Acid-Base disorders

Question 1

Normal pH

Answer 1

7.4

Question 2

Normal anion gap

Answer 2

The normal anion gap is 12 ± 2 and is made of phosphates, sulfates, organic acids, and negatively charged plasma proteins

Question 3

HAGMA: causes

Answer 3

1. M: Methanol
2. U: Uremia
3. D: DKA or alcoholic ketoacidosis; drugs*
4. P: Phosphate or paraldehyde
5. I: Ischemia or isoniazid (rare) or iron toxicity (rare)
6. L: Lactate
7. E: Ethylene glycol
8. S: Starvation or salicylates

Question 4

HAGMA: Workup

Answer 4

1. Thorough history and physical examination,
2. Ketones
3. Lactate
4. Toxicology screen
5. Salicylate level

Question 5

Mechanisms of metabolic acidosis

Answer 5

1. Increased acid generation: lactic acidosis, ketoacidosis
2. Bicarbonate loss: diarrhea
3. Renal tubular acidosis

Question 6

Abnormally low bicarbonate

Answer 6

< 22

Question 7

Blood gas data, respiratory compensation calculations, delta-delta calculations: when are they needed?

Answer 7

Serum or plasma electrolytes, calculation of the anion gap, and a detailed history and physical examination are frequently sufficient to determine the cause of the metabolic acidosis and guide therapy.

However, in complicated patients, a definitive evaluation of metabolic acidosis usually requires the following (see ‘Evaluation’ above):

• Measurement of the arterial pH and pCO2 (see ‘Measurement of the arterial pH and pCO2’ above)
• Determining whether respiratory compensation is appropriate (see ‘Determination of whether respiratory compensation is appropriate’ above)
• Assessment of the serum anion gap to help identify the cause of acidosis (table 1) and calculation of the Δanion gap/ΔHCO3 ratio in patients who have an elevated anion gap (see ‘Assessment of the serum anion gap’ above)

Question 8

Hypercholermic metabolic acidois is the same as

Answer 8

Normal anion gap acidosis

Question 9

HAGMA clues

Answer 9

1. Methanol: alcoholism, blindness, profound acidosis
2. Uremia: BUN > 100, Cr > 5
3. DKA: glucose > 500
4. Alcoholic ketoacidois: + alcohol
5. Metformin: Meds, recent contrast study
6. Lactic acidosis: + lactate, hypotension
7. Ethylne glycol: oxalate in urine
8. Salciylates: Mixed acid-base + aspirin > 20
9. Solvents: spray paint on face

Question 10

In this group, the increased anion is chloride (Cl−); therefore, the anion gap does not change

Answer 10

NAGMA

Metabolic Acidosis with Normal Anion Gap

Question 11

NAGMA: causes

Answer 11

1. D: Diarrhea
2. U: Ureteral diversion
3. R: Renal tubular acidosis
4. H: Hyperalimentation
5. A: Addison disease, acetazolamide, ammonium chloride
6. M: Miscellaneous (chloridorrhea, amphotericin B, toluene,* others)

Question 12

Urine anion gap: when is it needed?

Answer 12

Calculation of the urine anion gap may be helpful in evaluating normal anion gap metabolic acidosis to differentiate renal tubular acidoses (RTAs) from other causes of normal anion gap metabolic acidosis

Question 13

Renal response to acidosis

Answer 13

Normal kidney response to acidosis is to excrete acid in the form of NH4+, which is balanced by increases in urine chloride, so urine chloride is a marker of urine acid excretion.

In type 1 or type 4 RTA, NH4+ excretion does not occur, and urine chloride is low.

Question 14

Type 1 and Type 4 RTA: NH4+ abnormality

Answer 14

In type 1 or type 4 RTA, NH4+ excretion does not occur, and urine chloride is low.

Question 15

Urine anion gap: formula and significance

Answer 15

(Na +K) - Cl

1. Normally: < 0
2. If > 0, RTA 1 or 4 likely

Question 16

Metabolic Acidosis with Decreased Anion Gap: causes

Answer 16

May be caused by hypoalbuminemia, multiple myeloma, ingestion of bromide

The acid-base disorders in these diseases are of little clinical consequence

Question 17

Delta-Delta

Answer 17

1. Concept relevant to high anion gap metabolic acidosis.
2. Theoretical utility: distinguishing (shock lactic acidosis and DKA) from obscure causes of high anion gap metabolic acidosis (HAGMA).
3. Assumption: baseline serum AG is known or can be estimated.
4. Delta AG == change in Anion gap
5. Delta HCO3- = change in bicarb concentration.
6. The delta AG/delta HCO3 ratio in a HAGMA (eg, shock-induced lactic acidosis or diabetic ketoacidosis) is usually between 1 and 1.6.
7. Early-stage chronic kidney disease often have preserved acid anion excretion but more severe tubular damage, which greatly reduces urine ammonium excretion. This leads to a hyperchloremic metabolic acidosis and a delta AG/delta HCO3 ratio below 1.

Question 18

Major unmeasured anion contributing to anion gap

Answer 18

albumin

Question 19

High AG gap acidosis: commonest causes

Answer 19

1. Lactic acidosis
2. Ketoacidosis

Question 20

Osmolar gap calculation

Answer 20

Measured - (2*Na + glucose/18 + BUN/2.8)

Question 21

Winter’s formula

Answer 21

The body compensates for metabolic acidosis by creating respiratory alkalosis. Pco2 may be predicted by the following equation (Winter’s formula):

PCO2_Predicted = 1.5*HCO3+8

If the Pco2_actual < PCO2_predicted, second disorder is respiratory alkalosis

If the Pco2_actual > PCO2_predicted, second disorder is respiratory acidosis

Question 22

Metabolic alkalosis due to bicarb gain: examples

Answer 22

Administration of sodium bicarbonate, or medication formulations that include citrate or lactate

Question 23

Metabolic alkalosis: mechanisms

Answer 23

1. Loss of acid
   
   1. Gastric losses, such as vomiting or nasogastric suction
   2. Renal causes: diuretics), as well as administration of nonresorbable anions (e.g., IV penicillin or carbenicillin)
   3. Hypermineralocorticoid states
2. Gain of bicarb (NaHCO3 administration, lactate or citrate containing dugs.

Question 24

Contraction alkalosis: mechanism

Answer 24

1. The kidney responds to volume depletion by becoming Na+avid
2. Na+ is resorbed along with HCO3- because urine Cl− is low in volume depletion.

Question 25

States favoring maint of alkalosis by kidney

Answer 25

1. Volume depletion: The kidney responds to volume depletion by becoming Na+avid, and Na+ is resorbed along with bicarb (i.e., , because urine Cl− is low in volume depletion)
2. Hypermineralocorticoid states: Mineralocorticoids stimulate renal hydrogen ion (H+) excretion; examples include hyperaldosteronism (Conn syndrome; Fig. 31-3) and Cushing disease

Question 26

Metabolic acidosis in diarrhea: components

Answer 26

Combined HAGMA + NAGMA

Mechanims as follows:

1. Hyperchloremic acidosis (NAGMA) due to loss of bicarbonate in stool;
2. HAGMA due to lactic acidosis (due to hypovolemia);
3. HAGMA due reduced renal function
4. delta AG/delta HCO3 ratio is less than 1.

Question 27

High δ/δ : causes

Answer 27

Vomiting, diuretic use

Delta/Delta is: (change in anion gap)/(change in HCO3)

A higher-than-expected value (ie, delta AG/delta HCO3 ratio above 1.6 with lactic acidosis) reflects a mixed acid-base disorder in which a high AG acidosis coexists with a process that increases HCO3.

The high bicarbonate concentration may be due to a preexisting or concurrent metabolic alkalosis, as with vomiting or diuretic use.

Question 28

Delta-delta: why do we use the ratio instead of the simple difference?

I.e why: delta AG/delta HCO3 and not (δAG - δHCO3)?

Answer 28

Don’t know

Question 30

Acid base disorder common to sepsis and salicylate poisoning

Answer 30

Metabolic acidosis, Respiratory alkalosis

Question 31

Mechanism of respiratory alkalosis in salicylate poisoning

Answer 31

Respiratory stimulation

Question 32

Renal tubular acidosis: classification parameters

Answer 32

1. Defect
2. Serum K
3. Ability to acidify urine ( to less than 5.5)
4. Response to NaHCO3

Question 33

RTA types

Answer 33

Distal (type 1), Proximal (type 2),

Hyperkalemic which is the same thing as hypoaldosteronism (type 4)

Obscure: Hyperkalemic RTA includes a disorder called voltage-dependent RTA, which is sometimes considered a subtype of distal RTA.

Question 34

Impaired H+ secretion in the distal nephron

Plasma bicarbonate concentration can fall below 10 meq/L if not treated.

Hypokalemia due to renal potassium wasting. Occasionally, the hypokalemia is sufficiently severe (ie, serum potassium below 2 meq/L) to produce muscle paralysis or respiratory arrest

Answer 34

Distal (Type 1) RTA

Question 35

Type of acidosis, effect on K

Answer 35

NAGMA, low K

Non-anion gap metabolic acidosis

Distal (type 1): impaired H+ secretion in the distal nephron. If severe, leads to inability to excrete the daily acid load (50 to 100 meq on a typical Western diet), resulting in H+ retention and a NAGMA.

HCO3 can fall below 10 meq/L if not treated

Distal RTA commonly causes hypokalemia due to renal potassium wasting. Occasionally, this is severe (ie, K < 2 meq/L) enough to cause muscle paralysis or respiratory arrest.

Question 36

RTA 1: basic defect

Answer 36

Impaired H+ dumping in the distal nephron

Question 37

Distal RTA (Type 1): potassium

Answer 37

Low

1. H+ excretion into the lumen of the distal tubule is accomplished by H-K-ATPase pumps that results in hydrogen ion secretion and potassium reabsorption.
2. The defect in RTA 1 is a H+ secretion problem.
3. Since H+ is not being secreted, K is not re-absorbed, as it normally is.

In other words, the intercalated cells’ apical H+/K+ antiporter is non-functional, resulting in proton retention and potassium excretion. Since calcium phosphate stones demonstrate a proclivity for deposition at higher pHs (alkaline), the substance of the kidney develops stones bilaterally; this does not occur in the other RTA types.

Question 38

RTA 1: causes

Answer 38

also known a Distal RTA: failure of H+ secretion in the distal nephron.

1. Congenital autosomal dominant disorder (most common cause of type 1 RTA)
2. Other genetic disorders (Marfan syndrome, Ehlers-Danlos syndrome)
3. Autoimmune (SLE, RA, Sjögren syndrome)
4. Amphotericin, lithium, and high doses of salicylates
5. Urinary tract obstruction
6. sickle cell anemia

Question 39

RTA 1

Answer 39

Failure of H+ secretion in the distal nephron leading to hypokalemia and NAGMA.

Question 40

RTA Type 2

Answer 40

Failure of the proximal nephron to reabsorb bicarbonate (bicarbonate wasting).

AKA: Proximal RTA (pRTA)

Serum K: relatively normal

The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the distal nephron can acidify the urine to a pH of less than 5.

Question 41

RTA 2: causes

Answer 41

1. Defective resorption of other molecules, such as glucose and amino acids (as seen in Fanconi syndrome)
2. carbonic anhydrase inhibitors, outdated tetracycline, lead and mercury toxicity

Question 42

where there is also phosphaturia, glycosuria, aminoaciduria, uricosuria and tubular proteinuria.

Answer 42

Fanconi syndrome

Question 43

RTA Type 4: error

Answer 43

Hyporeninemic hypoaldosteronism

Question 44

RTA Type 4: is this primarily a tubular disorder?

Answer 44

No

The primary problem is hypoaldosteronism (diabetic nephropathy causes low renin which leads to hypoaldosteronism) which leads to renal adaptation.

Type 4 RTA is not a tubular disorder at all nor does it have a clinical syndrome similar to the other types of RTA.

Included in the classification of renal tubular acidoses as it is associated with a mild NAGMA due to a physiological reduction in proximal tubular ammonium excretion which is caused by hypoaldosteronism, and results in a decrease in urinary acid buffering.

Cardinal feature is hyperkalemia, and measured urinary acidification is normal, hence it is often called hyperkalemic RTA.

Question 45

RTA Type 4: cardinal clinical feature

Answer 45

Hyperkalemia

RTA 4 is not primarily a renal disorder but consequent to hypoaldosteronism.

It was included in the classification of renal tubular acidoses as it is associated with a mild (normal anion gap) metabolic acidosis due to a physiological reduction in proximal tubular ammonium excretion (impaired ammoniagenesis), which is secondary to hypoaldosteronism, and results in a decrease in urine buffering capacity.

Question 46

RTA Type 2: treatment

Answer 46

Bicarbonate + phosphate

• The defect in proximal RTA (also known as Type 2) is bicarbonate wasting.
• in some patients, hypophosphatemia.

Treatment of acidemia is more difficult in proximal RTA than in distal RTA because raising the serum bicarbonate concentration increases the filtered bicarbonate load above the reduced reabsorptive capacity, resulting in a bicarbonate diuresis and enhanced urinary potassium losses.

•Patients with proximal RTA may require up to 10 to 15 meq/kg per day of alkali to exceed urinary bicarbonate losses.

Adding a thiazide diuretic may help

Question 47

Metabolic acidosis + hypokalemia: which RTA

Answer 47

Distal (Type 1)

failure of H+ secretion into lumen of nephron by the alpha intercalated cells in the distal nephron.

Question 48

Metabolic acidosis + hyperkalemia: which RTA?

Answer 48

Hyperkalemic RTA (Type 4)

Question 49

Diabetic nephropathy: how does it cause RTA 4?

Answer 49

1. The driver of RTA 4 is hypoaldosteronism.
2. Diabetic nephropathy leads to low renin.
3. Which leads to low aldosterone.

Question 50

Select causes of hypoaldosteronism

Answer 50

Reduced aldosterone production

1. Hyporeninemic hypoaldosteronism
   
   1. Diabetic nephropathy
   2. NSAID
2. ACEI
3. Primary adrenal insufficiency (eg: Addison’s)
4. Genetic disorders

Aldosterone resistance:

1. Spironolactone and similar drugs
2. K+ sparing diuretics
3. Trimethoprim

Question 51

Type 1 RTA: associated clinical features

Answer 51

Calcium oxalate stones

Formed due to alkaline urine

Hypercalciuria: rickets, osteomalacia

Question 52

Distal RTA (Type 1): Dx and Rx

Answer 52

Dx: Clinical + NH4Cl leades to worsening acidemia without urinary acidification

Rx: NaHCO3

• finding of urinary pH of greater than 5.3 in the face of a of serum bicarbonate of 20 mmol/l or less.
• short ammonium chloride test in which ammonium chloride capsules are used as the acid load

Question 54

Respiratory processes (both acidosis and alkalosis) have an acute compensatory phase, in which _ _ help maintain pH; and a chronic phase, in which the _ participates

Answer 54

Respiratory processes (both acidosis and alkalosis) have an acute compensatory phase, in which plasma buffers help maintain pH; and a chronic phase, in which the kidney participates

Question 55

How long does it take for plasma buffer and kidneys to respond to acid-base challenges?

Answer 55

1. Plasma buffers: minutes to hours
2. Kidneys: 3 to 5 days

Respiratory processes (both acidosis and alkalosis) have an acute compensatory phase (minutes to hours), in which plasma buffers help maintain pH; and a chronic phase(3 to 5 days), in which the kidney participates

Question 56

Acute and chronic respiratory acidosis: HCO3 compensation

Answer 56

1. Acute: 1 meq/L for every 10 mmHg
2. Chronic: 3-5 meq/L for every 10 mmHg

The compensatory response to acute respiratory acidosis increases the serum HCO3 concentration by about 1 meq/L for every 10 mmHg (1.3 kPa) elevation in the PCO2 .

If the elevated PCO2 persists, the serum HCO3 will continue to gradually increase and, after three to five days, the disorder is considered chronic. Studies mostly performed in hospitalized patients found that the serum HCO3 increases by 3.5 to 4 meq/L for every 10 mmHg elevation in PCO2 in patients with chronic respiratory acidosis . However, a later study in stable outpatients with chronic respiratory acidosis found a greater compensatory rise in serum HCO3 of about 5 meq/L per 10 mmHg (1.3 kPa) elevation in PCO

Question 57

Acute respiratory acidosis: For every 10 mm Hg increase in Pco2, pH decreases by _, and serum HCO3 increases by _

Chronic respiratory acidosis: For every 10 mm Hg increase in Pco2, pH decreases by _ and serum HCO3 increases by _ to _

Answer 57

Acute respiratory acidosis: For every 10 mm Hg increase in Pco2, pH decreases by 0.08, and serum HCO3 increases by 1

Chronic respiratory acidosis: For every 10 mm Hg increase in Pco2, pH decreases by 0.03, and serum HCO3 increases by 3 to 4.

Uptodate gives slightly different values:

Question 58

Acute respiratory alkalosis: For every 10 mm Hg decrease in Pco2, HCO3 decreases by 2.5

Chronic respiratory alkalosis: For every 10 mm Hg decrease in Pco2, HCO3 decreases by 5; maximum compensation of is 15

Answer 58

Acute respiratory alkalosis: For every 10 mm Hg decrease in Pco2, HCO3 decreases by 2.5

Chronic respiratory alkalosis: For every 10 mm Hg decrease in Pco2, HCO3 decreases by 5; maximum compensation of is 15

Uptodate: The compensatory response to acute respiratory alkalosis reduces the serum HCO3 concentration by 2 meq/L for every 10 mmHg (1.3 kPa) decline in the PCO2 (figure 3) [9,22]. If the reduced PCO2 persists for more than three to five days, then the disorder is considered chronic and the serum HCO3 concentration should fall by about 4 to 5 meq/L for every 10 mmHg (1.3 kPa) reduction in the PCO2 (figure 4) [9,25].

Question 59

Why are there acute and chronic compensation variants of respiratory acid-base disorders but not of metabolic disorders?

Answer 59

Renal compensation for respiratory problems takes 3 to 5 days.

There are four primary acid-base disorders: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. Because the renal compensation to respiratory disorders takes three to five days to complete, the primary respiratory disorders can be further divided into acute and chronic respiratory acidosis and respiratory alkalosis.

Question 60

Jean-Claude bought a $119.84 snow board. He paid 25% right away and paid the rest in seven equal monthly payments. How much was each monthly payment?

Answer 60

By solving the linera equation

Let X = the value of each 12.84 monthly installment.

119. 84 - (0.25)(119.84) = 7X
120. 84 - 29.96 = 7X
121. 88 = 7X

6 89.88 / 7 = X 12.84 = X Therefore, each monthly installment is $12.84.