Hyponatraemia

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?

a.

Addison’s disease b. Compulsive water drinking c.

Treatment with diuretics d. Syndrome of inappropriate antidiuresis

Answer

d. Syndrome of inappropriate antidiuresis How do you prove ?

Paired serum / urine for: Sodium Osmolality

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 Urea = 7.2 mmol/L Glucose = 3.5 mmol/L LFT = NAD Urine sodium = 82 mmol/L Potassium = 4.9 mmol/L Creatinine = 67 mmol/L Osmo = 263 mosmol/Kg TFT = NAD 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 failure Analgesic nephropathy Over 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 • • • • Uses Assessment of volume status Diagnosis of hypoNa and ARF Evaluation of calcium and urate excretion in stone formers Chloride Potassium Osmolality pH • • 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’s Renal artery stenosis  bp with thiazides

Mrs D B age 35 Aug 02 FH PMH DH Referred by GP for management of hypercholesterolaemia Chol = TG 9.8 mmol/l = 1.2 mmol/l Father uco DBF for FHC 2 brothers – normal cholesterol Grandfather – DM Nil Simvastatin 10mg nocte Loguynon [Atorvastatin caused muscle pain]

SH married non smoker, no alcohol no children sells travel insurance SQ diet poor asymptomatic O/E BMI 25.2

Fit Euthyroid Bp = P = 100/70 68sr HS I + II + O

Investigations Cholesterol LFTs Cr = Na = 6.5 mmol/l normal 61  mol/l 138 mmol/l K = 2.7 mmol/l Repeat @ GP 22.8.02

Cr = Na = K = 56  mol/l 134 mmol/l 2.5 mmol/l ?

cause of Hypokalaemia

Hypokalaemia

Redistribution Inadequate intake Excessive loss

• • Renal Extrarenal

Mx 18.9.02

Mx 1. GP question re:diuretic abuse, liquorice 2. Simvastatin 20 mg 3. Effervescent K+ 4 tabs/day Cr = 65  mol/l Na = 136 mmol/l K = 2.6 mmol/l Eff K+ - 6 tabs/day

Seen in Oct 2002 Well, asymptomatic bp = 110/70 DH Simvastatin 20mg Loguynon Eff K+ 6/day Investigations Cr Na K ? further investigations = = = 47  mol/l 135 mmol/l 3.1 mmol/l

24 hour urine K+ = 155.2 [40-120 mmol] Na+ = 249 [100-250 mmol] Serum Cr Na = 53  mol/l = 135 mmol/l K = 3.0

cCa = 2.49

Magnesium = 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 confirmed Rx Magnesium glycerophosphate ii tds Eff K 6/day Simvastatin 20 mg nocte Seen 5.2.03

Well Asymptomatic U = 5.8 mmol/l Na K = 136 = 3.2

Mg = 0.56

Chol = 7.0

Rx Add spironolactone 50 mg OD

Further investigations Cr Clearance Calcium creatinine ratio Urine osmolality Urine magnesium Urine K+ Urine Ca = 152 ml/mn = 0.18

= 708 mosm/kg = 6.32 mmol/l = 140 = 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 10 9 / L [4 –11] Platelets = 1195 x 10 9 / 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 Calcium = NAD Glucose = NAD TFT = 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 Prolactin 167 mU/l Other U&E NAD Cortisol (08:30 am) = 208 nmol/l Testosterone = 2.9 nmol/L 1.9 U/l, LH = 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]

51-year-old female on routine vascular risk programme was found to have following blood test results CHOL = HDL = TG = 8.4 mmol/L 2.2 mmol/L 0.9 mmol/L What tests would you request next: a.

Fasting glucose b.

c.

d.

e.

9 am Cortisol Bone profile FT 4 TSH LFTs

Answer

d. TFTs e. LFTs

Case (cont)

FT 4 TSH ALB = AST = ALP = Bil = normal 38 gl/L 40 u/L 280 iu/L [<120] 28 µmol/L ? What test/s next a. 24 hour urine protein b. Immunoglobulins c. Auto antibodies d. FBC (p.133)

Answer

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

2

A 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

Gilberts Haemolysis Unconjugated bilirubin

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

Sodium = 138 mmol/L Urea = 3.3 mmol/L Albumin = 37 g/L ALP = 83 IU/L Potassium = 4.1 mmol/L Creatinine = 48 umol/L Bili = 11 umol/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

Ostoemalacia Pagets Tumour 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 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?

a. Aspartate transaminase activity 60 IU/L b.

 -Glutamyl transpeptidase acitivity 120 IU/L c.

Total cholesterol 9.6 mmol/L d. Triglycerides (fasting) 4.2 mmol/L e. Urate concentration 0.48 mmol/L (p.134)

Answer

c. Cholesterol 9.6 mmol/L

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 a. Chronic osteomyelitis b. Multiple myeloma c.

d.

Osteoarthritis Paget’s disease of bone e. Renal osteodystrophy

Answer

a. Osteomyelitis b. 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 PTH Ca  Malabsorption 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

Hyperprolactinaemia is recognised to occur in patients with a.

b.

c.

d.

Hypothyroidism Non prolactin-secreting pituitary tumours Normal pregnancy Sheehan’s syndrome e. Amisulpiride therapy

Answer

a. Hypothyroid b. Non prolactin-secreting pituitary tumours c. Normal pregnancy e. Amisulpiride

Miss EV

PMH

DH FH SH SQ age 19 years referred by GP with secondary amenorrhea Seen in 2001 with 2 ° amenorrhea by Gynaecologist Investigations LH, FSH, PRL, etc all normal COC Hypertension Lives with parents Care Assistant No boy friend 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

Stop COC, baseline LH, FSH, TFTs and PRL Progress Results 1.

2.

3.

FT4 TSH LH FSH PRL Diet Stop COC Hormone profile = = = = = Preg test = 18 pmol/L [12 – 23] 1.6 mU/L [0.6 – 4.8] 1.1 U/L 2.7 U/L 9,823 U/L [70 - 566] negative

Question 2

What would you do next?

Progress

Answer

Repeat Prolactin Screen for Macroprolactin Repeat PRL >11,000 U/L All Monomeric PRL MRI scan “very large pituitary tumour with 2cm suprasellar extension elevating the optic chiasm”

Mr DW PMH dob 20/8/41 LVF A fibrillation CABG 1989 Angioplasty 2004 MI – 1998 Hypertension Hypercholesterolaemia Type 2 DM

DH Allergies SH FH Frusemide Clopidogrel Nicorandil Amiodarone Simvastatin Ezetimibe Warfarin Ramipril Bisoprolol None Ex smoker Occasional alcohol Lives with wife none

O/E p bp chest basal crackles JVP  5 cm No ankle oedema HS = = 130 AF 143/76 I and II and 0

U Cr Na K = = = = 10.7 mmol/l [2.5 – 6.5] 124 mmol/l [60 – 120] 131 mmol/l 3.6 mmol/l FT 4 = TSH = 100.2 pmol/l [12 – 23] <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 Amiodarone PTU

14

25-year-old female with menorrhagia FT 4 = TSH = 11.5 pmol/L [10 – 20] 8.3 mu/L [0.4 – 4.5] What do you do next?

a. Repeat in 3 months b. Measure serum anti-TPo abs c.

Treat with levothyroxine d. Measure 9 am Cortisol

Answer

a. Repeat in 3 months b. 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 Investigations U = 25.2 mmol/l (2.5 – 6.5) Creatinine 122 mmol/l Calcium 3.2 mmol/l (2.2 – 2.6) US abdo - grossly distended bladder – chronic retention CT head PTH = 8.3 pmol/l

Progress Rehydrated Long term catheter Biphosphate for  Ca

BUT

Progress CA 125 = 8017 U/ml (<20) CT pelvis ?thickening of anal – rectal junction Gynae outpatient review and other investigations

CA 125 normal within 38 days

Elevated CA 125 seen in Heart failure Ascites Hypothyroidism Advanced 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

Topics 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

Causes of redistribution hypokalaemia

In vitro redistribution

Uptake by white blood cells (eg in leukaemia) Uptake by erthrocytes following

in vitro

insulin administration

In vivo redistribution

Alkalosis Increased plasma bicarbonate Insulin administration  -Adrenergic agonists Toxic chemicals (toluene, soluble barium salts) Hypokalaemic periodic paralysis

Extrarenal loss

Inadequate intake

Fasting anorexia during rapid cell synthesis

Increased loss

Excessive sweating Gastrointestinal fistula diarrhoea cation exchange geophagia

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 WHAT IS DIAGNOSIS 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.

• Baby A.

• Previous NEC treated surgically • Persistent metabolic acidosis - ? RTA, ? Stoma losses underestimated (bag leaking) / underreplaced. Clinically no concerns re volume status.

PLASMA

Sodium = 144 Potassium = 5.2

Urea = 3.5

Creatinine 19 Phosphate = 1.54

URINE

Sodium = < 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 Ca 2+ - 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, V 3 – V 5 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: noted Imp as above, but no obvious evidence of anorexia 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.