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NEPHROLOGY

ACID-BASE DISTURBANCES

GENERAL

Definitions

•  Acidemia → pH <7.36, alkalemia → pH >7.44

•  Acidosis → process that increases [H+]; alkalosis → process that decreases [H+]

•  Primary disorders: metabolic acidosis or alkalosis, respiratory acidosis or alkalosis

•  Compensation

respiratory: hyper- or hypoventilation alters PaCO2 to counteract 1° metabolic process renal: excretion/retention of H+/HCO3 to counteract 1° respiratory process respiratory compensation occurs in minutes; renal compensation takes hours to days compensation never fully corrects pH; if pH normal, consider mixed disorder

Workup

•  Determine primary disorder: ✓ pH, PaCO2, HCO3

• Determine if degree of compensation is appropriate

Mixed disorders (more than one primary disorder at the same time)

•  If compensation less or greater than predicted, may be 2 disorders:

PaCO2 too low → concomitant 1° resp. alk.

PaCO2 too high → concomitant 1° resp. acid.

HCO3 too low → concomitant 1° met. acid.

HCO3 too high → concomitant 1° met. alk.

•  Normal pH but …

↑ PaCO2 + ↑ HCO3 → resp. acid. + met. alk.

↓ PaCO2 + ↓ HCO3 → resp. alk. + met. acid.

normal PaCO2 & HCO3but ↑ AG → AG met. acid. + met. alk.

normal PaCO2, HCO3, & AG → no disturbance or non-AG met. acid. + met. alk.

•  Cannot have resp. acid. (hypoventilation) and resp. alk. (hyperventilation) simultaneously

Figure 4-1 Acid-base nomogram

• ABG vs. VBG: concordant for pH (~0.04), HCO3 (~2 mEq) but not PaCO2 (~8±17 mmHg) VBG can be used to screen for hypercarbia w/ PaCO2 cutoff ≥45 mmHg (100% Se), but does not accurately assess degree of hypercarbia (Am J Emerg Med 2012;30:896)

METABOLIC ACIDOSIS

Initial workup (Nat Rev Nephol 2010;6:274)

•  ✓ anion gap (AG) = Na+ – (Cl- + HCO3-) = unmeasured anions - unmeasured cations

if ↑ glc, use measured not corrected Na

expected AG is [albumin] × 2.5 (ie, 10 if albumin is 4 g/dL, 7.5 if albumin is 3 g/dL)

↑ AG → ↑ unmeasured anions such as organic acids, phosphates, sulfates

↓ AG → ↓ alb or ↑ unmeasured cations (Ca, Mg, K, Li, bromine, immunoglobulin)

•  If ↑ AG, ✓ delta-delta (ΔΔ = DAG/DHCO3) to assess if there is an additional metabolic acid-base disturbance; DAG = (calculated AG – expected AG), DHCO3 = (24 – HCO3)

ΔΔ = 1–2 → pure AG metabolic acidosis

ΔΔ < 1 → AG metabolic acidosis and simultaneous non-AG acidosis

ΔΔ > 2 → AG metabolic acidosis and simultaneous metabolic alkalosis

Workup for AG metabolic acidosis

•  ✓ for ketonuria (dipstick acetoacetate) or plasma b-hydroxybutyrate (bOHB) nb, urine acetoacetate often not present in early ketoacidosis due to shunting to bOHB; ∴ acetoacetate may later turn , but does not signify worsening disease

•  If  ketones, ✓ renal functionlactatetoxin screen, and osmolal gap

•  Osmolal gap (OG) = measured osmoles – calculated osmoles

calculated osmoles = (2 × Na) + (glucose / 18) + (BUN / 2.8) (can + [EtOH/4.6] if have EtOH level and want to test if other ingestions)

OG >10 → suggests ingestion (see below)

for methanol/ethylene glycol: early on, OG precedes AG; later OG may be nl with  AG

Workup for non-AG metabolic acidosis (CJASN 2012;7:671)

•  Evaluate history for causes (see above)

•  ✓ urine anion gap (UAG) = (UNa + UK) – UCl

UAG = unmeasured anions – unmeasured cations; as NH4+ is primary unmeasured cation, UAG is indirect assay for renal NH4+ excretion (NEJM 1988;318:594)

•   UAG → ↑ renal NH4+ excretion → appropriate renal response to acidemia Ddx: GI causes, proximal RTA, ingestions or dilutional

•   UAG → failure of kidneys to secrete NH4+ Ddx: distal or hypoaldo RTA, early renal failure

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

•  UAG evaluation assumes Pt volume replete (UNa >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 HCO3

1° (Fanconi’s syndrome = ↓ proximal reabsorption of HCO3, PO4, 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 → ↓ NH3 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, PO4 as needed

•  Lactic acidosis: treat underlying condition, avoid vasoconstrictors

•  Renal failure: hemodialysis

•  Methanol & ethylene glycol: early fomepizole, vit. B6 (ethylene glycol), folate (methanol), hemodialysis (esp. if late presentation) (NEJM 2009;360:2216)

•  Alkali therapy: NaHCO3 (eg, three 50-mmol amps in 1 L D5W) to get serum HCO3 >8 and pH >7.2 (estimate mmol of HCO3 needed as 8-[HCO3]serum × wt × 0.5) side effects: ↑ volume, ↑ Na, ↓ ICa, ↑ PaCO2 (& ∴ intracellular acidosis), overshoot

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

•  THAM (proton acceptor) in Pts w/ ↑ PaCO2

METABOLIC ALKALOSIS

Pathophysiology

•  Saline-responsive etiologies require initiating event and maintenance phase

•  Initiating event: gain of HCO3 or loss of acid

loss of H+ from GI tract or kidneys

exogenous alkali: iatrogenic HCO3 administration, milk alkali syndrome

contraction alkalosis: diuresis → excretion of HCO3-poor fluid → extracellular fluid “contracts” around fixed amount of HCO3 → ↑ HCO3 concentration

posthypercapnia: respiratory acidosis → renal compensation with HCO3 retention; rapid correction of respiratory disorder (eg, with intubation) → transient excess HCO3

•  Maintenance phase

volume depletion → ↑ proximal reabsorption of NaHCO3 and ↑ aldosterone (see next)

hyperaldosteronism (either 1° or 2°) → distal Na reabsorption in exchange for K+ and H+ excretion (and consequent HCO3 retention)

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

Workup

•  Check volume status and UCl

UCl <20 mEq/L → saline-responsive

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

(UNa unreliable determinant of volume status as alkalemia → ↑ HCO3 excretion → ↑ Na excretion; negatively charged HCO3 “drags” Na+ along)

If UCl >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, O2 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

•  Lung parenchyma abnormalities (often cause hypoxia → ↑ RR → resp. alk., but eventual muscle fatigue → resp. acid.): pneumonia, pulmonary edema, restrictive lung disease

•  Thoracic cage abnormalities: pneumothorax, flail chest, kyphoscoliosis

•  Post infusion of bicarbonate in acidemic Pt w/ limited ability to ↑ minute ventilation

RESPIRATORY ALKALOSIS

Etiologies (NEJM 2002;347:43)

•  Hypoxia → hyperventilation: pneumonia, pulm. edema, PE, restrictive lung disease

•  Primary hyperventilation

CNS stimulation, pain, anxiety, fever, trauma, stroke, voluntary

drugs: salicylates, progesterone, methylxanthines, nicotine pregnancy, sepsis, hepatic failure

•  Pseudorespiratory alkalosis: ↓ perfusion w/ preserved ventilation (eg, CPR, severe HoTN) → ↓ delivery of CO2 to lungs for excretion; low PaCO2 but ↑ tissue CO2