Glomerulo nephritis

Glomerulonephritis is an infamation of the glomerular capilaries

Causes of nephritic syndrome

Primary glomerulonephritis– Acute GN

• Post streptoccocal• Non streptococal

Rappidly progressive GNMembranoproliferative GNFocal GNIgA nephropathy GN

Systemic disease:SLEPolyarteritis nodosaWegener’s granulomatosisHenoch schonlein purpuracryoglobulinaemia

Classification of glomerular disease

Primary glomerulonephritis– Acute GN

• Post streptoccocal• Non streptococal

Rappidly progressive GNMinimal change GNMembranous GNMembranoproliferative GNFocal GNIgA nephropathy GNChronic GN

SECONDARY SYSTEMIC GLOMERULAR DISEASE

Lupus nephritisDiabetic nephropathyAmyloidosisPolyarteritis nodosaWegener’s granulomatosisHenoch schonlein purpuraGoodspasture’s syndromeSystemic infectious diseases

Hereditary nephritis

Alport’s syndromeFabry’s diseaseNail patella syndrome

Nephritis Caused by Circulating immune Complexes

With circulating immune complex-mediated disease, the gromerulus is considered “innocent bystander” because it does not incite the reaction. The antigen is not of glomerular origin. It may be endogenous, as in the GN associated with SLE, or it may be exogenous, as is probable in the GN that follows certain bacterial, viral, parasitic and spirochetal infections.Often the inciting antigen is unknown, as in most cases of membranous nephropathy.

Whatever the antigen may be, antigen-antibody complexes are formed in situ or in the circulation and are then trapped in the glomeruli,

where they produce injury, in large part through the activation of complement and the recruitment of leukocytes.

Regardless of the mechanism, the glomerular lesions usually consist of leukocytic infiltration into glomeruli and variable proliferation of endothelial, mesangial, and parietal epithelial cells.

Electron microscopy reveals the immune complexes as electron-dense deposits or clumps that lie at one of three sites:

in the mesangium,

between the endothelial cells and the GBM, or

between the outer surface of the GBM and the podocytes.

Seen in most cases of poststreptococcal or acute infection-related GN.

Nephritis Caused by in Situ Immune Complexes

Anti-Glomerular Basement Membrance (GBM) Antibody

Glomerulonephritis.

In this type of injury,

antibodies are directed against fixed antigens in the GBM.

Cell-Mediated Immune Glomerulonephritis

It has often been suggested that sensitized T cells, formed during the course of a cell-mediated immune reaction, can cause glomerular injury.

In some forms of experimental GN in rodents, the disease can be induced by transfer of sensitized T cells.

T cell-mediated injury may account for the instances of GN in which either there are no deposits of antibodies or immune complexes or the deposits do not correlate with the severity of damage.

Mediators of Immune Injury

Glomerular damage, reflected by loss of glomerular barrier function, is manifested by proteinuria and, in some instances, by reduction in GFR.

A major pathway of antibody –initiated injury is complement-leukocyte-mediated

Activation of complemnt leads to the generation of chemo tactic agents and the recruitment of neutrophils and monocytes.

Neutrophils release proteases, which cause GBM degradation; oxygen-derived free radicals, which cause cell damage; and arachidonic acid metabolites, which contribute to reduction in GFR.

This mechanism applies only to some types of GN.

Some models suggest complement-dependent but not neutrophil-dependent injury, due to an effect of the C5 lytic component of complement,

which causes epithelial cell detachment and stimulates mesangial and epithelial cells to secrete various mediators of cell injury.

Thus giving rise to altered GBM composition and thickening.

Other mediators of glomerular damage include (1)monocytes and macrophages, which infiltrate the glomerulus in antibody- and cell-mediated reactions and, when activated, release a vast number of biologically active molecules;

(2) platelets, which aggregate in the glomerulus during immune-mediated injury and release prostaglandins and growth factors;

(3) Resident glomerular cells, which can be stimulated to secrete mediators such as cytokines arachidonic acid metabolites, growth factors, nitric oxide, and endothelin; and

(4) fibrin-related products, which cause leukocyte infiltration and glomerular cell proliferation as a consequence of intraglomerular thrombosis.

Other Mechanisms of Glomerular Injury

Two that deserve special mention are podocyte injury and injury secondary to nephron loss.

Podocyte Injury:

This can be induced by antibodies to visceral epithelial cell antigens; by toxins, certain cytokines; or by still poorly characterized factors, as in some cases of focal and segmental glomerulosclerosis.

Such injury is reflected by morphologic changes in the podocytes, which include effacement of foot processes, vascularization, and retraction and detachment of cells from the GBM, and functionally by proteinuria.

In most forms of glomerular injury, loss of normal slit diaphrangms is key in the development of proteinuria.

Nephron Loss. Once any renal disease,

glomerular or otherwise, destroys sufficient functioning nephrons to reduce the GFR to 30% to 50% of normal progression to end-stage renal failure often proceeds. develop proteinuria, and their kidneys show widespread glomerulosclerosis.

These remaining glomeruli undergo hypertrophy to maintain renal function.

This is associated with hemodynamic

changes, including increases in single nephron, GFR, blood flow, and transcapillary pressure.

These adaptations in the intact glomeruli are ultimately maladaptive and lead to further endothelial and epithelial cell injury, increased glomerular permeability to proteins, and accumulation of proteins and lipids in the mesangial matrix.

TYPES OF GLOMERULONEPHRITIS:-There are different types of GNIt may involve either the nephrotic

syndrome or nephritic syndromeDiagnosis made by C/F or by renal

biopsy

Types of glomerulonephritis (ACUTE NON STREPTOCOCAL)

Minimal change diseaseIs a benign disorderFrequent cause of nephrotic

syndrome in childrenHere the glomeruli shows a diffuse

effacement of podocyte foot process.

1. MINIMAL CHANGE DISEASE (LIPOID NEPHPOSIS)

It is a begin disorder. Frequence cause of nephrotic

syndrome. Different affacement of pocodeyti

foot processes (they appear flattened

CAUSESIdiopathicSystemic disease (hodgkins disease,

HIV infection) & drug therapy (NSAID)

PATHOGONESIS:

Protenuria has been attributed to T cell derived factor that cause podoeyte enjury & affacement.

C/F:- Protein LossPrognosis – good, Rx is corticosteroids

Focal & segmental to slecrosis :Characterized by sclerosis

affecting some but not all the glomeruli

CAUSESAssociated with HIV infectionIgA nephropathyMaladaptation after nephron lossCongenital malformation in

podocytes

PATHOGENS:UnknownInvestigators have said that FSGS

and MCD are continuous – MCD may transform into PSGS

C/F:Variable protunuriaNot responding to corticosteroids

Prognosis: PoorRecurs after transplantation

3. MEMBRANOUS NEPHROPATHY (MENBRANEOUS GN)

Occurs between 30 & 50 years.Subepithelial depositsCausing thickening of the capillary wall.

Causes:idiopathic secondary toInfections (chronic hepatitis, syphillis,

malaria)Malignant tumors of lung & colonSLE & other auto immune disordersDrugs (NSAID’S)

C/FHeavy protenuriaDoes not respond to

cortecosteroidsThey may respond to prednisolone.

PROGNOSIS :-Variable30% may have spontaneous

remission

Menbranoproliferative FN:-Alteration in the GBM & mesangiumProliferation of glomerular cell

TYPES:Mesengial cells are found between

the endothelium & GBMImmune deposits are found in

subendotheal region

(SLE)

(bacterial endocardites, HIV, hepatitis

TYPE IIIs autoimmune disease called

IgG autoantibodies called c3 nephretic factor

Causing lipodystrophy loss of subcutaneous fat from the upper half of the body.

IGA NEPHROPATHY :Affects childrenAssociated with gross hematuriaAssociated with loin painHere there is deposition of IgA is

mesangium (due to IgA production & clearance abnormal)

It is due to some infection is to respiratory or GI tract.

These activates the alternative complement pathway

Glomerular injury

C/FHematuriaRed blood cell cast on urine

analysis.

Acute glomerulonephritis

PATHOPHYSIOLOGY:Antigen (group A seta – hemolylic

streptococcus

Antigen – antibody products

Deposition of antigen – antibody complexes in glomerulers

Increase production of epithelial cells lining the glonerulus

Luekocyte infiltration of glomerulus

Thickening of the GF membrane

Scarring and loss of glomerular filtration membrane

Decreased glomerular filtration rate (GFR)

CLINICAL MANIFESTATIONS:HematuriaProtinuriaEdemaAzotemiaHypertensionAbdominal or flank painOliguriaFever, chills, weakness, pallor,

anorexia, nausea and vomitting may be present.

Elderly patient may experience circulattory ocurroal, with dyspnea, engorged nec ceeins, cardionegely and pulmonary edema.

Hypoalbuninenia and hyperlipedemia.

DIAGNOSTIC STUDIES:-History and physical examinationUrinalysisCBC BUN, seum creatinine and albunminComplement levels and ASO titreRenal biopsy.Signs of overloadPeriorbital edemaEdema and hypertension due to overloadCracklesElevated jugular venous pressureRashesPallor

Physical examination:

Lab studies:Urine analysisComplement levelsTwenty-four hours urine test for

total proteinAnti sterptolysin O titreDipstick testImaging studiesRenal biopsy: cellular infiltration,

granular deposits of immunoglobulin.

Treatment: Antimicrobial therapy:Penicillin 500000 IU q6 q8 hourlyLoop diuretics:Frusemide:Edema: 40-80mg to 20- 40mg 6th

hourly.Hypertension: 20- 40mg bid PO bidVasodilators:Sodium nitroprusside0.5-8mcg/kg/mim IV infusion

Diet:

Sodium and fluid restrictionProtein restriction 0.6 – 0.75g/kg/wtWater restriction to 600ml plus the

previous days urine output.Sodium restriction; 2 to 4g

depending on the degree of edema.Avoid high sodium food.

Chronic glomerulonephritis

Pathophysiology:Acute GN (repeated episodes)

Cause hardening of renal arteries

Reducing the size

Scar tissue formation (numerous glomerulus and branches of renal

arteries are thickened)

Severe glomerular damage

End stage renal failure

Clinical features:HypertensionElevated BUNNosebleedEdema of the optic discGeneral symptoms like malaise,

weight loss, edema, mental cloudiness,

Gallop rhythm, distended neck veins, symptoms of heart failure.

crackles

Poorly nourishedMucous membrain pale because of

edema.Urine analysis shows hematuria,

protienuria, scanty, dark, smoky, cola coloured,

Peripheral neuropathyConfusion

Diagnostic findings:

History collectionPhysical assessmentUrine analysisBlood investigationsRadiographyBiopsy

Treatment:

Medical care:

Drug therapy:

Angiotensin converting enzyme inhibitors

Eg: enalapril

Dose: 2.5-10 mg orally not to exceed 40mg 1 day)

Diuretics:

Fruosimide (lasix)

1-2 mg. 1kg oral/IV/bid not to exceed 600 mg /d

0.1-0.4 mg/kg/hour continuous iv infusion

Metdazone

5-20 mg orally qdCalcium channel blockers:

Amlodipine

2.5 – 10 mg qd.

NefidipineShort acting – 10mg orally tidLong acting – 30 mg orally qd not

to exceed 120 – 150 mg qd

Beta adrenergic blockersMetoprolol – 50 mg oral bidAlpha adrenergic blockersClonidine (catapress)

Dose : 0.1 – 0.2 mg orally bid/tid not to exceed 2.4 mg qid

Surgical treatmentRenal replacement therapyHemodialysisPeritoneal dialysisRenal transplantation

Diet managementProtein restricted diet (0.4 – 0.6 g

1kg/dFluid instruction to 600ml

ComplicationsMetabolic acidosisPulmonary edema PericarditisUremic encephalopathyUremic nueropathySevere anemia & hypocalemiahyperkelemia

NEPHTOTIC SYNDROME

Nephrotic syndrome is a cluster of clinical findings, including

Marked increase in protein (particularly albumin) in the urine (protienuria)

Decreased in albumin in the blood (hypoalbuminenia)

Edema, hypercholesterolemia & normal renal function.

The causes can be classified also Primary glomerulonephrills Minimal change disease Membranous GN Menbranoproliferative GN Focal segmental

glomerulosclerosis Focal GN IgA nephropathy

II. systemic disease Diabetes mellitus Amyloidosis SLE

III. Systemic decease Viral infection Bacterial infection (endocardites,

syphillis, leprosy) Protozoa & parasites

(P.falciparum malaria, filariasis

IV. HypersensitivityDrugs. (heavy metal compounds

like gold & mercury, heroin addiction,

Bee sting, snake bite, poison ivy

V. MalignancyCarcinomasMyelomaHodgkins disease

VI. PregnancyToxemia of pregnancy

VII. Circulatory disturbanceRenal vein thrombosisConstructive pericarditis

VIII. Hereditary diseasesAlports diseaseFabry’s diseaseNail patella syndrome

Clinical features

Heavy protienuriaHypolepidemiaHypoalbumenemiaEdemalipiduriaHercoagulability

Pathophysiology:Damage to the glomerular capillary

membrane

Loss of plasma protein

Stimulate synthesis hypoalbuminimea

of liporotiens

Hyperlipidemia decreased oncotic press

generalized edema

renin angeotensin

edema