1. Clinical Biochemistry MDL 474 Introduction

2. Assessment WeekAssessmentGrade 4Quiz 15 11Quiz 210 7-8Mid-term20 14-15Final Laboratory Exam15 16-17Final Exam40 Laboratory attendance – 5 Marks Laboratory continuous assessment – 5 Marks

3. Homeostasis Ability to maintain stable internal state.

4. Clinical biochemistry Branch of laboratory medicine in which chemical and biochemical methods are applied to the study of disease. Comprise over 1/3 of all hospital laboratory investigations.

6. How biochemical tests are used?

8. Fluid and electrolyte balance

9. The major body constituent is water. The body has two main fluid compartments, the intracellular fluid (ICF) and the extracellular fluid (ECF, interstitial fluid and plasma). The ICF is twice as large (~28 L) as the ECF (14 L). Water retention will cause an increase in the volume of both ICF and ECF. Water loss (dehydration) will result in a decreased volume of both ICF and ECF.

10. Sodium ions are the main ECF cations, anions are chloride and bicarbonate. Potassium ions are the main ICF cations, anion is phosphate (and proteins). The volume of the ECF and ICF are estimated from knowledge of the patient's history and by clinical examination.

12. Concentration Ration of two variables (i.e amount of Na (solute) and the amount of water). A concentration can change because either or both variables have changed. For example, a sodium concentration of 140 mmol/L may become 130 mmol/L because the amount of sodium in the solution has fallen or because the amount of water has increased.

13. Osmolality Measurement of particles concentration in kg of solvent. Body fluids vary greatly in their composition. However, while the concentration of substances may vary in the different body fluids, the overall number of solute particles, the osmolality, is IDENTICAL. The osmolality of the ICF is normally the same as the ECF. Osmotic pressure must be the same at both side of the semi-permeable membrane

14. Determination of Osmolality Specimen: Serum or Urine. Na, K, Cl, and biocarbonate provide the largest contribution to the osmolality value of serum. Plasma is not recommended because osmotically active substances may be introduced into the specimen from the anticoagulant.

15. Determination of Osmolality Freezing point depression and vapor pressure decrease are the most frequently used methods of analysis. Sample must be free of particulate matter to obtain accurate results. Turbid serum or urine samples should be centrifuged before analysis.

16. Freezing point depression

17. Osmometers Used to measure the concentration of solute particles in a solution.

18. Osmolal gap Is the difference between measured serum osmolality and calculated serum osmolality. If this gap falls within an acceptable range, then it is assumed that sodium, glucose, BUN are indeed the major dissolved ions and molecules in the serum. If, however, the calculated gap is above an acceptable range, then it is an indication that there is something else dissolved in the serum.

19. Osmolal gap Increased in cases of -Alcohol (ethanol intoxication, methanol ingestion) -Sugar (Mannitol and sorbitol) -Lipid (hypertriglycaemia) -Protein (Hypergammaglobinemia)

20. Osmolality disorders Increased urea in renal disease. Hyperglycemia in diabetes mellitus. The presence of ethanol or some other ingested substances (methanol or ethylene glycol).

21. Reference ranges for osmolality Serum275-295 mOsm/kg Urine (24 h)300-900 mOsm/kg Urine/serum ratio1.0 -3.0 Random urine50-1200 mOsm/kg Osmolal gap5-10 mOsm/kg

22. Homework What is the difference between the oncotic pressure and the hydrostatic pressure?

23. Water and sodium balance Failure to maintain ECF volume, with the consequences of impaired blood circulation, rapidly leads to tissue death due to lack of oxygen and nutrients, and failure to remove waste products.

24. Water balance Water intake largely depends on social habits and is very variable. Water loss is normally seen as changes in the volume of urine produced. Water excretion by the kidney is tightly controlled by the antidiuretic hormone (ADH) or Arginine vasopressin (AVP).

25. ADH and the regulation of osmolality Specialized cells in the hypothalamus sense differences between their intracellular osmolality and that of the extracellular fluid, and adjust the secretion of ADH from the posterior pituitary gland. ADH causes water to be retained by the kidneys.

26. Sodium balance Most of the sodium is in the ECF. The sodium concentration is tightly regulated around 140 mmol/L. In disease, the gastrointestinal tract is often the major route of sodium loss (infantile diarrhoea may result in death from salt and water depletion.

27. Sodium balance the effect of Aldosterone Decreases urinary Na secretion. Increases Na re-absorption in the renal tubules at the expense of K and hydrogen ions. Stimulate Na conservation by the sweat glands and the mucosal cells of the colon. ECF volume is the major stimulus to Aldosterone secretion.

28. Sodium balance the effect of Aldosterone Cont. Specialized cells in the juxtaglomerular apparatus of the nephron, sense decreases in the blood pressure and secrete renin, the first step in a sequence of events that leads to the secretion of aldosterone by the glomerular zone of the adrenal cortex.

29. Homework What is the effect of the Atrial natriuretic peptide to sodium balance?

30. A patient who has been vomiting and has diarrhoea from a gastrointestinal infection. With no intake? -The patient becomes fluid depleted. -Water and sodium have been lost. -Because the ECF is low, aldosterone secretion is high. Thus, as the patient begins to take fluids orally, any salt ingested is maximally retained. -As this raised the ECF osmolality, ADH action then ensures that water is retained too. -This aldosterone and ADH interaction continues until ECF fluid volume and composition return to normal.

31. Hyponatraemia Defined as a serum sodium concentration below the reference intervals of 133-146 mmol/L. It is the electrolyte abnormality most frequently encountered in clinical biochemistry. Two causes: -Water retention -Sodium loss

32. 1- Water retention Usually results from impaired water excretion, and rarely from increased intake. Syndrome of inappropriate antidiuresis (SAID). -Infection -Malignancy -Chest disease -Trauma (including surgery) -Drug-induced

33. SIAD Inappropriate secretion of ADH. ADH normal 0-5 pmol/L. in SAID up to 500 pmol/L. Non-osmotic stimuli including hypovolaemia and/or hypotension, nausea, vomiting, hypoglycemia, and pain determine the wide spread of SIAD.

34. 2- Sodium loss Sodium depletion occurs ONLY when there is pathological sodium loss, either from the gastrointestinal tract or in urine. Gastrointestinal losses: vomiting, diarrhoea, patients with fistulae due to bowl disease. Urinary losses: mineralocorticoids deficiency (aldosterone), drugs that antagonize aldosterone (spironolactone).

35. Sodium loss Does sodium concentration by itself could provide information about presence or severity of sodium depletion? Hyponatraemia indicates that the ration of sodium to water is reduces.

37. 3- Pseudohyponatraemia In patients with severe hyperproteinaemia or hyperlipidaemia. More protein or lipoprotein and less water in plasma. Na and other electrolytes distributed only in water. Normal Na concentration in the plasma. Normal osmolality! And low sodium concentration (110 mmol/L). Assessed by osmolal gap?

38. Hyponatraemia clinical examination

39. Oedema (Edema) Accumulation of fluid in the interstitial compartment.

40. Treatment Increase sodium intake (sodium depleted patients) Fluid restriction (normovolaemic and - likely water retention). Oedematous patients should be given a diuretic to induce natriuresis and be fluid restricted. Severe cases (hypertonic solution).

42. Hypernatraemia Is an increase in the serum sodium concentration above the reference interval of 133-146 mmol/L. Causes: -Water loss -Sodium gain

43. 1- Water loss Decreases water intake in elderly patients. Stop drinking voluntarily, or because of unable to get something to drink – unconscious patient after a stroke. Less common, Diabetes insipidus -Failure of ADH secretion or action (Central) -Renal tubules do not respond to ADH (Nephrogenic).

44. 2- Sodium gain Less common than water loss. Salt poisoning. High sodium bicarbonate intake is life-threatening acidosis. Increase NaCl intake in infants. Conn’s syndrome: excess aldosterone secretion causes increase Na retention by the renal tubules. Cushing’s syndrome: excess cortisol secretion (weak mineralocorticoid activity). Na concentration in both cases is rarely above 150 mmol/L.

46. Clinical features Decrease skin turgor because of dehydration.

47. Treatment Increase water intake. Intravenously, 5 % dextrose. Not recommended with salt poisoning patients ? Dehydration with sodium loss, sodium should be administered. Salt poisoning can be managed by diuretics.

48. The End