a. Addison’s disease
b. Compulsive water drinking
c. Treatment with diuretics
d. 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
What is most likely diagnosis?
d. Syndrome of inappropriate antidiuresis
How do you prove ?
Paired serum / urine for:
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
A middle-aged woman with a long history of
rheumatoid disease complains of fainting
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
Over treatment with diuretics
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
• 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)
• 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.
• 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,
• Diagnosis of RTA
• Volume status
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
What are the possible diagnoses/
explanations which explain all these findings?
Renal artery stenosis
↑ bp with thiazides
Mrs D B age 35
Aug 02 Referred by GP for management of
Chol = 9.8 mmol/l
TG = 1.2 mmol/l
FH Father uco DBF for FHC
2 brothers – normal cholesterol
Grandfather – DM
DH Simvastatin 10mg nocte
[Atorvastatin caused muscle pain]
non smoker, no alcohol
sells travel insurance
SQ diet poor
O/E BMI 25.2
Bp = 100/70
P = 68sr
HS I + II + O
Investigations Cholesterol 6.5 mmol/l
Cr = 61 µmol/l
Na = 138 mmol/l
K = 2.7 mmol/l
Repeat @ GP
22.8.02 Cr = 56 µmol/l
Na = 134 mmol/l
K = 2.5 mmol/l
? cause of Hypokalaemia
CLINICAL VIGNETTE - HYPERKALAEMIA
67 yr old female.
Seen by multiple GP’s within her practice over a 12
Seen by Consultant vascular surgeon for intermittent
claudication – commenced clopidogrel.
Known diabetic with persistent hyperkalaemia (5.8 – 6.9
Relatively poor diagnostic investigation of
Normal creatinine. And renal function.
Clinical Biochemist D/W GP.
Repeat bloods (not in community)
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
Patient seen 7 days later
‘Barn door’ primary polycythaemia
Immediate venesection 1/52 repeats
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
•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
•Patients with acute illness (e.g. acute renal failure, ketoacidosis)
•Consider spurious hyperkalaemia in the absence of all the above.
• 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
19yr old female.
Polydipsia + polyuria. Drinks approx 5 – 7 litres per day.
U+E = NAD TFT = NAD
Calcium = NAD
Glucose = NAD
What is best screen for GP to perform:
Early morning urine 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
PC: Moderate increase in sweating; ? Some weight loss.
fT4 = 6 pmol/L [12 – 25]
TSH 1.23 mU/L [0.35 – 5.5]
• 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/L
HDL = 2.2 mmol/L
TG = 0.9 mmol/L
What tests would you request next:
a. Fasting glucose
b. 9 am Cortisol
c. Bone profile
d. FT4 TSH
51-year-old female on routine vascular risk programme
was found to have following blood test results
FT4 TSH normal
ALB = 38 gl/L
AST = 40 u/L
ALP = 280 iu/L [<120]
Bil = 28 µmol/L
? What test/s next
a. 24 hour urine protein
c. Auto antibodies
b. Immunogloblins (↑ 1 gM)
c. Auto antibodies (antimitochondrial dbs)
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?
17 yr girl – known anorexia. Recently commenced monitored re-
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
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?
Tumour metastases to liver
12 month infant
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/L
β. γ-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
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
a. Chronic osteomyelitis
b. Multiple myeloma
d. Paget’s disease of bone
e. 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
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
↓ 25-0H vitamin D
Malabsorption of fat
• 14 yr old female, hirsute, lack of
secondary sexual characteristics, primary
• Testosterone = 2.7 nmol/L
• LH = <0.5; FSH = 3.6, oestradiol
• TFT = NAD
• 5pm cortisol = 944 nmol/L
b. Non prolactin-secreting pituitary tumours
c. Normal pregnancy
d. Sheehan’s syndrome
e. Amisulpiride therapy
Hyperprolactinaemia is recognised to occur in
b. Non prolactin-secreting pituitary
c. Normal pregnancy
Miss EV age 19 years
referred by GP with secondary amenorrhea
PMH Seen in 2001 with 2° amenorrhea by
Investigations LH, FSH, PRL, etc all normal
SH Lives with parents
No 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
bp = 110/70
a. Repeat in 3 months
b. Measure serum anti-TPo abs
c. Treat with levothyroxine
d. 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?
• 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
• 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
Born at term. At approx 45 mins age noted to have no cardiac
output. Resuscitated, RIP few days later.
Troponin = 2.9 ng/ml
83 year old female admitted with confusion and
Dx chest infection and congestive cardiac failure
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
PTH = 8.3 pmol/l
Long term catheter
Biphosphate for ↑ Ca
CA 125 = 8017 U/ml (<20)
Progress CT pelvis ?thickening of anal – rectal junction
Gynae outpatient review and other investigations
CA 125 normal within 38 days
Elevated CA 125 seen in
Advanced ovarian cancer
• CA 125 estimation
• Extra 10 days IP
• CT pelvis
• Repeat USS pelvis
• Repeat CA125 x2
• Sigmoidoscopy x2
• Rectal biopsy
• Gynae OPD
Cost at tariff = £5,000
Cholesterol and lipids
Deep vein thrombosis
(DVT) or pulmonary
Drug safety monitoring
Infections – viral
of chronic diarrhoea
Liver function tests
Causes of redistribution hypokalaemia
In vitro redistribution
Uptake by white blood cells (eg in leukaemia)
Uptake by erthrocytes following in vitro insulin
In vivo redistribution
Increased plasma bicarbonate
Toxic chemicals (toluene, soluble barium salts)
Hypokalaemic periodic paralysis
during rapid cell synthesis
Potassium mmol/100 ml
Normal adult intake 40-120 mmol/day
• 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
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
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.
• 24yr old female
• Presented for asthma check. But
reported generalised headache and ‘off
– 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
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%
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
? Laxative abuse, ? Vomiting after feeds, ? anorexia
1L saline + 40 mmol potassium (x 2)
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
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.