2/ Kidney stones 🪨 💎🔶♦️💠are a worldwide issue with increasing prevalence. Calcium stones (oxalate > phosphate) - most common (75%).
📍Which of the following contribute to stone formation?
3/ All the above.
Nevertheless, dietary factors are modifiable.
Look, now we have some control, eh...🤓🦾
4/Let's focus on Salt🧂:
⬆️dietary intake of NaCl🧂 → ⬆️ urinary Ca
📌1 teaspoon of NaCl (2.3 g of Na) → urinary calcium excretion by 40 mg/day pubmed.ncbi.nlm.nih.gov/7666985/
📌dietary salt intake >10 g/day → increased prevalence of hypercalciuria pubmed.ncbi.nlm.nih.gov/9092314/
This is difficult to achieve as the common food additive/ preservative is🧂
6/ And, most of the delicious 😋 foods are high in salt. #empathizewithpatients
🥓🥨🥐🍩🍜🍔🍟🥖🧀🍕🍝🌮🍿
7/ Before understanding the mechanism of salt-induced calciuria, let’s understand the mechanism of Ca transport.
Quiz time: Where is Ca absorbed in the Nephron?
8/ Ans: everywhere
9/ What is the predominant mechanism of Ca+2 absorption in PT?
10/ Ans: Paracellular
📍PT and the thick ascending limb (TAL) of the loop of Henle - mostly paracellular (depends on transepithelial electrochemical gradient & tight junction’s permeability)
📍reminder in DT- transcellular
✴️Let’s look at Ca transport across various cells✴️
11/ PT: ~ 55-65% of Ca reabsorbed
📌Mostly paracellular- mediated by claudin-2 (CLDN2)
📌Early PT: (dependent on Na)
Na reabsorption (Na-H exchanger (NHE3) & Na-K ATPase)→ osmotic gradient→ H2O absorption→ Ca solute drag
📌late PT: transcellular absorption across Ca gradient
12/ Ca reabsorption in PT & Parathyroid hormone (PTH)
📌PTH→⬇️ Calcium reabsorption by attenuating its driving force (Sodium)
📌PTH + PTHR (apical & basolateral)→ activates protein kinases A & C→ inhibits NHE3
📌apical PTHR→ preferential PKC activation→ inhibits Na/ K ATPase
13/ Other actions of PTH →
⬇️ tight-junction permeability in the PT
⬆️active vitamin D3 synthesis
A word about FGF23 - What does FGF23 do to Vit D3 activation?
15/ Let’s look at the mechanisms of Ca absorption at the remaining sites of the nephron
📌TAL & DT: mediated by PTH & vitamin D
📌TAL: ~20% - paracellular- via CLDN 16/19
Other factors that influence Ca handling: EC volume status & acid-base balance
16/ DT: 5-10% of filtered calcium - Transcellular reabsorption
📌PTH (PTHR - basolateral membrane)→ activation of protein kinase A&C pathways → ⬆️ number and activity of TRPV5 (apical) → Ca influx
17/ In short,3 factors affect Ca reabsorption majorly-
📌PTH : ⬆️TAL & DT (⬇️ PT)
📌Extracellular Volume : Vol Contraction → Na & Ca reabsorption (eg., Thiazide diuretic)
📌Acid-base balance: Acidosis → leaching of Ca from bone🦴 & ⬇️ Ca binding to proteins → calciuria
18/ Let’s come back to our first question❓
🧂salt-induced calciuria
⬆️ Na intake→⬇️ Na and H2O reabsorption in PT→ osmotic diuresis 🚽→⬇️ Ca reabsorption in PT→Calciuria→Stone 🪨💎💠♦️🔶formation
Also, PO4 reabsorption in the PT is dependent to some degree on Na transport
19/ So, the Low-Salt Diet prevents stone formation by ⬇️calciuria
👉👉DIET👈👈 is considered THE MOST IMPORTANT factor for management and recurrence
2/ 💥Let’s begin with Cilia-
📌Motile cilia- generate flow of mucus & CSF
📌Non-motile/sensory cilia (inner ear, retina, & olfactory epithelium)
- plays a part in important pathways [Hedgehog, Wnt (wingless-Int-1), & PCP (planar cell polarity) signaling] ncbi.nlm.nih.gov/pmc/articles/P…
3/Now let’s move on to💥Cystoproteins💥
📌These are proteins in cilia when mutated → cystic kidney diseases in humans, mice, or zebrafish
📌expressed in primary cilia, basal bodies or centrosomes
1/ A 55 year old man👨🏻 with urothelial cancer
✂️transurethral tumor resection, radical cystectomy & neobladder reconstruction 3 mons ago
✂️B/L PCNs & ileostomy - postop (urinary and bowel leak)
2/ He was admitted🏥 6 days ago due to increased ostomy output💩🌊 (>4L/day) & dehydration, and has been receiving NS 💧@ 150mL/h
His BMP is-