SINDROMUL NEFROTIC

DEFINIIESN = caracterizat prin :Edeme (tumefiere prin acumularea de lichid interstiial) proteinurie nefrotic -masiv > 40 mg/mp/h sau > 100 mg/kg/ziHipoalbuminemie < 2,5 g%+ modificri metabolism lipidic (hiper-lipidemie, hiper-colesterolomie)

EDEME

Alergice Cardiace RENALE hipo- Endocrine Limfatice

proteine-

mice

Sdr. nefritic SDR. NEFROTIC

P-urie = 4-40 mg/mp/h P-urie > 40 mg/mp/h

= 10-100 mg/kg/zi > 100 mg/kg/zi

Sdr. nefritic sau sdr. nefrotic ?

Nephrotic syndrome:

1. Massive proteinuria2. Hypoalbuminemia3. Edema4. Hyperlipidemia/hyperlipiduria

Nephritic syndrome:

1. Hematuria2. Oliguria3. Azotemia4. Hypertension

Edema is defined as a palpable swelling produced by expansion of the interstitial fluid volume.

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx).

the fenestrated endothelium, glomerular basement membrane, and glomerular epitheliumare the glomerular filtration barrier

The glomerular structural changes that may cause proteinuria are damage to the endothelial surface, the glomerular basement membrane, or the podocytes.

The mechanism of damage to these structures is unknown in primary and secondary glomerular diseases, but evidence suggests that T cells may up-regulate a circulating permeability factor or down-regulate an inhibitor of permeability factor in response to unidentified immunogens and cytokines. Other possible factors include hereditary defects in proteins that are integral to the slit diaphragms of the glomeruli, activation of complement leading to damage of the glomerular epithelial cells and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells.

An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema.

Capillary hydrostatic pressure and the gradient of plasma to interstitial fluid oncotic pressure determine the movement of fluid from the vascular compartment to the interstitium. The oncotic pressure is mainly determined by the protein content.

With a high enough capillary hydrostatic pressure or a low enough intravascular oncotic pressure, the amount of fluid filtered exceeds the maximal lymphatic flow, and edema occurs. In patients with nephrotic syndrome, this causes a reduction in plasma volume, with a secondary increase of sodium and water retention by the kidneys.

An alternative hypothesis is that a condition of renal sodium retention occurs because of the proteinuria, but this is not related to intravascular volume or to serum protein concentration. The evidence supporting this so-called overfill hypothesis includes the facts that (1) sodium retention is observed even before the serum albumin level starts falling and (2) intravascular volume is normal or even increased in most patients with nephrotic syndrome. This could occur if intraluminal protein directly stimulated renal epithelial sodium reabsorption.[5]

A third possible mechanism is an enhanced peripheral capillary permeability to albumin, as shown by radioisotopic technique in human studies of 60 patients with nephrotic syndrome.[6] This would then lead to increased tissue oncotic pressure and fluid retention in the peripheral tissues.

Sdr. nefritic sau sdr. nefrotic ?Sindrom nefrotic:1. Edeme 2. Proteinurie masiv > 40 mg/mp/h (> 100 mg/kg/zi) 3. Hipoalbuminemie (< 2,5 g/dl) 4. + Hiperlipidemia

Sindrom nefritic:1. Edeme2. Hematurie (frecvent macroscopic)3. Proteinurie sub-nefrotic (4-40 mg/mp/h=10-100 mg/kg/zi)4. HTA5. + Azotemie, + oligurie

SN CLASIFICARE ETIOLOGIC

SN primar (90-95%) SN secundar (5-10%)

Fr GN:

- leziuni glomerulare minime

Infecii (GN post-str, VHB, lues)

- scleroz glomerular focal

Colagenoze (LES, PSH)

i segmentar Boli maligne (limfoame, leucemii)

- nefropatie membranoas Tromboz v. Renal, SHU

- SN congenital Toxice sau medicamente

Boli metabolice (DZ, amiloidoz)

Cu GN:

- GN mezangioproliferativ

- GN membranoproliferativ

Determinarea proteinuriei

0 N 10 GN 100 SN mg/kg/zi

0 N 4 GN 40 SN mg/mp/h

EDEME

Alergice Cardiace RENALE hipo- Endocrine Limfatice

proteine-

mice

Sdr. nefritic SDR. NEFROTIC

P-urie = 4-40 mg/mp/h P-urie > 40 mg/mp/h

= 10-100 mg/kg/zi > 100 mg/kg/zi

SN CLASIFICARE ETIOLOGIC

SN primar (90-95%) SN secundar (5-10%)

Fr GN:

- leziuni glomerulare minime

Infecii (GN post-str, VHB, lues)

- scleroz glomerular focal

Colagenoze (LES, PSH)

i segmentar Boli maligne (limfoame, leucemii)

- nefropatie membranoas Tromboz v. Renal, SHU

- SN congenital Toxice sau medicamente

Boli metabolice (DZ, amiloidoz)

Cu GN:

- GN mezangioproliferativ

- GN membranoproliferativ

Proteinurie neselectiv Proteinurie selectiv

Nephrotic syndrome:

1. Massive proteinuria2. Hypoalbuminemia3. Edema4. Hyperlipidemia/hyperlipiduria

Nephritic syndrome:

1. Hematuria2. Oliguria3. Azotemia4. Hypertension

Edema is defined as a palpable swelling produced by expansion of the interstitial fluid volume.

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx).

the fenestrated endothelium, glomerular basement membrane, and glomerular epitheliumare the glomerular filtration barrier

The glomerular structural changes that may cause proteinuria are damage to the endothelial surface, the glomerular basement membrane, or the podocytes.

The mechanism of damage to these structures is unknown in primary and secondary glomerular diseases, but evidence suggests that T cells may up-regulate a circulating permeability factor or down-regulate an inhibitor of permeability factor in response to unidentified immunogens and cytokines. Other possible factors include hereditary defects in proteins that are integral to the slit diaphragms of the glomeruli, activation of complement leading to damage of the glomerular epithelial cells and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells.

An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema.

Capillary hydrostatic pressure and the gradient of plasma to interstitial fluid oncotic pressure determine the movement of fluid from the vascular compartment to the interstitium. The oncotic pressure is mainly determined by the protein content.

With a high enough capillary hydrostatic pressure or a low enough intravascular oncotic pressure, the amount of fluid filtered exceeds the maximal lymphatic flow, and edema occurs. In patients with nephrotic syndrome, this causes a reduction in plasma volume, with a secondary increase of sodium and water retention by the kidneys.

An alternative hypothesis is that a condition of renal sodium retention occurs because of the proteinuria, but this is not related to intravascular volume or to serum protein concentration. The evidence supporting this so-called overfill hypothesis includes the facts that (1) sodium retention is observed even before the serum albumin level starts falling and (2) intravascular volume is normal or even increased in most patients with nephrotic syndrome. This could occur if intraluminal protein directly stimulated renal epithelial sodium reabsorption.[5]

A third possible mechanism is an enhanced peripheral capillary permeability to albumin, as shown by radioisotopic technique in human studies of 60 patients with nephrotic syndrome.[6] This would then lead to increased tissue oncotic pressure and fluid retention in the peripheral tissues.

Nephrotic syndrome:

1. Massive proteinuria2. Hypoalbuminemia3. Edema4. Hyperlipidemia/hyperlipiduria

Nephritic syndrome:

1. Hematuria2. Oliguria3. Azotemia4. Hypertension

Edema is defined as a palpable swelling produced by expansion of the interstitial fluid volume.

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx).

the fenestrated endothelium, glomerular basement membrane, and glomerular epitheliumare the glomerular filtration barrier

The glomerular structural changes that may cause proteinuria are damage to the endothelial surface, the glomerular basement membrane, or the podocytes.

The mechanism of damage to these structures is unknown in primary and secondary glomerular diseases, but evidence suggests that T cells may up-regulate a circulating permeability factor or down-regulate an inhibitor of permeability factor in response to unidentified immunogens and cytokines. Other possible factors include hereditary defects in proteins that are integral to the slit diaphragms of the glomeruli, activation of complement leading to damage of the glomerular epithelial cells and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells.

An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema.

Capillary hydrostatic pressure and the gradient of plasma to interstitial fluid oncotic pressure determine the movement of fluid from the vascular compartment to the interstitium. The oncotic pressure is mainly determined by the protein content.

With a high enough capillary hydrostatic pressure or a low enough intravascular oncotic pressure, the amount of fluid filtered exceeds the maximal lymphatic flow, and edema occurs. In patients with nephrotic syndrome, this causes a reduction in plasma volume, with a secondary increase of sodium and water retention by the kidneys.

An alternative hypothesis is that a condition of renal sodium retention occurs because of the proteinuria, but this is not related to intravascular volume or to serum protein concentration. The evidence supporting this so-called overfill hypothesis includes the facts that (1) sodium retention is observed even before the serum albumin level starts falling and (2) intravascular volume is normal or even increased in most patients with nephrotic syndrome. This could occur if intraluminal protein directly stimulated renal epithelial sodium reabsorption.[5]

A third possible mechanism is an enhanced peripheral capillary permeability to albumin, as shown by radioisotopic technique in human studies of 60 patients with nephrotic syndrome.[6] This would then lead to increased tissue oncotic pressure and fluid retention in the peripheral tissues.

Nephrotic syndrome:

1. Massive proteinuria2. Hypoalbuminemia3. Edema4. Hyperlipidemia/hyperlipiduria

Nephritic syndrome:

1. Hematuria2. Oliguria3. Azotemia4. Hypertension

Edema is defined as a palpable swelling produced by expansion of the interstitial fluid volume.

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx).

the fenestrated endothelium, glomerular basement membrane, and glomerular epitheliumare the glomerular filtration barrier

The glomerular structural changes that may cause proteinuria are damage to the endothelial surface, the glomerular basement membrane, or the podocytes.

The mechanism of damage to these structures is unknown in primary and secondary glomerular diseases, but evidence suggests that T cells may up-regulate a circulating permeability factor or down-regulate an inhibitor of permeability factor in response to unidentified immunogens and cytokines. Other possible factors include hereditary defects in proteins that are integral to the slit diaphragms of the glomeruli, activation of complement leading to damage of the glomerular epithelial cells and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells.

An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema.

Capillary hydrostatic pressure and the gradient of plasma to interstitial fluid oncotic pressure determine the movement of fluid from the vascular compartment to the interstitium. The oncotic pressure is mainly determined by the protein content.

With a high enough capillary hydrostatic pressure or a low enough intravascular oncotic pressure, the amount of fluid filtered exceeds the maximal lymphatic flow, and edema occurs. In patients with nephrotic syndrome, this causes a reduction in plasma volume, with a secondary increase of sodium and water retention by the kidneys.

An alternative hypothesis is that a condition of renal sodium retention occurs because of the proteinuria, but this is not related to intravascular volume or to serum protein concentration. The evidence supporting this so-called overfill hypothesis includes the facts that (1) sodium retention is observed even before the serum albumin level starts falling and (2) intravascular volume is normal or even increased in most patients with nephrotic syndrome. This could occur if intraluminal protein directly stimulated renal epithelial sodium reabsorption.[5]

A third possible mechanism is an enhanced peripheral capillary permeability to albumin, as shown by radioisotopic technique in human studies of 60 patients with nephrotic syndrome.[6] This would then lead to increased tissue oncotic pressure and fluid retention in the peripheral tissues.

Bariera filtrant glomerularPodocite; GBM = membran bazal glomerular; Endoteliu capilar fenestrat;

ESL = celule endoteliale de suprafa (glycocalyx).

Fiziologie filtrare glomerularPresiunea de filtrare

Fiziologie filtrare glomerularFiltrate :ap electroliiuree Nefiltrate (dimensiuni i sarcini electrice): CeluleProteine plasmatice

Nephrotic syndrome:

1. Massive proteinuria2. Hypoalbuminemia3. Edema4. Hyperlipidemia/hyperlipiduria

Nephritic syndrome:

1. Hematuria2. Oliguria3. Azotemia4. Hypertension

Edema is defined as a palpable swelling produced by expansion of the interstitial fluid volume.

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx).

the fenestrated endothelium, glomerular basement membrane, and glomerular epitheliumare the glomerular filtration barrier

The glomerular structural changes that may cause proteinuria are damage to the endothelial surface, the glomerular basement membrane, or the podocytes.

The mechanism of damage to these structures is unknown in primary and secondary glomerular diseases, but evidence suggests that T cells may up-regulate a circulating permeability factor or down-regulate an inhibitor of permeability factor in response to unidentified immunogens and cytokines. Other possible factors include hereditary defects in proteins that are integral to the slit diaphragms of the glomeruli, activation of complement leading to damage of the glomerular epithelial cells and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells.

An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema.

Capillary hydrostatic pressure and the gradient of plasma to interstitial fluid oncotic pressure determine the movement of fluid from the vascular compartment to the interstitium. The oncotic pressure is mainly determined by the protein content.

With a high enough capillary hydrostatic pressure or a low enough intravascular oncotic pressure, the amount of fluid filtered exceeds the maximal lymphatic flow, and edema occurs. In patients with nephrotic syndrome, this causes a reduction in plasma volume, with a secondary increase of sodium and water retention by the kidneys.

An alternative hypothesis is that a condition of renal sodium retention occurs because of the proteinuria, but this is not related to intravascular volume or to serum protein concentration. The evidence supporting this so-called overfill hypothesis includes the facts that (1) sodium retention is observed even before the serum albumin level starts falling and (2) intravascular volume is normal or even increased in most patients with nephrotic syndrome. This could occur if intraluminal protein directly stimulated renal epithelial sodium reabsorption.[5]

A third possible mechanism is an enhanced peripheral capillary permeability to albumin, as shown by radioisotopic technique in human studies of 60 patients with nephrotic syndrome.[6] This would then lead to increased tissue oncotic pressure and fluid retention in the peripheral tissues.

Fiziopatologie edemLeziuni ale elementelor barierei filtrante (mecanisme puin cunoscute) creterea permeabilitii pentru diverse componente din sngeIpoteze:- Ag sau citokine lf T stimulare factor circulant de permeabilitate defect genetic al proteinelor structurale ale endoteliului fenestrat sau MBGAcivare imunologica a C` leziuni celule endoteliale (ESL) pierdere sarcini negative aqle ESL + MBG

Fiziopatologie edemCretere permeabilitate albuminurie hipoalbuminemie scade presiunea coloidosmotic a plasmei edeme + scdere volum plasmatic retenie hidrosalin secundar accentuare edem . Albuminurie creterea presiunii oncotice tisulare retenie ap n esuturiProteine filtrate intraluminale stimularea reabsorbiei Na retenie hidrosalin edem

Nephrotic syndrome:

1. Massive proteinuria2. Hypoalbuminemia3. Edema4. Hyperlipidemia/hyperlipiduria

Nephritic syndrome:

1. Hematuria2. Oliguria3. Azotemia4. Hypertension

Edema is defined as a palpable swelling produced by expansion of the interstitial fluid volume.

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx).

the fenestrated endothelium, glomerular basement membrane, and glomerular epitheliumare the glomerular filtration barrier

The glomerular structural changes that may cause proteinuria are damage to the endothelial surface, the glomerular basement membrane, or the podocytes.

The mechanism of damage to these structures is unknown in primary and secondary glomerular diseases, but evidence suggests that T cells may up-regulate a circulating permeability factor or down-regulate an inhibitor of permeability factor in response to unidentified immunogens and cytokines. Other possible factors include hereditary defects in proteins that are integral to the slit diaphragms of the glomeruli, activation of complement leading to damage of the glomerular epithelial cells and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells.

An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema.

Capillary hydrostatic pressure and the gradient of plasma to interstitial fluid oncotic pressure determine the movement of fluid from the vascular compartment to the interstitium. The oncotic pressure is mainly determined by the protein content.

With a high enough capillary hydrostatic pressure or a low enough intravascular oncotic pressure, the amount of fluid filtered exceeds the maximal lymphatic flow, and edema occurs. In patients with nephrotic syndrome, this causes a reduction in plasma volume, with a secondary increase of sodium and water retention by the kidneys.

An alternative hypothesis is that a condition of renal sodium retention occurs because of the proteinuria, but this is not related to intravascular volume or to serum protein concentration. The evidence supporting this so-called overfill hypothesis includes the facts that (1) sodium retention is observed even before the serum albumin level starts falling and (2) intravascular volume is normal or even increased in most patients with nephrotic syndrome. This could occur if intraluminal protein directly stimulated renal epithelial sodium reabsorption.[5]

A third possible mechanism is an enhanced peripheral capillary permeability to albumin, as shown by radioisotopic technique in human studies of 60 patients with nephrotic syndrome.[6] This would then lead to increased tissue oncotic pressure and fluid retention in the peripheral tissues.

SN tablou clinicEdemeOligurie + cretere ponderal+ HTA, tahicardie+ Ascit, hidrotorace (+ insuficien respiratorie)Manifestri digestive

Evaluarea SNExaminri paraclinice- Proteinurie Calitativ = bandeleta Semicantitativ din eantion : - proteinurie (mg/dl) / creatininurie (mg/dl) > 3,5Cantitativ > 40 mg/mp/hSelectiv cnd albuminuria > 80% din total proteine urinare

Determinarea proteinuriei

0 N 10 GN 100 SN mg/kg/zi

0 N 4 GN 40 SN mg/mp/h

EDEME

Alergice Cardiace RENALE hipo- Endocrine Limfatice

proteine-

mice

Sdr. nefritic SDR. NEFROTIC

P-urie = 4-40 mg/mp/h P-urie > 40 mg/mp/h

= 10-100 mg/kg/zi > 100 mg/kg/zi

SN CLASIFICARE ETIOLOGIC

SN idiopatic SN secundar

GN acute/persistente

Infecii sistemice (VHB, CMV, lues)

Tromboz v. renal

Toxice sau medicamente

Boli metabolice (DZ, amiloidoz)

Colagenoze (LES, PSH)

Boli maligne (Hodgkin)

Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx).

the fenestrated endothelium, glomerular basement membrane, and glomerular epitheliumare the glomerular filtration barrier

The glomerular structural changes that may cause proteinuria are damage to the endothelial surface, the glomerular basement membrane, or the podocytes.

The mechanism of damage to these structures is unknown in primary and secondary glomerular diseases, but evidence suggests that T cells may up-regulate a circulating permeability factor or down-regulate an inhibitor of permeability factor in response to unidentified immunogens and cytokines. Other possible factors include hereditary defects in proteins that are integral to the slit diaphragms of the glomeruli, activation of complement leading to damage of the glomerular epithelial cells and loss of the negatively charged groups attached to proteins of the GBM and glomerular epithelial cells.

An increase in glomerular permeability leads to albuminuria and eventually to hypoalbuminemia. In turn, hypoalbuminemia lowers the plasma colloid osmotic pressure, causing greater transcapillary filtration of water throughout the body and thus the development of edema.

Capillary hydrostatic pressure and the gradient of plasma to interstitial fluid oncotic pressure determine the movement of fluid from the vascular compartment to the interstitium. The oncotic pressure is mainly determined by the protein content.

With a high enough capillary hydrostatic pressure or a low enough intravascular oncotic pressure, the amount of fluid filtered exceeds the maximal lymphatic flow, and edema occurs. In patients with nephrotic syndrome, this causes a reduction in plasma volume, with a secondary increase of sodium and water retention by the kidneys.

An alternative hypothesis is that a condition of renal sodium retention occurs because of the proteinuria, but this is not related to intravascular volume or to serum protein concentration. The evidence supporting this so-called overfill hypothesis includes the facts that (1) sodium retention is observed even before the serum albumin level starts falling and (2) intravascular volume is normal or even increased in most patients with nephrotic syndrome. This could occur if intraluminal protein directly stimulated renal epithelial sodium reabsorption.[5]

A third possible mechanism is an enhanced peripheral capillary permeability to albumin, as shown by radioisotopic technique in human studies of 60 patients with nephrotic syndrome.[6] This would then lead to increased tissue oncotic pressure and fluid retention in the peripheral tissues.

SN leziuni minime tablou clinicEdeme (pleoape, gambe, scrot) albe, depresibile (semnul godeului)Oligurie+ ascit, hidrocel, hidrotorace+ HTA, + dispnee, cianoz+ manif. digestive (inapeten, vrsturi)+ (evoluie lung) malnutriie, modificri trofice ale tegumentelor si fanerelor

SN leziuni minime laboratorUrinDiurez diminuatProteinurie nefrotic, frecvent selectiv + hematurie microscopic+ ITUSnge-hipo-proteinemie cu disproteinemie* scad albumina si gama-globulinele* cresc alfa-2 i beta-globulinele (relativ) Cresc colesterolul i trigliceridele VSH accelerat+ cretere creatinin (IRA)- dgs. etiologic: AgHBs, ASLO, C3, CIC

(Pierderi + 250-300 ml)

+ Spironolactona 3 mg/kg/zi

TratamentRar puncii evacuatoare :- edeme masive- ascit - hidrotorace

Schema standard = 4 = 4 saptamaniSchema lunga = 6 + 6 sapt (recidive mai rare)

+ corticodependen, corticorezisten, cortico-toxicitate