Integrative Physiology II Flashcards
ECF K+ tightly regulated
at — meq/L.
4.2
Increase of only 3 to 4
mEq/L can cause (3)
cardiac
arrhythmias, cardiac
arrest, or fibrillation.
Mechanisms controlling K+
Homeostasis (2)
- Control of K+ distribution
between the ECF and ICF - To keep [K+]ECF constant; rate of K+ excretion must equal rate of K+ input.
High [K+ ]ECF:
Hyperkalemia
Low [K+ ]ECF:
Hypokalemia
Factors That Shift K+ Into Cells (decrease [K+]ECF) (7)
insulin aldosterone beta2 adrenergic stimulation alkalosis decrease ECF osm increase na/k ATPase activity dilute ICF, decrease ΔEC for diffusion out of K+ cell
Factors That Shift K+ Out of Cells (increase [K+]ECF) (8)
increased insulin deficiency aldosterone deficiency beta2 adrenergic antagonists acidosis increase ECF osm strenuous exercise decrease Na+/K+ ATPase Activity concentrate ICF, increase ΔEC for diffusion out of cell
Acidosis =
Hyperkalemia
Alkalosis =
Hypokalemia
Three Factors in Tubular Processing of K+
(Filtration; Reabsorption; Secretion)
Day to Day regulation of [K+]ECF is function of
late Distal Tubule/Collecting Duct
High K+ intake increases
K+ secretion (principal cells)
Low K+ intake increases
K+ reabsorption (alpha intercalated cells)
Factors that Determine Rate of K+
Secretion by Principal Cells (3)
- Na+/K+ ATPase Activity
- Transepithelial potential difference
(TEPD) between blood and lumen - Permeability of apical membrane for K+
Factors that Control Principal Cell K+ Secretion
Results in increased K+ Secretion (4)
- increase [K+]ECF
- increase Aldosterone
- increase Distal Tubule Flow Rate
- Acid/Base Status
Alkalosis –
increase K+ Secretion
Acidosis –
decrease K+ secretion
↑[K+]ECF Increases K+ Secretion
Mechanisms (4)
- increase Na+/K+ ATPase activity
- TEPD is more lumen
negative (due to increased
Na+ reabsorption) which
favors K+ secretion - increase # K+ channels in apical
membrane - Stimulates aldosterone
secretion.
Increased Distal Tubule Flow Rate: increase K+ Secretion
Causes (3)
increase ECF volume
Na+ loading
Some Diuretics
Increased Distal Tubule Flow Rate: increase K+ Secretion
Mechanisms (2)
1. Increased tubule flow rate keeps luminal K+ lower, maintaining ΔC for secretion 2. Increases #BK channels in apical membrane
Causes of Hyperkalemia (5)
Renal failure
Decreased distal nephron flow (heart failure, severe
volume depletion, NSAID, etc.)
Decreased aldosterone or decreased effect of
aldosterone
Metabolic acidosis (hyperkalemia is mild)
Diabetes (kidney disease, acidosis, decreased insulin)
Decreased aldosterone or decreased effect of
aldosterone: (3)
- adrenal insufficiency
- resistance to aldosterone
- K+ sparing diuretics (spironolactone)
Causes of Hypokalemia (6)
Very low intake of K + GI loss of K+ - diarrhea Metabolic alkalosis Excess insulin Increased distal tubular flow Excess aldosterone
Increased distal tubular flow: (3)
- salt wasting nephropathies
- osmotic diuretics
- loop diuretics
Diuretic is a
drug that increases urine volume output.
Most diuretics act by
decreasing Na+ reabsorption from some
part of the nephron.
Natriuresis causes
diuresis by an osmotic mechanism.
Natriuresis also affects reabsorption of (3)
Cl-, K+, and other
electrolytes.
Most common reason for use of diuretics is to (3)
reduce ECFV (extracellular fluid volume).
– Reduces edema
– Reduces MAP (mean arterial pressure)
Diuretics Increase
Solute and H2O
Excretion until
Compensatory
Mechanisms Re-
establishes
Balance
— Transport is a Target
for many Diuretics
Na+
(Where goes the Na+
goes the H2O)
Osmotic Diuretics
Nonabsorbable substance is filtered (ex. mannitol,
sucrose).
Osmols in tubular fluid require —.
water
Osmotic Diuretics
Similar to effects of
endogenous substances
(glucose, urea).
- Diuresis caused by hyperglycemia.
Osmotic Diuretics
May increase excretion of
other solutes.
Carbonic Anhydrase Inhibitors (3)
Acetazolamide. More than 80% of HCO3- reabsorption and H+ secretion occurs in proximal tubule. CA inhibitors block Na+ reabsorption (and H+ secretion) indirectly.
Loop Diuretics
ex (3)
Furosemide, ethacrynic acid,
bumetanide
Loop Diuretics
Inhibit
Na+-K+-2Cl- - cotransport
pump on luminal membrane of
TAL of Henle.
Loop Diuretics
Most powerful
diuretics
available (30% of GFR may
appear in urine!).
Loop Diuretics
Overwhelm downstream
— capacity.
absorptive
Loop Diuretics
Disrupt
countercurrent
multiplier.
Thiazide Diuretics
ex (2)
Hydrochlorothiazide,
chlorthalidone, etc.
Thiazide Diuretics
Block
Na+-Cl- cotransport
mechanism in early distal
tubule
Thiazide Diuretics
More distal tubular
segments have limited
ability to
respond to
increased load of Na+, Cl-,
H2O.
class: Osmotic (mannitol)
mechanism:
site of aciton:
↑ osmolarity of tubular
fluid
Mainly proximal tubule
class: Loop (furosemide)
mechanism:
site of aciton:
↓ Na-K-2Cl cotransport
TAL of Henle
class: Carbonic anhydrase inhibitor
(acetazolamide)
mechanism:
site of aciton:
↓ H+ secretion, HCO3- ab-
sorption (↓Na-H exchange)
Proximal tubule
class: Thiazide (hydrochlorothiazide)
mechanism:
site of aciton:
↓ Na-Cl cotransport
Early distal tubule
class: Aldosterone antagonists
(spironolactone)
mechanism:
site of aciton:
↓ Na+ absorption & K+
secretion
Late distal & Collecting
tubule
class: Na channel blocker
(triamterene)
mechanism:
site of aciton:
Block ENaC & ↓ K+
secretion
Late distal & Collecting
tubule
K+ Sparing Diuretics (2)
Aldosterone antagonists
(spironolactone)
Na channel blocker
(triamterene)
Many Diuretics Cause K+ Loss (Hypokalemia) (3)
Increasing flow rate of filtrate through distal nephron decreases K+ reabsorption. Keeps luminal K+ concentration low supporting secretion Hypokalemia may result.
Aldosterone antagonists reduce levels of (3)
Na+/K+ ATPase,
ENaC, K+ channel.
ENaC blockers reduce
3
Na+ uptake, Na+/K+
activity, K+ secretion
