NEPHROTIC SYNDROME AND

ACUTE GLOMERULONEPHRITIS

ABDUL HADI BIN MOHD JIMINABDUL HAMID BIN OMARAHMAD KHAIRULHIJAN BIN MOHAMED@HARUN

2008402008402252

200840

WHAT DO THE KIDNEY DO???

Excretion of waste products.

Prevent loss of bloods protein and cells.

Regulation of water and salt.

Maintenance of acid balance.

Secretion of hormones and by product.

STRUCTURES AND DISEASEGlomeruli ( Immune damage

)Tubuli ( Toxic or infection )

Interstitium ( Toxic or Infection )

Blood vessels ( Metabolic )

CLINICAL SYNDROMES OF GLOMERULAR DISEASE

NEPHRITIC SYNDROME NEPHROTIC SYNDROME ACUTE RENAL FAILURE CHRONIC RENAL FAILURE

Electron microscopy:

Consists of capillaries invested by epithelial cells, and surrounded by Bowman’s Capsule

GBM

Pathogenesis of Glomerular Injury

Non-Immune mechanisms

Nephron Loss (Renal ablation glomerularnephropathy)

Immune mechanisms (most common)

Antibody-mediated immune injury

T-cell mediated immune injury

Activation of Alternate Complement Pathway

Pathogenesis of Glomerular Injury

Antibody-mediated immune injury

The most common forms of antibody-mediated GN are caused by:

1. Deposition of circulating immune complexes, which may involve

Exogenous antigens (e.g. infectious agents, drugs).

Endogenous antigens (e.g. DNA, immunoglobulins).

2. In situ immune complexes, in which the antibodies are formed against

Fixed intrinsic tissue antigens as Goodpasture antigen (antibody-GBM nephritis),

Planted antigens which may be exogenous or endogenous

3. Cytotoxic antibodies to endothelial, epithelial or mesangial cells Immune complexes is fixed in glomeruli activate classical

complement pathway attracts neutrophils (lysosomal enz., Reactive

oxygen species) and increased vac. perm membrane damage.

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Antibody-mediated immune injury

Pathogenesis of Glomerular Injury

Antibody-mediated immune injury

Cytotoxic antibodies Antibodies (against epithelial cell antigens,

epithelial injury and detachment Protein leakage through defective GBM and filtration slits

protein

Ab

Pathogenesis of Glomerular Injury

Cell Mediated Immune injury10

Sensitised T-cells

Released chemokines(e.g. macrophage chemottractant protein-1; macrophage

migration inhibitoy factor)

Recruitment of macrophages

Damage to glomerulus

e.g. crescentic nephritis

Pathogenesis of Glomerular Injury

Non-Immune mechanisms

Renal ablation glomerulonephropathy Once any renal disease destroys functioning

nephrons and GFR to 30-50% of normal will leads to : Hypertrophy of functional nephrons endothelial

damage thrombosis; proteinuria azotaemia uraemia

Immune deposits appear by E.M. as an electron dense deposits and by I.F as granular or linear deposits.

Immunufluorescence

Granular pattern Linear pattern

Electron microscopy

Types of Deposits

1.Subepithelial deposits =under epithelial cells

2.Epimembranous deposits= along the basement membrane (GBM)

3.Subendothelial deposits = between the endothelial cells and GBM

Clinical Presentation of Glomerular Diseases

Nephrotic Syndrome Proteinuria > 3.5 gm/24 hours Hypoalbuminemia Edema Hyperlipidemia and lipiduria

Nephrotic SyndromePathogenesis

The initial event is a derangement in the capillary walls of the glomeruli

increased permeability to plasma proteins (Proteinuria)

serum albumin is decreased (hypoalbuminemia.)

drop in plasma colloid osmotic pressure

generalized edema

Hyperlipidemia is caused by increased synthesis of lipoproteins in the liver. The lipiduria, in turn, reflects the increased permeability of the GBM to lipoproteins.

Nephrotic syndrome

Causes of nephrotic syndrome Primary glomerular diseases:

Minimal change disease Membranous glomerulonephritis Focal segmental glomrulosclerosis Membranoproliferative glomerulonephritis

Secondary diseases : Diabetes Systemic lupus erythematosus Amyloid Drugs (gold, penicillamine, "street heroin")

Infections (malaria, syphilis, hepatitis B, HIV)

Malignancy (carcinoma, melanoma)

Nephritic Syndrome

The nephritic syndrome is a clinical complex, usually of acute onset, characterized by

Hematuria with red cell casts in urine oliguria and azotemia Hypertension Some proteinuria

Causes: Primary glomerular diseases:

Acute proliferative (poststreptococcal) glomerulonephritis Rapidly progressive (crescentic) glomerulonephritis IgA nephropathy (Berger's disease) Hereditary nephritis (Alport syndrome)

Secondary diseases : SLE Vasculitis

Nephritic Syndrome

Pathogenesis

The inflammatory reaction associated with the causative disease

Injures the capillary walls

Escape of red cells into the urine (hematuria), and induces hemodynamic changes that lead to a reduction in the GFR

(oliguria and azotemia).

Hypertension results from fluid retention and some augmented renin release from the ischemic kidneys.

Nephrotic and nephritic

noninflammatory inflammatory

Started from infancy More in the school age group

Glomerular basement changes: decrease charge selectivity, size selctivity, or increase permeability

Capillary changes

Sudden onset of hematuria (brown urine), RBC , RBC casts, and WBC, and granular casts present

Massive proteinuria, mainly albuminuria (>1g/m2/24 hrs)

mild proteinuria

Hypoalbuminemia (serum albumin <2.5g/dL)

Hypoalbuminemia

Nephrotic Nephritic

Edema (dt hypoalbuminemia) Edema (salt and water retention)

Hyperlipidemia (>250 mg/dL) dt increase lipoprotein

Lipiduria No lipid in the urine

Piss it all away and get fat (edema and hyperlipidemia)

Immune, inflammation, I can’t pee, I can’t see (HTN)