Hyponatraemia

a. Addison’s diseaseb. Compulsive water drinkingc. Treatment with diureticsd. Syndrome of inappropriate antidiuresis

A 54-year-old male smoker complaining of weight loss and haemoptysis, who is found to have a plasma sodium concentration of 114 mmol/L.

What is most likely diagnosis?

Answer

d. Syndrome of inappropriate antidiuresis

How do you prove ?

Paired serum / urine for:SodiumOsmolality

Hypo – ‘rhubarb’

• Serum rhubarb• Serum renal function and electrolytes• Urine creatinine, sodium and rhubarb• Urine and plasma osmolality• ALL SHOULD BE PAIRED

49yr old female - Low sodium - ? SIADH

Sodium = 125 mmol/L Potassium = 4.9 mmol/L

Urea = 7.2 mmol/L Creatinine = 67 mmol/L

Glucose = 3.5 mmol/L Osmo = 263 mosmol/Kg

LFT = NAD TFT = NAD

Urine sodium = 82 mmol/L Urine osmo = 467 mosmol/Kg

Is this SIADH ?

What else do you need to know ?

What other tests are required ?

Cortisol = < 25 nmol/l

Why is the potassium normal ?

• What is the single most important clinical assessment to make in a patient with hyponatraemia ?

A middle-aged woman with a long history of rheumatoid disease complains of fainting episodes.

Plasma sodium concentration is 128 mmol/L.

The sodium concentration of a random urine sample is 80 mmol/L.

Postural hypotension is demonstrable.

What diagnoses are compatible with these findings?

Answer

Adrenal failureAnalgesic nephropathyOver treatment with diuretics

LEARNING POINT:

You must know the volume status of your patient.

CAUSES OF HYPONATRAEMIA:– Depletion of sodium – eg Adrenocortical insufficiency– Water excess – eg SIADH, iatrogenic (excess administration

of hypotonic fluids such as 5% dextrose– Combined water and sodium excess – eg CCF.

KEY INVESTIGATION OFTEN OVERLOOKED

• Urine electrolytes

• Assess urine at same time as plasma, and when plasma abnormalities still present.

• If in ‘reasonable’ steady state, then 24 hour collections may be required.

• If serum ‘analyte’ sufficiently abnormal then comparison to random urine may be possible (is urine chemistry appropriate to plasma chemistry). Will need to look for patterns (eg high / low Na and K)

SODIUM• In hyponatraemia, the kidney should conserve sodium to

less than 20 mmol/L

• Urine concentration can be influenced by water reabsorption – thus use FeNA

• Distinguish inappropriate renal loss (typically ATN) from volume depletion

• Dividing line often stated as 1% (much higher in neonates) but can vary in states effecting amount of sodium filtered.

URINE CHEMISTRY• Parameter

Sodium

Chloride

Potassium

Osmolality

pH

• Uses• Assessment of volume status• Diagnosis of hypoNa and ARF• Evaluation of calcium and urate

excretion in stone formers

• Diagnosis of metabolic alkalosis• Urine anion gap

• Diagnosis of hypokaleamia, ratio to sodium in neonatal supplementation

• HypoNa, hyperNa, ARF, DI, concentrating ability

• Diagnosis of RTA• Volume status

• HYPOKALEAMIA:

What clinical observation is most important to drive investigations ?

A 40yr old patient has a plasma potassium concentration of 2.8 mmol/L; plasma bicarbonate is 34 mmol/L.

What clinical observation is required to help drive investigations ?

BLOOD PRESSURE – this patient is hypertensive

What are the possible diagnoses/ explanations which explain all these findings?

Answer

Conn’sRenal artery stenosis bp with thiazides

Mrs D B age 35Aug 02 Referred by GP for management of

hypercholesterolaemia

Chol = 9.8 mmol/lTG = 1.2 mmol/l

FH Father uco DBF for FHC2 brothers – normal cholesterolGrandfather – DM

PMH Nil

DH Simvastatin 10mg nocteLoguynon[Atorvastatin caused muscle pain]

SH marriednon smoker, no alcoholno childrensells travel insurance

SQ diet poorasymptomatic

O/E BMI 25.2FitEuthyroidBp = 100/70P = 68srHS I + II + O

Investigations Cholesterol 6.5 mmol/lLFTs normalCr = 61 mol/lNa = 138 mmol/lK = 2.7 mmol/l

Repeat @ GP

22.8.02 Cr = 56 mol/lNa = 134 mmol/lK = 2.5 mmol/l

? cause of Hypokalaemia

Hypokalaemia

• Renal• Extrarenal

Redistribution

Inadequate intake

Excessive loss

Mx 1. GP question re:diuretic abuse, liquorice

2. Simvastatin 20 mg3. Effervescent K+ 4 tabs/day

18.9.02 Cr = 65 mol/lNa = 136 mmol/lK = 2.6 mmol/l

Mx Eff K+ - 6 tabs/day

Seen in Oct 2002

Well, asymptomaticbp = 110/70

DH Simvastatin 20mgLoguynonEff K+ 6/day

Investigations Cr = 47 mol/lNa = 135 mmol/lK = 3.1 mmol/l

? further investigations

24 hour urine K+ = 155.2 [40-120 mmol]Na+ = 249 [100-250 mmol]

Serum Cr = 53 mol/lNa = 135 mmol/lK = 3.0cCa = 2.49Magnesium = 0.54 [0.8-1.00]Bicarbonate = 31

Hypomagnasaemic hypokalaemia alkalosis

24 hour urine calcium = 1.35 [2.5-7.5 mmol]

chloride = 277 mmol

Urine calcium/creatinine = 0.08

? DDX

Gitelman’s confirmedRx Magnesium glycerophosphate ii tds

Eff K 6/daySimvastatin 20 mg nocte

Seen 5.2.03WellAsymptomatic

U = 5.8 mmol/lNa = 136K = 3.2Mg = 0.56Chol = 7.0

Rx Add spironolactone 50 mg OD

Further investigations

Cr Clearance = 152 ml/mn

Calcium creatinine ratio = 0.18

Urine osmolality = 708 mosm/kg

Urine magnesium = 6.32 mmol/l

Urine K+ = 140

Urine Ca = 2.15

CLINICAL VIGNETTE - HYPERKALAEMIA

67 yr old female.

Seen by multiple GP’s within her practice over a 12 month period.

Seen by Consultant vascular surgeon for intermittent claudication – commenced clopidogrel.

Known diabetic with persistent hyperkalaemia (5.8 – 6.9 mmol/L).

Relatively poor diagnostic investigation of hyperkalaemia.

Normal creatinine. And renal function.

Clinical Biochemist D/W GP.

Advise:

Repeat bloods (not in community)

Urine potassium.

Full blood count.

FBC showed gross primary polycythaemia:

Haemoglobin = 18.7 g/dL [11.5 - 16.5]

WBC = 13.4 x 109 / L [4 –11]

Platelets = 1195 x 109 / L [150 –450]

Packed Cell Volume = 57% [37 – 47]

Biochemist liaises with Consultant Haematologist:

GP advised by Biochemist that:

FBC accounts for hyperkalaemia

Patient at high risk of thrombotic event

Haematologist advises start aspirin ASAP and will see urgently in OPD.

Patient seen 7 days later

‘Barn door’ primary polycythaemia

Immediate venesection 1/52 repeats

Immediate hydroxycarbamide

US abdomen to assess spleen and assess palpable pulsatile mass ? aneurysm

GP’s frequently see spurious hyperkalaemia

What should I do about high serum potassium?

Identify patients at risk of having true rather than spurious hyperkalaemia or at risk from its effects:

•Those with known chronic kidney disease (CKD)

•Patients on potassium-raising drugs, notably, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and, potassium-sparing diuretics, potassium salts

(including LO salt®) or laxatives (Movicol, Kleenprep Fybogel)

•Patients with obstructive uropathy

•Patients with clinical features such as myopathy, paralysis, arrhythmias, bradycardia

•Those at greater risk from severe hyperkalaemia: elderly (> 70 years), serum urea (> 8.9 mmol/L)

•Patients with acute illness (e.g. acute renal failure, ketoacidosis)

•Consider spurious hyperkalaemia in the absence of all the above.

http://www.bettertesting.org.uk/?id=-1379

POTASSIUM• Appropriate response to hypokalaemia is to

conserve to less than 10mmol/L

• <10 confirms extra-renal losses

• > 25 confirms some degree of renal wasting

• TTKG – should be < 5 in hypoK and > 9 in hyperK

19yr old female.

Polydipsia + polyuria. Drinks approx 5 – 7 litres per day.

Investigations:

U+E = NAD TFT = NAD

Calcium = NAD

Glucose = NAD

? DI

What is best screen for GP to perform:

Early morning urine osmolality.

OSMOLALITY

• Hypoosmolar hyponatraemia should abolish AVP release (ie maximally dilute urine < 100 mosmol/Kg)

• Hypernatraemia Uosmol should be > 600 mosmol/Kg. If less than plasma omso then primary renal water loss

• Urine osmo > 750 makes DI unlikely

• Urine osmolality– In children old enough to stay dry overnight

(with low index of clinical suspicion), consider early morning (first urine passed) osmo – value above 750 mosmol/Kg excludes DI. Do not attempt if urine volumes > 30 ml/Kg body weight, or high index of suspicion to avoid hypertonic states.

56yr male

PC: Moderate increase in sweating; ? Some weight loss.

Routine TFT:

fT4 = 6 pmol/L [12 – 25]

TSH 1.23 mU/L [0.35 – 5.5]

Sick euthyroid

Poor compliance

T3 therapy

• Further investigations:

• Sodium = 128 nmol/l Other U&E NAD• Cortisol (08:30 am) = 208 nmol/l

Prolactin 167 mU/l• Testosterone = 2.9 nmol/L LH =

1.9 U/l, FSH = 2.8 U/l

Dx: Infarcted pituitary adenoma.

• 60 year old female, generally unwell, abdominal pain.

• U+E = NAD• LFT = NAD• Calcium = 2.9 mmol/L

• PTH = 5.9 pmol/L [1.5 – 7.7]

CHOL = 8.4 mmol/LHDL = 2.2 mmol/LTG = 0.9 mmol/L

What tests would you request next:a. Fasting glucoseb. 9 am Cortisolc. Bone profiled. FT4 TSH

e. LFTs

51-year-old female on routine vascular risk programme was found to have following blood test results

Answer

d. TFTse. LFTs

Case (cont)FT4 TSH normalALB = 38 gl/LAST = 40 u/LALP = 280 iu/L [<120]Bil = 28 µmol/L? What test/s nexta. 24 hour urine proteinb. Immunoglobulinsc. Auto antibodiesd. FBC

(p.133)

Answer

b. Immunogloblins ( 1 gM)c. Auto antibodies (antimitochondrial dbs)

2A 18-year-old man is noticed by a friend to be jaundiced immediately following a mild ‘flu-like’ illness. He has otherwise been well. His serum biochemical results are: bilirubin 80 µmol/L, aspartate aminotransferase 42 IU/L, alkaline phosphatase 82 IU/L, albumin 44 g/L. His urine tests negative for bilirubin.

What is the most likely Dx?

(p.133)

Answer

GilbertsHaemolysisUnconjugated bilirubin

17 yr girl – known anorexia. Recently commenced monitored re-feeding regime.

Sodium = 138 mmol/L Potassium = 4.1 mmol/L

Urea = 3.3 mmol/L Creatinine = 48 umol/L

Albumin = 37 g/L Bili = 11 umol/L

ALP = 83 IU/L ALT = 534 IU/L

? Cause of raised ALT

? What other tests required

? Follow-up

4

A fit, elderly man has biochemical tests performed as part of a ‘well-man’ screen. The only abnormality is a serum alkaline phosphatase activity of 200 iu/L.

What are the possible causes?

Answer

OstoemalaciaPagetsTumour metastases to liver

12 month infant

Admitted D+V

Bilirubin = 10 umol/L

Albumin = 40 g/L

Protein = 64 g/L

ALT = 27 IU/L

ALP = 2879 IU/L

a. Aspartate transaminase activity 60 IU/Lb. -Glutamyl transpeptidase acitivity 120 IU/Lc. Total cholesterol 9.6 mmol/Ld. Triglycerides (fasting) 4.2 mmol/Le. Urate concentration 0.48 mmol/L

A 40-year-old journalist with a history of excessive alcohol ingestion undergoes an ‘executive health screen’. Which of the following biochemical results from analysis of serum suggest the presence of an additional problem?

(p.134)

Answer

c. Cholesterol 9.6 mmol/L

a. Chronic osteomyelitisb. Multiple myelomac. Osteoarthritisd. Paget’s disease of bonee. Renal osteodystrophy

An elderly woman complains of back pain: serum total protein concentration 85 g/L; albumin, 30 g/L. The presence of the following condition could explain these abnormalities

Answer

a. Osteomyelitisb. Myeloma

The following results are found in an adult patient presenting with weight loss, diarrhoea and abdominal discomfort: serum calcium concentration 1.95 mmol/L, phosphate 0.6 mmol/L, albumin 32 g/L, alkaline phosphatase 230 iu/L.

What further biochemical investigations would you request?

Answer

25-0H vitamin D PTHCaMalabsorption of fat

• 14 yr old female, hirsute, lack of secondary sexual characteristics, primary amenorrhoea

• Testosterone = 2.7 nmol/L• LH = <0.5; FSH = 3.6, oestradiol undetectable• TFT = NAD• 5pm cortisol = 944 nmol/L

a. Hypothyroidismb. Non prolactin-secreting pituitary tumoursc. Normal pregnancyd. Sheehan’s syndromee. Amisulpiride therapy

Hyperprolactinaemia is recognised to occur in patients with

Answer

a. Hypothyroidb. Non prolactin-secreting pituitary

tumoursc. Normal pregnancye. Amisulpiride

Miss EV age 19 yearsreferred by GP with secondary amenorrhea

PMH Seen in 2001 with 2° amenorrhea by GynaecologistInvestigations LH, FSH, PRL, etc all normal

DH COCFH HypertensionSH Lives with parents

Care AssistantNo boy friend

SQ K = 12 Para = 0+0 II = 28 until May 2001 GP started her on COC Headaches on and off for 2 years

O/E BMI 28

Euthyroid

No hirsuitism

No galactorrhea

bp = 110/70

Question 1

What would you do next?

Answer

Progress 1. Diet2. Stop COC3. Hormone profile

Results FT4 = 18 pmol/L [12 – 23]TSH = 1.6 mU/L [0.6 – 4.8]LH = 1.1 U/LFSH = 2.7 U/LPRL = 9,823 U/L [70 - 566]Preg test = negative

Stop COC, baseline LH, FSH, TFTs and PRL

Question 2

What would you do next?

Answer

Repeat PRL >11,000 U/LAll Monomeric PRL

MRI scan“very large pituitary tumour with 2cm suprasellar extension elevating the optic chiasm”

Repeat ProlactinScreen for Macroprolactin

Progress

Mr DW dob 20/8/41LVFA fibrillation

PMH CABG 1989Angioplasty 2004MI – 1998HypertensionHypercholesterolaemiaType 2 DM

DH FrusemideClopidogrelNicorandilAmiodaroneSimvastatinEzetimibeWarfarinRamiprilBisoprolol

Allergies None

SH Ex smokerOccasional alcoholLives with wife

FH none

O/E p = 130 AF

bp = 143/76

chest basal crackles

JVP 5 cm

No ankle oedema

HS I and II and 0

U = 10.7 mmol/l [2.5 – 6.5]

Cr = 124 mmol/l [60 – 120]

Na = 131 mmol/l

K = 3.6 mmol/l

FT4 = 100.2 pmol/l [12 – 23]

TSH = <0.06 mu/ml [0.35 – 5.5]

Question

In addition to treating his AF and LVF, how do you think the patient’s deranged thyroid function should be treated?

Answer

Stop AmiodaronePTU

14

a. Repeat in 3 monthsb. Measure serum anti-TPo absc. Treat with levothyroxined. Measure 9 am Cortisol

25-year-old female with menorrhagia

FT4 = 11.5 pmol/L [10 – 20]

TSH = 8.3 mu/L [0.4 – 4.5]

What do you do next?

Answer

a. Repeat in 3 monthsb. Anti TPO abs

• 58 year old male with strong FHx of CHD. Non-smoker with BMI = 26.5.– Fasting glu = 4.6 mmol/L– Chol = 8.4 mmol/L– HDL = 1.1 mmol/L– Trig = 2.1 mmol/L

• GP initiates simvastatin.• 3/52 – complaining of malaise• CK = 850 U/L [<170]

• What test(s) are required to investigate the raised CK ?

• a). CK isoenzymes• b). FBC• c). TFT’s• d). HbA1c• e). U+E

• a). TFT

• Which one of the following findings in a patient with primary hypothyroidism could not be explained by this condition ?

• a). Hyponatraemia• b). Increased mean red cell volume• c). Plasma cholesterol of 7.2 mmol/L• d). Plasma ALP 2x the ULN• e). Plasma CK 2x the ULN

• d). Plasma ALP 2x the ULN

• Elderly female with weight loss and abdo pain radiating to the back.– Bilirubin = 225 µmol/L– Albumin = 36 g/L– Protein = 68 g/L– AST = 42 U/L– ALP = 455 U/L– Gamma-GT = 72 U/l– Urine positive for bilirubin

• What is the provisional diagnosis ?• a). Hepatic mets form ca colon• b). Primary biliary cirrhosis• c). Carcinoma of the head of pancreas• d). Autoimmune chronic hepatitis• e). Sclerosing cholangitis

• c). Carcinoma of the head of pancreas

Male infant.

Born at term. At approx 45 mins age noted to have no cardiac output. Resuscitated, RIP few days later.

Troponin = 2.9 ng/ml

Interpret ?

83 year old female admitted with confusion and mobility

Dx chest infection and congestive cardiac failure

InvestigationsU = 25.2 mmol/l (2.5 – 6.5)

Creatinine 122 mmol/lCalcium 3.2 mmol/l (2.2 – 2.6)US abdo - grossly distended

bladder – chronic retentionCT headPTH = 8.3 pmol/l

Progress RehydratedLong term catheterBiphosphate for Ca

BUT

CA 125 = 8017 U/ml (<20)

Progress CT pelvis ?thickening of anal – rectal junctionGynae outpatient review and other investigationsCA 125 normal within 38 days

Elevated CA 125 seen in Heart failureAscitesHypothyroidismAdvanced ovarian cancer

The cost• CA 125 estimation

= £8.55• Extra 10 days IP• CT pelvis• Repeat USS pelvis• Repeat CA125 x2• Sigmoidoscopy x2• Rectal biopsy• Gynae OPD

Cost at tariff = £5,000

Antenatal testing

Allergy

Anaemia

Anticoagulant monitoring

Arthritis, inflammatory

Blood count abnormalities

Cancer testing

Cholesterol and lipids

Deep vein thrombosis (DVT) or pulmonary embolism (PE)

Diabetes

Drug safety monitoring

Erythrocyte sedimentation rate

Infections

Infections – viral

Laboratory investigations of chronic diarrhoea

Liver function tests

Myeloma, electrophoresis, immunoglobins

Myocardial infarction

Peptic ulcer/ Helicobacter

Renal/Electrolytes

Sex hormones

Thyroid testing

Topics

Causes of redistribution hypokalaemia

In vitro redistributionUptake by white blood cells (eg in leukaemia)Uptake by erthrocytes following in vitro insulin

administrationIn vivo redistribution

AlkalosisIncreased plasma bicarbonateInsulin administrationb-Adrenergic agonistsToxic chemicals (toluene, soluble barium salts)Hypokalaemic periodic paralysis

Extrarenal lossInadequate intakeFasting

anorexiaduring rapid cell synthesis

Increased lossExcessive sweatingGastrointestinal

fistuladiarrhoeacation exchangegeophagia

Fruit Juice

Tomato

Orange

Grapefruit

Apple

Farmhouse cider

Potassium mmol/100 ml

8.2

3.0

3.0

3.2

3.2

Normal adult intake 40-120 mmol/day

Renal causes of potassium depletion

• Acidosis• Alkalosis + Normotension• Alkalosis + Hypertension

• 6 week old female. Choking episodes, ? Seizure, FHx of endocrine disease.

• Adjusted calcium = 2.94 mmol/L• Phosphate = 1.88 mmol/L• U+E, LFT, Mg = NAD• PTH = 5.7 pmol/L

• Random urine calcium = <0.5 mmol/L• Random urine creatinine = 1.4 mmol/L• Random urine phosphate = 5.9 mmol/L

• TFT = NAD• Vit D = 45 nmol/L

38yr female

Referred to lipid clinic for FH.

Coincidentally noted to have serum potassium of 2.5 mmol/L (confirmed on repeat).

24hr urine K = 155 mmol/L, sodium = 249 mmol/L

? Provisional interpretation

? Follow –up tests

? Follow –up tests

Bicarb (32) or ABG

Magnesium – 0.54 mmol/L

TTKG (11) / FeNa

Urine chloride (277 mmol/L) – WHY USE THIS ?

Urine calcium creatinine ratio = 0.08

Urine magnesium = 6.9 mmol/L

? CK

Renin (9.8) / aldosterone / cortisol (? Dynamic test)

Note specific requirements of PRA for drug

Hx and K level.

If suspicious store sample for diuretic screen.

WHAT IS DIAGNOSIS

• Baby A.• Previous NEC treated surgically• Persistent metabolic acidosis - ? RTA, ? Stoma losses

underestimated (bag leaking) / underreplaced. Clinically no concerns re volume status.

PLASMASodium = 144

Potassium = 5.2

Urea = 3.5

Creatinine 19

Phosphate = 1.54

URINESodium = < 10

Potassium = 111

Osmolality = 776

pH = 5.0

Phosphate = 106

PTH = 94

• 24yr old female• Presented for asthma check. But

reported generalised headache and ‘off colour’ 2-3/7.

• PMH:– Depression 2-3 years previous, now

resolved and much better, some some ‘stress’ over financial debt

– TOP 3-4 years previous.

U+E from GP shows potassium of 1.9mmol/L

Lab add phosphate, Mg and Ca2+ - all normal

Patient referred to AAU for O/C medical team

Lab D/W O/C medical SpR – advises admission urine for electrolytes and store for laxative / diuretic screening

Medical review:

No reported diarrhoaea, vomiting or other GI symptoms. No dysuria or polyuria

Patient currently fasting for Ramadan, but normally eats poorly – usually skips breakfast and often lunch also. Denies laxative or diuretic abuse.

BP 93/65 PR 78 and RR 22 and sats 99%

No organomegaly

Well perfused with no oedema

Hint of u wave in II, V3 – V5

Weight 42 Kg

Venous gas confirms potassium of 1.9mmol/L with significant alkalosis (pH 7.53, bicarb 44 mmol/L, BE +19.2)

No documented assessment of nutritional status and risk

Imp:

? Laxative abuse, ? Vomiting after feeds, ? anorexia

Rx:

1L saline + 40 mmol potassium (x 2)

Ward round:

Imp as above, but no obvious evidence of anorexia noted

Despite no evidence of cortisol excess, only investigation for hypokalemia was 9am cortisol and 24hr UFC. Only urine studies were from lab adding onto UFC sample.

Urine electrolytes results (K+ = <10mmol/L) noted in record but not interpreted and significance not documented.

9am cortisol result interpreted incorrectly

Following admission, significant hypophosphataemia (0.35 mmol/L) occurred, but no intervention, no discussion in record and no repeat testing.

Patient discharged as soon as potassium >3mmol/L.