Renal Pathology Flashcards
What is the most common cause of tubulointerstitial nephritis (TIN)?
Acute pyelonephritis
What changes can occur in the kidney if bacterial pyelonephritis is left untreated?
It will progress to chronic pyelonephritis, characterized by scarring and fibrosis –> thyroidization, and tubular atrophy. These changes lead to hypertension and renal failure.
What is this process called and what is it a result of?
Thyroidization of the kidney due to chronic pyelonephritis.
What the hell is the difference between tubulointerstitial nephritis (TIN) and acute interstitial nephritis/interstitial nephritis (AIN/IN)?
TIN is a general term for inflammation of the tubules or interstitium. AIN/IN is inflammation not caused by bacteria; usually caused by a hypersensitivity reaction to drugs.
Name the drugs that have the potential to cause what is seen in the photo. What is this disease called?
Intersitial nephritis - caused by penicillins (esp. methicillin), NSAIDs, sulfonamides
What is the cause of analgesic nephropathy? Briefly describe the pathogenesis of the disease and the morphological changes that occur in the kidney as a result.
Due to chronic use of acetaminophen + aspirin for >3 years.
Pathogenesis: NSAIDs inhibit COX, so there is no PGE2 synthesis by macula densa cells –> no vasodilation of the afferent arteriole to increase GFR.
Reduced blood flow due to an inability to make PGE2 and vasodilate ultimately leads to papillary necrosis.
Name four substances that have the potential to cause acute tubular necrosis (ATN).
Aminoglycosides, heavy metals, contrast dyes, myoglobin (from rhadbomyolysis)
Your patient has a slightly reduced GFR and they got a radiocontrast CT to evaluate renal function. They develop acute kidney failure. Biopsy shows the following. What is your Dx?
Acute tubular necrosis (ATN)
Can severe hypotension cause acute tubular necrosis?
Yeah
You have been managing a patient with resistant hypertension and note an increase in their serum creatinine. Check the pic. What is that called?
Hyalinosis
Describe two vascular changes in the kidneys that can occur in the setting of malignant hypertension (>180/120).
Fibrinoid necrosis (plasma proteins getting squeezed out of the arteriole) and onion skin lesions (intimal thickening and smooth m. and collagen proliferation).
Name the mutated genes and their corresponding chromosomes involved in autosomal dominant polycystic kidney disease (ADPKD).
PKD1 on chromosome 16
PKD2 on chromosome 4
Describe the morphological changes that occur in the kidneys of a patient with ADPKD.
Both kidneys become enlarged, with cysts that destroy the renal parenchyma
Name two major comorbidities associated with ADPKD.
- Berry aneurysms
- Polycystic liver disease
Is ADPKD common?
Yeah!
What is the genetic mutation involved in autosomal recessive polycystic kidney disease (ARPKD)? What is the typical outcome from this disorder?
PKHD1 fibrocystin gene mutation
Non-functioning kidneys in the fetus –> oligohydramnios –> lung hypoplasia and death
If fetus survives to birth, there is usually also congenital hepatic fibrosis needing a transplant.
Can patients with ESRD on prolonged dialysis develop a cystic kidney disease?
Yeah
Very simply, what is nephrotic syndrome?
Podocyte damage –> lots of proteins leak into the filtrate
Name four clinical findings suggestive of nephrotic syndrome.
1) Proteinuria –> 2) Hypoalbuminuria leading to 3) Edema
4) Hyperlipidemia cuz the liver thinks that will make up for the loss of protein
Name five differential diagnoses for nephrotic syndrome.
Glomerular-specific diseases:
- Minimal change disease
- Focal segmental glomerular sclerosis
- Membranous glomerulopathy
Systemic diseases:
- Diabetic nephropathy
- Lupus
Which glomerular disease is the most common cause of nephrotic syndrome in kids? How is it treated and what is usually the outcome?
Minimal change disease. Treat w/ steroids, typically resolves completely.
Describe the microscopic pathological changes of minimal change disease that can be seen on microscopy.
On light microscopy, shit looks normal.
On EM, you can see podocyte foot effacement (the feet look like they have coalesced).
Focal segmental glomerular sclerosis (FSGS) causes ________ syndrome clinically and is seen predominantly what patient population?
FSGS causes nephrotic syndrome and is seen mostly in black older teens and young adults
Describe the cellular pathological changes that occur in FSGS.
Podocytes get injured
Some podocytes die, exposing the underlying basement membrane.
Parietal epithelial cells reach out and attach to the exposed basement membrane.
Fibrosis ensues in these areas.
You see a 16 year old black patients who presents with sudden onset of 10 pound weight gain. On exam you note bilateral lower limb edema. You do a UA in the office and it shows 3+ proteinuria. Biopsy shows the following. What is at the top of your DDx?
FSGS
What is membranous glomerulopathy and what causes it?
Primary cause:
Auto-antibodies to PLA2-R on podocytes cause subepithelial injury –> proteinuria/nephrotic syndrome.
Secondary causes:
Malignancies
Drugs (penicillamine, captopril, gold, NSAIDs)
Lupus
Infections (HCV, HBV, syphilis, malaria)
What is the histopathological hallmark of membranous glomerulonephritis?
Thick capillary walls with subepithelial basement membrane spikes.
What is the leading cause of end-stage renal disease in the US?
Diabetic nephropathy
Name four histopathological changes seen in diabetic nephropathy.
- Basement membrane thickening
- Mesangial cell proliferation
- Arterial hyalinosis
- Nodular glomerulosclerosis aka Jimmy Kimmelstiel Wilson nodules
Your patient with diabetes now has what you suspect to be nephrotic syndrome. To confirm, you get a renal biospy that shows this. What are those things at the arrows? What does the patient have?
Kimmelstiel Wilson nodules. The patient has diabetic nephropathy causing nephrotic syndrome.
Name four clinical features of nephritic syndrome.
- Oliguria
- Hypertension
- Hematuria
- Azotemia
Describe the typical clinical scenario of post-streptococcal glomerulonephritis. Briefly describe the pathogenesis of the disease.
Happens roughly a week after infection with GAS (Strep. pyogenes). Immune complexes deposit in the glomeruli –> inflammation and glomerular capillary rupture –> hematuria
Name three tests you could get for a patient that you suspect has post-strep glomerulonephritis.
ASO titer will be elevated
UA will show hematuria
Urine microscopy will show RBC casts
What are two histopathological findings of post-strep glomerulonephritis?
Hypercellularity (inflammatory cell infiltrate) and subepithelial humps from immune complex deposition.
Name five potential causes of rapidly-progressing glomerulonephritis (RPGN).
- Post-strep (most common cause)
- Lupus
- IgA nephropathy
- Goodpasture syndrome (autoantibodies against the GBM)
- Pauci-immune (ANCA-associated)
What is the histopathological hallmark of RPGN?
Crescents: a proliferation of cells between the glomerular tuft and Bowman’s capsule as well as deposition of fibrin in Bowman’s space due to rupture of glomerular capillaries.
What is P-ANCA and what diseases is it associated with?
What about C-ANCA?
P-ANCA:
peri-nuclear ANCA against myeloperoxidase
Churg-Strauss syndrome and Microscopic polyangiitis
C-ANCA:
cytoplasmic ANCA against PR-3 (proteinase 3)
Granulomatosis with polyangiitis (Wegener’s)
Why do some diseases preferentially affect both the lungs and kidneys? Name six such diseases.
These organs use similar proteins in their basement membranes, so in systemic diseases damage to both organs occurs.
- Goodpasture’s syndrome (anti-GBM syndrome)
ANCA-associated:
- Granulomatosis with polyangiitis (Wegener’s)
- Microscopic polyangiitis
- Eosinophilic polyangiitis (Churg-Strauss syndrome)
Immune complex:
- Lupus
- Henoch-Schonlein Purpura
What specifically causes Goodpasture syndrome? How does it manifest clinically? Name two histopathologic findings.
Auto-antibody against the alpha-3 subunit against type IV collagen, expressed in the BM of the lungs and kidneys.
Clinical manifestations:
Pneumonitis with hemoptysis
RPGN
Histopathology:
Crescentic morphology
Linear immunofluorescence
What causes Alport syndrome? How does it manifest clinically?
Mutation in type 4 collagen gene (COL4A5)
Clinical manifestations:
Nephritic syndrome
Hearing loss
Problems with the lenses of the eyes
