14 - Glomerular Disease Pathology I Flashcards
What are the disease we will cover in these two lectures?
- Congenital
- Cysts
- Pathology terms
- Glomerular
- Tubular/interstitial
- Tumors
We will focus on glomerular disease - the “meat” of these lectures
Tubular/interstitial disease is less important, but tumors are very important
What are the four congenital disease?
- Agenesis
- Hypoplasia
- Ectopic kidney
- Horseshoe
What is agenesis?
- Kidney fails to differentiate
- Most commonly bilaterally
- Incompatible with life if bilateral
- Enlarged adrenals
Agenesis = failure of kidney to grow
What is hypoplasia?
- Failure of kidneys to develop to a normal size
- This is more commonly UNILATERAL
- This is compatible with life if unilateral
What is an ectopic kidney?
- Usually located in the pelvic region
- Usually just above the pelvic brim
- Usually normal (or slightly small)
- Kinking or tortuosity of the ureters may occur, causing obstruction and predisposing to infection (and even stone formation)
- The problem is that infections and stones will be recurrent **
- If you have recurring infections or stones, you NEED to figure out what the problem is - EMPHASIZED ***
What is a horseshoe kidney?
- Does not need surgery
- The kidneys are connected in a horseshoe shape
- Unless there are infections or stones, there is no intervention needed
- There is some blocking effect of the ureters, but not as severe as the ectopic kidney
What are renal cysts?
- There are several causes
- Most are just a single simple cyst
- You will see a lot of this in clinical practice - very common
What are the types of cystic disease?
- Autosomal Dominant (AD for ADults**)
- Autosomal recessive (CHILDREN ***)
- Acquired cystic disease (dialysis-associated, we don’t know why)
- Simple cysts
Describe autosomal dominant cystic disease
Autosomal dominant polycystic kidney disease (ADPKD)
- Seen in ADULTS
- Two genes (PKD1 and PKD2***)
- Complex genetics, but follows autosomal dominant pedigree
- You will see multiple expanding cysts in the kidney
- Eventually destroys the kidney, causes end stage renal disease (4th leading cause)
What will 1/3 of autosomal dominant cystic disease patients develop?
- 1/3 of patients will also have cysts on the liver, but they do NOT interfere with hepatic function
What will 10% of autosomal dominant cystic disease patients develop?
** EMPHASIZED **
- *****10% of patients will have a severe disease called BERRY ANEURYSMS
- The berry aneurysm is located in the circle of Willis in the brain which can rupture and cause a FATAL subarachnoic hemorrhage *****
Describe the renal functional decline seen in ADPKD patients
- Renal function is related to the increase in kidney size and cystic volume
- In the beginning, the size is small and the renal function is normal
- Once more than 2/3 of the kidney is destroyed, the renal function will begin to decline
- The progression will be rapid at an exponential rate
Describe the morphology of ADPKD
- Kidneys will be grossly enlarged
- Polycystic appearance on the surface (dark due to blood)
- Both right and left kidney affected
- Each kidney will measure 30 cm in length (VERY large)
- Normal = 12 cm length, 6 cm width, 3 cm depth
- The kidneys are more than doubled in size
- NO recognizable normal kidney tissue
Describe Autosomal Recessive Polycystic Kidney Disease (ARPKD)
- CHILDHOOD disease
- Less important than ADPKD
- You will see huge, white, SMOOTH-surfaced kidneys at birth
- Cysts of 1-2 mm in diameter will develop from the collecting ducts
- This is associated with congenital hepatic fibrosis
- Remember, ADPKD is associated with other cysts (liver, pancreas, spleen) but this is associated with fibrosis
Describe simple cysts
- Cortical cysts
- Very, very, very common
- Also called “retention” cysts
- Can also be “acquired”
- Incidentally found (we don’t go looking for these), asymptomatic (not generally clinically significant)
- Tell patient they should NOT worry
- Only need to be concerned when there are more than 5 cysts or 5 mm cysts
- Can break open and you can feel pain, but still no concerning
Now we will discuss pathology terms of renal pathology
This can be complicated, so pay attention
What are the 3 assessment modalities for renal biopsy
- Light microscopy (LM)
- Immunofluorescence (IF) microscopy
- Electron microscopy (EM)
When you get a renal biopsy, these are the three things that they will do - NEED TO DO ALL OF THESE *** (or you could miss something!)
In our lectures, you need to understand the changes we will see in light microscopy
MOST kidney disease involves immunologic, so that’s why we do IF microscopy
We need electron microscopy because some diseases cannot be found in the other two types (minimal changes in nephrotic syndrome - everything would look normal in the other two) * THIS IS CRITICAL*
For each disease we cover, know what it looks like in the LM, IF and EM - VERY IMPORTANT
Describe the anatomy of a glomerulus
- The “heart” of the nephron
- Glomerular is encapsulated by the Bowman’s capsule
- Inside the Bowman’s capsule is the urinary space
- There is a vascular pole at the bottom and the tubular pole at the top
- Inside the capillary we see the mesangium (contains matrix material and cells - endothelial cells in capillaries)
- BOWMAN’S CAPSULE EMPHASIZED (epithelial cells are found here)
What is VERY important to know about the image on slide
- If you want to understand kidney pathology, you need to understand this image
- In the center of this image we see mesangial cells and the mesangial matrix
- The outside is the parietal epithelial cells
- The inside is visceral epithelial cells which produce the FOOT PROCESSES
- Foot processes are normal, if you don’t have them you have a disease
- There are large pores or fenestrae in the endothelium
- KNOW WHERE THE CELLS ARE LOCATED ***
What does focal mean?
A localized problem, less than 50% of the glomeruli are involved
What does diffuse mean?
The whole kidney is involved, more than 50% of the glomeruli are involved
What does global mean?
Need to zoom in to look at only one glomeruli… The whole glomerulus is involved
Does NOT mean all of the glomeruli are involved, just that when they are involved, the entire glomeruli is involved
What does segmental mean?
Need to zoom in to look at only one glomeruli… Only a portion of each glomeruli is involved
One “segment” of a the glomeruli is involved
What does primary disease mean?
Renal problem
What does secondary disease mean?
Systemic problem
What does idiopathic disease mean?
Unknown etiology
What are the three patterns of imunoflourescence (IF) staining we see in glomerulus staining?
- Linear loop pattern
- Granular capillary loop pattern
- Mesangial pattern
What does linear loop pattern indicate?
Anti-GBM disease
What does granulary capillary loop pattern indicate?
Membranous nephropathy or lupus nephritis
What does mesangial pattern indicate?
IgA nephropahty or lupus nephritis
Describe the immune components that are screened for in a renal biopsy?
FINISH SLIDE **
THe renal biopsy is routinely stained for immunoglobins G, A and M and complemnts C3
FINISH SLIDE **
What else do we call the glomerular epithelial cells?
The glomerular epithelial cell is also called a PODOCYTE *** because they have foot processes (podi = greek for foot)
What are the possible pathogenesis of immune-mediated renal disease?
- Antibodies against native GBM (glomerular basement membrane)
- Antibodies against “planted” antigens
- Trapping of Ag-Ab complexes
- Antibodies against glomerular cells (mesangial cells, podocytes, etc.)
- Cell mediated immunity (sensitized T-cells as in TB)
What are immune mediators?
- Neutrophils, monocytes
- Macrophages, T-cells, NK cells
- Others
Not very important
What are the 3 main clinical renal syndromes?
- Acute renal failure (TUBULE injury in most cases, NOT glomerular problem)
- Nephrotic syndrome (severe proteinuria with GLOMERULUS injury)
- Nephritic syndrome (hematuria, blood in urine with GLOMERULUS injury)
