Non-Anion Gap Metabolic Acidosis

Question 1

Non-anion gap metabolic acidosis is by definition _______ acidosis

How is this type of acidosis possible?

Answer 1

Hyperchloremic

—Loss of alkali (bicarb) can be from GI tract or kidneys

—Reciprocal changes in chloride and bicarb result in normal AG

—Pure non-AG acidosis: increase in Cl- = decrease in HCO3

Question 2

Calculation of urine anion gap

What does a negative vs. positive value indicate?

Answer 2

UAG = [Na + K] - [Cl]

When Cl > (Na + K), the anion gap is negative and indicates NH4 is appropriately secreted, suggesting non-renal cause for the acidosis

When UAG is positive, NH4 is low, suggesting a renal cause for the acidosis

Question 3

Clinical presentation of NAGMA

Answer 3

Metabolic acidosis: fatigue, loss of appetite, HA, increased HR; when severe may see rapid shallow breathing, confusion, and sleepiness

Hypokalemia: muscle weakness or paralysis, fatigue, constipation, myalgia

Pyelonephritis with obstructive uropathy: fever, vomiting, foul smelling urine

Question 4

Causes of hyperchloremic metabolic acidosis

Answer 4

Inadequate NH3 production (renal failure, hypoaldosteronism, PHA)

Defect in HCO3 reclamation (proximal RTA)

Defect in H+ secretion (distal RTA)

Extrarenal loss of base acid load (diarrhea, pancreatic fistula, ureteral diversions, NH4Cl/HCL, NaCl load

Excretion of organic anions (toluene ingestion, DKA) — these start as HAGMA but may become NAGMA d/t compensation

Question 5

Describe lab findings if NAGMA is d/t type I RTA [classic distal RTA]

Answer 5

Hypokalemia
Positive UAG
pH > 5.5

Question 6

Describe lab findings if NAGMA is d/t type II RTA [proximal RTA, fanconi syndrome]

Answer 6

Glycosuria
Generalized aminoaciduria
Phosphaturia
Bicarbonaturia

Question 7

Describe lab findings if NAGMA is d/t type IV RTA [distal RTA]

Answer 7

Hyperkalemia

Positive UAG

Question 8

Describe classic distal RTA (RTA type I)

Answer 8

Inability of distal tubule to acidify the urine; inability to secrete H+ leads to decreased NH4 in the tubule —> high urine pH (>5.5) and positive UAG; hypokalemia d/t augmented K+ secretion in lieu of H+ in exhange for Na reabsorption

Question 9

Possible etiologies for RTA type I

Answer 9

Familial disorders: defective HCO3/Cl exchanger and H-ATPase

Associated with autoimmune disorders: SLE, Sjogren syndrome, cryoglobulinemia

Drugs: Lithium, toluene, amphotericin

Question 10

Complications in RTA type I

Answer 10

Pts have hypocitraturia and hypercalciuria so they are prone to nephrolithiasis, nephrocalcinosis, and bone disease

Potential for calcium oxalate stones

Children may have rickets; adults may have osteomalacia or osteoporosis

Question 11

Changes in potassium associated with hypoaldosteronism type IV RTA

Answer 11

Hyperkalemia and metabolic acidosis

[hyperkalemia is mild because of changes in aldosterone; decreased ammoniagenesis is d/t the hyperkalemia]

Question 12

Is the urine pH increase, decreased, or normal in RTA type IV?

Answer 12

Normal

Hypoaldosterone —> low Na+ with normal function of proton pump which maintains pH of urine

Question 13

What might make RTA type IV worse?

Answer 13

Any drug that affects RAAS: ACE inhibitors, ARBs, and NSAIDs

Also made worse by increased potassium intake and potassium sparing diuretics

Question 14

RTA type IV is usually a presumptive diagnosis because it must be proven by low _____ and _____ levels

Answer 14

Renin; aldosterone

Question 15

What serum lab might make you think of RTA type IV?

Answer 15

Potassium — if it is slightly elevated

Question 16

Causes of hypoaldosterone

Answer 16

Hyporeninemic hypoaldosteronism: type IV RTA

Drugs: ACE inhibitors, ARBs, heparin

CKD and DM: potentially low renin state leads to hypoaldosteronism

Question 17

Describe proximal RTA (Type II) and how it is diagnosed

Answer 17

Inability to reclaim filtered HCO3 in PT

When serum HCO3 is less than 15 mmol/L, urine pH < 5.5

When serum HCO3 is near normal (24 mmol/L), there is HCO3 spillage into urine and pH > 6.5

Diagnosis is made by delivering HCO3 and measuring its fractional excretion (UFE HCO3 > 15% with bicarb challenge)

Question 18

Causes of RTA type II

Answer 18

Carbonic anhydrase deficiency
Hormonal: hyperparathyroidism, Vit D def.
Hereditary fanconi syndrome
Lead poisoning
Wilson disease

Drugs: aminoglycosides, carbonic anhydrase inhibitors, topiramate, acetazolamide

Other causes: hereditary tubule disorders, NaHCO3 cotransport mutations, generalized PT dysfunction, cystinosis, glycogen storage disease, multiple myeloma, lysozymuria, sjogren, renal transplant, cobalt, mercury

Question 19

Describe lab findings with generalized tubular defect

Answer 19

Both H+ and K+ secretion are impaired

Elevated serum K+

Urine pH > 5.5

Associated with interstitial kidney disease: SLE, sickle cell anemia, obstructive uropathy

Question 20

Describe acid/base change with diarrhea

Answer 20

HCO3 loss in stool leads to acidosis and volume depletion

K+ is also lost in stool

Net effect is HYPOKALEMIA and HYPOBICARBEMIA

The hypokalemia causes increased renal production of NH4, providing urinary buffer that increases urine pH

Check for urine anion gap to differentiate from RTA

Question 21

Describe acid/base changes with chronic progressive kidney disease (normokalemic)

Answer 21

Decrease in ammoniagenesis is proportionate to loss of nephrons

GFR < 40 unable to secrete daily acid load

Less ammonia —> less anion secretion —> hyperchloremic acidosis

Question 22

Characteristics of chronic tubulointerstitial disease

Answer 22

Isosthenuria with polyuria
Moderate proteinuria
Very few cells
Type I, II, or IV RTA
Broad waxy casts
Small kidneys

Question 23

Causes of chronic tubulointerstitial disease

Answer 23

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Prostate (obstructive uropathy)
Analgesics (NSAIDS)
VU reflux
Lead (heavy metals)
Gout
Myeloma