9/21- Histopathology Review and ATN & IS Nephritis Flashcards
What are the overall characteristics (clinical findings) in Nephrotic Syndrome?
- Proteinuria
- Edema
- Hypoalbuminemia
- Hypercholesterolemia
- Lipiduria
What are the overall characteristics (clinical findings) in Nephritic Syndrome?
- Hematuria
- Mild proteinuria
- HTN
What are the overall characteristics (clinical findings) in Acute Renal Failure?
- Oliguria or anuria
- Elevated BUN and creatinine
What are the overall characteristics (clinical findings) in Chronic Renal Failure?
- Chronic elevation of BUN and creatinine
What is seen here?
V = vessel
G = glomerulus
- Can see vascular pole on lower left of glomerulus
- Normal loops are open; nothing within (including blood)
- Can see mesangium (“branches of trees”)
pT = proximal tubule
- pink, much cytoplasm, big lumen
dT = distal tubule
- less pink, smaller lumen
What is seen here?
pT = proximal tubule
dT = distal tubule
Into what 3 categories can renal diseases be divided?
Diseases affecting:
- Glomeruli
- Tubulo-interstitium
- Vessels
What are the glomerular patterns of injury?
Hypercellularity
- Mesangial cells
- Endothelial cells
- Leukocyte infiltrates
- Crescents
Basement membrane abnormalities
- Too thick, too thin, abnormal structure
Hyalinosis and Sclerosis
What is seen here?
Left (A): Mesangial hypercellularity ( > 3 cells per mesangial region)
- Cap loops nice and open, but too many nuclei in mesangial region
Right (B): Endocapillary proliferation; hypercellularity occludes capillary lumens
- Not too many open capillary loops
- Cellularity occluding loop
What is seen here?
Intracapillary neutrophils
- Can see tri-lobed nucleus
What is seen here?
Cellular crescent
- Cellularity in tubular/lumen space
What is seen here?
Left: Normal thickness glomerular basement membranes with preserved foot processes
- Podocyte foot processes can be seen angling down toward bottom right, covering GBM
- Foot processes standing straight and upright (“like Stonehenge”)
- Hazy gray area is intra-cap
Right: thin and irregular GBM with a basket-woven appearance
- Hereditary nephritis- Alports
What is seen here?
Left: Thickened glomerular basement membranes with effaced foot processes
- Altered charge potential and selective permeability
- Diabetes
Right: Thin, but normal structure GBM (B, note size measurement of 87 nm, normal is 350 nm in adult)
- RBCs can squeeze across these thin GBM
- Benign familial hematuria
What is seen here?
Left: Globally sclerotic glomerulus
- Typically accompanied by:
Right: tubular atrophy and interstitial fibrosis
The atrophic tubules have cast material and resemble thyroid tissue (“thyroidization”).
Immunofluorescence (IF) stains are used to highlight what processes? Examples?
Antibody mediated diseases
- anti-GBM disease
- membranoproliferative GN (type II)
- *pauci-immune GN is antibody mediated but IF is negative Immune complex mediated diseases
- systemic lupus erythematosus
- postinfectious glomerulonephritis
What is seen here?
Linear GBM staining, IgG
- “Linearly” green
- Typically seen in anti-GBM disease (evenly distributed along basement membrane)
What is seen here?
Mesangial staining
- SLE (could be IgA, IgG…)
Electron microscopy is necessary to detect what types of abnormalities?
- Confirm IF findings (electron dense deposits)
- Evaluation of foot processes: effaced or preserved, only way to diagnosis minimal change disease
- Evaluation of basement membrane thickness and composition
- Drug effects (mitochondrial alterations)
- Viral infections
- Storage disease
What is seen here?
- Electron dense deposits
- Left: Mesangial; could be lupus, IgA/IgG nephropathy… just showing mesangial electron dense deposits
- Right: Epimembranous (“humps”); very characteristic of post-glomerulonephritis
What is seen here?
Effaced foot processes
- Can see endothelial cell nucleus protruding into cap lumen
- Foot processes look like “melted Hershey kisses”)
What is seen here?
Viral (BK) particles
- Commonly seen in kidney biopsies in transplant population
Case 1)
- 61 year-old lawyer was admitted for a triple coronary bypass surgery for coronary atherosclerosis; op was successful and the pt recovered from the surgery
- Two days post-postoperatively, he developed progressive SOB and chest pain and a diagnosis of ARDS was made - At the same time, urine output was decreased and he became anuric.
- The serum creatinine was 6.5 mg/dl but there was no protein excretion in his urine.
- The serum creatinine before the operation was 0.9 mg/dl and there was no proteinuria by dip stick.
- The patient was put on hemodialysis, but multiorgan failure developed and he expired 5 days after surgery. An autopsy was performed.
What syndrome does this pt have?
Possible causes overall and then in this patient?
Syndrome of acute renal failure
- This syndrome is characterized by decreased renal function and anuria of sudden onset.
- The normal renal function before the operation also supports the diagnosis of acute renal failure - The absence of protein is also a characteristic feature of acute renal failure.
Possible causes of acute renal failure are multiple and can be classified into 3 categories: Pre-renal, renal, and post-renal
- Pre-renal causes are related to sudden and bilateral loss of renal perfusion
- The renal causes are mainly related to severe involvement of one of the three main renal compartments (glomerular, tubulointerstitial, or vascular)
- The post-renal causes are related to sudden bilateral obstruction of the urine outflow.
In this patient: hypoperfusion leading to acute tubular necrosis
There are two types of acute tubular necrosis.
- One is related to ischemic injury secondary to severe and prolonged renal hypoperfusion, and the other is related to nephrotoxins.
- Acute tubular necrosis of ischemic type is much more frequent and is most probably the cause of acute renal failure in this patient.
What are nephrotoxic drugs associated with ATN?
- Aminoglycosides
- Contrast agents
…
Case 1 cont’d)
For the pt with ischemic injury 2ndary to severe/prolonged renal hypoperfusion causing acute renal failure
Tubular changes are mostly related to apoptosis, necrosis, and regeneration of the tubular epithelial cells and vary according to the stages of disease
- There is focal necrosis or flattening of the tubular epithelial cells
- Interstitial edema, vascular congestion, and minimal interstitial inflammation, may also be present in ischemic acute tubular necrosis
What is seen here?
- Tubular dilation
- Acute injury to tubular cells with complete loss of tubular epithelial cells
- dTs look okay, but pTs are dying/dead
- Interstitial edema
- Reactive/regenerative nuclear changes (nucleolus dot in central nucleus; also abnormal and big nucleus just top/right of center)
What is seen here?
Left arrow: can see tubule completely sloughed of cells; BM still attached (could recover)
What is seen here? Significance?
Mitotic figure indicates that cells were alive and time of observed changes
What is seen here?
Naked tubular basement membranes (*) due to complete necrosis of epithelium, focal thinning of epithelium (arrow)
- Cells can slough off downstream and clog tubule, raising intra-glomerular pressure
Case 1 cont’d)
For the pt with ischemic injury 2ndary to severe/prolonged renal hypoperfusion causing acute renal failure in electron microscopy?
A tubule showing necrosis of some of the epithelial cells and center tubule consisting of mostly residual basement membrane only
What is seen here?
A tubule showing necrosis of some of the epithelial cells and center tubule consisting of mostly residual basement membrane only
- Internal stuff is cellular debris
- Can see residual cell (darkened spot top left of center)
- Sad little brush borders in bottom right
Case 1 cont’d)
What would you expect to see in glomerular and vascular compartments in this patient?
They are normal
Case 2)
- An 18-year-old woman presented with progressive decrease in urine output in the past week
- She reports recent antibiotic use for a URI but otherwise has no significant past medical history
- Specifically, the renal function was normal and there was no proteinuria by dip stick during a routine check-up about 1 year previously.
- Physical examination revealed skin rashes involving mostly her trunk and lower extremities.
- Laboratory findings shows a serum creatinine of 5.8 mg/dl; urine analysis showed no protein, 2-3 RBCs and 5-7 WBCs/HPF. All serologic tests were negative.
What renal syndrome does this pt have?
This patient has acute renal failure.
- Acute renal failure is characterized by a progressive decrease of urine output, increased serum creatinine, and normal renal functions in the recent past.
Case 2 cont’d)
- Laboratory findings shows a serum creatinine of 5.8 mg/dl; urine analysis showed no protein, 2-3 RBCs and 5-7 WBCs/HPF. All serologic tests were negative.
- What important test could have been performed on the urine?
The clinical features of this patient (ARF with skin rash) are quite typical for allergic acute tubulointerstitial nephritis
- Allergic acute tubulointerstitial nephritis is most frequently drug-induced
- Eosinophilia in both the circulation and urine is typically observed, especially in the early phases of the disease
- In the majority of cases of allergic acute tubulointerstitial nephritis, there is no or little proteinuria.
Case 2 cont’d)
What is the indication for renal biopsy in this pt?
This patient has acute renal failure.
- There are multiple causes of acute renal failure; some of them have a much better prognosis than others and the treatment of these conditions are quite different
- Therefore, acute renal failure is a fairly uniform indication for a renal biopsy.
Case 2 cont’d)
What does the renal biopsy show?
RECAP:
- An 18-year-old woman presented with progressive decrease in urine output in the past week
- She reports recent antibiotic use for a URI but otherwise has no significant past medical history
- Specifically, the renal function was normal and there was no proteinuria by dip stick during a routine check-up about 1 year previously.
- Physical examination revealed skin rashes involving mostly her trunk and lower extremities
- Laboratory findings shows a serum creatinine of 5.8 mg/dl; urine analysis showed no protein, 2-3 RBCs and 5-7 WBCs/HPF. All serologic tests were negative.
The renal biopsy shows acute tubulointerstitial nephritis probably of an allergic type
- There is edema of the interstitial compartment with infiltration by mononuclear cells, primarily lymphocytes and macrophages
- Eosinophils and neutrophils may be present, often in large numbers
- Occasional plasma cells may be found.
- Variable degrees of tubular necrosis and regeneration may be present (see following images).
What is seen here?
Acute tubulointerstitial nephritis
- Interstitial edema and inflammation
- Nonspecific acute tubular cell injury
- Those bright red/pink cells are eosinophils
What is seen here?
Acute tubulointerstitial nephritis
- Interstitial edema and inflammation
- Nonspecific acute tubular cell injury
- A few eosinophils are seen; quite a few lymphocytes
What is seen here?
Acute tubulointerstitial nephritis
- Severe interstitial inflammation
- A few eosinophils are seen
Case 2)
What do you see on EM?
This shows a tubule with infiltration of the tubular epithelium by inflammatory cells (lymphocytes)
What is seen here?
Tubulitis characterized infiltration of tubular epithelium by inflammatory cells.
Case 2 cont’d)
What do you see in glomeruli?
They are normal in tubulointerstitial nephritis
What is seen here?
Normal glomerulus
What is the treatment and prognosis of this pt (Allergic acute tubulointerstitial nephritis)?
Allergic acute tubulointerstitial nephritis is usually self-limited and a specific treatment may not be needed
- Steroids may facilitate the recovery
In general, the prognosis is excellent
- Within a month or so, the renal functions go back to normal
- This course was encountered in this patient.
