• Information
  1. Consequences of Severe Acidemia (pH < 7.20)
  2. Considerations in Correcting Acidemia
  METABOLIC ACIDOSIS
  1. Increased Production or Presence of Nonvolatile Acids
  2. Lactic Acidosis
  3. Chronic Renal Failure
  4. Abnormal Buffering System
  5. Hyperchloremic (Normal Anion Gap) Acidosis
  6. Treatment
  RESPIRATORY ACIDOSIS
  1. Introduction
  2. Chronic Obstructive Pulmonary Disease
  3. Hypoventilation
  4. Delta Delta (DD): Mixed Disorders

A. Consequences of Severe Acidemia (pH < 7.20)

1. Cardiovascular
   1. Impaired cardiac contractility
   2. Arteriolar dilation, venoconstriction, centralization of blood volume
   3. Increased pulmnary vascular resistance
   4. Reduced cardiac output and blood pressure
   5. Reduced renal and hepatic blood flow
   6. Increased risk of reentrant arrhythmias and ventricular fibrillation
   7. Reduced cardiovascular response to catecholamines
2. Respiratory
   1. Hyperventilation
   2. Reduced respiratory muscle strength
   3. Dyspnea
3. Metabolic
   1. Increased metabolic demands
   2. Insulin resistance
   3. Inhibition of anaerobic glycolysis
   4. Reduction in ATP synthesis
   5. Hyperkalemia (through H+/K+ cell membrane pumps)
   6. Increased protein catabolism (degradation)
   7. Suppression of lactate consumption by liver and kidney
4. Cerebral
   1. Inhibition of metabolism and normal cell volume regulation
   2. Cerebral blood vessel dilation
   3. Obtundation and coma
5. Others
   1. Nausea and vomiting
   2. Confusion
   3. Muscle fatigue, myalgias

B. Considerations in Correcting Acidemia

1. Rapidity of change in blood pH can have marked effects on urgency of therapy
2. Slowly changing pH is better tolerated than rapid pH changes
3. Therapy should initially be directed at making pH > 7.20
4. Permissive hypercapnia with acidosis may be beneficial in critically ill patients []

1. Ketoacidosis (Diabetic, starvation)
2. Lactic Acidosis: ischemia, infarction
3. Infection
4. Uremic acidosis
5. Toxins: Methanol, Ethylene Glycol, Salicylates, Paraldehyde, Toluene
6. Note that Salicylates also cause a respiratory alkalosis (mixed disorder)
7. Mnemonic is "MUD PILES"

B. Lactic Acidosis

1. Type A L-Lactate Acidosis
   1. Impaired tissue oxygenation present
   2. Oxidative phosphorylation is impaired, and pyruvate generates lactate
2. Type B L-Lactate Acidosis
   1. Absence of tissue oxygenation problems
   2. Toxin generated
3. Diagnosis confirmed by elevated serum L-lactate levels and presence of anion gap
4. Arterial lactate level may be the best predictor of outcome in acetaminophen overdose [5]
5. D-lactate acidosis may be associated with short bowel syndrome [4]
6. Treatment Considerations
   1. Type A: Correction of tissue hypoxemia is mainstay of therapy
   2. Type B: Detoxification, fluid support, organ function support for therapy
   3. Addition of HCO3- is important in severe cases
   4. Dicholoracetate is investigational in treatment of lactic acidosis

C. Chronic Renal Failure

1. Failure to excrete metabolic byproducts)
2. Reduced acid excretion; less HCO3- resorption by the kidney (increased anion gap)
3. Hyperphosphatemia and Hypersulfatemia
4. Treatment: dialysis

D. Abnormal Buffering System

1. Hyperproteinemia (increased anion gap)
   1. Albumin makes up ~65% of normal anion gap
   2. Note that globulins are negatively charged and will lower the anion gap
2. Usually with low HCO3-

E. Hyperchloremic (Normal Anion Gap) Acidosis [1]

1. Generally grouped by serum potassium
2. Low or Normal Serum Potassium
   1. Type I Renal tubular acidoses (RTA)
   2. Non-renal causes
3. High Serum Potassium
   1. Type IV Renal Tubular Acidosis (low renin and low aldosterone)
   2. Hypoaldosteronism - adrenal insufficiency, others
   3. K+ sparing diuretics
4. Loss of Alkali with Low Serum Potassium
   1. Diarrhea leads to HCO3- and Na+ loss and results in hyperchloremic acidosis
   2. This occurs despite volume depletion
   3. Carbonic anhydrase inhibition (such as acetazolamide, Diamox®) was a common cause
   4. Other losses (ileal bladder conduit, ileostomy, short bowel syndrome)
5. Ammonium chloride and cationic amino acids
6. Dilutional Acidosis
   1. Sizeable expansion of extracellular fluid volume without HCO3-
   2. Often in severe right ventricular infarction with heavy exogenous fluid administration
7. Overexuberant crying - mainly in infants (tears contain bicarbonate)

F. Treatment

1. Generally directed first at underlying cause
2. Diagnosis helped by determining Urinary Anion Gap (UAG)
   1. This is UAG = [Na+]+[K+] - [Cl-]
   2. Negative UAG signifies normal renal NH4+ excretion (ie. nonrenal cause of acidosis)
   3. This assumes urine pH < 6.1 and euvolemia (hypovolemia may impair acid excretion)
3. Sodium Bicarbonate (HCO3-)
   1. Parenteral HCO3- treatment should be instituted for pH < 7.20-7.25
   2. Symptoms of severe acidosis will occur around this pH
   3. Respiratory compensation will be maximal around this pH
   4. Potassium is generally required with HCO3- because serum K+ with pH elevations
   5. Initial dose of HCO3- depends on desired change in serum HCO3- and weight
   6. HCO3- mmoles ~ weight (kg) x 0.5 x delta(HCO3-) given over 30-120 minutes
   7. HCO3- is usually best administered as 3 ampules (50mmole each) in D5W solution
4. Oral HCO3- replacement
   1. Bicarbonate tablets 325-650mg
   2. Bicitra (citrate tablets) are better tolerated with less bloating
   3. Usually replace 2-4gm per day of HCO3-
5. Problems with HCO3-
   1. Extracellular fluid overload (may use loop diuretics to reduce this)
   2. Sodium loading
   3. Stimulation of organic acid production and 6-phosphofructokinase activity
   4. Increased 6-PFK activity increases glycolysis and lactate production (generates ATP)
   5. Buffering of protons by HCO3- leads to CO2 release: HCO3- + H+ --> H20 + CO2
   6. Care must be taken to ventilate patient adequately to remove CO2
   7. If CO2 is not removed, intracellular acidosis may be worsened by HCO3- therapy

1. Ventilatory Failure
   1. Rapid increase in blood pCO2
   2. This is because metabolic production of CO2 is very rapid
2. Plasma HCO3- levels initially increase slightly
   1. This occurs in response to increased pCO2
   2. Magnituted of change is about 1mM of HCO3- per 10mm pCO2 rise
3. Chronically, HCO3- increases ~3mM for every 10mmHg rise in pCO2
4. Permissive Hypercapnia [2]
   1. Permissive hypercapnia with respiratory acidosis may be beneficial in critical patients
   2. There may be protective roles of carbon dioxide excess in these situations
   3. Therefore, correction of hypercapnia to "normal" range should be reconsidered

B. Chronic Obstructive Pulmonary Disease

1. Emphysema
2. Bronchitis
3. Bronchiolitis
4. Hypercarbia increases blood pressure (frank HTN) in COPD exacerbations [3]
   1. Elevates norepinephrine
   2. Elevates endothelin 1 levels
   3. Effects are independent of blood oxygen levels

C. Hypoventilation

1. Musculoskeletal
   1. Obesity (Pickwickian syndrome)
   2. Muscle Disease - eg. myasthenia gravis, Guillian Barre Syndrome
2. Depression of respiratory center
   1. Medications
   2. Cerebral disease - especially stroke

D. Delta Delta (DD): Mixed Disorders

1. Useful in high anion gap states
2. Calculate Anion Gap and Change in (anion gap) = True Gap - Normal Gap (~12)
3. Calculate Change in (Bicarbonate) = Normal HCO3- (~24) - True HCO3-
4. Calculate Change in (AG) ÷ Change in (HCO3- ) or "Delta-Delta" (DD)
5. Interpretation
   1. DD < 1 means combined normal and high anion gap acidosis
   2. DD > 2 means concurrent metabolic alkalosis
   3. DD ~ 1-2 means uncomplicated high anion gap acidosis
6. Bicarbonate therapy should only be used when a metabolic acidosis exists

References

1. Adrogue HJ and Madias NE. 1998. NEJM. 338(1):26
2. Laffey JG and Kavanagh BP. 1999. Lancet. 354(9186):1283
3. Fontana F, Bernardi P, Tartuferi L, et al. 2000. Am J Med. 109(8):621
4. Gavazzi C, Stacchiotti S, Cavalletti R, Lodi R. 2001. Lancet. 357(9265):1410 (Case Report)
5. Bernal W, Donaldson N, Wyncoll D, Wendon J. 2002. Lancet. 359(3306):558
6. Cukierman T, Gatt ME, Hiller N, Chajek-Shaul T. 2005. NEJM. 353(5):509 (Case Discussion)