Biochemistry case studies. Dr Narelle Hadlow Clinical Associate Professor School of Medicine, UWA
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1 Biochemistry case studies Dr Narelle Hadlow Clinical Associate Professor School of Medicine, UWA
2 72 y.o. woman History of HT, diuretics History of hypertension, complains thirsty, feels under the weather BP 120/85 (usually 135/90) Na 111 mmol/l ( ) K 2.3 mmol/l ( ) Bic 35 mmol/l (22-32) Urea 3.7 mmol/l ( ) Creat 63 umol/l (50-95) Na 128 mmol/l K 3.7 mmol/l Bic 28 mmol/l Urea 3.9 mmol/l Creat 58 umol/l After cessation of thiazide (inhibit Na/Cl transporter in distal tubule and collecting duct, Na/H and Cl/HCO exchanges)
3 A case of recurrent HypoNa 63 year old man
4 feels crook Turned up to ED Date 17/02/11 Time 22:23 -- Whole Blood -- Specimen VEN ph 7.43 ( ) Sodium 117 mmol/l ( ) * Potassium 3.1 mmol/l ( ) * Chloride 75 mmol/l (98-108) * Anion gap 10 mmol/l (7-17) Admitted to hospital
5 2 days later recovered spontaneously Date 19/02/11 Units Reference Time 08:25 Interval Plasma/Serum Sodium 131 mmol/l ( ) Potassium 3.2 mmol/l ( ) Bicarbonate 36 mmol/l (22-32) Urea 5.1 mmol/l ( ) Creatinine 66 umol/l (60-110) egfr > 60 ml/min/1.73m^2
6 LFT s Total Protein 70 g/l (60-80) Albumin 35 g/l (35-50) Globulins 35 g/l (23-35) Bilirubin 19 umol/l (< 20) ALT 84 U/L (< 40) Alk Phos 79 U/L (35-135) Gamma GT 261 U/L (< 60)
7 Further history No medications No diuretics Better after a few days in hospital? Cause and sent home
8 Re-admitted with hypona 19/6/2011 UREA & ELECTROLYTES (Plasma) * Sodium mmol/l ( ) * Potassium mmol/l ( ) * Bicarbonate mmol/l (22-32) * Urea mmol/l ( ) Creatinine umol/l (< 120) egfr > 60 ml/min/1.73m^2 (> 60) LIVER FUNCTION TESTS (Plasma) Total Protein g/l (60-80) Albumin g/l (35-50) Globulins g/l (25-44) * Bilirubin umol/l (< 20) Alk. Phos U/L (35-135) * ALT U/L (< 40) * Gamma GT U/L (< 60) GENERAL CHEMISTRY (Plasma) Lipase U/L (20-210)
9 Haemtology HAEMATOLOGY * RED CELLS WHITE CELLS * Hb ( ) g/l Count x10 ^9 /L ( ) * * RCC 3.08 ( ) x10 ^12 /L * * Hct 0.36 ( ) * MCV 116 (80-100) fl * MCH 40.6 ( ) pg MCHC 351 ( ) g/l The red cells show moderate macrocytosis. Macrocytosis - common causes include vitamin B12/folate deficiency, drugs, alcohol and liver disease.
10 Masterful observation. Date 19/06/11 20/06/11 20/06/11 Units Reference Time 22:59 02:18 07:42 Intervals -- Whole Blood -- Specimen VEN VEN VEN ph ( ) * pco mmhg (37-50) * po mmhg (36-44) * Bicarbonate mmol/l (22-28) * Base excess mmol/l (-3-3) * O2 Sat % (70-80) * Sodium mmol/l ( ) * Potassium mmol/l ( ) * Chloride mmol/l (98-108) * Anion gap mmol/l (7-17)
11 Date 19/06/11 20/06/11 20/06/11 Time 22:00 06:00 10:48 P Osmolality 236 ( ) U Osmolality ( ) What does the urine osmolality tell us?
12 The real history.. That his kidney is doing the right thing Heavy drinker Had had a bit of a binge for few days before admission ~ Drinking most of the day little to eat Some vomiting and diarrhoea
13 Beer Potomania Ingestion of a normal diet results in the excretion of 600 to 900 mosmol of solute per day (primarily sodium and potassium salts and urea). Eg- minimum urine osmolality is 60 mosmol/kg, Maximum urine output will be 10 to 15 L/day (eg, 900 mosmol/day 60 mosmol/kg = 15 L). If solute intake drops..can only put out less volume Low dietary solute intake Beer drinkers /malnourished patients (including those with low-protein, high water intake diets) reduction in water excretory capacity -directly mediated by poor dietary intake.
14 Potomania Beer - little or no sodium, potassium, or protein, carbohydrate load will suppress endogenous protein breakdown and therefore urea excretion. So- daily solute excretion may fall below 250 mosm leading to a reduction in the maximum urine output to below 4 L/day even though the urine is maximally dilute. Hyponatremia -if more than this amount of fluid is taken in. Water logged!
15 Beer and nuts! Motto of the story Have some high protein and salt filled snacks with your beer!!
16 Plasma Urine 62 y.o. woman. Routine check up Na 119 mmol/l ( ) K 4.0 mmol/l ( ) HCO3 25 mmol/l (22-32) Urea 3.2 mmol/l ( ) Creat 85 umol/l (50-95) Osmolality 243 mmol/kg ( ) Na 97 mmol/l Osmolality 543 mmol/kg ( )
17 What does urine osm mean? Low urine osm DILUTE Drank a lot of water recently excreting Unable to concentrate urine (D.I) High urine osm Concentrated Not had much to drink so saving water Inappropriately concentrating urine (SIADH)
18 If you don t have Serum Osmolality can Calculate it! 2 x (Na + K) + Urea + Glucose Serum osm High Osmolality concentrated solution Low osm dilute solution water logged! More water than Na!
19 Osmolality second Volume first
20 Plasma Urine 62 y.o. woman. Routine check up Na 119 mmol/l ( ) K 4.0 mmol/l ( ) HCO3 25 mmol/l (22-32) Urea 3.2 mmol/l ( ) Creat 85 umol/l (50-95) Osmolality 243 mmol/kg ( ) Na 97 mmol/l Osmolality 543 mmol/kg ( )
21 SIADH a Dx of exclusion! Feels well On questioning, has lost 1.5 kg weight BP 125/85 no postural drop. Does not appear dehydrated, not thirsty Euvolaemic (one exclusion down!) Dehydration Is this SIADH??? 2 more things to exclude Medications (Drugs) Endocrine disorders (Disease)
22 62 y.o. woman. Routine check up- NO medications Plasma Na 119 mmol/l ( ) K 4.0 mmol/l ( ) HCO3 25 mmol/l (22-32) Urea 3.2 mmol/l ( ) Creat 85 umol/l (50-95) Osmolality 243 mmol/kg ( ) Urine Na 97 mmol/l Osmolality 543 mmol/kg ( ) Cortisol 450 nmol/l ( ) T4 15 pmol/l (9-19) TSH 2.7 mu/l ( ) Prolactin 430 U/L (<500) Glucose 4.8 mmol/l (< 5.5)
23 SIADH- Dx of exclusion Normal volume status, HypoNa, Hypo-osm, inapprop conc urine No interfering drugs/meds DIURETICS Anti-convulsants (Carbemazepine, Valproate, Oxcarbazepine) Anti-depressants Amitryptilline, SSRI Anti-Ca Vincristine, Vinblastine, Cisplatin, Cyclosphosphamide Anti-Pain- NSAID, Opiod like Tramadol, Opiates Anti-arrhythmic- Amiodarone Anti-biotics- Ciprafloxacin Anti-H2 Omeprazole Nicotine No disease (NOT SICK!!) No acute DKA Normal CORTISOL Normal T4/TSH Normal Prolactin No significant Renal, Cardiac disease
24 No meds -Yes this is SIADH LFTs: TP 70 g/l (60-80) Alb 41 g/l (35-50) Bili 7 umol/l (<20) Alk Phos 178 U/L (35-135) ALT 16 U/L (<40) NSE 45.5 ug/l (<12.5) SIADH Small Cell Lung Cancer
25 Criteria for SIADH Hyponatraemia Low plasma osmolality Inappropriately high urine osmolality +/- Urine sodium >20 mmol/l NO dehydration -volume depletion or oedema NO disease -Endocrine disorder renal, adrenal, pituitary and thyroid function, not Diabetes! NO drugs -diuretic or other SIADH potentiating meds
26 Ms O H 16 year old girl History of Lethargy
27 Mum worried about daughter Tired all the time Sleeps in until 11am after noon No other specific symptoms No medications On questioning- Has lost 2 kg weight, drinking more, thirsty? Should I lock the fridge she is drinking all night!!! O/E BP 90/45, PR 88 Thin girl, lungs clear, soft abdomen
28 Electrolytes Date 01/07/13 Time 13:06 Sodium 126 ( ) * Potassium 4.0 ( ) Bicarbonate 17 (22-32) * Urea 9.2 ( ) * Creatinine 64 (45-90)
29 Other tests Na 126 mmol/l BSL 3.0 mmol/l ( ) Serum Osm 270 mosm/kg ( ) Urine Osm 650 mosm/kg ( ) Urine Na 45 mmol/l Is this SIADH??
30 Never make a Dx of SIADH In Dehydration (including recent Diuretics) And in someone who looks unwell -until you have excluded Drugs meds Disease Diabetes Addisons
31 Repeated electrolytes next day- as? Lab error Date 01/07/13 02/07/13 Time 13:06 08:48 Sodium ( ) * Potassium ( ) Bicarbonate (22-32) * Urea ( ) * Creatinine (45-90)
32 Further results Date 02/07/13 Time 08:48 Growth Hormone 5.0 mu/l (< 10) Oestradiol 290 pmol/l FSH 2 U/L LH 2 U/L Prolactin 690 mu/l, Resting (< 420) * S Cortisol < 30 nmol/l ( )am *
33 ACTH 1640!!!! pmol/l ( ) Primary adrenal insufficiency
34 Follow-up electrolytes Date 01/07/13 02/07/13 04/07/13 Reference Units Time 13:06 08:48 12:30 Range Sodium ( ) Potassium ( ) Bicarbonate (22-32) Urea ( ) Creatinine )
35 Traps for the unwary!
36 Traps for the unwary! SIADH only Dx when Volume status normal and NOT sick!! VOLUME first!!!- Osmolality/fine tuning next SIADH only Dx when excluded Dehydration, Drugs/Meds and Disease
37 35 y.o. female, dizzy, unsteady, weak, feels dreadful Na 123 mmol/l ( ) K 7.7 mmol/l ( ) HCO3 21 mmol/l (22-32) Urea 17.6 mmol/l ( ) Creat 220 umol/l (50-95) Osmolality 265 mmol/kg ( ) Urine Na 64 mmol/l Osmolality 584 mmol/kg ( )
38 Synacthen Stimulation Test Time (min)p. Cortisol (nmol/l) 0 60 ( ) (>550) (>550) Addison s disease
39 5 year old boy Nausea, vomiting, abdominal pain for several days, no fever.
40 13:20 UREA & ELECTROLYTES (Plasma) Sodium mmol/l ( ) Potassium..... HAEM * mmol/l Bicarbonate mmol/l (20-30) Urea mmol/l ( ) Creatinine umol/l (< 45) HAEM * = Haemolysed sample unsuitable for analysis. Please recollect if clinically indicated. Please repeat Potassium to confirm results.
41 18:30 UREA & ELECTROLYTES (Plasma) Sodium mmol/l ( ) Potassium mmol/l ( ) Bicarbonate mmol/l (20-30) Urea mmol/l ( ) Creatinine umol/l (< 45) COMMENTS * Sample not haemolysed, potassium result is analytically correct
42 LIVER FUNCTION TESTS (Plasma) Total Protein g/l (60-80) Albumin g/l (32-48) Globulins g/l (23-35) Bilirubin umol/l (< 20) Alk. Phos U/L ( ) * ALT U/L (< 30) * * Gamma GT U/L (< 20) * GENERAL CHEMISTRY (Plasma) C-Reactive Protein.. < 5 mg/l (< 10) BSL mmol/l ( )
43 ? SIADH Time 07:25 Interval P Osmolality 229 mmol/kg ( ) * U Osmolality 409 mmol/kg ( ) Date /11/12 Time :25 URINE - SPOT * Sodium mmol/l Potassium mmol/l
44 What should Cortisol do when you are SICK?? BIOCHEMISTRY IMMUNOASSAY RESULTS Date 02/11/12 Units Reference Time 02:45 Interval S Cortisol 220 nmol/l (60-420) am
45 A new lab measure of WOW ACTH 325 pmol/l ( ) *
46 81 y.o. man Plasma Na 126 mmol/l ( ) K 4.2 mmol/l ( ) HCO3 25 mmol/l (22-32) Urea 5.3 mmol/l ( ) Creat 70 umol/l (50-95) egfr >60 ml/min/1.73m 2 (>60) LFTs normal
47 TFTs: Free T4 7 pmol/l (9-19) TSH 0.79 mu/l ( ) Testo <0.8 nmol/l (10-35) LH 1 U/L (2-7) FSH 4 U/L (1-8) Prolactin 600 mu/l (<340)
48 Pituitary adenoma Noon Cortisol <30 nmol/l (AM ) Synacthen stimulation 30 min cortisol nmol/l (should be greater than 550 nmol/l) Hyponatraemia due to hypopituitarism - increased ADH Rx: Cortisone acetate then thyroxine
49 23 year old girl CUMULATIVE ELECTROLYTES (Serum) Na K Cl HCO3 Urea Creat Date Time ( )( )(95-108) (22-32) ( ) (30-100) 10/09/11 02: * 10/09/11 04: * 10/09/11 06: * 10/09/11 14: egfr : > 90 ml/min/1.73m ^2 egfr result does not exclude renal disease (MJA 2005;183(3): )
50 10/09/11 02:00 Sodium 119 Request: all OSMOLALITY Urine Osmolality.... : 107 mmol/kg URINE CHEMISTRY (Spot) Sodium Concentration..... : 41 mmol/l ? What is the diagnosis
51 History from clinician Psychogenic polydypsia History of excessive water consumption. Psychiatric admissions
52 31 y.o. female Plasma Na 117 mmol/l ( ) K 4.0 mmol/l ( ) HCO3 28 mmol/l (22-32) Urea 4.1 mmol/l ( ) Creat 55 umol/l (50-95) Osmolality 245 mmol/kg ( ) Urine Na 2 mmol/l Osmolality 93 mmol/kg ( ) Psychogenic polydypsia drinking too much water
53 38 y.o. female Plasma Na 135 mmol/l ( ) K 7.9 mmol/l ( ) HCO3 31 mmol/l (22-32) Urea 4.4 mmol/l ( ) Creat 80 umol/l (50-95)
54 What to ask? Who collected this?? WHEN In the fridge before it was separated (spun/centrifuged) Shaken vigorously or difficult collect eg child (haemolysed) Left for > 4-6 hours before spin/separate? Right tube order? (K+EDTA-purple top first)
55 38 y.o. female Practitioner put sample in fridge overnight prior to courier Plasma Na 135 mmol/l ( ) K 7.9 mmol/l ( ) HCO3 31 mmol/l (22-32) Urea 4.4 mmol/l ( ) Creat 80 umol/l (50-95) Repeat collection K 4.5 mmol/l
56 84 y.o. male in ED Plasma 18:25 20:07 Na mmol/l ( ) K mmol/l ( ) HCO mmol/l (22-32) Urea mmol/l ( ) Creat umol/l (60-120) 18:25 specimen haemolysed
57 70 y.o. male intern collected Plasma 18:30 19:20 Na mmol/l ( ) K mmol/l ( ) Creat umol/l (60-120) Alb g/l (35-50) Ca mmol/l ( ) Alk Phos U/L (35-135) K-EDTA Contamination EDTA chelates calcium
58
59 63 y.o. female Plasma Na 137 mmol/l ( ) K 7.5 mmol/l ( ) HCO3 20 mmol/l (22-32) Urea 2.0 mmol/l ( ) Creat 46 umol/l (50-95) WCC 616 x 10 9 /L (4-11) Venous whole blood potassium 3.2 mmol/l Chronic Lymphocytic Leukemia
60 23 y.o. female,? Too thin.. Na 136 mmol/l ( ) K 1.9 mmol/l ( ) HCO3 48 mmol/l (22-32) Urea 5.5 mmol/l ( ) Creat 69 umol/l (50-95) Previously normal electrolytes
61 Hypokalaemic Alkalosis Depends on clinical history Renal loss of K+ and HCO - - Diuretic therapy (excess Na+ in DCT for exchange) - Mineralocorticoid Excess - Glucocorticoid Excess - Excessive licorice ingestion (glycyrrhizic acid inhibiting 11- HSD) - Bartter s Syndrome (defective renal Cl - reabsorption) - Gitelman s Syndrome (mutation in thiazide-sensitive Na+/Cl- cotransporter in DCT) GI loss of K+ and H+ - Vomiting (urine Cl - <10 mmol/l) - Diarrhoea eg: villous adeno
62 How do you test your hypothesis? Add serum Cl Check urinary K and urinary Cl Vomiting loss of HCL low serum and urine Cl, Loss of Acid further, -try to conserve H in renal tubule and save H and let K go!
63 23 y.o. female Plasma Na 136 mmol/l ( ) K 1.9 mmol/l ( ) HCO3 48 mmol/l (22-32) Chloride 81 mmol/l (95-108) Urea 5.5 mmol/l ( ) Creat 69 umol/l (50-95) Urine K 102 mmol/l Cl <6 mmol/l Surreptitious Vomiting Renal loss of K due to metabolic alkalosis
64 67 year old woman with muscle weakness and cramps U&Es Na 148 mmol/l ( ) K 2.0 mmol/l ( ) HCO 3 40 mmol/l (22-32) Urea 5.7 mmol/l ( ) Creat 68 umol/l (45-90) Glucose 8.7 mmol/l Spot urine K 67 mmol/l
65 67 y.o. woman with weakness Aldosterone 249 pmol/l (80-800) Renin 20.0 mu/l (7-50) Plasma K 2.3 mmol/l ( ) Not Conn s Increased Renin/Aldosterone ratio Autonomous Renin (no medications)
66 67 y.o. woman with weakness 24 hr UFC UFC 21,000 nmol/d (<900) Creat 7.9 mmol/d ( ) Vol 3.05 L Plasma ACTH 43.3 pmol/l (2-10) Cushing s Syndrome - ectopic
67 RTA Save the hardest for last!!!!
68 26 year old male Date 10/08/11 11/08/11 11/08/11 12/08/11 Time 16:30 01:05 05:45 06:10 Sodium ( ) Potassium ( ) Bicarbonate (22-32) Urea ( ) Creatinine (45-90) egfr > 60 > 60 > 60 > 60 (> 60) SEVERE hypok ACIDOSIS Think of RTA
69 Initial confirmation whilst acidotic, cant acidy urine to < 5.3 ph Fluid Description Urine Fluid ph 6.20 With a serum Bicarbonate of 11 mmol/l
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