Glomerulonephritis 3

Fusion of podocyte foot processes is the correct answer. Fusion of podocyte foot processes. The light microscopic appearance of glomeruli in minimal change glomerulopathy is essentially normal. However, electron microscopic examination of glomeruli reveals total effacement of visceral epithelial cell foot processes. This retraction presumably results from extensive cell swelling and occurs in virtually all cases of proteinuria in the nephrotic range. It is not a specific marker, but is characteristic of minimal change glomerulopathy. Minimal change disease is not characterized by deposits of immune complexes (choices B and C) and does not reflect changes in the basement membrane (choice A). Choice E is incorrect because minimal change disease involves changes in glomeruli, not renal tubules.

Question 10 1 / 1 pts A 6-year-old boy is brought to the clinic with swelling of the legs and ankles. Physical examination reveals pitting edema of the lower extremities. Urinalysis show 2+ proteinuria. The urinary sediment contains no inflammatory cells or red blood cells. Serum levels of BUN and creatinine are normal. The patient recovers completely after a course of corticosteroids. Electron microscopy of a renal biopsy specimen prior to treatment would most likely demonstrate which of the following abnormalities? Fusion of podocyte foot processes Duplication of capillary basement membranes Electron-dense immune deposits in the mesangium Loss of microvilli by the tubular lining cells Electron-dense immune deposits in the capillary basement membranes

Focal segmental glomerulosclerosis is the correct answer. Focal segmental glomerulosclerosis. Focal segmental glomerulosclerosis (FSGS) is characterized by glomerular scarring (sclerosis) that affects some (focal), but not all, glomeruli and initially involves only part of an affected glomerular tuft (segmental). By light microscopy, varying numbers of glomeruli show segmental obliteration of capillary loops by increased collagen and the accumulation of lipid or proteinaceous material. FSGS is the cause of the nephrotic syndrome in 30% of adults and 10% of children. It is also the most common renal complication of intravenous drug abuse. Clinically, it presents with proteinuria, which occasionally may be so massive as to produce nephrotic syndrome. Nephropathy associated with HIV infection is a severe and rapidly progressive collapsing form of FSGS. Patients typically progress to end-stage renal disease in less than

Question 11 1 / 1 pts A 48-year-old woman with a history of drug addiction presents to the outpatient with progressive swelling of her his ankles and abdomen over the past four weeks. Urinalysis shows heavy non-selective proteinuria (6.1 g per 24 hours), but no evidence of inflammatory cells or RBCs. Laboratory studies reveal hyperlipidemia and hypoalbuminemia. Serum creatinine and BUN levels are normal. The blood test for ANCA is negative. The patient responds well to treatment with corticosteroids, but edema and proteinuria recur the following year. The steroid treatment is repeated with the same results. Upon the third recurrence of edema and proteinuria, the patient becomes steroid resistant. Light (PAS-stained section) and electron microscopic appearance of kidney glomerulus is shown in the image. Which of the following is the most likely diagnosis for this patient's glomerulopathy? glumerulonephritis_3_q12.png glumerulonephritis_3_q12_b.jpg Minimal change disease Focal segmental glomerulosclerosis Crescentic glomerulonephritis Membranous glomerulopathy Acute proliferative glomerulonephritis Membrano-proliferative glomerulonephritis

Effacement of podocyte foot processes is the correct answer. A child with nephrotic syndrome and no other clinical findings is most likely to have minimal change disease, a name that reflects the paucity of pathologic findings. There is fusion of podocyte foot processes, which can be seen only by electron microscopy. This fusion leads to selective proteinuria of low molecular weight proteins (albumin). Variability of basement membrane thickening may be seen in Alport syndrome. The mesangial matrix is expanded in some forms of glomerulonephritis (e.g., IgA nephropathy) and other diseases, such as diabetes mellitus, but not in minimal change disease. Reduplication of glomerular basement membrane may be seen with membranoproliferative GN. Subepithelial electron-dense humps represent immune complexes and are seen in postinfectious GN.

A 6-year-old girl has become increasingly lethargic over the past 2 weeks. On examination she has puffiness around the eyes. Her temperature is 36.9 C, and blood pressure is 100/60 mm Hg. Laboratory findings show serum creatinine, 0.7 mg/dL; urea nitrogen, 12 mg/dL; and cholesterol, 217 mg/dL. Urinalysis shows pH, 6.5; specific gravity, 1.011; 4+ proteinuria; lipiduria; and no blood or glucose. The 24-hour urine protein level is 3.8 g. The child 's condition improves after glucocorticoid therapy. Which of the following findings by electron microscopy is most likely to characterize this disease process? Increased mesangial matrix Reduplication of glomerular basement membrane Areas of thickened and thinned basement membrane Subepithelial electron-dense humps Effacement of podocyte foot processes

IgA nephropathy (Berger disease) is the correct answer. Berger disease is the most common form of glomerulonephritis in adults. Deposition of IgA-dominant immune complexes is the cause of the nephropathy, but the constituent antigens and the mechanism of accumulation have not been determined Exacerbations of IgA nephropathy are often initiated by infections of the respiratory or gastrointestinal tracts. The diagnostic finding on renal biopsy is intense mesangial staining for IgA, which is almost always accompanied by staining for C3. IgA nephropathy manifests a continuum of glomerulopathies, ranging from no discernible light microscopic changes to chronic sclerosing glomerulonephritis. Patients frequently present with hematuria and proteinuria, and 20% of patients develop renal failure after 10 years. Membranous nephropathy does not feature RBC casts. Hereditary nephritis (Alport syndrome) affects males predominantly

Question 12 1 / 1 pts A 43-year-old woman complains of recurrent hematuria since her youth. The hematuria typically occurs following upper respiratory tract infections. Vital signs are normal. Urinalysis shows proteinuria, hematuria, and a few red blood cell casts. Laboratory studies disclose normal levels of BUN and creatinine. The ANA and ANCA tests are negative. Which of the following is the most likely diagnosis? Membranous glomerulopathy Granulomatosis with polyangiitis (Wegener granulomatosis) IgA nephropathy (Berger disease) Hereditary nephritis (Alport syndrome) Thin basement membrane nephropathy (TBMN)

Granular complexes in the mesangium is the correct answer. Granular immune complexes in the mesangium. IgA nephropathy (Berger disease) is caused by immune complexes of IgA, which are located within the mesangium, where they most likely activate complement through the alternative pathway. The diagnostic finding is mesangial staining that is more intense for IgA than for IgG or IgM.

Question 13 1 / 1 pts For the patient described in the previous question, which of the following patterns of IgA immunofluorescence would be expected in the renal biopsy? Perivascular immune complexes Granular subepithelial complexes Linear complexes in the GBM Negative immunofluorescence pattern Granular complexes in the mesangium Granular subendothelial complexes

Dysfunction of the podocyte slit diaphragm apparatus is the correct answer. Corticosteroid-resistant hematuria and proteinuria leading to hypertension and renal failure is typical for focal segmental glomerulosclerosis (FSGS). FSGS is now the most common cause of nephrotic syndrome in adults in the United States. Specialized extracellular areas overlying the glomerular basement membrane between adjacent foot processes of podocytes are called slit diaphragms, and these exert control over glomerular permeability. Mutations in genes affecting several proteins, including nephrin and podocin, have been found in inherited cases of FSGS; podocyte dysfunction, possibly caused by cytokines or unknown toxic factors, may be responsible for acquired cases of FSGS. FSGS with collapsing glomerulopathy is seen in patients with HIV-associated nephropathy. Immune complexes containing microbial antigens cause postinfectious glomerulon

Question 2 1 / 1 pts A 46-year-old Hispanic man has had increasing malaise with headaches and easy fatigability for the past 3 months. Physical examination reveals his blood pressure is 200/100 mm Hg. There are no palpable abdominal masses and no costovertebral tenderness. Laboratory studies show hemoglobin, 9.5 g/dL; hematocrit, 28.3%; MCV, 92 m3; creatinine, 4.5 mg/dL; and urea nitrogen, 42 mg/dL. Urinalysis reveals 3+ hematuria and 3+ proteinuria, but no glucose or leukocytes. A renal biopsy is done; light microscopic examination of the biopsy specimen shows that approximately 50% of the glomeruli appear normal, but the rest show that a portion of the capillary tuft is sclerotic. Immunofluorescence staining shows IgM and C3 deposition in these sclerotic areas. His history is significant for repeated episodes of passing dark brown urine, which failed to respond to corticosteroid therapy. Which of the following mechanisms is most likely responsible for his disease? Inherited defect in the basement membrane collagen Deposition of immune complexes containing microbial antigens Deposition of C3 nephritic factor (C3NeF) Dysfunction of the podocyte slit diaphragm apparatus Attachment of anti glomerular basement membrane antibodies

Cytokine-mediated visceral epithelial cell injury is the correct answer. Steroid-responsive proteinuria in a child is typical of minimal change disease, in which the kidney looks normal by light microscopy, but fusion of foot processes is visible with electron microscopy. The most likely cause of foot process fusion is a primary injury to visceral epithelial cells caused by T cell derived cytokines. Acute cellular renal transplant rejection is mediated by CTL-mediated injury with tubulitis. IgA nephropathy with mesangial IgA deposition and consequent glomerular injury causes recurrent gross or microscopic hematuria and, far less commonly, nephrotic syndrome. Immune complex deposition in membranous nephropathy can cause nephrotic syndrome, but is less common in children than in adults and is not steroid responsive. Certain verocytotoxin-producing Escherichia coli strains can cause hemolytic uremic syndrome by injury t

Question 3 1 / 1 pts A 7-year-old boy has become less active over the past 10 days. On physical examination, the boy has facial puffiness. Urinalysis shows no blood, glucose, or ketones, and microscopic examination shows no casts or crystals. The serum creatinine level is normal. A 24-hour urine collection yields 3.8 g of protein. He improves after corticosteroid therapy. He has two more episodes of proteinuria over the next 4 years, both of which respond to corticosteroid therapy. What is the most likely mechanism causing his disease? Verocytotoxin-induced endothelial cell injury Immune complex mediated glomerular injury Cytotoxic T cell mediated tubular epithelial cell injury Cytokine-mediated visceral epithelial cell injury IgA-mediated mesangial cell injury

Mesangial IgA staining by immunofluorescence is the correct answer. IgA nephropathy (also known as Berger disease) can explain this nephritic condition with the presence of recurrent hematuria in a young adult. Nephrotic syndrome is not present, and mesangial IgA deposition is characteristic. The initial episode of hematuria usually follows an upper respiratory infection. IgA nephropathy occurs with increased frequency in patients with celiac disease and liver disease. It proceeds to chronic renal failure within 20 years in up to half of cases. Diffuse proliferation and basement membrane thickening denote membranoproliferative glomerulonephritis (GN), with IgG and C3 deposited in the glomeruli. Granular staining of basement membrane with IgG antibodies denotes immune complex deposition, which may occur in postinfectious GN, along with subepithelial deposits seen on electron microscopy. Patients with these changes als

Question 4 1 / 1 pts A 25-year-old man has a 5-year history of celiac sprue. Four days after a mild upper respiratory infection, he begins passing dark red-brown urine. The dark urine persists for the next 3 days and then becomes clear and yellow, only to become red-brown again 1 month later. There are no remarkable findings on physical examination. Urinalysis shows a pH of 6.5; specific gravity, 1.018; 3+ hematuria; 1+ proteinuria; and no glucose or ketones. Microscopic examination of the urine shows RBCs, but no WBCs, casts, or crystals. A 24-hour urine protein level is 200 mg. A renal biopsy specimen from the glomeruli of this patient is most likely to show which of the following alterations? Thrombosis within the glomerular capillaries Mesangial IgA staining by immunofluorescence Granular staining of the basement membrane by anti-IgG antibodies Subepithelial electron-dense deposits Diffuse cellular proliferation and basement membrane thickening

Mesangium is the correct answer. Development of recurrent hematuria after a viral illness in a child or young adult is typically associated with IgA nephropathy. A renal biopsy specimen will show diffuse mesangial proliferation and electron-dense deposits in the mesangium. In these patients, some defect in immune regulation causes excessive mucosal IgA synthesis in response to viral or other environmental antigens. IgA complexes are deposited in the mesangium and initiate glomerular injury. Defects in the structure of glomerular basement membrane are a feature of hereditary nephritis, and antibodies against type IV collagen are formed in Goodpasture syndrome. The parietal epithelium may react with proliferation to form crescents when fibrinogen leaks into the Bowman space with severe glomerulonephritis. Podocytes may be affected by many forms of glomerular disease, but singularly malfunction in minimal change disease

Question 5 1 / 1 pts One week after a mild flulike illness, a 9-year-old boy has an episode of hematuria that subsides within 2 days. One month later, he tells his parents that his urine is red again. On physical examination, there are no significant findings. Urinalysis shows a pH of 7; specific gravity, 1.015; 1+ proteinuria; 1+ hematuria; and no ketones, glucose, or urobilinogen. The serum urea nitrogen level is 36 mg/dL, and the creatinine level is 3.2 mg/dL. Serum electrophoresis shows increased IgA. Which of the following glomerular structures is most likely to show structural alterations in this boy? Podocytes Basement membranes Capillaries Mesangium Parietal epithelium

Mutation in a gene encoding type IV collagen is the correct answer. Alport syndrome is a form of hereditary nephritis. Hematuria is the most common presenting feature, but proteinuria is often present and may be in the nephrotic range. Patients progress to chronic renal failure in adulthood. An X-linked pattern of inheritance is present in 85% of cases, but autosomal dominant and autosomal recessive pedigrees also exist. The foamy change in the tubular epithelial cells and ultrastructural alterations of the basement membrane are characteristic features. The genetic defect results from mutation in the gene for the 5 chain of type IV collagen. IgA nephropathy is a form of glomerulonephritis that does not produce tubular epithelial changes. TTP is often associated with inherited or acquired deficiencies of ADAMTS13, leading to thrombotic microangiopathy, similar to hemolytic uremic syndrome from Escherichia coli Shiga t

Question 6 1 / 1 pts A 15-year-old boy has been passing dark-colored urine for the past month. On physical examination, he has bilateral sensorineural hearing loss and corneal erosions. Urinalysis shows a pH of 6.5; specific gravity, 1.015; 1+ hematuria; 1+ proteinuria; and no ketones, glucose, or leukocytes. The serum creatinine level is 2.5 mg/dL, and the urea nitrogen level is 24 mg/dL. A renal biopsy specimen shows tubular epithelial foam cells by light microscopy. By electron microscopy, the glomerular basement membrane shows areas of attenuation, with splitting and lamination of lamina densa in other thickened areas. What is the most likely diagnosis? Toxic injury to slit diaphragm proteins Acquired deficiency of ADAMTS13 metalloprotease Mutation in a gene encoding type IV collagen Autoimmune destruction of pancreatic beta cells Increased synthesis of abnormal IgA

Hypertension is the correct answer. These findings describe end-stage renal disease, the appearance of which can be similar regardless of the cause (e.g., vascular disease or glomerular disease). The characteristics of progressive renal damage include glomerulosclerosis (starting with focal segmental glomerulosclerosis) and tubulointerstitial fibrosis. With advanced renal destruction, hypertension almost always supervenes, even if it was absent at the onset of renal disease. Many such cases are referred to as chronic glomerulonephritis (GN), for want of a better term. Hemoptysis occurs in Goodpasture syndrome that involves lungs as well as kidneys. Lens dislocation is a feature of Alport syndrome, from thinning of the anterior lens capsule. Pharyngitis with group A streptococcal infection may precede postinfectious GN. A skin rash might have preceded the postinfectious GN.

Question 7 1 / 1 pts An autopsy study is performed involving persons with gross pathologic findings of bilaterally small kidneys (less than 100 g) that have a coarsely granular surface appearance. Microscopic examination shows sclerotic glomeruli, a fibrotic interstitium, tubular atrophy, arterial thickening, and scattered lymphocytic infiltrates. Which of the following clinical findings was most likely reported in these patients ' medical histories? Skin rash Lens dislocation Hypertension Hemoptysis Pharyngitis

Minimal change disease is the correct answer. This patient has minimal change glomerulopathy with nephrotic syndrome. The nephrotic syndrome is characterized by heavy proteinuria. (greater than 3.5 g protein per 24 hours), hypoalbuminemia, hyperlipidemia, and edema. In minimal change glomerulopathy, there is effacement of visceral epithelial cell (podocyte) foot processes, which allows protein to be lost from the plasma into the urine (proteinuria).

Question 8 1 / 1 pts An 11-year-old boy is brought to the outpatient clinic with slowly increasing swelling of the eyelids, abdomen, and ankles over the past two weeks. A chest x-ray shows bilateral pleural effusions, without evidence of lung disease. Urinalysis reveals proteinuria of 6.5 g/24 hours. A percutaneous needle biopsy of the kidney discloses no morphologic abnormalities by light microscopy. Which of the following is the most likely diagnosis? Alport syndrome Acute pyelonephritis Membranous glomerulopathy Minimal change disease Focal segmental glomerulosclerosis

Minimal change disease is the correct answer. Minimal change disease that causes 90% of the nephrotic syndrome in young children and 15% in adults. Proteinuria is generally more selective (albumin greater than globulins) than in the nephrotic syndrome caused by other diseases, but there is too much overlap for this selectivity to be used as a diagnostic criterion. This disease is characterized pathologically by fusion (effacement) of visceral epithelial foot processes; however, this can be visualized only by electron microscopy. Minimal change glomerulopathy is successfully treated with corticosteroids and does not progress to renal failure. Focal segmental glomerulosclerosis (FSGS) is the cause of nephrotic syndrome in 10% of children and 30% of adults. FSGS is the term applied to a heterogeneous group of glomerular diseases that have different causes, including mutations, viruses, drugs, and serum factors. Henoch-S

Question 9 1 / 1 pts A 7-year-old girl is brought to the pediatrician with of her feet for the past week. She is otherwise healthy, with no known previous illness. Vital signs are normal. Physical examination reveals pitting edema of the lower legs and a swollen abdomen. Urinalysis shows 4+ protein but no RBCs or WBCs. Which of the following is the most likely diagnoses to consider in your evaluation of this patient? Focal segmental glomerulosclerosis Kawasaki disease Minimal change disease Henoch-Schonlein purpura Acute proliferative glomerulonephritis Acute pyelonephritis