• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content


Flash Player 9 (or above) is needed to view presentations.
We have detected that you do not have it on your computer. To install it, go here.

Like this presentation? Why not share!

SSU Week 3



RDE SSU Lecture 3

RDE SSU Lecture 3
Focus on Sodium



Total Views
Views on SlideShare
Embed Views



2 Embeds 7

http://www.infovisionary.co.uk 6
http://www.slideshare.net 1



Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
Post Comment
Edit your comment

    SSU Week 3 SSU Week 3 Presentation Transcript

    • RDEH Journal Club 5 th May 2006 Disorders of Sodium Balance Clinical Review BMJ Vol 332 25 th March 2006 Rebecca Reynolds (+) A case of ? Salt Poisoning Presented by John O’Connor
    • Sources of Information
      • Consensus from systematic reviews (medline search)
      • Less than a dozen RCT’s on treatment of Sodium disorders
      • Despite frequency, no review in the Cochrane Library
    • Control of Sodium Balance
      • Maintained in tight limits 135 – 145 mmol/L
      • Na +HCO3+Cl accounts for 80% ECF Osmolality
      • [2*Na] + Glucose + Urea
      • Main determinant [Na] = plasma water content
    • Daily Water Balance Under Normal Conditions
    • Pathways Through Which Dehydration Stimulates Hypothalamic Thirst Centers
    • Relationship Between Sodium Intake, Water Balance and Hormones
    • Series of Events in Water Intoxication
    • Role of ADH in Water Balance
    • Summary of Hormones Involved in Water Balance
    • Biochemical Homeostasis
    • Etiologies of Hyponatremia Poor Intake of Sodium Increased Urinary Loss of Sodium Diuretics Proximal RTA Aldosterone deficiency/resistance Increased GI Loss of Sodium (Fluid loss must be followed by repletion with free water). Vomitting Diarrhoea Increased Transcutaneous Loss of Sodium (Fluid loss must be followed by repletion with free water). Excessive Intake of Water (1 ° polydipsia) Psychosis Decreased Urinary Excretion of Water Decreased GFR Increased ADH Decreased effective circulating volume True volume depletion (any cause) Apparent volume depletion Heart failure Cirrhosis SIADH Reset osmostat Transmembrane Shift of Water Hyperglycemia Primary Sodium Loss Primary Water Excess
    • Symptoms
      • Relate to severity and rapidity of fall
      • Creates an osmotic gradient between the ECF and ICF in brain cells
      • Water moves into brain cells, oedema raising intracranial pressure
      • Nausea and malaise 125 –130 mmol/L
      • Headaches, lethergy disorientation 115-120
      • If fall is rapid: seizures, coma permenent brain damage, brain stem herniation
      • If gradual, brain regulates itself, Transporters initiate movement of NaCl KCl, Glutamate, Taurine, myo-inositol to ECF, moving water with them
    • History, Examination Investigation
      • Spot Urine Na
      • > 30 mmol/L = hypovolaemic hyponatraemia
      • < 30 mmo/L = extrarenal loss
      • In Hypervolaemic hyponatraemia Ur Na > 30
      • Box 2: Examination and investigations in patient with hyponatraemia Evaluation of volume status
      • Skin turgor Pulse rate Postural blood pressure Jugular venous pressure Consider central venous pressure monitoring Examination of fluid balance charts General examination for underlying illness
      • Congestive cardiac failure Cirrhosis Nephrotic syndrome Addison's disease Hypopituitarism Hypothyroidism Porphyria
      • Investigations
      • Urinary sodium Plasma glucose and lipids * Renal function Thyroid function Peak cortisol during short synacthen test Plasma and urine osmolality If indicated: chest x ray, and computed tomography and magnetic resonance imaging of head and thorax
    • Management
      • Try to avoid gining the patient central pontine myelinolytis
      • Do not alter S Na > 12 mmol/L 24 hrs
      • Little evidence that using hypertonic saline 3% NaCL, in asymptomatic patients is wise
      • Even more heroic is to use the above with a loop diuretic like furosemide (increases free water clearance)
    • Management
      • Fluid restriction (< 1 L day) initial approach
      • No trials have ever been done
      • Demeclocycline (inhibits ADH working on kidney) drug of choice especially inn SIADH
      • New drugs aquaretics (tolvaptan) are ADH antagonists at clearing free water. Good in SIADH, Cirrhosis, CHF
    • Etiologies of Hypernatremia Primary Sodium Excess Excess Intake of Sodium Decreased Urinary Excretion of Sodium Hyperaldosteronism Primary Water Loss Poor Intake of Water Impaired access to water (i.e. infants, elderly patients with dementia or whom are bedbound) Impaired thirst sensation Hypothalamic lesions Increased Urinary Loss of Water ADH deficiency (Central DI) ADH resistance (Nephrogenic DI) Increased GI Loss of Water Increased Transcutaneous Loss of Water Transmembrane Shift of Water (most often due to rapid production of intracellular lactate)
    • Hypernatraemia
      • Not common
      • Usually reflects net water loss
      • Severe symptoms Na > 158 mmol/L
      • Sensation of intense thirst (protective)
      • Anorexia, muscle weakness, nausea early
      • Later stupor, coma, brain shrinkage and rupture
      • SAH
      • Box 3: Classification of hypernatraemia
      • Hypovolaemia
        • Dermal losses—for example, burns, sweating Gastrointestinal losses—for example, vomiting, diarrhoea, fistulas Diuretics Postobstruction Acute and chronic renal disease Hyperosmolar non-ketotic coma *
      • Hypervolaemia
        • Iatrogenic (hypertonic saline, tube feedings, antibiotics containing sodium, or hypertonic dialysis) Hyperaldosteronism
      • Euvolaemia
        • Diabetes insipidus (central, nephrogenic, or gestational) Hypodipsia Fever Hyperventilation Mechanical ventilation
    • Management
      • If hypernatraemia has developed over a short period (hours), rapid correction (1 mmol/Hr) improves prognosis
      • If longstanding slow correction is recommended
      • Central Diabetes Insipidus treat with desmopressin
    • Summary of Hormones Involved in Sodium Balance
    • Guilty or Not Guilty LORD JUSTICE RICHARDS MR JUSTICE PENRY-DAVEY and HER HONOUR JUDGE GODDARD QC (sitting as a Judge of the Court of Appeal Criminal Division Be tween: Regina Respondent - v - Angela Alison Gay Ian Anthony Gay Appellants
      • On his admission to hospital on 8 December 2002, Christian age 3 was suffering from hypernatraemia, an abnormally high concentration of sodium in his blood. His blood (or plasma) sodium on admission to the Russells Hall Hospital was at the dangerously high level of 184 millimoles per litre (&quot;mmol/l&quot;). A normal level is in the region of 140 mmol/l. He was given an intravenous saline solution (which, on the face of it, may seem odd, but is explained by the need to bring down the level of sodium gradually in order to reduce the risk of damage to the cells). By the time of his transfer to the Birmingham Children's Hospital in the evening of 8 December the level was down to 173 mmol/l. Although the regime adopted at that hospital was expected to continue to bring the level down, it remained at or above 170 mmol/l for the next 24 hours, i.e. throughout 9 December. This was the &quot;plateauing effect&quot; to which reference is made in the expert evidence considered below. On 10-11 December the level did fall further but did not get below 157 mmol/l, still much higher than normal.
    • PM Report
      • There was evidence of trauma to Christian's head. The post mortem revealed 11 sub-scalp bruises which appeared to be recent. There were areas of subdural haemorrhaging and bruising, and the brain was grossly swollen. There were also retinal haemorrhages.
      • There was an area of infarction (in effect, death of the muscle) in the left ventricle of the heart, which had probably occurred while Christian was in hospital. It was the kind of injury that might be caused by a heart attack in an adult, but was most unusual in a young child. There was also some older infarction of a capillary muscle elsewhere in the heart.
    • Sodium Balance: Intake & Excretion Figure 20-11: Homeostatic responses to eating salt
    • Prof Haycock (Prosecution)
      • Two of the possible causes of such a high level of sodium have been ruled out:
      • (1)      severe dehydration, PH suggested expansion in the extracellular (low for blood urea and creatinine, haemoglobin and plasma albumin.)
      • (2)      known pre-existing metabolic disorders or other diseases.
      • Very sophisticated testing was done … to rule out all known existing disorders which might have caused that high level of salt.
      • Evidence drinking lots just before admission
      • Usually has to be persuaded to drink
      • PH opinion: Hypernatraemia was due to ingestion of salt (30-40g)
      •   Every reason to suppose that the kidneys were normal.
      • He should have excreted the excess sodium back to normal. Yet the sodium readings showed that the level did not fall as expected (in particular, there occurred the plateauing effect mentioned above), and a further set of readings for the &quot;fractional excretion of sodium&quot; showed likewise that the excess sodium was not being excreted.
      • PH thought that the most likely explanation for this was severe cardiac dysfunction. The premise being that cardiac dysfunction would increase Aldosterone secretion and sodium resorbtion
      • Congestive Heart Failure (CHF) and the effective circulating volume. In CHF there can be chronic  ECF volume (oedema) as an adaptation to decreased cardiac output because the effective circulating volume is low.
      • Cardiac Output and renal perfusion pressure are low 
              •  renin, AII, aldo,  sympathetic output
              • more Na + retention and more oedema
              • atrial stretch  restore cardiac output and perfusion of vital organs at the expense of expanded ECF volume
      • This new steady state depends on the persistent error signal of  ECF. ANP doesn’t correct this because the anti-natriuretic hormones increase Na + reabsorption proximal to the inner medullary collecting duct where ANP works. That is, not enough gets to the IMCD to have an impact.
    • Defence Dr Walters retired CP (Bristol)
      • Rejects the view that the hypernatraemia was caused by ingestion of salt.
      • First, there was the failure to excrete the load of salt allegedly taken.
      • Aldosterone Normal and heart showed some ventricular damage not enough to cause increase in Aldosterone (but post mortem sample)
      • Walters pointed out trials of salt ingestion leading to a low aldosterone
      •   Provided the regulatory systems are working normally, the body rejects excess sodium. Christian would have had to ingest an enormous amount of salt for his plasma sodium concentration to be so high. That should have led to a high rate of excretion of sodium. There was a high rate initially, but it tailed off and was back at a more normal rate after about 12 hours. It should have continued at the higher rate for at least 48 hours after admission.
      • Normally administering water will lower sodium
      • First, the excretion of sodium in the urine is enhanced: (dependent on the amount of urine formed)
      • Secondly, water is also retained through the action ADH: the effect is to dilute the concentration of sodium in the ECF.
      • The fluid balance charts show that towards the end Christian was being given only very dilute solutions of salt, and he passed large volumes of urine, but without a correspondingly high concentration of sodium.
      • At some stage during his admission he retained a lot of water, with some sodium, but still the sodium concentration did not fall below about 160 mmol/l.
      • Sodium concentration is regulated by the hypothalamus by osmoreceptors, known collectively as the osmostat, which trigger the release of ADH, and water retention
      • Thus, if the plasma sodium concentration rises, ADH is released so that a small volume of concentrated urine is formed, the amount of water retained in the body is increased and the sodium concentration is thereby brought down.
      • If the sodium concentration falls, the release of ADH is inhibited so that a large volume of dilute urine is passed, the amount of water retained in the body is reduced and the sodium concentration is thereby brought up.
      • A high sodium concentration results in the sensation of thirst,(Osmostat) which leads to drinking. In concert with the increased action of ADH on the kidney tubules, this enables lost water to be replaced.
      • The normal osmostat setting is 140 mmol/L
      • Case reports suggest the osmostat setting can be disturbed.
      • Most of the reported cases involve physical damage to the hypothalamus, e.g. as a result of surgery.
      • There are other, less common, cases in which no identifiable cause has been found: the description &quot;idiopathic&quot; is given to such cases.
      • Most of those other cases involve the downward resetting of the osmostat, so that the patient has a persistently low sodium concentration.
      • The upward resetting of the osmostat, resulting in a high sodium concentration, is much rarer.
      • There are, however, two documented cases of it: a 1985 paper by Gill, Baylis and Burn, A case of 'essential' hypernatraemia due to resetting of the osmostat , and a 1987 paper by Thompson, Freeman, Record and Baylis, Hypernatraemia due to a reset omsostat for vasopressin release and thirst, complicated by nephrogenic diabetes insipidus .
      • W's opinion: there is no reason in principle why the same event could not happen in a child,
      • Second possibility: Reduced sensitivity of the osmostat, such that the release of ADH or increase in thirst occurs much more slowly than with a normal osmostat.
      • Combined with an abnormality in his thirst mechanism.
      • It may be that Christian did not know what thirst was until the late stages when his plasma sodium concentration went abnormally high and he displayed frantic thirst on the morning he died
      • Routine tests in 1999 and 2000 (1 yr) showed normal sodium levels (135 to 140 mmol/l).
      • W’s hypothesis therefore required something to have happened thereafter to the hypothalamus to cause the osmostat to reset to a higher level
      • W considered that a reset could occur at any time (the trigger being unknown)
      • Change of this kind would not have affected Christian's ability to live a normal life.
      • Still difficult, however, to explain the sudden onset of acute illness, with the sodium level of 184 mmol/l on admission to hospital.
      • W considered that this was possible if Christian had been running with a plasma sodium level of, say, 160 or 165 mmol/l and then for some reason had become water depleted. If that happened there would be a surge in the plasma sodium and it could reach 184 mmol/l without clinical signs of dehydration.
      • Professor Haycock response
      • He could not see an event or illness in Christian's history that might have led to a change in the osmostat setting.
      • In all the cases of osmoreceptor dysfunction that he had seen himself or had studied in the literature, the patients had shown little or no thirst; and in none had there been anything like the frantic thirst displayed by Christian on 8 December
      • Nor did any of them involve the kind of catastrophic collapse seen in this case.
      • Christian's thirst on 8 December suggested a rapid rise in sodium concentration over a very short space of time. Ingestion of salt would do it. So would lack of access to water, but it would take a few hours at least to get to the point of severe thirst.
      • There then occurred the following important exchange:
      • &quot;Q. … Now just as you at trial … postulated heart failure as an explanation, do you agree that what Dr Walters has done is a quite legitimate exercise in postulating an alternative hypothesis; is that right?
      • A. Yes.
      • Q. And you are not in a position, are you, to say that he is wrong?
      • A. No, I am not.&quot;
      • Professor Haycock was asked a number of questions about why he had not mentioned the other possible cause of hypernatraemia,
      • A number of other matters were canvassed with Professor Haycock in cross-examination, including criticisms of certain of his analyses and calculations
    • Summing UP
      • Mr Mansfield (Defence). Not only was there a remarkable combination of features, including trauma to the head and hypernatraemia,
      • The damage to the heart was in itself a highly unusual feature in a child of this age.
      • The prosecution case on the cause of the hypernatraemia relied not simply on the existence of that damage to the heart, but on the hypothesis that there was heart failure sufficient to (increase Aldosterone )override the body's normal mechanisms for the excretion of excess sodium. (to explain the plateau)
    • The verdict
      • For the reasons we have given, the appeals are allowed on the ground relating to fresh evidence and the appellants' convictions of manslaughter on count 2 are quashed. We will hear submissions from counsel on whether a retrial should be ordered.
    • Guilty v Not Guilty
      • Why no Ur Osmolality or Ur Sodium measurements
      • If W is right and his normal running Na 165 mmol/L, trying to force it lower with infusions would precipitate CPM??
      • Injuries to head, could he have had Central DI ??
      • What if he had become so hypovolaemic that the low BP stimulated increase in Aldosterone. Only a small amount of salt ingestion could have pushed the sodium which would happen very quickly