Test 2 (Regulation of K+, Ca2+, PO4 3-, and Mg2+) Flashcards
Importance of Renal Control of K+ Balance
Normal Range of EC [K+]: 3.5 to 5 mEq/L
- HYPERKALEMIA: > 5.0 mEq/L
- HYPOKALEMIA:
Acute effect son Extracellular K+ Concentration on Resting Membrane Potential of Excitable Tissues
HYPERKALEMIA:
- Resting Membrane Potential is Closer to the Normal Threshold therefore there is an Increase in Contractions
HYPOKALEMIA:
- Resting Membrane Potential is Further from the Normal Threshold therefore there is a Decrease in Contractions
**Dangerous Rhythm disturbances can occur if K+ Concentration deviates from the Normal Range
Factors Affecting Movement of K+ Between Intracellular and Extracellular Pools
1) Diabetics are at a risk of HYPERKALEMIA because the Insulin helps bring the K+ back into the Cell
2) ACIDOSIS can lead to HYPERKALEMIA
- High H+ Concentration causes the H+ to move into the cell and therefore the K+ and Na+ will move OUT OF the cell
3) AKLALOSIS can lead to HYPOKALEMIA
- Low H+ Concentration causes the H+ to move out of the cell and therefore the K+ and Na+ will Moe INTO the Cell
Renal Tubular Handling of K+
- Freely filtered into Bowman’s Capsule: 72- mEq/day at 4 mEq/L Plasma K+
K+ Handling in different Nephron Segments:
1) 67% Reabsorbed in Proximal Tubule:
- Paracellular: Solvent Drag and Diffusion (+Lumen)
2) 20% Reabsorbed in Thick Ascending Limb of Henle’s Loop (Na+, K+, 2Cl- Cotransport)
3) Physiological Control exerted in Collecting Duct
4) PRINCIPAL CELL: Either Reabsorbed or Secrete K+, depending on body’s K+ Balance
Renal Tubular K+ Handling in response to differences in Dietary K+ intake
Dietary K+ Depletion:
- Only 1% of K+ Secreted
Normal and Increased Dietary K+ Intake:
- 15 to 80% of K+ Secreted
K+ Secretion
- K+ is Secreted by the PRINCIPAL CELLS in the COLLECTING DUCT
- Situation that change the activity of the Na/ L ATPase will change the amount of K+ EXCRETED!!!!
Five Factors which affect K+ SECRETION in Collecting Duct
1) Extracellular K+ Concentration
2) Na+ Reabsorption: Negative Luminal Voltage “Attracts K+”
3) Luminal Fluid Flow Rate: Dilution of Secreted K+ resulting in CONCENTRATION GRADIENT
4) Extracellular pH: K+ and H+ EXCHANGE across Cell Membranes
5) Aldosterone: Stimulates K+ Secretion in Collecting Duct to maintain Electroneutrality when Na+ is Reabsorbed
**NEED TO MAINTAIN ELECTRONEUTRALITY so if a Positive goes out or in then another Positive must go out or in!!!!!!
Urinary K+ Excretion
- Urinary K+ Excretion INCREASES with Plasma K+ Concentration
Tubular Flow rate and K+ Secretion
- When there is a HIGH K+ Diet, the K+ Secretion will INCREASE Significantly when the Tubular Flow Rate Increases!!!
- Control and Low K+ diet see a much less Increase in K+ Secretion when the Tubular Flow Rate Increases!!!
Situations that Alter K+ Handling
- Most classes of DIURETICS Increase Na+ and Volume Delivery to LATE DISTAL TUBULE and COLLECTING DUCT, which INCREASES K+ SECRETION!!!!!!!!!
- Low Sodium Diet: Less Na+ delivery to Late Distal Tubule, Collecting Duct —-> Less K+ Secretion and Excretion —–> may cause HYPERKALEMIA
***HYPERKALEMIA may be treated by Increasing downstream delivery of Na+ to DISTAL TUBULES. COLLECTING DUCTS. Results in Increased Na+ Reabsorption and K+ Secretion
K+ Secretion by Distal Nephron: Effects of Plasma K+ Concentration and Plasma pH
- At lower pHs there is more H+ in the Blood and these H+ Ions will be Excreted and therefore the K+ will be REABSORBED which INCREASES the Plasma K+ Concentration!!!!!
Aldosterone and K+ Secretion
- Aldosterone stimulate K+ SECRETION in Distal Tubule and Collecting Duct
- Aldosterone levels INCREASE with HYPERKALEMIA because it si trying to bring the K+ level back to NORMAL!!!
**ALDOSTERONE stimulate K+ SECRETION by the PRINCIPAL CELLS!!!!!!
- Increased Plasma [K+} stimulates ALDOSTERONE SECRETION!!!! (Aldosterone then Reabsorbs Na+ and Secretes K+)
**Aldosterone can also FEEDBACK to cut off the production of Renin!!!!
Disorders of Aldosterone Secretion
1) PRIMARY HYPERALDOSTERONISM (Conn’s Disease):
- Aldosterone Secreting Tumor is Adrenal Cortex
- K+ Secretion by Collecting Duct is Inappropriately stimulated
- Consequence: HYPOKALEMIA with HYPERNATREMIA
2) ADDISON’S DISEASE (Hypoaldosteronism):
- Destruction of Adrenals: Aldosterone ISN’T SECRETED
- Decreased K+ Secretion in Collecting Duct
- Consequence: HYPERKALEMIA with HYPONATREMIA
Diuretics
- Drugs that INCREASE Urine Excretion by Inhibiting Tubular Solute and Water Reabsorption (Increasing Excretion)
- Purpose: To help ELIMINATE EXCESS Volume to Treat Volume OVERLOAD DISORDERS (Edema, CHF)
- Several different Diuretic Classes exist, which act in different Nephron segments by Different Mechanisms
Diuretics acting in Proximal Tubule
1) Osmotic Diuretics (Mannitol): Inhibit Reabsorption of Water and Secondarily Na+
2) Carbonic Anhydrase Inhibitors (Ascetazolamide): Inhibit NaHCO3- Reabsorption
- Altitude Sickness
Diuretics Acting in Loop of Henle “Lood Diuretics”
- Examples: FUROSAMIDE (Lasix), Bumetanide (Bumex) Ethacrynic Acid
- Inhibits Na+, K+, 2Cl- Cotransproter by competing for Cl-
- Increase TOTAL RBF and dissipated HIGH SOLUTE Concentration of Medullary Interstitial
- Lessens Water Reabsorption in DESCENDING LIMB of Henle’s Loop, Medullary Collecting Duct
- Powerful: REQUIRE CAREFUL MEDICAL SUPERVISION
Diuretics acting in Distal Nephron Segments
1) THIAZIDE Diuretics: Dital Convoluted Tubule
- Inhibit Na+, CL- Cotransport!!!!!!!
- INCREASE Na and Cl Excretion as well as K+
- Results in DECREASED Ca2+
- Example: HYDROCHLOROTHIAZIDE
2) Collecting Duct: “Potassium-Sparing” Diuretics
- Inhibit Na+ Reabsorption, K+ Secretion
- Often used in combination with other Diuretic classes that INCREASE K+ Excretion
- Ex: Amiloride, Triamterene (Block Na+ Channels); Spironolactone (Aldosterone Antagonist)
Sites of Action: Diuretics
1) Carbonic Anhydrase Inhibitors:
- Proximal CT
2) Loop Diuretics:
- TAL
- BARTTER’s SYNDROME
3) Thiazides:
- DCT
- GITELMAN’S SYNDROME
4) K+ Sparing Diuretics:
- Collecting Duct
Importance of EC Ca2+
1) Affects activity of Excitable Tissues: Nerve, Muscle, Myocardium
- Ca2+ can dampen action potentials in Blocking Na+ Channels
- Low EC Ca2+ can produce HYPOCALCEMIA TETANY!!!!!
- Ca2+ is REQUIRED for Neuromuscular Transmission
- MYOCARDIUM: EC Ca2+ can affect Contractile Strength
2) Enzyme Cofactor; Component of Bone; Cellular Signaling; Blood Clotting
Some Plasma Ca2+ is Protein- Bound
- Total Palsma [Ca2+] 4.5 to 5 mEq/L
- 45% is bound to Plasma Proteins
- FREE PALSMA [Ca2+] 1.2 to 1.5 mM (ONLY Free Ca is Biologically Active)
Effect of Plasma pH on Free [Ca2+]
- H+ COMPETE with Ca2+ for Bidning Sites on Plasma Proteins:
1) ACIDEMIA —> INCREASE Plasma Free [Ca2+]
2) ALKALEMIA —> DECREASE Plasma Free [Ca2+]
Several Organs Help Determine EC [Ca2+]
1) GI (+ Calcitriol)
2) Kidney (+ PTH, Calcitriol, Calcitonin)
3) Bone (+PTH and Calcitriol; - Calcitonin)
4) Extracellular ([H+], [PO4 3-]
PTH:
- Changes the Vit D to activated Vit F
- This has an effect on Your GI Tract to make you INCREASE the amount of Ca2+ Reabsorption
- Increase Reabsorption of Bone too!
Ca2+ Handling by the Nephron
- Most of the Ca2+ (70%) in reabsorbed in the PT!!!!!
Mechanism of Proximal Tubular Ca2+ Reabsorption
- The same Transcellualr Mechanisms of Ca2+ Reabsorption operate in the Distal Tubule (major Site of PTH and Vit D Regulation of Ca2+ Excretion), but PARACELLULAR Ca2+ reabsorption is PREVENTED from occurring there due to the TIGHT JUNCTION Protein CLAUDIN-8 (CLDN8)!!!!!!!!!!!!!
***3Na+ in, while 1 Ca2+ out!!!
Paracellular Ca2+ Reabsorption in Thick Ascending Limb of Henle’s Loop
- Paracellular Reabsorption of Ca2+, via channels in the Tight Junctions is driven by the 6mV TRANSEPITHELIAL POTENTIAL.
What effect will Loop Diuretics have on this process?
- The Reabsorption of Ca2+, Na+, NH2, Mg2+ will DECREASE!!!!!
Transcellular Ca2+ Reabsorption in Distal Tubular Cells
- In the Kidney, the DCT Reabsorbs about 8% of the filtered Ca2+ Load. This occurs via Epithelial Ca2+ Channels.
- In the steady state, the cell must EXTRUDE all enters Ca2+, which occurs via a Ca2+ ATPase, and also through Na+/ Ca2+ EXCHANGER located on the VASOLATERAL surface of the Cells of the Distal Tubule!!!!!!
- Thiazides INHIBIT the Na+/ Cl- Symport in the Early DCT, thus causing a DECREASE in INTRACELLULAR Na.
- This in turn, ENHANCES the activity of the Na+/ Ca2+ Exchanger, creating an INCREASED Driving Force for Ca2+ REABSORPTION through the Epithelial Ca2+ Channels
- FINAL EFFECT: Increased Ca2+ Reabsorption (Decreased Urinary Excretion) that can cause HYPERCALEMIA!!!!!!
***CALBINDIN: a Vit D Depedent Ca- Binding Protein
Physiological Control fo Tubular Ca2+ Reabsorption
- Control exerted in Thick Ascending Limb of Henle’s Loop, Dital Convoluted Tubule
- Reabsorption stimulated by PARATHYROID HORMONE (PTH), Calcitriol (Vit D3), Calcitonin
- Decreased Plasma [Ca2+] induces Cells in PARATHYROID Gland to Secrete PTH
- OVERALL EFFECT of PTH: INCREASE EC [Ca2+]!!!!!!!!!
Plasma Ca2_ Regulates PTH, Calcotonin
INCREASE Plasma [Ca2+]:
- Decreased PTH Levels
- Increases Calcitonin Levels
***PTH and Calcitriol combine to INCREASE EC [Ca2+] Levels!!!!!!!
Phosphate Handling by the Nephron
- 80% Reabsorbed in PT
- 10% Reabsorbed in DT
- 10% Excreted!!!
Mechanism of Proximal Tubular Phosphate Reabsorption
1) Na+ and P+ COTRANSPORTER!!!!!!
2) P+ and A- (Anion) COUNTETRANSPORTER!!!!
- Puts Pi into he Blood
**THis mechanism is INHIBITED by PTH!!!!
Proximal Tubular Phosphate Reabsorption is SATURABLE (has a Tm)
- Most of what is filtered is Excreted when the Tm is reached!!!!!!!
PTH inhibits Proximal Tubular Phosphate Reabsoprtion
- This effect of PTH INCREASES the Amount of Phosphate EXCRETED at any given Plasma Phosphate Concentration!!!!!
**The Tm for the Phosphate Reabsorbed has DECREASED!!!
Renal Handling of Mg2+
Mg2+ is carried in Plasma in 3 forms:
1) 60%: Free Mg2+
2) 20%: Complexed with Inorganic, Small Organic Anions
3) 20%: Bound to Plasma Proteins
**About 2g Mg2+ FILTERED into Nephrons EACH DAY!!!!!!
Mg2+ Handling by Nephron
- The bulk of FILTERED Mg2+ is REABSORBED in the THICK ASCENDING LIMB of Henle’s Loop by PARACELLULAR Movement
***The positive Charge in the lumen from the K+ causes the Mg2+ to be REABSORBED (Loop Diuretics can mess this up)
- Approximately 10% of Mg2+ is Excreted!!!
Mechanisms of Mg2+ Reabsorption in Thick Ascending Limb
- Magnesium is REABSORBED via the PARACELLULAR Route
- The 6 mV TRANSEPITHELIAL Potential (lumen Positive) is the DRIVING FORCE for Mg2+ Reabsorption!!!!!!
