Acid

Acid-Base Homeostasis: Role of the Respiratory System

Overview of acid-base balance

Basics of acid-base balance

Acid-base imbalance occurs when there is an inequality in the production and excretion of acids and bases.
Normal metabolism yields:

carbonic acids that are excreted by the lungs
non-carbonic acids and certain bases that are excreted by the kidneys

Several systems help to minimize or correct acidosis or alkalosis:

buffer systems – instantaneous action

respiratory system – active within 1-12 minutes

renal system – requires 48-72 hours for maximum effect

Buffer Systems

Three different buffer systems – bicarbonate, phosphate, and protein; buffers are both intra- and extracellular
Bicarbonate buffer system

H₂O + CO₂ = H₂CO₃ = H⁺ + HCO₃^- (reaction catalyzed by the enzyme carbonic anhydrase)
CO₂ equilibrates rapidly between intracellular and extracellular compartments, so its measurement is useful in evaluation of acid-base balance.
Henderson-Hasselbalch equation describes relationship of pCO₂ and HCO₃^- in maintaining acid-base balance:

pH = 6.1 + log HCO₃^-/0.03 (pCO₂)

Each element of the Henderson-Hasselbalch (HCO₃, pCO₂) equation can be regulated.

HCO₃^- – renal control
pCO₂ – respiratory control
Ratio of HCO₃^- to pCO₂ is what determines the pH

Carbonic Acid Production

15,000 mmole of CO₂/day is formed from carbohydrate, fat and proteins.
Transport to the lung occurs via proteins in red blood cells; in the lung, CO₂ is exhaled.

Non-carbonic acid production

Sulfates, phosphates and bases are formed from amino acid metabolism.
Excess acid is excreted by the kidney in the form of titratable acid and NH₄.
For each unit of acid excreted, one unit of HCO₃^- is generated.

Chemical control of respiration

Chemosensitive Area of the Respiratory Center

Located near ventral surface of the medulla; this area excites other areas of the respiratory center.

Very sensitive to changes in pCO₂ and H⁺ concentration.

Effect of CO₂ is indirect, through formation of H⁺ and HCO₃^- (after penetration into CSF); H⁺ ions stimulate it

A ß in pH from 7.4 to 7.0 causes 4-5 fold Ý in alveolar ventilation; pH thus returns to 7.2-7.3 within 3-12 minutes

Peripheral Chemoreceptor System

Carotid bodies – contains large number of chemoreceptors; afferent nerve fibers through Hering's nerves to glossopharyngeal nerves to dorsal respiratory area of medulla
Aortic bodies – afferent nerve fibers through the vagi to dorsal respiratory area of medulla
Blood flow through the bodies is extremely high
Drop in paO₂ increases rate of nerve transmission; impulse rate most sensitive at PaO₂ between 60-30 mm Hg.
Mild effect on pCO₂ and pH (one-seventh that of respiratory center).

The respiratory system can only accomplish a 50-75% correction for metabolic acidosis/alkalosis.

Acid-Base Imbalances

Respiratory Acidosis

Cause: hypoventilation

global alveolar hypoventilation – neuromuscular or respiratory muscle disease, drug overdose, anesthetics
regional alveolar hypoventilation – in patients with underlying pulmonary disease

Increased CO₂ drives equation CO₂ + H₂O Þ H₂CO₃ Þ H⁺ +HCO₃^- to right with resultant ß in pH

Buffer response – H₂CO₃ + OH^- Þ HCO₃^- + H₂O – mostly intracellular; has a moderate effect on HCO₃^-

HCO₃^- seldom > 30 meq/L in first 24 hours; buffering accounts for 35% of compensation

Renal response – H⁺ secretion with HCO₃^- reabs; more effective than buffering, accounts for 65% of compensation

Total compensation never completely normalizes pH

Respiratory Alkalosis

Cause: low paCO₂ – abnormal lung or chest wall mechanics, hypoxemia, liver disease, fever, septic shock, brainstem injury, psychogenic, ASA

Buffer response – H₂O + CO₂ Þ HCO₃^- + H⁺– ß HCO₃^- with Ý pH; lactate production enhanced from activation of PFK

Renal response – H⁺ reabsorbed, HCO₃^- secreted

Metabolic Acidosis – rate of production of non-carbonic acid exceeds excretion

Causes – Diabetic ketoacidosis, lactic acidosis, methyl alcohol and ethylene glycol poisoning, renal insufficiency (inability to excrete acid load), bowel fistula or diarrhea (loss of HCO₃^-)

Buffering – HCO₃^- is primary EC buffer; H⁺ + HCO₃^- Þ CO₂ + H₂O; cellular buffering early; skeletal buffering late

Respiratory response – Ý alveolar ventilation in response to ß pH – ventilatory response proportional to acidosis

Biphasic response: (1) acute ß pHÞ peripheral chemoreceptors; (2) chronic ß pHÞ central chemoreceptors

Kussmaul's respiration – rapid, deep ventilation

Cheyne-Stokes respiration – episodic respiratory pattern Þ tidal volume changes between breaths

Renal response – Ý H⁺ excretion via titratable acid and NH₄⁺

Metabolic Alkalosis – rate of non-carbonic acid excretion exceeds rate of production; there is a primary Ý in HCO₃^-

Causes – vomiting, gastric suctioning with loss of HCl (HCO₃^- reclaimed), diuretics (Ý Na⁺ delivery to distal tubule with Ý excretion of acid), volume depletion (HCO₃^- retained in urine), K⁺ deficiency (Ý H⁺ excretion), hyperaldo

Buffer response – small amount of extracellular protein and hemoglobin; intracellular (CO₂+H₂O Þ H⁺+HCO₃^-); slight Ý lactate production

Respiratory response

acute – ß alveolar ventilation brings ratio toward normal

chronic – ß sensitivity of respiratory center

pCO₂ seldom >55 mm Hg; respiratory compensation is always incomplete

Renal response

acute – HCO₃^- excreted in urine
chronic – stim.of Na⁺ reabs with H⁺ excretion(paradoxical aciduria)

Equations and Normal Values

Equations:

Buffer systems Þ HPO₄^-² + H⁺ = H₂PO₄^-

Prot^- + H⁺ = Hprot

Hb^- + H⁺ = HHb

Bicarbonate buffer system Þ H₂O + CO₂ = H₂CO₃ = HCO₃^- + H⁺

Henderson-Hasselbalch equation Þ pH = 6.l + log HCO₃^-/0.03 (pCO₂)

Anion gap Þ AG = Na⁺ - (Cl^- + HCO₃^-)

Normal Values:

serum pH: 7.36-7.44
serum CO₂: 36-44 mm Hg
serumHCO₃: 22-26 meq/l

Rules of Compensation

Metabolic Acidosis and Alkalosis

	Metabolic Acidosis	Metabolic Alkalosis
expected pCO₂	1.5 (HCO₃^-) + 8(±2)	0.7 (HCO₃^-) + 2.0(±1.5)
Respiratory Response	pCO₂ ß 1.0-1.5 mmHg for every 1 meq/l ß HCO₃^-	pCO₂ Ý 0.6-0.7 mm Hg for every 1 meq/l Ý HCO₃^-

Respiratory Acidosis and Alkalosis

	Respiratory Acidosis	Respiratory Alkalosis
acute pH response	pH ß 0.089 for every 10 mmHg Ý pCO₂	pH Ý 0.08-0.108 for every 10 mmHg ß pCO₂
chronic pH response	pH ß 0.039 for every 10 mmHg Ý pCO₂	pH Ý 0.0178 for every 10 mmHg ß pCO₂
Buffer Response	HCO₃^- Ý 1 meq/l for every 10 mmHg Ý in pCO₂	HCO₃^- ß 1.5 meq/l for every 10 mmHg ß in pCO₂
Renal Response	HCO₃^- Ý 2 meq/l for every 10 mmHg Ý in pCO₂	HCO₃^- ß 3.0 meq/l for every 10 mmHg ß in pCO₂