Regulation of electrolytes - Michaels Flashcards by Stephen Schaffner

Na+, mEq/l 144 136-145

                  K+, mEq/l                                   2.5                3.5-5.0

                  Cl-,  mEq/l                                  90                 96-106

                  HCO3-, mEq/l                             35                  23-29

                  Glucose, mg/dl                           90                 70-115

                  BUN, mg/dl                                14                  11-23

Further lab work reveals low plasma renin (0.5 ng/ml/hr; normal 0.9-3.3 ng/ml/hr) and high plasma aldosterone (550 ng/l; normal 10-160 ng/l). Abdominal CT scan reveals a 3 cm mass in the rt. adrenal.
Why is this woman hypokalemic?

Conn’s disease - an aldosterone secreting tumor in the adrenal cortex is present. This leads to increased secretion of K+ by the collecting duct.

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What are two things extracellular K+ impacts?

•EC [K+] affects resting membrane potential and excitability of muscle and nerve tissue

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What ranges define hyper and hypokalemia?

–Hyperkalemia: > 5.0 mEq/l
–Hypokalemia: < 3.5 mEq/l

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What danger is there if K+ concentration deviates from the normal range?

Dangerous rhythm disturbances can occur

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In what two segments of the nephron is K+ reabsorbed primarily?

–67% reabsorbed in proximal tubule
–20% reabsorbed in thick ascending limb of Henle’s loop (Na+,K+,2Cl- cotransport)

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Where is physiological control over K+ exerted?

How is this accomplished?

the collecting duct

–Principal cells: either reabsorb or secrete K+, depending on body’s K+ balance

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What is the magnitude of K+ secretion determined by?

the magnitude of K+ secretion is determined by the size of the electrochemical gradient for K+ across the luminal membrane.

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Name 6 causes of increased K+ secretion

High K + diet

Hyperaldosteronism

Alkalosis

Thiazide diuretics

Loop diuretics

Luminal anions

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Name 4 causes of decreased K+ secretion

Low K + diet

Hypoaldosteronism

Acidosis

K +-sparing diuretics

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What are 5 factors that influence K+ secretion in the collecting duct

EC - [K+]

Aldosterone

EC - pH

Diuretics

Luminal Anions

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What does aldosterone do regarding K+ levels?

•alters Na+ reabsorption and stimulates K+ secretion in collecting duct

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How do diuretics impact K+ reabsorption?

Na+ reabsorption: negative luminal voltage ‘attracts’ K+ and luminal fluid flow rate: dilution of secreted K+

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How do luminal anions influence K+ secretion in the collecting duct?

By altering the electronegativity of the lumen

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What causes primary hyperaldosteronism? What stimulus is there? The consequence?

–Aldosterone secreting tumor in adrenal cortex
–K+ secretion by collecting duct is inappropriately stimulated
–Consequence: hypokalemia

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What is the cause of Addison’s disease?

What is the consequence?

–Destruction of adrenals: aldosterone isn’t secreted
–Decreased K+ secretion in collecting duct
–Consequence: hyperkalemia

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What do most classes of diuretics do with regard to K+?

•Most classes of diuretics increase Na+ and volume delivery to late distal tubule and collecting duct, which increases K+ secretion and may result in hypokalemia

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What are the consequences of a low-sodium diet?

•Low-sodium diet: less Na+ delivery to late distal tubule, collecting duct —> less K+ secretion, excretion —> may cause hyperkalemia

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What are 6 factors that push for K+ secretion?

Hypokalemia
acidemia
hyperosmolality
Ischemia; cell damage
Alpha-adrenergic agonists
heavy exercise
7.

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What are 4 factors that push for K+ uptake?

Hyperkalemia
Alkalemia
Beta-adrenergic agonists
Insulin

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What cell type is this?

Alpha-Intercalated Cell

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Cell type?

Principle cell

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What do osmotic diuretics do?

•(e.g. mannitol): inhibit reabsorption of water and, secondarily, Na+

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Carbonic anhydrase inhibitors do what?

(e.g. acetazolamide): inhibit NaHCO3- reabsorption

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What mechanism do loop diuretics impact?

•Inhibits Na+,K+,2Cl- cotransporter by competing for Cl-

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What impact do loop diuretics have on RBF? How about the solute concentration of the medullary interstitium?

Increase total RBF and dissipate high solute concentration of the medullary interstitium.

What is the ultimate impact of loop diuretics on the loop of henle?

What mechanism do Thiazide diuretics inhibit?

–Na+,Cl- cotransport

What is the consequence of thiazide diuretics inhibition of Na+,Cl- cotransport?

–Increase Na & Cl excretion as well as K+

Where do Thiazide diuretics work?

Distal Convoluted tubule

Where do potassium sparing diuretics function?

The collecting duct

What do potassium sparing diuretics do?

–Inhibit Na+ reabsorption, K+ secretion

What is an important clinical feature of potassium sparing diuretics?

It is commonly used in to offset the excretion of K+ promoted by other diuretics

Name the diuretics that work at each location denoted by a box

•A 35 y.o. woman visits her internist with complaints of headaches that are unresponsive to aspirin. Her blood pressure is 170/100 mm Hg. Physical exam is significant for hypertensive retinopathy. Plasma chemistries: Normal Na+, mEq/l 144 136-145 K+, mEq/l 2.5 3.5-5.0 Cl-, mEq/l 90 96-106 HCO3-, mEq/l 35 23-29 Glucose, mg/dl 90 70-115 BUN, mg/dl 14 11-23 * Further lab work reveals low plasma renin (0.5 ng/ml/hr; normal 0.9-3.3 ng/ml/hr) and high plasma aldosterone (550 ng/l; normal 10-160 ng/l). Abdominal CT scan reveals a 3 cm mass in the rt. adrenal. * Why is this woman's HCO3- elevated?

Due to hypokalemia, the K+/H+ exchange across cell membranes is decreased, leading to less H+ interacting with the HCO3- and a higher level of HCO3-.

How do diuretics work generally?

•Drugs that increase urine excretion by inhibiting tubular solute and water reabsorption (increasing excretion)

What is the purpose of diuretics?

• to help eliminate excess volume to treat volume overload disorders (e.g. edema, congestive heart failure)

What are symptoms of hypocalcemia? | (4)

• twitching, muscle cramps, tingling and numbness

What are symptoms of hypercalcemia? | (6)

• constipation, polyuria, polydipsia, lethargy, coma, death

In what form is calcium most found in plasma?

Ionized, roughly 50%

In what forms do we find the other 50% of plasma calcium (not ionized)?

~45% protein bound ~5% complexed

What is the major form we find PO₄^-3in plasma?

~84% ionized

What are 5 key reasons extracellular Ca2+ is important?

1. •Affects activity of excitable tissues: nerve, muscle, myocardium 2. •Enzyme cofactor; 3. component of bone; 4. cellular signaling; 5. blood clotting

How does Ca2+ dampen action potentials?

By blocking Na+ channels

What is a danger of low EC Ca2+?

Can produce hypocalcemic tetany

–Ca2+ is required for _________________ transmission –\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_: EC Ca2+ can affect contractile strength

neuromuscular Myocardium

* What is [Ca2+] in Bowman’s capsule? Why? * Total plasma [Ca2+] c. 4.5-5 mEq/l (c. 2.5 mM)

## Footnote 60% of plasma [Ca2+] is filterable, so, ((4.5mM+5mM)/2)\*.60= **2.85mM**

What is the effect of acidemia on plasma [Ca²⁺] levels?

Since H+ competes with Ca2+ for binding sites on plasma proteins... •Acidemia: increased [H+] ⇒ Increased plasma free [Ca2+]

What would be the impact of alkalemia on [Ca²⁺]_free in the plasma?

•Alkalemia: decreased [H+] ⇒ decreased plasma free [Ca2+]

What organs (or body components) are involved in [Ca²⁺]_EC?

GI Kidney Bone Parathyroid gland

What percentage of Ca2+ is filtered at each location?

Based on the pictured mechanism of Ca++ reuptake where is this cell located in the nephron?

Proximal convoluted tubule

Shown is the transport mechanisms of cells in the proximal tubule, how would Ca++ reabsorption be different if we were looking at a cell in the distal tubule?

There would be no paracellular Ca++ reabsorption

Where is this cell located in the nephron?

The Thick ascending limb of the loop of henle

What is paracellular reabsorption of Ca++ driven by in the thick ascending limb? How would loop diuretics impact this process?

Paracellular reabsorption of Ca2+, via channels in the tight junctions is driven by the ~6 mV transepithelial potential. \ Since K+ is responsible for the potential difference across the epithelium that drives paracellular reabsorption of Ca++ and Mg++, you would see increased excretion of both ions.

Where in the nephron is this cell located?

Distal tubule

Where is physiological control of tubular Ca++ reabsorption wielded?

Thick ascending limb and distal convoluted tubule

What impact does a decrease in [Ca++]_plasma have on the parathyroid gland?

Secretion of PTH - increases extracellular [Ca++]

Through what 3 mechanisms (boxed over in the image) does PTH work to re-establish [Ca++]_EC?

What are the percentages of phosphate excretion/reabsorption in each of the indicated areas of the nepron?

Where is this cell located? (determine by indicated mechanisms) What substance inhibits the mechanism of phosphate reabsorption here?

Proximal tubule Inhibited by parathyroid hormone

In what way is phosphate reabsorption similar to glucose reabsorption?

It is saturable.

How does PTH increase phosphate excretion?

It lowers the T_m for phosphate reabsorption (saturation of transport occurs sooner)

In what form is Mg++ primarily found in plasma?

~60% free Mg++

Apart from the free Mg++ found in plasma, in what other forms/percentages will you find Mg++?

–20%: Complexed with inorganic, small organic anions –20%: Bound to plasma proteins

Where is most filtered Mg++ reabsorbed? By what mechanism?

Thick ascending limb paracellular movement

Where is this cell found? What drives the paracellular reabsorption of Mg++?

Thick ascending limb ## Footnote The 6 mV transepithelial potential (lumen positive) is the driving force for Mg2+ reabsorption.

* Your 60 y.o. female patient with congestive heart failure has pulmonary congestion and peripheral edema. You prescribe furosemide, a loop diuretic. Two weeks later she is rushed to the E.R. with muscle spasms and dyspnea. Plasma chemistries reveal severe hypokalemia and hypomagnesemia, and moderate hypernatremia. The patient admits taking three times the prescribed dose of furosemide because she wasn’t feeling well. * Explain the abnormalities in her plasma electrolytes.

The hypernatremia is the result of volume depletion. The diuretics inhibit reuptake of the Mg++ and K+, leading to hypomagnesemia and hypokalemia.