<br>  # .black[Hypernatraemia] ### UCL Physiology Course 2023 | Robert W Hunter --- class: center, middle, inverse # .white[Thanks to Robert Zietse] --- # Learning objectives - pathogenesis of hypernatraemia - urinary concentrating mechanism - causes of hypernatraemia - correction of hypernatraemia - slides at: https://www.kidneyfish.net/talks/ .RWH_footer_pearl[clinical pearls] --- # A case 60M (72 kg) admitted with stroke (MCA infarct). Keeps pulling out NG tubes. PNa normal on admission but rises steadily during the first week to 173 mM. <br> Do we need to worry? --- class: RWH_bg_black  .RWH_footnote_right[.RWH_footer_style[.white[Machino (Neurology, 2006)]]] -- .RWH_footer_pearl[high mortality] ??? Risks of: intracerebral and sub-arachnoid bleeds; dural sinus thrombosis; ODS; cerebral oedema during treatment. Mortality: up to 40%. Around a third of that adjudicated to be [due to hyperNa itself](https://pubmed.ncbi.nlm.nih.gov/8533994/). --- # Consequences of soy ingestion `$$P_{Na} \propto \frac{Na_{e} + K_{e}}{TBW}$$` -- <br> - Na_e = 40 mmol/kg; K_e = 60 mmol/kg; Na_e + K_e = 100 mmol/kg - ...= 7000 mmoles in 70 kg man -- - 1L soy (15% NaCl) = 150 g NaCl = 2600 mmoles - therefore 2600 mmoles = 37% increase in body solute (and 2% increase in TBW) - ...predicting Na rise from 140 to 192 mM .RWH_footnote_right[.RWH_footer_style[Carlbergy (J Emerg Med, 2013)]] ??? ...which is exactly what was observed in this second case-report. --- class: center, middle, inverse # .white[Pathogenesis of hyperNa] --- # Pathogenesis `$$P_{Na} \propto \frac{Na_{e} + K_{e}}{TBW}$$` -- <br> <table> <thead> <tr> <th style="text-align:center;"> Na gain </th> <th style="text-align:center;"> water loss </th> <th style="text-align:center;"> hypotonic fluid loss (renal) </th> <th style="text-align:center;"> hypotonic fluid loss (other) </th> </tr> </thead> <tbody> <tr> <td style="text-align:center;"> NaHCO\(_3\) </td> <td style="text-align:center;"> insensible losses </td> <td style="text-align:center;"> osmotic diuresis (glucose, urea…) </td> <td style="text-align:center;"> vomiting / NG losses </td> </tr> <tr> <td style="text-align:center;"> NaCl </td> <td style="text-align:center;"> hypodipsia </td> <td style="text-align:center;"> post-obstructive diuresis </td> <td style="text-align:center;"> diarrhoea </td> </tr> <tr> <td style="text-align:center;"> soy ingestion </td> <td style="text-align:center;"> NDI </td> <td style="text-align:center;"> post-ATI diuresis </td> <td style="text-align:center;"> burns </td> </tr> <tr> <td style="text-align:center;"> sea water </td> <td style="text-align:center;"> central DI </td> <td style="text-align:center;"> loop diuretics </td> <td style="text-align:center;"> sweating </td> </tr> <tr> <td style="text-align:center;"> primary aldosteronism </td> <td style="text-align:center;"> gestational DI </td> <td style="text-align:center;"> </td> <td style="text-align:center;"> </td> </tr> </tbody> </table> .RWH_footnote_right[.RWH_footer_style[Adrogue & Madias (NEJM, 2000)]] -- .RWH_footer_pearl[Drs cause hyperNa] ??? Incidence (> 150 mM): 0.2% on admission; 1 -- 3% in hospital-acquired; 8 -- 9% in ITU. In most case-series, hospital-acquired hypoNa much more common than hyperNa on presentation (e.g. https://pubmed.ncbi.nlm.nih.gov/8533994/, (https://pubmed.ncbi.nlm.nih.gov/21358313/, http://www.biomedcentral.com/1471-2369/15/37, https://pubmed.ncbi.nlm.nih.gov/30948456/...) 50 ml 8.4% HCO3 = 50 mmoles. Probably need to delivery several 100s mmoles to induce good-going hyperNa... ---  .RWH_footnote_right[.RWH_footer_style[Hoorn (NDT, 2008)]] ??? Dutch case-series of 130 ITU patients with Na > 150 mM. NaHCO₃ use, manitol use and hypoK all RFs for hyperNa. --- class: center, middle, inverse # .white[Control of water homeostasis] --- # Osmosensing  .RWH_footnote_right[.RWH_footer_style[Bourque (Nat Rev Neurosci, 2008)]] ??? All very complicated. Peripheral and central osmoreceptors. Key role for neurones in the OVLT in the hypothalamus: one of the circumventricular organs, devoid of BBB. --- # Osmosensing  .RWH_footnote_right[.RWH_footer_style[Naeini (Nat Neurosci, 2005)]] ??? Trpv1 is the capsaicin receptor. --- # Urinary concentration  .RWH_footnote_right[.RWH_footer_style[Knepper & Burg (Am J Physiol, 1983)]] ??? Water permeability of isolated rabbit tubules - diluting segment then CCD. --- # Urinary concentration  .RWH_footnote_right[.RWH_footer_style[Hargitay & Wirz (Basel, 1946)]] ??? Syrian Golden Hamster (accessible papillae). ---  ---  ??? Dehydration stimulates thirst and AVP release. Therefore you drink and reabsorb water from the dilute tubular fluid. ---  -- .RWH_footer_pearl[auto-compensation] ??? At-risk groups = neonates, elderly, ITU... ...and uncontrolled DM. ---  .RWH_footnote_right[.RWH_footer_style[Davison (JCI, 1988)]] ??? Vasopressinase in pregnancy degrades oxytocin to prevent preterm labour. This from a series of five normal pregnancies. Usually doesn't cause DI. GDI in ~1:50,000 pregnancies (in third trimester). Liver disease a RF (hepatocytes degrade vasopressinase). Treat with ddAVP - safe in pregnancy. Will resolve a few weeks post-partum. --- class: center, middle, inverse # .white[Diagnosis in hyperNa] ---  ??? UOsm should be maximal in hyperNa; if inappropriately not high then DI. ---  .RWH_footnote_right[.RWH_footer_style[Christ-Crain (Eur J Endo, 2019); Kamel (JAMA, 2022)]] --- class: center, middle, inverse # .white[Correction of hyperNa] --- # How much to replace? 60M (72 kg) admitted with stroke (MCA infarct). Keeps pulling out NG tubes. PNa normal on admission but rises steadily during the first week to 173 mM. <br> How much water do we need to replace? And how quickly? --- # How much to replace? `$$\text{water deficit} = TBW \times (\frac{P_{Na}}{140} - 1)$$` -- `$$\text{water deficit} = TBW \times (\frac{P_{Na} - 140}{140})$$` `$$\text{water deficit} \approx 45 \times (\frac{P_{Na} - 140}{140})$$` `$$\text{water deficit} \approx \frac{45}{140} \approx \frac{1}{3} \times ({P_{Na} - 140})$$` `$$\color{red}{\text{water deficit} \approx \frac{({P_{Na} - 140})}{3}}$$` -- `$$\text{water deficit} \approx \frac{(173 - 140)}{3} \approx \frac{33}{3} = 11L ^*$$` -- .RWH_footer_pearl[more than you think!] ??? * remember also to account for ongoing losses In small [case-series](https://pubmed.ncbi.nlm.nih.gov/21358313/) (and [again](http://www.biomedcentral.com/1471-2369/15/37)), only 30% patients corrected after 3 days of treatment. --- # How fast to replace? --  .RWH_footnote_right[.RWH_footer_style[Chauhan (CJASN, 2019)]] -- .RWH_footer_pearl[10 mmol per day... <br> ...too conservative] ??? Retrospective case-series of c. 450 patients with hyperNa (~75% hospital-acquired). Data here for the in-hospital group (but similar for patients with hyperNa at presentation - arguably higher risk). No evidence of seizures / neurological toxicity from case-note review. [Sterns](https://doi.org/10.2215/CJN.02950319) points out that guideline limits of 10 mmol/day (or 0.5 mmol/hr) were largely derived from observations of "rehydration seizures" in neonates. No convincing case report of cerebral oedema from rapid hyperNa correction in adults! Also that uncontrolled rapid correction of hypoNa is often a realistic prospect (e.g. if diuresis ensures following volume resuscitation), whereas over-correction in hyperNa can only occur as the result of IV therapy. --- # How fast to replace?  .RWH_footnote_right[.RWH_footer_style[Chauhan (CJASN, 2019)]] ??? Data here from the group with hyperNa at presentation. This is in-hospital mortality. Caution with these subgroup analysis in an observational study. But certainly no evidence of harm from rapid correction. --- # Correction of hyperNa - water (oral, NG, 5%G) - 0.9% NaCl if hypovolaemic / hypotensive - diuretics if volume expanded - central / gestational DI: ddAVP - NDI: low Na diet, thiazide, amiloride, acetazolamide --- # Take-home points - hypernatraemia is caused by solute excess or water loss - high mortality - frequently iatrogenic - historically, we have corrected too slowly - safe (and preferable?) to meet or exceed 12 mmol per day - need more aq than you think .RWH_footnote_right[.RWH_footer_style[slides at: https://www.kidneyfish.net/talks/; see presenter notes for suggestions for futher reading]] ??? # Futher reading [Sterns sodium review (NEJM 2015)](https://doi.org/10.1056/NEJMra1404489) [Sterns editorial (CJASN 2019)](https://doi.org/10.2215/CJN.02950319) --- class: center, middle, inverse # .white[Supplemental slides] --- # Edelman  --- # Derivation of Edelman `$$ECF_{Osm} \approx 2 \times P_{Na}$$` .RWH_footnote_right[.RWH_footer_style[Verbalis (Am J Med, 2013); Rose (Am J Med, 1986)]] -- <br> `$$ECF_{Osm} = ICF_{Osm} = \frac{\text{total body solutes}}{\text{total body water}} \approx \frac{(2 \times Na_{e}) + (2 \times K_{e})}{TBW}$$` -- <br> `$$ECF_{Osm} \approx \frac{2 \times (Na_{e} + K_{e})}{TBW} \approx 2 \times P_{Na}$$` -- <br> .red[ `$$P_{Na} \approx \frac{Na_{e} + K_{e}}{TBW}$$` ]