Channel Your Enthusiasm
Chapter Eighteen, part 1
Episode guests
Podcast summary created with Snipd AI
Quick takeaways
- The host's introduction of Aldo, his rescue dog, highlights the emotional bond and joy pets can bring into our lives.
- A detailed discussion outlines the distinction between chloride depletion and volume depletion in the context of metabolic alkalosis and homeostasis.
- The significance of managing potassium levels is emphasized, as hypokalemia complicates metabolic alkalosis and affects cellular functions significantly.
Deep dives
Introduction of Aldo and the Team
The host introduces Aldo, his new rescue dog, emphasizing the connection and affection felt for the pet. Notably, Aldo's approach and demeanor seem to resonate deeply with the host. In an amusing exchange, the group discusses humorous elements of one member's pharmacy-related humor, showcasing the camaraderie within the team. This light-hearted tone sets the stage for a deeper discussion regarding a more serious medical topic.
Understanding Metabolic Alkalosis
The conversation shifts focus to metabolic alkalosis, explored in detail through discussions about its causes and implications. The group highlights key aspects of renal physiology, particularly how the kidneys function to manage bicarbonate levels and maintain overall pH balance in the body. The distinction between metabolic alkalosis generated by various factors, such as chloride depletion or volume depletion, is examined, emphasizing the intricate balance required for homeostasis. The presenters engage in a lively debate about the relevance and implications of maintaining bicarbonate levels, showcasing their deep knowledge and contrasting opinions.
Generating and Maintaining Metabolic Alkalosis
A detailed exploration of how metabolic alkalosis is generated focuses on two main phases: the generation phase and the maintenance phase. The host explains that a sustained metabolic alkalosis must involve both the generation of excess bicarbonate and the inability to excrete it adequately. Specific causes, such as gastrointestinal losses or treatment with diuretics, are presented as primary avenues for generating alkalosis. This mechanism is contrasted with the maintenance side, where kidney functions and responses to volume and chloride levels determine how long the condition persists.
Role of Chloride and Volume Depletion
The discussion deepens into the roles of chloride depletion and volume status in perpetuating metabolic alkalosis. Members highlight how chloride depletion's significance often gets overshadowed by the notion of volume depletion, with relevant experimental evidence supporting this distinction. Intriguingly, they discuss scenarios where chloride can be administered without sodium, pointing out how measures like potassium chloride can correct alkalosis while maintaining volume status. These insights underline the complexity of electrolyte balance and the kidney's role in maintaining metabolic stability.
Hypokalemia's Influence on Alkalosis
Finally, the group examines hypokalemia as a critical factor influencing metabolic alkalosis maintenance. They discuss how a deficit in potassium not only affects overall cellular processes but also enhances hydrogen secretion in the distal nephron, further complicating the alkalosis. The intricate interplay between potassium and bicarbonate reflects the profound impact of electrolyte management in clinical practice. This segment emphasizes the need for a holistic approach toward treating metabolic imbalances by considering all elements influencing the body's acid-base status.
We are a bit slappy at the beginning of the episode since we had just recorded our conversation with the Glaucomfleckens.
References
Chapter 18 Metabolic alkalosis!
Part 1 February 23, 2023
It is chloride depletion alkalosis, not contraction alkalosis classic review by Galla and Luke, the metabolic alkalosis mavens who review the role of chloride.
On the mechanism by which chloride corrects metabolic alkalosis in man and this is the study when they induced a metabolic alkalosis and studied the effect of treating with KCl vs NaPhos and found the former (with chloride) reversed the alkalosis but not the sodium containing protocol.
Some elegant reports on the increased proximal reabsorption of bicarbonate above normal stimulated by Ang II.
Tubular transport responses to angiotensin | American Journal of Physiology-Renal Physiology
THE RENAL REGULATION OF ACID-BASE BALANCE IN MAN. III. THE REABSORPTION AND EXCRETION OF BICARBONATE 1949 this is the correct figure for 11.14 and shows what happens when filtered bicarb exceeds normal threshold in normal human (men) and appears in the urine.
Masterful review Symposium on acid-base homeostasis. The generation and maintenance of metabolic alkalosis by Seldin and Rector
And a modern review from Michael Emmet! Metabolic Alkalosis - PMC (so many favorite reviews on this exciting topic!) and this one from Soleimani Metabolic Alkalosis Pathogenesis, Diagnosis, and Treatment: Core Curriculum 2022 both of these elaborate on pendrin’s role.
The effect of prolonged administration of large doses of sodium bicarbonate in man (Clin Sci. 1954 Aug;13(3):383-401)
Kidney v Renal: KDIGO versus Don’t
Plus: We got a little off topic and discussed the Kidney Failure Risk Equation: https://kidneyfailurerisk.com/
Outline: Chapter 18Metabolic Alkalosis
Elevation of arterial pH, increased plasma HCO3, and compensatory hypoventilation
High HCO3 may be compensatory for respiratory acidosis
HCO3 > 40 indicates metabolic alkalosis
Pathophysiology: Two Key Questions
How do patients become alkalotic?
Why do they remain alkalotic?
Generation of Metabolic Alkalosis
Loss of H+ ions
GI loss: vomiting, GI suction, antacids
Renal loss: diuretics, mineralocorticoid excess, hypercalcemia, post-hypercapnia
Administration of bicarbonate
Transcellular shift
K+ loss → H+ shifts intracellularly
Intracellular acidosis
Refeeding syndrome
Contraction alkalosis
Same HCO3, smaller extracellular volume → increased [HCO3]
Seen in CF (sweating), illustrated in Fig 18-1
Common theme: hypochloremia is essential for maintenance
Maintenance of Metabolic Alkalosis
Kidneys normally excrete excess HCO3
Example: Normal subjects excrete 1000 mEq NaHCO3/day with minor pH change
Impaired HCO3 excretion required for maintenance
Table 18-2
Mechanisms of Maintenance
Decreased GFR (less important)
Increased tubular reabsorption
Proximal tubule (PT): reabsorbs 90% of filtered HCO3
TALH and distal nephron manage the rest
Contributing factors:
Effective circulating volume depletion
Enhances HCO3 reabsorption
Ang II increases Na-H exchange
Increased tubular [HCO3] enables more H+ secretion
Distal nephron HCO3 reabsorption
Stimulated by aldosterone (↑ H-ATPase, ↑ Na reabsorption)
Negative luminal charge impedes H+ back-diffusion
Chloride depletion
Reduces NaK2Cl activity → ↑ renin → ↑ aldosterone
Luminal H-ATPase co-secretes Cl → low Cl increases H+ secretion
Cl-HCO3 exchanger needs Cl gradient → low Cl impairs HCO3 secretion
Key conclusion: Cl depletion > volume depletion in perpetuating alkalosis
Albumin corrects volume but not alkalosis
Non-N Cl salts correct alkalosis without fixing volume
Hypokalemia
Stimulates H+ secretion and HCO3 reabsorption
Transcellular shift (H/K exchange) → intracellular acidosis
H-K ATPase reabsorbs K and secretes H
Severe hypokalemia reduces Cl reabsorption → ↑ H+ secretion
Important with mineralocorticoid excess
Respiratory Compensation
Hypoventilation: 0.7 mmHg PCO2 ↑ per 1 mEq/L HCO3 ↑
PCO2 can exceed 60
Rise in PCO2 increases acid excretion (limited effect on pH)
Epidemiology
GI Hydrogen Loss
Gastric juice: high HCl, low KCl
Stomach H+ generation → blood HCO3
Normally recombine in duodenum
Vomiting/antacids prevent recombination → alkalosis
Antacids (e.g., MgOH)
Mg binds fats, leaves HCO3 unbound → alkalosis
Renal failure impairs excretion
Cation exchange resins (SPS, MgCO3) → same effect
Congenital chloridorrhea
High fecal Cl-, low pH → metabolic alkalosis
PPI may help by reducing gastric Cl load
Renal Hydrogen Loss
Mineralocorticoid excess & hypokalemia
Aldosterone → H+ ATPase stimulation, Na+ reabsorption → negative lumen → ↑ H+ secretion
Diuretics (loop/thiazide)
Volume contraction
Secondary hyperaldosteronism
Increased distal flow and H+ loss
Posthypercapnic alkalosis
Chronic respiratory acidosis → ↑ HCO3
Rapid correction (ventilation) → unopposed HCO3 → alkalosis
Gradual CO2 correction needed
Maintenance: hypoxemia, Cl loss
Low chloride intake (infants)
Na+ reabsorption must exchange with H+/K+
H+ co-secretion with Cl impaired if Cl is low
High dose carbenicillin
High Na+ load without Cl
Nonresorbable anion → hypokalemia, alkalosis
Hypercalcemia
↑ Renal H+ secretion & HCO3 reabsorption
Can contribute to milk-alkali syndrome
Rarely causes acidosis via reduced proximal HCO3 reabsorption
Intracellular H+ Shift
Hypokalemia
Common cause and effect of metabolic alkalosis
H+/K+ exchange → intracellular acidosis → ↑ H+ excretion
Refeeding Syndrome
Rapid carb reintroduction → cellular shift
No volume contraction or acid excretion increase
Retention of Bicarbonate
Requires impaired excretion to become significant
Organic anions (lactate, acetate, citrate, ketoacids)
Metabolism → CO2 + H2O + HCO3
Citrate in blood transfusion (16.8 mEq/500 mL)
8 units → alkalosis risk
CRRT + citrate anticoagulant
Sodium bicarbonate therapy
Rebound alkalosis possible with acid reversal (e.g., ketoacidosis)
Extreme cases: pH up to 7.9, HCO3 up to 70
Contraction Alkalosis
NaCl and water loss without HCO3
Seen in vomiting, diuretics, CF sweat
Mild losses neutralized by intracellular buffers
Symptoms
Often asymptomatic
From volume depletion: dizziness, weakness, cramps
From hypokalemia: polyuria, polydipsia, weakness
From alkalosis (rare): paresthesias, carpopedal spasm, lightheadedness
More common in respiratory alkalosis due to rapid pH shift across BBB
Physical exam not usually helpful
Clues: signs of vomiting
Diagnosis
History is key
If unclear, suspect:
Surreptitious vomiting
CF
Secret diuretic use
Mineralocorticoid excess
Use urine chloride
Table 18-3: urine Na is misleading in alkalosis
Table 18-4: urine chemistry changes with complete HCO3 reabsorption
Vomiting: low urine Na, K, Cl + acidic urine
Sufficient NaCl intake prevents this stage
Exceptions to low urine Cl:
Severe hypokalemia
Tubular defects
CKD
Distinguishing from respiratory acidosis
Use pH as guide
Caution with typo (duplicate pCO2)
A-a gradient might help
Treatment
Correct K+ and Cl− deficiency → kidneys self-correct
Upper GI losses: add H2 blockers
Saline-responsive alkalosis
Treat with NaCl
Mechanisms:
Reverse contraction component
Reduce Na+ retention → promote NaHCO3 excretion
↑ distal Cl delivery → enable HCO3 secretion via pendrin
Monitor urine pH: from 5.5 → 7–8 with therapy
Give K+ with Cl, not phosphate, acetate, or bicarbonate
Saline-resistant alkalosis
Seen in edematous states or K+ depletion
Edema (CHF, cirrhosis): use acetazolamide, HCl, dialysis
Acetazolamide: may ↑ CO2 via RBC carbonic anhydrase inhibition
Mineralocorticoid excess: K+ + K-sparing diuretic (use caution)
Severe hypokalemia:
eNaC Na+ reabsorption must be countered by H+ if no K+
Corrects rapidly with K+ replacement
Restores saline responsiveness
Renal failure: requires dialysis
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