Dr.Fouzia MD (general medicine)

1. Diabetic Keto Acidosis

2. Diabetic Keto Acidosis is an acute metabolic complication of
diabetes mellitus .
-It is characterised by uncontrolled hyperglycemia, ketone
body formation severe enough to cause metabolic acidosis.
-DKA is characteristically associated with type 1 diabetes.
- it also occurs in type 2 diabetes under conditions of extreme
stress such as:
1. severe infection
2.trauma,surgery, burns
3.cardiovascular emergencies (myocardial infarction , stroke)

3. Pathophysiology:
• Extracellular concentration of glucose is primarily
regulated by 2 hormones- i.e insulin and glucagon ( a
counter regulatory hormone)
• As serum glucose concentration increases after a
glucose meal , glucose enters the pancreatic beta
cells, leading to insulin release .
• Insulin restores normoglycemia by:
- Hepatic glucose production by reduction in both
gluconeogenesis and glycogenolysis, by inhibiting
glucagon secretion
Glucose uptake by skeletal muscle and adipose tissue.

4. Absolute insulin
deficiency
Counter regulatory
hormones
Lipolysis
FFA to Liver
Ketogenesis
Triacylglycerol
Hyperlipidemia
Ketoacidosis
Protein
Synthesis
Proteolysis
Gluconeogenic
substrates
Glucose
utilisation Gluconeogenesis
Glycogenolysis
Hyperglycemia
Impaired renal function
glucosuria
Loss of water and electrolytes Dehydration

5. Ketone Production(in liver mitochondria)
Insulin deficiency
Cause enhanced lipolysis
from peripheral fat stores by
Increased activity of
hormone sensitive lipase
Release of FFA , glycerol
Fatty acid taken up by hepatocyte
FA+ Coenzyme A fattyacyl coA
Entry of acyl coA into mitochondria
by carnitine palmatoyl transferase
reaction
Beta oxidation of FA in
mitochondria into acetyl coA
Acetoacetyl coA + acetyl coA=
HMGcoA
Acetoacetate
Beta hydroxy butarate
Acetone
-co2

6. • Ketone bodies are organic acids that dissociate at physiological ph , and
neutralised by Hco3 . At high concentrations, they contribute large H+ ions
, that consumes maximum HCO3 -, leading to metabolic acidosis with high
anion gap

7. Precipitating factors:
1. Infection (Pneumonia/UTI)
2. Discontinuation/ inadequate insulin therapy
3. Acute major illness such as CVA/sepsis/pancreatitis/MI
4. New onset type 1 diabetes mellitus ; in which DKA is a common presentation
5. In established type1 diabetes mellitus, omission of insulin in setting of gastro
enteritis , when patient stops insulin due to decreased oral intake.
6. Poor compliance with insulin regimen
7. Pregnancy
8. SGLUT 2 inhibitors ( sodium glucose co-transpoter 2 inhibitors i.e
Canagliflozin( 100mg, 300mg /d) , Dapagliflozin (5-10 mg/d) ,
Empagliflozin(10mg , 25 mg/d), used in type 2 diabetes mellitus

8. • MOA: SGLUT2 inhibitors inhibit reabsorption of
glucose at PCT in kidney, increase glucose excretion
and lower blood glucose levels
• SGLUT 2 inhbitors are responsible for DKA by:
- lowering blood glucose via urinary excretion ,
resulting in decreased insulin secretion from
pancreatic cells, thus increased lipolysis, leading to
increased free fatty acid production
- stimulate secretion of counter regulatory hormone
glucagon, which contributes to overproduction of
ketone bodies.
- by decreasing renal clearance of ketone bodies.

10. Clinical features:
• DKA evolves rapidly over 24 hr period.
• Early symptoms of marked hyperglycemia- polyuria,
polydypsia, weight loss.
• Nausea /Vomiting
• Abdominal pain
• Shortness of breath
Physical findings:
• Tachycardia
• Dehydration/hypotension : signs of volume depletion
• Tachypnea / kussmal respiration/respiratory distress
• Abdominal tenderness (resembling acute pancreatitis )
• Lethargy/cerebral oedema /coma

11. Abdominal pain in DKA
• Abdominal pain is associated with severity of
metabolic acidosis.
Causes for pain abdomen in DKA include:
• Delay in gastric emptying induced by metabolic
acidosis . Metabolic acidosis impair smooth muscle
function ,mainly affects gastric antral rhythm, thus
causing pain abdomen.
• Other causes for abdominal pain such as acute
pancreatitis, acute appendicitis , renal abscess should
be ruled out , when occuring in absence of severe
metaolic acidosis and persisting after resolution of
keto acidosis.

12. • Patient with DKA has fruity odour ( due to exhaled ketone
(acetone) and deep respirations reflecting compensatory
hyperventilation (k/a Kussmal respiration)

13. Essentials of diagnosis:
1. Hyperglycemia (>250 mg/dl)
2. Metabolic acidosis with blood ph <7.3; serum
bicarbonate <15 meq/l
3. Serum positive for ketones .
• Hyperventilation is a compensatory
mechanism which reduces the partial
pressure of co2 and decrease the fall in PH

14. Laboratory abnormalities and diagnosis
1. Serum glucose: 250-600 mg/dl
2. BUN , Serum creatinine : elevated levels indicate intravascular volume depletion.
3. Serum ketones are present at significant levels.( beta hydroxybutyrate is 3 fold greater
rate than acetoacetate.
4. Nitroprusside test is used to detect urine ketones.
5. CBP: leukocytosis proportional to degree of ketonemia.
- leucocytosis unrelated to infection occur as a result of hypercortisolemia, increased
catecholamine secretion.
- WBC count > 25000/microltr raise the suspicion of infection and to be evaluated.
6. ABG: Severe acidosis (Ph- 6.9 to 7.2) ,pa co2 is low (15-20mmhg) related to
compensatory hyperventilation, s. bicarbonate: 5 to 15 meq/l,( high anion gap
metabolic acidosis)
7. Serum electrolytes:
- serum sodium : hyponatremia (125-135 meq/l ). The measured serum sodium is
reduced as a consequence of hyperglycemia. (hypertonic hyponatremia). For each
100mg/dl rise in serum glucose , serum Na+ fall by 1.6 meq/l
Hyperglycemia plasma osmolality pulls water out of cells expand ECF
s.Na+ conc.

15. 8. Serum potassium: initially elevated followed by fall in serum K+. Avg total
body potassium deficit is about 3-5 meq/kg.
• plasma potassium is raised initially due to disproportionate loss of water ,
protein break down and displacement of potassium from intracellular
comparment by H+ ions . After insulin treatment , there is a fall in plasma
potassium due to dilution of extracellular potassium by i.v fluids , and shift of
k+ into cells by insulin and the renal loss of potassium.
• ECG is helpful in diagnosing and monitoring potassium status:
• Flattened t waves with U waves – sign of hypokalemia
• Tall peaked t waves – sign of hyperkalemia
9.Serum phosphate levels are depleted .
10.Non specific elevations of serum amylase and lipase occurs in about 16-25%
cases of DKA, and imaging study is necessary for diagnosis of acute
pancreatitis.
11.In infected patients , pyrexia may not be present initially due to
vasodilatation secondary to acidosis( hypothermia).

16. Management of DKA
:
IV fluids Serum K+ ACIDOSIS
ECFV
Severe
deficit(shock
)
Mild – moderate
deficit
0.9 %NS
1-2 l/hr to
correct
hypotension
0.9%NS 500ml/hr×
4 hrs then 250
ml/hr ×4hrs
<3.3 meq/l
>3.3 meq/l
<5-5.5 meq/l
Give 40 meq/L
Kcl + no insulin
till K+ >3.3
meq/L
Give 10-40
meq/L Kcl, less
aaggressively
If K+ > 3.3
meq/L, short
acting insulin
0.1U/kg/h
If ph<7.0
Consider NaHCo3
1amp/hr until
PH>7.0, avoid
hypokalemia
Adjust rate of insulin
infusion based on
anion gap resolution,
avoid hypokalemia and
hypoglycemia
Once euvolemic
Corrected s. Na+
<135 meq/L
Corrected s. Na +
normal /High
Continue 0.9%
NS at 500 ml/hr
0.45 % NS @ 500 ml/hr to
provide electrolyte free water
Dextrose added to saline solution when serum glucose
reaches 200- 250 mg/dl
Foods high in K+:(given when
accepted orally)
Banana(10 meq)
Tomato juice (14 meq/240ml)
Coconut water (10-20meq)

17. Management of DKA
1. Fluid replacement:
Infusion of isotonic saline –
o to expand ECF volume
o Increase insulin responsiveness by lowering plasma osmolality , decreasing
vasoconstriction , improving perfusion and decreasing stress hormone levels.
2.Correction of potassium deficit:
3.Insulin therapy:
I.V regular insulin/ rapid acting insulin analogues are equally effective In treating DKA
, but preferred due to low cost.
I.V regular Insulin:
• Initiated with I.V bolus of regular insulin ( 0.1 U/kg bodywt) followed with in 5
min by continuous infusion of regular insulin of 0.1 U/kg/hr ( equalent to 6U/hr in
60 kg individual)
• These doses of I.V regular insulin , decrease serum glucose by approx. 50-70
mg/dl/hr
• Higher doses donot produce prominent hypoglycemic effect , as the insulin
receptors are saturated and activated by lower dose.
• If serum glucose doesn’t fall by 50-70 mg/dl/hr , within 1 st hr, infusion rate is
doubled every hr, till a steady decline in serum glucose is achieved.

18. • The fall in serum glucose is the result of both insulin activity and
volume repletion.
 Volume repletion alone can initially reduce serum glucose by 35-
70 mg/dl/hr due to- ECF volume expansion and dilution
 Increased urinary loss resulting from improved renal perfusion and
GFR
 Decreased stress hormone levels which oppose effects of insulin
 If serum glucose reaches 200 mg/dl , dextrose is added to NS and
infusion rate is decreased to 0.02-0.05 U/kg/hr.
3. Dextrose is added:
 for better intracellular distribution of free water( correct
intracellular dehydration )
 To prevent hypoglycemia and resolution of ketone bodies
 As a prophylactic measure to prevent late cerebral oedema
syndrome.
4. Transition to subcutaneous insulin regimen:
Once DKA is controlled and patient is awake and able to eat , s/c insulin
therapy is initiated.

19. Requirement of insulin:
 In type 1 DM , due to significant insulin deficiency, a total daily insulin dose
of approx 0.6U/kg is given.
 Amount of insulin required in the previous 8 hrs is helpful in estimating
initial insulin doses.
 Half of the daily dosing is given as long acting basal insulin and other half as
short acting insulin pre meals .
 The overlap of s/c insulin action and insulin infusion is necessary to prevent
relapse of DKA , hence the patient should receive s/c rapid acting insulin
analog with first meal and infusion discontinued 1 hr later.
5.Sodium bicarbonate:
Administered in DKA if arterial PH <7.0 with careful monitoring to prevent
overcorrection.
Infusion:
• 1-2ampoules of NaHCo3 (44 meq/50 ml) added to 1ltr of 0.45%NS with 20
meq KCl, can be given till PH reaches 7.1.
• It should not be given when pH is >7.1 as metabolic alkalosis cause shift of
K+ from serum into cells , causing fatal cardiac arrhythmias.

20. Differential diagnosis:
1. HONK /HHS (hyperosmolar non ketotic coma / hyperglycemic hyperosmolar
state)
• ESSENTIALS OF DIAGNOSIS:
1. Hyperglycemia > 600 mg/dl
2. Serum osmolality >310 mosm/kg( normal- 285-295 mosm/kg)
3. No ketosis , blood PH > 7.3
4. serum bicarb> 15 meq/L
5. Normal anion gap (<14 meq/L)
2. Other causes of high anion gap metabolic acidosis:
- lactic acidosis
- ketoacidosis ( alcoholic/ diabetic/starvation)
- acute / chronic renal failure
- ingested toxins ( salicylates, ethylene glycol, methanol)

21. DKA HHS
Serum glucose 250-600 600-1200
Sodium(meq/L) 125-135 135-145
Potassium Normal to high normal
creatinine Slight rise Moderate rise
Osmolality (mosm/ml) 300-320 330-380
Plasma ketones ++++ +/-
Serum bicarbonate(meq/L) <15
Arterial PH 6.8-7.3 >7.3
Anion gap high normal

22. Prognosis
1. Mortality rate < 5 % seen with low dose insulin infusion , fluid , electrolyte
replacement with careful monitoring of patient’s clinical and lab response
to therapy .
2. Mortality rate of DKA >20% in elderly pt. , and pt. in profound coma I
whom treatment is delayed.
3. Acute MI following prolonged hypotension worsen the outcome
4. End stage CKD and prior renal dysfunction worsen the prognosis.
5. Rapid correction of hyperglycemia , excess volume administration in first 4
hrs, severe baseline acidosis may result in symptomatic cerebral oedema(
with onset of headache / deterioration in mental status) .I.V mannitol 1-
2g/kg given over 15 min is mainstay of treatment.
6. Excess cystalloid infusion can precipitate pulmonary odema
7. ARDS is a rare complication of DKA

23. DKA in pregnancy
1. DKA in pregnancy is a medical emergency, both mother and fetus are at risk
for morbidity and mortality.
2. Physiological changes in pregnancy( adaptation to pregnancy)-
• Acid base status of pregnancy is compensated respiratory alkalosis .
• Fall in Hco3- occurs to compensate for primary respiratory alkalosis,
resulting in metabolic acidosis .
• Pregnancy , being a diabetogenic state due to certain hormones( HPL, HCG,
progesterone , cortisol) lead to insulin resistance , high in 2 nd and early 3
rd trimester.
• CAUSES:
• 1. cessation of insulin therapy -m/c
• 2. previously undiagnosed DM
• 3. infection

24. Maternal concerns Fetal concerns
1.Severe dehydration – hypotension
2. Acidosis - organ dysfunction
3. Electrolyte imbalance-cardiac arrhythmias
•Maternal hyperglycemia fetal
hyperglycemia and fetal osmotic diuresis
•Fetus get acidotic from ketones that cross
Placenta
Acedemia uterine blood flow , tissue
perfusion oxygenation.
•Maternal treatment must be aggressive with reassessment of biochemical
parameters 1 -2 hrs
•Immediate delivery is not indicated until maternal metabolic condition is corrected.
•Emergency caeserean delivery in case of decomensated DKA worsens maternal
condition.

25. THANK YOU