Interstitium
- 100 mL ->
What will happen to body compartment volume upon administration of 1 L normal saline?
All of the fluid stays in the ECF
- 250 mL -> Plasma
- 750 mL -> Interstitial space
Note: administration of normal saline can lead to edema
What are the side effects of thiazide diuretics?
- Electrolyte imbalances
- Hypokalemia
- Hyponatremia
- Hypercalcemia
- Impotence, impaired glucose tolerance, increased cholesterol
What is the mechanism of action of thiazide diuretics?
Where do they act?
Give some examples
Inhibit the Na+/Cl- cotransporter in the distal convoluted tubule
- Hydrochlorothiazide
- Chlorthalidone
- Metolazone
List 3 reasons why you would would you want to give IVF:
- Replete volume (Expland plasma compartment)
- Treate dehydration (Replete water)
- Maintain fluid (if the patient can’t eat or drink)
Why do thiazide diuretics cause hypokalemia?
Thiazides block the Na+/Cl- cotranporter
- -> Increased Na+ delivery to the cortical collecting duct
- -> Increased Na+ reabsorption in the cortical collecting duct
- -> Hypokalemia
What are the estimated water needs for a stable NPO patient?
Every day, a patient probably needs…
- 100 cc/kg for the first 10 kg
- 50 cc/kg for the next 10 kg
- 20 cc/kg for every kg over 20 kg
Note: Don’t give all of this with normal saline! Would be way too much sodium (A person with functioning kidneys could probably sort it out, but someone with renal impairment would be in trouble)
Who do you prescribe K+ sparing diuretics to?
- People who are on diuretics and at risk for hypokalemia
- Usually an add-on (not first line) therapy for HTN
- Use caution if the patient is at risk for hyperkalemia!
When would you give ½ normal saline?
When you’re not sure if the patient is dehydrated, hypovolemic, or both; will allow for some expansion of intravascular volume and some rehydration of cells if necessary
(But honesly none of our CBL cases really called for 1/2 normal saline that I can recall, and I think the general idea is that it’s more important to treat hypovolemia than dehydration acutely…)
Half normal saline contains _____ grams of NaCl in 1 liter of water
Half normal saline contains 4.5 grams of NaCl in 1 liter of water
(also called 0.45% saline)
What kind of diuretic is acetazolamide?
Describe the mechanism of action
Acetazolamide = PCT diuretic
Inhibits carbonic anhydrase
- Normally carbonic anhydrase promotes the absorption of Na+ with bicarbonate
- Inhibiting carbonic anhydrase causes less Na+ reabsorption, less bicarbonate reabsorption, and less H+ secretion
Note: not often used because not very effective - distal Na+ reabsorption mechanisms compensate
How much sodium is in 1 level teaspoon of salt
2 grams
