Flashcards in Renal Pathology- Warren Deck (147):
What nephrotoxic cause of ATN will you see oxalate crystals?
What are 2 types of ATN?
What are causes of nephrotoxic ATN?
Crush injury (myoglobin)
Urate (from tumor lysis syndrome)
Normal BUN: Cr ratio?
What kind of casts do you see in ATN?
Brown, granular casts
What kind of nephritis do NSAIDs, penicillin, and diuretics cause?
Acute Interstitial Nephritis (connective tissue between tubules)
What is found in the urine in Acute Interstitial Nephritis?
Eosinophils! High yield
Name one pharmacological cause of renal papillary necrosis.
Chronic analgesic abuse
What major protein is lost in nephrotic syndrome?
Why do patients with nephrotic syndrome develop a hypercoaguable state?
They lose Antithrombin III
Why do patients with nephrotic syndrome get hyperlipidemia and hypercholesteremia?
Liver reacts by throwing excess fat into the blood because the blood gets "thin"
What is the most common cause of nephrotic syndrome in kids?
Minimal change disease
What can Minimal change disease be associated with?
Hodgkin Lymphoma (massive overproduction of cytokines from Reed Sternberg cells)
What do you lose in MCD?
Foot processes flatten/efface because of cytokine production
What histology hallmark is present in MCD?
NORMAL Glomeruli on H&E stain
EFFACEMENT of foot processes on EM
What is the only protein lost in MCD?
(don't lose immunoglobulin)
What holds together lobules of the glomerulus?
What is the most common cause of Nephrotic syndrome in Hispanics and African Americans?
FSGS: Focal Segmental Glomerular Sclerosis
What can FSGS be associated with?
Sicke Cell Disease
What does "segmental" mean in FSGS?
Only a single part of the glomerulus will be involved
What does "focal" mean in FSGS?
Only some of the glomeruli in the kidney will be involved
FSGS is the progression of what disease if it doesn't respond to steroids?
Minimal Change Disease
Does FSGS respond to steroids?
No...progreses to Chronic renal failure
Most common cause of nephrotic syndrome in caucasian adults?
Causes of Membranous Nephropathy?
SLE-->most common cause of death is renal failure!
Usually patients with SLE don't present with nephrotic syndrome, but if they do, what is it?
What is happening in Membranous Nephropathy histologically?
Glomerular basement membrane becomes really thick!
Why does the membrane become thick in Membranous Nephropathy?
Immune complex deposition
Where is the immune complex deposition in Membranous Nephropathy?
Right under the podocytes (epithelial cells)
How do podocytes respond to immune complex deposition?
Try to lay down more basement membrane!
What is the EM description of membranous nephropathy?
Spike and dome subepithelial deposits
What do you see in Membranoproliferative Glomerulonephritis?
Thick capillary membranes on H and E with "tram track appearance" due to Immune complex deposition
What are the 2 types of Membranoproliferative glomerulonephritis based upon?
Location of deposits
What are the 2 types of Membranoproliferative glomerulonephritis?
Why are there neutrophils in nephritic syndrome?
Inflammation is driven by immune complexes which activate complement. A byproduct of this is C5a--these attract neutrophils which mediate damage.
What are RBC casts a sign of?
What virulence factor of some Group A Beta hemolytic streps increase the changes of PSGN?
M protein! This defines nephritogenic strains
When does PSGN usually occur?
2-3 weeks post infection
Is PSGN nephritic or nephrotic?
What do you see on EM in PSGN?
What is RPGN histology?
Crescents! Made of Fibrin and macrophages --Inflammatory Debris
What disease have positive p-ANCA?
Most common nephropathy worldwide?
Where do IgA complexes like to deposit?
What is Alport Syndrome?
Inherited Defect in Type IV collagen that results in thinning and splitting of GBM
What is the genetics of Alport Syndrome?
What does Alport syndrome present as?
Sensory hearing loss
How is polycystic kidney disease inherited?
Infant from - autosomal recessive
Adult form - autosomal dominant
What are two things associated with the autosomal recessive form of polycystic kidney disease?
Congenital hepatic fibrosis
What three things are associated with the autosomal DOMINANT form of polycystic kidney disease? (adult form)
mitral valve prolapse
What genes are mutated in adult PKD? what do they code for?
APKD1 = encodes polycystin 1 = integral membrane protein
APKD2 = encodes polycystin 2 = Ca+ channel
What is medullary cystic kidney disease? (aka medullary sponge kidney)
Cysts in the MEDULLARY COLLECTING DUCTS
What is a gross feature that would distinguish PKD from medullary cystic kidney disease?
In PKD kidneys appear enlarged
In medullary the kidneys appear shrunken
What are the hallmarks of acute renal failure?
Severe decrease in renal function with in days
AZOTEMIA (increased BUN and creatinine)
How do you distinguish pre-renal azotemia and intrarenal azotemia?
Pre-renal will have BUN:Cr>15 (more BUN is getting reabsorbed)
Intra-renal will have BUN:Cr
What will you see in acute tubular necrosis?
BROWN granular casts
Inability to concentrate urine (urine osm
What cancer can minimal change disease be associated with?
Effacement of foot processes on EM
Selective loss of Albumin
Associated w/ Hodgkin's lymphoma
Minimal Change Disease
Large hypercellular glomeruli
Sub epithelial "humps"
Normal in children
Describe Type 1 RPGN
Anti-bodies to the basement membrane show a LINE on IF
Good pasture syndrome
Presents with hematuria, hemoptysis, in young adult males
Describe Type 2 RPGN
Immune complex depsoition
Usually PSGN or diffuse proliferative glomerulnephritis
Describe Type 3 RPGN
Negative IF (pauci-immune)
Wegener granulomatosis, microscopic polyangitiis, Churg-Strauss syndrome
What is the antigen in Anti-GBM glomerulonephritis?
NC1 - a component of the noncollagenous domain of Type IV collagen
What is the antigen in Membranous glomerulonephritis?
M-type phospholipase A2 receptor
What is a "planted antigen"?
Antigen is non-glomerular in origin, but is localized in the kidney
What do you see histologically in Acute Poststreptococcal GLomerulonephritis?
What does the EM of Acute Poststreptococcal Glomerulonephritis look like?
Subepithelial humps like a camel
Is Acute poststreptococcal glomerulonephritis nephritic or nephrotic?
How would you describe the urine in Poststreptococcal Glomerulonephritis?
When you look at a child with poststreptococcal glomerulonephritis, what is one striking thing you can see instantly?
What do you see histologically in Rapidly progressive GN?
How many of the glomeruli have crescents in Rapidly progressive GN?
Describe the immunofluorescence of Type I RPGN.
Linear deposits (anti-GBM)
Describe the Immunofluorescence of Type II RPGN.
Lumpy-bumpy pattern (immune complex mediated)
What is present in Type III RPGN?
P or C-ANCA
Is RPGN nephritic or nephrotic?
What is the most common nephrotic syndrome in kids?
Minimal Change Disease
In what disease do you see uniform, diffuse thickening of capillary walls and on silver stain you see "spikes"?
on IF, what are the granular deposits along the GBM in Membranous Glomerulonephropathy composed of?
IgG and C3
What disease has an increased incidence with Hodgkin's Lymphoma?
Minimal Change Disease
What can you use to tx Minimal Change Disease?
What do you see on EM in Minimal Change Disease?
Diffuse effacement of foot processes of the visceral epithelial cells (podocytes)
FSGS results from genetic abnormalities to what?
Nephrin and Podocin proteins
What type of FSGS has the worst prognosis?
What pathological condition is a mix between nephrotic and nephritic syndromes?
What appearance of Membranoproliferative GN do you see on silver stain?
"Tram-track" or double contour due to mesangial cell interposition into the GBM!
What is the pathogenesis of Type I MPGN?
Immune complex deposition with activation of classical and alternative complement pathways
What do you see on EM in Type I MPGN?
What is another name for Type II MPGN?
Dense Deposit Disease
Lamina densa of the GBM is ribbon-like and extremely electron dense due to deposits of unknown material
When do patients usually get Berger Disease?
following an upper respiratory, GI, or urinary tract infection
What is the triad in Alport Syndrome?
Sensorineural hearing loss
What is the genetics behind Alport Syndrome?
X-linked Dominant Inheritance
What is the mutation in Alport Syndrome?
Alpha 5 chain of Type 4 collagen
What GN is most likely to give you chronic GN?
Rapidly Progressive GN
How would you describe the IF staining for SLE?
"Full house" - stains with everything! So lots of immune components present
List the Nephritic syndromes we need to know!
"MIA DAR" Kinda dumb i know...but since there is an "i" we know they are nephritic
Acute Poststreptococcal GN
Diffuse Proliferative GN
Rapidly Progressive GN
List the 3 main nephrotic syndromes we need to know!
Minimal Change Disease
What are the other 2 general nephrotic syndromes?
What is the diagnostic lesion on LM for Diabetic GN?
What do you see under LM for amyloidosis?
Congo Red Stain
Most common cause of death in SLE patients?
Diffuse Proliferative Glomerulonephritis
Describe the pathogenesis of diabetic nephropathy
-high serum glucose leads to noneznymatic glycosylation of the vascular basement membranes
-Results in arteriolosclerosis, thickened GBM and increased mesangial matrix
When would you see Kimmelstiel Wilson nodules?
They are hyaline masses at the periphery of the glomerulus
What is the most common causes of acute renal failure? (and presents as acute loss of renal function)
Acute Tubular Necrosis
Describe the pathology of Acute Tubular Necrosis
-Tubular epithelial necrosis (due to ischemia or toxins)
-Sloughing of tubular cells into the lumen (obstruction leads to increased intratubular pressure and DECREASED GFR)
-Hyaline and granular casts
Interstitial edema and increased lymphocytes
-Toxic ATN may show specific changes (like calcium oxalate crystals in ethylene glycol ingestion)
How would you distinguish an acute from chronic nephritis?
Acute - many neutrophils and edema
Chronic- fibrosis and atrophy
What are you at increased risk for if you have vesicoureteral reflux?
When are the only two times you will really see any damage to the calyces?
and anlagesic nephropathy
Name 5 risk factors for acute pyelonephritis?
1. indwelling urinary catheter
2. urinary tract obstruction
3. Vesicourecteral reflux
4. Diabetes mellitus
When is onset of acute drug-induced interstitial nephritis after exposure to drug?
approx. 15 days
Acute Drug-induced interstitial nephritis is a mixture of what two types of hypersensitivities?
Type 1 (IgE mediated) and
Type 4 (delayed or T-cell mediated)
Why do you common see interstitial nephritis in multiple myeloma patients?
BENCE JONES proteinuria and cast nephropathy
Directly toxic to tubules!!!
Can combine with Tamm-Horsfall to cause obstructions
What is nephrosclerosis? Describe its pathogenesis.
The renal pathology associated with the sclerosis of renal arterioles and small arteries
-medial and intimal vessel thickening secondary to variety of factors
-Hyaline deposition in arterioles due to endothelial injury with extravasation of plasma proteins and increased basement membrane matrix
What is malignant nephrosclerosis?
Renal disease associated with malignant hypertension
What would a "flea bitten" appearance on the gross pathology of the kidney indicate?
What would you think if you saw and "onion-skin" appearance of a blood vessel?
hyperplastic arteriolosclerosis which involves thickening of vessel wall by hyperplasia of smooth muscle
It is a consequence of...
What are two possible causes of hypertension that is not responsive to HTN medications?
Renal Artery stenosis
Fibromuscular Dysplasia (young women)
Describe the pathogenesis of HUS/TTP
-endothelial cell injury
-Denuded endothelium reveals thrombogenic tissues
-Reduced prostaglanding I2 and NO
-Platelet activation and aggregation
What causes 75% of Typical/Classical HUS?
Verocytotoxin producing E. Coli 0157:H7
What four things could cause atypical HUS?
1. Antiphospholipid syndrome
3. Vascular renal diseases
4. Drug related
What is deficient in familial HUS?
Inhertited deficiency of the complement regulatory protein FACTOR H
-Factor H typically protects cells from uncontrolled complement activation
What is the defect in idiopathic TTP?
Due to an acquired or genetic defect in the protesase that cleaves large von Willebrand multimers
What is hydronephrosis? what is it usually caused by?
Distention/dilation of renal pelvis and calyces
Usually caused by urinary tract obstruction
Leads to compression and possible atrophy of renal cortex and medulla
Which gender is more likely to get urolithiasis? What is the peak ago of onset?
Men > women
20-30 years old
What are the four main types of stones?
Ammonium magnesium phosphate (struvite)
What causes struvite (ammonium magnesium phosphate) stones?
Caused by infection with urease + bugs that hydrolyze urea to ammonia (resulting in alkalinization of urine)
Commonly form staghorn calcuil
Which 3 organisms are urease + that can cause struvite stones?
What is the most common type of stone?
Which two types of stones appear radiopaque on x-ray?
Struvite (ammonium magnesium phosphate)
Which two types of stones appear radioucent on x-ray and precipitate at low pH?
Which stones have the coffin lid appearance?
Struvite (Ammonium magnesium phosphate)
Cystine stones are rare, what usually causes them?
Autosomal recessive condition in which cystine-reabsorbing PCT transporter loses function
Cystine is poorly soluble- thus stones form in urine
common in kids
What is an angiomyolipoma?
Bengin renal tumor composed of vessels, smooth muslce, and fat
Associated with Tuberus Sclerosis
What is an oncocytoma?
Benign renal epithelial cell tumor
Presents with painless hematuria, flank pain, and abdominal mass
What color is an oncocytoma on gross pathology?
What is most common primary renal malignancy?
Renal cell carcinoma
What is the most important risk factor for renal cell carcinoma?
Tobacco use (2x more incidence in smokers)
What is the classic triad for renal cell carcinoma?
(patients rarely present with all 3)
May also see fever, weight loss, or paraneoplastic sydnrome
What gene is deleted in renal cell carcinoma?
loss of VHL gene on chromosome 3
Acts as a tumor suppressor gene --> encodes a protein that is part of the ubiquitin ligase complex (which targets proteins for degradation)
Thus specific proteins that increase transcription and promote angiogenesis are not degraded
What is Von Hippel Lindau syndrome associated with?
Renal cell carcinoma
Autosomal dominant disorder
Associated with inactivation of the VHL gene leading to increased risk of renal cell carcinoma
What are the three subtypes of renal cell carcinoma?
Clear cell carcinoma (most common)
Where does renal cell carcinoma like to metastasizes to?
Lung or bone
"silent" cancer because commonly presents as a metastatic neoplasm!
Why do you sometimes see a left sided varicocele in renal cell carcinoma?
Invades the renal vein, and can block drainage of testicular vein
Then goes to the IVC and spreads hematogenously
Which renal neoplasm commonly causes paraneoplastic syndromes?
Renal cell carcinoma
What is the most common tumor of the urinary tract system?
Transitional cell carcinoma (urothelial carcinoma)
Usually arises in bladder
What is the number one risk factor for urothelial carcinoma?