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DIABETIC KETOACIDOSIS

Introduction
Triad of Hyperglycemia + Ketosis + High anion gap Metabolic Acidosis
Classically seen in T1DM, also in T2DM with triggering factors
Physiology
T1DM - Immune system mediated destruction of pancreatic beta cells - Absolute Insulin
Deficiency
T2DM - Beta cells overwork/overtime for few years before they give up and burnout Relative Insulin Deficiency
Glycogenesis: Glucose converted and stored as Glycogen
Lipogenesis: Acetyl CoA > Fatty Acids > Triglycerides
Glycogenolysis: Breakdown (lysis) of glycogen into glucose
Gluconeogenesis: Conversion of amino acids and lactate into glucose
Lipolysis: Triglyceride breakdown into Fatty Acids > Acetyl CoA > Ketones

Insulin is anabolic: favours energy storage i.e favours glycogenesis, lipogenesis and
inhibits glycogenolysis, gluconeogenesis and lipolysis
Glucagon and counter regulatory hormones (Cortisol, epinephrine, GH) are catabolic
i.e favour glycogenolysis, lipolysis, gluconeogenesis and inhibit glycogenesis and
lipogenesis.
After a meal as the extracellular concentration of glucose rises, glucoses enters the
pancreatic beta cells and triggers insulin release. Insulin restores normoglycemia by
reducing glycogenolysis, gluconeogenesis and also by increasing the glucose uptake by
resting skeletal muscle and adipose tissue. Insulin mobilises the GLUT 4 receptors from
the cytoplasm to the cell membrane. These receptors then act as channels to facilitate the
entry of glucose into cells. If insulin is absent, glucose cant be taken into the cells (reduced
glucose uptake) causing hyperglycemia.
Pathogenesis of DKA

Either insulin deficiency/resistance OR glucagon/counter regulatory hormone


excess
Unopposed action of glucagon in the absence of insulin
T2DM have insulin resistance (not deficiency), so they always have some insulin
available making DKA is less likely unless triggered with infection, illness, ischemia
(ACS/CVA/PE), illicit drug use
Due to less insulin, glucose uptake is decreased into the cells > Hyperglycemia

Cells starve due to lack of glucose > perceive this as hypoglycemia and start
uncontrolled lipolysis (TG breakdown) > Free fatty acids (FFA) generation >
FFA undergo beta oxidation and produce Acetoacetyl CoA > Ketongenesis
(KetoAcidosis i.e acidosis due to ketonemia)
Glucagon stimulates glycogenolysis and gluconeogenesis worsening hyperglycemia.

Nausea and Vomiting: Ketone bodies irritate CTZ in brainstem


Fruity breath: Lungs excrete acetone giving breath a fruity odour
Metabolic Acidosis: due to the production of Ketoacids + hypoperfused kidneys fail to
handle acid-base imbalance
Polyuria: due to hyperglycemia and osmotic diuresis
Pan electrolyte depletion: Lost in urine due to diuresis (Whole body hypoK but
extracellular hyperK)
Hypovolumia > Pre renal azotemia > Metabolic acidosis
Kussmaul breathing - Stimulation of central respiratory centre
Abdominal Pain: Delayed GIT emptying and acidosis induced ileus
AMS: as a result of hyperosmolality and severe acidosis
DD - MUDPILES
Methanol
Uremia
DKA
Propylene Glycol/Phenphormin/Metformin
INH/Iron
Lactic acidosis
Ethylene Glycol/ Ethanol
Salicylates
Diagnosis
Blood Glucose (usually above 250)
Serum Ketones
CBC
RFT
Urine Analysis/Ketones
Venous Blood gas (just call it blood gas!)
ECG (We cannot afford to miss a silent MI!)
Other investigations based on history and examination (Cultures/Imaging etc)
Expect:
Hyponatremia (i.e. the plasma sodium concentration decreases by 2 mEq/L for
every 100 mg/dL increase in the plasma glucose concentration above 100mg/dL)
Leucocytosis due to catechol surge (watch for the band forms)
Amylase/Lipase often bump in DKA - Do imaging if there is a concern for
pancreatitis

Elevated creat due to renal hypoperfusion

Note: BHB is the predominate ketone in DKA but urine dipsticks often do not detect this
ketone body. You are not yet done if Urine dipstick test negative for ketones. Ask for serum
ketones.
Normal BHB/Acetoacetate ratio is 1:1 but can go upto 10:1 in DKA.
Management
ABC
Look for the precipitating events
1. Hydration
2. Potassium Replacement
3. Insulin (go straight to infusion, NO BOLUS INSULIN) - Start let and end late
Don't stop the insulin if sugars start dropping instead switch to dextrose containing fluids
from NS. Stop insulin when the anion gap is normal.
Sodium Bicarb: I dont support regular use of bicarb. It is a desperate measure with
potential downsides like paradoxical CSF Acidosis, HypoK, left shift of O2 dissociation curve
Give ONLY if they look toxic and peri-arrest, may buy you some time.
Replace Mg, Phosphorus as required.
Key Points:

Insulin shifts GLUT4 from the cytoplasm to the cell membrane to facilitate
glucose uptake.
Majority of KB produced in DK is Beta Hydroxybutyrate but urine dipsticks do
not detect this. Go one step further and ask for serum ketones.
Treatment of DKA (in order)> Hydration then watch potassium and only
then Insulin infusion (No bolus)
Ask yourself - What is the precipitating event?
Venous pH is acceptable

Insulin Deficiency or Insensitivity or


Glucagon excess

Decreased Serum
glucose uptake

Hyperglycemia
Glycosuria
Osmotic Diuresis
Electrolyte Depletion

Increased
Catabolism
Increased plasma
amino acids and
nitrogen loss in
urine
Dehydration and
Acidosis
Coma/Death

Questions/Comments/Feedback
Lakshay Chanana
drlakshay_em@yahoo.com
Twitter @EMDidactic

Increased lipolysis

Increased plasma
FFA, Ketogenesis
Ketonemia and
Ketonuria