k + homeostasis. the need: ecf k + concentration is critical for the function of excitable cells...

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K + Homeostasis

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Page 1: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Homeostasis

Page 2: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Homeostasis

The need:ECF K+ concentration is critical for the function of excitable cells

However, about 98% of is in K+ ICFICF concentration of K+ – 120-140 mmol/LICF volume – twice the ECF volumeBUTThe kidney has to regulate K+ handling based on K+ level in ECFIncrease in in the body will have a smaller effect on ICF than ECF

Page 3: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Homeostasis

The need:

ECF K+ concentration needs to be maintained

Page 4: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Extracellular & Intracellular K+

K+ K+

Equilibrium between Intracellular and extracellular K+

• Helps stabilise ECF K+

Page 5: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Glomerular Filtration of K+

Freely filtered at the glomerulus

Page 6: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Tubular Handling of K+

Fate of filtered K+

Percentage of filtered load reabsorbed /secreted

Variable

60-70 %

20 %

Variable

Page 7: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Reabsorption in the Proximal Tubule

K+ dependent on Na+

reabsorption

Na+ reabsorption ismostly a constant fractionof filtered load

K+ reabsorption is alsoa constant fractionof filtered load

Na+

Na+

K+

K+

Na+

Na+

TubularLumen

Capillary

water

K+ K+

K+K+

water

Page 8: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Reabsorption in Loop of Henle

Thick ascending limb

Absorbed with Na+Percentage absorbed constant

Na+

Na+

K+

K+

K+2Cl-

TubularLumen Capillary

Na+

Page 9: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Handling in the Distal Tubule

Principal cells – regulated by aldosterone K+ is secreted in

exchange for Na+ at the luminal surface

Na+

Capillary

K+

Na+

K+

Na+

Lumen

Page 10: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Handling in the Distal Tubule

Intercalated cells

H+ is secreted in exchange for K+ at the luminal surface K+

Capillary

H+

Lumen

Page 11: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Handling by Kidney

K+ reabsorption / secretion1. Linked to reabsorption or secretion of other ions

Mostly Na+ H+ to a lesser extent

2. Depends on aldosterone Secretion is regulated mostly by renin-angiotensin

mechanism Serum K+ also has a direct effect on aldosterone secretion

Page 12: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Handling by Kidney

Regulatory mechanism for Plasma K+

1. Intracellular K+ - depends on several factors dietary K+ content Acid base status Insulin – increases influx of K+

2. Increased plasma K+ stimulates aldosterone secretionHowever, aldosterone is mainly a Na+ regulator

K+ handling by the kidney is determined more by other factors than plasma K+ itself

Page 13: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

K+ Excretion

K+ excretion by kidney is increased by

1. Aldosterone 2. Alkalosis3. Increased delivery of Na+ to the distal tubule4. Increased dietary K+

5. Exit of from K+ cells – damage to cells, lack of insulin High K+ levels result in increased filtration of K+

Page 14: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

ICF and ECF K+ Equilibrium

Factors affecting K+ flux between ICF and ECF

1. Acid base status2. Insulin3. Sympathetic neurotransmitters4. Exercise5. Damage to cell membrane

Page 15: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Ca2+ Handling by the Kidney

Page 16: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Glomerular Filtration of Ca2+

Ca2+ In blood1. Free – 55-60%

Ionised Complexed with organic anions

2. Bound to protein – 40-45%

Only the free Ca2+ is filterable

Page 17: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Tubular Handling of Ca2+

Fate of filtered Ca2+

Reabsorption onlyNo secretion

8 %

65 %

25 %

2 %

Page 18: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Proximal tubular Reabsorption of Ca2+

Passive Paracellular Due to concentration

gradient created by Na+

reabsorption

Na+ dependent reabsorption

Na+

Na+

K+

K+

Na+

Na+

TubularLumen

Capillary

water

Ca2+ Ca2+

water

Page 19: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Thick Ascending Limb Reabsorption of Ca2+

Passive Paracellular Due to concentration

gradient created by Na+

reabsorption

Na+ dependent reabsorption

Na+

Na+

K+

K+

K+2Cl-

TubularLumen Capillary

Na+

Ca2+ Ca2+

Page 20: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Reabsorption of Ca2+

Approximately 90% of Ca2+ reabsorption is Na+ dependent

Page 21: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Distal Tubular Reabsorption of Ca2+

Active transcellular Regulated by parathormone Ca2+

TubularLumen Capillary

Na+Ca2+

Page 22: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Regulation of Tubular Reabsorption of Ca2+

Na+ reabsorption Parathormone – sensitive to ionised calcium level in blood Acid base status – acidosis inhibits reabsorption and alkalosis

enhances reabsorption

Page 23: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Phosphate Handling by the Kidney

Page 24: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Glomerular Filtration of Phosphate

Phosphate In blood1. Free – 90-95%

2. Bound to protein – 5-10%

The free phosphate is freely filtered

Page 25: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Tubular Handling of Phosphate

Fate of filtered phosphate

Reabsorption almostentirely in the proximaltubule

85 %

15 %

Page 26: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Proximal Tubular Reabsorption of Phosphate

Symport system coupled to Na+ reabsorption Has tubular maximum Parathormone inhibits reabsorption

The phosphate that is excreted in urine performs an important function – buffering secreted H+

Page 27: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Magnesium Handling by the Kidney

Page 28: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Glomerular Filtration of Magnesium

Magnesium in blood1. Free – 50-60 %

2. Bound to protein – 40-50 %

The free magnesium is filtered

Page 29: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Tubular Handling of Magnesium

Fate of filtered magnesium

Highest reabsorption in the thick ascendinglimb

30 %

5 %

60 %

5 %

Page 30: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Tubular Reabsorption of Magnesium

Passive Mostly paracellular route Dependent on Na+ reabsorption

Page 31: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Urate Handling by the Kidney

Page 32: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration

Renal Handling of Urate

Freely filtered at the glomerulus Proximal tubule

Passively reabsorbed in the early part Actively secreted in the mid proximal tubule Passively reabsorbed in the late segment

Secretion is regulated by plasma levels of urateReabsorption > secretion

Page 33: K + Homeostasis. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration