Acid-Base disorders Flashcards
Normal pH
7.4
Normal anion gap
The normal anion gap is 12 ± 2 and is made of phosphates, sulfates, organic acids, and negatively charged plasma proteins
HAGMA: causes
- M: Methanol
- U: Uremia
- D: DKA or alcoholic ketoacidosis; drugs*
- P: Phosphate or paraldehyde
- I: Ischemia or isoniazid (rare) or iron toxicity (rare)
- L: Lactate
- E: Ethylene glycol
- S: Starvation or salicylates
HAGMA: Workup
- Thorough history and physical examination,
- Ketones
- Lactate
- Toxicology screen
- Salicylate level
Mechanisms of metabolic acidosis
- Increased acid generation: lactic acidosis, ketoacidosis
- Bicarbonate loss: diarrhea
- Renal tubular acidosis
Abnormally low bicarbonate
< 22
Blood gas data, respiratory compensation calculations, delta-delta calculations: when are they needed?
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)
Hypercholermic metabolic acidois is the same as
Normal anion gap acidosis
HAGMA clues
- Methanol: alcoholism, blindness, profound acidosis
- Uremia: BUN > 100, Cr > 5
- DKA: glucose > 500
- Alcoholic ketoacidois: + alcohol
- Metformin: Meds, recent contrast study
- Lactic acidosis: + lactate, hypotension
- Ethylne glycol: oxalate in urine
- Salciylates: Mixed acid-base + aspirin > 20
- Solvents: spray paint on face
In this group, the increased anion is chloride (Cl−); therefore, the anion gap does not change
NAGMA
Metabolic Acidosis with Normal Anion Gap
NAGMA: causes
- D: Diarrhea
- U: Ureteral diversion
- R: Renal tubular acidosis
- H: Hyperalimentation
- A: Addison disease, acetazolamide, ammonium chloride
- M: Miscellaneous (chloridorrhea, amphotericin B, toluene,* others)
Urine anion gap: when is it needed?
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
Renal response to acidosis
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.
Type 1 and Type 4 RTA: NH4+ abnormality
In type 1 or type 4 RTA, NH4+ excretion does not occur, and urine chloride is low.
Urine anion gap: formula and significance
(Na +K) - Cl
- Normally: < 0
- If > 0, RTA 1 or 4 likely
Metabolic Acidosis with Decreased Anion Gap: causes
May be caused by hypoalbuminemia, multiple myeloma, ingestion of bromide
The acid-base disorders in these diseases are of little clinical consequence
Delta-Delta
- Concept relevant to high anion gap metabolic acidosis.
- Theoretical utility: distinguishing (shock lactic acidosis and DKA) from obscure causes of high anion gap metabolic acidosis (HAGMA).
- Assumption: baseline serum AG is known or can be estimated.
- Delta AG == change in Anion gap
- Delta HCO3- = change in bicarb concentration.
- The delta AG/delta HCO3 ratio in a HAGMA (eg, shock-induced lactic acidosis or diabetic ketoacidosis) is usually between 1 and 1.6.
- 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.
Major unmeasured anion contributing to anion gap
albumin
High AG gap acidosis: commonest causes
- Lactic acidosis
- Ketoacidosis
Osmolar gap calculation
Measured - (2*Na + glucose/18 + BUN/2.8)
Winter’s formula
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
Metabolic alkalosis due to bicarb gain: examples
Administration of sodium bicarbonate, or medication formulations that include citrate or lactate
Metabolic alkalosis: mechanisms
- Loss of acid
- Gastric losses, such as vomiting or nasogastric suction
- Renal causes: diuretics), as well as administration of nonresorbable anions (e.g., IV penicillin or carbenicillin)
- Hypermineralocorticoid states
- Gain of bicarb (NaHCO3 administration, lactate or citrate containing dugs.
Contraction alkalosis: mechanism
- The kidney responds to volume depletion by becoming Na+avid
- Na+ is resorbed along with HCO3- because urine Cl− is low in volume depletion.
States favoring maint of alkalosis by kidney
- 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)
- Hypermineralocorticoid states: Mineralocorticoids stimulate renal hydrogen ion (H+) excretion; examples include hyperaldosteronism (Conn syndrome; Fig. 31-3) and Cushing disease
Metabolic acidosis in diarrhea: components
Combined HAGMA + NAGMA
Mechanims as follows:
- Hyperchloremic acidosis (NAGMA) due to loss of bicarbonate in stool;
- HAGMA due to lactic acidosis (due to hypovolemia);
- HAGMA due reduced renal function
- delta AG/delta HCO3 ratio is less than 1.
High δ/δ : causes
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.
Delta-delta: why do we use the ratio instead of the simple difference?
I.e why: delta AG/delta HCO3 and not (δAG - δHCO3)?
Don’t know
Acid base disorder common to sepsis and salicylate poisoning
Metabolic acidosis, Respiratory alkalosis
Mechanism of respiratory alkalosis in salicylate poisoning
Respiratory stimulation
Renal tubular acidosis: classification parameters
- Defect
- Serum K
- Ability to acidify urine ( to less than 5.5)
- Response to NaHCO3
RTA types
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.
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
Distal (Type 1) RTA
Type of acidosis, effect on K
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.
RTA 1: basic defect
Impaired H+ dumping in the distal nephron
Distal RTA (Type 1): potassium
Low
- 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.
- The defect in RTA 1 is a H+ secretion problem.
- 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.
RTA 1: causes
also known a Distal RTA: failure of H+ secretion in the distal nephron.
- Congenital autosomal dominant disorder (most common cause of type 1 RTA)
- Other genetic disorders (Marfan syndrome, Ehlers-Danlos syndrome)
- Autoimmune (SLE, RA, Sjögren syndrome)
- Amphotericin, lithium, and high doses of salicylates
- Urinary tract obstruction
- sickle cell anemia
RTA 1
Failure of H+ secretion in the distal nephron leading to hypokalemia and NAGMA.
RTA Type 2
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.
RTA 2: causes
- Defective resorption of other molecules, such as glucose and amino acids (as seen in Fanconi syndrome)
- carbonic anhydrase inhibitors, outdated tetracycline, lead and mercury toxicity
where there is also phosphaturia, glycosuria, aminoaciduria, uricosuria and tubular proteinuria.
Fanconi syndrome
RTA Type 4: error
Hyporeninemic hypoaldosteronism
RTA Type 4: is this primarily a tubular disorder?
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.
RTA Type 4: cardinal clinical feature
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.
RTA Type 2: treatment
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
Metabolic acidosis + hypokalemia: which RTA
Distal (Type 1)
failure of H+ secretion into lumen of nephron by the alpha intercalated cells in the distal nephron.
Metabolic acidosis + hyperkalemia: which RTA?
Hyperkalemic RTA (Type 4)
Diabetic nephropathy: how does it cause RTA 4?
- The driver of RTA 4 is hypoaldosteronism.
- Diabetic nephropathy leads to low renin.
- Which leads to low aldosterone.
Select causes of hypoaldosteronism
Reduced aldosterone production
- Hyporeninemic hypoaldosteronism
- Diabetic nephropathy
- NSAID
- ACEI
- Primary adrenal insufficiency (eg: Addison’s)
- Genetic disorders
Aldosterone resistance:
- Spironolactone and similar drugs
- K+ sparing diuretics
- Trimethoprim
Type 1 RTA: associated clinical features
Calcium oxalate stones
Formed due to alkaline urine
Hypercalciuria: rickets, osteomalacia
Distal RTA (Type 1): Dx and Rx
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
Respiratory processes (both acidosis and alkalosis) have an acute compensatory phase, in which _ _ help maintain pH; and a chronic phase, in which the _ participates
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
How long does it take for plasma buffer and kidneys to respond to acid-base challenges?
- Plasma buffers: minutes to hours
- 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
Acute and chronic respiratory acidosis: HCO3 compensation
- Acute: 1 meq/L for every 10 mmHg
- 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
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 _
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:
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
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].
Why are there acute and chronic compensation variants of respiratory acid-base disorders but not of metabolic disorders?
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.
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?
By solving the linera equation
Let X = the value of each 12.84 monthly installment.
- 84 - (0.25)(119.84) = 7X
- 84 - 29.96 = 7X
- 88 = 7X
6 89.88 / 7 = X 12.84 = X Therefore, each monthly installment is $12.84.
