Renal Potassium Handling - Rogachev Flashcards
What are the concentrations of sodium and potassium inside and outside the cell?
Inside the cell: [Na+] = 20 [K+] = 120 Outside: [Na+] = 140 [K+] = 4 Resting potential = -70
Potassium input and export from body and cells
Normal diet: 50-100 mEq/day 3500mEq in intracellular fluid 70mEq in extracellular fluid (2%-baseline regulated by insulin, defence regulated by catecholamines) 90mEq excreted renally (mainly corticocollecting duct from principal cells, in some forms of distal RTA impaired H+ excretion results in K+ wasting and hypokalemia with H+/K+ ATPase) 10mEq excreted by GI
How is potassium regulated in the cortical collecting duct principal cells?
Na/K ATPase on cell membrane of basolateral side Regulated by distal delivery of Na and mineralicorticoid activity (also nonreabsorbable anions) Na channel on luminal membrane (motivated by charge) ROM-K channel lets K flow out- regulated by mineralicorticoid activity- more on basolateral side
How do mineralocorticoid and distal delivery fluctuations affect K+ secretion in the CCD (table)?
DDx of Hypokalemia
• Pseudohypokalemia (lab error) • Cell Shift Into cells a bit from alkalosis from H/K and ATPase exchanger, more from vomiting, insulin and beta-adrenergic anabolism (deprived then quick uptake), hypothermia (J- point), barium intoxication, malaria/psych drugs Hypokalemic periodic paralysis • Inadequate intake (rare) • Gastrointestinal loss Diarrhea most common cause if Urinary K+ < 20 mEq/day; or K+/Creatinine ratio (mmol/mmol) < 1; or FeK+ < 10%; or TTKG < 3 [K+] 30-50mEq/L in secretions Vomiting [K+] 5-10 mEq/L -not enough so renal loss Small intestine effect-hypoK with normal anion gap acidosis with bicarbonate loss (conc. 20 mEq/day, no history of diarrhea, primary increase in mineralocorticoids (high BP and volume expansion) or distal Na delivery (low/normal BP and volume contraction)
Hypokalemic Periodic Paralysis
• Intermittent acute attacks of muscle weakness with hypokalemia (
Transtubular K Gradient (TTKG)
• Determination of TTKG is indirect way to asses whether renal response to abnormality in the serum K+ concentration were appropriate • K+ concentration in the final urine will exceed the concentration on the end of the collecting duct as a result of water reabsorption along the length of collecting duct • Dividing by UOSM/POSM accounts for this effect TTKG= UK+ POSM PK+ UOSM • Normal TTKG 8-9 will increase to >11 with increased K intake • In chronically hyperkalemic patients TTKG < 5 result of aldosterone deficiency or resistance • In patients with extrarenal K loss TTKG should fall to values < 3
Laxative abuse and GI hypokalamia
Laxative effect in colon–> • K+ depletion • Intracellular acidosis •
Types of primary mineralicorticoid increase
• Primary Hyperreninism
• Primary Hyperaldosteronism
• Primary Increase in Nonaldosterone
Mineralocorticoids
• Cortical Collecting Duct abnormalities
Primary Hyperreninism
Are renin/aldosterone low/high?
• Elevated renin and aldosterone levels (not volume volume contraction)
• Saline suppression test distinguishes volume
contractions (if secondary, renin decreases)
• DDx
-Malignant hypertension: 50% have hypokalemia
-Renal artery stenosis: 15% have hypokalemia
-Renin secreting tumor (hemangiopericytoma-also causes decreased P from increased FGF23)
Primary hyperaldosteronism
• Elevated aldosterone suppressed renin level (if volume contraction wouldn’t have high aldo without renin)
• DDx
- Conn’s syndrome:
(aldosterone secreting adenoma)
-Bilateral adrenal cortical hyperplasia
- Glucocorticoid remediable aldosteronism (mutated 11-beta-1 and -2 hydroxylase so that ACTH stimulates aldosterone production, vulnerable to brain aneurysm d/t HTN-cured by prednisone)
Work up:
Aldosterone/renin ratio > 25, CT scan, adrenal
vein sampling (to check for increase at site)
Serum aldosterne > 15ng/dL
Primary Increase in Nonaldosterone Mineralocorticoid
• Depressed renin and aldosterone levels
• DDx
-Cushing syndrome
-Congenital adrenal hyperplasia
11-hydroxylase deficiency (virilization)
17-hydroxylase deficiency (decreased sex hormones)
-Genetic causes
-Syndrome of apparent mineralocorticoid excess
(acquired-licorice-11-betaHSD2 causes HTN looks like Cushing’s bc MCR activated by cortisol)
- Liddle’s syndrome (not a problem with MCR but with PY segment in ENaC in CCD more distal to receptor and not degraded, cured with kidney transplant)
- Activating mutations of the MC receptor (any steroid can activate the receptor-more exacerbated in pregnancy and with spironolactone because activates rather than blocks the receptor)
Clinical presentation of Bartter’s Syndrome
How does it compare to Gitelman’s?
Bartter’s
Mutation in ThAL mostly in basolateral Chloride channel, others in Na/K/2Cl transporter or ROMK
• Normal blood pressure
• Hypokalemic alkalosis
• Elevated angiotensin II and aldosterone levels
• Hyperplasia of the renal juxtaglomerular apparatus
and adrenal zona glomerulosa
• Spironolactone caused serum K+
to rise
• Infusion of angiotensin II leads to subnormal
increase in blood pressure
Low blood volume, looks like furosemide
All Gitelman patients have hypomagnesemia, only some of Bartter’s do. Bartters have hypercacliuria and Gitelman’s hypocalciuria. Gitelman’s can concentrate urine and Bartter’s can’t. Bartter’s presents earlier. Gitelman’s is a loss of function of Na/Cl transporter in DCT (like thiazides). Both have hyperchloremic alkalosis.
Flowchart of hypokalemia
Causes of hyperkalemia
Pseudohyperkalemia: mistake in blood sample
• Cell damage – rhabdomyolysis,
tumor lysis, massive hemolysis
• Diabetic ketoacidosis, nonketotic
hyperosmolar hyperglycemic state (Na/K ATPase)
• Lactic acidosis (cell ischemia)
• Toxins/drugs – digoxin, palytoxin,
tetrodotoxin
• Hyperkalemic periodic paralysis
HCl (inorganic) can cause cell shift (organic acids don’t)
• Autosomal dominant
• Mutation in voltage activated
(tetrodotoxin-sensitive) Na+ channel
(on nerve and muscles cells)
• Younger age of onset, greater
frequency of attacks and shorter
duration
• Hyperkalemia and paralysis
precipitated by fasting, could exposure,
rest after exercise, or ingestion of small
amount of potassium
• Primary decrease in
mineralocorticoids
• Primary decrease in distal delivery
of Na+
• Abnormal CC
Not due to low effective blood volume
Primary Decrease in Mineralocorticoid (hypo hypo)
• Oliguric ARF
• Acute poststreptococcal
glomerulonephritis
• Pseudohypoaldosteronism Type II
(Gordon’s syndrome-hyperkalemic acidosis with HTN correctable by thiazides, enhanced Na absorption proximal to CCD)
Renal K+ retention due to abnormal CCD
Pseudohypoaldosteronism
-Recessive ENaC inactivation–> early death (pulmonary infections)
-AD: inactivating MCR mutation
Hyperkalemia Summary
