Chapter Twenty One: Respiratory Alkalosis

References

Chapter 19, Part 3 August 30, 2023Biff Palmer’s Ted Talk-Why not? Biff Palmer at TEDxSMU 2013

Anna mentioned this issue of lactic acidosis in a panic disorder: The Lactic Acid Response to Alkalosis in Panic Disorder | The Journal of Neuropsychiatry and Clinical Neurosciences

Reminder of important clinical lesson: Lactate: panicking doctor or panicking patient? - PMC

Melanie regaled the group with an excerpt (page 351) Cohen, J. J., Kassirer, J. P. (1982). Acid-base. United States: Little, Brown.

Biff Palmer! Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023

Melanie loves this study of chronic respiratory alkalosis on participants to traveled to the High ALpine research station on the Jungfraujoch in the Swiss Alps Chronic Respiratory Alkalosis — The Effect of Sustained Hyperventilation on Renal Regulation of Acid–Base Equilibrium | NEJM (and here’s a great picture: Services: Jungfraujoch Research Station - Climate and Environmental Physics (CEP)

JC mentioned that there are cells in the carotid body which are called glomus cells Neurobiology of the carotid body.

JC discussed respiratory alkalosis in cirrhosis and here’s a review he had melanie write that addresses this topic: Acid Base Disorders in Cirrhosis - Advances in Kidney Disease and Health and here are some reviews he likes: The hyperventilation of cirrhosis: progesterone and estradiol effects and Acid-base disturbance in patients with cirrhosis: relation to hemodynamic dysfunction and Blood-Brain Barrier Permeability Is Exacerbated in Experimental Model of Hepatic Encephalopathy via MMP-9 Activation and Downregulation of Tight Junction Proteins

The finding of respiratory alkalosis in pregnancy is not a new concept. Here’s a study from 1962: Acid-base balance of arterial blood during pregnancy, at delivery, and in the puerperium - American Journal of Obstetrics & Gynecology

Melanie reminded us of the Charlie Brown sad face that occurs after bicarbonate infusion and delay in bicarbonate movement to the CSF! Spinal-Fluid pH and Neurologic Symptoms in Systemic Acidosis | NEJM (part 2 of chapter 11)

Josh mentioned this report from Andrew Tarulli (a great neurologist previously at BIDMC who has moved to Overlook Hospital in NJ) Central Neurogenic Hyperventilation: A Case Report and Discussion of Pathophysiology | Allergy and Clinical Immunology | JAMA Neurology

He also mentioned this important transporters that affect the pH. The choroid plexus sodium-bicarbonate cotransporter NBCe2 regulates mouse cerebrospinal fluid pH

Refractory Central Neurogenic Hyperventilation: A Novel Approach Utilizing Mechanical Dead Space

Outline: Chapter 21

Respiratory Alkalosis

Increased pH, low pCO2, variable reduction in HCO3

Differentiate from metabolic acidosis where pH is decreased

(but pCO2 and HCO3 are likewise decreased)

PATHOPHYSIOLOGY

Primary decrease in pCO2 when effective alveolar ventilation is increased beyond that needed to eliminate daily CO2 production

How does the body respond to hypocapnia

Mass action

Reduction in H+ induced by hypocapnia can be minimized by lowering HCO3

One: rapid cell buffering

Two: later decrease in net renal acid secretion → lower HCO3

These two strategies explain the difference between acute and chronic respiratory alkalosis

Acute Respiratory Alkalosis

Within 10 minutes, H ions move into extracellular fluid

H+ combines with HCO3 → fall in plasma HCO3

Converted to CO2 and H2O

H+ comes from intracellular buffers

Protein, phosphate, hemoglobin

H+ may also come from alkalemia-induced increase in cellular lactic acid production (1)⁉️

Enough H+ enters ECF to lower HCO3 by 2 mEq for each 10 mmHg decrease in pCO2 (Fig 20-3)

Example: pCO2 falls to 20

HCO3 falls by 4 → ~20 mEq/L

pH ~7.63

Not very efficient at protecting pH

Without compensation pH would be ~7.70

Chronic Respiratory Alkalosis

Compensatory ↓ renal H secretion

Begins within 2 hours

Not complete for 2–3 days

Due to parallel rise in tubular cell pH

Manifested by

HCO3 loss

Decreased NH4 in urine

4 mEq drop in HCO3 for each 10 mmHg decrease in pCO2

Example: pCO2 20 → HCO3 16 → pH ~7.53

ETIOLOGY

Respiration governed by two sets of chemoreceptors

Central (respiratory center in brainstem)

Peripheral (carotid bodies at bifurcation, aortic bodies at arch)

Central chemoreceptors

Stimulated by ↑ pCO2 or metabolic acidosis

Peripheral chemoreceptors

Stimulated by hypoxia (and acidosis)

Thus hyperventilation can be produced by

Hypoxemia

Anemia

Reduction in arterial pH

Other stimuli

Pain

Anxiety

Mechanoreceptors

Direct stimulation of respiratory center

Table 21-1

Hypoxemia

Respiratory response occurs in stages

Stage 1

Peripheral chemoreceptor activation

Hyperventilation → respiratory alkalosis

Increased cerebral pH inhibits central respiratory center

Limits hyperventilation

No significant hyperventilation until pO2 < 50–60 mmHg

If lung disease prevents pCO2 reduction

Hypoxia stimulates ventilation at PaO2 < 70–80 mmHg

Stage 2⁉️

Persistent hypoxemia → ↓ HCO3

Lowers pH toward normal

Removes alkalosis inhibition

Allows greater ventilatory response

Pulmonary Disease

Common in pneumonia, PE, interstitial fibrosis

Also pulmonary edema (though acidosis more common)

Hyperventilation may be due to hypoxemia

Often not corrected by oxygen

Other contributors

Mechanoreceptors in airways, lungs, chest wall

Signals via vagus nerve

Juxtacapillary receptors (interstitium)

Irritant receptors (epithelium)

Activated by inflammation or inhaled irritants

(asthma, pneumonia)

These contribute to dyspnea even without hypoxia

Direct Stimulation of Medullary Respiratory Center

Cortical input (psychogenic hyperventilation)

Retained amines in hepatic failure (not prostaglandins⁉️)

Bacterial toxins (gram-negative sepsis)

Salicylates

Progesterone (pregnancy, luteal phase)

Persistent acid CSF after rapid correction of metabolic acidosis

NaHCO3 raises extracellular pH

Peripheral chemoreceptors reduce ventilation → ↑ pCO2

CO2 crosses BBB rapidly, HCO3 does not

Brain senses ↑ pCO2 → ↓ CSF pH

Paradoxical prolongation of hyperventilation

Neurologic disorders

Pontine tumors → local acidosis → ↓ CSF pH → ↑ ventilation

Hypocapnia in acute cerebral accidents

Mechanical Ventilation

Overventilation can cause respiratory alkalosis

Correct by

Increasing dead space (no explanation given 🤷🏻‍♂️)

Decreasing tidal volume

Decreasing respiratory rate

SYMPTOMS

Due to increased CNS and peripheral nerve excitability

Lightheadedness

Altered consciousness

Paresthesias (extremities, circumoral)

Cramps

Carpopedal spasm

Syncope

Cardiac

Supraventricular and ventricular arrhythmias

Mechanisms

Impaired cerebral function

Increased membrane excitability

↓ cerebral blood flow

35–40% reduction if pCO2 drops by 20 mmHg

Psychogenic hyperventilation symptoms

Dyspnea

Headache

Chest pain

Symptoms more prominent in acute disease (rapid pH change)

Electrolytes

↓ phosphate (as low as 0.5–1.5 mg/dL)

Due to intracellular shift

Increased glycolysis → ↑ phosphorylated compounds

DIAGNOSIS

Tachypnea

But could be acidosis or alkalosis

Consider sepsis

Compensation equations can be ambiguous

Example: 7.48 / 20 / XX / 16

Could be chronic respiratory alkalosis

Or acute respiratory alkalosis + metabolic acidosis 😖

Case 21-1

5-year-old with AMS, playing with aspirin

TREATMENT

Usually not necessary

Do NOT give

Respiratory depressants

HCl

Paper bag rebreathing

↑ inspired CO2

Can correct acute respiratory alkalosis

If chronic → may leave patient with metabolic acidosis

Can treat with NaHCO3

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