Clinical biochemistry

1. Clinical biochemistry Emma Louise Ross 0605819r

2. Learning points • Fluid balance • Acid-base • Electrolyte disturbances • Exam questions

3. Fluid balance • Total body fluid = 42L (60% body weight) • 2/3 intracellular (28L) • 1/3 extracellular (14L) • 1/3 intravascular (5L blood) • Normal daily requirements • 2500ml fluid • 100mmol Na • 70 mmol K • “Dextrose dextrose saline” • 2L 5% dextrose • 1L 0.9% saline • 20mmol K per litre of fluid • * per 30h

4. Underfilled Tachycardia Postural hypotension ↓ CRT ↓ urine output Cool peripheries Dry mucous membranes ↓ skin turgor Sunken eyes Overfilled ↑ JVP Pitting oedema Tachypnoea Bibasal crepitations Pulmonary oedema on CXR Assessing fluid balance

5. 5% dextrose (glucose) • 5% = 50g/L • Isotonic • 1L = 10% energy intake • Glucose metabolised by liver • 1/9 remains intravascular • Use = HYDRATION • Excess → water overload and hyponatraemia

6. 0.9% saline • Isotonic, similar [Na] to plasma • Equilibrate rapidly throughout extracellular compartment only • Longer to reach intracellular space • 1/3 remains intravascular • FLUID RESUSCITATION (+ hydration) • Alternative: Hartmann’s

7. Colloids • Gelofusine • High osmotic content • Remain intravascular • FLUID RESUSCITATION • N.B • Expensive • Risk anaphylaxis

8. Summary

9. Acid base balance Normal + 7.40 +/- 0.05 • Look at pH • Acidosis <7.35 • Alkalosis >7.45 • Is Co2 abnormal? (4.7-6.0kPa) • If so, is change in keeping with pH? • CO2 is acidic gas • If so = respiratory cause • Is HCO3 abnormal? (22-28mmol/L) • If so, is change in keeping with pH? • HCO3 is alkaline- ↑ in alkalosis, ↓ acidosis • If so = metabolic cause

10. Anion gap • Estimates unmeasured plasma anions (fixed/organic acids) • Phosphate • Ketones • Lactate • Difference between plasma cations (Na +K) and anions (Cl + HCO3) • Normal range: 10-18mmol/L • Helpful in determining cause of metabolic acidosis

11. Metabolic acidosis • pH ↓, HCO3 ↓ • Increased anion gap • ↑ production/↓excretion fixed acids • Lactic acidosis- shock, ischaemia • Urate- RF • Ketones- DKA, alcohol • Drugs/toxins- salicyclates, methanol • Normal anion gap: • Loss of bicarbonate or ingestion of H+ • Renal tubular acidosis • Diarrhoea • Addison’s disease • Pancreatic fistula • Ammonium chloride ingestion • Drugs (acetozolamide)

12. Metabolic alkalosis • pH ↑, HCO3 ↑ • Causes • Vomiting • K+ depletion (diuretics) • Burns • Ingestion of base

13. Respiratory acidosis • pH ↓, CO2 ↑ • Causes • Type II respiratory failure • Lung disease (COPD) • Neuromuscular disease • Beware: exhaustion in asthma, pneumonia or pulmonary oedema

14. Respiratory alkalosis • PH ↑, CO2 ↓ • Result of hyperventilation of any cause • CNS causes: stroke, subarachnoid bleed, meningitis • Others: anxiety, altitude, pregnancy, PE, pyrexia, pain, drugs (salicylates)

15. Electrolytes • Normal values: • Na 135-145mmol/L • K 3.5- 5.0 mmol/L • Ca (total) 2.12-2.65mmol/L • Emergencies: • Na <120 or > 155 mmol/L • K < 2.5 or > 6.5 mmol/L • Ca (corrected) <2.0 or >3.5mmol/L

16. Hypernatraemia • S&S: lethargy, thirst, weakness, irritability, confusion, coma, fits + signs of dehydration • Usually due to water loss in excess of sodium loss • Fluid loss w/o water replacement (d&v, burns) • Excessive saline • Diabetes insipidus • Osmotic diuresis • Primary aldosteronism

17. Hypernatraemia • Management • Oral fluids • 5% dextrose iv slowly (1l/6h) • Use 0.9% saline if hypovolaemic • Avoid hypertonic solutions • Fluid replacement guided by urine output

18. Hyponatraemia • Plasma [Na] depends on amount of both Na and water in plasma • Hyponatraemia ≠sodium depletion • Assessing fluid status is key to making diagnosis

19. Hyponatreamia S&S: • Initially: anorexia, nausea, malaise • Then: headache, irritability, confusion, weakness, ↓GCS, seizures • (cardiac failure or oedema) • * S&S depend on severity and rate of change in serum [Na]

20. Pictures should be offset to the right. Caption. OHCM- 8th ed. p. 687

21. Hyponatraemia • Management • Correct underlying cause • Never tx on [Na] alone • Consider: • Presence of symptoms • Chronicity • State of hydration

22. Hyponatraemia • Asymptomatic chronic hyponatraemia • e.g. CCF • Fluid restriction • +/- Demeclocycline (ADH antagonist) • Acute or symptomatic hyponatraemia or dehydrated • Cautious fluid resus- 0.9% saline • Do not correct changes rapidly! • Central pontine myelinolysis • Consider using furosemide if not hypovolaemic to avoid fluid overload

23. Hyperkalaemia • Emergency: >6.5mmol/L • Myocardial hyperexcitability: VF, cardiac arrest • Is the patient well? (?Artefact) • Concerning features: • Fast, irregular pulse • CP, palpitations • Weakness • Light-headedness • ECG • Small, flat p waves • Wide QRS, eventually becomes sinusoidal • Tall tented t waves • VF

24. Hyperkalaemia Causes: • Oliguric RF • K+-sparing diuretics • Rhabdomyolysis • Metabolic acidosis (DKA) • Excess K+ therapy • Addison’s disease • Massive blood transfusion • Burns • Drugs: ACEI • Artefact (haemolysis, contamination, thrombocythaemia)

25. Hyperkalaemia • Tx underlying cause, review medications • Monitor ECG • Calcium resonate- binds K+ in gut Emergency: • 10mL calcium gluconate (10%) iv over 2min, repeat as needed • Cardioprotection • Insulin + glucose • e.g 50mL 50% glucose + 10U rapidly acting insulin over 30 min • Nebulise salbutamol (2.5mg) • Dialysis

26. Hypokalaemia • Emergency if K+ < 2.5mmol/L * Hypokalaemia exacerbates digoxin toxicity • S&S: • muscle weakness, hypotonia, hyporeflexia, cramps, tetany • palpitations, light-headedness (arrythmias) • ECG: • small or inverted T waves • prominent U waves (after T wave) • long PR interval • Depressed ST segments

27. ECG changes http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/electrolyte_disorders/disorders_of_potassium_concentration.html

28. Hypokalaemia • Causes • Diuretics • D&V • Pyloric stenosis • Intestinal fistula • Cushing’s/steroids/ACTH • Conn’s syndrome • Alkalosis • Purgative and liquorice abuse • Renal tubular failure

29. Hypokalaemia 3 • Tx • n.b. importance of Mg • Mild (>2.5): give oral K+ supplements (sando-K) • If taking thiazides- K+ > 3.0mmol/L rarely needs tx • Severe (<2.5) +/or dangerous symptoms: give iv K+ catiously. • Senior • Do not give K+ if oliguric • NEVER GIVE K+ AS FAST STAT BOLUS

30. Hypercalcaemia • “Bones, stones, groans and psychic moans” • Abdo pain, vomiting, constipation, polyuria, polydipsia, anorexia, weight loss, depression, tiredness, weakness, hypertension, confusion, pyrexia, renal stones, RF, ectopic calcification • Cardiac arrest • ECG: QT interval ↓

31. Hypercalcaemia • Causes: • Malignancy • Primary hyperparathyroidism • Vit D intoxication • Sarcoidosis • Thyrotoxicosis • Lithium • Tertiary hyperparathyroidism

32. Hypercalcameia • Investigations • Main distinction between malignancy and primary HPT • 1 HPT: ↑ PTH • Ca: ↓ albumin,↑phosphate,↓alk phos, • Tx • Correct dehydration • Bisphonates- pamidronate • Tx of cause e.g. chemotherapy

33. Hypocalcaemia • Spasms • Perioral paraestheis • Anxious, irritable, irrational • Seizures • Muscle tone ↑ • Orientation impaired (T,P,P), confusion • Dermatitis • Impetigo herpetiformis • Cardiomyopthy- long QT interval Chvostek’s sign Cataract Choreoathetosis

34. Cause ↑ phosphate CKD HPT Rhabdomyolysis Vit D def ↓ Mg ↔ or ↓phoshate Osteomalacia Acute pancreatitis Over-hydration Resp. alkalosis Hypocalcaemia

35. Hypocalcaemia Tx • Mild: give Calcium 5mmol/6h po with daily levels • Severe: 10mL of 10% calcium gluconate iv over 30 min. Repeat if necessary • In CKD: Alfacalcidol (vit D analogue) • In resp. alkalosis: correct alkalosis

36. Exam question • A 30 year-old woman with a 10-year history of asthma is admitted to acute medical receiving ward with a 24 hour history of increasing shortness of breath, and wheeze. She has an upper respiratory tract infection, which has been treated with antibiotics by her GP. • Her ABGs on room air are: • PaO2 8.3 kPa (10.5-14 kPa); • PaCO2 3.8 kPa (4.7-6 kPa) • pH 7.51 (7.37-7.42) • H+ 32 nm (35-45 nm) • HCO3 - 24 (24-28 mmol/L)

37. Exam question • Suggest six factors in this history and examination that will help you assess the severity of this asthma attack at the bedside. • Give three initial treatments • How would you explain the blood gas abnormalities (<50 words.) • What would happen to the patient’s blood gases if her condition continued to deteriorate? • What course of action should be considered if the clinical situation continues to deteriorate and does not correct itself with your first line management?

38. Exam question • A 5-week old boy is brought for the second time in one week to A&E with persistent vomiting. The parents say that his vomiting started 10 days earlier and that after the vomiting he is always hungry. At the last visit he was diagnosed as having gastrooesophageal reflux and started on thickened feeds and gaviscon. Until the age of one month he was well and had been thriving. You are working as a House Officer in A&E and examine the child and perform an ABG. • The results are as follows: • pH 7.50 (normal range 7.35-7.45) • pCO2 5.0kPa (normal range 4.6-6kPa) • pO2 12kPa (normal range 10-13.5kPa) • Base deficit +5.8 (normal = 0)

39. Exam question • How would you assess his degree of dehydration? List 5 indicators of dehydration • Describe the abnormalities seen in the blood gas results • Please describe, in <50 words, how these results arise • On more detailed examination you notice gastric peristalsis and you feel a pyloric tumour in the upper abdomen. What is the most appropriate next investigation? • What is the most likely diagnosis in this given this clinical scenario? • What would be the operative procedure of choice?

40. Thank you! • Questions?

41. References • Longmore M, Wilkinson I, Davidson E, Foulkes A, Mafi A. Oxford handbook of Clinical Medicine. 8th ed. Ch 15- clinical chemistry.