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MS2 Renal > 9/21- Histopathology Review and ATN & IS Nephritis > Flashcards

9/21- Histopathology Review and ATN & IS Nephritis Flashcards

1
Q

What are the overall characteristics (clinical findings) in Nephrotic Syndrome?

A
  • Proteinuria
  • Edema
  • Hypoalbuminemia
  • Hypercholesterolemia
  • Lipiduria
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2
Q

What are the overall characteristics (clinical findings) in Nephritic Syndrome?

A
  • Hematuria
  • Mild proteinuria
  • HTN
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3
Q

What are the overall characteristics (clinical findings) in Acute Renal Failure?

A
  • Oliguria or anuria
  • Elevated BUN and creatinine
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4
Q

What are the overall characteristics (clinical findings) in Chronic Renal Failure?

A
  • Chronic elevation of BUN and creatinine
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5
Q

What is seen here?

A

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
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6
Q

What is seen here?

A

pT = proximal tubule

dT = distal tubule

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7
Q

Into what 3 categories can renal diseases be divided?

A

Diseases affecting:

  • Glomeruli
  • Tubulo-interstitium
  • Vessels
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8
Q

What are the glomerular patterns of injury?

A

Hypercellularity

  • Mesangial cells
  • Endothelial cells
  • Leukocyte infiltrates
  • Crescents

Basement membrane abnormalities

  • Too thick, too thin, abnormal structure

Hyalinosis and Sclerosis

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9
Q

What is seen here?

A

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
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10
Q

What is seen here?

A

Intracapillary neutrophils

  • Can see tri-lobed nucleus
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11
Q

What is seen here?

A

Cellular crescent

  • Cellularity in tubular/lumen space
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12
Q

What is seen here?

A

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
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13
Q

What is seen here?

A

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
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14
Q

What is seen here?

A

Left: Globally sclerotic glomerulus

  • Typically accompanied by:

Right: tubular atrophy and interstitial fibrosis

The atrophic tubules have cast material and resemble thyroid tissue (“thyroidization”).

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15
Q

Immunofluorescence (IF) stains are used to highlight what processes? Examples?

A

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
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16
Q

What is seen here?

A

Linear GBM staining, IgG

  • “Linearly” green
  • Typically seen in anti-GBM disease (evenly distributed along basement membrane)
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17
Q

What is seen here?

A

Mesangial staining

  • SLE (could be IgA, IgG…)
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18
Q

Electron microscopy is necessary to detect what types of abnormalities?

A
  • 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
19
Q

What is seen here?

A
  • 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

20
Q

What is seen here?

A

Effaced foot processes

  • Can see endothelial cell nucleus protruding into cap lumen
  • Foot processes look like “melted Hershey kisses”)
21
Q

What is seen here?

A

Viral (BK) particles

  • Commonly seen in kidney biopsies in transplant population
22
Q

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?

A

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.
23
Q

What are nephrotoxic drugs associated with ATN?

A
  • Aminoglycosides
  • Contrast agents

…

24
Q

Case 1 cont’d)

For the pt with ischemic injury 2ndary to severe/prolonged renal hypoperfusion causing acute renal failure

A

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
25
Q

What is seen here?

A
  • 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)
26
Q

What is seen here?

A

Left arrow: can see tubule completely sloughed of cells; BM still attached (could recover)

27
Q

What is seen here? Significance?

A

Mitotic figure indicates that cells were alive and time of observed changes

28
Q

What is seen here?

A

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
29
Q

Case 1 cont’d)

For the pt with ischemic injury 2ndary to severe/prolonged renal hypoperfusion causing acute renal failure in electron microscopy?

A

A tubule showing necrosis of some of the epithelial cells and center tubule consisting of mostly residual basement membrane only

30
Q

What is seen here?

A

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
31
Q

Case 1 cont’d)

What would you expect to see in glomerular and vascular compartments in this patient?

A

They are normal

32
Q

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?

A

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.
33
Q

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?
A

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.
34
Q

Case 2 cont’d)

What is the indication for renal biopsy in this pt?

A

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.
35
Q

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.
A

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).
36
Q

What is seen here?

A

Acute tubulointerstitial nephritis

  • Interstitial edema and inflammation
  • Nonspecific acute tubular cell injury
  • Those bright red/pink cells are eosinophils
37
Q

What is seen here?

A

Acute tubulointerstitial nephritis

  • Interstitial edema and inflammation
  • Nonspecific acute tubular cell injury
  • A few eosinophils are seen; quite a few lymphocytes
38
Q

What is seen here?

A

Acute tubulointerstitial nephritis

  • Severe interstitial inflammation
  • A few eosinophils are seen
39
Q

Case 2)

What do you see on EM?

A

This shows a tubule with infiltration of the tubular epithelium by inflammatory cells (lymphocytes)

40
Q

What is seen here?

A

Tubulitis characterized infiltration of tubular epithelium by inflammatory cells.

41
Q

Case 2 cont’d)

What do you see in glomeruli?

A

They are normal in tubulointerstitial nephritis

42
Q

What is seen here?

A

Normal glomerulus

43
Q

What is the treatment and prognosis of this pt (Allergic acute tubulointerstitial nephritis)?

A

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.

MS2 Renal (25 decks)

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