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Diabetic Emergencies: Diabetic Ketoacidosisand Hyperglycemic Hyperosmolar SyndromeALISHA WORTHNCSU CVM C/O 2015
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
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
Quick Review: Normal Cellular Respiration
• ATP: currency of life!• From breakdown of
glucose• From Kreb’s cycle• From electron
transport chain
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!”
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 urineKitties: 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
Clinical Pathology of DKA
Metabolic acidosis with a increased anion gapBonus 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
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 MnemonicMethanolAcetoneEthanolDiuretics (mannitol, sorbitol)IsopropanolEthylene glycol
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.
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)
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)
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.
Diabetes Comorbidities and DDX
Dogs: Hyperadrenocorticism Acute pancreatitis Urinary tract infections Cataracts
Cats: Hepatic lipidosis Chronic renal failure Acute pancreatitis Bacterial/viral infections neoplasia
DKA Treatment: Fluids and Elytes
Fluid TherapyReplacement 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/dLElectrolyte Abnormality CorrectionsPotassium: 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
DKA: Insulin TherapyInsulin 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).
Handy Insulin CRI Protcol courtesy of Dibartola
Blood Glucose Conc (mg/dL)
Intravenous Fluid Solution
IV Insulin Solution Rate
250 0.9% saline 10200-250 0.9% saline, 2.5%
dextrose7
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
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
Hyperglycemic, Hyperosmolar State
What makes a patient HHS?
Extreme hyperglycemia: >600 mg/dl
Serum osmolality: > 350 mOsm/kg
Little or no ketonuria
Decreased GFR severe dehydration
Pathophysiology of HHS
Similar to DKA: ↓ insulin; ↑ glucagon, cortisol, growth hormone Small amounts of insulin help prevent ketone formation
HyperglycemiaAnd
hyperosmolality
Osmotic diuresis
dehydration
Reduced GFR
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
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
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.