understand diabetic ketoacidosis, its pathophysiology and management.

1. Dr. Amish Bhutani
DIABETIC KETOACIDOSIS

2. DEFINITION
• DKA is defined as hyperglycemia with metabolic acidosis
resulting from generation of ketones in response to insulin
deficiency (relative / absolute ) and elevated counter-regulatory
hormones.
• Counter regulatory hormones – Glucagon, cortisol,
catecholamines & GH

3. PRECIPITATING EVENTS
• Inadequate insulin administration
• Infection – pneumonia / UTI / gastroenteritis / sepsis
• Infarction – cerebral, myocardial, mesenteric, peripheral
• Drugs – cocaine, thiazide like diuretics
• Pregnancy
• Alcohol

4. CLINICAL FEATURES
• Symptoms
• Nausea / vomiting – often prominent
• Abdominal pain – can be severe
• Shortness of breath
• Polydipsia / polyuria
• Lethargy

5. PHYSICAL FINDINGS
• Patient restless
• Tachypnoea – kussmaul’s breathing and a fruity odor
• Tachycardia
• Dehydration / hypotension
• Lethargy / obtundation / possibly coma
• Abdominal tenderness – severe
* Cerebral edema – more common in children

7. • Insulin deficiency & counter-regulatory hormones excess –
hallmark
Insulin : Glucagon ratio decreases
Gluconeogenesis
Glycogenolysis
Ketone body formation
Pathophysiology

8. Pathophysiology contd.
• Insulin deficiency ----- > decrease in GLUT4 glucose transporter
------- > decrease uptake in skeletal muscles and adipose tissue
------ > increase in free fatty acids ----- > altered hepatic
metabolism ----- > activation of enzyme Carnitine Palmitoyl
transferase 1 ----- > ketone body formation
• as bicarbonate stores are depleted, metabolic acidosis prevails
which is further augmented by lactic acid formation

9. ASSESSMENT
• History:
Symptoms of hyperglycemia, precipitating factors ,
diet and insulin dose.
• Examination:
 Look for signs of dehydration, acidosis, and
electrolytes imbalance, including shock,
hypotension, acidotic breathing, CNS status…etc.
 Look for signs of hidden infections (Fever
strongly suggests infection) and If possible, obtain
accurate weight before starting treatment.

10. DIFFERENTIAL DIAGNOSIS
ANION GAP ACIDOSIS
• Alcoholic ketoacidosis
• Starvation ketoacidosis
• Lactic acidosis
• Renal failure
• Ethylene glycol or methyl alcohol poisoning
• Starvation in late pregnancy or lactation (rare)

11. LAB INVESTIGATIONS
• Leukocytosis
• Ketosis
• Hyperglycaemia
• ABG- high anion gap acidosis
• BUN and creatinine – elevated due to dehydration (
intravascular depletion )
** Acetoacetate interferes and falsely elevates creat
• TGL –raised & lipoprotein – raised

12. • S. amylase – markedly raised
• Doesn’t signify pancreatitis necessarily
• This amylase in DKA is SALIVARY in origin
• Check s.lipase levels to r/o pancreatitis
• S. Na – mostly will be low , BUT !
• certain electrolytes are undermeasured due to hyperglycaemia
/ dehydration
• What is corrected Na ?
for every 100 mg/dl increase in glucose = 1.6 mmol of Na is
reduced

13. • Beta- hydroxybutyrate is synthesized at 3 times greater than other
ketone bodies
• Hence, measurement of this ketone body in the serum is more
specific

15. MANAGEMENT
• Aims –
• IV fluid replacement
• Insulin therapy,
• The agent or event that precipitated the event should be
targeted
• careful monitoring
• Correction of metabolic dearangments

16. FLUID MANAGEMENT
• 2-3 L of 0.9% NS over first 1-3 hr (15-20 mL/kg per hour);
subsequently,
• 0.45% saline at 250-500 mL/h;
• monitor RBS 1 hourly
• When RBS < 200mg/dl then change to 5% glucose and 0.45%
saline at 150-250 mL/dl

17. INSULIN THERAPY
• A bolus of IV (0.1 units/kg) short-acting insulin should be
administered immediately,
• IV insulin should be continued until the acidosis resolves and
the patient is metabolically stable. As the acidosis and insulin
resistance associated with DKA resolve, the insulin infusion rate
can be decreased (to 0.05 - 0.1 units/kg per hour).
• When the patient starts eating - Long-acting insulin, in
combination with SC short-acting insulin, should be
administered. It is crucial to continue the insulin infusion until
adequate insulin levels are achieved by administering long-
acting insulin by the SC route. Even relatively brief periods of
inadequate insulin administration in this transition phase may
result in DKA relapse.

18. • Hyperglycemia usually improves at a rate of 75-100 mg/dL per
hour as a result of insulin-mediated glucose disposal, reduced
hepatic glucose release, and rehydration.
• Rehydration reduces catecholamines, increases urinary glucose
loss, and expands the intravascular volume.

19. POTASSIUM SUPLEMENTATION
• Potassium stores are depleted in DKA
• Estimated deficit 3-5 meq/kg
• insulin-mediated potassium transport into cells,
• resolution of the acidosis (which also promotes potassium entry
into cells), and
• urinary loss of potassium salts of organic acids.
• Thus, potassium repletion should commence as soon as adequate
urine output and a normal serum potassium are documented.
• If the initial serum potassium level is elevated, then potassium
repletion should be delayed until the potassium falls into the
normal range.

20. BICARBONATE SUPPLEMENTATION
• Bicarbonate administration and rapid reversal of acidosis may impair
cardiac function, reduce tissue oxygenation, and promote
hypokalemia.
• one study in children found that bicarbonate use was associated with
an increased risk of cerebral edema.
• However, in the presence of severe acidosis (arterial pH <6.9), the
ADA advises bicarbonate 50 meq/L of sodium bicarbonate in 200 mL
of sterile water with 10 meq/L KCl per hour for 2 h until the pH is
>7.0.
• Hypophosphatemia may result from increased glucose usage. If the
serum phosphate < 1 mg/dL, then phosphate supplement should be
considered and the serum calcium monitored.
• Hypomagnesemia may develop during DKA therapy and may also
require supplementation.

21. COMPLICATIONS OF DKA
• Infection
• Shock
• Vascular thrombosis
• Severe dehydration
• Cerebral vessels
• Cerebral Edema
• Pulmonary Edema
• Result of aggressive
fluid resuscitation

22. DIFFERENTIATING IT FROM HHS

23. • DKA
• RBS > 300 and usually
<500 mg %
• S. osmolarity – variable
• Urine – ketones present
• Acidosis . Ph < 7.3
• HHS
• RBS upto 1000 mg %
• S.osmolarit- > 320
mosmol/l
• Urine ketones- absent
• Acidosis- absent ph > 7.3