Chapter Five: Functions of the Distal Nephron
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Hypercalcema
One of the postulatin mechanisms for thiside inds hyper calcema is because of a stimulation ofthe volume depletion leading to reactive increasing proximate toe absorption. So asso, what is it you vodepleve with athiasod aso, we become hiper calcemic, or youre not. And if you have a thia adi blockit, you cannot depend upon this dium calcium exchange on the basilateral side. That is going to pull sodium and kind of feed the pump. It drags calcium through the opical side and promotes more calciumr absorption.
References for Chapter 5--the Distal Nephron
Roger pointed out the fact that the distal nephron can achieve very low urinary sodium as evidenced by observations in people from the Yanomamo tribe Blood pressure and electrolyte excretion in the Yanomamo Indians, an isolated population in this report, 84% of the participants had urinary sodium < 1mmol/24 hours.
Information about the Yanomamo Tribe. It looks like they’re starting to make chocolate, now!
The Yanomami are great observers of nature
The Amazon's Yanomami utterly abandoned by Brazilian authorities: Report
Yanomami Amazon reserve invaded by 20,000 miners; Bolsonaro fails to act
I believe this is the original study looking at urine sodium and blood pressure in the Yanomamo Indians, but the INTERSALT trial linked above I believe had more robust urine data
This study mentions the average lipid profile for men and women along with BMI.
I didn’t mention in the “Voice of God” overview, but there is some interest looking at the Yanomamo and rate of cancer as it relates to the correlation with intracellular potassium to sodium ratios
Josh referred back to his notes and realized that the tightest junctions are in the TOAD not FROG bladders Physiology and Function of the Tight Junction
An excellent review from McCormick and Ellison on the Distal convoluted tubule in Comprehensive Physiology.
We flirt with the disorder of Gordon’s syndrome: Familial Hyperkalemic Hypertension | American Society of Nephrology and its alter ego, Gitelman syndrome: Gitelman Syndrome | Hypertension
JC spoke about this beautiful report on how calcineurin inhibitors lead to hyperkalemia (and mimic Gordon’s syndrome). The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension
This superb review of the DCT includes all the highlights of Rose’s chapter 5 with a modern lens including “braking” from DCT hypertrophy Distal Convoluted Tubule | American Society of Nephrology
Echos of the lessons learned in the DCT can be seen in this review: Diuretic Treatment in Heart Failure | NEJM
Anna reminds us of the ALL HAT trial which showed that chlorthalidone was superior to the lisinopril and amlodipine groups (and the alpha blocker dropped out earlier) Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic
Nice review of drug induced Hyperuricemia with a deep dive into the mechanisms of diuretic induced Hyperuricemia. Drug-induced hyperuricaemia and gout
Plus, despite the concerns that thiazides are weaker than loop diuretics and may not work in CKD, this report suggests that it can still be of use. Chlorthalidone for poorly controlled hypertension in chronic kidney disease: an interventional pilot study
If you love diuretics, you will love this classic paper from Craig Brater on diuretics Diuretic Therapy | NEJM which also includes the t1/2 of various diuretics and points out that chlorthalidone’s half life is 24-55 hours so eliminated after 4-10 days.
The hypercalcemia seen in some patients who take thiazides may be the unmasking of primary hyperparathyroidism Thiazide-Associated Hypercalcemia: Incidence and Association With Primary Hyperparathyroidism Over Two Decades
As we discussed the relative importance of DCT vs Proximal tubule for the hypercalcemia seen with thiazides, Amy reminded us of about the TRPV5 knockout mice: JCI - Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5
JC mentioned the defect in TRPM6 that can cause severe hypomagnesemia: Novel TRPM6 Mutations in 21 Families with Primary Hypomagnesemia and Secondary Hypocalcemia
We enjoyed talking about Liddle syndrome Hypertension caused by a truncated epithelial sodium channel γ subunit: genetic heterogeneity of Liddle syndrome
We wondered about the role of pendrin which was discovered after this book was published. Here’s a nice review: The role of pendrin in renal physiology and also a potential therapeutic target for pendrin: Pendrin—A New Target for Diuretic Therapy? | American Society of Nephrology
More Bradykinen Chronic Overexpression of Bradykinin in Kidney Causes Polyuria and Cardiac Hypertrophy
We ended on a high note when we considered the urothelium of the American black bear. These magnificent creatures have aquaporins 1 &3 that allow them to reabsorb their own urine during hibernation. The urothelium of a hibernator: the American black bear
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