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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?
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 OVERLOOKE D
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, concentrating ability
Diagnosis of RTA
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?
Renal artery stenosis
bp with thiazides
Mrs D B age 35 Aug 02 Referred by GP for management of hypercholesterolaemia Chol = 9.8 mmol/l TG = 1.2 mmol/l FH Father uco DBF for FHC 2 brothers – normal cholesterol Grandfather – DM PMH Nil DH 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 = 100/70 P = 68sr HS I + II + O
Investigations Cholesterol 6.5 mmol/l LFTs normal Cr = 61 mol/l Na = 138 mmol/l K = 2.7 mmol/l Repeat @ GP 22.8.02 Cr = 56 mol/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 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
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.
Hypernatraemia Uosmol should be > 600 mosmol/Kg. If less than plasma omso then primary renal water loss
Urine osmo > 750 makes DI unlikely
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
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:
9 am Cortisol
FT 4 TSH
51-year-old female on routine vascular risk programme was found to have following blood test results
FT 4 TSH normal
ALB = 38 gl/L
AST = 40 u/L
ALP = 280 iu/L [<120]
Bil = 28 µmol/L
? What test/s next
24 hour urine protein
Immunogloblins ( 1 gM)
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)
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?
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
Aspartate transaminase activity 60 IU/L
-Glutamyl transpeptidase acitivity 120 IU/L
Total cholesterol 9.6 mmol/L
Triglycerides (fasting) 4.2 mmol/L
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)
Cholesterol 9.6 mmol/L
Paget’s disease of bone
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 request?
25-0H vitamin D
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
Non prolactin-secreting pituitary tumours
Hyperprolactinaemia is recognised to occur in patients with
Non prolactin-secreting pituitary tumours
Miss EV age 19 years referred by GP with secondary amenorrhea PMH Seen in 2001 with 2° amenorrhea by Gynaecologist Investigations LH, FSH, PRL, etc all normal DH COC FH Hypertension SH Lives with parents Care Assistant 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 Euthyroid No hirsuitism No galactorrhea bp = 110/70
Answer Repeat PRL >11,000 U/L All Monomeric PRL MRI scan “ very large pituitary tumour with 2cm suprasellar extension elevating the optic chiasm” Repeat Prolactin Screen for Macroprolactin Progress
Mr DW dob 20/8/41 LVF A fibrillation PMH CABG 1989 Angioplasty 2004 MI – 1998 Hypertension Hypercholesterolaemia Type 2 DM
DH Frusemide Clopidogrel Nicorandil Amiodarone Simvastatin Ezetimibe Warfarin Ramipril Bisoprolol Allergies None SH Ex smoker Occasional alcohol Lives 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 FT 4 = 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?
Repeat in 3 months
Measure serum anti-TPo abs
Treat with levothyroxine
Measure 9 am Cortisol
25-year-old female with menorrhagia FT 4 = 11.5 pmol/L [10 – 20] TSH = 8.3 mu/L [0.4 – 4.5] What do you do next?
Repeat in 3 months
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
Which one of the following findings in a patient with primary hypothyroidism could not be explained by this condition ?
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 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 Heart failure Ascites Hypothyroidism Advanced ovarian cancer
CA 125 estimation = £8.55
Extra 10 days IP
Repeat USS pelvis
Repeat CA125 x2
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 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
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
Previous NEC treated surgically
Persistent metabolic acidosis - ? RTA, ? Stoma losses underestimated (bag leaking) / underreplaced. Clinically no concerns re volume status.
Presented for asthma check. But reported generalised headache and ‘off colour’ 2-3/7.
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: 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.