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

H + HCO3 = CO2 + H2O pH [H+] pCO2 - + Metabolic acidosis 6.92 7.0 7.1 7.22 7.40 7.52 7.70 7.80 Metabolic acidosis respiratory acidosis Draw this on your IPAD Metabolic alkalosis respiratory alkalosis pCO2

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

Case 1: data pH 6.85 PCO2 = 2.3 kPa (N 4-5) PO2 = 15 kPa

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

What is the acid/base abnormality? Low pH = acidosis ie: excess H+ ions HCO3- + H+ = CO2 + H20 Low CO2 = low bicarbonate

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

H + HCO3 = CO2 + H2O pH [H+] pCO2 - + Metabolic acidosis Type in your CID now H + HCO3 = CO2 + H2O - + pH [H+] 6.92 7.0 7.1 7.22 7.40 7.52 7.70 7.80 Metabolic acidosis respiratory acidosis Metabolic alkalosis respiratory alkalosis pCO2

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

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

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 ?

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

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

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

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

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

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

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

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

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)

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 ?

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

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

H + HCO3 = CO2 + H2O pH [H+] pCO2 - + Metabolic acidosis 6.92 7.0 7.1 7.22 7.40 7.52 7.70 7.80 Metabolic acidosis respiratory acidosis Slows down spontaneously Primary hyperventilation Metabolic alkalosis respiratory alkalosis pCO2

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

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

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 ?

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.

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 ?

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 ?

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.

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 PCO2=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 :

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 PCO2=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 :

Case 4. What is the osmolality : Na: 140, K: 4.0, U 4.0, pH 7.10, Glucose 4.0 PCO2=1.3 kPa. Cl = 90. Bicarb = 4.0 mM Osmo=2(Na+K) + U + G

Case 4. What is the anion gap: Na: 140, K: 4.0, U 4, pH 7.10, Glucose 4.0 PCO2=1.3 kPa. Cl = 90. Bicarb = 4.0 mM Urine is negative for ketones. Anion Gap = (Na+K) - bic - chloride

Case 4. What is the anion gap: Na: 140, K: 4.0, U 4, pH 7.10, Glucose 4.0 PCO2=1.3 kPa. Cl = 90. Bicarb = 4.0 mM Urine is negative for ketones. Anion Gap = (Na+K) - bic - chloride

Case 4. What is the anion gap: Na: 140, K: 4.0, U 4, pH 7.10, Glucose 4.0 PCO2=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

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

Case 4. What is the acid-base disturbance? pH 7.10 (acidosis) pCO2 = 1.3 kPa (very low)

Case 4. What is the acid-base disturbance? pH 7.10 (acidosis) pCO2 = 1.3 kPa (very low) Metabolic acidosis

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)

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

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

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).

Acid base graph: CID