Base Excess - Definition

• Normal range: -2 to +2 mEq/L
• Positive BE (> +2): Metabolic alkalosis - excess base present
• Negative BE (< -2, also called base deficit): Metabolic acidosis - base deficient

Note: A base deficiency cannot be corrected simply by calculating the difference between normal standard bicarbonate (24 mEq/L) and the actual value and giving that amount of NaHCO3 - because bicarbonate is distributed throughout a larger volume than plasma alone.

Renal Compensation for Acid-Base Imbalance

1. Reabsorbing filtered HCO3- (mainly in the proximal tubule)
2. Secreting H+ ions into tubular fluid (in exchange for Na+)

1. Renal Compensation for Respiratory Acidosis (high PaCO2)

• Elevated PaCO2 raises intracellular CO2 in tubular cells → more H2CO3 forms via carbonic anhydrase → more H+ available for secretion
• Renal tubular H+ secretion increases, removing H+ from the body
• Even though plasma HCO3- is already elevated, HCO3- reabsorption is further increased (since HCO3- is reabsorbed by exchange for H+)
• Net result: plasma HCO3- rises further, partially restoring pH toward 7.40
• Cl- excretion increases, plasma Cl- falls as plasma HCO3- rises

2. Renal Compensation for Respiratory Alkalosis (low PaCO2)

• Low PaCO2 → less CO2 in tubular cells → H+ secretion is hindered
• HCO3- reabsorption is depressed → HCO3- is lost in urine
• Plasma HCO3- falls further, pulling pH back toward normal

3. Renal Compensation for Metabolic Acidosis (low HCO3-)

• Glutamine synthesis in the liver increases
• Glutamine is delivered to the kidneys as substrate for NH4+ production
• NH3 secretion adapts upward over days
• Metabolism of glutamine also generates α-ketoglutarate → decarboxylated → new HCO3- enters the bloodstream, directly buffering the acid load

2NaHCO3 + H2SO4 → Na2SO4 + 2H2CO3

Na2SO4 + 2H2CO3 → 2NaHCO3 + 2H+ + SO4²- (H+ excreted as titratable acidity + NH4+)

4. Renal Compensation for Metabolic Alkalosis (high HCO3-)

• Elevated plasma HCO3- → increased filtered load of HCO3-
• More renal H+ secretion is needed just to reabsorb this increased load
• When plasma HCO3- exceeds 26-28 mEq/L, HCO3- appears in urine (renal threshold exceeded)
• The rise in PCO2 (from respiratory compensation of metabolic alkalosis) actually inhibits renal compensation slightly by facilitating acid secretion
• Net result: HCO3- is excreted, plasma HCO3- falls toward normal

Summary Table

Part 1: The Countercurrent Mechanism in the Kidney

A. Countercurrent Multiplier - Loop of Henle

Key structural properties (from tubule characteristics table):

Stepwise generation of the medullary gradient:

1. The loop fills with isosmotic fluid at 300 mOsm/L (equal to plasma)
2. The thick ascending limb actively pumps Na+/K+/2Cl- out into the interstitium (via the NKCC2 carrier), creating a 200 mOsm/L gradient between tubular lumen and interstitium. The thick ascending limb is impermeable to water, so solute leaves without water following - this is the "single effect"
3. Water osmotically leaves the descending limb (which is highly water-permeable via AQP-1 aquaporins) to equilibrate with the now-hypertonic interstitium. Tubular fluid in the descending limb becomes concentrated
4. This hyperosmotic fluid from the descending limb flows around the bend into the ascending limb
5. The thick ascending limb pumps ions out again, raising interstitial osmolarity further
6. Descending limb fluid equilibrates again with the higher interstitial osmolarity
7. Steps 4-6 repeat - this "multiplication" of the single 200 mOsm effect progressively concentrates the medullary interstitium to 1200-1400 mOsm/L at the papilla

Role of Urea

• In the presence of ADH, the inner medullary collecting duct becomes permeable to urea (via UT-A1 and UT-A3 transporters), allowing urea to diffuse into the medullary interstitium
• This urea then enters the thin descending limb (via UT-A2), travels up through the ascending limb and distal tubule, back down the collecting duct, and recirculates - progressively concentrating
• Urea recirculation is an essential component of the concentrating mechanism

B. ADH and the Collecting Duct - Final Urine Concentration

• Without ADH: Collecting duct is impermeable to water. Hypotonic fluid (100-140 mOsm/L) exits the loop and dilute urine is excreted
• With high ADH: ADH inserts aquaporin-2 (AQP-2) channels into the apical membrane of the collecting duct. Water is reabsorbed down the osmotic gradient. Final urine osmolarity approaches 1200 mOsm/L, equal to the medullary interstitium

C. Countercurrent Exchanger - Vasa Recta

• Medullary blood flow is deliberately low - less than 5% of total renal blood flow - minimizing solute washout
• As blood descends into the medulla, solutes (NaCl, urea) passively diffuse in and water diffuses out - blood becomes hyperosmotic to match the interstitium
• As blood ascends back toward the cortex, solutes diffuse back out into the interstitium, and water re-enters the blood
• The U-shaped hairpin architecture ensures that solutes picked up on the way down are returned on the way up - there is little net solute removal from the interstitium

Important: If vasodilators or high arterial pressure markedly increase medullary blood flow, solutes are "washed out" and urine-concentrating ability falls - even with maximal ADH levels.

Part 2: Perioperative Renal Protection Strategies

Why perioperative AKI matters

How anesthesia and surgery threaten renal function

• Most anesthetics cause dose-dependent hypotension via cardiac depression and vasodilation
• When MAP falls below the autoregulatory threshold, renal blood flow (RBF) and GFR fall proportionally
• Spinal/epidural anesthesia reduces sympathetic tone → venous pooling → decreased cardiac output

• Pain, surgical stimulation, anxiety → catecholamine surge → renal arterial constriction → reduced RBF and GFR
• Release of ADH (non-osmotic), aldosterone, angiotensin II → sodium and water retention (perioperative oliguria is partly physiological)

• NSAIDs (ketorolac): block vasodilatory prostaglandins, reducing RBF - especially dangerous in low-flow states
• Aminoglycosides, radiocontrast agents, ACE inhibitors, hydroxyethyl starch

Renal Protection Strategies

1. Optimize Fluid Management

• Maintain normovolemia - hypovolemia is the most preventable cause of perioperative AKI
• Balanced crystalloids (Plasma-Lyte, lactated Ringer's) are preferred over 0.9% normal saline, since hyperchloremia from large-volume saline causes renal vasoconstriction and metabolic acidosis
• Exception: use saline in patients with alkalosis/hypochloremia; avoid LR in hyperkalemia
• Avoid hydroxyethyl starch in critically ill patients or those with preexisting renal impairment - associated with increased AKI risk and death
• Goal-directed fluid therapy using stroke volume/cardiac output monitoring intraoperatively

2. Maintain Renal Perfusion Pressure

• Keep MAP within the autoregulatory range (65-80 mmHg; higher targets in hypertensive patients)
• Use vasopressors (norepinephrine) to treat anesthesia-induced hypotension when volume is adequate
• Avoid excessive PEEP in ventilated patients (reduces venous return and cardiac output)

3. Avoid and Remove Nephrotoxins

• Stop NSAIDs preoperatively; substitute alternative analgesics
• Use contrast-sparing imaging where possible; pre-hydrate before contrast administration
• Avoid/dose-adjust aminoglycosides; monitor levels
• N-acetylcysteine has not shown benefit in the perioperative setting (except potentially for radiocontrast nephropathy)

4. Drugs - What Doesn't Work and What May Help

• Mannitol: No evidence of protection or conversion from oliguric to nonoliguric failure. High doses are actually nephrotoxic. May mask hypovolemia by increasing urine output
• Low-dose dopamine ("renal dose"): No protection against AKI despite causing natriuresis and diuresis
• Fenoldopam (dopamine-1 agonist): Does not reduce AKI or need for dialysis
• Loop diuretics (furosemide): No protection - loop diuretics impair the countercurrent gradient by blocking the NKCC2 pump in the thick ascending limb
• Sodium bicarbonate infusion: Not proven effective

• Dexmedetomidine: Some evidence of renoprotection via anti-inflammatory, anti-sympathetic mechanisms
• Remote ischemic preconditioning: Brief cycles of limb ischemia/reperfusion before aortic or cardiac surgery
• Cold renal perfusion (4°C): Used in vascular surgery with juxtarenal/suprarenal cross-clamping; metabolic suppression reduces ischemic injury

5. Anesthetic Agent Considerations

• Volatile agents: Isoflurane, desflurane, sevoflurane generally decrease renal vascular resistance. Sevoflurane compound A accumulates at low fresh gas flows in rats but no clinical injury in humans - use ≥2 L/min FGF as a precaution
• Ketamine: May relatively preserve RBF during hemorrhagic hypovolemia
• Propofol/opioids: Minimal direct renal effects

6. Surgical Considerations

• Aortic cross-clamping: Suprarenal/juxtarenal clamping causes direct renal ischemia; minimize clamp time; consider sequential/rapid clamping, renal cooling, or perfusion
• Avoid prolonged supine lithotomy position which can increase intra-abdominal pressure
• Treat intraoperative sepsis aggressively

7. Monitoring

• Hourly urine output (target >0.5 mL/kg/hr) - an early warning sign but sensitive to non-renal factors
• Serum creatinine equilibrates 48-72 hours after GFR changes - a late marker
• Novel biomarkers (NGAL, KIM-1, cystatin C) detect tubular injury earlier but not yet routine
• BUN:creatinine ratio >15:1 suggests prerenal azotemia (tubular reabsorption of urea increases)

Summary