1. Diabetic Ketoacidosis
EPU Team (Dr. Uko P., Dr. Eke E.P.,
Dr. Jemide O., Dr. Osang S.)
FMC Keffi
28th
of May, 2014

2. Outline
 Overview of Diabetic Mellitus
 Diabetic Ketoacidosis: Introduction
 Epidemiology
 Physiology
 Pathophysiology
 Clinical Presentation
 Diagnosis
 Complications
 Treatment/Monitoring
 Prevention
 Conclusion
 References 2

3. Overview of Diabetes Mellitus
Diabetes mellitus is a group of
metabolic diseases characterized by
chronic hyperglycaemia resulting
from defects in insulin secretion,
insulin action or both.

4. Criteria for diagnosis
Symptoms of DM and casual plasma
glucose conc. > 11.1mmol/L(200mg/dl) (10
for venous)
Fasting Plasma Glucose > 7.0mmol/L
(126mg/dl) (6.3 for venous and capillary)
2hr post load of glucose >11.1mmol/L
during an OGTT

5. Types of DM
1. Type 1 Diabetes Mellitus (T1DM):- β
cell destruction leading to absolute
insulin deficiency. Immune mediated,
idiopathic
2. Type 2 Diabetes Mellitus (T2DM):-
insulin resistance with relative insulin
deficiency
3. Other types
 Gestational DM

6. Genetic defects of
◦ β cell function
◦ Insulin action
Diseases of the pancreas
Endocrinopathies
Infections
Drug or chemical induced
Genetic syndromes
Uncommon forms of immune related

7. TYPE 1 DM
Type 1 DM is the most common
endocrine metabolic disorder of
childhood and adolescence.
Autoimmune mechanisms are factors in
the genesis of T1DM.
• Most cases are primarily due to T-cell
mediated pancreatic islet β-cell
destruction.

8. Serological markers of an autoimmune
pathologic process, including islet cell,
glutamic acid decarboxylase (GAD), islet
antigen (IA)-2, IA-2b, or insulin
autoantibodies (IAAs), are present in 85–
90% of individuals when fasting
hyperglycaemia is detected
8

9. Etiology of T1Diabetes
Environmental
Factors
•Cow’s milk?
•Viruses ?
•Nitrates?
Genetic
Susceptibility
•DM1: HLADR3,DR4↑
•Protective DRB1,DQB1↓
•DM2
Autoimmunity & Insulitis
Destruction of pancreatic β cells

10. EPIDEMIOLOGY
 T1DM accounts for about 10% of all diabetes,
affecting 1.4million in the USA and over 15million
in the world.
 While it accounts for most cases of diabetes in
childhood, it is not limited to this age group; new
cases continue to occur in adult life and
approximately 50% of individuals with T1DM
present as adults.

11. The incidence of type 1 DM is highly
variable among different ethnic groups.
Girls and boys are almost equally affected
but there is a modest female preponderance
in some low risk populations (e.g the
Japanese).
There is no apparent correlation with
socioeconomic status.

12. Peaks of presentation occur in 2 age
groups: at 5-7 years of age and at the time
of puberty.
The first peak may correspond to the time
of increased exposure to the infectious
agents coincident with the beginning of
school;

13. The 2nd
peak may correspond to the
pubertal growth spurt induced by gonadal
steroids and the increased pubertal growth
hormone secretion( which antagonizes
insulin).
These possible cause-and-effect
relationships remain to be proved.
13

14. Morbidity and mortality stem from acute
metabolic derangement and long-term
complications (usually in adulthood) that
affect small and large vessels resulting in
retinopathy, nephropathy, neuropathy,
ischaemic heart disease and arterial
obstruction with gangrene of the
extremities.

15. The acute clinical manifestations are due to
hypoinsulinaemic hyperglycaemic
ketoacidosis.
Individuals with TIDM confront serious
lifestyle alteration that include an absolute
daily requirement for exogenous insulin,
the need to monitor their own glucose
level, and the need to pay attention to
dietary intake. 15

16. Predisposing Factors for T1DM
The major histo-compatibility complex on
chromosome 6 – greatest contribution
Viral infections: Congenital rubella
syndrome, Enteroviruses, Mumps virus.
Diet: Breast-feeding may lower the risk of
T1DM either directly or by delaying
exposure to cow’s milk protein.

17. Hygiene Hypothesis: Possible protective
role of infections. Lack of exposure to
childhood infections may somehow
increase an individual’s chances of
developing autoimmune diseases
including T1DM.
Psychologic stress

18. T2DM
 Heterogenous disorder characterized by
peripheral resistance and failure of the β-cell to
keep up with increasing insulin demand.
 These patients have relative rather than absolute
insulin deficiency.
 Generally they are not ketosis prone, but
ketoacidosis may develop in some circumstances.
 Aetiology is not known, but these patients do not
have autoimmune destruction of β-Cell nor do they
have any of the known causes of secondary
diabetes mellitus.

19. DKA: INTRODUCTION
Diabetic ketoacidosis (DKA) is a metabolic
derangement caused by the absolute or
relative deficiency of insulin
It is one of the most important causes of
mortality and severe morbidity in children
with diabetes, particularly at the time of first
diagnosis.
 Early recognition and careful management
are essential if death and disability are to be
avoided
19

20. HISTORY
The first full description of diabetic
ketoacidosis is attributed to Julius
Dreschfeld, a German pathologist working in
Manchester, United Kingdom in 1886
The condition remained almost universally
fatal until the discovery of insulin in the
1920s;
20

21. Insulin was first isolated from the pancreas
in 1922 by Banting and Best.
The entity of cerebral oedema due to DKA
was described in 1936 by a team of doctors
from Philadelphia.
21

22. EPIDEMIOLOGY
Few data are available
In the United Kingdom national study,
60% of all cases occurred in patients with
known diabetes
In the USA, 25% of new cases of Type 1
DM present with ketoacidosis,
approximate incidence of 4 per 100,000
children annually.
22

23. 88% of patients first present in the children's
emergency room with Diabetic ketoacidosis
(DKA) (Ugochi Ibekwe et al, Federal Teaching
Hospital Abakaliki)
 DKA has been found in the range of 7-80%
in newly diagnosed patients and 25-90% in
children who have already been diagnosed with
diabetes.
This high prevalence of DKA is attributed to
the lack of awareness among health workers
and the community at large (Adesiyan et al) 23

24. In FMC Keffi:
From January 2013 to May 2014, a total of
6 patients were admitted for DKA
5 females and 1 male
Age range: 8-11years (except the male,
3years 9months)
2 cases were admitted in May 2014
24

25. Sex: Although no difference in DKA rates
exists between the sexes at diagnosis and
during early childhood, adolescent girls with
diabetes are twice as likely to develop DKA
as adolescent boys.
Age:
– Preschool aged children are at greatest risk of
presenting with DKA because the diagnosis of
diabetes in children is often missed.
– Adolescents are more likely to develop DKA
after diagnosis of diabetes 25

26. PHYSIOLOGY
Insulin is a polypeptide containing two
chains of amino acids linked by disulfide
bridges
The net effect of the hormone is storage of
carbohydrate, protein, and fat. Therefore,
insulin is appropriately called the
“hormone of abundance”
26

27. Rapid (seconds)
 Increased transport of glucose, amino acids, and K+
into
insulin-sensitive cells
Intermediate (minutes)
 Stimulation of protein synthesis
 Inhibition of protein degradation
 Activation of glycolytic enzymes and glycogen
synthase
 Inhibition of phosphorylase and gluconeogenic
enzymes
Delayed (hours)
 Increase in mRNAs for lipogenic and other enzymes
Principal Actions of Insulin
27

28. Insulin inactivates liver phosphorylase
Increases the activity of the enzyme
glucokinase which causes the initial
phosphorylation of glucose after it diffuses
into the liver cells.
Increases the activity of glycogen
synthase
Insulin inhibits the action of hormone-
sensitive lipoprotein lipase 28

29. Adipose tissue
 Increased glucose entry
 Increased fatty acid synthesis
 Increased glycerol phosphate synthesis
 Increased triglyceride deposition
 Inactivation of lipoprotein lipase
 Inhibition of hormone-sensitive lipase
 Increased K+
uptake
Effects of Insulin on Various Tissues
29

30.  Increased glucose entry
 Increased glycogen synthesis
 Increased amino acid uptake
 Increased protein synthesis in ribosomes
 Decreased protein catabolism
 Decreased release of gluconeogenic
amino acids
 Increased ketone uptake
 Increased K+
uptake
Muscle
30

31.  Decreased ketogenesis
 Increased protein synthesis
 Increased lipid synthesis
 Decreased glucose output due to decreased
gluconeogenesis, increased glycogen
synthesis, and increased glycolysis
General
 Increased cell growth
Liver
31

32. INFLUENCE OF FEEDING (HIGH INSULIN) OR OF
FASTING (LOW INSULIN) ON SOME METABOLIC
PROCESSES IN LIVER, MUSCLE AND ADIPOSE TISSUE
HIGH PLASMA INSULIN
(POSTPRANDIAL STATE)
LOW PLASMA INSULIN (FASTED
STATE)
Liver Glucose uptake Glucose production
Glycogen syntheses Glycogenolysis
Absence of gluconeogenesis Gluconeogenesis
Lipogenesis Absence of lipogenesis
Absence of ketogenesis Ketogenesis
Muscle Glucose uptake Absence of glucose uptake
Glucose oxidation Fatty acid and ketone oxidation
Glycogen synthesis Glycogenolysis
Protein synthesis Proteolysis and amino acid release
Adipose Tissue Glucose uptake Absence of glucose uptake
Lipid synthesis Lipolysis and fatty acid release
Triglyceride uptake Absence of triglyceride uptake 32

33. PATHOPHYSIOLOGY
Insulin deficiency exaggerates the normal
response to fasting: gluconeogenesis and
glycogenolysis.
 Peripheral glucose uptake is impaired and
levels of the main counter-regulatory
hormones increase (glucagon, cortisol,
catecholamines, growth hormone).
A variety of metabolic consequences
follow. 33

34.  Secondary to insulin deficiency and the action of
counter-regulatory hormones (glucagon), blood
glucose increases due to glycogenolysis and
gluconeogenesis, leading to hyperglycemia and
glucosuria.
 Blood glucose levels rise above the renal threshold
for glucose reabsorption, causing an osmotic diuresis,
leading to waterwater & electrolyte loss.
 In the absence of insulin activity the body fails to
utilize glucose as fuel and uses fats instead. This leads
to ketosis. 34

35. The excess of ketone bodies will cause metabolic
acidosis, the latter is also aggravated by lactic
acidosis caused by dehydration & poor tissue
perfusion.
Vomiting due to an ileus, plus increased
insensible water losses due to tachypnea will
worsen the state of dehydration.
Electrolyte abnormalities are secondary to their
loss in urine & trans-membrane alterations
following acidosis & osmotic diuresis.
35

36. Because of acidosis, K+
ions enter the circulation
leading to hyperkalemia, this is aggravated by
dehydration and renal failure.
 Depending on the duration of DKA, serum K+
at
diagnosis may be high, normal or low, but the
intracellular K+
stores are always depleted.
 Phosphate depletion will also take place due to
metabolic acidosis.
 Na+
loss occurs secondary to the hyperosmotic
state & the osmotic diuresis. 36

37. The dehydration can lead to decreased
kidney perfusion and acute renal failure.
Accumulation of ketone bodies contributes
to the abdominal pain and vomiting.
The increasing acidosis leads to acidotic
breathing and acetone smell in the breath
and eventually causes impaired
consciousness and coma.
37

38. Fluid and electrolytes
Fluid losses are considerable, typically 3-10%
of body weight.
Most water is lost by osmotic diuresis, with
important contributions from hyperventilation
and vomiting.
The diuresis also leads to considerable urinary
losses of potassium, sodium, phosphate, and
magnesium ions 38

39. Ketoacidosis
Insulin inhibits the lipolytic action of cortisol
and growth hormone, so insulin deficiency
increases circulating levels of fatty acids.
These are oxidized in the liver, producing the
acidic ketone bodies: beta-hydroxybutyrate
and acetoacetate, from which acetone
spontaneously forms.
The resulting acidosis primarily is due to
circulating ketone bodies, with a smaller
contribution from excess fatty acids and lactic
acidosis, as a consequence of poor tissue
perfusion. 39

40. Absolute insulin deficiency OR
Stress, infection or insufficient insulin intake
Counter-regulatory hormones:  Glucagon, Cortisol,
Catecholamines, GH
Lipolysis
 FFA to liver
 Ketogenesis
 Alkali reserve
Acidosis
 Lactate
Glucose
utilization
 Proteolysis
 Protein synthesis
 Glycogenolysis
Gluconeogenic substrates
 Gluconeogenesis
Hyperglycemia
Glucosuria (osmotic diuresis)
Loss of water and electrolytes
Dehydration
Impaired renal function
Hyperosmolarity
40

41. Clinical Presentation
Features of DKA are progressive.
Symptoms are aggravated by presence of some
precipitating factors.
 Inter current infections
 Drugs e.g steroids, thiazides, terbutaline,
dobutamine
 Psychological stress
 Trauma
 Alcohol and drug abuse
 Insulin omission in already diagnosed diabetics 41

42. Features include:
Polyuria- nocturia
Nocturnal enuresis
Polydipsia
Hyperphagia
Weight loss
Vaginitis
Muscle cramps and pains
42

43. Abdominal discomfort or pain
Nausea, vomiting
Dehydration- moderate to severe
Deep, heavy and rapid breathing-
Kussmaul’ s breathing
Fruity acetone breath
Lethargy
Altered mental state from disorientation to
coma 43

44. Diagnosis – Cardinal Features
44

45. DKA can present;
Shock
Dehydration with no shock
Presence of complications
Presence of cardinal features otherwise
stable
45

46. Classification of DKA
Mild Moderate Severe
HCO3
(mmol/L)
10-15 5-10 <5
CO2
(mEq/L)
16 - 20 10 - 15 < 10
pH 7.25 – 7.35 7.15 – 7.25 < 7.15
Clinical state Oriented, alert
but fatigued
Oriented but
sleepy;
arousable;
Kussmaul
respiration
Kussmaul or
depressed
respiration;
sleepy to
depressed
sensorium to
coma 46

47. Work up
 Plasma glucose – hyperglycemia
 HbA1c
 Serum ketone assay
 Urinalysis – glucosuria, ketonuria, evidence of
infection
 E, U, Cr – K+, Na+, HCO3, PO4, elevated BUN
 Arterial Blood gases – acidosis
 FBC – infection
 Malaria parasite, Cultures – infection
 ECG
47

48. Insulin / Islet cell Antibodies
Thyroid function tests/ thyroid auto
antibodies
Brain CT
Abdominal X rays/ Abdominal USS
48

49. Differential Diagnosis
1. Non-ketotic Hyperosmolar Coma/ HHS
2. Urinary tract infection
3. Acute gastroenteritis with dehydration
4. Acute pancreatitis
5. Acute abdomen
6. Meningitis
7. ARI – pneumonia, bronchiolitis
8. Status asthmaticus
9. Hysterical hyperventilation
49

50. 50

51. Complications
1. Cerebral edema
2. Intracranial infarction
3. Cerebral venous thrombosis
4. Acute Tubular Necrosis
5. Deep Venous Thrombosis
6. Pulmonary edema
7. Electrolyte derangement(s)
8. Cardiac dysrhythmias 51

52. Cerebral Edema
Occurs in 0.5 – 1% of children.
Accounts for 90% of neurological
complications of DKA
Carries a high mortality risk – 70%.
Only about 15% recover without sequelae.
Typically occurs 6 – 10 hours after
initiation of treatment.
It often follows a period of clinical
improvement.
52

53. Mechanism not fully understood but few
theories-
Loss of cerebral autoregulation
Vasogenic mechanism of edema formation.
Cerebral ischemia
53

54. Risk factors
Younger age - < 5 years
Rapid rehydration
Prolonged duration of symptoms prior to
therapy
Administration of IV bicarbonate
High initial glucose concentration
Hypernatremia or persistent hyponatremia.
54

55. Clinical features
Headache, lethargy, confusion
Pupillary changes
Incontinence
Deteriorating consciousness
Seizures
Cushings triad – hypertension,
bradycardia, irregular respiration
55

56. Diagnosis
Based on a single criterion:
Decorticate or decerebrate posture
Cranial nerve palsy – iii, iv, vi
Abnormal respiration
Abnormal verbal or motor response to pain
56

57. Major Criteria
Altered mental state
Bradycardia
Incontinence
57

58. Minor Criteria:
Vomiting
Headache
Lethargy
Hypertension DBP> 90mmHg
Age < 5
2 major, or 1 major + 2 minor 58

59. Treatment of DKA
DKA is an emergency; but, it is managed with
cautious urgency
Treatment of DKA requires frequent eyes-on,
hands-on and brain-on reassessment
It should never be “auto-pilot” or managed
from the call room
Team consultant must be informed

60. Emergency assessment +
Resuscitation
Quick history
Weigh the child/ estimate
Assess consciousness (Glasgow Coma
Scale)
Bedside tests ( RBS, Urinalysis, PO2)

61. Examination
General state/level of consciousness
Level of hydration (usually overestimated)
3% -just detectable
5% -dry mucus membranes/reduced skin
tugor
8%-slow cap. Refill(>3sec)/sunken eyes
>10%-shock, weak pulses, ↓BP

62. Respiration
Hyperventilation
Irregular in cerebral edema
Congestion/consolidation
Cardiovascular
Low volume/thready pulse
Tachycardia
Bradycardia in ↓ ICP

63. Eyes
Papilloedema
Abdomen
Tenderness
Reduced bowel sounds (ileus)

64. Resuscitation
Airway
Suction
Oropharyngeal airway
NG tube for gastric emptying
Breathing
 100% O2 by face mask
Circulation
Insert iv canula; collect all blood samples

65. Modalities
Fluid replacement
Electrolyte replacement
Insulin infusion
Treatment of infections
Correct complications
Monitoring

66. Fluid replacement
Deficit + maintenance
Correction of deficit: 10-20ml/kg in 1st
hr
IVF N/S OR Ringer’s bolus (max 3 doses
in shock)
Maintenance + remainder of deficit over
48hrs
IVF N/S
Change to 0.45% saline + 5% DW (when
RBS ≤ 15 mmol/L)

67. Age (yrs) Weight
(kg)
Maintenance
fluid/24hr
< 1 3-9 80
1-5 10-19 70
6-9 20-29 60
10-14 30-50 50
> 15 > 50 35

68. Fluid calculation
Deficit= estimated% dehydration x wt x 10
(mls)
Maintenance= wt x 100ml/kg (1st
10kg)
+50ml/kg (2nd
10kg)
+20ml/kg (subsequent kg)
Example; 20kg child, 10% dehydrated
Deficit= 10x 20 x10 = 2000 ml
Maintenance= 20 x 60= 1200 x2=2400/48hrs
Total fluids over 48hr= 4800ml @ 33dpm

69. Electrolyte replacement
 Electrolyte depleted in DKA include; K+
,Na+
PO4
,
and Mg2+
 Total body K+
always depleted in DKA (≈4-
6mmol/kg)
 initial level of K+
may be low, normal or high
 K⁺ Should not be started until shock is corrected
 Requires ECG monitoring

70. Rate of infusion is usually 3mmol/kg/24hr
(max dose 0.5mmol/kg/hr)
Hypokalemia; give after initial fluid
resuscitation
20mmol/L
Eukalemia; at the time of insulin
introduction
40mmol/L (20 as KCl, 20 as KPO4)

71. Insulin
Insulin is required to reverse the metabolic
abnormalities by further decreasing blood
glucose and inhibiting ketone body
formation.
Only give when shock has been reversed
Usually started in the 2nd
hr of management

72. Recommended initial dose is 0.1U/kg/hr of
soluble insulin
Subcutaneous insulin 0.3U/kg stat, then
0.1U/kg/hr if iv access not possible: provided
good peripheral circulation
Insulin can be reduced to 0.05U/kg/hr (if pH
> 7.3, HCO3
-1
, rate of fall of glucose >
5mmo/L/hr)
If RBS falls to < 4mmol/L (give 2ml/kg of
10% DW bolus)

73. Insulin Therapy
10 units of short-acting Insulin with 0.9%saline into a
soluset/syringe pump to make up 100ml, producing a
concentration of 1U/10ml
E.g. a seven year old weighing 30kg requiring 0.1U/kg/hour
of insulin
0.1 x 30 = 3U/hour
Since 10ml=1U, then 3U/hour = 30ml/hour
60drops = 1ml
Hence 30 x 60 = 1800drops/hour (60mins =1hour)
30 drops/minute

74. Correction of acidosis
Usually autocorrected by IVF and insulin
administration ( improved GFR)
NaHCO3 is given cautiously if there is;
pH< 6.9
HCO3
-1
< 5mmol/L
Given empirically at dose of 1-2mmol/kg
over 1hr as infusion

75. Treat infections
Commonest precipitant of DKA
Usually started empirically until blood
culture is available
May include treatment for malaria,
pneumonia, meningitis etc as
appropriate

76. Monitoring treatment complications
Cerebral edema
Major cause of mortality
Complicated by early commencement of
insulin
Overzealous rehydration also a culprit
Also implicated is correction of acidosis
with NaHCO₃
Severe hyperglycemia with high
osmolality (Sosm>350 mOsm /L)

77.  Treatment includes;
 Reduction of IVF to ½ or 2/3rd
of maintenance
 Elevate head 30 to the horizontal⁰
 IV mannitol 0.5-1g/kg/dose 6-8hrly (iv furosemide as
adjunct)
 IV 3% (hypertonic) saline 2-4ml/kg alternative
 Hyperventilation
 Dialysis

78. Hypoglycemia
Usually caused by high insulin doses/bolus
injections
Prevented by regular blood sugar monitoring
while patient is on insulin infusion
Corrected by giving 2-4ml/kg of iv 10% DW
bolus, continuing ivf 0.45% saline + 5% DW
(which may be increased to 10% DW)
Dose of insulin infusion may be reduced by
0.025U up to 0.5U/kg/hr

79. Cardiac dysrhythmia
Usually secondary to hypokalemia
/acidosis
Need for cardiac monitoring
Usually corrected when cause is treated

80. Monitoring
 Neurological assessment: ½ -1hourly
 Vital signs: Pulse rate, respiratory rate BP - hourly
 Strict intake / output chart
 Random blood sugar & urine/blood ketones hourly
 Electrolytes: initially 2hourly. When K and Na are
normal and HCO > 15mmol/L 4-6 hourly₃⁻

81. Transition to subcutaneous insulin
When dehydration, acidosis and hyperglycemia
are corrected
Blood ketone levels are low (<1mmol/L)
Patient is tolerating orally, no longer vomiting
Target blood sugar before commencement 8.3-
13.8 mmol/L

82. Dose; 0.5-0.7U/kg/dose of soluble insulin
8 hourly
Dose up to 1.0U/kg/day of mixtard on
discharge
 < 30kg: 0.3U/kg/day; 2/3rd
AM,1/3rd
PM
 > 30kg: 0.6U/kg/day; 2/3rd
AM, 1/3rd
PM
Stop insulin infusion ½ to 1hour after
commencement of subcutaneous injection

83. Counseling for discharge
Treatment is lifelong
Educating patient and family members on:
Basic pathophysiology of DM
Importance of adequate control to avoid
complications
Survival skills:
How to check/monitor blood glucose
Monitor urine glucose and ketones
Preparation and injection of insulin
How to recognize hypoglycemia and hyperglycemia
How to plan meals

84. Long term monitoring
HbAIC; Normal < 6%:
In diabetics;
6-7.9: good control
8.0-9.9: fair control
>10: poor control
Early treatment of infections/injuries
Growth monitoring

85. Regular eye check
Renal status check
Regular neurological checks
Cardiovascular assessment: BP, arterial wall
thickness

86. 02/24/15 86

87. |

88. Prevention
General Health Promotion: enlightenment
Specific prevention
Early diagnosis and treatment
Limitation of disability
Rehabilitation
88

89. Conclusion
DKA is a common complication of
paediatric diabetes melitus
It carries significant risk of death and/or
morbidity especially with delayed
treatment
High index of suspicion is required for
early detection and treatment
Treatment is done with cautious urgency in
order to forestall complications of 89

90. References
Nelson Textbook of Paediatrics, 19th
Edition
Medscape: Paediatric Diabetes Mellitus
Paediatric Management of Paediatric
DKA; Guidline No. 13; 3rd
Edition by Dr.
Carrihill and Greening
BSPED Recommended DKA Guidelines
2013
Endocrinology update 2012/2013 90

91. Thank You!
91