Chemical Pathology: Electrolyte and Acid-Base Disorders

1. Pakistan Society Of Chemical PathologistsDistance Learning Programme In Chemical PathologyLesson No 8Electrolyte and Acid Base DisordersBy Surg Commodore AamirIjazMCPS, FCPS, FRCP (Edin)Professor of Pathology / Consultant Chemical PathologistBahria University Medical &Dental College / PNS SHIFA KarachiDrShaguftaYousafFCPS Part II TraineePNS SHIFA

2. Q 1:Fractional excretion of sodium is used to assess :a. Extracellular volumeb. Glomerular function of the kidneyc. Osmotic pressure in the kidneyd. Sodium homeostasis e. Tubular function of the kidney • Best Answer: • e. Tubular function of the kidney

3. Fractional Excretion of Sodium • Fractional excretion of sodium (FExNa) is a good marker for the assessment of tubular function • FExNa can be estimated by simultanous estimation of Na and Creatinine

4. Q 2: Osmolality of blood is :a. Calculated by measuring creatinineb. Cannot be measured directly c. Controlled by atrial pressured. Equal to urinary osmolalitye. Tightly controlled in a narrow range. • Best Answer: • e. Tightly controlled in a narrow range.

5. Osmolality of Blood : • Osmolality of blood is controlled by osmo-receptors • Osmolality of blood is maintained by variations in urinary osmolality

6. Q 3: A 32 years sanitary worker was brought to the A&E Department in a semi-conscious state. He improved with preliminary treatment but became blind by next morning. The facilities for Blood Methanol Assay were not available in the hospital laboratory. Which of the following investigations would be most helpful in reaching a diagnosis:a. Blood osmolalityb. Creatinine Clearance c. Osmolality gapd. Plasma electrolyte e. Urinary osmolality • Best Answer: • c. Osmolality gap

7. Osmolality Gap • Osmolality gap is = • Measured Osmolality – Calculated Osmolality • It is increased in acute alcoholic poisoning

8. Q 4:A hospitalized patient was advised blood counts and biochemical profile. Results of some of his biochemical tests were: • Na : 136 mmol/L (132-144) • K : 8.7 mmol/L (3.5-5.0) • Total Calcium : 0.41 mmol/L (2.10-2.55) • Urea : 9.2 mmol/L (3.5 – 6.3)• The Medical Officer incharge of the ward has called to inform you that the patient is not that sick as indicated in the lab results. How will you justify this non-correlation of the results with the clinical condition of the patient?a. EDTA contaminationb. Haemolysed samplec. Prolonged use of tourniquetd. Sample collected in Lithium Heparin tubee. Sample taken in plain tube • Best Answer: • a. EDTA contamination

9. Transfer of EDTA crystals by tip of syringe from one sample tube to another EDTA contamination

10. Types of EDTA Gross Contamination Subtle Contamination

11. False Hypocalcaemia False Hyperkalaemia Normal Renal Functions No hemolysis (Normal LDH) Signs of Gross Contamination

12. Very difficult to diagnose in individual cases Should be prevented collectively Very important in any lab setting Subtle EDTA Contamination

13. Correct Filling Order Estimation of EDTA in each sample Single sample tube How to prevent EDTA Contamination ?

14. 1st : Lithium Heparin 2nd :Plain tube 3rd : Glucose Then: Blood CP and other tubes Correct Filling Order

15. Q 5:A 1 year old child has following biochemical profile :• pH : 7.52 (7.35 – 7.45)• HCO3 : 39 mmol/L (23 – 28)• BE : 2.4 <+3- -3• PO2 : 92 mmHg (80 – 110)• PCO2 : 48 mmHg (35-45) • Na : 138 mmol/L (132-144) • K : 2.6 mmol/L (3.5 – 5.0)• Urinary K : Raised• Urinary Ca : 980 mmol/mol of Creat (565)• Aldosterone : 567 ng/dl (5-90)• Renin Activity: 15.5 ng/ml/h (0.2-1.6)What is the most probable diagnosis in this case?a. Addison Diseaseb. Barter Syndromec. Gitelman Syndromed. Primary Hyperaldosteronisme. Renal Tubular Acidosis • Best Answer: • b. Barter Syndrome

16. Barter and Gitelmansyndrome Autosomal recessive disorders  Hyperplasia of the juxtaglomerular apparatus Secondary Hyperaldosteronism and Hyperreninism Metabolic Alkalosis Hypokalaemia Increased Urinary Potassium Hypomagnesemia (in some patients)

17. Difference Between Barter`s Syndrome Gitelman syndrome

18. Q 6:A 5 months baby has following biochemical profile :• pH : 7.30 (7.35 – 7.45)• HCO3 : 10 mmol/L (23 – 28)• BE : -7.4 <+3- -3• PO2 : 88 mmHg (80 – 110)• PCO2 : 24 mmHg (35-45) • Na : 141 mmol/L (132-144) • K : 2.44 mmol/L (3.5 – 5.0)What is the most probable diagnosis in this case?a. Barter`s Syndromeb. Diabetic Ketoacidosisc. Primary Hypoaldosteronismd. Renal Tubular Acidosis Type 1e. Renal Tubular Acidosis Type 4 • Best Answer: • d. Renal Tubular Acidosis Type 1

19. Renal Tubular Acidosis The term "renal tubular acidosis" (RTA) refers to a group of disorders Characterized by: Well-preserved Glomerular Filtration Rate, Metabolic Acidosis Normal Anion Gap Hyperchloremia

20. Types of RTA Distal or type 1 RTA Proximal or type 2 RTA Type 3 RTA (genetic defect of Carbonic Anhydrase 2) Hypoaldosteronism or type 4 RTA

21. Diagnosis of various types of RTA

22. Differential Diagnosis of Metabolic Acidosis based on Anion Gap

23. Q 7:A 62 years old male has been brought in emergency department with persistent vomiting but no diarrohea. Some of his biochemical results are:• pH : 7.53 (7.35 – 7.45)• HCO3 : 42 mmol/L (23 – 28)• BE 2.4 <+3- -3• PO2: 98 mmHg (80 – 110)• PCO2: 49 mmHg (35-45)• Na : 128 mmol/L (132-144) • K : 2.4 mmol/L (3.5 – 5.0)• Chloride : 72 mmol/L (98 – 108)What is the most probable diagnosis in this case?a. Acetazolamide Therapyb. Alkali Administrationc. Gastric Outlet Obstructiond. Respiratory Failuree. Uretero-Ileal Anastomosis • Best Answer: • c. Gastric Outlet Obstruction

24. Two Most Common Causes of Metabolic Alkalosis External loss of gastric secretions due to vomiting or nasogastric suction Diuretic therapy.

25. Q 8:A 34 years female has been admitted in hospital with vague complaints. His Biochemical Profile is as following:• pH : 7.34 (7.35 – 7.45)• HCO3 : 21 mmol/L (23 – 28)• BE : -4.4 <+3- -3• PO2 : 108 mmHg (80 – 110)• PCO2 : 39 mmHg (35-45)• Na : 124 mmol/L (135–150) • K : 6.0 mmol/L (3.5 – 5.0)• Cl: 96 mmol/L (98-108)• Urea : 12 mmol/L (3.3 – 6.6)• Uric Acid: 150 µmol/L (130-370)• Osmolality: 273 mmol/L (285-295)What is the most probable diagnosis in this case?a. Addisons Diseaseb. Chronic Kidney Diseasec. Con`s Syndromed. Salicylate poisoninge. Syndrome of Inappropriate Antidiuresis • Best Answer: • a. Addisons Disease

26. Biochemical Features of Addison Disease Hyponatraemia Hyperkalaemia Metabolic Acidosis (Less Common): Due to concomitant Hypoaldosteronisn. Low levels of aldosterone stimulation of the renal distal tubule leads to sodium wasting in the urine and H+ retention in the serum.

27. Q 9:You have received sample of a 2 years child from Paediatric Ward without any clinical notes (as usual). His biochemical profile is as following:• pH : 7.31 (7.35 – 7.45)• HCO3 : 14 mmol/L (23 – 28)• BE : -6.3 <+3- -3• PO2 : 108 mmHg (80 – 110)• PCO2 : 39 mmHg (35-45)• Na : 136 mmol/L (135–150) • K : 2.5 mmol/L (3.5 – 5.0)• Chloride : 112 mmol/L (98-108)• Urea : 7.2 mmol/L (3.3 – 6.6)• Anion Gap : 12 mmol/L (7 – 17)What is the most probable diagnosis in this case?a. Dehydrationb. Diarrhoeac. Lactic Acidosisd. Renal Impairmente. Renal Tubular Acidosis • Best Answer: • b. Diarrhoea

28. Hypokaleamic Metabolic Acidosis Most common cause: Diarrhoea due to loss of HCO3 and K Other causes: RTA Acetazolamide therapy Ureteroillealanastamosis

29. Q 10:A 55 years male, presented in semi-conscious state. His Biochemical Profile is as following: • pH : 7.38 (7.35 – 7.45)• HCO3 : 24 mmol/L (23 – 28)• BE : 2.3 <+3- -3• PO2 : 102 mmHg (80 – 110)• PCO2 : 39 mmHg (35-45)• Na : 153 mmol/L (135–150) • K : 4.5 mmol/L (3.5 – 5.0)• Chloride : 118 mmol/L (98-108)• Urea : 15.2 mmol/L (3.3 – 6.6)• Osmolality : 353 mmol/Kg (275 – 295) • Glucose (R) : 43 mmol/L (3.5 – 11.1)Urine:• Ketones TraceWhat is the most likely diagnosis?a. Accidental ingestion of sea water b. Dehydration due to severe diarrhoeac. Diabetic Ketoacidosisd. Hyperglycaemic Hyperosmolar Diabetic Statee. Primary Hyperaldosteronism • Best Answer: • d. Hyperglycaemic Hyperosmolar Diabetic State

30. Short answer questions

31. Q 11:Composite systems of Electrolyte and Arterial Blood Gasses (ABGs) estimation are commonly used now-a-day. Please answer following questions regarding theses analyses:a. Write THREE points regarding these analyses which distinguish them from rest of the laboratory tests. b. What is the advantage of using a composite system of Electrolyte and ABGs in terms of patient care?c. Name ONE important parameter of ABGs analyses which is calculated and please write formula used for its calculation.d. Write TWO lines about the sample collection (only collection not transport) of these analyses.e. Various modes are available in this system. Which mode you will like to keep this machine in your lab and why?

32. Samples to reach lab within 15 minutes No incubation or reagent mixing Instant results Invalid if result delayed “bedside use” with some precautions Some unique things of ABG Measurement

33. ABG’S AND ELECTROLYTES • Measured • pH • Partial Pressure of Carbon dioxide (PCO2) • PO2 • HCO3 • BE • Calculated

34. GETTING AN ARTERIAL BLOOD GAS SAMPLE Lyophilized Heparin Syringe Radial Artery

35. Suggested Answer to Q.11a Write THREE points regarding these analyses which distinguish them from rest of the laboratory tests. Very high diagnostic yield 95% No reagent mixing or incubation Sample should reach lab within 15 minutes, invalid if result delayed, Instant results, instant interpretation and instant correction

36. Suggested Answer to Q.11b What is the advantage of using a composite system of Electrolyte and ABGs in terms of patient care? Composite system of ABGs and electrolyte system determines pH, PCO2, HCO3 , PO2, Na+, K+, Cl-, Ca+simultaneously. This simultaneous analysis allows determination of indices like anion gap, delta ratio and predicted bicarbonate which helps in diagnosis of triple disorder. So composite system is extremely helpful in critically ill patients because rapid and effective diagnosis of acid base disorders is essential for the management of seriously ill patient.

37. Suggested Answer to Q.11c Name ONE important parameter of ABGs analyses which is calculated and please write formula used for its calculation. Bicarbonate is important parameter which is calculated by Henderson Hasselbalchequation as under: pH =pK+ log {HCO3}/{H2CO3} (for bicarbonate system pk is 6.1)

38. Suggested Answer to Q.11d Write TWO lines about the sample collection (only collection not transport) of these analyses. Sample of whole blood for ABGs should be taken in lyophilized lithium heparin syringe (ideally from radial artery) Don’t shift sample into tube and send to lab within 15 minutes. Must ask from lab about ABGs analyser in functioning or not)

39. Suggested Answer to Q.11e Various modes are available in this system. Which mode you will like to keep this machine in your lab and why? Standby Mode Ready Mode In lab with high workload ABGs analyser should be kept in ready mode because in other mode, delayed test invalidate the result due to changes in blood gases from metabolism of blood cell and also addition of gases from environment. In lab with lesser work load, standby mode to save reagents but SOS should include co-ordination with lab prior to sending sample.

40. Q 12:While working in a Hospital Laboratory you have carried an Audit of Electrolyte Estimation of last one month. To your surprise it has been found that no case of HYPOKALAEMIA has been reported from your lab while the percentage of patients with hyperkalaemia is quite reasonable. All your Internal and External Quality Controls and Assurance checks are perfectly within acceptable range. Please answer following questions regarding this situation:a. Write TWO possible causes of this problem?b. Write the most important ONE step you will like to take in the SOP of “Sample collection procedure for electrolytes” to avoid this problem in future.c. What notice you would like to paste in the Blood Collection Area of your Lab?d. Name the system of Quality Check you will like to install in your laboratory to avoid such problems in other analytes.

41. Suggested Answer to Q.12 a Write TWO possible causes of this problem? Such problem can arise due to leakage of K from RBCs into the serum and masking Hypokalaemia. Prolonged contact of RBCs with serum will enhance it. So sample collection in a plain tube without gel is the most common cause of this pre-analytical error. Subtle EDTA contamination (tube contain Na / K EDTA anticoagulant) can also mask hypokalaemia Mild and invisible haemolysis because of prolong tourniquet and improper chain of transfer and storage of sample can also increase serum potassium and mask hypokalaemia. .

42. Suggested Answer to Q.12 b Write the most important ONE step you will like to take in the SOP of “Sample collection procedure for electrolytes” to avoid this problem in future. Most Important:Sample for electrolytes should be taken in lithium heparin tube. (If using plain tube, serum must be separated in other aliquot immediately after centrifuge to avoid masking of hypokalaemia and pseudo-hyperkalaemia. Electrolytes should be dealt like ABGs) .

43. Suggested Answer to Q.12 c What notice you would like to paste in the Blood Collection Area of your Lab?To assure the accuracy of patient test result, test tube must be filled in particular order to avoid cross contamination between test tubes additives, CLSI recommended following order of draw: ORDER OF DRAW 1. Blood culture 2. Sodium citrate tube for coagulation profile 3. Plain or jell tube for chemistry test 4. Lithium heparin for ABGs and electrolytes 5. Na K EDTA tube for whole blood haematology 6. Sodium fluoride for glucose, lactate and alcohol .

44. Suggested Answer to Q.12 d Name the system of Quality Check you will like to install in your laboratory to avoid such problems in other analytes ‘Serum Indices’ which include: Quality check for haemolysis H index Quality check for icterus I index Quality check for lipemia L index Delta check system can also be helpful to avoid this problem .

45. Thank You and Best Of Luck