Test 2 (Regulation of K+, Ca2+, PO4 3-, and Mg2+) Flashcards Preview

Renal I > Test 2 (Regulation of K+, Ca2+, PO4 3-, and Mg2+) > Flashcards

Flashcards in Test 2 (Regulation of K+, Ca2+, PO4 3-, and Mg2+) Deck (35):
1

Importance of Renal Control of K+ Balance

Normal Range of EC [K+]: 3.5 to 5 mEq/L
- HYPERKALEMIA: > 5.0 mEq/L

- HYPOKALEMIA:

2

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

3

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

4

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

5

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

6

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!!!!

7

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!!!!!!

8

Urinary K+ Excretion

- Urinary K+ Excretion INCREASES with Plasma K+ Concentration

9

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!!!

10

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

11

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!!!!!

12

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!!!!

13

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

14

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

15

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

16

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

17

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)



18

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

19

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

20

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)

21

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+]

22

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!

23

Ca2+ Handling by the Nephron

- Most of the Ca2+ (70%) in reabsorbed in the PT!!!!!

24

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!!!

25

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!!!!!

26

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

27

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+]!!!!!!!!!

28

Plasma Ca2_ Regulates PTH, Calcotonin

INCREASE Plasma [Ca2+]:
- Decreased PTH Levels

- Increases Calcitonin Levels

***PTH and Calcitriol combine to INCREASE EC [Ca2+] Levels!!!!!!!

29

Phosphate Handling by the Nephron

- 80% Reabsorbed in PT

- 10% Reabsorbed in DT

- 10% Excreted!!!

30

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!!!!

31

Proximal Tubular Phosphate Reabsorption is SATURABLE (has a Tm)

- Most of what is filtered is Excreted when the Tm is reached!!!!!!!

32

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!!!

33

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!!!!!!

34

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!!!

35

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!!!!!!