No inflammation is seen.
IF pattern would be granular and peripheral, which correlates with the immune complex deposits between spikes.
This patient presented with nephrotic syndrome. He had marked albuminuria, low serum albumin, and consequent generalized edema. Hyperlipidemia is also often seen in patients with nephrotic syndrome. This gives rise to lipiduria, seen as oval fat bodies in the urine. Note the absence of red cells.
On the GBM.
Granular. This pattern corresponds to the immune complex deposition. It is the immune complexes that are stained.
The deposits are located in the outer aspect of the basement membrane under the visceral epithelium of the Bowman's capsule. Thus, they are subepithelial.
No. The spikes are part of the GBM that lies between the deposits.
The biopsy reveals a membranous glomerulopathy, with subepithelial deposits of electron dense, immune complex type material. By light microscopy, this is illustrated by lack of increased glomerular cellularity, and uniformly thickened GBMs. A special stain (silver) shows "spikes" of GBM material projecting between the deposits, a feature better understood on the EM photo. Immunofluorescence shows the typical granular, peripheral capillary loop staining with IgG and C3, typical of membranous GN.
After the diagnosis of nephrotic syndrome was made, the clinician did serological tests to rule out some secondary causes of membranous glomerulonephritis that account for about 40% of cases. This is important, because they can in many cases be treated. These include SLE, hepatitis B, malaria, gold and penicillamine for rheumatoid arthritis, Captopril (an angiotensin-converting enzyme inhibitor), and occult carcinoma.
Although the peak incidence is between two and six years of age, adults may also be affected.
It is normal.
In children primary renal disease accounts for 95% of the cases, the most common cause being minimal change disease. By comparison primary renal diseases are responsible for 60% of cases in adults; membranous glomerulonephritis is the most common primary renal cause.
No. The only abnormality is foot process effacement.
No deposits are seen in MCD.
This is not fully understood. There is no evidence of anti GBM antibodies or immune complexes. There seems to be some form of primary injury to glomerular epithelial cells that effaces foot processes and causes secondary alterations in GBM.
IF will be positive in the sclerotic focus, and will stain with IgM and C3.
IF is negative in the nonsclerotic part.
No. The basic lesion in primary FSGS is disruption of visceral epithelial cells by unknown mechanisms. The sclerosis and entrapment of plasma protein, including IgM and C3, are non specific. They result from hyperpermeability at sites of epithelial cell damage.
FSGS is a descriptive term that implies sclerosis of some, but not all, glomeruli (i.e., focal), and in the affected glomerulus only a portion of the capillary tuft is involved (i.e., segmental). Such changes may occur in glomerular diseases secondary to HIV infection or heroin abuse; these may also occur in IgA nephropathy. In addition, idiopathic FSGS is a distinct clinicopathologic entity.
Both FSGS and minimal change disease present with nephrotic syndrome, (the latter is more common). It is essential to distinguish them because their course and prognosis are different. FSGS is less steroid responsive and, unlike the benign course in minimal change disease, 50% of cases with FSGS end up with renal failure in 10 years.
Mesangial cells, monocytes, and lymphocytes.
Mesangiocapillary GN.
The double contour appearance is caused by an apparent "splitting" of the basement membrane. This split appearance results from the intercalation of mesangial cell processes into the peripheral capillary loops.
IF would show granular and peripheral patterns with/without mesangial pattern.
No spikes are seen in MPGN.
Yes, because in SLE the immune complexes can deposit in the mesangium or along the basement membrane.
There are two types of primary MPGN. Type I, the more common form is an immune complex disease and shows granular pattern of IgG and C3 deposition by IF. The immune complexes are subendothelial by EM. Type II, the less common form has C3 but not IgG in a granular-linear pattern on the basement membrane and as aggregates in the mesangium. The two are distinguished best by electron microscopy
Extension of the mesangial cells.
It can occur in association with SLE, hepatitis B or C antigenemia, and a-1-antitrypsin deficiency.
This patient presented initially with two of the three symptoms associated with acute nephritic syndrome (hypertension, hematuria, and evidence of renal failure, e.g., increased creatinine). The most common cause of the acute nephritic syndrome is poststreptococcal (post-infectious) glomerulonephritis. This is an immune-complex mediated disease, with IgG and C3 seen along the GBMs by IF ("lumpy-bumpy" pattern) and large subepithelial "humps" by EM.
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oliguria/anuria - |
by history and observation |
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uremia/azotemia - |
by history, nausea and vomiting by laboratory, creatinine and BUN |
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fluid retention - |
by history, ankle swelling by exam, ankle edema, hypertension by lab, decreased hematocrit |
This patient had RBCs and RBC casts in his urine; this is pathognomonic of glomerular disease. Can you think why?
IF findings can help classify RPGN into three categories: type I RPGN (anti-GBM) has a linear pattern; type II RPGN is caused by immune complexes and has a granular pattern; type III RPGN is defined by lack of anti-GBM or immune complex etiology. IF is normal.
Antineutrophil cytoplasmic antibody (ANCA). ANCA is negative in type I and type II crescentic GN, and it is positive in type III.
Anti-GBM disease.
No.
This patient had type I (anti GBM) crescentic glomerulonephritis. This is supported by immunofluorescence, EM and absence of ANCA. Plasmapheresis was done to remove the anti-GBM antibodies that damage the kidney.
No, because no deposits are seen.
No.
The histologic features of Henoch-Schonlein purpura and IgA GN are similar.
You confirm the diagnosis by IF staining with anti IgA.
IgA nephropathy is a disease of children or young adults who present with hematuria within a day or two of an episode of respiratory, urinary or gastrointestinal infection. The hematuria usually subsides but recurs within weeks to months. IgA nephropathy is an important cause of recurrent hematuria. Mild proteinuria may be present. This slowly progressive disease results in renal failure in as many as half of the cases. The cause of IgA nephropathy is not clear. It is thought there is an increased synthesis of IgA in response to mucosal infections. The IgA forms immune complexes that deposit in the mesangium.
Alport syndrome and thin GBM disease are also associated with asymptomatic hematuria.
There is deposition of IgA in the mesangium.
The EM will show mesangial deposits.
While these two conditions have similar histologic changes in the kidney, Henoch-Schonlein purpura is a systemic disorder involving skin (purpura), gastrointestinal tract (abdominal pain, intestinal bleeding), and joints (arthritis). Some consider IgA nephropathy to be a localized form of Henoch-Schonlein purpura.
No. Spikes are seen in membranous GN because the immune complexes deposit on the basement membrane.
By EM.
LM is not enough.
No it is not. Focal segmental glomerulosclerosis can be seen in many other conditions. It may be idiopathic, superimposed on IgA nephropathy, or secondary to HIV disease.
Alport Syndrome is a hereditary nephritis presenting with hematuria and accompanied by nerve deafness and ocular disorders such as lens dislocation and cataracts. It results from mutation in the gene for type IV collagen, causing defective GBM synthesis.
Yes, the EM changes of the GBM are diagnostic of Alport Syndrome.
The presence of WBC (neutrophils) and casts indicates that acute tubular inflammation of the kidney is present. Thus they may also be seen in acute tubulointerstitial nephritis and acute tubular necrosis.
Areas of necrosis that resemble infarction.
Diabetes mellitus, acute pyelonephritis with obstruction, and nephritis associated with analgesic abuse.
Predisposing factors in this patient might include female sex, diabetes mellitus, history of bladder infections (congenital anomaly or vesico-ureteral reflux, or perhaps a neurogenic bladder from diabetes). A renal stone would not be unusual in this patient and would probably be of the calcium oxalate type.
This is complication requires the presence of three factors:
a. acute pyelonephritis
b. obstruction to urine flow, as with a stone or neurogenic bladder in diabetes
c. compromised blood supply as with diabetes or sickle cell anemia
It results from a combination of ischemia and infection. Ischemia, in diabetes results from microangiopathy and diabetics are also more prone to infections.
Diabetes and urinary tract infection.
WBC casts.
1. Calcium stones (75%)
2. Triple stones Mg++, NH3, PO4 (15%)
3. Uric acid stones (5%)
4. Cystine stone (rare)
Stones in the ureter may cause intense pain (renal colic); they may cause hematuria and, most importantly, predispose to urinary tract infection.
Acute inflammation (pus).
Acute pyelonephritis is caused most commonly by enteric gram negative rods that reach the kidney by ascending infection. This type of infection is favored by instrumentation (e.g., catheters) and by obstruction in the lower urinary tract (e.g., prostate enlargement). Incompetence of the vesicoureteral orifice is also important because reflux of the urine from the bladder allows the infection to move upward to the kidney.
Recurrent inflammation and scarring because of obstruction or reflux.
The scars of pyelonephritis are wide and irregular and affect the two kidneys unequally; by comparison, scars of hypertension result from diffuse small vessel narrowing, and hence they are fine, uniform, and bilaterally symmetrical.
Diabetes mellitus and chronic glomerulonephritis, because they cause diffuse scarring of glomeruli.
The patient's medical history reveals a middle-aged black man with a history of untreated hypertension and the kidney shows severe damage. The clinical features are consistent with the manifestation of renal failure.
a. Chest pain - retrosternal and burning and worse on inspiration. This is classic for pericarditis. The muffled heart tones suggest this as well, while the negative cardiac enzymes would seem to rule out an MI.
b. The chest X-ray, history of dyspnea, and presence of rales would indicate volume overload. Congestive heart failure due to atherosclerotic coronary artery disease might be a consideration as the cardiomegaly on chest X-ray is noted (but this is due to the pericardial effusion instead), but the elevated creatinine and small kidneys would seem to point to renal failure in this case.
c. Other evidence of uremia can be seen besides the pericarditis; this includes intractable nausea and vomiting, bleeding time prolongation and bruising with normal platelet numbers (platelet dysfunction), and hyperuricemia.
Fibrinoid necrosis of small and medium size arteries and hyperplastic arteriolosclerosis.
Fibrinous exudate collected due to uremia. In renal failure, toxic substances not removed by the kidney may damage the pericardium.
Friction rub.
Left ventricle shows concentric hypertrophy of the heart muscle.
The most likely cause is hypertension.
Long-standing hypertension has caused renal failure.
With renal damage the 1-a-hydroxylase present normally in the proximal tubular cells is reduced. The enzyme is essential for formation of active vitamin D. Thus vitamin D levels are reduced, and, consequently, calcium absorption from the gut falls. This contributes to hypocalcemia.
The child's course after treatment is suggestive of an allergic reaction to the drug he is taking, with development of a rash and itching. Because kids often itch and get rashes, it was not until joint pain, fever, and listlessness developed that the child was returned to the doctor. The fever and rash are likely additional immune features of the hypersensitivity reaction, but the listlessness and loss of appetite is worrisome, when combined with the laboratory findings.
The laboratory findings reveal:
a. renal compromise - a creatinine of 2.1 in a healthy boy is too high and implies renal impairment if there are no features of hypovolemia.
b. there is a mildly increased WBC count, with eosinophilia - an indicator of hypersensitivity.
c. the urinalysis findings, the presence of blood, protein, and WBCs suggest glomerulonephritis in a patient with a history of a strep infection. Although glomerulonephritis following so soon after a strep infection would be unusual (usually 2-4 weeks); it is not unknown.
Because glomeruli appear normal without hypercellularity or inflammation.
In inflammation caused by allergic reactions, or parasitic infestations.
Diffuse is opposite to focal. Global is opposite to segmental.
No crescents are seen in the image.
Streptococcal infection is the most common cause of this form of glomerulonephritis. One to four weeks after a patient recovers from a b-hemolytic strep infection, there is deposition of immune complexes in the glomeruli.
Both in poststreptococcal GN and in membranous GN the immune complex deposits are subepithelial. There are some differences in size and distribution, but they are not distinctive.
No. You need a clinical correlation.
The classic triad of presenting symptoms is:
1. Pain
2. Palpable mass
3. Hematuria
However, together these are seen only in 10% of patients. Most reliable is hematuria, seen in 90%.
The typical age: 60s - 70s. Male/Female = 3/1.
Wilms' tumor.
Wilms' has "blue cells" with sparse cytoplasm. Renal cell carcinoma has clear cells and abundant cytoplasm.
A tendency to invade the renal vein and grow as a cord, extending sometimes to the heart via the inferior vena cava is characteristic of this tumor. Renal cell cancers may metastasize widely before local symptoms are noted.
Renal cell carcinoma is a great mimic. It may cause polycythemia, hypercalcemia, Cushing's syndrome, and amyloidosis.
The microscopic appearance of the pelvis and bladder tumor is transitional cell carcinoma.
Wilms' tumors are associated with deletion of WT-1 or WT-2 loci on chromosome 11.
Survival rate for Wilms' is 90% with treatment combining chemotherapy-radiation and surgery.
Other blue cell tumors:
1. Neuroblastoma
2. Ewing sarcoma
3. Lymphoma
4. Embryonal rhabdomyosarcoma