L9 - Kidney III Acid-Base Disorder

What are the 3 major systems that regulate acid-base balance, and how quickly do they act?

1) Chemical buffer systems = immediate/first line of defense; 2) Respiratory system = minutes; 3) Kidneys = hours to days and are the slowest.

What are the 4 major chemical buffer systems and where are they most important?

Bicarbonate = most important extracellular/plasma buffer; Phosphate = renal tubules and intracellular fluid; Ammonia = renal tubules; Proteins = most plentiful buffers and primarily intracellular.

What is the bicarbonate buffer equation?

CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-. H2CO3 is the weak acid and HCO3- is the base.

What happens when the bicarbonate system buffers a strong acid?

HCO3- accepts H+ → H2CO3 → H2O + CO2. CO2 increases, so ventilation increases to eliminate the excess CO2.

What happens when the bicarbonate system buffers a strong base?

The base consumes H+, shifting the reaction to replace H+. CO2 decreases, so ventilation decreases to retain CO2.

Why is the bicarbonate buffer system effective even though its pKa is not close to blood pH?

Its components can be physiologically regulated: the lungs regulate CO2 and the kidneys regulate HCO3-.

How does the HCO3-/pCO2 ratio determine pH?

HCO3- represents the base and pCO2 represents the acid side. ↑ HCO3-/pCO2 ratio = ↑ pH/alkalosis; ↓ ratio = ↓ pH/acidosis.

What is the Henderson-Hasselbalch relationship for the bicarbonate system?

pH = 6.1 + log([HCO3-]/0.03 × pCO2). Therefore, increasing HCO3- or decreasing pCO2 raises pH; decreasing HCO3- or increasing pCO2 lowers pH.

What should you know about the phosphate buffer system?

It consists of H2PO4- and HPO4^2- and primarily buffers renal tubular and intracellular fluid. It is effective in renal tubules because phosphate is concentrated there and its pKa (~6.8) is relatively close to tubular pH.

Why is phosphate not a major blood buffer?

Phosphate concentrations are too low in blood for it to contribute significantly to extracellular buffering.

What should you know about the protein buffer system?

Proteins are the most plentiful buffers and provide about 60-70% of chemical buffering in body fluids. They are especially important intracellularly because their pKa values are close to intracellular pH.

How does hemoglobin function as a buffer?

Hemoglobin accepts H+: H+ + Hb- → HHb. This makes hemoglobin an important protein buffer in blood.

What should you know about the ammonia buffer system?

It consists of NH3 and NH4+ and functions primarily in renal tubules. It allows H+ to be trapped and excreted as NH4+ while generating new HCO3-.

What acid-base component do the lungs regulate?

The lungs regulate CO2/pCO2, which represents the volatile acid component of acid-base balance.

How does alveolar ventilation affect pCO2 and pH?

↑ ventilation → ↑ CO2 expiration → ↓ pCO2 → ↑ pH. ↓ ventilation → CO2 retention → ↑ pCO2 → ↓ pH.

How does blood pH affect ventilation?

↓ blood pH stimulates ↑ alveolar ventilation; ↑ blood pH causes ↓ alveolar ventilation.

How do the lungs compensate for metabolic acid-base disorders?

Metabolic acidosis → hyperventilation → ↓ pCO2. Metabolic alkalosis → hypoventilation → ↑ pCO2. Respiratory compensation begins within minutes.

What are the 3 major ways the kidneys regulate acid-base balance?

1) Secretion of H+, 2) Reabsorption of filtered HCO3-, and 3) Production of new HCO3-.

What do the kidneys do during acidosis versus alkalosis?

Acidosis → increase H+ excretion, conserve/reabsorb HCO3-, and generate new HCO3-. Alkalosis → increase HCO3- excretion and decrease acid-excreting/conserving responses.

Why can't the kidneys excrete the body's acid load as free H+ alone?

Minimum urine pH is about 4.5, so only a small amount of free H+ can be excreted. Phosphate and ammonia buffers allow much larger quantities of H+ to be eliminated.

How is filtered HCO3- reclaimed by the kidney?

H+ is secreted into the lumen and combines with filtered HCO3-. Carbonic anhydrase facilitates conversion to CO2 + H2O; CO2 enters the tubular cell and ultimately allows HCO3- to return to blood.

What is the net result of renal HCO3- reclamation?

One H+ is secreted into the lumen and one filtered HCO3- is returned to the blood. This SAVES existing bicarbonate; it does NOT create new bicarbonate.

Where is most filtered HCO3- reabsorbed?

About 80% is reabsorbed in the proximal tubule.

What do Type A (alpha) intercalated cells do?

Type A = Acid out. They secrete H+ into urine and reabsorb HCO3- into blood, making them important during acidosis.

What do Type B (beta) intercalated cells do?

Type B = Bicarbonate out. They secrete HCO3- into urine and move H+ toward the blood, making them important during alkalosis.

What is the difference between HCO3- reclamation and HCO3- generation?

Reclamation saves filtered HCO3- that already exists. Generation creates NEW HCO3- to replace bicarbonate consumed while buffering nonvolatile acids.

What are the 2 major mechanisms for generating new HCO3- in the kidneys?

Phosphate buffering and ammonia buffering. Both allow H+ excretion while adding new HCO3- to the blood.

How does phosphate buffering generate new HCO3-?

Secreted H+ binds phosphate and is excreted as H2PO4-. The process adds one new HCO3- to blood for each H+ excreted.

How does ammonia buffering generate new HCO3-?

Renal cells metabolize glutamine to produce NH4+ and HCO3-. NH4+ is excreted while HCO3- enters the blood.

What is produced from one glutamine molecule during renal ammoniagenesis?

2 NH4+ and 2 HCO3-. The NH4+ is ultimately excreted and the HCO3- is added to blood.

What are the 4 major acid-base disorders and their primary abnormalities?

Metabolic acidosis = ↓ HCO3-; Metabolic alkalosis = ↑ HCO3-; Respiratory acidosis = ↑ pCO2; Respiratory alkalosis = ↓ pCO2.

What causes respiratory acidosis versus respiratory alkalosis?

Respiratory acidosis = hypoventilation → CO2 retention → ↑ pCO2 → ↓ pH. Respiratory alkalosis = hyperventilation → excessive CO2 removal → ↓ pCO2 → ↑ pH.

What are the major mechanisms of metabolic acidosis?

Loss/consumption of HCO3- or accumulation of acid. Examples include lactic acidosis, ketoacidosis, impaired renal acid excretion, bicarbonate loss, and chloride gain.

How can excess chloride cause metabolic acidosis?

Cl- increases and replaces HCO3- to maintain electroneutrality. Large amounts of 0.9% NaCl can therefore cause hyperchloremic metabolic acidosis.

What are the major mechanisms of metabolic alkalosis?

Loss of acid or gain of base. Examples include vomiting/HCl loss, hyperaldosteronism with increased renal H+ secretion, and excessive NaHCO3 administration.

What is the basic rule for compensation in acid-base disorders?

The OTHER physiological system compensates. Metabolic disorder → lungs compensate. Respiratory disorder → kidneys compensate.

What are the primary change and compensation in metabolic acidosis?

Primary ↓ HCO3- → lungs hyperventilate → ↓ pCO2 → pH moves toward normal.

What are the primary change and compensation in metabolic alkalosis?

Primary ↑ HCO3- → lungs hypoventilate → ↑ pCO2 → pH moves toward normal.

What are the primary change and compensation in respiratory acidosis?

Primary ↑ pCO2 → kidneys increase H+ excretion and HCO3- retention/generation → ↑ HCO3-.

What are the primary change and compensation in respiratory alkalosis?

Primary ↓ pCO2 → kidneys decrease HCO3- reabsorption/increase HCO3- excretion → ↓ HCO3-.

How does acute versus chronic compensation differ in respiratory acidosis?

Acute respiratory acidosis is initially compensated by intracellular buffers such as hemoglobin/proteins. Chronic respiratory acidosis causes renal generation of new HCO3- and increased NH4+/H+ excretion.

How does acute versus chronic compensation differ in respiratory alkalosis?

Acute respiratory alkalosis is initially compensated by intracellular buffering. Chronic respiratory alkalosis causes decreased renal HCO3- reabsorption and decreased NH4+ excretion, lowering blood HCO3-.

What pattern do HCO3- and pCO2 follow after compensation in a simple acid-base disorder?

They ultimately move in the SAME direction: metabolic acidosis = both ↓; metabolic alkalosis = both ↑; respiratory acidosis = both ↑; respiratory alkalosis = both ↓.

What is electroneutrality?

The total concentration of cations must equal the total concentration of anions. When one measured ion decreases, another measured or unmeasured ion must compensate to maintain electrical neutrality.

What is the serum anion gap and its equation?

The anion gap estimates the difference between measured cations and measured anions and reflects primarily unmeasured anions. AG = Na+ - (Cl- + HCO3-).

Why is the anion gap clinically important?

It helps determine the cause/type of metabolic acidosis by showing whether decreased HCO3- has been replaced by unmeasured anions or by chloride.

What causes high-anion-gap metabolic acidosis?

Accumulation of an unmeasured acid such as lactic acid or ketoacids. HCO3- is consumed buffering H+, while the unmeasured anion accumulates.

What happens to HCO3-, Cl-, and unmeasured anions in high-anion-gap metabolic acidosis?

↓ HCO3-, ↑ unmeasured anions, and Cl- remains relatively unchanged. Therefore, it is generally a normochloremic metabolic acidosis.

Why does lactic acidosis increase the anion gap?

HCO3- buffers H+ from lactic acid and decreases, while unmeasured lactate accumulates and effectively replaces the lost HCO3-, increasing the gap.

What causes normal-anion-gap metabolic acidosis?

Loss of HCO3- or gain of Cl-. Cl- replaces the decreased HCO3- to maintain electroneutrality, so the anion gap does not increase.

What is the key difference between high-AG and normal-AG metabolic acidosis?

High AG = ↓ HCO3- + ↑ unmeasured anions while Cl- stays relatively normal. Normal AG = ↓ HCO3- + ↑ Cl-, so it is also called hyperchloremic metabolic acidosis.