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Chapter Nine: Regulation of Plasma Osmolality
Oct 31, 2022
01:40:11
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Quick takeaways
- Understanding electrolyte-free water clearance is pivotal in sodium homeostasis.
- Thirst plays a crucial role in maintaining normal sodium levels despite reduced ADH release.
- Age-related decline in maximal urine concentration can impact urinary dilution/concentration.
- Distinct nephron segments regulate water reabsorption and osmolality for efficient water excretion.
Deep dives
Types of Advertisements Discussed in the Podcast
The podcast episode explores different types of advertisements, highlighting the speaker's preference for Tolvaptan advertisements over others. Examples include the Tolvaptan ads focused on PKD and the excitement evoked by a specific PKD advertisement featuring a bed going over a crevice. The speaker expresses admiration for the engaging nature of these advertisements.
Significance of a Chapter on Sodium Homeostasis
The podcast delves into a crucial chapter related to sodium homeostasis, emphasizing the speaker's personal connection to the topic. The speaker recounts their experience writing a chapter on sodium homeostasis during their fellowship, attributing a profound understanding of sodium to a pivotal 1986 article by Bud Rose in the American Journal of Medicine, which elucidated electrolyte-free water clearance.
Role of Thirst in Maintaining Homeostasis
The podcast underscores the essential role of thirst in maintaining homeostasis, particularly in scenarios where ADH release is reduced. The discussion highlights how access to water can compensate for diminished ADH activity, ensuring that despite ADH suppression, normal sodium levels can be maintained as long as an individual has access to water and remains conscious.
Age-Related Changes in Maximum Urine Concentration
The podcast points out age-related differences in maximum urine concentration, with observations suggesting a decline with age. While younger individuals exhibit higher urine osmolality levels, older individuals demonstrate a decreased ability to concentrate urine at levels comparable to those seen in younger counterparts. This age-related alteration in maximal urine concentration may impact urinary dilution and concentration levels in older individuals.
Renal Water Excretion Process
The podcast details the renal process of water excretion, highlighting distinct mechanisms in different segments of the nephron. It explains how water is predominantly reabsorbed passively in the proximal tubule and the descending limb of the loop of Henle for volume regulation, whereas concentrated segments like the ascending loop of Henle and distal nephrons focus on adjusting osmolality for effective water concentration elsewhere in the nephron. By segmenting these functions, the podcast emphasizes the critical role each plays in maintaining osmolality and proper water excretion.
Factors Affecting Water Excretion in Hyponatremia
Water retention leading to hyponatremia occurs when there's a defect in water excretion or when water intake exceeds excretory capacity. Factors that diminish water excretion include reduced fluid delivery to the loop of Henle in conditions like renal failure or volume depletion, inhibition of sodium chloride reabsorption by diuretics, particularly thiazides, and presence of ADH in conditions like effective volume depletion or syndrome of inappropriate ADH secretion. These comprise the complete differential diagnosis of true hyponatremia, organizing the thinking based on the physiology.
Clinical Implications of Understanding Water Clearance Factors
Understanding the factors influencing water clearance in patients with hyponatremia and hypo-osmolality has significant clinical implications. Water excretion depends on various steps, such as fluid delivery rate to the loop of Henle, sodium chloride reabsorption inhibition by diuretics, and actions of ADH. Categorizing hyponatremic disorders into these factors provides a systematic approach to diagnosis and highlights the critical nature of the differential diagnosis based on the physiological mechanisms involved.
Utility of Free Water Clearance in Patient Management
The utility of free water clearance becomes apparent in patient management, particularly in cases of SIADH or heart failure. Specific medications such as a Vapten's or loop diuretics like Torsamide can alter the urine concentration gradient and the response to ADH, influencing water retention or excretion. Understanding and utilizing the concept of free water clearance aids in adjusting treatment strategies to correct hyponatremia effectively while avoiding over-correction, providing a valuable tool in clinical practice.
References for Chapter 9
One of the few papers that Rose wrote as a single author explores electrolyte free water clearance. This seminal paper explores the issue in greater detail than the book. A New approach to disturbances in the plasma sodium concentration
Wondering about the volume of sweat? Josh taught us that the volume of “transepidermal volume loss” is not affected by humidity https://www.jidonline.org/article/S0022-202X(15)48145-X/pdf but is greatly affected by temperature: Skin temperature and transepidermal water loss
Regarding normal sweat physiology, there is a nice review (with figures!) titled Physiological mechanisms determining sweat composition which describes all the important cells and channels which make up sweat glands. And an important follow on paper titled Higher Bioelectric Potentials due to Decreased Chloride Absorption in the Sweat Glands of Patients with Cystic Fibrosis describing specifically the sweat characteristics of patients with cystic fibrosis.
Melanie was enchanted by work from RA McCance who did early experiments to induce sodium deficiency using very low sodium diets and a homemade sauna-like tent. His musings are fascinating. Lancet 1936 Experimental human salt deficiency MEDICAL PROBLEMS IN MINERAL METABOLISM
Age-related decline in urine concentration may not be universal: Comparative study from the US and two small-scale societies from Jeff Sands (of urea transport fame!)
In this initial report, after continually water loading 21 volunteers, the younger group (mean age 31) had a urine osmolality of 52 mOsm/kg compared to in the older group (mean age 84). Influence of age, renal disease, hypertension, diuretics, and calcium on the antidiuretic responses to suboptimal infusions of vasopressin. In a later report older subjects (mean age 72) vs younger controls (mean age 26) drank 20 ml/kg over 40 minutes. The younger group excreted more of the water in the first 2 hours and had a lower mean urine osmolality 86 vs 112 mOsm/kg compared to the older participants. Age-associated Alterations in Thirst and Arginine Vasopressin in Response to a Water or Sodium Load
Howard Furst suggests the urine to plasma electrolyte ratio as a simpler strategy to consider the free water clearance: https://nephrology.edublogs.org/files/2014/03/Water-Restriction-in-Hyponatremia1-1eb8n40.pdf or via pubmed: The urine/plasma electrolyte ratio: a predictive guide to water restriction
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