Sp r training 2012 salt and water

Salt and Water

SpR training July 2012

Roderick Warren

Salt and water physiology

Aldosterone Vasopressin Where they act What they do What happens with the crisps and beer

Collecting duct principal cell – aldosterone and ADH receptors

ADH release:

• Osmolality (responds to 1% change)

• Effective blood volume (responds to 5-10% change)

Aldosterone release:

• Potassium

• Effective blood volume (detected at JGA)

ENaC – epithelial sodium channel

NCCT – sodium-chloride cotransporter

NKCC2 – sodium-chloride-potassium cotransporter

Other natriuresis pathways

ANP Release: atrial distension (and other triggers) Effects: increases GFR (affects renal blood

flow); decreases Na resorption by NCCT

BNP Similar to ANP

Pressure natriuresis

In the pub

1. Eat crisps and nuts

2. Feel thirsty, drink beer

3. Go to loo

Salt intakeIncreased osmolalityADH release

Fluid intakeIncreased volumeAldosterone suppressed

Excrete salt and water

Sodium balance

Recommended intake <100 mmol per day– 6g sodium chloride per day– 2.4g sodium per day

Average intake 150-200 mmol per day

Water

Salt

Sodium balance

IN

2 litres water

150 mmol salt

OUT

2 litres water

150 mmol salt

Causes of hyponatraemia

Pseudohyponatraemia?

Incorrect measurement due to presence of lots of lipid or protein

e.g. hypertriglyceridaemia

Often wrongly used to mean hyponatraemia due to another osmotic substance

Non-hypotonic hyponatraemia

Glucose Urea Mannitol Ethylene glycol

All draw water into blood Reduce serum osmolality

Detect by discrepancy between calculated and actual osmolality

(PS basically, serum osmo = plasma osmo)Bunting et al, Crit Care Med 1986; 14: 650

Calculated versus actual osmolality

Na 122 K 4.0 Urea 3.4 Gluc 4.5 Osmo = (122+4) x 2

+ 3.4 + 4.5

= 260

Measured osmo 320

Gap 370-240=60

Ethylene glycol intoxication

When to measure osmolality

Reasonable practice in all cases But remember what it’s for:

– to diagnose a non-measured solute– ethanol– methanol– ethylene glycol

Hyperglycaemia

Osmotic effect of high glucose draws water into blood, and dilutes sodium (and everything else)

Correction factor– 1 mmol/L Na = 3.5 mmol/L glucose

Possibly more pronounced at glucose > 25 mmol/L– 1 mmol/L Na = 1.4 mmol/L glucose

Ref Hiller et al, Am J Med, 1999; 106: 399. Penne et al Diabetes Care 2010; 33: e91.

Hyperglycaemia

Admission – simple hyperglycaemia

Na 124

Glucose 45

Urea 8.2

After IV insulin

Na 139

Admission – HONK

Na 146

Glucose 45

Urea 28.2

After IV insulin

Na 160

Hypotonic hyponatraemia: causes

Shout them out

Diuretics

Primary adrenal failure

Primary renal disease

Pseudohypoaldosteronism

SIADH

Glucocorticoid deficiency

Pregnancy

Reset osmostat

Excess water intake

Heart failure

Cirrhosis

Nephrotic syndrome

GI loss (vomiting, diarrhoea)

Skin loss (burns, sweating)

Third space (pancreatitis)

Dietary deficiency (anorexia)

Hypovolaemic Euvolaemic Hypervolaemic

Renal sodium loss

Diuretics




SIADH


Pregnancy

Reset osmostat

Excess water intake

Heart failure

Cirrhosis

Nephrotic syndrome

Other sodium loss

GI (vomiting, diarrhoea)

Skin (burns, sweating)



Assessing volume status

Either: obvious or euvolaemic

Think you can do better? Two expert nephrologists

carefully reviewed 58 patients with hyponatraemia

Clinical judgement compared with response to IV saline

Actual

Dry Normal

ClinicalDry 7 22

Normal 8 21

For detecting volume depletion:

• sensitivity 47%

• specificity 49%

Chung et al Am J Med 1987; 83: 905

Hypovolaemic hyponatraemia

Cause Clue

Diuretic Obvious

Primary adrenal Symptoms, signs, cortisol

Primary renal Renal failure, urine dipstick

D&V Usually obvious from history

Anorexia Usually obvious

Skin loss Usually obvious from context

“Third space” Uncommon

If in doubt

Renal sodium loss

Diuretics




Urine Na not low

Other sodium loss





Urine Na low (<20 mmol/L)

Diuretic-induced hyponatraemia

Gitelman syndrome (like thiazide treatment) – hypokalaemia, alkalosis, hypocalciuria, hypomagnesaemia

Bartter syndrome (like loop diuretic) – alkalosis, hypokalaemia, hypovolaemia, hypercalciuria

Diuretic-induced hyponatraemia

94% of reported cases are with thiazides Rapid onset (hours-days) – longer with loops Why? Possible causes:

– patients on thiazides are in water balance or slight water excess (perhaps due to ADH release)

– short half-life of loop diuretics (brief electrolyte excretion, then avid retention)

Adrenal failure

Aldosterone deficiency– normally protects sodium (at expense of

potassium)

Cortisol deficiency– tonic inhibition of ADH– profound cortisol deficiency causes SIADH-like

picture

Hypervolaemic hyponatraemia

Usually clinically obvious Said to be dilutional (though I think poorly

understood) ADH stimulated by reduced stretch receptor

stimulus due to...– poor cardiac output– reduced intravascular volume

Hypothyroidism is not a cause

Serum sodium distribution in 1000 hypothyroid patients and 5000 controls

95% ranges:132-144 (hypothyroid)134-144 (control)

Hypothyroidism lowers serum Na by 0.48 mmol/L

Warner et al, Clin Endo 2006; 64: 596.

Syndrome of inappropriate antiduretic hormone

Causes of SIADH

Drug causes Non-drug causes

Tricyclic antidepressants;Selective serotonin reuptake

inhibitors;Opioids;Antipsychotics (e.g. haloperidol,

chlorpromazine, flupentixol, trifluoperazine);

Dopamine agonists;Nicotine;MDMA (Ecstasy).Anti-epileptics (carbamazepine,

valproate);

Malignancy: most, but especially lung.Infections: pulmonary (pneumonia,

TB, empyema); cerebral (e.g. meningitis,

abscesses).Nervous system disease: haemorrhage; infarction; demyelination (e.g. MS,

Guillain-Barré).

Normal ADH release

a – Random

b – Non-suppressible basal ADH levels, but normal response to raised plasma osmolality

c – Reset osmostat. ADH rises in response to plasma osmolality, but is always higher than it should be.

Patterns of SIADH

What happens in SIADH?

Syndrome of inappropriate antidiuretic hormone

Why doesn’t the patient swell up?


Water

Salt

Normal state

Inappropriate ADH

Water

Salt

Hyponatraemia

Tendency to hypervolaemia

Compensatory mechanisms – aldosterone etc

Water

Salt

Hyponatraemia

Euvolaemia

Water retention

Salt and water

excretion

http://www.google.co.uk/imgres?imgurl=http://openclipart.org/people/sillius/becher.svg&imgrefurl=http://openclipart.org/detail/104647/becher-by-sillius&usg=__nQmzgiXzQT2up2eD50UkicmiWBI=&h=400&w=400&sz=5&hl=en&start=37&sig2=gm8kwF8UJFDYK-3-nkKj3g&zoom=1&tbnid=iNq1Tj8L25nYBM:&tbnh=124&tbnw=124&ei=WcntT8zDM4PU0QWz3Yn_DQ&prev=/images%3Fq%3Dbeaker%2Bimage%26start%3D21%26hl%3Den%26sa%3DN%26gbv%3D2%26tbm%3Disch&itbs=1



Experimental SIADH

Leaf et al 1953 J Clin Invest 1953; 32: 868

SIADH in theory

24-hour urine

sodium excretion

Serum sodium concentration

Onset Maintenance Recovery

SIADH in theory

1. Fluid intake is required to become hyponatraemic

2. During onset, urine sodium excretion is high

3. SIADH = euvolaemia with total sodium deficit

4. In steady state, urine sodium = sodium intake

5. Sodium intake is required to correct hyponatraemia

6. In recovery, urine sodium is low (as for recovery from hyponatraemia of any cause)

Limitations: urinary sodium

Range of sodium intake 60-250 mmol Range of water intake 1200-4000 mL Urinary sodium concentration

– from 15 mmol/L to 208 mmol/L

Limitations: urinary osmolality

“Urine osmolality < serum osmolality excludes SIADH”

Average protein intake 70g/d = 350 mmol urea Average sodium + chloride = 300 mmol Average potassium = 60 mmol

Total about 700 mmol Average urine osmo = about 3-400 mOsm/kg

http://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/19710023044_1971023044.pdf

SIADH may be steady state

24-hour urine

sodium excretion



Average urine osmo about

3-400

Average urine osmo = about 3-400 mOsm/kg

Maybe 6-800 on waking Maybe 200 after drinking

Limitations: urinary osmolality

So how can we diagnose SIADH?

By ruling out other diagnoses.

But you can exclude if: random urine osmolality <100 mOsm/kg random urine sodium <20 mmol/L except in the recovery phase

Low urine Na (and osmo) during recovery phase

24-hour urine

sodium excretion



Example 1

76-year old admitted with chest infection.

Clinically euvolaemic.Day 1 2 3 4 5 6 7

S Na 130 125 118 117 119

S Osmo 260 250

S Urea 5.6 4.3 4.0 4.8

S Creat 65 68 58 63

S Cort 680

U Na 76

U Osmo 420

Example 1

Hyponatraemia Clinically euvolaemic No renal failure Normal cortisol Non-low urine sodium and osmolality Could well be SIADH

Example 2

45-year old admitted with D&V.

Looks dry.Day 1 2 3 4 5 6 7

S Na 130 125 118 117 119

S Osmo 260 250

S Urea 5.6 6.3 8.0 9.8

S Creat 65 68 98 123

S Cort 680

U Na <20

U Osmo 180

Example 2

Hyponatraemia Clinically hypovolaemic Degree of renal failure Normal cortisol Low urine sodium and osmolality History of GI loss

Example 3

76-year old admitted with chest infection.

Clinically euvolaemic.Day 1 2 3 4 5 6 7

S Na 130 125 118 117 119 124 130

S Osmo 260 250

S Urea 5.6 4.3 4.0 5.8 6.9 5.8 5.7

S Creat 65 68 58 73 76 68 65

S Cort 680

U Na <20

U Osmo

Example 3

Hyponatraemia Clinically euvolaemic No renal failure Normal cortisol Low urine sodium DURING RECOVERY Uninterpretable

Example 4

66-year old with heart failure.

Oedematous.Day 1 2 3 4 5 6 7

S Na 126 127 125

S Osmo 260 260

S Urea 9.6 11.3 12.0

S Creat 124 136 140

S Cort 680

U Na 40

U Osmo

Example 4

Clinical picture is heart failure So that’s the diagnosis Non-low urine sodium excludes GI loss In steady-state, urine sodium = sodium intake,

including if hypervolaemic Fluid restriction is appropriate even if SIADH

superimposed

Treatment of hyponatraemia

Treatment of hypotonic, hypovolaemic hyponatraemia

Hypovolaemic

Renal sodium loss

Diuretics




Other sodium loss





Treatment:

• Salt and water

• +/- Glucocorticoids

Treatment of hypotonic, hypervolaemic hyponatraemia

Treat underlying cause:

• e.g. rate control, digoxin

• e.g. sepsis

Remove fluid:

• paracentesis

• diuretics?

Fluid restrict

Hypervolaemic

Renal sodium loss

Heart failure

Cirrhosis

Nephrotic syndrome

Other sodium loss

Treatment of hypotonic, euvolaemic hyponatraemia

Euvolaemic

Renal sodium loss

SIADH


Pregnancy

Reset osmostat

Excess water intake

Other sodium loss

Treat cause of SIADH:

• e.g. stop drug

• e.g. antibiotics or chemotherapy

Fluid restrict:

Give drugs:

• demeclocycline

• vaptan

When is acute treatment needed?

Sodium Effect

130-135 Usually asymptomatic

120-130 Non-specific malaise

<120 Confusion, ataxia, headache

Lower Depressed consciousness, seizures, death

When is acute treatment needed?

Acute vs chronic (> or < 48 hr) Acute: increased risk of cerebral oedema Chronic: increased risk of CPM

Condition Confusion, seizures, other neurology

Sodium concentration 120 mmol/L is a common threshold

Pragmatism Availability of HDU/ICU, and of hypertonic saline

What is acute treatment?

Boluses of hypertonic saline If neurologically obtunded 100mL bolus of 3% saline, up to three times Will raise serum Na by 5-6 mmol/L

Infusion of hypertonic saline 0.5 ml/kg/hr Will raise serum Na by 7-10 mmol/L/24 hr

Mohmand et al Clin J Am Soc Nephrol 2007; 2: 1110

What about normal saline?

Exacerbates hyponatraemia…?

Infusion of 2 litres normal saline

Mean pre-treatment Na 126; n=17

Saline seems to help if urine osmolality <500

Musch et al Q J Med 1998; 91: 749

What do you do in a normal UK hospital?

Serum sodium = 117 mmol/L If significant neurological symptoms,

definitely admit to ICU Otherwise:

– send serum osmo, cortisol, urine osmo early– zero oral fluid– give 1 litre 0.9% saline initially– monitor Na frequently

Rate of correction

Urgent correction needed e.g. seizures 5-8 mmol/L in the first hour

First day 8-12 mmol/L

First 48 hours 12-18 mmol/L

Fluid restriction

In milder cases, begin at one litre More liberal restriction may be OK if previous

fluid intake was high

Very tight restriction may be needed E.g. 500ml or zero

Fluid restriction

Needs to be strict and tight Must be thirsty, or ineffective Will cause rise in urea/creatinine


Water

Salt

Normal state

Inappropriate ADH

Water

Salt

Hyponatraemia

Tendency to hypervolaemia

Compensatory mechanisms – aldosterone etc

Water

Salt

Hyponatraemia

Euvolaemia

Water retention

Salt and water

excretion




What happens in fluid restriction?

Water

Salt

Normal state (but a bit dry)

Fluid restriction

Water

Salt

Hyponatraemia

Euvolaemia

Water

Salt

Hyponatraemia

Hypovolaemia

Aldosterone ↑

ANP, BNP ↓

Dehydration Salt and water retention

Demeclocycline

Dose 600-1200mg daily Induces nephrogenic DI in 70% of cases Usually 2-3 days to take effect

– but can be dramatic onset

Problems Avoid if eGFR<30 Can cause irreversible nephrotoxicity Nausea Photosensitivity Hypersensitivity to tetracyclines (anaphylaxis, urticaria)

Vaptans

V2-receptor antagonists Directly inhibit ADH

Vaptans

Tolvaptan

SALT-1 and SALT-2 trials 448 patients with hyponatraemia Euvolaemic or hypervolaemic CCF, cirrhosis, SIADH Randomized to:

– placebo– tolvaptan 15mg od, increased as needed

Schrier et al N Eng J Med 2006; 355: 2099.

Vaptans

Schrier et al N Eng J Med 2006; 355: 2099.

Vaptans

Problems Few side effects – thirst, dry mouth Cost:

– £75-£150 per day– £27,000 to £54,000 per year– to raise serum Na by about 5 mmol/L

Restricted use– recurrent profound hyponatraemia

Urea

Osmotic diuretic Rapid entry into cells – avoids sudden plasma

volume explansion Barely penetrates brain – avoids cerebral oedema 0.5 – 1 g/kg/day

Unavailable in UK 10 cans of baked beans 1kg meat

Why treat chronic hyponatraemia?

No decent long-term therapy Why bother? Long-term adaptation to hyponatraemia?

But possibly: Gait disturbance Falls Osteoporosis

Gait and hyponatraemia

Centre of pressure path, while walking right to left•Before correction (Na 124)•After correction (Na 135)

Renneboog et al Am J Med 2006 119 e1-8

Profound cortisol deficiency

Causes SIADH-like picture (or just SIADH?) Cortisol is tonic inhibitor of ADH secretion

Acute reversal with glucocorticoid Rapid excretion of free water Rapid rise in serum sodium Risk of myelinolysis

Profound hyponatraemia needs intensive monitoring

Frequent checks of serum sodium Meticulous fluid balance If rising too rapidly consider:

– stop saline– give dextrose– desmopressin

Cerebral salt wasting

Described in neurosurgical patients Thought to be mediated by BNP (SIBNP?) Hyponatraemia post SAH Cue scratching of heads Is it SIADH? Is it CSW?

SIADH CSW

1. ADH ↑ 1. BNP ↑

causing water retention causing salt and water loss

2. Renin, aldo ↓ 2a. ADH ↑

causing salt and water loss causing water retention

2b. Renin, aldo ↑

salt and water retention

What’s the difference?

Fluid replete Potentially fluid deplete

Urine sodium ↑ or normal Urine sodium ↑ or normal

Maybe renin, aldo ↓ Maybe renin, aldo ↓

Treatment: fluid restrict or saline

Treatment: saline

Prevalence? 3/23 in a study from Kuwait

CXR In all

Further investigation e.g. CT If persistent If other symptoms/signs

SIADH and lung cancer

Serum osmolality Low (<270) High-treat cause-urea, glucose, toxins

Fluid volume status

Deplete-history of D&V?-diuretics?-cortisol?

Replete Overloaded- treat cause- CCF, liver

Check cortisol, urine osmo, urine Na

Low urine osmoLow urine NaLook for GI loss

RepleteNon-low urine osmoNon-low urine NaNormal cortisolProbable SIADH – fluid restrict

Sp r training 2012 salt and water

Health & Medicine

Transcript of Sp r training 2012 salt and water