Acid-Base Homeostasis

Renal Handling of H+ and HCO3-

HCO3- + H+ CO2

Active secretion in exchange for Na+

Diffusion down gradient

Normally, all filtered HCO3- is recovered

This process is speeded up by carbonic anhydrase on the surface of the tubular cells

In acidosis, extra H+ is secreted

HCO3- + H+ CO2

Diffusion down gradient

H+

H+ secretion rate increases; the extra H+

not neutralized by HCO3- is accepted by

other urinary buffers – primarily NH3 and Pi

In acidosis, the renal tubule can make some “new” bicarbonate

CO2 H+ + HCO3-

CA

Cl-

In alkalosis, all filtered HCO3- is not

recovered

HCO3- + H+ CO2

Diffusion down gradient

H+ secretion rate falls; all secreted H+ is recovered as CO2; the unrecovered HCO3

- appears in final urine

HCO3-

Regulation of tubular H+ secretion

• Three factors are important: – plasma Pco2 (the major intracellular source of

H+ ), – plasma pH

– plasma [HCO3-] (which determines the filtered

load of HCO3-)

Effects of plasma K+, Na+ and aldosterone

• Because of the need to maintain charge balance, it is as if H+ and K+ competed to be secreted in exchange for Na+ absorption in the distal tubule.

• Thus:– Increased plasma [K+] (hyperkalemia) tends to lead to acidosis,

hypokalemia to alkalosis

– Acidosis tends to lead to hyperkalemia, alkalosis to hypokalemia

– Excessive aldo (Cushing’s Syndrome) tends to cause hypernatremia and hypokalemia which can lead to alkalosis

– Anything that depresses Na+ absorption tends to also depress H+ secretion

Ammonia excretion: pH trapping

Glutamine

Glutamate

NH3 H++

NH4+

secreted

Penetrates to tubular fluid by diffusion

Is now trapped in tubular fluid by its charge

Carrier of amine group from deamination reactions in liver

Back to liver for more amine

Coordinated Action of Lungs and Kidneys in Acid-Base

Homeostasis

Body Buffer Systems

• Blood: – Bicarbonate– Hemoglobin– Plasma proteins– phosphate

• Cytoplasm– Proteins (mainly histidine residues)

Acid Base Status Falls into one of 5 categories

• Normal: pH=7.4, [HCO3-] = 24 mEq/l, PCO2 = 40

mmHg• One of 4 uncompensated disorders:

– Respiratory acidosis or alkalosis: Pco2 elevated or depressed

– Metabolic acidosis or alkalosis: excess or deficit of fixed acid

• Partially compensated disorder• Fully compensated disorder• Mixed acid-base disorder

A Davenport diagram represents the status of the bicarbonate buffer system

Blue curve: the relationship between plasma bicarbonate and pH if Pco2 is held at the normal value. If Pco2 is changed to 80 mmHg (respiratory acidosis), the relationship moves to the black curve. For a Pco2 of 20 (respiratory alkalosis), the orange curve shows the relationship. Note that the operating point moves along the red line which represents the contribution of buffers other than bicarbonate

Uncompensated Respiratory Disorders

• Uncompensated respiratory acidosis: Pco2 is elevated (hypercapnia); [HCO3

-] is elevated; pH is below normal.

• Uncompensated respiratory alkalosis: Pco2 is depressed (hypocapnia); [HCO3

-] is depressed; pH is above normal.

Uncompensated metabolic disorders

• In metabolic disorders, addition of fixed acid or fixed base moves the operating point along the Pco2 isobar

Generally, respiratory compensation for metabolic acidosis is rapid but initially

incomplete• Addition of fixed acid consumes some of the

plasma bicarbonate and depresses arterial pH• As hyperventilation begins, pH of plasma rises

toward the normal value, but drop in Pco2 causes central chemoreceptors to oppose the hyperventilation.

• If the acidosis is chronic, respiratory compensation can be complete only after several days of adaptation.

Generally, renal compensation for respiratory acidosis or alkalosis can be

complete, but is slow.Changes in renal H+ secretion begin

immediately, but it takes time for the renal response to restore plasma pH to normal.

Summary of Acid-Base Analysis

Some important issues

• The Davenport diagram shows that there is a world of difference between the blood chemistry of someone with well-compensated respiratory acidosis or alkalosis and someone with well-compensated metabolic acidosis or alkalosis.

• Is there still a disorder if the compensation is perfect? Yes indeed. The Davenport diagram shows this clearly.

Electroneutrality at work

Part A shows normal concentrations of the major plasma electrolytes. The ‘anion gap’ is a way of referring to the ions that don’t usually get measured in ordinary clinical practice. Historically, it amounted to [Na+] – ([Cl-]+ [HCO3

-]), which = 9-14 mEq/L.

Part B shows a situation in which the anion gap has increased at the expense of the bicarbonate and chloride. This is typical of metabolic acidoses in which the conjugate anion of the fixed acid is something other than Cl-.

Ethylene glycol-induced metabolic acidosis

• Ethylene glycol is sweet, so it is attractive to animals, children (and some adults, in situations where beverage ethanol is not available)

• Ethylene glycol is metabolized by the same enzymatic pathway as ethanol, yielding glyceraldehyde instead of acetaldehyde, and then oxalic acid instead of acetic acid.

• Oxalate occupies some of the space that had belonged to HCO3

- and Cl-, enlarging the anion gap.

Aspirin Intoxication

• In children and adolescents, aspirin mainly stimulates the release of organic acids from cells, causing a metabolic acidosis with increase in the gap.

• In adults, the main effect is stimulation of respiration, leading to respiratory alkalosis.

• In young teenagers, the metabolic and respiratory effects can compete, causing a mixed acid-base disorder.