DIABETIC KETOACIDOSISHYPEROSMOLAR HYPERGLYCEMIC STATE

LACTIC ACIDOSIS

HYPERGLYCEMIC CRISES

Pathogenesis of DKA

REDUCTION OF CIRCULATING INSULIN

ELEVATION OF COUNTERREGULATORYHORMONES

(glucagon, catecholamines, cortisol,growth hormone)

Pathogenesis of DKAREDUCTION OF CIRCULATING INSULIN

ELEVATION OF COUNTERREGULATORYHORMONES

↓1.increased hepatic glucose production

HYPERGLYCEMIA2. impaired glucose utilization in peripheral tissues

3.lipolysis ↑ - release of free fatty acids into the circulationand to unrestrained hepatic fatty acid oxidation to ketone bodies

(acetoacetat, β-hydroxibutyrat)↓

KETONEMIA( METABOLIC ACIDOSIS)

Hyperglycemia↓

Glycozuria↓

osmotic diuresis↓

Loss of water+electrolytes

Pathogenesis of DKA

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 ofhyperglycemia or ketoacidosis but relates to theunderlying precipitating illness.

INFECTION(30-50%)

DISCONTINUATION OF INSULIN(inadequate insulin)

NEW-ONSET TYPE 1 DIABETES

CEREBROVASCULAR ACCIDENTMYOCARDIAL INFARCTION

SEVERE TRAUMA PANCREATITIS

ALCOHOL ABUSEDRUGS

( ex.corticosteroids )

Precipitating Factors

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 (10000-15000mm³) 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 ˂7,30and an increased anion gap metabolic acidosisDKA intensity – pH, HCO3

-

AG = [Na+] - [Cl- + HCO3-] AG > 10-12 mmol/l indicate the

presence of increased anion gap metabolic acidosis.

Severe DKA AG = 25 – 35mmol/lKetonuria – not correlate with the intensity of acidosis

Diagnostic criteria for DKA

MILDEMILDE MODERAT MODERATEE SEVER SEVEREE Plasma glucosePlasma glucose >250 mg/dl >250 mg/dl >250 >250 mg/dl >250 mg/dl >250 mg/dlmg/dl

AArterial rterial pHpH 7,25-7,3 7,25-7,300 7-7,25 < 7 7-7,25 < 7

SerumSerumHCOHCO33--(mEq/i) 15-18 10-15 < 10(mEq/i) 15-18 10-15 < 10

Urine ketone Urine ketone pozitiv pozitivee pozitiv pozitivee pozitiv pozitiveeSerum ketone Serum ketone pozitiv pozitivee pozitiv pozitivee poziti pozitieeii

Serum osmolalitySerum osmolality. variab. variablele variab variablele variab variablele

AAnionnion gap gap >10 >12 >12 >10 >12 >12

Mental sMental status tatus alertalert alert/drowsyalert/drowsy stupor/comastupor/coma

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

DIFFERENTIAL DIAGNOSIS

Corection of:

Dehydration

Hyperglycemia

Electrolyte imbalances

± use of bicarbonate

Treatment of comorbid precipitating events

TREATMENT OF DKA

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.

!!! 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/kgCfollowed 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.

INSULIN therapy

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 expansiondecrease serum potassium concentration!

To prevent hypokalemia, potassium replacement is initiated after serum levels fall below 5mEq/l

ELECTROLYTE replacement

PH < 6,9 NaHCO3 – 100 mmol in 400ml steril water

PH > 7,0 No

BICARBONATE therapy

HYPOPOTASEMIA

HYPOGLYCEMIAare two common complications

CEREBRAL EDEMA prevention might include

avoidance of excessive hydration anda gradual decrease in serum glucose

PULMONARY EDEMA HYPERCHLOREMIC ACIDOSIS

DEATH

COMPLICATIONS

PREVENTION

Many cases of DKA and HHS can be prevented by :

better access to medical care,proper patient education, andeffective communication with a health care providerduring 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!Ketonuria and acidosis are missing!

Hyperglycemia↓

Glycozuria↓

osmotic diuresis↓

Loss of water+electrolytes

Pathogenesis of DKA

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 thirstpolyuriaweaknessmental 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 / comaOliguria 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 traumaDrugs diuretics - enhances dehydration, corticosteroids PhenytoinAntipsychotic 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 / PrognosticRhabdomyolysis(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

ShockSepsisEthanol toxicityHepatic diseaseDiabetic ketoacidosisDrugs: metformin/ phenforminInborn error of metabolism

Symptoms

Nousea, vomiting, abdominal painHyperventilation (to remove CO2)Severe anemiaHypotension Irregular heart rateTachycardia 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 withDiabetes/ADA Statements. Diabetes Care,vol.32(7),july 2009Joslin”s Diabetes Mellitus 13th Edition, edited byC.Ronald Kahn, Gordon C.Weir