Week 3: clinical disorders of acid base balance

Question 1

Review primary disorders of metabolic/respiratory acidosis and metabolic/respiratory alkalosis.

Answer 1

Metabolic acidosis: decreased HCO3-, decreased pCO2 compensation
Metabolic alkalosis: increased HCO3-, increased pCO2 compensation.
Respiratory acidosis: increased pCO2, increased HCO3- compensation
Respiratory alkalosis: decreased pCO2, decreased HCO3- compensation

Question 2

What are three ways of calculated compensation for metabolic acidosis?

Answer 2

1. Each 1 mEq/L decrease in HCO3- should have 1.2 mmHg decrease of pCO2
2. pCO2=1.5xHCO3- + 8 (+/-)2
3. pCO2= last 2 digits of pH

Question 3

How can you tell if its a mixed metabolic and respiratory disorder?

Answer 3

-If there is deviation from the expected result (the expected magnitude and direction of compensation of the primary disturbance), then it is a mixed disorder.

Question 4

What are 4 general causes of metabolic acidosis? What falls under each general cause.

Answer 4

1. Ingestion of acid
   - ethylene glycol
   - metahnol
   - toluene
   - salicylic acid
2. Endogenous generation of acid
   - lactic acidosis
   - ketoacidosis: DM or EtOH
   - Rhabdomyolysis
3. Defective acid excretion
   - Renal failure
   - distal renal tubular acidosis (problem in handling of acid load, NH4+ genesis)
4. Loss of alkali
   - diarrhea
   - proximal RTA (problem in PT handling HCO3- reabsorption)

Question 5

How do you calculate serum anion gap? Why is this significant?

Answer 5

• Serum anion gap is a conceptual gap since not all anions and cations are measured
• Serum anion gap=unmeasured anions-unmeasured cations = Na-(Cl+HCO3)
• normal 8-12 (due to albumin)
• unmeasured anions: albumin, PO4, SO4, lactate, pyruvate
• unmeasured cations: K, Ca, Mg, immunoglobulins*

Question 6

What is the ddx for high anion gap metabolic acidosis?

Answer 6

MUDPILES
-methanol
-uremia
-diabetic ketoacidosis
-paraldehyde
-iron and isoniazid
-lactic acidosis
-ethylene glycol and ethanol
-salicylates
ALSO
-rhabdomyolysis and toluene abuse

Question 7

What causes anion-gap acidosis?

Answer 7

• For example: in lactic acidosis, lactic acid generates H+ and Lactate-
• the H+ is buffered by bicarbonate, and lactate is the unmeasured anion produced

Question 8

How do you calculate serum osmolal gap? What is it used for?

Answer 8

Osmolal gap=measured Sosm-Calculated Sosm

• Calculated Sosm: 2Na+glucose/18+ BUN/2.8
• normal is <10 mOsm/kg
• use the serum osmolal gap when you suspect toxic ingestion

Question 9

What are common ddx in serum osmolal gap acidosis?

Answer 9

• Ethanol, ethylene glycol, propylene glycol, methanol toxic ingestion causes high osmolal gap and + anion gap
• isopropanol causes high osmolal gap and negative anion gap
• salicylates cause normal osmolal gap and +anion gap acidosis

Question 10

What are main causes of non gap metabolic acidosis?

Answer 10

-RTA and diarrhea

Question 11

What are types of renal tubular acidosis?

Answer 11

• Proximal Type 2: defective handling of HCO3- reabsorption. Has decreased serum K+, urine pH>5.5, high urine NH4+ and HCO3-.
• Distal Type I “Classic distal”: Decreased H+ secretion. low serum K+, urine pH>5.5, low urine NH4+ and HCO3-
• Distal Type 4 Hyporeninemic hypoaldosteronism: lack of response to aldosterone or hypoaldosteronism. inadequate ammoniogenesis. high serum K+, Urine pH<5.5, low urine NH4+ and HCO3-

Question 12

What are causes of RTA?

Answer 12

1. Proximal Type 2
   - most common: multiple myeloma and heavy metals
   - Cystinosis
   - Wilson’s
   - ifosfamide
2. Distal Type 1
   - most common: autoimmune-SLE and Sjogrens
   - cirrhosis
   - medullary sponge
   - amphotericin
3. Distal Type 4
   - DM
   - sickle cell
   - obstructive nephropathy
   - HIV

Question 13

What are the general causes of metabolic alkalosis? Also specific causes?

Answer 13

1. Ingestion of alkali
   - antacids
   - citrated blood (from blood transfusion, citrate is added to blood to prevent clotting)
2. Loss of Acid-GI loss
   - vomiting
   - NG suction
3. Loss of Acid- Renal loss
   - diuretics “contraction alkalosis”
   - Bartter/Gitelman
   - hyperaldosteronism
4. Cellular Shift
   - decrease in K+: K+ exits cell and H+ enters cell

Question 14

What is the ddx of hyperaldosteronism?

Answer 14

Hypokalemia, metabolic alkalosis and HTN

1. High aldosterone high renin
   - Renal artery stenosis (decreased perfusion–>increase renin)
   - reninoma-rare
2. High aldosterone low renin
   - Primary hyperaldosteronism
   - glucocorticoid-remediable aldosteronism (GRA)
3. Low aldosterone
   - Cushings
   - Liddles
   - Licorice
   - Syndrome of apparent mineralocorticoid excess (AME)

Question 15

What is required in the maintenance of alkalosis?

Answer 15

• impairment of renal excretion of excess bicarbonate even if origin of alkalosis was not renal
  1. effective circulating volume depletion:
• increased PT HCO3 reabsorption
• increased distal Na reabsorption
  2. Renal failure

Question 16

Describe the pathogenesis of contraction alkalosis.

Answer 16

Loss of Cl- and water in excess of HCO3-

• There is failure of renal HCO3- excretion due to:
  a. PT tubule Na+ reabsorption with HCO3-
  b. secondary hyperaldosteronism with distal tubule H+ secretion

Question 17

If the diagnosis is not obvious from history, may have cryptogenic metabolic alkalosis. How do you diagnose based on volume status and urine Cl-?

Answer 17

1. Hyperaldosteronism
   - increased volume status, Urine Cl->40 mEq/L
   - high Cl- in urine because of aldosterone escape, excretion of Na and Cl in urine. Pressure natriuresis.
2. Surreptitious vomiting, Urine Cl40 due to Cl- loss from diuretic

Question 18

In the treatment of metabolic alkalosis, which conditions are saline-response and which are saline-resistant?

Answer 18

Saline responsive
-vomiting/NG suction
-diuretics
-Bartter/Gitelman
Saline-resistant
-edematous states
-hyperaldosteronism
-renal failure