Control of Potassium, Calcium, Phosphate, & Magnesium Flashcards
Potassium
Tightly controlled – Usually changes less than
± 0.3 mEq/liter
Cell functions very sensitive to
changes Resting membrane potentials
98% of potassium located
intracellularly
Daily intake usually ranges between
50 mEq/liter to 200 mEq/liter
Small changes in extracellular K+ can
easily lead to hyper or hypokalemia
Only 5 to 10% of intake of K removed by
feces – rest must be removed by kidneys
After ingesting 40 mEq of K+ into ECF – [K+] would increase
by 2.8 mEq/liter
Most ingested K+ quickly moves into the cellular volume
moves potassium AND glucose into the cells following a meal
INSULIN
secretion stimulated by increased [K+]
aldosterone. In disease state, ability to move K+ into the cells AND K+ reabsorption are affected
Epinephrine stimulates
β2-adrenergic receptors increasing movement of K+ into the cell. β2-adrenergic blocking agents (treat hypertension) can lead to hyperkalemia
Factors that shifts K+ into cells (Potential hypo)
insulin, Aldosterone (also increases K+ secretion), Β-adrenergic stimulation, Alkalosis
Factors that shifts K+ out of cells (Potential hyper)
• Insulin deficiency (diabetes mellitus)
• Aldosterone deficiency (Addison’s disease)
• Β-adrenergic blockade• Acidosis
• Cell lysis • Strenuous exercise • Increased extracellular
fluid osmolarity
Potassium
Increased [H+] will reduce
action of Na-K ATPase with less transfer of K+ into the cells
Cell lysis dumps intracellular K+ in
extracellular compartment
Potassium. With an increase in extracellular osmolarity, water moves out of the cell which
increasing intracellular [K+] which increases the rate of K+ diffusion out of the cell
Excretion rate of K determined by:
Rate of potassium filtration Rate of potassium reabsorption Rate of potassium secretion
Constant fraction of filtered load reabsorbed in
proximal tubule and the loop of Henle – Does not change day-to-day
Renal Excretion of Potassium daily Filtration
180 liter/day x 4.2 mEq/liter = 756
mEq/day
consistent reabsorption of k percentage per part of kidney
65% proximal tubule
25 to 30% in loop (mainly thick ascending segment)
Flexible Reabsorption & Secretion
Principle cells of distal tubule and cortical collecting tubule
With normal K+ intake of 100 mEq/day Feces removes
8 mEq Kidneys must remove 92 mEq
Proximal tubule removes how much potassium
491 mEq leaving 265 mEq
Loop removes how much K
204 mEq leaving 61 mEq
Distal tubule & cortical collecting tubule MUST secrete how much K
31 mEq Approximately 1/3 of excreted potassium
During High potassium intake Distal tubule & cortical collecting tubule increase
potassium secretion
Very strong mechanism – rate of potassium excretion can exceed amount of potassium being filtered
during Low potassium intake secretion rate
decreases
Can decrease secretion to point where there is net reabsorption
Excretion can fall to 1% of filtered potassium (756 mEq/day x 0.01 = 8 mEq/day)
Principal Cells Make up
90% of cells in late distal and cortical collecting tubule
principal cells Secretion driven by
Na-K ATPase in basolateral border of cells
Move K+ into cell setting up concentration gradient
Concentrationgradientdrives diffusion from cell into tubular lumen
Tubular membrane contains
special channels for K+ diffusion
Usually provide high permeability for K+ movement out of the cell
Intercalated Cells
Reabsorb potassium especially during potassium depletion
Intercalated Cells Could be related to H-K ATPase
Located tubular membrane Pumps H+ from tubular cell into lumen (secretion)
Pumps K+ from tubular lumen into cell (reabsorption) K+ diffuses from cell into interstitial space via basolateral membrane
Major effect only during potassium depletion
Control of Potassium Secretion
Three factors control rate of K+ secretion
Activity of Na-K ATPase
Electrochemical gradient for K+ movement from the blood to the tubular lumen
Permeability of tubular membrane to K+
Stimulation of Potassium Secretion
Increased extracellular [K+] Increased [aldosterone] Increased tubular flow rate
Increased [H+] will DECREASE potassium secretion
Increased Plasma Potassium
Important control mechanism Always a certain level
of secretion even at normal [K+]
Increased [K+] stimulates action
Na-K ATPase. More K+ moved into cell from interstitial space which increased gradient from cell interior to tubular lumen
[K+] of renal interstitial fluid increases
(increased plasma concentration) which decreases amount of K+ diffusing from cell interior into interstitial space Increase [K+] in plasma stimulated release of aldosterone
Increased aldosterone increases
rate of sodium reabsorption by late distal tubule and collecting duct
Increases activity of Na-K ATPase – so an increase in sodium reabsorption will also increase potassium secretion
Increases tubular membrane permeability for potassium
Plasma Potassium & Aldosterone
Great example of
negative feedback control system
Factor being controlled (potassium) as feedback effect on controller (aldosterone)
Small change in plasma [K+] produced huge change in aldosterone concentration
Normal aldosterone level is approximately
6 nag/dL
Anything that affects our ability to produce aldosterone will have a big effect
on potassium excretion!!
High aldosterone (primary aldosteronism)=
Hypokalemia
Low aldosterone (Addison’s disease) =
Hyperkalemia
ncreased K+ intake with intact aldosterone feedback
Big change in intake (x7 increase)
mall change [K+] (4.2 to 4.3 mEq/liter)
Increased K+ intake with blocked aldosterone feedback
Big change in intake (x7 increase)
big change in [K+] (3.8 to 4.7 mEq/liter)
Increased distal tubular flow rate will
increase potassium secretion
Increased tubular flow rate can be caused by
volume expansion; high sodium intake; specific diuretics
Relationship between tubular flow rate and potassium secretion greatly affected
by potassium intake
Higher the intake, the greater the effect created by tubular flow
As potassium diffuses into tubular lumen, the increase in luminal concentration will
will decrease the gradient thus decreasing the movement of potassium
Increased tubular flow carries
potassium away thus helping to preserve the gradient. The higher the flow the better the gradient is preserved, the more potassium is secreted
Preserving K+ Excretion With Changing Na+ Intake
Assume high Na+ intake
Aldosterone secretion decreases which will produce
a decrease K+ secretion
BUT since sodium reabsorption is decreased, overall distal tubular flow is increased which results in an increase in K+ secretion
THE TWO OFF SET EACH OTHER
Acute Acidosis Decreases K secretion by…
Reduces the activity of Na-K ATPase – decreases driving force for moving potassium from cell interior to tubular lumen
Prolonged acidosis produces increased potassium excretion – Result of decreased reabsorption of sodium chloride and water in proximal tubule and increased distal tubular flow
Alkalosis (H+) increases potassium secretion
Total calcium in plasma:
5 mEq/liter
50% in ionized form
40% bound to plasma protein Amount bound to protein decreases with an increase in [H+]. Patients with
alkalosis more susceptible to hypocalcemic tetany 10% bound in non-ionized form to other ions (phosphate, citrate)
Normal ion concentration:
2.4 mEq/liter (1.2 mmol/liter)
Hypocalcemia:
: increases muscle and nerve excitability
hypocalcemic tetany
Hypercalcemia
epressed neuromuscular excitability which can lead to cardiac arrhythmias
99% of calcium stored
in bone
HUGE reservoir – if plasma concentration drops, body will move calcium from the bone – if plasma concentration rises, body will move calcium back into the bone
1% of calcium in
intracellular space and cell organelles 0.01% present in extracellular fluid
PTH most important control agent for
Ca. 90% excreted via gastrointestinal tract (feces) (≈900 mg/day) 10% excreted via kidneys (urine) (≈100 mg/day)
PTH regulation accomplished through 3 actions:
Stimulation of bone resporption of calcium
Stimulation of vitamin D which stimulates calcium reabsorption by intestines
Direct stimulation of renal tubule reabsorption of calcium
PTH Affect on Bone
As extracellular calcium concentration falls:
Parathyroid gland directly stimulated to increase secretion of
PTH
Increased PTH concentration stimulates bone to increase release of bone salts (resporption) which includes the release of large amounts of calcium
PTH Affect on Bone. As extracellular calcium concentration increases:
Parathyroid gland decreases PTH secretion
Decreased PTH concentration decreases salt resporption to point where calcium will be added to the bone
Calcium Excretion
Freely filtered, reabsorbed BUT NOT secreted
Excretion rate = Filtration – Reabsorption
Only filtering a very small percentage of the calcium that is actually present in the body!!!!!
Calcium Excretion proximal tubule, LOH, Distal/collecting tube
Proximal tubule: 65% filtered load reabsorbed
Loop of Henle: 25 to 30% filtered load reabsorbed
Distal tubule / Collecting tubule: 4 to 9% filtered load reabsorbed
Normally only 1% of filtered load is excreted Changes as plasma concentration changes (i.e. intake changes)
Proximal Tubule Reabsorption of Ca++
80% of amount
reabsorbed carried by water via paracellular pathway
20% of amount reabsorbed via a transcellular pathway
Proximal Tubule Reabsorption of Ca++ . Diffusion through luminal membrane into cell driven by
chemical gradient (higher [Ca++] in lumen than inside cell) AND by electrical gradient (interior of cell negative with respect to lumen Pumped out of cell across basolateral membrane via Ca ATPase pump and Na-Ca counter-transport mechanism
Thick Ascending Loop – Ca++ Reabsorption
Paracellular pathway accounts for
50% of reabsorption in loop
Passive diffusion down electrical gradient – lumen has slight positive charge compared to interstitial fluid
Thick Ascending Loop transcellular pathway accounts for
0% of reabsorption in loop
Active process stimulated by PTH, Vitamin D (Calcitrol), and calcitonin (PTH concentration most important)
Distal Tubule – Ca++ Reabsorption
Almost all transport via
Transcellular pathway Active transport across basolateral membrane –
diffusion into cell
i distak tubule increased [PTH] increases
Ca++ reabsorption
Reabsorption also increased by Vitamin D and calcitonin
REMINDER: increased Reabsorption =
increased Excretion
Regulation of Ca++ Reabsorption / Excretion. PTH is primary controller and stimulates
increased reabsorption in Loop and Distal Tubule
Regulation of Ca++ Reabsorption / Excretion. PTH has no effect in
Proximal Tubule (Following sodium and water reabsorption)
regulation of Ca++ Reabsorption / Excretion. Δ in EC fluid volume and blood pressure cause
inverse changes in sodium & water reabsorption which causes parallel changes in calcium reabsorption
regulation of Ca++ Reabsorption / Excretion. [H+] major affect is on the transport mechanisms in the
Distal Tubule
regulation of Ca++ Reabsorption / Excretion. [Phosphate] affects [PTH] – As [Phosphate] increases
[PTH] increases
things that increase Ca++ Reabsorption
increase [PTH] decrease EC Fluid Volume decrease Blood Pressure increase Plasma Phosphate Metabolic Acidosis
things that decrease Ca reabsorption
decrease [PTH] increase EC Fluid Volume increase Blood Pressure decrease Plasma Phosphate Metabolic Alkalosis
Phosphate
Normal tubular maximum of
0.1 mMol/minute If filtered load under Tmax, all phosphate reabsorbed If filtered load over Tmax, phosphate is excreted
Phosphate. Plasma threshold level approximately
0.8 mMol/liter
phosphate Normal plasma concentration around
1 mMol/liter – Large intake of phosphate each day (milk & meat)
Phosphate Reabsorption
Proximal Tubule: percentage of filtered plasma reabsorbed and how
75 to 80%
Phosphate Reabsorption enters cells from
lumen via Na-Phosphate co-transport mechanism
Phosphate Reabsorption exits cells from
leaves cell via counter-transport mechanism across basolateral membrane ?????
Phosphate Reabsorption in LOH
Very small amounts
Phosphate Reabsorption in Distal tubule
10% of filtered phosphate reabsorbed
Phosphate Reabsorption in collecting tubule
Very small amounts
Approximately 10% of filtered phosphate is
excreted
Regulation of Phosphate
Tmax can change based
on intake Low intake, Tmax will increase over time
Regulation of Phosphate arathyroid Hormone As PTH increases bone resorption of
calcium,
phosphate is also resorbed
Regulation of Phosphate. increasing [PTH] decreases the
Tmax for phosphate so less phosphate is reabsorbed and more is excreted
Magnesium
>50% stored in
bone
Magnesium. Most of what is left is located in the
intracellular volume <1% located in extracellular volume
TOTAL plasma magnesium =
1.8 mEq/liter BUT >50% is bound to plasma proteins so free ionized is 0.8 mEq/liter
magnesium Daily intake
≈ 250 to 300 mg/day BUT only 50% is actually absorbed by the gastrointestinal tract (125 to 150 mg/day)
The amount absorbed is the amount the kidneys must excrete each day
Renal excretion of magnesium is ≈
10 to 15 of filtered load
Magnesium Reabsorption
Proximal Tubule:
25% of filtered load
Magnesium Reabsorption. Loop of Henle:
Primary site of reabsorption – 65% of
filtered load
Magnesium Reabsorption. distal Tubule / Collecting Tubule:
<5% of filtered load
Magnesium Reabsorption. Control mechanisms not clearly defined increase [Magnesium] results in
decrease reabsorption and increase excretion
Magnesium Reabsorption. increase EC fluid volume results in reabsorption and excretion
decrease reabsorption and increase excretion
Magnesium Reabsorption. increase [Ca++] results in
decrease reabsorption and increase excretion
