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Nephro t i c syndro me o characterized by increased basement membrane permeability o urinary loss of plasma proteins , particularly low-weight proteins ,

such as albumin. o Clinical manifestations

Massive proteinuriacharacterized by excretion of more than 4 grams of protein per day. (MCQ)Unlike glomerulonephritis, proteinuria in the nephroticsyndrome is unaccompanied by increased urinary red cells or white cells.

Hypoalbuminemiamarked by a serum concentration of less than 3g/100 mL . (MCQ)

Generalized edemafrom d ecreased plasma colloid oncotic pressure.

Hyperlipidemia and hypercholesterolem ia caused by increased h epatic lipoprotein synthesis. (MCQ)

o Conditions presenting with Nephrotic syndrome on Renalbiopsyo Minimal change diseaseo Focal segmental glomerulosclerosiso Membranous glomerulonephritiso Diabetic nephropat hy o Renal amyloidos iso Lupus nephropa thy Minimal change disease (lipoid nephrosi s)

o seen most often in young childreno can also occur in older children and adultso Lipid-laden renal cortic es

lipids are intracytoplasmic in tubular cells, particularly in cellsof proximal convoluted tubule s

o Why is it called Minimal change ?Light microscopy demonstrates normal-appearingglomeruli.

o Electron microscopy shows disappearance or fus in g of epi thel ial foo t p rocesses . (MCQ)

o responds well to adrenal steroid therapy. (MCQ) Focal segmental glomerulosclerosis

o clinically similar to minimal change diseaseo occurs in somewhat older patients o characterized by sclerosis within capillary tufts of deep

juxtamedullary glomeruli with focal or segmental distribution . Focal distribution is involvement of some, but not all, of the

glomeruli. Segmental distribution is involvement of only a part of the

glomerulus. Membranous glomerulonephritis

o immune complex disease of unknown etiology.

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o This condition is another cause of the nephrotic syndrome .o Predominant ly subendothelial and mesangial amyloid deposi ts

are characteristic. (MCQ)o The amyloidosis can be identified by

reactivity of amyloid with special stains (e.g., Congo red,

crystal violet, thioflavin T ) birefringence under polarized light.

a characteristic criss-cross fibrillary pattern of amyloid by electron microscopy. (MCQ)

o associations with chronic inflammatory diseases as rheumatoid ar thr i t i s , mu l t ip le myeloma. (MCQ)

Lupus nephropa thy o This is the renal component of SLEo the severity of the renal lesion often determines the overall

prognosis in patients with SLE.o It is often manifest as the nephrotic syndromeo many cases also have major nephritic features.o WHO classification of Lupus nephropathy

Type Ino observable renal involvement.

Type II mesangial form of lupus nephropathy.

Focal and segmental glomerular involvement with anincrease in the number of mesangial cells quantitative increase in mesangia l matr ix ischaracteristic.

results most often in slight proteinuria and it is usually of little clinical consequence . Type III (focal proliferative form)

usually involves less than half of the glomeruli can cause extensive damage to individual glomeruli.

Type IV (diffuse proliferative form)prototype of lupus nephropathy

most severe form of the disease. (MCQ)Often, there is a combination of the nephrotic andnephritic syndromes.Almost all of the glomeruli are involved.Glomerular changes include

o marked inflammation with sm al l focal th romboses and mesangial proliferation

o result in extensive sc arr ing. o Characteristic changes include the wire-loop

abnormality (MCQ) a light microscopic finding result from

immune complex deposition gross thickening of the glomerular

basement membran e,

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endothelial cell proliferation,which is often prominent byelectron microscopy.

o marked subendothelial immune complexdeposition -- a major diagnostic feature

Type V (membranous form)indistinguishable from primary membranousglomerulonephritis .

Nephr i ti c syndrom e o characterized by

i n f l amm atory rup tu re of the glomerular capillaries bleeding into the urinary space proteinuria and edema may be present but usually are mild.

o Clinical findings Oligur ia Azotemia Hypertension Hematur ia

results from leakage of red cell s directly fromglomerular capillaries into the Bowman space .Many of the red cells are aggregated into the shapeof the renal tubules and embedded in a proteinaceousmatrix forming red cell casts that can be observed inthe urine

" s m o k y b r o w n u r i n e ." (MCQ) Red cell casts can degenerate and become pigmented

granular casts. Poststreptococcal glomerulonephritis (acute proliferativeglomerulonephritis)

o prototype of the nephritic syndromeo an immune complex disease with the antigen of streptococcal

origin . (MCQ)o most often follows or accompanies infection ( tonsi l l i t i s ,

s t reptococ cal impet igo, infected ins ect b i tes ) with nephritogenic strains of group A -hemolytic streptococci.

o Complete recovery in almost all children and many adults followso A very small minority develop RPGN (MCQ)o Laboratory abnormalities are characteristic

urinary red cells and red cell castsazotemia

decreased serum C3 Renal function begins to improve within 1 to 2 weeks and

complement levels normalize within 6 weeks with PSGN . If renal insufficiency, hypocomplementemia, or nephrotic

syndrome persist , MPGN should be suspected and a renal biopsy should be performed after SLE, mixed cryoglobulinemia,and bacterial endocarditis have been excluded with appropriatetests. (MCQ)

increased titers of antistreptococcal antibodies are evidenceof recent streptococcal infection

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antistreptolysin O [ASO] anti-DNAase B anticationic proteinase

o An intense inflammatory reaction involving almost all glomeruli inboth kidneys results in:

Innumerable punctate hemorrhages on the surface of bothkidneys

Enlarged, hypercellular, swollen, bloodless glomeruliwith proliferation of mesangial and endothelial cells andsometimes neutrophils (MCQ)

o Glomerular basement membrane retains normal thickness and uniformity despite theextensive inflammatory changes (MCQ)

o Characteristic electron-dense "humps" on the epithelial side of the basement membrane (subepithelial localization) (MCQ)

o "Lumpy-bumpy" immunofluorescence (extremely coarsegranular immunofluorescence for IgG or C3) (MCQ)

Rapidly progressive (crescentic) glomerulonephritis (RPGN)o By definition, RPGN is the nephritic syndrome that progresses

rapidly to renal failure within weeks or months o histologically defined by the formation of crescents between the

Bowman capsule and the glomerular tuft o result from

deposition of fibrin in the Bowman space (MCQ) proliferation of parietal epithelial cells of the Bowmancapsule ; cells of monocytic origin are often involved. (MCQ)

o

Etiology Type I - Immune complex mediated forms of RPGN -ANCA-negative (MCQ)

poststreptococcal in approximately 50% of cases with immune complex deposition

lupus nephropathy IgA nephropathy

Type II- Antiglomerular basement membrane forms of RPGN - ANCA-negative (MCQ)

Goodpasture syndrome . Antiglomerular basement membrane antibodies

(nonstreptococcal) are presentcharacteristic in approximately 10% of cases

Type III- Pauci-immune form of RPGN- ANCA-positive(MCQ)

associated with antineutrophil cytoplasmicantibodies (ANCAs)

Goodpasture syndromeo antiglomerular basement membrane antibodie so directed against antigens in glomerular and pulmonary alveolar

basement membranes.o Fluorescent antibody studies for IgG demonstra te linear

immunofluorescenc e . (MCQ) o Clinical manifestations include:

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Nephritic syndro me Pneumonitis with hemoptys is (hemorrhagic pneumonitis)

Peak incidence in men in their mid-2 0s RPGN crescentic morpholo gy with linear

immunofluorescence (MCQ)

Focal glomerulonephrit iso It is focal and segmental o differs from focal segmental glomerulosclerosis in that the

changes are inflammatory and proliferative rather than sclerot ico Most often this is an immune complex disease , occurring as a

manifestation of various disorders, including (MCQ) SLE subacute bacterial endocarditis polyarteritis nodosa Goodpasture syndrome Wegener granulomatosis IgA nephropathy primary (idiopathic) form.

Alport syndromeo hereditary nephritis (MCQ) o associated with nerve deafness (MCQ) o associated with ocular disorders , such as lens dislocation and

cataracts (MCQ) o Clinical characteristics

nephritic syndrome,often progress to end-stage renal disease by 30 years of age. (MCQ) The cause is a mutation in the gene for the 5 chain of typeIV collagen (MCQ) Irregular glomerular basement membrane thickening withfoci of splitting of the lamina densa is seen. (MCQ)

IgA nephropathy (Berger disease)o extremely common entity o defined by deposition of IgA in the mesangium. (MCQ) o Most frequently, the disease is characterized byo benign recurrent hematuria in childreno usually follows an infection (MCQ) o

syn Pharyngitic hematuria (MCQ) episodic hematuria which usually starts within a day or two of a non-specific upper respiratory tract infection (hencesynpharyngitic) as opposed to post-streptococcalglomerulonephritis which occurs some time (weeks) after initial infection

o last 1 2 days o usually of minimal clinical significance.o Focal glomerulonephritis may be a presenting feature.o can be a component of enoch - ch n ein i ea e (MCQ)

Membranoproliferative glomerulonephritis o slowly progresses to chronic renal disease.

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o Histologic characteristics include bot h basement membranethickening and cellular proliferation.

o Disease is marked by tram-track appearance (MCQ) reduplication of glomerular basement membrane into two

layers

occur due to expansion of mesangial matri x into theglomerular capillary loops

o Type I MPGN (MCQ) immune complex nephritis

associated with an unknown antigen It has a striking tram-track appearance

o Type II (dense deposit disease) has a tram-track appearance that is not as apparent as thatof type I.

Irregular electro n-dense m aterial deposited within theglomerular basement membrane is characteristic. (MCQ)

C3 is demonstrable adjacent to but not withi n the densedeposits (MCQ)

serum C3 is characteristically markedly reduced. (MCQ) The possible cause is an IgG autoantibody (C3 nephritic factor ) with specificity for the C3 convertase of the alternatecomplement pathway . (MCQ)