ATS Book Flashcards
At what part of the nephron do the following act
(a) Loop diuretics
(b) Thiazide diuretics
(c) Aldosterone antagonists
(a) Loop diuretics: block Na/K/Cl on thick ascending limb => block Na reabsorption into capillary
(b) Thiazides block NaCl in the distal convolute tubule => block Na reabsorption
(c) Spironolactone works in the distal DCT/early collecting duct, blocking Na reabsorption
Mechanism by which spironolactone can cause
(a) K imbalance (high or low?)
(b) Acid/base disturbance (acidosis or alkalosis?)
Aldosterone antagonists side effects
(a) Hyperkalemia- hence why also called a K-sparing diuretic
(b) Metabolic acidosis b/c reduces H/K antiporter in the collecting duct (reduces acid, H+ secretion into tubule)
Where does ADH act in the nephron?
ADH drugs = vaptans (tolvaptan)
-ADH activates NaKCl transporter in the thick ascending limb => increases Na reasborption
-ADH increases water reabsorption in the collecting duct
Location of acetazolamide vs. metolazone activity in the nephron
Carbonic anhydrase inhibitor (diamox = acetazolamide) work in the proximal tubule
vs. Thiazides (metolazone) in the distal tubule) to inhibit Na reabsorption by inhibiting NaCl transporter
Mechanism by which acetazolamide causes
(a) Diuresis
(b) Change in acid/base status
Acetazolamide = diamox = carbonic anhydrase inhibitor, inhibits enzyme in the proximal convoluted tubule which allows recycling of bicarb and Na back into the bloodstream
=> more Na and bicarb excreted in urine (b/c less reabsorbed) => water follows sodium (diuresis) and helps dump bicarb into urine (so helps improve a metabolic alkalosis)
Explain the electrolyte imbalance expected in hyperaldosteronism
Aldo => tubular NaCl reabsorption and K excretion
=> NaCl/water retention = hypertension
=> hypokalemia
Explain how RAAS system stimulation causes vasoconstriction
Renin stimulates angiotensinogen –> angiotensin I –> ATII which directly causes vasoconstriction to increase BP
RAAS system
(a) How initially stimulated (what releases renin and why)
RAAS system stimulated by renin release from juxtaglomerular apparatus in kidney in response to low renal perfusion
Renin then converts angiotensinogen (made by liver) to angiotensin I –> ATII –> Aldo
3 ways in which angiotensin II helps increases blood pressure
ATII increases BP by
(a) Direct vasoconstriction
(b) Stimulating aldosterone release from adrenal gland => increase NaCl reabsorption from kidney to increase blood volume
(c) Stimulates ADH release from pituitary gland to increase aquaporin activity in collecting duct => increase water reabsorption
ADH
(a) Where secreted from
(b) Action
ADH
(a) secreted from the posterior lobe of the pituitary gland
(b) increases aquaporin activity to increase water reabsorption in the collecting duct
Define SIADH
ADH is typically secreted from posterior lobe of the pituitary gland in response to hyperosmolality and low effective circulating blood volume. Secretion of ADH in absence of these hyperosmolality and low effective circulating blood volume = inappropriate
ADH release stimulated by
(a) What blood osmolality
(b) High or low effective circulating blood volume
ADH release from posterior pituitary stimulated by
(a) High blood osmolality (over 295)
(b) Low effective circulating blood volume
Two examples of hypertonic hyponatremia
Hyperglycemia
Mannitol
High osmotic substances => osmotic shift of water out of cells, total Na content not actually low
Formula for serum osmolality
Serum osmolality = 2[Na] + glucose/18 + BUN/2.8
Feared complication of rapid overcorrection of
(a) Hyponatremia
(b) Hypernatremia
(a) Osmotic demyelination
(b) Cerebral edema
p.4 hyponatremia - 10
Differentiate central from nephrogenic diabetes insipidus
Central = loss of ADH production from posterior lobe of the pituitary
Nephrogenic = loss of function of ADH receptors in collecting ducts (lack of renal responsiveness to ADH)
Both therefore cause reduction in free water reabsorption (inability to concentrate urine) => hypernatremia
Mechanism by which the following cause hypernatremia
(a) Mineralocorticoid excess
(b) Central diabetes insipidus
Hypernatremia
(a) Hyperaldo => increased Na reabsorption by tubules so too much Na reabsorption
(b) Central DI = no ADH production => reduced free water reabsorption in collecting duct
Etiologies of nephrogenic DI
- Congenital
- (way more common) Acquired due to typically meds: lithium, amphotericin etc
Why not to suspect diabetes insipidus with a Na of 155
Na typically doesn’t exceed 150 in diabetes insipidus (either ADH not secreted or kidneys don’t respond to it) b/c thirst mechanism is still intact
So Na rarely > 150 unless there is restricted access to free water
Differentiate urine Na and Urine osms in diabetes insipidus vs. hyperaldo
Diabetes insipidus
(a) urine osms < 300 mOsm/kg (no ADH response = water not reabsorbed = very dilute urine)
(b) Urine Na < 20 mEq/L
Mineralocorticoid excess: too much aldo = too much Na reabsorption so very concentrated urine
(a) Urine osm > 600
(b) Urine Na < 20
24 goal correction for hypernatremia if
(a) Acute
(b) Chronic
Hypernatremia correction
(a) Acute- develops in <48 hrs: reduce Na by 1-2 mEq/L/h until 145
(b) Chronic- >48 hrs: reduce Na by 0.4 mEq/L/hr to a max of 10 mEq/L/d (some say 6-8)
Formula for free water deficit
Free water deficit (L) = ([Actual Na]-[Desired Na]) / [Desired Na] x TBW
TBW (total body water = weight (kg) x 0.6 (men) or 0.5 (women)
Describe the mechanism of hyponatremia in
(a) CHF
(b) Cirrhotics
(a) CHF: reduced cardiac output = low effective circulating volume detected by the JGA in the kidneys causing renin release (RAAS activation) => retention of water out of proportion to Na
(b) Cirrhosis: NO causes splanchnic and peripheral vasodilation = low effective circulating volume => RAAS activation
K+ disorders p10
p10-39
Describe 2 main receptor irregularities that play a role in EtOH withdrawal
EtOH withdrawal- autonomic dysfunction due to
Upregulation and uninhibited NMDA (excitatory) and downregulation and decrease response to GABA (inhibitory)
Differentiate Wernicke’s encephalopathy and Korsakoff syndrome
Neurologic complications of chronic ethanol use, both associated with thiamine (B1) deficiency
Wernicke’s = acute neurologic complication
Korsakoff = late neurologic complication with amnesia
Two enzymes involved in ethanol metabolism
Ethanol – (ethanol dehydrogenase) –> acetaldehyde – (acetaldehyde dehydrogenase) –> acetate
Explain why IV ethanol can be used to treat methanol and ethylene glycol toxicity
(a) what else can be used to treat methanol toxicity
Same enzyme used to break ethanol –> acetaldehyde as metahnol –> formaldehyde
Name of the game is reducing production of toxic byproducts of methanol (antifreeze, windshield wiper fluid) => can use ethanol to competitively inhibit alcohol dehydrogenase
(a) Fomepizole also works as competitive inhibitor of ethanol dehydrogenase
Aside from CNS toxicity, what key clinical feature distinguishes methanol from ethylene glycol toxicity
Methanol associated with vision loss, ethylene glycol associated with renal failure
Differentiate which toxic alcohols cause elevated osmolar gap vs. anion gap
Elevated osmolar gap, normal anion gap = ethanol, isopropyl alcohol (hand sanitizers)
Elevated osmolar and anion gap = methanol and ethylene glycol (antifreeze, windshield washer fluid) and propylene glycol (in high doses of IV benzos)
Differentiate urine studies in prerenal vs. intrinsic AKI
(a) urine Na
(b) urine osm
(c) UA
Prerenal
(a) Urine Na- <20 (trying to reabsorb salt)
(b) Urine osms > 600 (very concentrated)
(c) UA bland
Intrinsic (ex: ATN)
(a) Urine Na > 40 (kidneys damaged can’t resorb Na)
(b) Urine Osms < 500 (can’t concentrate urine effectively)
(c) UA with classic muddy brown casts in ATN
