HYPERGLYCEMIC CRISES

DIABETIC KETOACIDOSIS
HYPEROSMOLAR HYPERGLYCEMIC STATE
LACTIC ACIDOSIS

Pathogenesis of DKA

REDUCTION OF CIRCULATING INSULIN

ELEVATION OF COUNTERREGULATORY
HORMONES
(glucagon, catecholamines, cortisol,growth hormone)

Pathogenesis of DKA
REDUCTION OF CIRCULATING INSULIN
ELEVATION OF COUNTERREGULATORY
HORMONES

1.increased hepatic glucose production

HYPERGLYCEMIA
2. impaired glucose utilization in peripheral tissues
3.lipolysis - release of free fatty acids into the circulation
and to unrestrained hepatic fatty acid oxidation to ketone bodies
(acetoacetat, -hydroxibutyrat)

KETONEMIA( METABOLIC ACIDOSIS)

Pathogenesis of DKA
Hyperglycemia

Glycozuria

osmotic diuresis

Loss of water+electrolytes

Epidemiology

Annual incidence of DKA 0,5-0,8%

Two-third of DKA patients were considered to have
type1 diabetes
Mortality rate 2-5%
Death is rarely due to the metabolic complications of
hyperglycemia or ketoacidosis but relates to the
underlying precipitating illness.

Precipitating Factors

INFECTION(30-50%)
DISCONTINUATION OF INSULIN
(inadequate insulin)
NEW-ONSET TYPE 1 DIABETES
CEREBROVASCULAR ACCIDENT
MYOCARDIAL INFARCTION
SEVERE TRAUMA
PANCREATITIS
ALCOHOL ABUSE
DRUGS
( ex.corticosteroids )

DKA clinical picture:

The metabolic alterations typical of

DKA- usually evolve within a short time frame,
< 24 h.
SYMPTOMS:
Polyuria, polydipsia, weight loss, weakness,
Nausea,vomiting( emesis which may be
,,cofee- ground), diffuse abdominal pain.
Polypnea;the breath has an acetone odor.
Clouding of sensoria and finally coma.

DKA clinical picture:

PHYSICAL FINDINGS:
Dehydration- poor skin turgor, dry mouth
Kussmaul respiration, deep, noisy
pH < 7,2
Cardiovas.Tachycardia;
Hypotension or normal BP;
Neuro. mental status can vary from full
alertness to profound lethargy or coma
Hypotermia ( peripheral vasodilation );

LABORATORY FINDINGS
Glucose(mg/dl)
PH
Bicarbonate(mEq/l)
Osmolality
Ketonemia/Ketonuria
Na(mEq/l), K(mEq/l)
Anion gap = [Na+] - [Cl- + HCO3-]
BUN, creatinine,complete blood count,
ECG, chest X-ray
Urine or blood cultures,etc.

DKA....Laboratory

Hyperglycemia is a key diagnostic criterion of DKA,

however, a wide range of plasma glucose can be
present on admision.
~10% of DKA presents glucose levels 250mg/dl due
to antecedent food restriction, inhibition of
gluconeogenesis or insulin injection en route to the
hospital.
Leukocytosis (10000-15000mm) is the rule in DKA
and may not be indicative of an infectious process.

DKA....Laboratory
Hyperamylasemia has been reported but there is little correlation
with the presence of gastrointestinal symptoms

Na+ =

N or ( usually low because of the osmotic flux

of water from intracellular to extracellular space)

K+

, N or

( usually elevated because of an

extracellular shift of potassium caused by acidemia )

DKA....Laboratory
Accumulation of ketoacids results in pH 7,30

and an increased anion gap metabolic acidosis

DKA intensity pH, HCO3AG = [Na+] - [Cl- + HCO3-]

AG > 10-12 mmol/l indicate the

presence of increased anion gap metabolic acidosis.

Severe DKA

AG = 25 35mmol/l

Ketonuria not correlate with the intensity of acidosis

Diagnostic criteria for DKA

MILDE
Plasma glucose
mg/dl
Arterial pH
SerumHCO3-(mEq/i)
Urine ketone
Serum ketone

>250 mg/dl

7,25-7,30
15-18
pozitive
pozitive

Serum osmolality.

variable

Anion gap

>10

Mental status
stupor/coma

alert

MODERATE
>250 mg/dl

SEVERE
>250

7-7,25

<7

10-15

< 10

pozitive
pozitive

pozitive
pozitiei

variable
>12
alert/drowsy

variable
>12

DIFFERENTIAL DIAGNOSIS

ALCOHOLIC KETOACIDOSIS
STARVATION KETOSIS
Other METABOLIC ACIDOSIS
(lactic acidosis, ingestion of salicylate ,methanol,ethylenglycol,paraldehyde)
GASTROINTESTINAL SYMPTOMS
(ex. serum lipase determination may be beneficial in the dif.diag.of pancreatitis)
COMA

TREATMENT OF DKA
Corection of:
Dehydration
Hyperglycemia
Electrolyte imbalances
use of bicarbonate
Treatment of comorbid precipitating events

Frequent patient monitoring !!!!

2 h. control

glycemia
electrolytes
physical examination

Fluid therapy
Isotonic saline (0,9% NaCl) is infused at a rate
of 15-20 ml/kc body w./h or 1l during first hour
Subsequent choice for fluid replacement depends on
hemodynamics,the state of hydration, serum electrolyte
levels and urinary output.

5% dextrose should be added when plasma

glucose is 250 mg/dl.

INSULIN therapy
!!! REGULAR INSULIN !!!
The administration of continuous intravenous infusion
of regular insulin is the preferred route

Treatment algorithms recommended the adm. of an

initial intravenous dose of regular insulin
0,1u/kgC
followed by the infusion of 0,1u/kg/h
If serum glucose does not fall by 10% in first hour
(50- 70mg/dl/h) the insulin infusion shoud be increased
every hour.

ELECTROLYTE replacement

POTASSIUM < 3,3 mEq/l

+ 40 mEq K
3,3 5 mEq/l + 20-30 mEq K
5,0 mEq/l
NO
Insulin therapy,correction of acidosis and volume expansion
decrease serum potassium concentration!
To prevent hypokalemia, potassium replacement is initiated after
serum levels fall below 5mEq/l

BICARBONATE therapy

PH < 6,9

NaHCO3 100 mmol in

400ml steril water
PH > 7,0

No

COMPLICATIONS
HYPOPOTASEMIA
HYPOGLYCEMIA
are two common complications

CEREBRAL EDEMA
prevention might include
avoidance of excessive hydration and
a gradual decrease in serum glucose

PULMONARY EDEMA
HYPERCHLOREMIC ACIDOSIS
DEATH

PREVENTION

Many cases of DKA and HHS can be prevented by :

better access to medical care,
proper patient education, and
effective communication with a health care provider
during an intercurent illness.

HYPEROSMOLAR HYPERGLICEMIC STATE

Definition:
Hyperosmolarity(Osm > 320-330 mosm/kg)
Hyperglycemia
Dehydration
Occurs in middle-aged and older adults with

type 2 diabetes
In most patients with HHS, restricted water intake is
due to patient being bedridden and is exacerbated by
the altered thirst response of the elderly.

Ketonuria and acidosis are missing!

Pathogenesis of DKA
Hyperglycemia

Glycozuria

osmotic diuresis

Loss of water+electrolytes

Pathogenesis of HHS

Insulin levels in HHS are inadequate to facilitate

glucose utilization by insulinsensitive tissues but
adequate to prevent lipolysis and subsequent
ketogenesis!

HHS clinical picture:

The process of HHS usually evolves over several days

to week !
intense thirst
polyuria
weakness
mental status can vary but coma is more frequent.

focal neurologic signs(hemianopsia, hemiparesis)

and seizures(focal or generalized) may also be
features of HHS
(exam. CT)

HHS clinical picture:

Physical examination

Severe dehydration (hypoT, tahycardia shock)

stupor / coma
Oliguria suggests Acute renal failure due to

dehydration (prerenal azotemia or preexisting

chronic renal failure)

DIAGNOSIS

Precipitating Factors
Infection- particulary pneumonia or gram-negative

sepsis, is the most common initiating event.

Myocardial infarction, cerebrovascular accident, TE,
Pancreatitis
Burns /
Severe trauma
Drugs
diuretics - enhances dehydration,
corticosteroids
Phenytoin
Antipsychotic drugs

HHS....Laboratory

Severe hyperglycemia (800.2400 mg/dl)

Hyperosmolarity - (320 -440 mOsm/kg)

Na+ = , N or
Osm pl = 2 x (Na +glu / 18) N = 290-310 mOsm/kg

Treatment of HHS

COMPLICATIONS / Prognostic
Rhabdomyolysis(non-traumatic.)
CreatinKinase (> 1000U/l)
One of the dreaded complications of R. is Kidney failure.

Pulmonary thromboembolism;
Peripheral venous thrombosis

- Mortality attributed to HHS is considerably higher than

that attributed to DKA(10 times)
- The prognostic is substantially worsend at the
extremes of age in the presence of coma, hypotension
and severe comorbidities.

Lactic Acidosis
LA may develop in any state of:
1. Diminished tissue oxygenation(eg.vascular shock)excessive lactat production.
2. Hepatic dysfunction (and diminished conversion of lactat
to glucose)
LA is characterized by low pH acompanied by the buildup of
lactat.

Abnormal anion gap + Lactat level > 7 mmol/l

Causes of LA

Shock
Sepsis
Ethanol toxicity
Hepatic disease
Diabetic ketoacidosis
Drugs: metformin/ phenformin
Inborn error of metabolism

Symptoms

Nousea, vomiting, abdominal pain

Hyperventilation (to remove CO2)
Severe anemia
Hypotension
Irregular heart rate
Tachycardia
Anxiety/ lethargy

Treatment of LA

1.Sodium bicarbonat administration !

2.The primary condition underlying the acidosis should
be corrected.
3. hemodialysis.

References
Abbas E. et.al Hyperglycemic Crises in Adult Patiens with
Diabetes/ADA Statements. Diabetes Care,vol.32(7),
july 2009
Joslins Diabetes Mellitus 13th Edition, edited by
C.Ronald Kahn, Gordon C.Weir