Methods to Interconvert pH and [H+]:The 0.1 pH Change Rule:

PHConversion Factor[H+] nmol/L

6.90 100 / 0.8 125

7.00 100 100

7.10 100 X 0.8 80

7.20 100 X 0.8 X 0.8 64

Henderson Equation:

24 X Pco2

[H+] = --------------

[HCO3-]

A patient has diabetic ketoacidosis and the following laboratory data: pH=7.10, Paco2= 30 mm Hg, [Hco3-] = 13 mmol/L, AG= 25 mEq/L, what do you conclude?

pH= 7.10, thus [H+] is 70-80 nmol/L

AG is 25, thus added anion concentration is 25-12= 13

24 X Pco2

[H+] = --------------

[HCO3-]

80'24 X 30/ 13

80'56

Tests Used in Acid-Base Diagnoses:

The anion gap in plasma

The osmolal gap in plasma

The urine net charge

The osmolal gap in urine

The urine pH

The urine Pco2

Anion Gap in Plasma:

The difference between measured major positive and negative charges

[Na+] -[Cl-] - [HCO3-]

The normal value is 12 ? 2 mEq/L

Expect close to 1:1 reciprocal change in anion gap and [HCO3-]

The anion gap changes with blood pH, but this change is small: 0.5 mEq/L for each 0.1 unit change in pH

An increased anion gap may be the only clue that metabolic acidosis is present in a mixed acid-base disorder

Charge Balance:

Cations (mEq/L) Anions

(mEq/L)

Na+140 CL- 103

K+4 HCO3- 25

Ca2+5 Proteins: albumin 16

Mg2+2 Organic 4

H+0.00004(40 nmol/L)Other inorganics: HPO4-SO43

Example: Lactic acid'H+ and Lactate:

Plasma

(mEq/L) [Na+] [Cl-] [HCO3-] Anion Gap

Normal 140 103 25 12

+10 mmol/L 140 103 15=25-1022=12+10

lactic acid

If the concentration of albumin in plasma is half of normal, what adjustments should be made when interpreting the plasma anion gap?

Include all the major positive charges in solution: K+: 4 mmol/L

The normal value for AG would be 16 instead of 12

albumin has a valence of 16 (16 mEq/L) and concentration of 4 g/dL and 0.5 mmol/L

The expected value for plasma AG should be reduced when albumin falls to 2 mg/dL

Patients with MM may have a protein in plasma that bears a net positive charge. What the impact of this protein on the value of the plasma anion gap?

IgG myeloma adds a lysine-rich or arginin-rich protein in plasma

This paraproteins carry a net positive charge

These unmeasured positive charges are associated with measured Cl-

The plasma AG falls, or may become negative if the concentration of paraproteins is high enough

The Osmolal Gap in plasma:

The osmolal gap is useful means of detecting the presence of uncharged molecules in plasma

Calculated osmolality 2[Na+] + [Glucose] (mmol/L) + [Urea] (mmol/L)

Osmolal gap is the difference between measured and calculated osmolality of plasma

Increased osmolal gap indicates the presence of an unmeasured compound that is not charged: most likely alcohol

Conversion Between mg/dL and mmol/L

ConstituentMolecular Weightmg/dL mmol/L

Glucose 180 90 5

Urea 60 30 5

BUN 28 14 5

The Urine Net Charge:

Measured NH4+ excreted with Cl-

Most hospital biochemistry laboratory do not routinely measure NH4+ in the urine

In normal urine the major cations are Na, K and NH4+ and the major anions are Cl- and HCO3-

NH4+ is usually excreted along with Cl-

Thus if are plentiful in urine, there will be a much greater quantity of Cl- than the measured cations Na+ plus K+

If the sum of Na+ and K+ is greater than Cl-, there will be no electrical room for NH4+ unless there are large amount of unmeasured anions in the urine

The Urine Net Charge:

[Cl-] > [Na+] + [K+] = high [NH4+ ]

[Cl-] < [Na+] + [K+] = either a low [NH4+ ] or excretion of

NH4+ with an anion other than Cl-

The Osmolal Gap in Urine:

Is used to detect NH4+

In chronic metabolic acidosis, it is expected to find more than 200 mmol of NH4+ excreted each day

This is excreted usually with Cl- and the urine net charge is very negative

If the urine net charge is not negative and the patient is acidotic, consider the osmolal gap

Osmolal Gap:

Measured osmolality minus calculated

Calculated osmolality= 2 ([Na+] + [K+]) + [Glucose] + [Urea] all in mmol/L

When osmolal gap is high, thus unmeasured anions exist in large amount

Those usually be ketoacids anions, drug metabolites or hippurate (toluene intoxication)

Example:

[Na+] 50

[K+] 50

[Cl-] 25

[NH4+] 200

Glucose 0

[Urea] 250

Osmo urine, measured850

Osmo urine, calculated450

Osmo gap 400

Expected Responses to Primary Acid-Base Disorders:

Disorder Response

Metabolic acidosisDrop the 7 and the decimal point from the pH

For every mmol/L fall in HCO3 from 25, Paco2 drops 1 mm Hg

Metabolic alkalosisDrop the 7 and the decimal point from the pH

For every mmol/L rise in HCO3 from 25, Paco2 should rise 0.7 mm Hg

Acute respiratory acidosisFor every twofold increase in Paco2, the plasma HCO3 should increase by 2.5 mmol/L from 25

Chronic respiratory acidosisFor every mm Hg increase in Paco2, the plasma HCO3 should increase by 0.3 mmol/L from 25

Acute respiratory alkalosisFor every mm Hg fall in Paco2, the plasma H+ should fall by 0.8 mmol/L from 40

Chronic respiratory alkalosisFor every mm Hg in Paco2, the plasma HCO3 should fall by 0.5 mmol/L from 25

Guidelines for the Diagnosis of Mixed Disorder:

Calculate the plasma AG, if it is very low or negative, there is probably an error in one of the electrolytes

Henderson equation, detect errors

If AG is elevated more than 5 mEq/L, the patient probably has metabolic acidosis

Compare the magnitude of the fall in plasma HCO3 with the increase in plasma anion gap: they should be similar

A rise in plasma AG that is less than the fall in plasma HCO3 suggest that a component of metabolic acidosis involves loss of NaHCO3 or renal tubular acidosis is present

A rise in plasma AG that is much greater than the fall in HCO3 suggest that there is a coexistent metabolic alkalosis (additional source of HCO3)

In metabolic acidosis or alkalosis, look for the expected change in PCO2

A 23-year-old woman with rheumatoid arthritis increased her dose of salicylates because of a flare-up. She then developed epigastric pain and vomited frequently for 2 days. She went to the local hospital, where the following blood results were obtained:

H+ 20 nmol/L

pH 7.70

Paco2 25

Anion gap17

Causes:

Metabolic alkalosis: vomiting

Respiratory alkalosis: salicylate intoxication

Metabolic acidosis with high AG: salicylic acid

A 50-year-old woman underwent intestinal bypass for morbid obesity. Because she was having 10-15 watery stools per day, she was treated with tincture of opium and found somnolent and somewhat hypotensive the next morning. Plasma values were:

Na+ 130 H+ 96 nmol/L

K+ 3.2 pH 7.02

Cl- 102 Paco2 40

Albumin 4 HCO3 10

Causes:

Metabolic acidosis: diarrhea

Lactic acidosis:hypotension

Ketoacidosis: starvation

Respiratory acidosis: suppression of ventilation

PlasmaNormal

PH7.40

HCO325

AG12

PCO240

PlasmaNormal

PH7.407.30

HCO32515

AG1212

PCO24030

Plasma NormalLoss of NaHCO3

(10 mmol/L)

PH 7.407.30

HCO3 2515

AG 1212

PCO2 4030

Plasma NormalLoss of NaHCO3

(10 mmol/L)

PH 7.407.307.13

HCO3 25155

AG 121222

PCO2 403015