1. Clinical Pathology B Case A Acute Diabetes The case history Mr CB, aged 40, has had type 1 diabetes since he was a child. He was brought in to the A & E confused & lethargic. One week ago he had an URTI & also developed polyuria, nausea & abdominal pain. His regular medications include Insulin & Ramipril. For the past three days he has been off his food. To compensate, he stopped injecting his insulin, despite increasing BSL levels ranging from 7.9 to 12.5 mmol/L. On examination he was lethargic, postural hypotension, HR 100, RR 30 & febrile. His mucous membranes were dry, skin trugor was poor, his breath was fruity in odour, disorientated & confused. Mr CB, aged 40, has had type 1 diabetes since he was a child. He was brought in to the A & E confused & lethargic. One week ago he had an URTI & also developed polyuria, nausea & abdominal pain. His regular medications include Insulin & Ramipril. For the past three days he has been off his food. To compensate, he stopped injecting his insulin, despite increasing BSL levels ranging from 7.9 to 12.5 mmol/L. On examination he was lethargic, postural hypotension, HR 100, RR 30 & febrile. His mucous membranes were dry, skin trugor was poor, his breath was fruity in odour, disorientated & confused.

2. Clinical Pathology B Case A Acute Diabetes What is DKA?  DKA: Metabolic disorder –3 concurrent abnormalities: Hyperglycemia, Hyperketonemia & Metabolic acidosis.Hyperglycemia, Hyperketonemia & Metabolic acidosis.  Generally caused by either: –Absolute deficiency of insulin OR –Relative deficiency: Excess of counterregulatory hormones:Excess of counterregulatory hormones: – Glucagon, Catecholamines, Cortisol & GH.

3. Clinical Pathology B Case A Acute Diabetes Pathophysiology of DKA  Hyperglycemia = osmotic diuresis –  ’s tubular reabsorption of fluid –Draws H 2 O, Na, K, Mg, Ca & P from circulation  urine. –Large losses of fluid in urine & vomiting leads to both intracellular & extracellular dehydration.

4. Clinical Pathology B Case A Acute Diabetes …Pathophysiology DKA  KA results from  ed ketone synthesis & release.   ’s in both acetoacetate & [beta]- hydroxybutyrate  hyperketonemia induces metabolic acidosis respiratory compensation.  Acetoacetic acid  Acetone accumulates & slowly disposed of by respiration.

5. Clinical Pathology B Case A Acute Diabetes Clinical Presentation  Polydipsia, polyuria,fatigue & weakness  osmotic diuresis  Abdominal pain & vomiting  ketoacidosis  Lethargy & alterations in consciousness  serum osmolality

6. Clinical Pathology B Case A Acute Diabetes …Clinical Presentation  Tachypnea & Kussmaul’s respiration's  compensate for metabolic acidosis  Fruity odor of acetone in breath  Signs of dehydration on physical examination –skin, mucous membranes

7. Clinical Pathology B Case A Acute Diabetes Laboratory Assessment  Urea17 mmol/L3-8  Creat0.225 mmol/L0.05-0.12  pH 7.157.36-7.44  Bicarb 9 mmol/L24-32  Glucose 38 mmol/L3-8  Osmolality 220 mmol/L265-285  Ketones Very high (multistix)

8. Clinical Pathology B Case A Acute Diabetes Explain the likely precipitating factors for DKA in this case.

9. Clinical Pathology B Case A Acute Diabetes The case history Mr CB, aged 40, has had type 1 diabetes since he was a child. He was brought in to the A & E confused & lethargic. One week ago he had an URTI & also developed polyuria, nausea & abdominal pain. His regular medications include Insulin & Ramipril. For the past three days he has been off his food. To compensate, he stopped injecting his insulin, despite increasing BSL levels ranging from 7.9 to 12.5 mmol/L Mr CB, aged 40, has had type 1 diabetes since he was a child. He was brought in to the A & E confused & lethargic. One week ago he had an URTI & also developed polyuria, nausea & abdominal pain. His regular medications include Insulin & Ramipril. For the past three days he has been off his food. To compensate, he stopped injecting his insulin, despite increasing BSL levels ranging from 7.9 to 12.5 mmol/L

10. Clinical Pathology B Case A Acute Diabetes What causes DKA?

11. Clinical Pathology B Case A Acute Diabetes Precipitating factors Mr CB, aged 40, has had type 1 diabetes since he was a child. He was brought in to the A & E confused & lethargic. One week ago he had an upper respiratory tract infection & also developed polyuria, nausea & abdominal pain. His regular medications include Insulin & Ramipril. For the past three days he has been off his food. To compensate, he stopped injecting his insulin, despite increasing BSL levels ranging from 7.9 to 12.5 mmol/L Mr CB, aged 40, has had type 1 diabetes since he was a child. He was brought in to the A & E confused & lethargic. One week ago he had an upper respiratory tract infection & also developed polyuria, nausea & abdominal pain. His regular medications include Insulin & Ramipril. For the past three days he has been off his food. To compensate, he stopped injecting his insulin, despite increasing BSL levels ranging from 7.9 to 12.5 mmol/L

12. Clinical Pathology B Case A Acute Diabetes  Lack of insulin leads to ketoacidosis because insulin has inhibitory effect on ketogenesis.  Free fatty acids are released from adipose tissue & oxidised. Long chain fatty acid CoA transporter facilitates uptake of the fatty acids in to the mitochondria. Insulin directly inhibits this transporter.  The ketoacids that are formed have the function of providing the body with energy when glucose isn’t available.

13. Clinical Pathology B Case A Acute Diabetes Can DKA occur in type 2 diabetes? YESrarely…

14. Clinical Pathology B Case A Acute Diabetes Type 2 diabetes  Glucotoxicty vs Insulin deficiency  Type 2 diabetics have insulin available to inhibit ketogenesis.  Thus ketoacids are not formed & there is no consequent acidity.

15. Clinical Pathology B Case A Acute Diabetes Sick Day Management  General Protocol –Continue Usual Insulin –Eat As Per Usual –If Not Have 15g Cho’s –If Not Fluids Every Few Minutes –Monitor Ketones & BSL –Test Urine for Ketones Every Time Urine Is Passed

16. Clinical Pathology B Case A Acute Diabetes What To Do With BSL Results  BSL -Check BSL every 2-4 hours if: >12mmol/L 12mmol/L<12mmol/L Unsweetened FluidsSweetened Fluids

17. Clinical Pathology B Case A Acute Diabetes Other Checks  Body Temp - elevated above 37.5º  Breathing rate -   Pulse -   Bodyweight -   Contact Dr or go to hospital if: –your BSL remains > 17mmol/L –Mod. to large ketones present in urine –Vomiting any food or fluids 

18. Clinical Pathology B Case A Acute Diabetes Implementation Avoids…  DKA - Diabetic ketone Acidosis  Dehydration  Coma