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.
8
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)
Top Related