1. Diabetes Clinical cases CID please… Chemical Pathology: Y5 Karim Meeran

2. H + HCO 3 = CO 2 + H 2 O respiratory acidosis respiratory alkalosis Metabolic acidosis Metabolic alkalosis + - pCO2 pH [H +] 6.92 7.0 7.1 7.22 7.40 7.52 7.70 7.80 Draw this on your IPAD

3. Case 1: 16 year old unconscious. Acutely unwell a few days. Vomiting Breathless.

4. Case 1: data pH 6.85 PCO 2 = 2.3 kPa (N 4-5) PO 2 = 15 kPa

5. What is the acid/base abnormality? A. Respiratory acidosis B. Metabolic acidosis C. Respiratory alkalosis D. Metabolic alkalosis pH 6.85 PCO2 = 2.3 kPa (N 4-5) PO2 = 15 kPa

6. What is the acid/base abnormality? Low pH = acidosis ie: excess H + ions HCO 3 - + H + = CO 2 + H 2 0 Low CO2 = low bicarbonate

7. What is the acid/base abnormality? Draw the following graph, which will always tell you the answer:

8. H + HCO 3 = CO 2 + H 2 O respiratory acidosis respiratory alkalosis Metabolic acidosis Metabolic alkalosis + - pCO2 pH [H +] 6.92 7.0 7.1 7.22 7.40 7.52 7.70 7.80 Type in your CID now

9. What is the acid/base abnormality? Low pH = acidosis Low CO2 = low bicarbonate Metabolic acidosis

10. Case 1: more data. Na: 145, K: 5.0, U 10, pH 6.85, Glucose 25. Why is he unconscious ? What is the osmolality ?

11. Case 1: more data. Na: 145, K: 5.0, U 10, pH 6.85, Glucose 25. Why is he unconscious ? Because brain enzymes cannot function at a very acid pH What is the osmolality ?

12. Case 1: osmolality : derivation* Na: 145, K: 5.0, U 10, pH 6.85, Glucose 25. Osmolality = charged molecules + uncharged =cations + anions + urea + glucose (Na, K) (Cl, HCO3) Since cations = anions, this can be reduced to: Osmolality = 2(Na+K) + U + G Also PO4, SO4, etc

13. Case 1: osmolality : derivation* Na: 145, K: 5.0, U 10, pH 6.85, Glucose 25. Osmolality = charged molecules + uncharged =cations + anions + urea + glucose (Na, K) (Cl, HCO3) Since cations = anions, this can be reduced to: Osmolality = 2(Na+K) + U + G What is the osmolality? Also PO4, SO4, etc

14. Case 1: osmolality Na: 145, K: 5.0, U 10, Glucose 25.

15. Case 1: anion gap* Cations (Na/K) = Anions (Cl, Bicarb, others) “Others” known as “anion gap”. Anion gap = Na + K – Cl – bicarb

16. Case 1: anion gap* Cations (Na/K) = Anions (Cl, Bicarb, others) “Others” known as “anion gap”. Anion gap = Na + K – Cl – bicarb

17. Case 1: anion gap* Cations (Na/K) = Anions (Cl, Bicarb, others) “Others” known as “anion gap”. Anion gap = Na + K – Cl – bicarb Normal AG =140+4.0 – 102 – 24 = 18 mM

18. Case 1: anion gap* Anion gap = Na + K – Cl – bicarb Normal AG =140+4.0 – 102 – 24 = 18 mM In this patient:

19. Case 1: anion gap* Anion gap = Na + K – Cl – bicarb Normal AG =140+4.0 – 102 – 24 = 18 mM In this patient calculate the anion gap now: 145 + 5.0 – 96 – 4.0

20. Case 1: anion gap* Anion gap = Na + K – Cl – bicarb Normal AG =140+4.0 – 102 – 24 = 18 mM In this patient: 145 + 5.0 – 96 - 4 = (high) Suggests extra anions (Ketones)

21. Case 2: A 19 year old known to have type 1 diabetes for several years presents unconscious. Results: pH 7.65 PCO2 = 2.8 kPa Bicarb = 24 mM (normal) PO2 = 15 kPa What is the acid-base abnormality ?

22. Case 2: What is the acid/base abnormality? A. Respiratory acidosis B. Metabolic acidosis C. Respiratory alkalosis D. Metabolic alkalosis pH 7.65 PCO2 = 2.8 kPa Bicarb = 24 mM (normal) PO2 = 15 kPa

23. What is the acid/base abnormality? High pH = alkalosis Low CO2 = respiratory

24. H + HCO 3 = CO 2 + H 2 O respiratory acidosis respiratory alkalosis Metabolic acidosis Metabolic alkalosis + - pCO2 pH [H +] 6.92 7.0 7.1 7.22 7.40 7.52 7.70 7.80 Primary hyperventilation Slows down spontaneously

25. What is the acid/base abnormality? High pH = alkalosis Respiratory alkalosis

26. Further results: Na = 140, K=4.0, bicarb=24, Cl=100 Glucose 1.3 mM What is the anion gap? What is the diagnosis ?

27. Further results: Na = 140, K=4.0, bicarb=24, Cl=100 Glucose 1.3 mM What is the anion gap? (normal) What is the diagnosis ?

28. Further results: Na = 140, K=4.0, bicarb=24, Cl=100 Glucose 1.3 mM What is the anion gap? (normal) What is the diagnosis ? Anxiety caused by hypoglycaemia.

29. Case 3. 60 year old man presents unconscious to casualty, with a history of polyuria and polydipsia. Investigations reveal: Na: 160, K: 6.0, U 50, pH 7.30, Glucose 60. What is the osmolality ? Why is he unconscious ?

30. Case 3. 60 year old man presents unconscious to casualty, with a history of polyuria and polydipsia. Investigations reveal: Na: 160, K: 6.0, U 50, pH 7.30, Glucose 60. What is the osmolality : mosm/kg Why is he unconscious ?

31. Case 3. 60 year old man presents unconscious to casualty, with a history of polyuria and polydipsia. Investigations reveal: Na: 160, K: 6.0, U 50, pH 7.30, Glucose 60. What is the osmolality : mosm/kg Why is he unconscious : because the brain is VERY dehydrated.

32. Case 4. 59 year old man known to have type 2 diabetes, on a good diet and metformin presents to casualty unconscious: Urine is negative for ketones. Na: 140, K: 4.0, U 4.0, pH 7.10, Glucose 4.0 PCO 2 =1.3 kPa. Cl = 90. Bicarb = 4.0 mM What is the osmolality : What is the anion gap: What is the acid-base disturbance Why is he unconscious :

33. Case 4. 59 year old man known to have type 2 diabetes, on a good diet and metformin presents to casualty unconscious: Urine is negative for ketones. Na: 140, K: 4.0, U 4.0, pH 7.10, Glucose 4.0 PCO 2 =1.3 kPa. Cl = 90. Bicarb = 4.0 mM What is the osmolality : What is the anion gap: What is the acid-base disturbance Why is he unconscious :

34. Case 4. What is the osmolality : Na: 140, K: 4.0, U 4.0, pH 7.10, Glucose 4.0 PCO 2 =1.3 kPa. Cl = 90. Bicarb = 4.0 mM Osmo=2(Na+K) + U + G

35. Case 4. What is the anion gap: Na: 140, K: 4.0, U 4, pH 7.10, Glucose 4.0 PCO 2 =1.3 kPa. Cl = 90. Bicarb = 4.0 mM Urine is negative for ketones. Anion Gap = (Na+K) - bic - chloride

36. Case 4. What is the anion gap: Na: 140, K: 4.0, U 4, pH 7.10, Glucose 4.0 PCO 2 =1.3 kPa. Cl = 90. Bicarb = 4.0 mM Urine is negative for ketones. Anion Gap = (Na+K) - bic - chloride

37. Case 4. What is the anion gap: Na: 140, K: 4.0, U 4, pH 7.10, Glucose 4.0 PCO 2 =1.3 kPa. Cl = 90. Bicarb = 4.0 mM Urine is negative for ketones. Anion Gap = (Na+K) - bic - chloride ie: there are an excess of anions

38. What is the acid/base abnormality? A. Respiratory acidosis B. Metabolic acidosis C. Respiratory alkalosis D. Metabolic alkalosis pH 7.10 PCO2 = 1.3 kPa (N 4-5) PO2 = 15 kPa

39. Case 4. What is the acid-base disturbance? pH 7.10 (acidosis) pCO 2 = 1.3 kPa (very low)

40. Case 4. What is the acid-base disturbance? pH 7.10 (acidosis) pCO 2 = 1.3 kPa (very low) Metabolic acidosis

41. Case 4. ie: there are an excess of anions Not ketones What else ? Methanol, ethanol, lactate Metformin in overdose can cause a lactic acidosis Lactate = 10 mM (N<2.0)

42. The Cori cycle: Glucose (muscle)Lactate GlucoseLactate circulation liver Inhibited by metformin

43. Case 4. Why is he unconscious? pH 7.10 (acidosis) The brain cannot function in such an acidic pH.

44. Definition (type 2 diabetes) Fasting glucose > 7.0 mM Glucose tolerance test (75 grams glucose given at time 0) Plasma glucose > 11.1 mM at 2 hours (2h value 7.8 – 11.1 = impaired glucose tolerance).

45. Acid base graph: CID