Glomerlonephritis | Anatomy2Medicine
Glomerulonephritis Types

Glomerlonephritis

 

  • Nephrotic syndrome
      • characterized by increased basement membrane permeability
      • urinary loss of plasma proteins, particularly low-weight proteins, such as albumin.
  • Clinical manifestations
        • Massive proteinuria
          • characterized by excretion of more than 4 grams of protein per day. (MCQ)
          • Unlike glomerulonephritis, proteinuria in the nephrotic syndrome is unaccompanied by increased urinary red cells or white cells.
        • Hypoalbuminemia
          • marked by a serum concentration of less than 3 g/100 mL. (MCQ)
        • Generalized edema
  • from decreased plasma colloid oncotic pressure.
        • Hyperlipidemia and hypercholesterolemia
  • caused by increased hepatic lipoprotein synthesis. (MCQ)
  • Conditions presenting with Nephrotic syndrome on Renal biopsy
  • Minimal change disease
  • Focal segmental glomerulosclerosis
  • Membranous glomerulonephritis
  • Diabetic nephropathy
  • Renal amyloidosis
  • Lupus nephropathy
    • Minimal change disease (lipoid nephrosis)
      • seen most often in young children
      • can also occur in older children and adults
      • Lipid-laden renal cortices
  • lipids are intracytoplasmic in tubular cells, particularly in cells of proximal convoluted tubules
    • Why is it called Minimal change ?
      • Light microscopy demonstrates normal-appearing glomeruli.
    • Electron microscopy shows disappearance or fusing of epithelial foot processes. (MCQ)
    • responds well to adrenal steroid therapy. (MCQ)
  • Focal segmental glomerulosclerosis
    • clinically similar to minimal change disease
    • occurs in somewhat older patients
    • 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
    • immune complex disease of unknown etiology.
    • a major primary cause of the nephrotic syndrome.
    • Common age group is teenagers and young adults.
    • When do you suspect the  diagnosis of Membranous glomerulonephritis (MCQ)
        • when the nephrotic syndrome is accompanied by azotemia
    • Morphologic characteristics
        • greatly thickened capillary walls visible by light microscopy
  • visible by electron microscopy as a 5- to 10-fold thickening of the basement membrane. (MCQ)
    • Ultrastructural findings i
        • numerous electron-dense immune complexes in intramembranous and epimembranous (subepithelial) locations within and on the basement membrane. (MCQ)
        • This immune complex disease can be mimicked in an animal model resulting from multiple repeated injections of foreign protein. (MCQ)
        • With special stains, a “spike and dome” appearance (MCQ)
          • result from the extension of basement membrane between and around the immune deposits is evident
          • the spikes are basement membrane material
          • domes are immune complex deposits.
  • Granular deposits of immunoglobulin G (IgG) or C3 are apparent on immunofluorescence (MCQ)
  • Granular immunofluorescence is a general characteristic of immune complex diseases. (MCQ)
    • It is a slowly progressive disorder
    • shows little response to steroid therapy.
    • Associations include (MCQ)
        • hepatitis B, syphilis, or malaria infection
  • drugs, such as gold salts or penicillamine
  • malignancy
      • seen in 10% of patients with SLE
  • sometimes causes renal vein thrombosis
    • Diabetic nephropathy
  • Often, it clinically manifests by the nephrotic syndrome.
      • Electron microscopy demonstrates a striking increase in thickness of the glomerular basement membrane
      • Thickening of vascular basement membranes observable by electron microscopy is one of the earliest morphologic changes in diabetes mellitus.
      • An increase in mesangial matrix results in two characteristic morphologic patterns:
  • Diffuse glomerulosclerosis is marked by a diffusely distributed increase in mesangial matrix. (MCQ)
        • Nodular glomerulosclerosis is marked by nodular accumulations of mesangial matrix material (Kimmelstiel-Wilson nodules). (MCQ)
    • Renal amyloidosis
      • This condition is another cause of the nephrotic syndrome.
      • Predominantly subendothelial and mesangial amyloid deposits are characteristic. (MCQ)
      • 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)
  • associations with chronic inflammatory diseases as rheumatoid arthritis , multiple myeloma. (MCQ)
    • Lupus nephropathy
  • This is the renal component of SLE
      • the severity of the renal lesion often determines the overall prognosis in patients with SLE.
  • It is often manifest as the nephrotic syndrome
      • many cases also have major nephritic features.
      • WHO classification of  Lupus nephropathy
        • Type I
          • no observable renal involvement.
        • Type II
          • mesangial form of lupus nephropathy.
          • Focal and segmental glomerular involvement with an increase in the number of mesangial cells
          • quantitative increase in mesangial matrix is characteristic.
  • 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 and nephritic syndromes.
          • Almost all of the glomeruli are involved.
          • Glomerular changes include
            • marked inflammation with small focal thromboses and mesangial proliferation
            • result in extensive scarring.
  • Characteristic changes include the wire-loop abnormality(MCQ)
              • a light microscopic finding
              • result from
                • immune complex deposition
                • gross thickening of the glomerular basement membrane,
                • endothelial cell proliferation, which is often prominent by electron microscopy.
  • marked subendothelial immune complex deposition — a major diagnostic feature
        • Type V (membranous form)
  • indistinguishable from primary membranous glomerulonephritis.
  • Nephritic syndrome
      • characterized by
        • inflammatory rupture of the glomerular capillaries
        • bleeding into the urinary space
        • proteinuria and edema may be present but usually are mild.
      • Clinical findings
  • Oliguria
  • Azotemia
  • Hypertension
  • Hematuria
          • results from leakage of red cells directly from glomerular capillaries into the Bowman space.
          • Many of the red cells are aggregated into the shape of the renal tubules and embedded in a proteinaceous matrix forming red cell casts that can be observed in the urine
  • “smoky brown urine.” (MCQ)
  • Red cell casts can degenerate and become pigmented granular casts.
    • Poststreptococcal glomerulonephritis (acute proliferative glomerulonephritis)
  • prototype of the nephritic syndrome
      • an immune complex disease with the antigen of streptococcal origin. (MCQ)
  • most often follows or accompanies infection (tonsillitis, streptococcal impetigo, infected insect bites) with nephritogenic strains of group A β-hemolytic streptococci.
      • Complete recovery in almost all children and many adults follows
      • A very small minority develop RPGN(MCQ)
      • Laboratory abnormalities are characteristic
        • urinary red cells and red cell casts
        • azotemia
        • 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 appropriate tests. (MCQ)
        • increased titers of antistreptococcal antibodies are evidence of recent streptococcal infection
  • antistreptolysin O [ASO]
  • anti-DNAase B
  • anticationic proteinase
      • An intense inflammatory reaction involving almost all glomeruli in both kidneys results in:
        • Innumerable punctate hemorrhages on the surface of both kidneys
        • Enlarged, hypercellular, swollen, bloodless glomeruli with proliferation of mesangial and endothelial cells and sometimes neutrophils(MCQ)
      • Glomerular basement membrane
  • retains normal thickness and uniformity despite the extensive inflammatory changes(MCQ)
  • Characteristic electron-dense “humps” on the epithelial side of the basement membrane (subepithelial localization) (MCQ)
      • “Lumpy-bumpy” immunofluorescence (extremely coarse granular immunofluorescence for IgG or C3) (MCQ)
    • Rapidly progressive (crescentic) glomerulonephritis (RPGN)
      • By definition, RPGN is the nephritic syndrome that progresses rapidly to renal failure within weeks or months
      • histologically defined by the formation of crescents between the Bowman capsule and the glomerular tuft
      • result from
        • deposition of fibrin in the Bowman space (MCQ)
  • proliferation of parietal epithelial cells of the Bowman capsule; cells of monocytic origin are often involved. (MCQ)
      • 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 present
          • characteristic in approximately 10% of cases
  • Type III- Pauci-immune form of RPGN- ANCA-positive (MCQ)
          • associated with antineutrophil cytoplasmic antibodies (ANCAs)
  • Goodpasture syndrome
  • antiglomerular basement membrane antibodies
  • directed against antigens in glomerular and pulmonary alveolar basement membranes.
      • Fluorescent antibody studies for IgG demonstrate linear immunofluorescence. (MCQ)
      • Clinical manifestations include:
  • Nephritic syndrome
        • Pneumonitis with hemoptysis (hemorrhagic pneumonitis)
        • Peak incidence in men in their mid-20s
        • RPGN crescentic morphology with linear immunofluorescence (MCQ)
    • Focal glomerulonephritis
      • It is focal and segmental
      • differs from focal segmental glomerulosclerosis in that the changes are inflammatory and proliferative rather than sclerotic
      • 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 syndrome
      • hereditary nephritis (MCQ)
  • associated with nerve deafness (MCQ)
      • associated with ocular disorders, such as lens dislocation and cataracts(MCQ)
      • 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 α5 chain of type IV collagen (MCQ)
  • Irregular glomerular basement membrane thickening with foci of splitting of the lamina densa is seen. (MCQ)
    • IgA nephropathy (Berger disease)
      • extremely common entity
      • defined by deposition of IgA in the mesangium. (MCQ)
      • Most frequently, the disease is characterized by
      • benign recurrent hematuria in children
  • usually follows an infection(MCQ)
  • syn Pharyngitic hematuria (MCQ)
        • episodic hematuria which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic) as opposed to post-streptococcal glomerulonephritis which occurs some time (weeks) after initial infection
      • last 1–2 days
      • usually of minimal clinical significance.
      • Focal glomerulonephritis may be a presenting feature.
      • can be a component of Henoch-Schönlein disease. (MCQ)
    • Membranoproliferative glomerulonephritis
      • slowly progresses to chronic renal disease.
      • Histologic characteristics include both basement membrane thickening and cellular proliferation.
      • Disease is marked by tram-track appearance(MCQ)
        • reduplication of glomerular basement membrane into two layers
        • occur due to expansion of mesangial matrix into the glomerular capillary loops
      • Type I MPGN (MCQ)
        • immune complex nephritis
        • associated with an unknown antigen
        • It has a striking tram-track appearance
      • Type II (dense deposit disease)
        • has a tram-track appearance that is not as apparent as that of type I.
        • Irregular electron-dense material deposited within the glomerular basement membrane is characteristic. (MCQ)
  • C3 is demonstrable adjacent to but not within the dense deposits(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 alternate complement pathway. (MCQ)