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Proteinele plasmatice

Concentraia proteinelor
plasmatice 60
60--80 g/l
= parametru dinamic, determinat de:
de:

Rata de sintez
Volumul de distribuie
Rata de catabolism

Absorbia fierului bariera mucoasei

Divalent Metal
Transporter
(DMT)

Transportul plasmatic al
Fierului rolul ceruloplasminei
si Xantinoxidazei

Valorile normale ale capacitii de fixare a fierului i a coeficientului de saturaie al transferinei


Parametrul

mol/l

g/dL

Capacitatea de fixare (IBC)

32 - 50

27 - 45

180 280

150 - 250

Capacitatea de fixare total (TIBC)

54 - 72

45 - 63

300 - 400

250 - 350

40 %

35 %

40 /dL

35 /dL

Coeficientul de saturaie

Ceruloplasmina transportul Cu

Boala Wilson degenerescena hepato-lenticular


Ceruplasmina seric sczut
Inel Kayser-Fleischer
Hepatita toxic
Manifestri neurologice

recesiv autosomal
300 mutaii ale genei ATP7B (crz 13)
La 35-65% din cazuri apare mutaia H1069Q
(Histidina este nlocuit de Glutamin)

Haptoglobina - transportorul plasmatic de


Hb liber

Haptoglobina este o 2-globulin. T1/2 5 zile


Leag hemoglobina
intravasculare.

eliberat

circulaie

timpul

hemolizei

Complexele haemoglobin-haptoglobin formate sunt indeprtate de


sistemul reticuloendotelial (t1/2 = 90 minute), concentratia haptoglobinei
plasmatice scznd (= indicator pentru hemoliza intravascular).

1-Antitripsina i 2-Macroglobulina
A1AT este un inhibitor natural de proteaze
Deficitul emfizemul i hepatita nou-nscutului

Homozygotes for the normal protein are termed Pi (protease inhibitor) MM. 1-Antitrypsin deficiency
is most frequently due to homozygosity for the Z allele (PiZZ), this genotype having a frequency of
about 1 in 3000. In affected individuals, plasma 1-antitrypsin concentration is reduced to between
10% and 15% of normal. The defect is due to a single amino acid substitution, which causes the
protein to form aggregates that cannot be secreted from the liver, and as a result, cause liver damage .
PiMZ heterozygotes have plasma 1-antitrypsin concentrations that are about 60% of normal; there is
probably only a very slightly increased tendency for these individuals to develop lung disease when
compared with normal PiMM homozygotes.
2-Macroglobulin (=panproteinase inhibitor) is a high molecular weight protein (820 kDa) that
constitutes approximately one-third of the 2-globulins. Its plasma concentration is increased in the
nephrotic syndrome. Like 1-antitrypsin, 2-macroglobulin is an inhibitor of proteases, though it has a
broader spectrum of activity.

Principalele caracteristici ale


proteinelor plasmatice
Funcii
I.Transportori

Denumire

Migrarea EF

GM (kD)

Concentraia

Albumin

68

35-45 g/L

Inainte de albumin

55

200-300 mg/L

RBP (retinol binding


protein)

1-globulin

21

20 60 mg/L

Transcortina

1-globulin

56

40-80 mg/L

Transferina

-globulin

77-88

2-4 g/L

Transcobalamina

1-globulin

Haptoglobina

2-globulin

100

2,5 4,5 g/L

TBG (tiroxin binding


globulin)

1-globulin

61

10 30 mg/L

ApoA

1-globuline

20-40

1,2 2,5 g/L

ApoB

2-globuline

250, 514

0,8 -1,5 g/L

Nespecifici
Albumina

Specifici
Prealbumina

1 5 mg/L

II. Antiproteaze

SerPIN-ce

1-antitripsina

1-globulin

54

2-3,8 g/L

1-antichimotripsina

1-globulin

68

350-550 mg/L

2-antiplasmina

2-globulin

70

40-80 mg/L

Antitrombina III

2-globulin

65

200-400 mg/L

PC Inh

2-globulin

57

3-6 mg/L

C1 Inh

1-globulin

104

200-300 mg/L

50

10-30 g/L

820

2,5-4 g/L

PAI

Neserpinice
2-macroglobulina

2-globulin

III. Aprare

specific

Ig G

1,2,3-globuline

130

6-16 g/L

Ig A

1,2-globuline

140 - 420

0,7-4 g/L

Ig M

1-globuline

900

0,4-2 g/L

-globuline

variabil

4-5 g/L

PCR (prot. C reactiv)

-globulin

140

3 mg/L

C3

-globulin

180

0,8-1,2 g/l

1-glicoproteina acid

1-globuline

44

0,6-1 g/L

Ceruloplasmina

2-globulin

132

300-400 mg/L

2-microglobulina

2-globuline

11,8

2 mg/L

nespecific

Factorii coagulrii

IV.Funcie
controversat

Proteinele de faz
faz acut
acut

Proteinele de faz acut sunt clasificate dup evoluia lor


n::
n
a. proteine cu creterea rapid (1
(1--2 ore) i intens (de
10--2000 ori) a concentraiei serice: PCR (proteina C
10
reactiv), amiloidul seric A (SAA),
b. proteine cu cretere mai lent (24 - 48 ore) i
moderat (de 22-5 ori): 1-AT, 1-GPac (
(1-glicoproteina
acid), haptoglobina i fibrinogenul,
c. proteine cu cretere lent (2
(2--3 zile) i modest
(maximum de 2 ori): Ceruloplasmina, C3, C4 i C1 Inh,
d. componentele negative ale reaciei de faz acut sau
proteine anti faz acut: albumina, prealbumina i
transferina

Aspectul grafic al unor densitograme normale (a) i patologice:


inflamaie acut (b); inflamaie cronic (c); ciroz (d); sindrom nefrotic
(e); gradient monoclonal M (f)

Principalele caracteristici ale claselor de imunoglobuline plasmatice


Principalele caracteristici ale claselor de imunoglobuline plasmatice
Clasa de Ig
(kD)
Ig G
zile
Ig A
zile
Ig M
zile
Ig D
zile
Ig E

GM
Uniti
150

Fab
1

Concentraie Subclase
2
6-16 g/l

T1/2
IgG 1 - 4

23

160

1,2

2,4

0,7-4 g/l

IgA 1 - 2

5-

900

0,4-2 g/l

185

< 40 mg/l

200

< 0,5 mg/l

3 zile

Concentraia proteinelor
plasmatice 6060-80 g/l
Parametru

dinamic, determinat de
trei factori principali:

rata de sintez
volumul de distribuie
rata de catabolism

Distribuia proteinelor ntre spaiul


vascular--interstiial
vascular

"cernerea molecular
molecular" se numete transudat: conine <
30 g/l proteine -> raport [Pt
[Pt] lichid intersti
interstiial / [Pt
[Pt]
ser < 0,5

Filtrul glomerular:
< 150 mg proteine/24h
< 30 mg Alb / 24 h
Proteinuria fiziologic
fiziologic: albumina, aa-1-microglobulina,
a-1-antitripsina, -2-microglobulina, lizozim,
cistatin C, urme: IgG, aa-1-glicoproteina acid,
transferina, RBP , proteinaTamm
proteinaTamm--Horsfall

Proteinurii patologice
Renale

> Postrenale > Prerenale


Renale:

Glomerulare (Selective / Semiselective /


Neselective); indicele de selectivitate:

= [IgG]urx[Alb]ser / [IgG]ser x [Alb] ur,


ur,
n mod normal fiind < 0,2.

Tubulo--interstiiale
Tubulo

Postrenale:

sngerri, inflamaii ale TUI


Prerenale: Bence Jones, Mioglobinurie

Proteinorahia

0,5% din proteinemie (max 0,4 g/l):

LCR ventricular: 0,1 0,15 g/l


LCR cisternal: 0,2 0,3 g/l
LCR cervical: 0,1 0,15 g/l
LCR toracal: 0,2 0,3 g/l
LCR lombar: 0,30,3-0,4 g/l

80% din proteinele prezente n mod normal n LCR , provin din


ser transport pasiv BHE (preAlb>, Ig<)Ig<)- Permeabilitatea
barierei hematohemato-encefalice !!; EF LCR:
Prealbumin: 55 -8 %
albumin: 6565-80 %
1-globuline: 2,02,0-4,0 %
2-globuline: 4,04,0-8,0 %
-globuline: 6,0 -12,0 %
-globuline: 6 8 %

Perturb
Perturb
ri ale permeabilit
permeabilitii
ii
barierei HE
QAlb=[Alb]LCR mg/l / [Alb] ser mg/l

< 10 x 10-3 pot fi ntlnite n scleroza multipl, encefalita cronic


din infecia HIV, polineuropatia alcoolic, herpes zoster.
10-- 20 x 10-3 pot fi ntlnite n meningite virale,
10
meningoencefalopatii cu germeni oportuniti, polineuropatia
diabetic, infarct cerebral, atrofia cerebral.
> 20 x 10-3 pot apare n sindromul GuillainGuillain-Barre, encefalitele cu
virus herpex simplex, bacteriene (n special cu BK)
BK)

Un alt indice util n diagnostic este Delpech Lichtblau:

= [IgG]LCRx[Alb]ser / [IgG]ser x [Alb] LCR,


LCR, n mod normal fiind < 0,7.

Creterea acestui indice indic producie de IgG intratecal.

Tulburri ale permeabilitii BHE


Diagrama Reiber
Felgenhauer

QIg=[IgG+IgA+IgM]LCR /
[IgG+IgA+IgM]ser
QAlb=[Alb]LCR / [Alb] ser
1 N x < 15 ani

xx 1515-40 ani

xxx 41 60 ani

2 perturbri ale transferului prin


BHE, fr sintez local de IgG;
3 - perturbri ale transferului prin
BHE, cu sintez adiional de IgG;
4 sintez local de IgG, fr
perturbri ale transferului prin BHE;
5 fr semnificaie clinic

Catabolismul
Proteinelor

Proteina

t1/2 n ser

Albumina

19-21 zile

1-antitripsina

4 zile

Complement C3

0,5 1 zi

Complement C4

0,5 1 zi

Ceruloplasmina

4 10 zile

PCR

12 24 ore

Feritina

10 minute

1- fetoproteina

4 zile

Fibrinogen

3 zile

Haptoglobina

2 4 zile

Ig A

6- 8 zile

Ig G

17 - 35 zile

Ig M

5 - 7 zile

Ig D

3 zile

Ig E

2 zile

Receptorul solubil al Transferinei

10 zile

2 - Macroglobulina

4 - 7 zile

2 - microglobulina

40 minute

Mioglobina

15 minute

Prealbumina

1 2 zile

Procalcitonina

24 30 ore

1- glicoproteina acid

5 - 6 zile

Transferina

7 10 zile

Clasificarea Enzimelor
Clase

Reacia

Enzime

1. Oxidoreductaze

A red + B ox A ox + B red Dehidrogenaze,


Peroxidaze

2.Transferaze
2.
Transferaze

AB+CA+B C

Transaminazele,
Hexokinaza,
Creatinkinaza

3. Hidrolaze

A B + H2O A H + B
OH

Tripsina, Lipaza,
Fosfatazele

4. Liaze

A (XH) B A X + B H

Anhidraza carbonic

5. Izomeraze

A izo A

Fosfoglucomutaza,
Triozofosfat izomeraza

6. Ligaze

A + B + ATP A B + ADP
+ Pi

Piruvat carboxilaza,
ADN ligaza

Clasificarea Enzimelor plasmatice


Clasa

Exemple

1. Enzime produse/secretate activ


in plasma care si desfasoara
activitatea in plasma

Factorii de coagulare, Plasmina,


Renina, Colinesteraza, LPL, LCAT,
Antitrombina III

2. Enzime care ajung in mod pasiv in


plasm (fiind secretate fiziologic in
alte compartimente)

Tripsina, Amilaza, Lipaza


pancreatic, Fosfataza
alcalin/acid, gGT

3. Enzime cu localizare
intracelular prezena lor n
plasm semnific citoliz

Transaminazele (GOT/AST
GPT/ALT), CPK, LDH

Enzime utilizate n diagnosticul clinic al


unor afeciuni
Enzima

Sursa tisulara

Utilitate diagnostic

ALT / GPT

Ficat, muchi miocardic,


scheletic, rinichi

Afeciuni hepatolitice,
miolitice

AST / GOT

Muchi miocardic, scheletic,


ficat, rinichi, creier

Afeciuni miolitice,
hepatolitice

LDH

Muchi miocardic, scheletic,


ficat, hematii

Afeciuni hepatolitice, tumori


hematologice

CK

Muchi scheletic, miocardic,


creier

Infarct miocardic, distrofie


muscular

Amilaza

Pancreas, glande salivare

Pancreatit acut, obstrucii


biliare

Lipaza

Pancreas

Pancreatit acut, obstrucii


biliare

GGT

Ficat

Exces de alcool, hepatite,


obstrucii biliare

Fosfataza alcalin

Osteoblati, canalicule
biliare, placent

Afeciuni osoase, tumori


osoase, obstrucii biliare

Fosfataza Acid

Prostat

Carcinom de prostat

Factorii care afecteaza


activitatea serica a enzimelor
L
eziunitisulare

R
atasintezei

M
asaesutului
productoralenzim
ei

R
ataintrriinsnge

A
ctivitateaseric

Inhibitori(otrvuri
organofosforice,
inhibitoride
colinesteraz)

R
atadendeprtare
C
learance

Inactivare

AMI evolution of enzyme


activity