COMPLICATIILE DZ

ACUTE
- HG
1cetoacidoza
CETOACIDOZA
DZrelativ/absolut
DZ
- deficit
de I
- urgente medicale
volemica
consecinte severe
- depletie

STATUSUL NONCETONIC,
HOSM
DZ 2
dg. si -status
masuri mental
terapeutice
prompte
alterat

CRONICE

COMPLICATIILE CRONICE ALE DZ

I. VASCULARE
- MICROVASCULARE - retinopatia DZ
- neuropatia DZ
- nefropatia DZ
- MACROVASCULARE - CAD
- boala vasculara periferica
- boli cerebrovasculare

II. NONVASCULARE
- Gastropareza
- TDS
- modificari cutanate

Chronic Complications of Diabetes Mellitus

Microvascular
Eye disease
Retinopathy (nonproliferative/proliferative)
Macular edema
Cataracts
Glaucoma
Neuropathy
Sensory and motor (mono- and polyneuropathy)
Autonomic
Nephropathy
Macrovascular
Coronary artery disease
Peripheral vascular disease
Cerebrovascular disease
Other
Gastrointestinal (gastroparesis, diarrhea)
Genitourinary (uropathy/sexual dysfunction)
Dermatologic

MECANISMUL FIZIOPATOLOGIC AL COMEI

CETOACIDOTICE
Circumstante de aparitie - factori precipitanti
- glucagon (relativ / absolut)
- deficit de insulina

- catecolamine
- glucocorticoizi (cortisol)

- hGH
- ca urmare a deficitului de I
conc. hormonilor de contrareglare
- intreruperea administrarii de I (la insulinecesitanti)
- catecolaminele (E NE) stimuleaza secretia de
- stres - fizic (infectii, interventii chirurgicale)
glucagon desi I-terapia

- psihic,
emotional
se mentine
blocheaza
eliberarea I si transportul transmembranar
de G indus de I

MECANISMUL FIZIOPATOLOGIC AL COMEI

CETOACIDOTICE

I / Glucagon
HIPERGLICEMIE
ACTIVAREA CETOGENEZEI

MECANISMUL HIPERGLICEMIEI DIN COMA

CETOACIDOTICA

- productiei hepatice de G
glicogenoliza
gluconeogeneza

- utilizarii periferice a G

MECANISMUL HIPERGLICEMIEI DIN COMA

CETOACIDOTICA

Glicogenolizei
- glucagon

deficit de I

- catecolamine

Utilizarii periferice a G
- deficitul de I nivelelor de GLUT 4
- preluarea G in tes. mm si adipos
- metabolismul intracelular al G

MECANISMUL HIPERGLICEMIEI DIN COMA

CETOACIDOTICA
- I / Glucagon
+

F-2,6-P

HIPERGLICEMIE

glicoliza,
activarii
viautilizarii
nivelulPF-kinazei
hepatic
de F-2,6-P
Modificarea
hepatice
a

piruvatului
:
gluconeogenezei,
via inhibarii
F-1,6-biP

GLUCOZURIE

- Hiperglicemie sinteza de glucoza

DIUREZA OSMOTICA

- I activitatea
PEP carboxi-kinazei
glicolizei

DEPLETIE VOLEMICA
- Glucagon activitatea piruvat-kinazei

DESHIDRATARE

MECANISMUL CETOGENEZEI DIN COMA

CETOACIDOTICA

Deficitul SUBSTRATULUI
de I
- DISPONIBILIZAREA
CETOGENEZEI
catecolamine,
hGH
FFA,LPL
AA FFA
activarea

Excesul de glucogon
activarea
sistemului CPT
- ACTIVAREA
CETOGENEZEI
(hepatice)
(carnitin-palmitoil-transferazelor)

SISTEMUL
CARNITINPALMITOILTRANSFERAZELOR
(CPT)

MECANISMUL CETOGENEZEI DIN COMA

CETOACIDOTICA
Excesul de glucagon activeaza sist. CPT pe 2 cai:
1) continutului hepatic de malonil-CoA
via intreruperii secventei metabolice :
G-6-P piruvat citrat acetil-CoA malonil-CoA
Malonil-CoA (primul intermediar pe cale sintezei G din FFA)
inhibitor competitiv al CPT I

2) continutul hepatic de carnitina

orientarea reactiei spre formarea acil-carnitina (efect de
masa)

CORPII CETONICI
- acetona (volatil)
- aceto-acetat :

N (plasma) < 100 mol/L SI

( < 1mg/dL )

- -OH-butirat : N (plasma) < 300 mol/L SI

(<3
mg/dL )
FFA : N (plasma) < 180 mg/L SI
( < 18 mg/dL )

Osmolalitate plasmatica :
N = 285-295 mmol/Kg apa serica = 285-295 mOsm/Kg apa

Glucagonemie bazala
N (plasma) = 10 - 100 ng/L SI

( 50 - 100 pg/mL )

Insulinemie bazala
N (plasma) = 43 - 186 pmol/L SI

( 6 - 26 U/mL )

Laboratory Values in Diabetic Ketoacidosis (DKA) and Nonketotic Hyperosmolar States (NKHS)
(Representative Ranges at Presentation)

DKA

NKHS

16.7-33.3 (300-600)
33.3-66.6 (600-1200)
Glucose,a mmol/L (mg/dL)
Sodium, meq/L
125-135
135-145
Normal
Potassium,a meq/L
Normal to b
Normal
Magnesium a
Normal b
Normal
Normal
Chloridea
Normal

Phosphatea
Creatinine, mol/L (mg/dL)
Slightly
Moderately
Osmolality, mOsm/mL
300-320
330-380

/
Plasma ketonesa
Normal to slightly
15 meq/L
Serum bicarbonate,a meq/L
Arterial pH
6.8-7.3
7.3
Arterial PCO2, mmHg
20-30
Normal
Normal to slightly

Anion gapa [Na (Cl HCO3)], meq/L

a Large changes occur during treatment of DKA.
b Although plasma levels may be normal or high at presentation, total-body stores are usually depleted.

Manifestations of Diabetic Ketoacidosis

Symptoms
Nausea/vomiting
Thirst/polyuria
Abdominal pain
Altered mental function
Shortness of breath
Physical findings
Tachycardia
Dry mucous membranes/reduced skin turgor
Dehydration / hypotension
Tachypnea / Kussmaul respirations/respiratory distress
Abdominal tenderness (may resemble acute pancreatitis or surgical
abdomen)
Fever
Lethargy /obtundation / cerebral edema / possibly coma
Precipitating events
Inadequate insulin administration
Infection (pneumonia/UTI/gastroenteritis/sepsis)
Infarction (cerebral, coronary, mesenteric, peripheral)
Drugs (cocaine)
NOTE: UTI, urinary tract infection.

MECANISMUL FIZIOPATOLOGIC
AL STATUS-ULUI (COMEI) NONCETONICE,
HIPEROSMOLARE
- Diabetic varstnic / singur

Factori precipitanti

- stroke / infectie severa / stres psihic

- inapt de a se hidrata corespunzator

- deficitul de I (mai putin important fata de DKA)
- proceduri : - hemodializa/dializa peritoneala

+ sol. cu formule Hprot.

- hranire pe tub cu
- perfuzii cu
cu cont.
HC (manitol)
/ uree
- aport inadecvat
desol.
fluide
- hidratare
inadecvata
- medicamente : - fenitoin
- imunosupresive (glucocorticoizi)
- diuretice

MECANISMUL STATUS-ului HIPEROSMOLAR

- la pacientii cu DZ 1 (insulinonecesitanti), la care I administrata :
suficienta pentru prevenirea KA
insuficienta pentru a controla glicemia

DE CE NU KA ?
- cetonemia ~ starvare ( 2 - 4 mmol/L)

- FFA < f.d. DKA

deficit de substrat pentru KA ???

- Hormonii de contrareglare < f.d. DKA

MECANISMUL STATUS-ului HIPEROSMOLAR

DE CE NU KA ?
Concentratia I in vena porta la DZ 2 > f.d. DZ 1
prevenirea activarii depline a sist. CPT

Rezistenta la glucagon
mentinerea unor nivele hepatice de Malonil-CoA
ciclul Cori :
- tesuturile periferice : G circulanta lactat reluare circuit
spre ficat (pt. gluconeogeneza)
Lactatul = precursor de Malonil-CoA

Abrevieri
-DKA = Diabetic Ketoacidosis = cetoacidoza diabetica
-NKHS = Non-ketonic Hyperosmolar States = statusul noncetonic, hiperosmolar
-Hosm = hiperosmolar