A. Introduction

1. Less common than acidosis in seriously ill patients
2. Respiratory forms more common in younger persons with anxiety reactions
3. Severe metabolic acidosis usually due to drug effects

B. Symptoms and Effects of Severe Alkalemia

1. Defined as blood pH>7.60
2. May compromise cerebral and myocardial perfusion
3. This is due to vasoconstrictive nature of alkalemia
4. Neurologic Abnormalities
   1. Tetany
   2. Seizures
   3. Lethargy, Delirium
   4. Stupor
5. Cardiovascular Effects
   1. Reduced coronary blood flow
   2. Reduced anginal threshold
   3. Predisposition to refractory supraventricular and ventricular tachycardias
6. Hypoventilation with compensatory hypercapnia
7. Metabolic Effects
   1. Stimulation of anaerobic glycosis (organic acid production)
   2. Hypokalemia
   3. Decreased plasma ionized calcium concentration
   4. Low serum magnesium and phosphate

C. Metabolic Alkalosis

1. Each 1mM rise in plasma HCO3- leads to ~0.6mM rise in pCO2
2. This is due to combination with water
3. Hypochloremic
   1. Volume depletion is usually underlying problem
   2. Caused by bomiting, fiuretics, laxative abuse, and post-hypercapnic alkalosis
   3. Long, intense exercise with hypovolemia may lead to contraction alkalosis
   4. Homeostatic correction is attempted by Na+ excretion without chloride
   5. Since volume is depleted, however, Na+ is retained (aldosterone levels elevated)
   6. The contraction perpetuates hypochloremic alkalosis
4. Hyperadrenocorticism
   1. Cushing Syndrome - Hypersecretion of glucocorticoids
   2. May be due to adrenal dysfunction or to hypersecretion of ACTH
   3. Hyperaldosteronism
   4. Conn Syndrome - increased aldosterone causes hypokalemia, alkalosis, hypernatremia
5. Hypoproteinemia
   1. The anion gap (acid) exists mainly because of negatively charged serum proteins
   2. Albumin is the primary contributor to negative charge in serum proteins
   3. Albumin contributes ~2 Anion Gap Units per 1gm/dL of serum albumin
   4. Normal anion gap is ~10, so normal albumin = 4gm/dL contributes about 8 charges
   5. Therefore, decreased anion gap occurs with low protein states leading to alkalosis
   6. Thus, one common cause of decreased anion gap with alkalosis is hypoalbuminemia
6. Severe Potassium Depletion
7. Excessive Alkali Intake
   1. Sodium Bicarbonate (NaHCO3) intake
   2. Sodium penicillin
   3. Na citrate - added to blood products as stabilizer
   4. Acetates or lactates can also cause alkalemia
8. Treatment
   1. Must reduce pH to <7.55 rapidly to avoid irreversible damage
   2. Patients with volume depletion require both sodium and potassium chloride replacement
   3. Acetazolamide 250-375mg qd-bid accelerates bicarbonate (HCO3-) loss (in urine)
   4. In severe cases, 0.1N-0.2N hydrochloric acid (HCl) can be infused
   5. HCO3- occupies about 50% of body weight
   6. Thus, to reduce plasma HCO3- from 50 to 40 mM in a 70kg person, consider following:
   7. HCl required ~ (50-40mM) x 70kg x 50% (0.5) = 350mmoles (3.5 L of 0.1N HCl solution)
   8. No advantage to arginine HCl or ammonium chloride over standard HCl
   9. Caution is critical in patients with cardiac or renal dysfunction (volume control)
   10. Spironolactone (Aldactone®) may be effective in Conn's Syndrome (with surgery)
9. Bartter Syndromes [2]
   1. Familial hypokalemic, hypochloremic metabolic alkalosis
   2. Set of closely related disorders: classic, Gitelman, antenatal
   3. Due to abnormalities in of renal tubular cells
   4. All variants have hypokalemic alkalosis
   5. All variants have high urinary chloride (Cl) excretion, Cl(urine) >20mM
   6. Hypertension is NOT present, despite high renin and angiotensin II levels
   7. Antenatal and classic forms due to abnormal renal transepithelial chloride transport
   8. Gitelman variant due to mutations in thiazide sensitive Na-Cl transporter
   9. Treat by normalizing electrolytes, drugs directed at specific hormonal anomalies

D. Respiratory Alkalosis (Hypocapnia) [3]

1. Increased Hypoxic Drive
   1. Acute or chronic hyperventilation, which lowers pCO2
   2. Acute and chronic COPD, heart disease, pulmonary emoblism
   3. High altitudes - altitude sickness may be attenuated by inducing metabolic acidosis
   4. Acetazolamide (Diamox®) causes HCO3- loss in urine and metabolic acidosis
2. Sepsis
   1. Often produces mixed disorders
   2. Metabolic acidosis (anion gap) with repiratory alkalosis (overcompensation)
   3. There is definitely a primary respiratory alkalotic component
   4. Result is a "Delta-Delta" >2 signifying a mixed disorders
   5. Mortality increases in direct proportion to severity of hypocapnia
3. Hepatic Cirrhosis
   1. Often seen with progressive hepatic failure
   2. May be due to failure of toxin removal by liver cells
4. Respiratory Center Stimulation
   1. Fever especially with Sepsis
   2. Salicylates - causes a mixed acid-base disorder
   3. Progestins
   4. Theophylline
   5. Other Stimulants
   6. Anxiety / Panic Attacks
5. Exercise
6. Compensatory Changes
   1. Acute reductions in plasma CO2 lead to small changes in plasma HCO3-
   2. Chronic reduced CO2 leads to persistant reductions in renal acidification
   3. This leads to substantial total body bicarbonate losses
7. Iatrogenic Hypocapnia [3]
   1. Hyperventilation to induce hypocapnia previoulsy advocated for head injury
   2. Also previously recommended for some coma, neonatal pulmonary hypertension
   3. In vast majority of patients, iatrogenic hypocapnia is detrimental
   4. Causes vasoconstriction and increased pulmonary shunting
   5. Exacerbates tissue hypoxia and cell death
   6. Increases metabolic demands on cells to counteract pH changes
   7. Hypocapnia may also increase airway resistance in asthma
   8. Iatrogenic hypocapnia should be instituted only when risks and benefits clarified
8. Correction of underlying causes is mainstay of therapy
9. Treatment of Anxiety-Hyperventilation Syndrome
   1. Reassurance
   2. Sedation
   3. Rebreathing into paper bag or other confined devise - prompt but temporary solution
   4. Pharmacologic therapy with or without psychotherapy is recommended long term

References

1. Adrogue HJ and Madias. 1998. NEJM. 338(2):107
2. Guay-Woodford LM. 1998. Am J Med. 105(2):151
3. Laffey JG and Kavanagh BP. 2002. NEJM. 347(1):43