Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (54 page)

•
UAG → failure of kidneys to secrete NH
₄
+ Ddx: distal or hypoaldo RTA, early renal failure

nb, plasma K usually ↓ in distal and ↑ in hypoaldo RTA

• UAG evaluation assumes Pt volume replete (U
_Na
>25) & no AG met. acid. (which causes
UAG due to excretion of organic anions)

Renal tubular acidoses (RTAs)
(
JASN
2002;13:2160;
Int J Clin Pract
2011;65:350)

•
Proximal
(Type II): ↓ proximal reabsorption of HCO
₃

1° (Fanconi’s syndrome = ↓ proximal reabsorption of HCO
₃
, PO
₄
, glc, amino acids), paraprotein (multiple myeloma, amyloidosis), meds (acetazolamide, heavy metals, ifosfamide), renal transplant, ↓ Vit D, NRTIs

•
Distal
(Type I): defective distal H+ secretion

1°, autoimmune (Sjögren’s, RA), nephrocalcinosis, meds (ampho, Li, ifosfamide); normally a/w ↓ K; if with ↑ K → sickle cell, obstruction, SLE, renal transplant

•
Hypoaldo
(Type IV): ↑ K → ↓ NH
₃
synthesis/delivery → ↓ urine acid carrying capacity

↓ renin: diabetic nephropathy, NSAIDs, chronic interstitial nephritis, HIV

normal renin, ↓ aldo synthesis: 1° adrenal disorders, ACEI, ARBs, heparin

↓ response to aldosterone

  meds: K-sparing diuretics, TMP-SMX, pentamidine, calcineurin inhibitors

  tubulointerstitial disease: sickle cell, SLE, amyloid, diabetes

• Combined (Type III): rarely discussed or clinically relevant, also called juvenile RTA, has distal & proximal features, can be due to carbonic anhydrase II deficiency

Figure 4-2 Approach to metabolic acidosis

Treatment of severe metabolic acidoses (pH <7.2)
(
Nat Rev Nephol
2012;8:589)

• DKA: insulin & IVF; AKA: dextrose, IVF, replete K, Mg, PO
₄
as needed

• Lactic acidosis: treat underlying condition, avoid vasoconstrictors

• Renal failure: hemodialysis

• Methanol & ethylene glycol: early fomepizole, vit. B
₆
(ethylene glycol), folate (methanol), hemodialysis (esp. if late presentation) (
NEJM
2009;360:2216)

• Alkali therapy: NaHCO
₃
(eg, three 50-mmol amps in 1 L D
₅
W) to get serum HCO
₃
>8 and pH >7.2 (estimate mmol of HCO
₃
needed as 8-[HCO
₃
]
_serum
× wt × 0.5) side effects: ↑ volume, ↑ Na, ↓ ICa, ↑ P
_a
CO
₂
(& ∴ intracellular acidosis), overshoot

No proven benefit in lactic acidosis or DKA (
Annals
1986;105:836 & 1990;112:492)

• THAM (proton acceptor) in Pts w/ ↑ P
_a
CO
₂

METABOLIC ALKALOSIS

Pathophysiology

• Saline-responsive etiologies require
initiating event
and
maintenance phase
•
Initiating event:
gain of HCO
₃
or loss of acid

loss of H
⁺
from GI tract or kidneys

exogenous alkali
: iatrogenic HCO
₃
administration, milk alkali syndrome

contraction alkalosis
: diuresis → excretion of HCO
₃
-poor fluid → extracellular fluid “contracts” around fixed amount of HCO
₃
→ ↑ HCO
₃
concentration

posthypercapnia
: respiratory acidosis → renal compensation with HCO
₃
retention; rapid correction of respiratory disorder (eg, with intubation) → transient excess HCO
₃

•
Maintenance phase

volume depletion
→ ↑ proximal reabsorption of NaHCO
₃
and ↑ aldosterone (see next)

hyperaldosteronism
(either 1° or 2°) → distal Na reabsorption in exchange for K+ and H+ excretion (and consequent HCO
₃
retention)

hypokalemia
→ transcellular K+/H+ exchange; intracellular acidosis in renal proximal tubular cells promotes bicarbonate reabsorption and ammoniagenesis

Workup

• Check
volume status
and
U
_Cl

U
_Cl
<20 mEq/L → saline-responsive

U
_Cl
>20 mEq/L → saline-resistant (unless currently receiving diuretics)

(U
_Na
unreliable determinant of volume status as alkalemia → ↑ HCO
₃
excretion → ↑ Na excretion; negatively charged HCO
₃
“drags” Na+ along)

If U
_Cl
>20 and volume replete, ✓
blood pressure

Figure 4-3 
Approach to metabolic alkalosis

Treatment of severe metabolic alkalosis (pH >7.6)

• If volume depletion: d/c diuretics and correct volume deficit with isotonic saline If cardiopulmonary disease precludes hydration, can use KCl, acetazolamide, HCl • If NGT drainage that cannot be stopped: PPI • Hyperaldosteronism: treat underlying condition

RESPIRATORY ACIDOSIS

Etiologies

•
CNS depression
: sedatives, CNS trauma, O
₂
in chronic hypercapnia (↓ hypoxemic drive), central sleep apnea

•
Neuromuscular disorders
: myasthenia gravis, Guillain-Barré, poliomyelitis, ALS, muscular dystrophy, severe hypophosphatemia, high spinal cord injury, drugs (paralytics)

•
Upper airway abnormalities
: acute airway obstruction, laryngospasm, obstructive sleep apnea, esophageal intubation

•
Lower airway abnormalities
: asthma, COPD