9/9- Physiology of Metabolic Acidosis and Alkalosis I & II Flashcards
What is the difference between acidemia and acidosis? (or alkalosis and alkalemia)
Acidosis is the process while acidemia is the net result of all “processes” (the same pt can have acidosis and alkalosis at the same time)
- Acidemia is only clear when you known the pH in ABG
pH values for acidemia? alkalemia?
Acidemia: pH under 7.35
Alkalemia: pH > 7.45
What are some consequences of acidemia (in terms of O2 affinity and also systemic effects?)
- Hgb has increased O2 affinity
- Impairs bone structure and formation
- Decreased contractility of myocardium
- Decreased excitability of the brain: Metabolic Encephalopathy
- Decreased peripheral vascular resistance
- Increased K+ levels – cellular shifts
What are some consequences of alkalemia (in terms of O2 affinity and also systemic effects?)
- Hgb binds O2 avidly
- Decreased respiratory center causing hypoventilation
- Decreased ionized Ca++ results in weakness
- Decreased K+ by cellular shifts
Increased irritability:
- Myocardium: arrhythmias
- CNS: seizures
When do you apply the concept of anion gap?
Metabolic acidosis
What is the anion gap?
Na + unmeasured cations = Cl + HCO3 + unmeasured anions
Na - (Cl + HCO3) = UMA - UMC = AG
Ex)
- pH = 7.13
- Na = 140
- Cl = 105
- HCO3 = 5
What is AG?
AG = Na - (Cl + HCO3)
AG = 140 - (105 + 5) AG = 30 (high)
What is pathogenesis of metabolic acidosis?
(From acid accumulation or low bicarbonate)
Normal acid production:
- Under excretion of acid (kidney failure)
- HCO3 wasting (renal, GI)
Excess acid production:
- Endogenous acid (lactate, ketones)
- Exogenous acid (salicylates, methanol, ethylene glycol, proylene glycol, acetaminophen)
What are chemical hallmarks of high AG metabolic acidosis?
Pathogenesis?
Hallmarks:
- Acid accumulation
- Low bicarbonate
Pathogenesis:
Normal acid production:
- Kidney failure -> underexcretion of acid
Excess acid production:
- Endogenous acid (lactate, ketones)
- Exogenous acid (salicylates, methanol, ethylene glycol, proylene glycol, acetaminophen)
What are chemical hallmarks of normal AG metabolic acidosis?
Pathogenesis?
Hallmarks:
- Loss of bicarbonate as sodium bicarb
- Sodium reabsorbed as sodium “chloride”
- High Cl
- Low bicarb compensated by high chloride
Pathogenesis:
Normal acid production:
- HCO3 wasting (renal, GI)
Case)
Frustrated by this acid-base talk, a medical student flies to Cancun for a break
- drinks tap water
- diarrhea
- On exam: PR 120/mt, BP 80/40.
- pH 7.26, pCO2 24, HCO3- 10
- Na 133, K 2.1, Cl 112 and HCO3 11
Analyze
- pH is low; acidemia
- Low K (lost in diarrhea)
- AG = 133 - (11 + 112) = 10 (normal)
This is normal AG metabolic acidosis from diarrhea
Summary of causes of metabolic acidosis
How can you calculate osmolarity?
Osm = 2Na + BUN/2.8 + glucose/18
(Osm in mmol/L and glucose in mg/dL)
Stepwise approach for acid-base problems?
- Look at pH (acidemia or alkalemia?)
- Determine if metabolic (HCO3 problem) or respiratory (PCO2 problem)
- AG and calculate delta AG
- Delta bicarbonate
- Adequate compensation?
- Simple vs. mixed
What is the equation for delta anion gap?
What does delta AG reflect?
Pt AG - Normal AG
Normal AG ~ 10
Delta AG indicates how much bicarbonate fell
Delta AG is equal to what?
Delta bicarbonate
What is the equation for delta bicarbonate?
What does it reflect?
Delta bicarbonate = 24 - pt’s bicarbonate
In simple high anion gap metabolic acidosis: Delta AG = Delta bicarbonate
In other terms: Initial HCO3 = Delta AG + pts HCO3
What is the expected pCO2 in terms of compensation? (For metabolic acidosis)
Expected pCO2 = (HCO3 x 1.5) + 8 +/- 2
(Winter’s formula)
In metabolic acidosis, if HCO3 is 10, what is expected PCO2?
EpCO2 = (10 x 1.5) + 8 +/- 2
= 21 -25 mmHg
What do the possible PCO2 values tell you about compensation (for metabolic acidosis)?
- PCO2 under 20: lungs hyperventilating; also has primary* respiratory alkalosis
- PCO2 21-25: just right
- PCO2 > 25: lungs hypoventilating; also has primary* respiratory acidosis
Example)
- 25 yo man consumes ethylene glycol and takes overdose of “sleeping pills” ABG:
- pH under 7
- pCO2 = 25
- HCO3 = 5
- Na = 140
- Cl = 105
- HCO3 = 5
Analayze
- Acidosis
- AG = 140 - (105+5) = 30 (high)
- Delta AG = 30 - 10 = 20
- Delta bicarbonate = 24 - 5 = 19
- Delta mismatch? No
- expected PCO2 = (5 x 1.5) + 8 +/- 2 = 13.5 - 17.5; not compensated!
This is high AG metabolic acidosis + respiratory acidosis
Example)
- Na 136
- HCO3 8
- Cl 108
- pH 7.44
- PaCO2 12
Analyze
- Normal pH - AG = 136
- (8 + 108) = 20 (high)
- Delta AG = 20 - 10
- Delta bicarbonate = 24 - 8 = 16
- Delta mismatch? Yes
- Expected PCO2 = (8 x 1.5) + 8 +/- 2 = 18 -22
This is:
- High AG metabolic acidosis
- Non AG metabolic acidosis
- Respiratory alkalosis
Could be due to: ARF + diarrhea + sepsis
T/F: A secondary response can bring the pH back to normal.
False!
Under NO circumstances, can a secondary response bring the pH back to normal. If the patient is normal, either:
- Pt is normal - Mixed disorder
What can cause lactic acidosis?
Type A: poor tissue perfusion
- Shock/circulatory failure
- Mitochondrial enzyme defect
Type B: adequate perfusion
- Malignancies
- Liver/renal failure
- Seizures
- Drugs
What is therapy for lactic acidosis?
- Treat underlying condition: restore perfusion
- Bicarb therapy: if pH is under 7.1
- Enough bicarbonate to increase pH to 7.2: lactate is “potential” bicarbonate once underlying condition is treated (risk of overshoot alkalosis)
Fun fact: in mild to moderate metabolic acidosis (7.1ish- 7.35), you expect the last 2 digits of your pH to be roughly equal to your pCO2 if it is compensated (not confirmative, but rough idea)
Ex)
- pH = 7.26
- pCO2 = 24
Compensated metabolic acidosis
What can cause ketoacidosis (broadly)?
- Diabetes mellitus
- Alcoholism
Pathogenesis of DM ketoacidosis?
- What is seen on dipstick?
- Treatment?
- Insulin deficiency AND any stress like infection, MI etc
- Dipstick picks up ONLY acetoacetate (not beta- OH-B)
- Bicarbonate used only with severe acidemia
- Ketones are “potential” bicarbonate
Pathogenesis of alcoholic ketoacidosis?
- What is seen on dipstick?
- Treatment?
- Predominantly beta-OH-B: not strongly (+) on dipstick
- Hypoglycemia, insulin low
- Treatment: volume replacement with saline and glucose.
Pathogenesis of ethylene glycol causing metabolic acidosis?
- Diagnosis?
- Treatment?
- Metabolized to oxalic acid, glycolic acid, lactic acid, and other acids
Gaps to remember:
- EG (before metabolism) causes “osmolar” gap
- Metabolites cause “anion” gap with acidosis
Diagnosis:
- Wood’s lamp of urine detects fluorescence that was added to anti-freeze (in which ethylene glycol is used)
Treatment:
- Fluids, thiamine, etc.
- Fomepizole or ethanol (alcohol dehydrogenase)
- Dialysis
What is seen in the pH, serum bicarb, and PCO2 with metabolic alkalosis?
- Increased arterial pH (pH > 7.45)
- High serum bicarbonate
- High PCO2 due to compensation
Recall: What are the consequences of alkalemia (systemically)?
- Hgb binds O2 avidly -> less O2 released to tissues
- Decreased respiratory center -> hypoventilation
Increased irritability:
- Myocardium: arrhythmias
- CNS: seizures
Also:
- Decreased ionized Ca++ -> weakness
- Decreased K+ by cellular shifts
What ion transport is occurring in Type A Intercalated Cells?
Volume contraction -> Aldosterone -> more H-ATPase action (excreting H from cell into tubular lumen)
K depletion -> increased NH3, which combines with H in tubular lumen -> NH4 excreted in urine
K depletion -> increased H-K-ATPase, getting K into the cell and H into tubular lumen
What are causes of metabolic alkalosis?
- Exogenous bicarbonate load: alkali therapy
- Loss of acid: vomiting (HCl loss), NG suction, etc.
- Decreased ECF volume/normal BP (sec hyperaldosterone)
—- Renal: diuretics/Bartter’s and Gitelman syndrome
- ECF expansion/hypertension
—- Mineralocorticoid excess (renal artery stenosis/primary aldosterone excess/adrenal enzyme defects/Cushing’s, etc.)
—- Low mineralocorticoid: Liddle’s syndrome
(Diuretics: alkali-free fluid lost in urine: concentration of bicarbonate increases)
Maintenance phase of alkalosis involves what?
- Persistent hyperaldosterone state/continued acid loss or alkali therapy
- Chloride depletion:
—- H loss in Type A intercalated cells
—- Alkali retention in Type B cells
How does chloride deficiency and H secretion (bicarb retention) affect Type A intercalated cells?
- Less H-ATPase function (excreting Cl into tubular lumen instead??)
How does chloride deficiency and H secretion (bicarb retention) affect Type B intercalated cells?
- HCO3-Cl exchange (main drive is Cl concentration gradient) sending Cl into cell and bicarb into tubular lumen
Treatment of metabolic alkalosis?
If volume contracted: “Chloride-sensitive”
- Replenish volume with normal saline
If volume overloaded and ECF expanded
- Treat primary disorder that resulted in high renin and aldosterone state
- “Chloride insensitive”
- Replace K+
