zwinthrop's version from 2015-05-18 13:49

Glomerular Diseases

Question Answer
What characterizes the nephrotic syndromes? (1 big concept, 4 resulting)PODOCYTE DISRUPTION --> proteinuria > 3.5 gm/day
(1) Hypoalbuminemia: dec oncotic pressure, inc interstitial fluid --> soft pitting edema (childrin = periorbital). Na+/H2- retention due to secondary hyperaldosteronism.
(2) Hypogammaglobulinemia: loss of immunoglobulin--> increased risk for infection (esp staph/pneumo)
(3) Hypercoaguable State: loss of Antithrombin III (protein S/C too) (prothrombotic state--> renal thrombosis/DVTs
(4)Hyperlipidemia/Hypercholesterolemia: loss of protein--> thin blood --> liver reacts by adding fat --> fatty casts in urine.
Describe the 3 categories of 2 nephrotic syndromes1) MCD/FSGS → Podocyte Effacement
2) Membranous Nephropathy/MPGN→ immune complexes in 3 locations of membrane
3) Systemic → Diabetes and Amyloid
Minimal Change DiseaseTYPE: Nephrotic
RISKS/EPI: Children 2-6 (most common nephrotic in children), Recent infection, Hodkin Lymphoma, NSAIDs.
PATHO: cytokines →podocyte effacement → "selective proteinuria" for albumin.
CLINICAL: Proteinuria w/ normal renal rxn→no hematuria.
HISTO:EM = podocyte effacement. TX: Corticosteroids (only one it works for).
Focal Segmental GlomerulosclerosisTYPE: Neprhotic
RISKS/EPI: Af american/Hispanic, HIV,Heroin, Sickle Cell
PATHO: Podocyte effacement w/ hyalinosis and focal/segmental sclerosis→abnormal leakage of proteins "nonselectively"; may progress to CKD.
CLINICAL: Proteinuria similar to MCD but may be hematuria and non-slective proteinuria. Worse prognosis.
HISTO: LM-segmental sclerosis/hyalinosis; IF-deposits of IgM, C3,C1; EM-podocyte effacement.
TX: Poor response to corticosteroids.
Membranous NephropathyTYPE: Nephrotic
RISKS/EPI: Caucasian, Hep B/C, Lupus (nephrotic lupus), NSAIDs, Pencillamine, Solid Tumors.
PATHO: PLA2R Autoantibodies → immune complex formation →sub-epithelial deposits→"Spike and Dome" formations→ thick filtration membrane (GBM)
CLINICAL: Proteinuria, HTN, Hematuria (mild); may progress to CKD.
HISTO:LM-GBM thickening; IF: Granular; EM: "Spike and Dome" sup-epithelial deposits
TX: poor response to steroids.
Membranoproliferative GlomerulonephritisTYPE: Nephritic/nephrotic
RISKS/EPI: Type 1: Hep B/C infection or idiopathic; Type 2: C3GN Nephritic Factor (stabilizes C3 converstase →serum C3 levels
PATHO: Type 1: Immune Complex Mediated→circulating immune complexes deposit subendothelial→"tram tracking"; Type 2: C3GN stops C3 converstase apoptosis→over activation of compliment→basement membrane/intramembranous dense deposit "ribbon-like" GBM>
CLINICAL: Dec Serum C3; High incidence of recurrence in transplant recipients
HISTO: Type 1: IF-Granular, EM-"tram-track"; Type 2: "dense deposits"
AmyloidosisTYPE: Nephrotic
RISKS/EPI: Multiple myeloma, TB, RA
PATHO: Amyloid deposits in mesangium → nephrotic syndrome (kidney most commonly involved organ)
CLINICAL: Bence Jones Proteinuria
HISTO: Apple-Green Birefringence w/ congo red stain
Diabetic GlomerulonephropathyTYPE: Nephrotic
RISKS/EPI: Most common cause of End-Stage Renal Disease (ESRD); 50% of type I DM progresses to ESRD, 10% Type II
PATHO: Inc serum [Glu] →NEG (non enzymatic glycosylation) of vascular basement membrane→efferent hyaline arteriolosclerosis due to vascular permeability→ inc GFR (microalbuminuria)→ sclerosis → nephrotic syndrome
HISTO:LM-Kimmelstiel-Wilson Nodules: sclerosis of mesangium
TX: ACE Inhibitors slow progression: ATII also squeezes down on efferent→ so if can dec renin it is helpful .
Acute Poststreptococcal Glomerulonephritis (PSGN)TYPE: Nephritic
RISKS/EPI: Children (6-10)→ resolve, Adults→ RPGN. 2 wks after group A strep inf of skin/pharynx (M protein virulence factor)
PATHO: Type II Hypersensitivty Rxn→inc anti-DNase B titers→ dec complement levels→proliferation of mesangial cells and endothelial cells→capillary collapse
CLINICAL: Coke colored Urine
Rapidly Progressive Glomerulonephritis (RPGN)TYPE: Nephritis
RISKS/EPI: Medical Emergency→Renal Failure in Wks/Months-3 types: Type 1-Goodpasture's (lung/kidney); Type 2-Post-Strep GN, DPGN, Henoch-Schonlein Purpura (IgA), SLE (cost common renal disease in lupus), Cryoglobulinemia; Type 3: Pauci-immune (ANCA)-Microscopic Polyangiitis (MPO-ANCA/p-ANCA), Wegner’s (PR3-ANCA/c-ANCA)
PATHO: Type 1: Type II hypersensitivity of GMB/alveolar antibodies→insitu IC formation; Type 2: Deposition of circulating ICs; Type 3: No immune complexes.
CLINICAL: Hematuria/hemoptysis, rapidly deteriorating renal function
HISTO: LM-Crescent in bowman's space (fibrin/macrophages) IF-Type 1: LINEAR Type 2: GRANULAR; Type 3: NONE
TX: Emergency Plasmapheresis.
IgA NephropathyTYPE: Nephritis.
RISKS/EPI: Most common nephritis in world; Adolescents/Young Males; Presents w/ Renal Insufficiency/Acute Gastroenteritis
PATHO:IgA immune complex deposition in mesangium
CLINICAL: Episodic gross/microscopic hematuria w/ RBC casts usually following mucosal infections→ excess IgA; Can progress to renal failure
HISTO: LM—mesangial proliferation (hypercellularity of mesangial stalk); EM—mesangial IC deposits.; IF—Granular-IgA-based IC deposits in mesangium. Renal pathology of Henoch-Schönlein purpura.
RISKS/EPI: X-linked: Type 4 collagen defect
PATHO:Thinning/splitting of basement membrane→ hematuria, hearing loss, ocular disturbance
CLINICAL: Hematuria, Hearing Loss, Occular Disturbance
HISTO: EM-Basket-Weave

Congenital Abnormalities

Question Answer
Ectopic KidneyTYPE: Embryonic Migration Abnormality
DEF: Kidney Out of Place-kinking may result in obstructive complications
Horseshoe KidneyTYPE: Embryonic Migration Abnormality
DEF: Inferior poles of both kidneys fuse - trapped under the mesenteric artery; Kidney normally function normal.
CLINICAL: Associated with: ureteropelvic junction obstruction, hydronephrosis, renal stones, infection, chromosomal aneuploidy syndromes (Edwards, Down, Patau, Turner),
Hydronephrosis –dilation of collecting system assoc. w/ atrophy of kidney caused by flow obstruction
Unilateral Renal AngenesisTYPE: Malformation of Renal Parnechyma
DEF: Absence kidney on one side; Interesting fact: Baby with low set ears may have renal agenesis; ears and kidneys formed at the same time.
TX:Why would ACE inhibitor be a good choice for hypertensive pt with unilateral renal agenesis?
Potter SequenceTYPE: Malformation of Renal Parnechyma
DEF: Bilateral renal agenesis.
Babies who can’t “Pee” in utero develop Potter sequence-POTTER seq assoc. with: Pulmonary hypoplasia: Oligohydramnios (trigger): Twisted face: Twisted skin; Extremity defects.
PATHO: ARPKD, obstructive uropathy (e.g., posterior urethral valves).
CLINICAL: Oligohydramnios → compression of developing fetus→ limb deformities, facial anomalies (e.g., low-set ears and retrognathia, compression of chest and lack of amniotic fluid aspiration into fetal lungs→ pulmonary hypoplasia (cause of death).Insufficient production of fetal urine or chronic uteroplacental deficiency (kidnys not being perfused and thus not producing enough urine), or amniotic leak.
Multicystic Renal DysplasiaTYPE: Embryonic Migration Abnormality
DEF: Nonfunctional kidney w/ Unilateral cysts, Disorganized connective tissue, Island of Cartilage
PATHO:Due to abnormal interaction btw ureteric bud and metanephric mesenchyme. • Most associated with, perhaps caused by, obstruction in lower urinary tract e.g. ureteral atresia.
CLINICAL: Renal function depends on percent of renal mass involved.
Autosomal Dominant Polycystic Kidney Disease (ADPKD)TYPE: Embryonic Migration Abnormality
DEF: Numerous cysts→ bilateral enlarged kidneys ultimately destroy kidney parenchyma.
ASSOC: berry aneurysms, mitral valve prolapse, benign hepatic cysts.
PATHO: Adult -Common (4th-5th decade); PKD1 →more common/severe; Always bilateral.
CLINICAL: flank pain, hematuria, hypertension, urinary infection, progressive renal failure.
Autosomal Recessive Polycystic Kidney Disease (ARPKD)TYPE: Embryonic Migration Abnormality
DEF: Formerly infantile polycystic kidney disease-can lead to Potter Sequence. PATHO: Children; Rare → invariably bilateral; PKHD1 mutation; Fibrocystin (CD, biliary duct); Hepatic Fibrosis → portal HTN; Associated with congenital hepatic fibrosis. CLINICAL: Systemic HTN, progressive renal insufficiency, and portal HTN from congenital hepatic fibrosis.
Nephronophthisis: Medullary Cystic Disease ComplexTYPE: Embryonic Migration Abnormality
DEF: Inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine.
PATHO: NPHP –NPH Gene Mutated ADMCD –MCKD Gene Mutated.
CLINICAL: Medullary cysts usually not visualized; shrunken kidneys on ultrasound. Poor prognosis.
Simple vs. Complex Renal CystsSIMPLE CYSTS: filled with ultrafiltrate (anechoic on ultrasound )→ single or mult unilocular cortical cyst; Very common and account for majority of all renal masses. Found incidentally and typically asymptomatic→ must distinguish from renal cell carcinoma
COMPLEX CYSTS: includes septated, enhanced, or have solid components on imaging require follow-up or removal due to risk of renal cell carcinoma.
Ureteral AtresiaTYPE: Malformation of Lower Urinary Tract
DEF: Abnormal organization of smooth muscle at uretero-pelvic junction (UPJ); Obstruction results in hydronephrosis; Common in young boys.
Bladder ExstrophyTYPE: Malformation of Lower Urinary Tract
DEF: Developmental failure of anterior wall of abdomen and bladder; Exposed mucosa undergoes glandular metaplasia and may develop adenocarcinoma
Tidbit – one of the rare circumstances in which patients develop adenocarcinoma of bladder. Bladder cancer usually urothelial carcinoma (transitional cell carcinoma).

Tubulointerstitial Nephritis

Question Answer
Actue Bacterial PyelonephritisTYPE: Tubulointerstitial Nephritis via Systemic Infection
RISKS/EPI: Ascedning UTI (E. coli, Klebsiella, Enterococcus); Ascending infection. Risks: Indwelling urinary catheter, urinary tract obstruction, vesicoureteral reflux, diabetes mellitus, pregnancy.
PATHO: Neutrophils infiltrate renal interstitium→ Affects cortex --relative sparing of glomeruli/vessels.
CLINICAL: Fevers, flank pain (costovertebral angle tenderness), WBC casts, Leukocytosis
HISTO: Intratubular Neutrophils, more severe near poles
TX: Abx.
Chronic PyelonephritisTYPE: Tubulointerstitial Nephritis via Systemic Infection
RISKS/EPI: Recurrent Acute Pyelonephritis; Pyelocalyceal Damage required; Predisposition to infection: Chronic kidney stones: Vesicoureteral reflux (VUR)→ 2 poles scarred
PATHO: Pelvic/calyceal cortical scarring;
CLINICAL: Thyroidization of kidney→ Eosinophilic Casts mimic thyroid tissue
HISTO: Irregular coarse parenchymal scarring - Pelvic and calyceal scarring - Tubular atrophy - microscopic; Relative preservation of glomeruli - microscopic.
Drug-Induced Interstitial NephritisTYPE: Tubulointerstitial Nephritis via Drug Reaction
RISKS/EPI: Antibiotics, Rifampin, NSAIDS, Phenindione, Diuretics, Phenylbutazone, Allopurinol
PATHO: Acute interstitial renal inflammation; Pyuria (classically eosinophils) and azotemia occurring after administration of drugs that act as haptens, inducing hypersensitivity; Nephritis typically occurs 1–2 wks after certain drugs (e.g., diuretics, penicillin derivatives, proton pump inhibitors, sulfonamides, rifampin), but can occur months after starting NSAIDs.
CLINICAL: Pyuria, Azotemia, Nephritis, Hematuria, Acute Renal Failure, Fever, Rash, Arthralgias, costovertebral angle tenderness, but can be asymptomatic
Analgesic NephropathyTYPE:Tubulointerstitial Nephritis via Drug Reaction
RISKS/EPI: Aspirin or Phenacetin over 3 year period; Females >> Men
PATHO: Special type of chronic interstitial nephritis
CLINICAL: Acute Paillary Necrosis ( SAAD papa)
Transplant RejectionTYPE: Tubulointerstitial Nephritis via Immmunologic Reaction
PATHO: Tubule shows tubulitis, lymphoif cells in tubule
CLINICAL: Acute Rejection, Vasculitis,
HISTO: interstitial inflammation and tubulitis.