Acid-Base

Question 1

Causes of gapped acidosis

Answer 1

MUDPALES:

Methanol

Uremia (kidney dysfunction)

Diabetic ketones

Para-aldehyde

Alcoholic ketones
• Often associated with volume depletion → sympathetic system → decreases insulin production

Lactic acidosis
Produced when anaerobic metabolism present
•	Types:
Type A: a problem with O2 delivery
o	Hypoxemia
o	Low BP
o	Severe anemia
o	Problems with O2 extraction 
Type B: problem with metabolism of lactate
o	Thiamine deficiency
o	Liver dysfunction 
o	Use of drugs (AZT, metformin)
D-lactic acidosis
o	Bowel syndromes; dis-coordination 

Ethylene glycol

Salicylates

Question 2

Causes of non-gapped acidosis

Answer 2

HARD-ASS:

Hyperalimentation (ex. TPN)
Addison's Disease (decreased aldosterone)
RTA
Diarrhea
Acetazolamide
Spironolactone (blocks aldosterone)
Saline infusion

Question 3

Types of RTA

Answer 3

General:
• From loss of HCO3- or lack of NH3 generation
• Kidneys can’t acidify urine
• Present in patients with normal kidney function

Type 1: distal RTA = due to failure of H+ secretion
o Hypo (usually) or hyperkalemic
o Urine pH > 6.0
o Serum HCO3- can be low

Type 2: proximal RTA = Due to failed HCO3- reabsorption
o Hypokalemic
o Urine pH < 5.0; >6.5 (variable)
o Serum HCO3- usually not that low
o Ex: interstial disease, Fanconi’s syndrome, low GFR

Type 3: Variable

Type 4: due to hypoaldosteronism
o Hyerkalemic
o Urine pH < 5.0
o Serum HCO3- can be low

Question 4

Utilize a stepwise approach to acid-base disorders.

Answer 4

• Look at pH → academic or alkalemic?
• Determine the primary disorder → metabolic or respiratory
• Apply compensation rules → is there a dual disorder?

Look at albumin and see if expected gap is <12
o Expected gap = 12- [4-albumin] x 2.5
• Calculated anion gap → compare to expected

o If higher than expected = MUDPALES

o If non-gapped metabolic acidosis → check urine anion gap:
• Negative urine gap = GI loss of HCO3-
• Positive urine gap = renal loss of HCO3- (an RTA)

Question 5

Recognize the factors that regulate kidney hydrogen excretion.

Answer 5

• Plasma pH
• Effective circulating volume
• Aldosterone
• Plasma K+ concentration

Question 6

Describe the underlying pathogenesis of metabolic alkalosis in the generation phase and the maintenance phase.

Answer 6

Generation Phase: inciting disturbance → increase in plasma HCO3-
Plasma H+ losses via:
• GI secretions
• Urine
• Movement of H+ into cells
Plasma HCO3- gain via giving HCO3- or a precursor metabolite for HCO3-
Volume contraction

Maintenance Phase: maintains the high HCO3- level:

Decreased GFR
• Leads to lower HCO3- filtration → higher serum HCO3- levels

Depletion of effective circulating volume
• Increased Angiotensin II levels → stimulates Na+/H+ exchangers and Na+/HCO3- cotransporters → increases H+ excretion in proximal tubule
• Increased Aldosterone levels → stimulated intercalated type A cells to increase H+ secretion = increases HCO3- reabsorption

Hypokalemia
• Causes K+ to shift from cells to plasma
• Exchanges with H+ (electroneutrality)
• Increased NH4+ production and excretion

Hypochloremia
• Secondary to hyperaldosteronism
• Low luminal Cl- → steeper concentration gradient for Cl- and H+ to be co-secreted
• Result: increased NH4+ excretion and increased HCO3- generation

Question 7

Explain the diagnostic approach to metabolic alkalosis.

Answer 7

What is the volume status (high or not?)

If low volume status → what do you expect urine sodium and chloride to be?
• Both high → renal salt wasting (diuretic like action)
• Urine Na+ high, Cl- low → active vomiting or addition of another anion
• Urine Na+ low, Cl- high → prior vomiting, prior diuretics

If not low volume status → what are the renin and aldosterone levels?
• If both low → Cushing’s, CAH, Liddle’s, Licorice
• If renin low, aldosterone high → primary hyperaldosteronism
• If both high → reninoma

Question 8

List the principles of therapy for metabolic alkalosis

Answer 8

Saline responsive (low volume status) = urine Cl < 15 mmol/L
o	Give saline to restore effective circulating volume and replace Cl- deficit 
o	Correct the ICF = correct the K+
•	Treat hypokalemia → shifts H+ back into ECF (decreases HCO3-); lowers NH4+ secretion and HCO3- generation 

Example cases:
•	GI losses of H+ (vomiting, gastric suction, villous adenoma, Cl- diarrhea
•	Kidney losses; diuretic therapy
•	Posthypercapnic
•	Severe K+ depletion 

Saline resistant (with primary hyperaldosteronism or edematous states with intravascular volume overload with high urine Cl-) = Urine Cl- > 20 mmol/L
o	Treat the underlying disorder 

Example cases:
•	Primary hyperaldosteronism
•	Cushing syndrome
•	Bartter syndrome
•	Steroids
•	Excess licorice intake
•	Hypokalemia