1. Diabetic Emergencies:
Diabetic Ketoacidosis
and
Hyperglycemic Hyperosmolar Syndrome
ALISHA WORTH
NCSU CVM C/O 2015

2. Diabetes Mellitus Overview
 Impaired carbohydrate metabolism due to inadequate insulin
 Pancreas: exocrine and endocrine function
 Exocrine: digestive enzymes
 Glucagon: ↑ [glucose]: glycogenolysis, gluconeogenesis
 Insulin: ↓ [glucose]: promotes glycogen formation;
glucose uptake into cells

3. Diabetes Mellitus Types
 Type I: Insulin-Dependent Diabetes Mellitus (IDDM)
 Immune-mediated destruction of beta cells
 Genetic or chronic pancreatitis
 50% of diabetic dogs
 Absolute insulin deficiency
 Type II: Non Insulin-dependent Diabetes Mellitus (NIDDM)
 Insulin resistance, decreased insulin secretion
 Obesity, inactivity, amyloid deposition in beta cells
 Most diabetic cats
 Relative insulin deficiency

4. Quick Review: Normal Cellular Respiration
• ATP: currency of life!
• From breakdown of
glucose
• From Kreb’s cycle
• From electron transport
chain

5. Glucose Behaving Badly:
Cellular Metabolic Derangements
Too much of a good thing
↑ glucose
+
↑ fatty acids
= too much acetyl coA
 Kreb’s cycle says “I can’t handle this!”
 Acetyl coA says “Well, I have to go somewhere!”
 Liver says “I got your back bro, let me convert you
into ketone bodies for an alternative source of
energy!”

6. DKA Pathophysiology, Redux
↓ insulin and ↑ glucagon
↑ lipolysis for energy → ↑ free fatty acids ↑ glucose release from liver:
glycogenolysis, gluconeogenesis
Mitochondrial B oxidation of FA → acetyl- CoA
Accumulation of acetyl- CoA
acetyl- CoA → ketones:
B-hydroxybutyrate, acetoacetate, acetone
Dissociation of these anions → ↑ [H+] → ketotic acidosis
↑ [glucose] in blood
Glucose spillover into urine
Kitties: 250 mg/dL [RR: 60-125 mg/dL]
Dogs: 200 mg/dL [RR: 60-125 mg/dL]
Osmotic diuresis → dehydration, urinary electrolyte
losses: Na, Cl, K, Phos

7. Clinical Pathology of DKA
Metabolic acidosis with a increased anion gap
Bonus NAVLE review time: Anion Gap!
 Body fluids are electrically neutral, aka equal amounts of anions and cations.
 Commonly measured cations: Na+, K+
 Commonly measured anions: Cl-, HCO3-
 Sum of the commonly measured cations < sum of commonly measured anions.
 Aka, there are more unmeasured anions (UA) than unmeasured cations (UC)  anion gap!
 Anion gap = (Na+ + K+) – (Cl- + HCO3-) = UA –UC
 Ketoacids are anions; ↑ ketoacid levels ↑ the anion gap!
 Other causes of ↑ AG: lactic acidosis, uremic acidosis, toxins: ethylene glycol,
ethanol, aspirin

8. Clinical Pathology of DKA: Chemistry
High serum osmolality. Due to hyperglycemia, azotemia, ketones.
Bonus NAVLE Review time: Osmolality!
 Osmolality = osmoles per kg of solvent. Vs. Osmolarity = osmoles per L of solution.
 Osmole = something that draws H2O toward it: Alcohols, sugars, lipids, proteins.
 Effective osmole = something that generates osmotic pressure b/c it draws and keeps H2O
on its side of a semipermeable membrane.
 Osmolality is both measured (osmometer), and calculated. The difference between these
two is the osmol gap, which is normally < 10 mOsm/kg.
 Calculated Osmlality = 2 (Na+ + K+) + BUN/2.8 + Glucose/18
 Why do I care about this?
 If you have a high osmolal gap, this raises your suspicion for unsuspected osmols in the
serum (MAE DIE), because you didn’t account for them in your calculated osmol gap.
 Reference Values: Dogs: 308-335 mOsm/kg. Cats: 290-310 mOsm/kg.
Osmole Mnemonic
Methanol
Acetone
Ethanol
Diuretics (mannitol, sorbitol)
Isopropanol
Ethylene glycol

9. Clinical Pathology of DKA: Chemistry
Hyponatremia
 True hyponatremia: urinary loss.
 Pseudohyponatremia: due to hyperglycemia. Correct for this below:
 Corrected Na: Measured Na + 0.016 x (serum glucose – 100)
 Corrected Na if glucose > 600 mg/dL: Measured Na + 0.024 x (serum glucose – 100)
Potassium
 Low: urinary loss, vomiting, anorexia, or binding to ketoacids.
 High: due to intracellular to extracellular shifting to correct for acidemia: H+ in, K+ out.

10. Clinical Pathology of DKA: Chemistry
 Hypophosphatemia: urinary loss, hemolysis (in cats: Heinz body anemia)
 Other Electrolytes: Hypochloremia, Hypomagnesemia, Hypocalcemia
 Hyperlactatemia: poor tissue perfusion 2o to hypovolemia from dehydration
 Azotemia: dehydration
 ↑ ALT, ALP, GGT, tibili (hepatocellular damage d/t altered metabolism; hepatic lipid infilitration
and 2o cholestasis or hemolysis of Heinz bodies)
 Hyperlipidemia
 ↑ amylase and lipase (pancreatitis)

11. Clinical Pathology of DKA: CBC, UA
 CBC:
 Stress or an inflammatory leukogram
 ↑ HCT/PCV and TS (dehydration)
 Heinz bodies in kitty RBCs  anemia (Heinz body formation associated with B-hydroxybutyrate
formation)
 Urine
 Ketonuria and glucosuria
 Pyuria, proteinuria, hematuria (diabetic animals are prone to UTIs)
 Low USG (medullary washout 2o to osmotic diuresis)

12. Clinical Signs: What DKA looks like!
 Runs the gamut: from BAR to severe
 Mentally dull
 Dehydrated (gums, skin tent, eyes)
 Vomiting/Anorexia
 Body condition: under or overweight
 Cranial organolmegaly
 Remember, this might be the first presentation for a previously unknown diabetic
animal.

13. Diabetes Comorbidities and DDX
 Dogs:
 Hyperadrenocorticism
 Acute pancreatitis
 Urinary tract infections
 Cataracts
 Cats:
 Hepatic lipidosis
 Chronic renal failure
 Acute pancreatitis
 Bacterial/viral infections
 neoplasia

14. DKA Treatment: Fluids and Elytes
Fluid Therapy
Replacement fluids
 Consider a buffered solution like LRS or Normosol-R; fine to use 0.9% NaCl, too
 Lactate converted into bicarbonate in the liver. How handy!
 Time over which to replace? Look at your patient!
Maintenance Fluids: 0.45% NaCl +/- 2.5% or 5% dextrose once BG ~250 mg/dL
Electrolyte Abnormality Corrections
Potassium: If low, supplement with a potassium CRI, not to exceed 0.5 mEq/kg/hr. Hyperkalemia
will often resolve as the acidemia improves with rehydration and insulin.
Phosphorus: potassium phosphate CRI (has 4.4 mEq of K and 3 mM/ml of Phos)
Magnesium: magnesium sulfate CRI 0.5-1 mEq/kg q24h

15. DKA: Insulin Therapy
Insulin Therapy
 Why: stops ketogenesis, ↑ utilization of ketones, ↓ gluconeogenesis, ↑ glucose utilization.
 Most effective if tissue perfusion has been restored
 When: 1-4 hours after you start your rehydration; wait longer (4-8 hours) if patient was
hypokalemic. Supplement your fluids with potassium.
 What: Regular insulin CRI, initially @ 10 ml/hr, in a separate line from fluids.
 Dogs: 2.2 U/kg of regular insulin added to a 250 ml bag of 0.9% NaCl
 Cats: 1.1 U/kg of regular insulin added to a 250 ml bag of 0.9% NaCl
 Recheck BG q2h; when <250, switch fluid to 0.45% NaCl + 2.5% dextrose and slow your insulin rate to 7
ml/hr; see next slide.
 Run 50 ml of the insulin solution through the administration set first (insulin can adhere to the plastic).

16. Handy Insulin CRI Protcol
courtesy of Dibartola
Blood Glucose Conc
(mg/dL)
Intravenous Fluid Solution IV Insulin Solution Rate
 250 0.9% saline 10
200-250 0.9% saline, 2.5% dextrose 7
150-200 0.9% saline, 2.5% dextrose 5
100-150 0.9% saline, 5% dextrose 5
<100 0.9% saline, 5% dextrose Stop the insulin

17. DKA Therapy Monitoring
 Monitoring plan
 BG q2h-4h Blood pressure
 Electrolytes q8-12h
 PCV/TS q8-12h: assess rehydration
 Body weight q24h: is your hydration plan working?
 mentation
 Other therapies:
 NUTRITION! We want these guys eating on their own again.
 Anti-emetics
 Heat support

18. Hyperglycemic,
Hyperosmolar State

19. What makes a patient HHS?
 Extreme hyperglycemia: >600 mg/dl
 Serum osmolality: > 350 mOsm/kg
 Little or no ketonuria
 Decreased GFR  severe dehydration

20. Pathophysiology of HHS
 Similar to DKA: ↓ insulin; ↑ glucagon, cortisol, growth hormone
 Small amounts of insulin help prevent ketone formation
Hyperglycemia
And
hyperosmolality
Osmotic
diuresis
dehydration
Reduced
GFR

21. HHS Therapy and Monitoring
 Similar to DKA Therapy:
 Treat hypovolemic shock: 20 ml/kg bolus for cats; 30 ml/kg bolus for dogs of an isotonic fluid
 Decrease sodium slowly to avoid cerebral edema: 1 mEq/L/hr or less!
 Nutrition
 Anti-emetics
 Monitoring, as before for DKA:
 BG q2h-4h Blood pressure
 Electrolytes q8-12h
 PCV/TS q8-12h: assess rehydration
 Body weight q24h: is your hydration plan working?
 mentation

22. Prognostic Information
 DKA:
 70% of dogs and cats survive until discharge
 Median time in hospital 6 days dogs; 5 days cats
 7% of dogs have a recurrence of DKA
 40% of cats have a recurrence of DKA
 HHS:
 Very little data in veterinary patients
 One study in cats: 64% mortality in hospital; 38% in dogs
 Human children: 72% mortality

23. References
 Ettinger, SJ & Feldman, EC. (2009). Textbook of Veterinary Internal Medicine, vol 7.
St. Louis, MO: Saunders Elsevier.
 Hopper, K & Silverstein D. (2015). Small Animal Critical Care Medicine. St. Louis,
MO: Elsevier Saunders.