#2 - Disorders of Fluid and Potassium

Question 1

Normal K+ concentration

Answer 1

3.5-5.3 mEq/L

Question 2

K+ distribution in body

Answer 2

98% in cells, 2% ECF

Question 3

K+ excretion

Answer 3

90% in urine, 10% in stool

GI excretion can increase in kidney failure to 50%

Question 4

K+ is reabsorbed by proximal tubule but

Answer 4

secreted by cortical collecting duct - rate of secretion determines K+ excretion rate

Question 5

K crosses collecting duct in 2 ways

Answer 5

Transcellular > paracellular
- Transcellular route - Na/K-ATPase on basolateral side makes high intracellular concentration, then diffuses along gradient into lumen which is less negative but conc. gradient favors it

Question 6

Rate of transcellular K secretion =

Answer 6

rate of K diffusion across luminal membrane
Increased by:
- Increased intracellular [K], permeability of luminal membrane to K, decreased luminal [K], and more negative lumen

Question 7

Insulin and B2-adrenergic stimulation both

Answer 7

shift K+ into cells, insulin after eating and B2/epinephrine during exercise

Question 8

Mineralocorticoid - Aldosterone

Answer 8

Secreted from zona glomerulosa of adrenal cortex in response to hyperkalemia and Ang. II

• Increases rate of Na+ absorption through luminal channel (makes lumen more negative)
• Increases K+ secretion through Na/K pump
• Increase K+ permeability of luminal membrane
• Increases H+ secretion by intercalated cell

Question 9

Decreased EABV normally causes

Answer 9

• Increased aldosterone from increased JG, renin, AII activity
• Decreased distal Na+ delivery due to increased proximal absorption

Question 10

Increased EABV normally causes

Answer 10

• Decreased aldosterone from decreased JG activity

- Increased distal Na delivery from decreased proximal absorption

Question 11

Distal delivery of Na and H2O are

Answer 11

correlated together

• Increased delivery of Na stimulates distal Na absorption which makes lumen more negative and increases K secretion, also making Na/K pump work faster
• Higher flow rates also remove positive charges in lumen more so more K can be secreted

Question 12

Non-reabsorbable anions effect on Na and volume

Answer 12

increase distal Na delivery because coupled with it, secondarily increasing K secretion, also making lumen more negative. More poorly reabsorbable anions will increase it more.

Question 13

Primary mineralocorticoid excess

Answer 13

E.g. aldosterone secreting tumor, primary aldosteronism - benign tumor of zona glomerulosa = Conn’s syndrome
- Increased aldosterone activity and distal delivery causes K+ loss and hypokalemia

Question 14

Primary increase in distal delivery

Answer 14

E.g. diuretics

- Increase distal delivery and Na loss with volume depletion and increased aldosterone causing K loss and hypokalemia

Question 15

Primary decrease in mineralocorticoid activity or distal Na delivery

Answer 15

Seen in destruction of adrenal gland, acute renal failure

- Cause decreased distal delivery and aldosterone causing K+ retention and hyperkalemia

Question 16

Hyperkalemia stimulates

Answer 16

cell K+ uptake directly, and also through hormones such as insulin and epinephrine

Question 17

Hypokalemia disorder causes

Answer 17

inadequate intake, GI loss, renal loss, cellular redistribution

Question 18

Hypokalemia from inadequate dietary intake because

Answer 18

some K always lost, unlike Na which can go to virtually zero excretion if necessary

Question 19

2 Most common causes of hypokalemia

Answer 19

• Diarrhea - fecal K+ wasting and acidosis causes K+ out of cells which partially helps
• Vomiting - greater K+ depletion, not from gastric loss but metabolic alkalosis which causes kidney to not reabsorb HCO3-, causing K+ wasting. Alkalosis also causes redistribution of K into cells worsening the hypokalemia
• Urinary K+ < 20 mEq

Question 20

Acidosis and alkalosis cause K+ to redistribute

Answer 20

out of and into cells, respectively

Question 21

Hypokalemic periodic paralysis

Answer 21

intermittent attacks of muscle weakness triggered by large carb meals (insulin) or rest post-exercise (epinephrine) where K+ gets acutely shifted into cells

• Inherited form - dominant a-1 mutation in Ca channel
• Acquired - hyperthyroidism

Question 22

Conn’s Syndrome

Answer 22

benign tumor of zone glomerulosa - produces excess aldosterone in absence of volume contraction > K+ loss and hypokalemia
- resolves if tumor removed

Question 23

Bilateral adrenal hyperplasia

Answer 23

HTN will not respond even to bilateral removal

Question 24

Primary aldosteronism

Answer 24

conditions where excess aldosterone secretion is cause of primary adrenal disease, e.g. Conn’s Syndrome and bilateral adrenal hyperplasia

Question 25

Cushing’s syndrome

Answer 25

elevated cortisol and increased secretion of deoxycorticosterone and corticosterone B which have intermediate mineralocorticoid activity, causing milder hypokalemia

Question 26

High renin and aldosterone points to

Answer 26

primary hyperreninemia such as renal artery stenosis or renin secreting tumor

Question 27

Low renin and high aldosterone points to

Answer 27

primary hyperaldosteronism, such as adrenal adenoma, bilateral adrenal hyperplasia, glucocorticoid suppressible hyperaldosteronism, Conn’s syndrome - aldosterone-secreting tumor

Question 28

Low renin and low aldosterone points to

Answer 28

increased level of non-aldosterone mineralocorticoid such as Cushing’s, 11 B or 17 a-hydroxylase deficiency, Liddle Syndrome

Question 29

Ectopic ACTH secreting tumors cause

Answer 29

very severe hypokalemia

Question 30

Glucocorticoid suppressible hyperaldosteronism

Answer 30

dominant disease forming chimeric protein joining ACTH response element with coding region of ADH synthase

Question 31

Syndrome of apparent mineralocorticoid excess

Answer 31

Can be genetic or acquired - e.g. Cushing’s or licorice/chewing tobacco which have Glycerrhetinic acid which inactivates 11B-hydroxylase which forms cortisol from cortisone

Question 32

Liddle Syndrome

Answer 32

Low renin and aldosterone, no response to inhibitor of aldo secretion or spironolactone
- Due to ENaC mutation that prevents its ubiquitination and degradation, leading to excessive Na reabsorption
Triamterene normalizes BP and K (also renal transplant)

Question 33

Diuretic ingestion can cause hypokalemia through

Answer 33

increased distal NaCl delivery and increased aldosterone levels for acetazolamide or thiazides which work proximal to CCD

Question 34

Bartter’s Syndrome

Answer 34

primary defect in loop of Henle salt absorption, causing increased distal delivery and hypokalemia with high renin and aldosterone

Question 35

Gitelman’s Syndrome

Answer 35

defect in distal convoluted tubule NaCl absorption, causing hypokalemia with high renin and aldosterone

Question 36

Nonreabsorbed anions can increase distal Na delivery and cause hypokalemia

Answer 36

HCO3-, ketoanions, Penicillins, hippurate (glue sniffing), salicylate (aspirin overdose)

Question 37

Vomiting primarily causes hypokalemia through

Answer 37

alkalosis > HCO3- excretion which increases NaHCO3 delivery and K excretion, with low Cl-

Question 38

Hypokalemia not due to renal dysfunction should not excrete more than

Answer 38

20 mEq of K per 24 hr

Question 39

Pseudohyperkalemia

Answer 39

errors in processing samples due to K release from thrombocytosis or leukocytosis; can confirm by re-drawing blood in heparinized tube

Question 40

Hyperkalemia caused by decreased renal excretion from

Answer 40

abnormal CCD function, decreased mineralocorticoid levels or distal salt delivery

Question 41

Chronic kidney disease adaptations

Answer 41

remaining nephrons more effective at excreting K, K can redistribute to cells faster and they can excrete more in stool

Question 42

Addison’s disease

Answer 42

aldosterone and cortisol deficiency due to destruction of adrenal glands

Question 43

ACE inhibitors and heparin decrease

Answer 43

synthesis of aldosterone synthesis which can cause hyperkalemia

Question 44

Hyporeninemic hypoaldosteronism

Answer 44

occurs in chronic kidney disease, diabetic nephropathy, interstitial kidney disease - renin and aldosterone both low due to decreased renin production by kidney

Question 45

Amiloride and triamterene inhibit

Answer 45

Na transport making lumen more positive and causing hyperkalemia

Question 46

Spironolactone

Answer 46

competes with aldosterone and blocks its effect, weakening defense against hyperkalemia

Question 47

Cellular redistribution more important as a cause of

Answer 47

hyperkalemia, especially from tissue damage which releases K from cells, rhabdomyolysis, burns, diabetics with high glucose levels, and depolarizing anesthetics such as succinylcholine

Question 48

Inorganic acid causes

Answer 48

K out of cells; organic acid does not cause a shift, so ketoacidosis and lactic acidosis K shifts out of cells are due to hyperosmolarity and insulin deficiency and cell ischemia

Question 49

Hypokalemia effects

Answer 49

• Neuromuscular - weakness and flaccid paralysis, rhabdomyolysis
• Cardiac arrhythmias
• Concentration defects and metabolic alkalosis; resistance to ADH > polyuria and polydipsia
• Glucose intolerance

Question 50

Hyperkalemia effects

Answer 50

Cardiac arrest

Neuromuscular - paresthesias leading to paralysis

Question 51

Cardiac complications of hypokalemia

Answer 51

ST depression, T wave flattening, increased U wave

Question 52

Cardiac complications of hyperkalemia

Answer 52

Causes depolarization block, peaked T wave > QRS and PR widening > “sin wave” of merged QRS and T waves > systole and death

Question 53

Treatment of acute hyperkalemia

Answer 53

• CaCl - blocks effect of K+ on heart
• NaHCO3, glucose, insulin, B2 agonists - shift K into cells
• kayexelate, dialysis - remove K from body

Question 54

Treatment of hypokalemia

Answer 54

address underlying cause

• Chronic - KCl liquid or slow
• Acute - IV KCl
• If hypokalemia accompanied by acidosis, treat hypokalemia first because it must be very severe as acidosis normally shifts K out of cells