hydrogen ion regulation, diuretics, and kidney diseases

alkalosis

• high pH / low H⁺ concentration

• respiratory → results from altered respiration

• metabolic → results from other causes

acidosis

• low pH / high H⁺ concentration

• respiratory → results from altered respiration

• metabolic → results from other causes

renal responses to acidosis

• sufficient H⁺ secreted to reabsorb all filtered HCO₃^- (normal response)

• more H⁺ secreted to contribute to addition of new HCO₃^- (excreted H⁺ bound to non-HCO₃^- buffer)

• tubular glutamine metabolism and ammonium excretion are enhances, contributing to addition of new HCO₃^- to plasma

net result of renal responses to acidosis

• more new HCO₃^- than usual is added to plasma

• urine is highly acidic (lowest pH = 4.4)

renal responses to alkalosis

• rate of H⁺ secretion is inadequate to reabsorb all filtered HCO₃^-, so significant amounts of HCO₃^- are excreted in urine

• little or no H⁺ secretion of non-HCO₃^- urinary buffers

• tubular glutamine metabolism and ammonium excretion are decreased so that little or no new HCO₃^- is contributed to plasma

net result of renal responses to alkalosis

• plasma HCO₃^- will decrease

• urine is highly alkaline (pH > 7.4)

classification of respiratory acidosis

• high H⁺ concentration

• high CO₂ concentration

  • primary change

• high HCO₃^- concentration

  • renal compensation

classification of respiratory alkalosis

• low H⁺ concentration

• low CO₂ concentration

  • primary change

• low HCO₃^- concentration

  • renal compensation

classification of metabolic acidosis

• high H⁺ concentration

• low HCO₃^- concentration

  • primary change

• low CO₂ concentration

  • reflex ventilatory compensation

classification of metabolic alkalosis

• low H⁺ concentration

• high HCO₃^- concentration

  • primary change

• high CO₂ concentration

  • reflex ventilatory compensation

clinical example of respiratory acidosis

respiratory failure with CO₂ retention

clinical example of respiratory alkalosis

hyperventilation (high altitude, pregnancy)

clinical examples of metabolic acidosis

• diarrhea (loss of HCO₃^- in diarrhea)

• renal failure (accumulation of inorganic acids)

clinical examples of metabolic alkalosis

• vomiting (loss of H⁺ in vomits)

• hyperaldosteronism (increased H⁺ secretion in distal convoluted tubule and cortical collecting duct)

diuretics

• drugs used clinically to increase volume of urine excreted

• act on tubules to inhibit reabsorption of sodium, along with chloride and bicarbonate, resulting in increased excretion of these ions → increased water excretion

loop diuretics

• acts on thick ascending limb of loop of Henle

• inhibits cotransport of sodium, chloride, and potassium

  • Na⁺/K⁺/2Cl^- cotransporter)

• commonly used

• ex: furosemide

potassium-sparing diuretics

• inhibit sodium reabsorption and potassium secretion in the cortical collecting duct

  • plasma concentration of potassium does not decrease

• either block the action of aldosterone or block aldosterone-regulated epithelial sodium channel in CCD

• ex: amiloride, spironolactone

amiloride

• potassium-sparing diuretic

• blocks epithelial sodium channel in cortical collecting duct

spingolactone

• potassium-sparing diuretic

• blocks aldosterone receptor in cortical collecting duct

clinical use of diuretics

• renal retention of salt and water → abnormal expansion of extracellular fluid (edema)

• congestive heart failure

  • cardiac failure leading to lower cardiac output

  • baroreceptors detect low blood volume → signal to kidneys to retain salt and water → can lead to pulmonary edema

• hypertension

  • in some patients, renal retention of salt and water contribute to high blood pressure

  • excess sodium from diet, eliminated with water

common features of kidney disease/failure

• proteinuria (protein found in urine)

• accumulation of waste products in blood (urea, creatinine, phosphate, sulfate)

  • usually present in low levels

• high potassium concentration in blood

• metabolic acidosis

• anemia (decreased secretion of erythropoietin)

• decreased secretion of 1,25-(OH)₂vitamin D

  • leading to hypocalcemia

kidney (renal) failure

more than 99% of nephrons stop working → cannot sustain life

types of renal replacement therapy

• hemodialysis

• peritoneal dialysis

• kidney transplantation

hemodialysis

• surgery needed in advance to connect artery to vein to make veins large enough

• 3.5-4 hours/session, 3x/week

• “arterial” blood from patient is pumped with anticoagulant to strands of dialysis tubing (surrounded by dialysis fluid)

• dialyzer removes waste products from blood

• dialysis fluid and ultrafiltrate of plasma are drained

• fresh dialysis fluid (concentrate and purified water) is pumped back to blood

• “venous” blood returns to patient after passing through air trap and air detector

peritoneal dialysis

• lining of patient’s own abdominal cavity (peritoneum) is used as dialysis membrane

• fluid is injected into the cavity via a tube inserted through the abdominal wall

• solutes diffuse into the fluid from person’s blood

• fluid is exchanged several times per day (can be done from home)

kidney transplantation

• either from recently deceased persons (cadaveric transplant) or from living related/unrelated donor

• anti-rejection treatments (immunosuppressants) have improved dramatically

• organ shortage is a problem

• donors function quite normally with one kidney

  • 50% of nephrons functional is sufficient to sustain life