Renal Pathology Part 4 Flashcards Preview

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Hereditary Nephritis

group of heterogeneous familial renal diseases associated with mutations collagen genes that manifest primarily with glomerular injury


Alport Syndrome

-hematuria with progression to chronic renal failure, accompanied by nerve deafness and various eye disorders, including lens dislocation, posterior cataracts, and corneal dystrophy
-usually X-linked
-most males progress to ESRD before 40 years of age
-mutations in COL4A5


Alport Syndrome Electron Microscopy

-GBM shows irregular foci of thickening alternating with attenuation (thinning), and pronounced splitting and lamination of the lamina densa, often producing distinctive basket-weave appearance.
-similar alterations in tubular basement membrane


Alport Syndrome Immunohistochemistry

-antibodies to a3, a4, a5 fail to stain both glomerular and tubular basement membranes
-absence of a5 staining in skin biopsy specimens


As Alport Syndrome progresses, there is

development of focal segmental and global glomerulosclerosis and other changes of progressive renal injury, including vascular sclerosis, tubular atrophy, and interstitial fibrosis


Most common presenting sign of Alport Syndrome is

-gross or microscopic hematuria, frequently accompanied by red cell casts
-proteinuria may develop later, and rarely, nephrotic syndrome develops


Alport Syndrome symptoms usually

appear at ages 5-20 years and onset of overt renal failure is between ages 20-50 years in men
-auditory defects may be subtle, requiring sensitive testing


Thin Basement Membrane Lesion

-familial asymptomatic hematuria--usually uncovered on routine urinalysis
-diffuse thinning of the GBM
-mild to moderate proteinuria may be present, renal function normal and prognosis good
-mutations in genes encoding a3 or a4 chains of type IV collagen
-usually autosomal inheritance
-homozygotes may progress to renal failure


Chronic Glomerulonephritis

-end-stage glomerular disease that may result from specific types of glomerulonephritis or may develop without antecedent history
-kidneys symmetrically contracted and have diffusely granular cortical surfaces
-cortex thinned, and there is an increase in peripelvic fat


In early cases of chronic glomerulonephritis,

-glomeruli may still show evidence of the primary disease


As chronic glomerulonephritis progresses,

-there eventually ensues obliteration of glomeruli, transforming them into acellular eosinophilic masses, representing a combination of trapped plasma proteins, increased mesangial matrix, basement membrane-like material, and collagen.
-marked atrophy of associated tubules, regular interstitial fibrosis, and mononuclear leukocytic infiltration of the interstitium


In most individuals, chronic glomerulonephritis develops

-insidiously and slowly progresses to renal insufficiency or death from uremia during a plan of years or possibly decades
-often present with nonspecific complaints such as loss of appetite, anemia, vomiting, weakness
-most are hypertensive


In nephrotic patients, as glomeruli become obliterated,

GFR decreases and protein loss in the urine diminishes


Lupus Nephritis

-Recurrent microscopic or gross hematuria, the nephritic syndrome, rapidly progressive glomerulonephritis, the nephrotic syndrome, acute and chronic renal failure, and hypertension


Henoch-Schonlein Purpura

-childhood syndrome with purpuric skin lesions, abdominal pain and intestinal bleeding, arthralgia along with renal abnormalities
-skin lesions involve extensor surfaces of arms and legs as well as buttocks; abdominal manifestations include pain, vomiting, an intestinal bleeding
-renal manifestations occur in 1/3 of patients and include gross or microscopic hematuria, nephritic syndrome, nephrotic syndrome, or some combination of these
-most common in children 3-8 years old; also occurs in adults in whom renal manifestations more severe
-strong background of atopy in about 1/3 of patients
-IgA in glomerular mesangium


Henoch-Schonlein Purpura Histologic exam

-renal lesions vary from mild focal mesangial proliferation and/or endocapillary proliferation to crescentic glomerulonephritis


Henoch-Schonlein Purpura fluorescence microscopy

-deposition of IgA, sometimes with IgG and C3, in the mesangial region, sometimes with deposits extending to capillary loops
-skin lesions consist of sub epidermal hemorrhages and a recruiting vasculitis involving small vessels of the dermis


Glomerulonephritis Associated with Bacterial Endocarditis and Other systemic infections

-initiated by complexes of bacterial antigen and antibody
-hematuria and proteinuria of various degrees; can have acute nephritic presentation


Diabetic Nephropathy

-leading cause of chronic kidney failure in the U.S.
-advanced or end-stage kidney disease occurs in as many as 40% of both type I and type 2 diabetics


Fibrillary Glomerulonephritis

-morphologic variant of glomerulonephritis associated with characteristic fibrillary deposits in the mesangium and glomerular capillary walls that resemble amyloid fibrils superficially but differ ultra structurally and do not stain with Congo red.
-selective deposition of polyclonal IgG, often IgG4, complement C3, and IgK and Ig-gamma light chains
-nephrotic syndrome, hematuria, and progressive renal insufficiency


Glomerular lesions in Goodpasture syndrome, microscopic polyangiitis, and granulomatosis

-foci of glomerular necrosis and crescent formation
-in early or mild forms, there is focal and segmental, sometimes necrotizing, glomerulonephritis, and most of these patients will have hematuria with mild decline in GFR.
-in more severe cases, which may be associated with RPGN, there is more extensive necrosis, fibrin deposition, and extensive formation of epithelial (cellular) crescents, which can become organized to form fibrocellular and fibrous crescents int the glomerular injury evolves into segmental or global scarring (sclerosis)


Essential mixed cryoglobulinemia

-systemic condition in which deposits of cryoglobulins composed principally of IgG-IgM complexes induce cutaneous vasculitis, synoitis, and a proliferative glomerulonephritis, typically MPGN
-most cases have been associated with infection with hepatitis C virus
-MPGN type I


Acute Tubular Injury (ATI)

-acute renal failure and often, but not invariable, morphologic evidence of tubular injury, in the form of necrosis of tubular epithelial cells.
-most common cause of acute kidney injury (acute renal failure)


ATI can be caused by

-ischemia, due to decreased or interrupted blood flow, examples of which include diffuse involvement of internal blood vessels such as in microscopic polyangiitis, malignant hypertension, microangiopathies and systemic conditions associated with thrombosis (e.g., hemolytic uremic syndrome, thrombotic thrombocytopenia pauper, and disseminated intravascular coagulation), or decreased effective circulating blood volume, as occurs in hypovolemic shock
-direct toxic injury to the tubules by endogenous (e.g., myoglobin, hemoglobin, monoclonal light chains, bile/bilirubin) or exogenous agents (e.g., drugs, radio contrast dyes, heavy metals, organic solvents)


ATI accounts for

some 50% of cases of acute kidney injury in hospitalized patients


ATI is a reversible process that arises in a variety of clinical settings:

-most of these, ranging from severe trauma to acute pancreatitis, have in common a period of inadequate blood flow to the peripheral organs, usually accompanied by marked hypotension and shock: ischemic ATI


Nephrotoxic ATI

caused by a multitude of drugs, such as gentamicin; radiographic contrast agents; poisons, including heavy metals (e.g., mercury); and organic solvents (e.g., carbon tetrachloride).


Combination of ischemic and nephrotoxic ATI

-mismatched blood transfusions and other hemolytic crises causing hemoglobinuria and skeletal muscle injuries causing myoglobinuria
-result in characteristic intratubular hemoglobin or myoglobin casts
-the toxic iron content of these global molecules contributes to the ATI


Critical events in both ischemic and nephrotoxic ATI are believed to be

-tubular injury and persistent and severe disturbances in blood flow


Tubular cell injury

-tubular cells are particularly sensitive to ischemia and are also vulnerable to toxins