Renal Flashcards
1
Q
Nephrotic Syndrome vs. Nephritic Syndrome
A
Nephrotic Syndrome
- Heavy proteinuria (>3.5g)
- Hypoalbuminemia
- Edema
- Hyperlipidemia & lipiduria
- Normal complement levels
- Oval fat bodies
- Free fat droplets
- Few cellular elements
- Fatty casts
. Nephritic Syndrome
- Variable proteinuria (<3.5g)
- Hypertension
- Hematuria
- Red Cell Casts/Granular casts
- White Blood Cells
2
Q
Minimal Change Disease
A
- ETIOLOGY: most common in children
- Idiopathic- Associated with Hodgkin’s lymphoma or renal cell carcinoma
- PATHOGENESIS: primary target is glomerular epithelial cells (podocytes)
- Injury results in increased glomerular permeability and proteinuira
- Unclear but maybe circulating “glomerular permeability factors”
- No immune complex depositon, non inflammatory injury
- MORPHOLOGY: foot process effacement, detachment of epithelial cells / basement membrane (seen only on EM)
- SYMPTOMS: selectiveproteinuriaàspecifically hypoalbuminemia
- Periorbital, pedal edema
- Normal blood pressure
- Bland urine sediment
- DIAGNOSIS: low albumin, normal creatinine
- Urine: proteinuria, bland urine sediment
- Physical exam: Normal BP, Edema (perioribital, pedal)
- LM- normal, IF- no immunoglobuilin deposit.
- TREATMENT: steroidtherapy (8 weeks)
- Frequent relapse when stopping steroids (1/3 of them)
- Renal failure & mortality rates are low although somewhat higher in adults than children
- Pts die of complications of NS or therapy
3
Q
Focal Segmental Glomerulosclerosis (FSGS)
- Focal (some glomeruli are affected bit not others)
- Segmental (affecting only a segment of each glomerulus)
- Glomerulo(of glomeruli)
- Sclerosis: scarring
A
- ETIOLOGY: African American adults
- Primary: idiopathic
- Secondary to: HIV, morbid obesity, heroin, chronic reflux nephropathy, malignancies (lymphoma)
- Anything that causes a reduction in renal mass will result in compensatory hyperfiltrationin remaining glomeruli leading injury pattern
- Glomerulonephritis
- Renal ablation nephropathy (partial nephrectomy)
- Congenital unilateral renal agenesis or aplasia
- PATHOGENESIS:
- Secondary: reduction in renal mass due to disease→ →compensatory hyperfiltration → intraglomerular HTN →hyperfiltration injury → sclerosis
- MORPHOLOGY: patchy fusion of foot processes and effacement
- SYMPTOMS: insidious onset of asymptomatic proteinuria
- Hypertension and renal insufficiency
- Foamy urine
- Progression to nephroticsyndrome with massive proteinuria & microscopic hematuria
- Degree of proteinuria is an important prognostic indicator
- Anasarca(generalized edema)
- ESRD by 5-20 years
- DIAGNOSIS: LM (FSGS), IF (negative or IgM& C3 deposits), EM (patchy fusion of the foot processes and effacement
- TREATMENT: no response to steroids
•
4
Q
Membranous Nephropathy
A
- ASSOCIATIONS: idiopathic, endogenous antigens (DNA “SLE”/ tumors) SLE, Hepatitis B, Syphilis, Malaria, Penicillamine, Gold, mercury, Captopril,
- Present with nephrotic syndrome, microscopic hematuria, HTN, renal insufficiency (late), renal vein thombosis
- PATHOGENESIS: deposition of immune complexes in sub-epithelial zone or the deposition of circulating ICs
- Resembles membranous nephropathy to experimental animal disease (HeymannNephritis)
- Ag-Ab reaction →complement activation → C5b-C9 insertion into podocyte membrane→ detachment of podocyte → GFM damage → increased permeability
- MORPHOLOGY: diffuse thickening of the GBM
- IF: Deposits of IgG and C3 along basement membrane
- EM: Growth of new GBM over depositions → spikes/domes
- SYMPTOMS: nephrotic syndrome, renal failure
- Renal HTN, microscopic hematuria
- Loss of antithrombin3 → hypercoagulablestate → DVT, PE , and renal vein thrombosis
- LM: diffuse thickening of the GBM with little increase in cellularity
- IF: fine granular deposits of IgG, C3 along with basement membrane – subepithelial
- EM: subepithelial immune complex deposits and proliferation & growth of new GBM “spikes” formation
- Poor prognosis:male, >50, >10gm proteinuria
5
Q
Diabetic Nephropathy
A
- ETIOLOGY: systemic hyperglycemia damages glomerulus and arterioles
- Leading cause of ESRD in USA
- PATHOGENESIS:
- Glycosylation, increased TGF-b →matrix formation → mesangium expansion
- Increased type IV collagen, increased fibronectin, decreased proteoglycan heparin sulfate → thickening GBM
- Hyperfiltration+ increased glomerular capillary pressure + glomerular hypertrophy → hypertrophy
- Earliest lesion: expansion of mesangial matrix and thickening of GBM
- Later lesions: diffuse global glomerulosclerosis with diffuse increase in mesangial matrix & diffuse thickening of GBM
- MORPHOLOGY: Kimmelstiel-Wilson nodules contains lipids and fibrin (plasma proteins)
- Ischemia causes tubular atrophy and interstitial fibrosis
- Hyaline arteriolosclerosis
- SYMPTOMS: initially hyperglycemia→ hyperfiltration, increased GFR
- 7-13 years: microalbuminuria(30-300mg/24hr), incipient nephropathy
- 10-20 years: macroalbuminuria(>300/24h), overt nephropathy
- Progressive proteinuria, HTN, decline in GFR (12 ml/min/year)
6
Q
Amyloidosis
A
- ETIOLOGY: no immune or inflammatory response elicited by amyloid fibrils
- AL (Primary): light chain produced by abnormal plasma cell clone (multiple myeloma)
- AA (Secondary): amyloid precursor protein, apolipoprotein produced by liver during chronic inflammation
- Rheumatoid arthritis, Behcetsyndrome, Crhonsdisease, osteomyelitis, TB, renal cell carcinoma, hodgkin’sdisease
- B-pleated sheets: Organized fibrillary aggregates resistant to removal
- PATHOGENESIS: organ damage/dysfunction due to infiltration by amyloid fibrilsand replacement of normal organ architecture (no inflammation)
- MORPHOLOGY: nodular hyaline material within mesangium and capillary lumens
- SYMPTOMS: Bence-Jones proteinuria, edema, nephroticsyndrome (proteinuria)
- Poor prognosis → COD due to end-organ failure
- Heart: CM/CHF, arrythmias, heart block
- GI: hepatomegaly, malabsorption, bleeding
- Neuro: ischemic stroke, neuropathy, orthostatic hypotension
- Skin: easy bruising, purpura
- DIAGNOSIS: biopsy of organ involved→ Congo Red Stain (kidney, skin, heart, liver)
- Polarizable apple green bifringence
- LM:nodular, amorphous hyaline material in the mesangium & capillary loops, with resultant narrowing or closing of capillary lumens
- EM: subendothelial & mesangial fibrils
7
Q
IgA Nephropathy
AKA Berger’s Disease, Mesangioproliferative Glomerulonephritis
A
- ETIOLOGY: most common type of glomerulonephritis, generally a prolonged benign course
- IgA Nephropathy→20-30 years old (Asians and Caucasians)
- Henoch-SchonleinPurpura (HSP) → children
- PATHOGENESIS: production of IgA immune-complexes (mucosal)
- MORPHOLOGY: segmental areas of increased mesangial matrix and hypercellularity
- Mesangial and subendothelial deposits of IgA and C3
- SYMPTOMS: hematuria worsens during URI or GI infections(gross hematuria), persistent microscopic hematuria between these episodes
- Non nephrotic range Proteinuria <3.5gm/day
- Normal C3/C4
- COMPLICATION: RPGN (nephritic → nephrotic) can progress to ESRD
- Type 2 Rapidly Progressing GN
- LM: segmental areas of increased mesangial matrix & hypercellularity
- IF: mesangial and subendothelia ldeposits of IgA& C3 (+/- IgG, IgM)
- EM: Mesangial and subendothelial deposits
- ASSOCIATIONS:
- Hepatic cirrhosis, gluten enteropathy, HIV, Minimal Change Disease, Ankylosing Spondylitis,Wegener’s small cell Carcinoma
8
Q
Post-Streptococcal Glomerulonephritis (PSGN)
A
- ETIOLOGY: 10 days following pharyngitis or 3 weeks following impetigo
- Children 6-10 years old
- PATHOGENESIS: infection with B-hemolytic streptococci
- MORPHOLOGY: subendothelial deposition of immune complexes
- Initially Hypercellular glomeruli (PMNs + monocytes)→ deposits cleared accounting for resolution of hematuria and renal failure
- LATER: EM:Subepithelial humps→ responsible for epithelial cell damage and proteinuria, IC deposits cleared slowly (separated from circulation by GBM) limiting their clearance
- LM: Diffuse proliferation of mesangium, endothelium, epithelial cells. Closure of capillary loops due to proliferation & swelling of endothelial cells & leukocyte infiltration
- IF:Deposits of IgG and C3 i nmesangium& along capillary walls
- EM: election dense deposits in sub epithelial space “humps”
- SYMPTOMS: abrupt onset of nephritic syndrome (proteinuria >2gm)
- Low levels of complement
- Children: spontaneous recovery, renal failure in <1% (10-40 years after)
- Some may develop renal insufficiency as long as 10-40 years after the initial illness
- COMPLICATIONS:
- Some glomeruli irreversibly damaged → compensatory hyperfiltration
- Chronic increase in capillary pressure → glomerulo sclerosis→ FSGS
- DIAGNOSIS: increased anti-streptolysin O or increased anti-DNAase B with low complement
9
Q
Membranoproliferative
Glomerulonephritis (MPGN)
A
- ETIOLOGY: thickening of GBM, mesangial proliferation, and infiltration of inflammatory cells
- 3 major types → all have same histology
- Differentiated via EM and IF
- Presents before age 30
- PATHOGENESIS:
- Type I: subendothelial deposits (C3 + IgG + C4)
- Classical Pathway
- Lupus, Hepatitis B/C, Endocarditis, cryoglobulinemia, parasitic infection
- Type II: deposition of unknown dense material along GBM
- Alternative pathway (decreased C3 due to C3 nephritic factor that stabilizes C3bBb) (C3 + BM+ IgG, C1q, C4 absent)
- Type III: subendothelial, mesangial, subepithelial deposits (C3 +/- IgG)
- MORPHOLOGY:
- Histology: mesangial expansion and hypercellularity with thickening of capillary loops to duplicated GBM → tram track appearance
- SYMPTOMS: presents before 30 years old
- 1) Hematuria or proteinuria
- 2) Acute nephritic syndrome (hematuria, HTN, edema)
- 3) Recurrent episodes of gross hematuria
- 4) Insidious onset of edema and nephrotic syndrome
- Progresses to ESRD in 10-15 years
•
10
Q
A
11
Q
Rapidly Progressive Glomerulonephritis (RPGN)
A
- ETIOLOGY: “Cresentic Glomerulonephritis”
- MORPHOLOGY: characterized by proliferative GN with prominent “crescent” formation in 30-70% of glomeruli and +/- segmental necrosis
- (parietal cells)
- Cellular→ Fibrocellular→ Fibrous
- SYMPTOMS: 75% die or are placed on dialysis within 2 years
- Severe oliguria
- Severe glomerular injury:
- Proteinuria (non-nephrotic), hematuria, RBC cast, HTN, Edema, oliguria
- Histosame regardless of cause
- DIAGNOSIS:
- Immunofluorescence
- Linear Staining: Type I RPGN → Anti-GBM Disease→ Goodpasture’s, idiopathic
- Granular Staining: Type II RPGN → Immune Complex Disease → SLE, IgA, Post-Infectious,henochschonlein, idipathic
- No Staining: Type III RPGN → Pauci-Immune→ Wegner’s, Microscopic PAN, Churg-Strauss
12
Q
Alport Syndrome
A
- ETIOLOGY: defects in collagen IV synthesis (bm)
- X-linked(80%)
- M > F, 5-20 years old
- PATHOGENESIS: COL4A4 & COL4A5 genes used to make BM
- MORPHOLOGY: basket-weaveappearance (alternating thick/thin of lamina densa)
- IF is negative for alpha 3,4,5 collagen
- EM: thin basement membrane with splitting and lamination
- SYMPTOMS:
- Nephritis (hematuria, proteinuria, renal failure)
- Nerve deafness
- Eye disorders → cataracts(juvenile form)
- Normal complement levels
- INVESTIGATIONS: biopsy, immunostain,
13
Q
Benign Hypertensive Nephrosclerosis
A
- ETIOLOGY: long standing history of hypertension, asymptomatic
- Young, black males
- PATHOGENESIS:
- Hypertension→ medial/intimal thickening → afferent arteriole luminal narrowing→ hyaline arteriosclerosis via leakage of plasma proteins to tunica media
- MORPHOLOGY:
- Vascular: medial and intimal thickening
- Hyaline arteriolosclerosis (due to extravasation of plasma proteins through injured endothelium)
- Glomerular: global sclerosis(ischemic injury).. leading to nephron loss
- Grainy leather
- Leading to nephron loss
- FSGS (adaptive injury), compensatory hyperfiltration due to nephron loss
- Tubules: tubular atrophy, interstitial fibrosis (ischemic mediated)
- SYMPTOMS: mild proteinuria (<1g/day)
- Normal or slightly reduced GFR
- No microscopic hematuria
- Slow progressive elevation in serum creatinine
- Risk Factors for ESRD: blacks,diabetes, HTN
- DIAGNOSIS: bland urine sediment
- LVH, retinopathy, stroke
14
Q
Malignancy Hypertensive Nephrosclerosis
A
- ETIOLOGY: renal disease associated with >180/120 mmHg
- Young black males
- PATHOGENESIS: develops in patients with pre-existing essential hypertension, secondary hypertension (pheochromocytoma, primary hyperaldosteronism)
- MORPHOLOGY: petechial hemorrhages on cortical surfaces
- Necrotizing arteriolitis& intravascular thrombosis
- Onion-skin lesion
- SYMPTOMS: look for end organ damage
- Malignant HTN Crisis: renal failure + other organ involvement developing over hours or days
- Hematuria, headache, encephalopathy, acute MI, aortic dissection, blurry vision
15
Q
Hemolytic Uremic Syndrome (HUS)
Thrombotic Thrombocytopenic Purpura (TTP)
A
- ETIOLOGY: disorders characterized by abnormal platelet aggregation
- HUS: seen in children→ following EHEC inflammatory diarrhea (0157:H7)
- TTP: associated with SLE, HIV
- PATHOGENESIS: thrombosis in small vessels results in mechanical injury to circulating RBCs → microangiopathichemolytic anemia
- Lead to ischemic injury to target organs: kidney, brain, heart
- HUS:
- Associatedw/ viral, Salmonella, or Shigella infection
- Induced by quinine, gemcitabine, cyclosporine, OCP
- SYMPTOMS
- HUS: more severe renal failure, less CNS involvement
- TTP: renal failure less severe, more CNS involvement
- DIAGNOSIS: Microangiopathic hemolytic anemia; schistocytes in peripheral blood smear
- Thrombocytopenia, acute renal failure, macroangiopathic hemolytic anemia, neurological abnormalities: headache, confusion, seizure, stroke, fever
16
Q
Renal Artery Stenosis (RAS)
A
- ETIOLOGY: narrowing of one or both renal arteries
- 75-90% due to occlusion by atheromatous plaque
- Takayasu’s arteritis, aortic/renal dissection
- SYMPTOMS: flank or epigastric bruit, acute renal failure
- Sudden onset of uncontrolled HTN in previously well-controlled patient
- Flash pulmonary edema with normal LV function
- Accelerated or malignant HTN
- Ischemic Nephropathy: diffuse ischemic atrophy, no arteriosclerosis within kidney due to stenotic renal artery but hypertensive arteriosclerosis in contra-lateral kidney, arterioles protected from transmission of high pressure due to stenoticrenal artery
- DIAGNOSIS: asymmetrical kidney size
- Renal arteriogram (gold standard)
- Renal artery doppleràmeasures renal:aortavelocities (>3.5 ratio = RAS)
- TREATMENT: angioplasty and stent
- Uncontrolledhypertention
- Declining renal function (elevated CR)
- Recurrent pulmonary edema
17
Q
Acute Tubular Necrosis (ATN)
A
- ETIOLOGY: acute injury to renal tubules, causing necrosis.. Acute renal failure
- PATHOGENESIS: toxic vs ischemic
- Toxic: exogenous (aminoglycosides) or endogenous (hemoglobinuria, myoglobinuria)
- Ischemic: hypotension, vasodilatory infection (septic shock), hemorrhagic shock, hypovolemic shock
- SYMPTOMS: hypotension, oliguria/anuria, uremia(pericardial rub)
- Elevated creatinine & BUN
- Anemia(decreased EPO)
- Metabolic acidosis
- Initiation Phase (36 hours): acute decrease in GFR, rapid increase in creatinine & BUN
- Maintenance Phase (3 weeks): plateau of creatinine/BUN, oliguria, uremia, acidosis, hyperkalemia
- Recovery Phase: tubular function restored, increasing GFR, increase urine volume, gradual decrease in creatinine& BUN
- DIAGNOSIS: muddy brown granular casts, epithelial cell casts, proteinuria
- Ischemic insult- hypotension, vasodilaroty, hemorrhagic shock: GI bleeding, Hypovolemic shock: vomiting, diarrhea
- Nephrotoxic insult
- Exogenous- Aminoglycosides, contrast media “CT/cardiac cath”
- Endogenous-Hemoglobinuria, myroglobinura
18
Q
Tubulointerstitial Nephritis
A
- ETIOLOGY: characterized by interstitial inflammation, edema, fibrosis, but normal glomeruli
- PATHOGENESIS:
- Acute: antibiotics (allergic reaction 2 weeks after starting), infection, idiopathic, sarcoidosis
- Drugs (antibiotics)
- Infections
- Idiopathic
- sarcoidosis
- Chronic: pyelonephritis (infection), analgesic abuse (ASA, Tylenol), urate nephropathy
- SYMPTOMS:
- Impaired urinary concentration (polyuria, nocturia)
- Salt wasting (hyponatremia)
- Metabolic acidosis (decreased ability to excrete acid
- No significant proteinuria or hematuria
- DIAGNOSIS: confirmation by renal biopsy
- if AIN → eosinophils, WBC casts, high K, low HCO3
19
Q
Acute Drug Induced Interstitial Nephritis (AIN)
A
- PATHOGENESIS: Onset usually two weeks after starting medication
- Penicillin (antibiotics),cephalosporin, NSAIDS, sulfonamides, ciprofloxacin
- SYMPTOMS: Allergic-typereaction (interstitial infiltration)
- 2 weeks after start of medication (first exposure)
- 3-5 days of second exposure
- Fever, rash, eosinophilia, ARF/oliguria
- DIAGNOSIS: Eosinophils, sterile pyuria, WBC casts, proteinuria
- Confirmation by renal biopsy
- Increased BUN and creatinine
- Tubular dysfunction: High K, low HCO3
- Urine microscopy:
- Eosinophils, sterile pyuria, WBC casts, proteinuria
- Blood Test:
- increased BUN & Creatinine, Increased eosinophil count, Tubular dysfunction: high K, low HCO3
