Renal- Pathology Flashcards
Note that the presence of casts in urine indicates that hematuria/pyuria is of glomerular or renal tubular origin
Bladder cancer, kidney stones- no casts, hematuria present
Acute cystitis- pyuria, no casts
When are RBC casts seen in urine?
Glomerulonephritis, malignant HTN
When are WBC casts seen in urine?
tubulointerstitial inflammation, acute pyelonephritis, transplant rejection
When are fatty casts seen in urine?
nephrotic syndrome
When are granular (muddy brown) casts seen in urine?
Acute tubular necrosis
When are waxy casts seen in urine?
ESRD/chronic renal failure
When are hyaline casts seen urine?
nonspecific, can be a normal finding, and often seen in concentrated urine samples
What is focal glomerular disease?
less than 50% of glomeruli involved (e.g. focal segmental glomerulosclerosis)
diffuse= 50+%
“Membranous” renal disease means what?
thickening of the glomerular basement membrane (e.g. membranous nephropathy)
Describe nephritic syndrome
an inflammatory process that leads to disruption of the GBM. When it involves the glomeruli, it leads to hematuria and RBC casts in the urine
What are the other signs of nephritic syndrome?
HTN (due to salt retention)
elevated BUN and creatine
oliguria
proteinuria often in the subnephrotic range (less than 3.5g/day) but can be worse
What diseases fall under the umbrella of nephritic syndrome?
Acute poststreptococcal glomerulonephritis
Rapidly progressive glomerulonephritis
IgA nephropathy (Berger disease)
Alport syndrome
Membranoproliferative glomerulonephritis
Describe Acute poststreptococcal glomerulonephritis
acute disease seen commonly in children, appearing ~2 weeks after a group A strep infection of the pharynx or skin (resolves spontaneously), and caused by deposition of immune complexes in the kidneys (Type III hypersensitivity)
What is this?
Acute poststreptococcal glomerulonephritis, marked by enlarged and hypercellular glomeruli
Acute poststreptococcal glomerulonephritis with the classic ‘starry sky’ granular appearance. What causes this?
due to IgG, IgM, and C3 deposition along the GBM and mesangium
Below: EM showing classic subepithelial humps
What additional lab findings are seen in acute poststreptococcal glomerulonephritis?
elevated anti-DNase B titers
decreased complement levels
How does acute poststreptococcal glomerulonephritis present?
nephritic syndrome
peripheral and periorbital edema
cola-colored urine and HTN
Describe rapidly progressive (cresentic) glomerulonephritis (RPGN)
Onset of rapidly deteriorating renal function (days to weeks) (poor prognosis) that can be seen in Goodpasture syndrome, microscopic polyangiitis, and granulomatosis with polyangiitis (Wegener)
What is Goodpoasture syndrome?
type II hypersensitivity with Abs to GBM and alveolar basement membrane (linear IF-below)
What is the classic appearance of RPGN in LM?
crescent moon shape formation (consists of fibrin and plasma proteins (e.g. C3b) with glomerular parietal cells, monocytes, and macrophages
What ANCA is associated with Wegener?
PR3-ANCA (aka c-ANCA)
What ANCA is associated with Microscopic polyangiitis?
MPO-ANCA (p-ANCA)
Diffuse proliferative glomerulonephritis (DPGN)
due to SLE and membranoproliferative glomerulonephritis (most common cause of death in SKE)
often presents as nephrotic and nephritic syndrome concurrently
IgA nephropathy findings on LM, IF, and EM
LM- mesangial proliferation
EM- mesangial IC deposits
IF- IgA based IC deposits in mesangium
What causes Alport syndrome?
mutation in type IV collagen causing thinning and splitting of glomerular basement membrane (most commonly X-linked)
How does Alport syndrome present?
eye problems (e.g. retinopathy, lens dislocation), glomerulonephritis, and sensorineural deafness
Describe Type I membranoproliferative glomerulonephritis (MPGN)
tram track appearance on PAS stain and HE stain due to GBM splitting caused by mesnagial ingrowth (below)
due to subendothelial immune complex (IC) deposits with granular IF
What are some associations of Type I membranoproliferative glomerulonephritis (MPGN)
secondary to hep B or C (may also be idiopathic)
What are some associations of Type II membranoproliferative glomerulonephritis (MPGN)?
C3 nephritic factor (stabilizes C3 convertase and decreases serum C3 levels)
Describe the findings of nephrotic syndrome
massive proteinuria (3.5+g/day) with
hypoalbuminemia, resulting edema, hyperlipidemia
frothy urine with fatty casts
What causes nephrotic syndrome?
podocyte damage disrupting the gomerular filtration charge barrier
May be primary (direct sclerosis of podocytes) or 2ndary to a systemic process (e.g. diabetes)
Note that sever nephritic syndrome may present with nephrotic syndrome features if damage to the GBM if severe enough to damage the charge barrier (e.g. MPGN)
Nephrotic syndrome is associated with a hypercoaguable state. How?
due to loss of antirhrombin (AT) III in urine and increased risk of infection due to loss of immunoglobulins in urine and soft tissue compromise by edema
What disease present with nephrotic syndrome?
Focal segmental gomerulosclerosis
Minimal charge disease
Membranous nephropathy
Amyloidosis
Diabetic glomerulonephropathy
What dis?
focal segmental glomerulosclerosis LM showing segmental sclerosis and hyalinosis
What does focal segmental glomerulosclerosis IF show?
nonspecific for focal deposits of IgM, C3, and C1
What does focal segmental glomerulosclerosis EM show?
effacement of foot processes (similar to minimal change disease)
Describe focal segmental glomerulosclerosis
the most common cause of nephrotic syndrome in AAs and Hispanics. Can be primaru or 2ndary to other conditions (e.g. HIV, SCD, heroin abuse, massive obesity, interferon tx, or chronic kidney disease due to congenital malformations)
What is this EM showing?
Foot process effacement in Minimal change disease
Note the MCD has a normal LM and a negative IF
Describe minimal change disease
This is the most common cause of nephrotic syndrome in children. Often primary and may be triggered by recurrent infection, immunization, and immune stimulus
Minimal change disease may rarely be 2ndary to what?
lymphoma (e.g. cytokine-mediated damage)
Tx difference between Minimal change disease and focal segmental glomerulosclerosis
MCS has a great response to steroids, while FSG doesn’t
What is this?
Membranous nephropathy LM marked by diffuse capillary and GBM thickening
Buzzword EM of Membranous nephropathy
‘Spike and dome’ with subEPIthelial deposits
Describe Membranous nephropathy
most common cause of primary nephrotic syndrome in Causasian adults. Can be primary (idiopathic) or 2ndary to other conditions such as Abs to phospholipase A2 receptors, drugs, and infections
primary disease has POOR reponse to steroids
What drugs have been shown to cause Membranous nephropathy?
NSAIDs, penacillamine
What infections have been shown to cause Membranous nephropathy?
HBV
HCV
SLE
solid tumors
What would a positive LM of amyloidosis show?
apple-green birefringence under polarized light
What is the most commonly affected organ in amyloidosis?
the kidneys
Amyloidosis is associated with what diseases?
chronic conditions (e.g. multiple myeloma, TB, and rheumatoid arthritis)
What are these?
Kimmelstein-Wilson lesioons seen in diabetic glomerulonephropathy
What are some of the major complications of kidney stones?
hydronephrosis and pyelonephritis
How do kidney stones present?
unilateral flank pain, colicky pain radiating to the groin, hematuria
encoruage fluid intke to tx and prevent
What are the major forms of kidney stones?
- Calcium (80%)
- Ammonium magnesium phosphate (15%)
Uric Acid (5%)
Cysteine (1%)
Describe calcium stones
precipitate at high (calcium phosphate) or low pH (calcium oxalate)
Radiopaque on X-ray
Envelope shaped stones
Oxalate crystals can result from what?
ethylene glycol (antifreeze) ingestion, vitC abuse,
hypocitraturia
malabsorption (e.g. Crohn disease)
How are calcium stones tx?
hydration, thiazides, and citrate
Describe ammonion magnesium phosphate stones (aka struvite stones)
precipitate at high pH
radiopaque on xray
coffin lid apperance
What causes struvite stones?
infection with urease +bugs (e.g. Proteus mirabalis, Stap sapro, Klebsiella) that hydrolyze urea to ammonia resulting in alkaline urine
What kind of stone is this?
Rhomoid crystals seen in uric acid stones
radioLUCENT on xray
Describe uric acid stones
strong association with hyperuricemia (e.g gout). Often seen in disease with increased cell turnover, such as leukemia
tx: alkalize urine (these form/precipitate at low pH), allopurinol
What are these?
Hexagonal shaped cysteine stones (precipitate in low pH)
radioLUCENT
Describe cysteine stones
hereditary (AR) condition in which cystine-resborbing PCT transporter loses function, causing cystinuria. Cystine is poorly soluble, thus stones form in urine.
Mostly seen in children
Cysteine stones are positive for what test?
Sodium cyanide Nitroprusside
What is hydronephrosis?
distention/dilation of the rena pelvis and calyces usually as a result of urinary tract obstruction (e.g. renal stones, BPH, cervical cancer, retroperitoneal fibrosis, vesicuretal reflux)
Serum creatinine becomes elevated only if the obstruction is bilateral or if the pt has only one kidney
What is the most common primary renal malignancy?
renal cell carcinoma
Where do renal cell carcinomas originate from?
originates from PCT cells, producing polygonal clear cells filled with accumulated lipids and carbs
Describe renal cell carcinomas
- most common in men 50-70 yo
- increased incidence with smoking and obesity
How do renal cell carcinomas present?
hematuria
palpable mass
secondary polycythemia
flank pain
fever, weight loss
Where do renal cell carcinomas MET to?
invades renal vein then IVC and spreads via heme to LUNG and BONE
What mutations are associated with renal cell carcinomas?
gene deletion on chromosome 3 (sporadic or inherited as von Hippel-Lindau syndrome)
RCC-3 letters= chromsome 3
Associations of renal cell carcinomas
paraneoplastic syndromes (e.g. ectopic EPO, ACTH, and PTHrP)
How are renal cell carcinomas tx?
resection if localizzed
immunotherapy or targeted therapy for advanced/METs
resistant to chemo and radiation therapy
Describe renal oncocytomas
Benign epithelial cell tumor (well-circumscribed mass with a central scar-below) that commonly present with painless hematuria, flnak pain, and/or an abdominal mass
What dis?
Renal oncocytoma showing round to polygonal shaped cells with granular eosinophilic cytoplasm and round nuclei (right)
left- normal
What is the most common renal malignancy of early childhood (2-4 yo)?
Wilm’s Tumor
What causes a Wilm’s Tumor?
loss of function mutations of tumor suppressot genes WT1 or WT2 on chromosome 11
What is Beckwith-Wiedemann syndrome?
Wilm’s tumor
macroglossia (big tongue)
organomegaly
hemihypertrophy
What is WAGR complex?
Wilm’s Tumor
Aniridia
Genitourinary malformation
mental Retardation
What is Aniridia
the absence of the iris, usually involving both eyes. It can be congenital or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a panocular condition with macular and optic nerve hypoplasia, cataract, and corneal changes.
What is the most common tumor of the urinary tract (can occur in renal calyces, renal pelvis, ureters, and bladder)?
Transitional cell carcinoma
What things are associated with Transitional cell carcinoma?
Pee SAC
Phenacetin
Smoking
Aniline Dyes
Cyclophosphamide
Describe the progression of squamous cell carcinoma of the bladder
chronic irriation of the urinary bladder causes squamous metaplasia, which can evolve to dysplasia and eventually squamous cell carcinoma
What are the main risk factors for squamous cell carcinoma of the bladder?
Schistoma haematobium infection (Middle east, chronic cystitis, smoking, chronic nephrolithiasis)
presents with painless hematuria
How does a UTI present?
presents as suprapubic pain, dysuria, urinary frequency, urgency
can have systemic signs of high fever, chills if ascends to the kidneys but usually absent in normal cases
What are the risk factors for a UTI?
- female (short urethra)
- Sex
- indwelling catheter
- diabetes mellitus
- impaired bladder emptying
What are the most common causes of UTIs?
E. Coli (most common)
Staph sapro- seen in active young women
Klebsiella
Proteus Mirabilis (urine has ammonia scent)
How is a UTI diagnosed?
- positive leukocyte esterase
- nitrites for gram-negative organisms (E. Coli)
- Sterile pyuria and negative urinary cultures suggest urethritis by Neisseria gonorrhoeae or Chlamydia trachomatis
Describe acute pyelonephritis
Usually due to ascending UTI and presents with fever, flank pain (positive CVAT test)
What are the main histo findings of acute pyelonephritis?
neutrophils infiltrating the renal interstitium (affects the cortex with relative sparing of the glomeruli and vessels)
What are the main complications of acute pyelonephritis?
chronic pyelonephritis
renal papillary necrosis
perinephric abscess
urosepsis
What is the classic histo finding of chronic pyelonephritis?
thyroidization of kidney tubules
Describe drug-induced interstitial nephritis (tubulointerstitial nephritis)
acute interstitial renal inflammation resulting in pyuria (classically eosinophils) and azotemia occurring after administration of drugs that act as haptens, inducing hypersensitivity
Nephritis typically occurs 1-2 weeks after certain drugs (but can occur months later)
What are some common causes of drug-induced interstitial nephritis (tubulointerstitial nephritis)?
diuretics
penicillin derivatives
PPIs
sulonamides
rifampin
How does drug-induced interstitial nephritis (tubulointerstitial nephritis) present?
can occur with fever, rash hematuria, and CVAT but can also be aymptomatic
What is diffuse cortical necrosis?
acute generalized cortical infarction of both kidneys likely due to a combo of vasospasm and DIC (associated with obstetric problems like aruptio placentae and septic shock)
What is the most common cause of acute kidney injury in hospitalized pts?
acute tubular necrosis (spontaneously resolves in most cases, but can be fatal, especially during the initial oliguric phase)
What are the stages of acute tubular necrosis?
- Inciting event
- Maintenance phase (oliguric- last 1-3 weeks; risk of hyperkalemia, metabolic acidosis, and uremia)
- Recovery phase (polyruic; BUN and creatinine fall; risk of hypokalemia)
What are these?
‘Muddy brown’ casts seen in ATN
ATN can be caused by ischemic or nephrotoxic injury. Explain these.
Ischemic- 2ndary to decreased renal BF (e.g. hypotension, shock, sepsis, hemorrhage, HF). Results in death of tubular cells that may slough into the tubular lumen (PCT and thick ascending limb are highly susceptible to injury due to active processes here)
Nephrotoxic- 2ndary to injury resulting from toxic substances (e.g. aminoglycoaides, radiocontrast agents, lead, cisplatin), crush injury (myoglobinuria), hemoglobinuria (PCT is susceptible)
What is this?
Renal Papillary necrosis, the sloughing of necoritc renal papillae causing gross hematuria and proteinuria
What are some triggers of renal papillary necrosis?
may be triggered by recent infrction or immune stimulus
associated with SCD or trait, acute pyelonephritis, NSAIDs, and DM
Mnemonic for renal papillary necrosis
SODA:
Sickle cell disease of trait
Obstruction (acute pyelonephritis)
Diabetes Mellitus
Opiates (analgesics)
Define acute kidney injury (acute renal failure)
an abrupt decline in renal function as meaured by increasing creatinine or BUN
What are the main categories of causes of acute kidney injury (acute renal failure)?
Prerenal azotemia
Intrinsic renal failure
Postrenal azotemia
Describe Prerenal azotemia
Due to decreased RBF (e.g. hypotension) resulting in decreased GFR. Na/H2O and BUn are retained in the kidney in an attempt to conserve volume causing an abrupt rise in the BUN/creatinine ratio (BUN is reabsorbed, creatinine is not)
Describe Intrinsic renal failure
generally due to acute tubular necrosis or ischemia/toxins, and less commonly due to acute glomerulonephritis (e.g. RPGN, HUS)
In ATN, patchy necrosis results in dbris obstructing the tubule and causing fluid backflow across the necrotic tubule (decreased GFR)
T or F. In Intrinsic renal failure, the BUN/creatinine ratio will be decreased
T. Bun reaborption is impaired
What causes psotrenal azotemia?
due to outflow obstruction (stones, BPH, neoplasia, etc.) Only develops with bilateral obstruction
What are the:
1) Urine osmolarity (mOsm/kg)
2) urine Na+ (mEq/L)
3) FENa
4) Serum BUN/Cr
findings of Prerenal azotemia
1) 500+
2) less than 20
3) less than 1%
4) 20+
What are the:
1) Urine osmolarity (mOsm/kg)
2) urine Na+ (mEq/L)
3) FENa
4) Serum BUN/Cr
findings of Intrinsic renal failure
1) less thn 350
2) 40+
3) 2+%
4) less than 15
What are the:
1) Urine osmolarity (mOsm/kg)
2) urine Na+ (mEq/L)
3) FENa
4) Serum BUN/Cr
findings of Postrenal azotemia
1) less than 350
2) 40+
3) 1+% (mild); 2+% (severe)
4) Varies
What are the consequences of renal failure?
MAD HUNGER
Metabolic Acidosis
Dyslipidemia (especially elevated TAGs)
Hyperkalemia
Uremia
Na/H2O retention (HF, pulmonary edema, HTN)
Growth retardation and developmental delay
EPO failure (anemia)
Renal osteodystrophy
How does uremia present?
elevated BUN
Nausea and anorexia
Pericarditis
Asterixis
Encephalopathy
Platelet dysfunction
What is renal osteodystrophy?
failure of vitD hydroxylation, hypocalcemia, and hyperphosphatemia resulting in 2ndary hyperPTHism. Causes subperiosteal thinning of bones
What are the 4 major renal cyst disorders?
- ADPKD
- ARPKD
- Medullary cystic disease
- Simple vs complex renal cysts
Describe ADPKD (formerly adult polycystic kidney disease)
the formation of the numerous cysts causing bilaterally enlarged kidneys and ultimately destroying kidney parenchyma
What causes ADPKD?
AD mutation in PKD1 (85% of cases, chromosome 16) or PKD2 (15%, chromosome 4)
How can ADPKD cause death?
complications of chronic kidney disease or HTN (caused by increased renin production)
How does ADPKD present/
flank pain, hematuria, HTN, unirary infection, and progressive renal failure
What are some associations with ADPKD?
berry aneurysms, mitral valve prolapse, benign hepatic cysts
Describe ARPKD (formerly infantile PKD)
AR disease presenting in infancy associated with congenital keptic fibrosis and resulting in significnat oliguric renal failure in utero (can lead to Potter sequence)
Concerns beyond neonatal period include systemic HTN, progressive renal failure, and portal HTN from the fibrosis
What is medullary cystic disease?
Inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine (poor prognosis)
kidneys are shrunken on ultrasound
Complex cysts require removal for risk of what?
progression to renal cell carcinoma
