Renal- Phatology Flashcards
Casts in urine
- WBC casts
- Fatty casts (“oval fat bodies”)
- RBC casts
Tubulointerstitial inflammation, acute pyelonephritis, transplant rejection.
Nephrotic syndrome. Associated with “Maltese cross” sign.
Glomerulonephritis, hypertensive emergency
Casts in urine
- Granular (“muddy brown”) casts
- Waxy casts
- Hyaline casts
Acute tubular necrosis (ATN)
End-stage renal disease/chronic renal failure
Nonspecific, can be a normal finding, often seen in concentrated urine samples
Nomenclature of glomerular disorders
- Focal
- Diffuse
< 50% of glomeruli are involved
> 50% of glomeruli are involved
Nomenclature of glomerular disorders
- Proliferative
- Membranous
Hypercellular glomeruli
Thickening of glomerular basement membrane (GBM)
Nephritic syndrome
- Types
- Acute poststreptococcal glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger disease)
- Alport syndrome
- Membranoproliferative glomerulonephritis
Nephrotic syndrome
- Types
- Focal segmental glomerulosclerosis (1° or 2°)
- Minimal change disease (1° or 2°)
- Membranous nephropathy (1° or 2°)
- Amyloidosis (2°)
- Diabetic glomerulonephropathy (2°)
Minimal change disease (lipoid nephrosis)
- Epidemiology
- Etiology
- Electromicroscopy
Most common cause in children.
1° (idiopathic) and may be triggered by recent infection, immunization, immune stimulus.
EM—effacement of podocyte foot processes
Focal segmental glomerulosclerosis
- Epidemiology
- Etiology
Most common cause in African-Americans and Hispanics.
Can be 1° (idiopathic) or 2° (eg, HIV infection, sickle cell disease, heroin abuse, massive obesity, interferon treatment, or congenital malformations).
Focal segmental glomerulosclerosis
- Light microscopy
- Inmunofluorecence microscopy
- Electronic microscopy
LM—segmental sclerosis and hyalinosis
IF—often ⊝ but may be ⊕ for nonspecific focal deposits of IgM, C3, C1
EM—effacement of foot processes similar to minimal change disease
Membranous nephropathy (membranous GN)
- Etiology
- LM, IF, EM
1° (eg, antibodies to phospholipase A2 receptor) or 2° to drugs (eg, NSAIDs, penicillamine, gold), infections (eg, HBV, HCV, syphilis), SLE, or solid tumors.
LM—diffuse capillary and GBM thickening
IF—granular due to IC deposition
EM—“Spike and dome” appearance of subepithelial deposits
Amyloidosis
- Light microscopy
LM—Congo red stain shows apple-green birefringence under polarized light due to amyloid deposition in the mesangium
Diabetic glomerulonephropathy
- Light microscopy
LM—Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)
Mogensen classification of diabetic nephropathy
1: Increased GFR, renal hypertrophy
2: Onset of histological changes
3: Early clinical nephropathy
4: Overt nephropathy
5: Renal failure
Acute poststreptococcal glomerulonephritis
- Epidemiology
- Presentation
in children. ~ 2–4 weeks after group A streptococcal infection of pharynx or skin
Presents with peripheral and periorbital edema, cola-colored urine, HTN. ⊕ strep titers/serologies, low complement levels (C3) due to consumption.
Acute poststreptococcal glomerulonephritis
- Light microscopy
- Inmunofluorecence microscopy
- Electronic microscopy
LM—glomeruli enlarged and hypercellular
IF—(“starry sky”) granular appearance (“lumpy bumpy”) due to IgG, IgM, and C3 deposition along GBM and mesangium
EM—subepithelial immune complex (IC) humps
Rapidly progressive (crescentic) glomerulonephritis - LM
LM—crescent moon shape. Crescents consist of fibrin and plasma proteins (eg, C3b) with glomerular parietal cells, monocytes, macrophages
Rapidly progressive (crescentic) glomerulonephritis
- Linear IF due to antibodies to GBM and alveolar basement membrane:
- Negative IF/Pauci-immune (no Ig/C3 deposition):
- Granular IF:
Goodpasture syndrome—hematuria/hemoptysis; type II hypersensitivity reaction; Treatment: plasmapheresis
Granulomatosis with polyangiitis (Wegener)—PR3 ANCA/c-ANCA or Microscopic polyangiitis—MPO ANCA/p-ANCA
PSGN or DPGN
Diffuse proliferative glomerulonephritis
- Etiology
Often due to SLE (think “wire lupus”).
*DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently.
Diffuse proliferative glomerulonephritis
- Light microscopy
- Inmunofluorecence microscopy
- Electronic microscopy
LM—“wire looping” of capillaries
IF—granular;
EM—subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
IgA nephropathy (Berger disease)
- Etiology
- LM, IF, EM
Episodic hematuria that occurs concurrently with respiratory or GI tract infections
LM—mesangial proliferation
IF—IgA-based IC deposits in mesangium;
EM—mesangial IC deposition
Alport syndrome
- Mutation
- Clinical findings
- EM
Mutation in type IV collagen. XD
Eye problems (eg, retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness
EM—“Basket-weave”
Membranoproliferative glomerulonephritis
- Type I
Type I 2° to hepatitis B or C or idiopathic.
Subendothelial IC deposits with granular IF
Membranoproliferative glomerulonephritis
- Type II
associated with C3 nephritic factor
Intramembranous deposits, also called dense deposit disease
Membranoproliferative glomerulonephritis
- Both types
In both types, mesangial ingrowth GBM splitting “tram-track” appearance on H&E and PAS stains.
Kidney
stones
Pag. 582
Renal cell carcinoma
- Histology
- Clinical manifestations
Polygonal clear cells filled with accumulated lipids and carbohydrate. Often golden-yellow
Manifests with hematuria, palpable masses, 2° polycythemia, flank pain, fever, weight loss.
Renal cell carcinoma
- Epidemiology
- Paraneoplastic syndromes
- Mutation
Most common in men 50–70 years old.
Associated with paraneoplastic syndromes: PTHrP, Ectopic EPO, ACTH, Renin
Associated with gene deletion on chromosome 3
Renal oncocytoma
- Histology
- Clinical presentation
Benign epithelial cell tumor arising from collecting ducts. Large eosinophilic cells with abundant
mitochondria without perinuclear clearing
Presents with painless hematuria, flank pain, abdominal mass
Nephroblastoma (Wilms tumor)
- Epidemiology
- Histology
- Presentation
Most common renal malignancy of early childhood (ages 2–4).
Contains embryonic glomerular structures.
Presents with large, palpable, unilateral flank mass and/or hematuria. WT1 or WT2 on chromosome 11.
WAGR complex
Wilms tumor, Aniridia (absence of iris), Genitourinary malformations, mental Retardation/intellectual disability (WT1 deletion).
Denys-Drash syndrome
Wilms tumor, Diffuse mesangial sclerosis (early-onset nephrotic syndrome), Dysgenesis of gonads (male pseudohermaphroditism), WT1 mutation
Beckwith-Wiedemann syndrome
Wilms tumor, macroglossia, organomegaly,
hemihyperplasia (WT2 mutation)
Transitional cell carcinoma (urothelial carcinoma)
- Epidemiology
- Presentation
- Associations
Most common tumor of urinary tract system (renal calyces, renal pelvis, ureters, and bladder)
Can be suggested by painless hematuria (no casts).
Associated with problems in your Pee SAC:
Phenacetin, Smoking, Aniline dyes, and Cyclophosphamide.
Squamous cell carcinoma of the bladder
- Risk factors include
Chronic irritation of urinary bladder squamous metaplasia dysplasia and squamous cell carcinoma
Schistosoma haematobium infection (Middle East), chronic cystitis, smoking, chronic nephrolithiasis. Presents with painless hematuria.
Urinary incontinence
Pag. 584
Urinary tract infection (acute bacterial cystitis)
- Clinical presentation
- Etiology
Presents as suprapubic pain, dysuria, urinary frequency, urgency. Systemic signs (eg, high fever, chills) are usually absent.
Causes:
E coli (most common).
Staphylococcus saprophyticus—seen in sexually active young women.
Klebsiella.
Proteus mirabilis—urine has ammonia scent
Urinary tract infection (acute bacterial cystitis)
- Lab findings
Lab findings: ⊕ leukocyte esterase. ⊕ nitrites (indicate gram ⊝ organisms).
Sterile pyuria and ⊝ urine cultures suggest urethritis by Neisseria gonorrhoeae or Chlamydia trachomatis
Acute pyelonephritis
- Clinical presentation
- Labs
Presents with fevers, flank pain (costovertebral angle tenderness), nausea/vomiting, chills.
Presents with WBCs in urine +/− WBC casts. CT would show striated parenchymal enhancement
Chronic pyelonephritis
- Phatophysiology
- Findings
result of recurrent episodes of acute pyelonephritis
Coarse, asymmetric corticomedullary scarring, blunted calyx. Tubules can contain eosinophilic casts resembling thyroid tissue
Xanthogranulomatous pyelonephritis
- Phatophysiology
rare; grossly orange nodules that can mimic tumor
nodules; characterized by widespread kidney damage due to granulomatous tissue containing foamy macrophages.
Associated with Proteus infection
Consequences of renal failure
Metabolic Acidosis
Dyslipidemia (especially triglycerides)
Hyperkalemia
Uremia—clinical syndrome marked by:
Na+/H2O retention (HF, pulmonary edema,
hypertension)
Growth retardation and developmental delay
Erythropoietin failure (anemia)
Renal osteodystrophy
Renal osteodystrophy
Hypocalcemia, hyperphosphatemia, and failure of vitamin D hydroxylation associated with chronic renal disease 2° hyperparathyroidism.
Causes subperiosteal thinning of bones.
Acute interstitial nephritis (tubulointerstitial nephritis)
- Etiology
- Clinical findings
Remember these P’s: Pee (diuretics) Pain-free (NSAIDs) Penicillins and cephalosporins Proton pump inhibitors RifamPin
Associated with fever, rash, hematuria, pyuria, and costovertebral angle tenderness
Acute tubular necrosis
- Stages
- Inciting event
- Maintenance phase—oliguric; lasts 1–3 weeks; risk of hyperkalemia, metabolic acidosis, uremia
- Recovery phase—polyuric;
*Key finding: granular (“muddy brown”) casts
Renal papillary necrosis
- Phatophysiology
- Associations
Sloughing of necrotic renal papillae gross hematuria and proteinuria. May be triggered by recent infection or immune stimulus
SAAD papa with papillary necrosis: Sickle cell disease or trait Acute pyelonephritis Analgesics (NSAIDs) Diabetes mellitus
Autosomal dominant polycystic kidney disease
- Clinical presentation
- Mutations
- Associations
Presents with flank pain, hematuria, hypertension, urinary infection, progressive renal failure in ~ 50%
Mutation in PKD1 (85% of cases, chromosome 16) or PKD2 (15% of cases, chromosome 4).
Associated with berry aneurysms, mitral valve prolapse, benign hepatic cysts, diverticulosis.
Autosomal recessive polycystic kidney disease
- Clinical features
Often presents in infancy. Associated with congenital
hepatic fibrosis. Significant oliguric renal failure in utero can lead to Potter sequence.
Systemic hypertension, progressive renal insufficiency, and portal hypertension from congenital hepatic fibrosis.
Autosomal dominant tubulointerstitial kidney disease (medullary cystic kidney disease)
- Phatophysiology
tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine.
Medullary cysts usually not visualized; smaller kidneys on ultrasound. Poor prognosis
Simple cysts
Are filled with ultrafiltrate (anechoic on ultrasound).
Very common and account for majority of all renal masses. Found incidentally and typically asymptomatic.
Complex cysts
including those that are septated, enhanced, or have solid components on imaging
Require follow-up or removal due to risk of renal cell carcinoma.
