Renal Flashcards

Question

**Basement Membrane Thickening**

Answer 1

* on PAS stain: see thickening of capillary walls * EM: has two forms: * 1. immune complex deposits on endothelial or epithelial side of GBM or within the GBM. fibrin, amyloid, cryoglobulins, and fibrillary proteins can deposit in GBM. * 2. increased synthesis of protein components (see in diabetic glomerulosclerosis).

Answer 2

* accumulation of material that is homogenous and eosinophilic by light microscopy. * EM: hyalin is extracellular and amorphous. * made of plasma proteins insudated from circulation * extensive ⇒ obliteration of capillary lumens of glomerular tuft. * consequence of endothelial or capillary wall injury, end result of glomerular damage. * found in **focal segmental glomerulosclerosis**

Answer 3

* accumulations of extracelular collagenous matrix, confined to mesangial areas (diabetic glomerulosclerosis) or involving capillary loops. * can ⇒ obliteration of capillary lumens ⇒ form fibrous adhesions between sclerotic portions and parietal epithelium and Bowman capsules.

Answer 4

* **_diffuse_** = involving all glomeruli * **_global_** = involving entire glomerulus * **_focal_** = involves only a portion of the glomeruli * **_segmental_** = affects part of each glomerulus * **_capillary loop or mesangial_** = affects predominantly the capillary or mesangial regions.

Answer 5

* 1. antibodies reacting in situ within glomerulus, binding to insoluble fixed glomerular antigens or to molecules planted within glomerulus. * 2. deposition of circulating antigen-antibody complexes in glomerulus.

Answer 6

* on EM: presence of numerous discrete electron-dense deposits along subepithelial aspect of GBM. * IF: **granular lumpy deposition**. * results from rxn of antibody with antigen comlex on basal surface of visceral epithelial cells and cross-reacting with brush border antigen. then complement activation and shedding of aggregates to form **subepithelial deposits.** * antigen = **megalin** = lipoprotein receptor (in rats) * anti-GBM antibody induced disease = autoimmune.

Answer 7

* Ab react in situ with antigens that are not normally present in glomerulus but planted there. * **planted antigens**: cationic molecules binding to anionic components of glomerulus; DNA, nucleosomes, nuclear proteins (affinity for GBM); bacterial products; immunoglobulins; immune complexes * induce **Ig deposition** * IF: **granular deposition**

Answer 8

* Ab directed against intrinsic fixed antigens that are normal components of GBM proper. * IF: **diffuse linear pattern** * cross-reactivity in the lungs ⇒ simultaneous lung and kidney lesions = **Goodpasture syndrome** * GBM antigen = component of **noncollagenous domain of the alpha3 chain of collagen type IV** (for GBM suprastructure). also the antigen in Goodpasture syndrome. * features: severe crescentic glomerular damage and rapidly progressive glomerulonephritis.

Answer 9

* caused by trapping of circulating Ag-Ab complexes within glomeruli. * localize not from affinity but from the physicochemical properties and hemodynamic factors of the glomerulus. * antigens can be endogenous or exogenous * microbial antigens: Hep B, Hep C, T. pallidum, Plasmodium falciparum. * glomerular lesions have leukocytic infiltrate and proliferation of mesangial and endothelial cells * EM: immune complexes in mesangium = **subendothelial deposits**, or **subepithelial deposits** = outer surface of GBM and podocytes. * IF: **granular deposits** * highly cationic antigen ⇒ subepithelial deposit; * highly anionic antigen ⇒ subendothelial deposit. * neutral ⇒ mesangial deposits

Answer 10

* Ab to mesangial cell ⇒ mesangiolysis then mesangial cell proliferation. * Ab to endothelial cell ⇒ endothelial injury and intravascular thrombosis * Ab to visceral epithelial cell ⇒ proteinuria. * IF: **granular deposits** along GBM or in mesangium.

Answer 11

* **sensitized T cells** may injure glomerulus. * clues: activated macrophages and T cells, injury by transpanting T cells. * T lymphocytes propogate the inflammation.

Answer 12

* aka MPGN type II or dense deposit disease. * through activation of alternative complement pathway

Answer 13

* **neutrophils/monocytes**: from activating complement and from Fc-mediated adherence/activation. release proteases ⇒ GBM degradation; O₂ free radicals; arachidonic acid metabolites. * **macrophages/T lymphocytes/NK cells**: in Ab and cell mediated rxn. * **platelets**: in immune-mediated injury. release eicosanoids and growth factors. * resident **glomerular cells**: mesangial cells. make: ROS, cytokines, chemokines, growth factors, eicosanoids, NO, and endothelin.

Answer 14

* **chemotactic complement components**: cause leukocyte influx ⇒membrane attack complex ⇒ stimulate mesangial cells to make oxidants, proteases, etc. without neutrophils ⇒ proteinuria. * **eicosanoids/NO/angiotensin/endothelin**: cause hemodynamic changes. * cytokines: **IL-1 and TNF** ⇒ leukocyte adhesion, etc. * chemokines: monocyte chemoattractant protein 1 and CCL5 promote monocyte and lymphocyte influx. * **PDGF** in mesangial cell proliferation. * **TGF-beta, CTGF, and FBGF** important for ECM deposition and hyalinization ⇒ glomerulosclerosis. * **VEGF** maintains endothelial integrity, helps regulate capillary permeability. * coagulation system: fibrin stimulates parietal epitheial cell proliferation (crescent formation). mediated by **macrophage procoagulant** activity. * **Plasminogen activator inhibitor-1 **⇒ ↑ thrombosis and fibrosis, inhibits degradation of fibrin and matrix proteins.

Answer 15

* tubular damage and interstitial inflammation. * from ischemia downstream of sclerotic glomeruli, acute/chronic inflammation, loss of peritubular capillary blood supply. * **proteinuria ⇒ direct injury** to and **activation** of tubular cells from iron, Ig, complement products, cytokines, lipid moieties, oxidated plasma proteins. * **active tubular cells** ⇒ cytokines, chemokines, growth factors ⇒ interstitial fibrosis

Answer 16

* includes **Poststreptococcal and Postinfectious glomerulonephritis**. * diffuse proliferation of glomerular cells, influx of leukocytes. * caused by **immune complexes**

Answer 17

* appears **1-4 weeks after beta hemolytic strep infection** of pharynx or skin. identify by **M protein**. * usually kids **6-10 yrs**. * low serum complement levels (used up), elevated titers of antibodies against strep. * IF: **granular deposits** IgG, IgM, and C3 in mesangium and along GBM. **focal and sparse**. * EM: discrete, amorphous, electron-dense **deposits on epithelial side of GBM**, look like **humps**. Subendothelial and intramembranous deposits common. * antigens: NAPlr, strep pyogenic exotoxin (SpeB), zSpeB. * morphology: **enlarged hypercellular glomeruli** from i**nfiltration by leukocytes, proliferation of mesangial and endothelial cells, crescent formation** in severe cases. involves **all glomeruli**. swelling of endothelial cells. interstitial edema, inflammation, **red cell casts**. * prognosis: most kids recover. 1% ⇒ rapidly progressive glomerulonephritis. some ⇒ chronic glomerlonephritis. 60% adults recover, the rest have persistent proteinuria, hematuria, and HTN which may ⇒ chronic glomerulonephritis or rapidly progressive glomerulonephritis. * bad prognosis: prolonged and persistent heavy proteinuria and abnormal GFR.

Answer 18

Poststreptococcal Glomerulonephritis

Answer 19

Poststreptococcal Glomerulonephritis

Answer 20

* **rapid and progressive loss of renal function** with **severe oliguria and nephritic syndrome**. * most commonly has **crescents in most glomeruli**. * group 1: **_anti-GBM antibody induced disease_**. * IF: **linear deposits of IgG** and C3 in GBM. * **_Goodpasture's Syndrome_** if also cross-react with pulmonary alveolar basement membrane. * tx: plasmapheresis * group 2: **_immune complex deposition_**. like from **IgA nephropathy, lupus nephritis, postinfectious GN, Henoch-Schonlein purpura**. * IF: **granular pattern** * **cellular proliferation within glomerulus tuft** and crescent formation. * tx: treat underlying disease. * group 3: **_pauci-immune type_**. lack of anti-GBM or immune complexes. have circulating antineutrophil cytoplasmic antibodies (**ANCA**s) ⇒ **cytoplasmic or perinuclear staining patterns**. * play a role in vasculitides. ex: **Wegener granulomatosis or microscopic polyangiitis** * morphology: **kidneys enlarged and pale**, petechial hemorrhages. * can have **focal necrosis, diffuse or focal endothelial proliferation, and mesangial proliferation**. * have **crescents** = proliferating parietal cells with monocytes and macrophages in urinary space. eventually obliterate Bowman space and compress glomerular tuft. later **undergo sclerosis but can go away with early aggressive treatment**. * prominent **fibrin strands** between layers in crescents. * EM can show **rupture in GBM** ⇒ leukocytes, proteins, and inflammatory mediators into urinary space for crescent formation. * features: hematuria, **RBC casts in urine**, mod proteinuria, variable HTN and edema. * tx: steroids and cytotoxic agents. may require chronic dialysis or transplantation

Answer 21

* rapidly progressive glomerulonephritis with **anti-GBM antibody and C3 deposits** that affect both the kidney and lungs ⇒ **pulmonary hemorrhage with renal failure**. * antigen = peptide in noncollagenous portion of the alpha3 chain of type IV collagen * features: recurrent hemoptysis or life-threatening pulmonary hemorrhage. * tx: plasmapheresis and steroids.

Answer 22

* Rapidly Progressive GN. * to differentiate we need to run anti-GBM antibody tests, ANCA tests, and antinuclear antibodies (immune complexes as well).

Answer 23

Goodpasture Syndrome that is rapidly progressive.

Answer 24

* in adults. has diffuse thickening of glomerular capillary wall from accumulation of electron-dense, Ig deposits along subepithelial GBM. * 2° membranous glomerulopathy when in association to other systemic diseases: SLE, infections (Hep B/C, syphilis, schistosomiasis, malaria), autoimmune disorders, malignant tumors, drugs (penicillamine, captopril, gold, NSAIDs). * 85% is idiopathic. * paucity of neutrophils, monocytes, platelets in glomeruli. MAC (C5b-C9) activates glomerular epithelial and mesangial cells ⇒ proteases and oxidants ⇒ capillary wall injury and ↑ protein leakage. * morphology: light microscopy = normal or diffuse thickening of glomerular capillary wall. * EM: thickening from irregular dense deposits of immune complexes between GBM and epithelial cells with effaced foot processes. irregular spikes of matrix protein from GBM on silver stain. thicken to domelike protrusions and close over deposits. * IF: granular deposits containing Ig and complement * sclerosis can occur, proximal tubules have protein reabsorption droplets, may be considerable interstitial mononuclear cell inflammation. * features: insidious onset nephrotic syndrome. hematuria and mild HTN, proteinuria not fixed by steroids, ↑ sclerosis, ↑ serum creatinine. * prognosis: sclerosis = bad, non-nephrotic proteinuria = good, women = good.

Answer 25

Membranous glomerulopathy.

Answer 26

* most frequent cause of nephrotic syndrome **in children** (peak btw 2-6). * diffuse effacement of foot processes of visceral epithelial cells in glomeruli on light microscopy. * **absence of immune deposits**. * associations: mostly visceral epithelial cell injury * sometimes follows respiratory infection or immunization. * has a **dramatic response to corticosteroid therapy**. * associated with atopic disorders (rhinitis, eczema) * ↑ certain HLA haplotypes * **↑ incidence of Hodgkin's lymphoma** (defects in T-cell mediated immunity) * proteinuria-inducing factors in plasma or lymphocyte supernatants * morphology: normal on light microscopy and EM. * visceral epithelial cells show uniform and diffuse effacement of foot processes * rim of cytoplasm showing vacuolization, swelling, and hyperplasia of villi = **fusion of foot processes** * cells of proximal tubules laden with lipid and protein = **lipoid nephrosis** * features: **massive proteinuria but good renal function**. protein is mostly albumin. * tx: corticosteroids

Answer 27

Minimal Change Disease

Answer 28

* **sclerosis of some glomeruli** (focal) and in the glomeruli **only part of the capillary tuft is involved**. * types: primary disease * associated with **HIV, heroin addiction, sickle-cell disease, massive obesity** * secondary event, scarring of previously active necrotizing lesions * adaptive to loss of renal tissue from reflux nephropathy, HTN nephropathy, unilateral renal agenesis. * inherited forms: like with slit diaphragm proteins. * initiated by adaptive change in unaffected glomeruli: **compensatory hypertrophy**. * hemodynamic changes = ↑ glomerular blood flow, filtration, and transcapillary pressure (**glomerular HTN**), systemic HTN. * podocytes can't proliferate ⇒ can't maintain filtration barrier ⇒ abnormal protein filtration and loss of support of GBM ⇒ **segmental loop dilation and fibrous attachment to Bowman capsule and sclerosis.** * _sequence_: endothelial/epithelial cell injury, ↑ glomerular permeability to proteins, accumulation of proteins in mesangial matrix, **proliferation of mesangial cells, infiltration by macrophages**, **↑ accumulation of ECM, segmental and global sclerosis of glomeruli**, ↓ nephron mass, activate compensatory mechanisms. * proteinuria and sclerosis ⇒ **uremia and sclerosis**. * tx: renin-angiotensin inhibitors * **_idiopathic FSGS_**: 10% nephrotic cases in kids, 35% in adults. ↑ incidence in Hispanics and African Americans. * **↑ incidence hematuria, ↓ GFR, HTN, non-selective proteinuria, poor response to steroids, progression to chronic kidney disease.** * hallmark is **epithelial damage from cytokines**, genetic defects of slit diaphragm. * **hyalinosis and sclerosis from entrapment of plasma proteins in hyperpermeable foci and ↑ ECM deposition**. * _morphology_: initially involve juxtamedullary glomeruli. sclerotic areas have **collapsed capillary loops, ↑ matrix, segmental deposition of plasma proteins along capillary wall (hyalinosis)**. * **lipid droplets and foam cells**. * light microscopy: ↑ matrix. * EM: **diffuse effacement of foot processes, denudation of underlying GBM**. * IF: **IgM and C3** in sclerotic areas or mesangium * profuse hyalinosis and **thickening of afferent arterioles**. * leads to profuse sclerosis, tubular atrophy, and interstitial fibrosis. * **_collapsing glomerulopathy_** - variant of FSGS with retraction or **collapse of entire glomerular tuft**. has **proliferation and hypertrophy of glomerular visceral epithelial cells**. * characteristic of HIV nephropathy. * prominent tubular injury with cyst formation. * genetic basis: **NPHS1 (nephrin); NPHS2 (podocin)** ⇒ kid onset steroid resistant nephrotic syndrome aut recessive. **alpha actinin 4** mutation is aut dominant. **TRPC6** mutation affects podocytes. * **_renal ablation FSGS_** = complication of glomerular diseases (reflux nephropathy, unilateral agenesis). may ⇒ progressive glomerulosclerosis and renal failure. * features: kids better prognosis. 20% pts have rapid course with intractable proteinuria and failure in 2 yr.

Answer 29

* occurs with: acute renal failure, acute interstitial nephritis from drugs/infection, thrombotic microangiopathies, postinfectious glomerulonephritis, **collapsing variant of FSGS** (most common). * more frequent in African Americans. * EM: large numbers of **tuberloreticular inclusions within endothelial cells** caused by IFN-alpha. * caused by HIV products: **vpr** and **nef**.

Answer 30

* **alterations in GBM, proliferation of glomerular cells, and leukocyte infiltration**. * aka mesangiocapillary glomerulonephritis. * 1° MPGN: type I and type II. * **_type I MPGN_**: evidence of immune complexes in glomerulus, **activation of both classic and alternative complement pathways**. * antigens unknown. associated with **Hep C and B**. * **_type II MPGN_**: aka **dense-deposit disease**. rare. abnormalities suggest **activation of alternative complement pathway. ↓ serum C3, normal C1 and C4. ↓ factor B and properdin.** * **C3 and properdin deposited in glomeruli**. * 70% have **C3 nephritic factor (C3NeF)** - circulating antibody that binds to alternate pathway C3 convertase ⇒ ↑ C3 activation and hypocomplementemia. **↓ synthesis C3 from liver** * _morphology_: light microscopy: **large, hypercellular glomeruli** from proliferation of mesangial cells and capillary endothelial cells and infiltrating leukocytes. may have **crescents**. **lobular appearance** from proliferating mesangial cells and ↑ mesangial matrix. **GBM thickened**, glomerular capillary wall looks 'double-contour' or **'tram-track'** on silver or PAS stain. * **_type I_**: presence of **subendothelial electron-dense deposits**. * IF: **granular pattern**. **C3 deposits, some IgG and early complement** (C1q and C4). * **_type II_**: lamina densa is **irregular, ribbon-like, extremely electron-dense** with dense deposits in GBM. * IF: **C3 deposits irregular granular or linear foci in GBM** but not in dense deposits. also in mesangium = **mesangial rings**. IgG absent as well as C1q and C4. * _presentation:_ **kid or young adult with nephrotic syndrome**, hematuria, mild proteinuria, mixed nephrotic-nephritic component. **slowly progressive**. some get crescents and look like RPGN. **50% ⇒ chronic renal failure**. **high recurrence in transplant kidneys**. * _tx_: steroids, immunosuppressive agents, antiplatelet drugs (**none effective**)

Answer 31

* more common in **adults**. * _found with_: **chronic immune comlex disorders** (SLE, Hep B, Hep C, endocarditis, chronic visceral abscesses, HIV, schistosomiasis); **alpha1 antitrypsin deficiency; malignant diseases; hereditary deficiencies of complement regulatory proteins.** * _presentation_: nephrotic syndrome.

Answer 32

* aka **Berger Disease** * prominent **IgA deposits in mesangial regions** on IF. * frequent cause of recurrent gross or microscopic hematuria, **most common type of glomerulonephritis\*\*\*\*** * **2° IgA nephropathy** in pts with liver and intestinal diseases. * **↑ plasma polymeric IgA, circulating IgA immune complexes**. IgA1 ⇒ nephritogenic deposits in mesangium. **uses alternative pathway** (C3 with no C1q or C4). * genetic influence. * **⇒ ↑ IgA synthesis ⇒ trapped in mesangium ⇒ activate alternative complement pathway ⇒ glomerular injury** * more common with **gluten enteropathy (Celiac disease) and liver disease** * _morphology_: can look normal, have mesangial widening and endocapillary proliferation, or rarely have crescents. may have leukocytes. * **healing ⇒ 2° focal segmental sclerosis**. * IF: **mesangial depositition of IgA**, some C3 and properdin, less IgG and IgM. * EM: presence of **electron-dense deposits in mesangium**. * _presentation_: **older children and young adults, gross hematuria after respiratory, GI, or urinary tract infection**, microscopic hematuria **with or without proteinuria**, few have acute nephritic syndrome. **hematuria lasts a few days and returns every few months**. * **slow progression to chronic renal failure** over 20yrs. * ↑ risk of progression: old age, heavy proteinuria, HTN, ↑ glomerulosclerosis. * **recurs in transplants**.

Answer 33

Type II MPGN

Answer 34

IgA Nephropathy

Answer 35

* a hereditary nephritis. **X-linked**. * **females typically limited to hematuria**. * due to abnormal alpha3 (COL4A3), alpha4 (COL4A4), or alpha5 (COL4A5) of type IV collagen. * **COL4A5 is the X-linked**. COL4A3 and COL4A4 are autosomal recessive. * ⇒ **defective assembly type IV collagen**, defective assembly of collagen network * _morphology_: early lesion EM: **diffuse GBM thinning, interstitial foam cells** filled with neutral fats and mucopolysaccharides. * later see **focal segmental and global glomerulosclerosis, vascular sclerosis, tubular atrophy, interstitial fibrosis.** * EM late: irregular foci of thickening alternates with thinning and splitting of lamina densa ⇒ **basket-weave appearance**. * **antibodies to alpha3, alpha4, alpha5 don't stain both glomerular and tubular basement membranes**. **alpha5 staining absent in skin biopsy** specimens. * _presentation_: onset **age 5-20 year**, gross **hematuria** with progression to chronic renal failure, **red cell casts, nerve deafness, eye disorders** (lens dislocation, posterior cataracts, and corneal dystrophy).

Answer 36

Alport Syndrome

Answer 37

* manifested clinically as **familial asymptomatic hematuria**. * **mutation in alpha3 or alpha 4 of type IV collagen. autosomal recessive**. * **homogenous pts may appear like Alport syndrome** and may progress to renal failure. * found on routine U/A * _morphology_: **diffuse thinning of GBM to 150-250nm**. * renal function normal but **may have mild to mod proteinuria**. good prognosis. * needs to be distinguished from IgA nephropathy and Alport syndrome.

Answer 38

* can come from IgA nephropathy, membranous nephropathy, MPGN, FSGS, crescentic GN, poststreptococcal GN, or unknown. * _morphology_: **cortex is thinned, granular cortical surfaces, ↑ peripelvic fat**. * **obliteration of glomeruli** ⇒ **acellular eosinophilic masses**. * accompanied by **HTN, arterial and arteriolar sclerosis, atrophy of associated tubules, irregular interstitial fibrosis, mononuclear leukocytic infiltration.** * dialysis ⇒ arterial intimal thickening, extensive deposition of calcium oxalate crystals, acquired cystic disease * _uremic changes_: **pericarditis, secondary hyperparthyroidism, LV hypertrophy, uremic pneumonitis, uremic gastroenteritis**. * _presentation_: **develops insidiously** then slowly **goes to renal insufficiency or death from uremia**. have nonspecific complaints like **loss of appetite, anemia, vomiting, or weakness**. * most pts **HTN**, have cerebral or cardiovascular manifestations. * **relentlessly progressive**. * nephrotic pts: glomeruli obliterated ⇒ ↓ GFR, protein loss in urine ↓. * if don't get dialysis or transplant, will die.

Answer 39

Chronic Glomerulonephritis

Answer 40

* _presentation_: recurrent microscopic or gross **hematuria**, **nephritic syndrome, nephrotic syndrome, chronic renal failure, and HTN.**

Answer 41

Lupus nephritis

Answer 42

* _presentation_: **purpuric skin lesions on extensor surfaces of arms and legs and buttocks, abdominal pain, vomiting, intestinal bleeding, nonmigratory arthralgia, renal abnormalities**. * renal problems = **gross or microscopic hematuria, nephritic syndrome, nephrotic syndrome** or a combo. * adults may get rapidly progressive GN with crescents. * **mostly kids 3-8 yrs** but may be in adults (renal more severe) * **strong background of atopy in 1/3 pts, onset follows upper resp infection** * **IgA deposited in glomerular mesangium** similar to IgA nephropathy * _morphology_: vary from mild focal mesangial proliferation to diffuse mesangial proliferation or endocapillary to crescentic GN. * IF: **deposition of IgA**, **some IgG and C3 in mesangial region**. * lesions: **subepidermal hemorrhages and necrotizing vsculitis of small vessels in dermis**. * vasculitis can be in other organs such as GI or rarely kidney. * _prognosis_: **excellent in kids**, worse if have diffuse lesions, crescents or nephrotic syndrome.

Answer 43

Henoch-Schönlein Purpura

Answer 44

* an immune complex nephritis **initiated by complexes of bacterial antigen and antibody**. occurs with bacterial endocarditis. * _presentation_: **hematuria and proteinuria**. can have acute nephritic presentation or RPGN. * IF: **glomerular immune deposits**.

Answer 45

Bacterial Endocarditis-Associated GN

Answer 46

* a **leading cause of chronic renal failure**. * _most common lesions of glomeruli_: **non-nephrotic proteinuria, nephrotic syndrome, chronic renal failure**. * causes **hyalinizing arteriolar sclerosis, papillary necrosis, and tubular lesions**. * _morphology_: **capillary basement membrane thickening, diffuse mesangial sclerosis, nodular glomerulosclerosis**. appear same in type I and type II diabetes. * caused by metabolic defect = insulin deficiency, hyperglycermia, or glucose intolerance. ⇒ ↑ type IV collagen and fibronectin and ↓ heparan sulfate proteoglycan * nonenzymatic glycosylation of proteins causes glomerulopathy * **end stage characterized by ↑ GFR, ↑ glomerullar capillary pressure, glomerular hypertrophy, ↑ glomerular filtration area**. * two processes: **metabolic defect ⇒ thickened GBM and ↑ mesangial matrix**; **hemodynamic effects** help develop glomerulosclerosis. **both ⇒ loss of podocytes**.

Answer 47

Diabetic Nephropathy

Answer 48

* **deposition of light-chain AA in the glomeruli**. * stains on Congo red in mesangium and capillary walls. can be in interstitium and blood vessel walls * **obliterates glomerulus**. * _presentation_: **nephrotic syndrome, die of uremia**. kidney size normal or increased.

Answer 49

Amyloidosis

Answer 50

* **fibrillar deposits in mesangium and glomerular capillary walls**. resemble amyloid but don't stain on Congo, also are larger in diameter than amyloid fibrils. * light microscopy: shows **membranoproliferative or mesangioproliferative patterns** * IF: **selective deposition of polyclonal IgG** of IgG4 subclass, **complement C3, and Igkappa and Iggamma light chains.** * _presentation_: **nephrotic syndrome, hematuria, progressive renal insufficiency**. * recurs in kidney transplants.

Answer 51

Fibrillary Glomerulonephritis

Answer 52

* **microtubular deposits**, 30-50 nm in width. have **circulating paraproteins or monoclonal Ig deposition in glomeruli.**

Answer 53

Immunotactoid Glomerulopathy

Answer 54

* deposits of cryoglobulins made of IgG-IgM complexes induce cutaneous vasculitis,, synovitis, and proliferative GN (mostly MPGN type I). * associated with hep C

Answer 55

* can induce glomerular lesions

Answer 56

* produce **circulating monoclonal Ig associated with amyloidosis, deposition of monoclonal Ig in GBM, distinctive nodular glomerular lesions** ⇒ depositionn of nonfibrillar light chains * aka **monoclonal Ig deposition disease** * characterized by **deposition of Igkappa or Iggamma light chains in glomeruli, PAS-pos mesangial nodules, lobular accentuation, and mild mesangial hypercellularity**. * _presentation_: **proteinuria or nephrotic syndrome, HTN, progressive azotemia**.

Answer 57

Multiple myeloma

Answer 58

* characterized by acute diminution of renal function and often has tubular injury. **reversible** lesion. * **most common cause of acute renal failure** (rapid ↓ renal function and urine flow, \<400mL per day) from ischemia, toxic injury to tubules, acute tubulointerstitial nephritis, and urinary obstruction. * **ischemic AKI** - from poor blood flow with hypotension and shock. * **nephrotoxic AKI** - from drugs, contrast, poisons, organic solvents. * **hemolytic crises ⇒ hemoglobinura; skeletal muscle injuries ⇒ myoglobinuria.** * **⇒ intratubular hemoglobin or myoglobin casts** * critical events: tubular injury, disturbed blood flow. * tubule cell injury - **sensitive to ischemia and toxins**. * _reversible changes_ = **loss of polarity**/brush border from redistribution of membrane proteins, ↑ Na delivery to distal tubules ⇒ ↑ tubuloglomerular feedback ⇒ vasoconstriction; **injured cells detach ⇒ luminal obstruction, ↑ intratubular pressure, ↓ GFR** * _irreversible changes_ = **necrosis and apoptosis** ⇒ tubular back-leak ⇒** ↓ tubular flow.** * disturbed blood flow - intrarenal vasoconstriction ⇒ ↓ glomerular blood flow, ↓ oxygen delivery to outer medulla tubular cells * **vasoconstriction caused by ↓ NO, ↓ PGI2, ↑ Renin-angiotensin, ↑ endothelin** * re-epithelization depends on growth factors and cytokines from tubular cells or inflammatory cells. * **TGF-alpha, insulin-like growth factor 1, and hepatocytes growth factor** important * _morphology_: **focal tubular epithelial necrosis, large skip areas** btw necrotic points with rupture of basement membrane and **occlusion by casts**. **mostly in proximal tubule and thick ascending limb in renal medulla**. * tubular damage = **loss of brush borders, simplification of cell structure, cell swelling, vacuolization, sloughing of non-necrotic tubular cells into lumen**. * **eosinophilic hyaline casts and granular casts in distal tubules and collecting ducts**. made of **Tamm-Horsfall protein** and plasma proteins. * _ischemic AKI_ - interstitial edema and leukocytes in dilated vasa recta. flattened epithelial cells with hyperchromatic nuclei and mitotic figures. * _toxic AKI_ - acute tubular injury mostly proximal convoluted tubules. * _mercury chloride_ causes **acidophili**c inclusions then necrosis, desquamate, and calcify. * _carbon tetrachoride_ accumulates neutral lipids in injured cells causes **fatty change then necrosis.** * _ethylene glycol_ causes **ballooning and hydropic or vacuolar degeneration** of **proximal convoluted tubules ⇒ calcium oxalate crystals**. * _presentation_: 3 stages. * 1. **initiation: 36 hrs long, slight ↓ urine output with ↑ BUN. oliguria from ↓ blood flow and ↓ GFR.** * 2. **maintenance: urine output btw 40-400 mL/day (oliguria), salt and water overload, ↑ BUN, hyperkalemia, metabolic acidosis, uremia**. tx: dialysis. * 3. **recovery: ↑ urine volume (up to 3L/day), ↑ urinary loss of water sodium and potassium, hypokalemia, ↑ risk infection**. * 50% do not have oliguria = **nonoliguric AKI** usually with nephrotoxins.

Answer 59

* **_acute_** = rapid onset with **interstitial edema**, leukocyte infiltration (**eosinophils and neutrophils) of interstitium** **and tubules, and focal tubular necrosis**. * **_chronic_** = infiltration with **mononuclear leukocytes, interstitial fibrosis, widespread tubular atrophy**. * _presentation of tubular defects_: **impaired concentration of urine, polyuria or nocturia, salt wasting**, diminished ability to excrete acids (**metabolic acidosis**), **isolated defects in tubular reabsorption or secretion**.

Answer 60

* caused by bacterial infection, **associated with UTI.** **usually gram (-) bacilli: E. coli**, Proteus, Klebsiella, Enterobacter. Also Strep faecalis and staph. * in immunocompromised can be from viruses: **Polyomavius**, CMV, adenovirus. * from bacteremia or **ascending spread** (most common) * starts in distal urethra and introitus, then moves to bladder, and can be aided by urinary tract obstruction and stasis or urine. * **incompetence of vesicoureteral reflex allows ascension to kidney**, allows reflux into ureter. * usually from congenital absence or shortening of intravesical portion of ureter * **intrarenal reflux** = infected bladder urine propelled upward to renal pelvis and into renal parenchyma through open ducts at tips of papillae. * common in upper and lower poles of kidney * _morphology_: **patchy interstitial suppurative inflammation, intratubular aggregates of neutrophils, and tubular necrosis**. damage mostly in **upper and lower poles**. * early = limited to interstitium. * **glomeruli usually okay until late** but are affected in fungal varieties. * complications: * **papillary necrosis in diabetics and pts with urinary tract obstruction**. distal 2/3 of pyramid is gray-white to yellow necrosis. has coagulative necrosis with preservation of tubule outlines * **pyonephrosis**: with **total or almost complete obstruction high in urinary tract**. suppurative exudate fills rnal pelvis, calyces, and ureter with pus. * **perinephric abscess**: extnsion of pus through renal capsule into perinephric tissue * _healing_: macrophages, plasma cells, and lymphocytes come in and cause irregular scars = fibrous depressions on cortical surface. have tubular atrophy, interstitial fibrosis, lymphocytic infiltrate in **patchy, jigsaw pattern with preserved parenchyma around it = pyelonephritic scar**. * associated with inflammation, fibrosis, and deformation of underling calyx and perlvis. * _presentation_: predisposing factors = **urinary tract obstruction, catheters, vesicoureteral reflux, pregnancy, female, preexisting renal lesions, diabetes mellitus, immunosuppression/deficiency**. * **sudden pain** at costovertebral angle with **fever and malaise, dysuria, frequency, urgency, pyuria, pus casts (leukocyte casts)**. * usually recovers in a few days with antibiotics. may persist with bacteremia for years. * superimposition of papillary necrosis ⇒ acute renal failure. * **_polyomavirus nephropathy_**: usually in **allograft pts**. viral infection of tubular epithelial cell nuclei ⇒ **nuclear enlargement and intranuclear inclusions made of virions**.

Answer 61

Acute Pyelonephritis

Answer 62

* caused by bacterial infection, **associated with UTI**. **usually gram (-) bacilli**: E. coli, Proteus, Klebsiella, Enterobacter. Also Strep faecalis and staph. * in immunocompromised can be from viruses: Polyomavius, CMV, adenovirus. * from bacteremia or **ascending spread (most common)** * starts in distal urethra and introitus, then moves to bladder, and can be aided by urinary tract obstruction and stasis or urine. * **incompetence of vesicoureteral reflex allows ascension to kidney**, allows reflux into ureter. * usually from congenital absence or shortening of intravesical portion of ureter * **intrarenal reflux** = infected bladder urine propelled upward to renal pelvis and into renal parenchyma through open ducts at tips of papillae. * common in **upper and lower poles of kidney** * chronic tubulointerstitial inflammation and renal scarring associated with **pathologic involvement of the calyces and pelvis.** * ⇒ end-stage kidney disease * 2 forms: * 1. **_Reflux Nephropathy_**: **more common** form. in **early childhood from UTI on top of congenital vesicoureteral reflux and intrarenal reflux** ⇒ uni or bilateral damage (scarring and atrophy) ⇒ chronic renal insufficiency. * 2. **_Chronic Obstructive Pyelonephritis_**: **recurrent infections on top of diffuse or localized obstructive lesions** ⇒ inflammation and scarring ⇒ chronic pyelonephritis. * parenchymal atrophy, can be bilateral ⇒ renal insufficiency. * **unilateral when occurs with calculi and unilateral obstructive anomalies of ureter.** * _morphology_: kidneys **irregularly scarred, asymmetric** (when bilateral). * _hallmarks_: **coarse, discrete, corticomedullary scars overlying dilated, blunted, or deformed calyces, flattening of papillae.** * mostly upper and lower poles. * **tubules have atrophy as well as hypertrophy or dilation**. can have **colloid casts**. * chronic interstitial inflammation and fibrosis in cortex and medulla. * can have **pus casts**. * obliterative intimal sclerosis in scarred areas, pts with HTN have **hyaline arteriosclerosis**. * **_Xanthogranulomatous pyelonephritis_**: rare form of chronic pyelonephritis with **accumulation of foamy macrophages with plasma cells, lymphocytes, polymorphonuclear leukocytes, and giant cells.** * associated with **Proteus** infections and obstructions. * **produce large, yellowish orange nodules** that can be confused with renal cell carcinoma. * _presentation_: **insidious in onset** or present as **recurrent acute pyelonephritis** with back pain, fever, pyuria, bacteriuria. * **with reflux may be silent** and present with **renal insufficiency and HTN** or find pyuria/bacteriuria as random finding. * **reflux discovered when kids have HTN**. * have **polyuria and nocturia**. * **asymmetrically contracted kidneys with coarse scars, and blunting and deformity of calyceal system. ** * proteinuria is mild, **may develop secondary FSGS**. poor prognosis.

Answer 63

Chronic Pyelonephritis

Answer 64

* occurs with **sulfonamides, synthetic penicillins, synthetic antibiotics (Rifampin), diuretics (thiazides), NSAIDs, and others (allopurinol, cimetidine)**. * begins **15 days after exposure** with **fever, eosinophilia, rash, and renal abnormalities** (hematuria, mild proteinuria, and leukocyturia). * **50% have ↑ serum creatinine level or acute renal failure with oliguria**. see in elderly. * immune response idiosyncratic and **not dose-related**. * **tubulitis** = infiltration of tubules by lymphocytes. very common. * **serum IgE levels ↑, IgE plasma cells and basophils in lesions** ⇒ involves **late phase IgE-mediated hypersensitivity (type I).** * mononuclear or granulomatous infiltrate and **positive for drug haptens = type IV hypersensitivity (T cell)**. * _morphology_: interstitium has **pronounced edema and infiltration by mononuclear cells** (lymphocytes and macrophages). **Eosinophils and neutrophils in clusters**. * **interstitial non-necrotizing granulomas** = have giant cells. **with thiazides and methicillin**. * **glomeruli unaffected except with NSAIDs with minimal change disease and nephrotic syndrome**. * _presentation_: may have **irreversible damage in elderly**.

Answer 65

Acute Drug-Inducd Interstitial Nephritis

Answer 66

* chronic renal disease caused by **excessive intake of analgesic mixtures and having chronic tubulointerstitial nephritis and renal papillary necrosis.** * usually **phenacetin, aspirin, caffeine, acetaminophen, and codeine**. usually two of them. * _sequence of events_: **papillary necrosis**, then **cortical tubulointerstitial nephritis** from impeded urine flow. also water depletion * phenacetin's metabolite = **acetaminophen ⇒ depletes cells of glutathione ⇒ oxidative metabolites** * **aspirin ⇒ inhibits vasodilation** from prostaglandins **⇒ ischemia** for papillae * _morphology_: **kidneys normal** or slightly small, **depressed areas of cortex = cortical atrophy over necrotic papillae.** * **papillae show stages of necrosis, calcification, fragmentation, and sloughing**. * _early_ = patchy necrosis. _late_ = entire papilla necrotic ⇒ **ghosts of tubules and foci of dystrophic calcification.** * _cortical changes_ = **atrophy of tubules, interstitial fibrosis and inflammation**. **cortical columns of Bertin are spared atrophy.** * _presentation_: more common in **women** (5:1). **prevalent in people with recurrent headaches and muscle plain, psychoneurotic patients, and factory workers**. * early findings = **hyposthenuria** (can't concentrate urine) and **distal tubular acidosis ⇒ kidney stones.** * symptoms = **headache, anemia, GI symptoms, and HTN**. 50% have **UTI**. can have **hematuria or renal colic if ureter obstructed**. * **MRI and CT** show papillary necrosis and calcifications. * can **progress to transitional papillary carcinoma of the renal pelvis**. * _tx_: drug withdrawal can cause stabilization or improvement.

Answer 67

Analgesic Nephropathy

Answer 68

* adverse effects related to ability to inhibit COX-dep PG synthesis. **COX-2 is in kidney**. * related syndrome: **acute renal failure** from ↓ blood flow; **acute hypersensitivity interstitial nephritis**; **acute interstitial nephritis and minimal change disease**; **membranous nephropathy**.

Answer 69

* chronic tubulointerstitial nephritis **from aristolochic acid found in herbal remedies**. * **forms adducts with DNA ⇒ renal failure and interstitial fibrosis** associated with **paucity of infiltrating leukocytes.** * increased incidence of carcinoma of kidney and urinary tract.

Answer 70

Aristolochic Nephropathy

Answer 71

* 3 types: * 1. **_acute uric acid nephropathy_** = from **precipitation of uric acid crystals in renal tubules, mostly collecting duct ⇒ obstruction of nephrons ⇒ acute renal failure** * common in those with **leukemias and lymphomas with chemo** * 2. **_chronic urate nephropathy_** = **gouty** nephropathy = protracted forms of hyperuricemia. **deposition of monosodium urate crystals in acidic milieu of distal tubules and collecting ducts and interstitium**. may form **birefrinent needle-like crystals in tubular lumens or interstitium.** * ⇒ **tophus** = made of **foreign-body giant cells, mononuclear cells, firbotic rxn**. * **tubular obstruction ⇒ cortical atrophy and scarring**. * **renal arterial and arteriolar thickening** from HTN. * may have **increased exposure to lead from moonshine**. * 3. **_nephrolithiasis_** = uric acid stones. in 22% of those with gout, 42% of those with secondary hyperuricemia.

Answer 72

Chronic Urate Nephropathy

Answer 73

* associate with **hypercalcemia** as found in hyperparathyroidism, multiple myeloma, vitamin D intoxication, metastatic cancer, and excess calcium intake (milk-alkali syndrome). * is **deposition of calcium in kidney's** or calcium stones. * can **cause chronic tubulointerstitial disease and renal insufficiency**. * **earliest damage done to tubular epithelial cells from mitochondrial distortion**. * then **deposits appear in mitochondria, cytoplasm, basement membrane.** * can **obstruct tubular lumen ⇒ atrophy of nephrons and 2° interstitial fibrosis and inflammation**. * have **alternating areas of scarred and normal parenchyma**. * earliest functional defect is **inability to concentrate urine**. can also get tubular acidosis and salt-losing nephritis. * **slowly progresses to renal insufficiency**

Answer 74

* **excessive accumulation of calcium phosphate crystals in tubules**. * in patients consuming **high doses oral phosphate (for colonoscopy)** * NOT HYPERCALCEMIC. have excess phosphate load. **dehydration can ⇒ precipitation of calcium phosphate ⇒ renal insufficiency a few weeks later.** * only **partially recover renal function**.

Answer 75

Acute Phosphate Nephropathy

Answer 76

* aka **_myeloma kidney_**. * is tubulointerstitial **from tumor** (hypercalcemia, hyperuricemia, obstruction of ureters) **or therapy** (irradiation, hyperuricemia, chemo, infections). * in multiple myeloma: * **Bence Jones proteinuria and cast nephropathy**. failure = amount Bence Jones protein. **combine with Tamm-Horsfall protein** in kidney under **acidic conditions to form large distinct tubular casts** that obstruc tubular lumens and **cause inflammation around casts**. * **amyloidosis** - AL type * **light-chain deposition disease:** **kappa type light chains deposit in GBMs and mesangium** in nonfibrillar forms, ⇒ glomerulopathy, or in **tubular basement membrane** ⇒ tubulointerstitial nephritis. * **hypercalcemia and hyperuricemia**. * _morphology_: pink or blue amorphous masses (**Bence Jones tubular casts**) distend lumen. surrounding **multinucleate giant cells** from phagocytes. interstitial tissue has **nonspecific inflammation and fibrosis**. sometimes get **granulomatous rxn**. * _presentation_: **chronic renal failure** develops insidiously (most common). * acute renal failure with oliguria. * _precipitating factors_: **dehyrdation, hypercalcemia, acute infection, treatment with nephrotoxic antibiotics**. * Bence Jones proteinuria in 70% multiple myeloma. * **non-light-chain proteinuria suggests amyloidosis or light-chain deposition disease**.

Answer 77

She has Light-Chain Cast Nephropathy. Expect her biopsy to show interstitial inflammation and fibrosis, Bence Jones casts with multinucleate giant cells around them.

Answer 78

* renal pathology associated with **sclerosis of renal arterioles and small arteries**. * ⇒ **focal ischemia by vessels with thickened walls and narrowed lumens** * _parenchymal effects_: **glomerulosclerosis, chronic tubulointerstitial injury ⇒ ↓ functional renal mass**. * more frequent in blacks, HTN, diabetes mellitus. * have **medial and intimal thickening and hyaline deposition in arterioles** from extravasation of plasma proteins in injured endothelium and ↑ deposition of basement membrane matrix. * _morphology_: kidneys normal or slightly smaller, **fine granularity** (grain leather) of cortex. * **hyaline arteriolosclerosis of small arteries and arterioles** * **microscopic subcapsular scars** with sclerotic glomeruli and tubular dropout. * **fibroelastic hyperplasia** = interlobular and arcuate arteries have medial hypertrophy, reduplication of elastic lamina, and ↑ myofibroblastic tissue in intima ⇒ narrowed lumen. * narrowing ⇒ **patchy ischemic atrophy** * **foci of tubular atrophy and interstitial fibrosis** * **collapse of GBM, deposition of collagen in Bowman space, periglomerular fibrosis, and total sclerosis of glomeruli.** * _Presentation_: **moderate ↓ renal blood flow, normal GFR** or slightly reduced. may have **mild proteinuria** * **↑ risk renal failure in: African Americans, HTN, diabetes mellitus**

Answer 79

* associated with **malignant or accelerated phase of HTN**. * often **superimposed on preexisting essential benign HTN, 2° forms HTN, or underlying chronic renal disease (GN or reflux nephropathy)** * frequenct cause of death from uremia in pts with scleroderma. * usually **young, men, black**. * _pathogenesis_: initial insult is **vascular damage to kidney** (long-standing HTN, arteritis, coagulopathy) * ⇒ ↑ permeability of small vessels to fibrinogen and plasma proteins, endothelial injury, focal death of vascular wall cells, platelet deposition ⇒ **fibrinoid necrosis of arterioles and small arteries, swelling of vascular intima, intravascular thrombosis**. * PDGF, plasma, and other cells ⇒ **hyperplasia of intimal smooth muscle cells ⇒ hyperplastic arteriolosclerosis.** * kidney becomes very ischemic ⇒ very **↑ plasma renin levels, ↑ aldosterone levels.** * all adds up to cuse malignant arteriolosclerosis * _morphology_: small **pinpoint petechial hemorrhages** on cortical surfaces = '**flea-bitten' appearance**. * **fibrinoid necrosis of arterioles** - eosinophilic granular change in blood vessel wall. * **onion-skinning** = intimal thickening by proliferating smooth muscle cells and accumulation of plasma protein and proteoglycans around blood vessel = **hyperplastic arteriolitis** * _presentation_: **systolic pressure \> 200 and diastolic \> 120, papilledema, retinal hemorrhages, encephalopathy, cardovascular abnormalities, renal failure.** * early symptoms: **headaches, nausea, vomiting, visual impairments** (scotomas aka spots) * HTN crises: **loss of consciousness or convulsions**. * **marked proteinuria and hematuria** * _tx_: anti-HTN drugs, this is a medical emergency.

Answer 80

Malignant Nephrosclerosis

Answer 81

* **unilateral** = 2-5% HTN * from stimulation of renin secretion by JGA and production of angiotension II * _morphology_: 70% from **_occlusion by atheromatous plaque_** at origin of renal artery. more in **men and increases with age and diabetes mellitus**. concentrically placed with **superimposed thrombosis**. * 2nd type = **_fibromuscular dysplasia of renal artery_**. **fibrous and fibromuscular thickening involving intima, media, or adventitia**. **medial** is most common. more common in **women, age 20-40**. usually **medial or distal part of renal artery**. can involve segmental branches and be bilateral. * ischemic **kidney is small** with **atrophy, crowded glomeruli, atrophic tubules, interstitial fibrosis, focal inflammatory infiltrates**. **unaffected kidney has more severe arteriolosclerosis** from HTN. * _presentation_: resemble essential HTN. may hear **bruit in affected kidneys. ↑ plasma or renal vein renin**.

Answer 82

* characterized by **microangiopathic hemolytic anemia, throbocytopenia, renal failure, thrombotic lesions in capillaries and arterioles in tissue beds**. * have **schistocytes** in blood smear. **normal coagulation profile, normal fibrin split products.** * two main forms: **HUS** and **TTP**. * two pathogenic triggers: **endothelial injury**, and **platelet activation and aggregation**. * **endothelial injury** ⇒ platelet activation and aggregation, thrombosis from ↓ PGI₂ and NO production, ↑ endothelin ⇒ vasoconstriction. adhesion molecules also recruit leukocytes which promote thrombosis. * **platelet aggregation** from ↑ large vWF from a **deficiency of ADAMTS13** caused by Ab (common) or inherited (not common) ⇒ activate platelet spontaneously * tissue dysfunction from **microthrombi, vascular obstruction, and tissue ischemia**.

Answer 83

* aka **epidemic, classic, diarrhea-positive**. * **follows infection with O157:H7 E. coli ⇒ Shiga-like toxin**. from **ground hamburger**, drinking water, raw milk, person-person transmission. * usually **kids** or elderly * _prodrome_ = influenza-like or diarrheal symptoms. then **sudden onselt hematemesis and melena, severe oliguria, hematuria, associated with microangiopathic hemolytic anemia, thrombocytopenia, and prominent neurologic changes**. **HTN** in 50%. * Shiga-like toxin **damages endothelium** ⇒ **↑ leukocytes adhesion molecules, ↑ endothelin, ↓ NO, with TNF have endothelial apoptosis ⇒ platelet activation and vasoconstriction** * **schistocytes** on blood smear, **normal coagulation times, normal fibrin split products**. * _morphology_: acute = **patchy or diffuse cortical necrosis, thickened capillary walls, subendothelial deposits of fibrin and cell debris, fibrinoid necrosis** of interlobular arteries and arterioles, **occlusive thrombi** * _tx_: dialysis

Answer 84

typical HUS

Answer 85

* aka non-epidemic, diarrhea-negative. * in **adults**. * 50% have **inherited deficiency of complement factors (ex. factor H**). a few have mutated **factor I or CD46**. * 50% have relapses and **progress to end-stage renal disease**. * associated conditions: antiphospholipid syndrome, pregnancy/postpartum, vascular diseases of kidney, chemo and immunosuppressive drugs, irradiation of kidney. * can have neurologic symptoms. * have **schistocytes** on blood smear, **normal coagulation times, and normal fibrin split products**. * _morphology_: **_acute_** = **patchy or diffuse cortical necrosis and subcapsular petechiae, glomeruli occluded by thrombi, capillary walls thickened, subendothelial deposits of cell debris and fibrin, interlobular arteries and arteriols have fibrinoid necrosis and occlusive thrombi.** * **_chronic_** = varying degrees of scarring. * LM: **glomerli hypercellular** with **thickened capillary walls** with splitting **'tram-track' basement membrane, onion-skinning of arteries and arterioles** * **manifests as renal failure and HTN**.

Answer 86

* **\*\*\*\*_pentad_**: **fever, neurologic symptoms, microangiopathic hemolytic anemia, thrombocytopenia, and renal failure.** * caused by **Ab or genetic defects ⇒ functional deficits in ADAMTS13** * most commonly by **inhibitory autoantibodies**. * present as **adults \<40yrs**. * **CNS involvement is dominant feature**, renal present in 50%. * _tx_: exchange transfusions and immunosuppressive therapy * have **schistocytes** on blood smear, **normal coagulation times, and normal fibrin split products**. * _morphology_: **_acute_** = **patchy or diffuse cortical necrosis and subcapsular petechiae, glomeruli occluded by thrombi, capillary walls thickened, subendothelial deposits of cell debris and fibrin, interlobular arteries and arteriols have fibrinoid necrosis and occlusive thrombi.** * **_chronic_** = varying degrees of scarring. * LM: **glomerli hypercellular** with **thickened capillary walls** with splitting **'tram-track' basement membrane, onion-skinning of arteries and arterioles** * manifests as **renal failure and HTN**.

Answer 87

* atherosclerotic unilateral renal artery stenosis ⇒ HTN * bilateral renal artery disease common cause of chronic ischemia with renal insufficiency in older adults * tx: surgical revascularization.

Answer 88

* **embolization** of atheromatous plaques from aorta or renal artery **into intraparenchymal renal vessels in elderly patients with severe atherosclerosis. ** * contain **cholesterol crystals** which you see as **rhomboid clefts**. * usually of no consequence. * **in elderly with compromised renal function may ⇒ acute renal failure usually after abd surgery on atherosclerotic aneurysms.**

Answer 89

* seen with Sickle-Cell disease or trait. * _presentation_: **hematuria and diminished concentrating ability (hyposthenuria), proteinuria**. * from **accelerated sickling in hypertonic hypoxic renal medulla**. **hyperosmolarity dehydrates RBC and ↑ intracellular HbS concentrations.** * have **patchy papillary necrosis**.

Answer 90

* usually **after an obstetric emergency like abruptio placentae, septic shock, or extensive surgery.** * **bilateral and symmetric = fatal** without supportive therapy. * _morphology_: massive ischemic necrosis **limited to cortex**. looks like acute ischemic infarct. * **glomerular and arteriolar microthrombi** usually focal. * **acute necroses of small arterioles and capillaries** * **lesions patchy with coagulative necrosis** * **hemorrhages into glomeruli with formation of fibrin plugs in glomerular capillaries**. * ⇒ **sudden anuria**, terminating rapidly in **uremic death**.

Answer 91

* has limited collateral circulation, is 'end-organ', and gets 1/4 CO. * most are due to **emboli from left atrium and ventricle after an MI**. * less frequently from vegetative endocarditis, aortic aneurysm, aortic atherosclerosis. * _morphology_: infarcts in kidney are white. ** After 24hrs are sharply demarcated, pale, yellow-white areas** with small irregular foci of hemorrhagic discoloration. * **ringed by zone of intense hyperemia.** * **wedge-shaped, apex points towards medulla**. * undergo progressive fibrous scarring ⇒ **V shaped depressed, pale, gray-white scars**. undergo **ischemic coagulative necrosis**. * _presentation_: **usually silent**. can have **pain with tenderness at CVA with red cells in urine**.

Answer 92

* have **bilateral agenesis** in stillborn kids. * associated with **limb defects and hypoplastic lungs** ⇒ **early death**. * **unilateral agenesis** is uncommon. can live as long as no other abnormalities. * **opposite kidney enlarged** from compensatory hypertrophy. * **can develop glomerular sclerosis** from adaptive changes in hypertrophied nephrons.

Answer 93

* **bilaterally** ⇒ renal failure in **early childhood**. * **unilateral** = acquire **scarring** from vascular, infectious, or parenchymal diseases. * **truly hypoplastic kidney has no scarring and has ↓ number renal lobes and pyramids (\<6)** * **_oligomeganephronia_** = small kidney with fewer nephrons that are hypertrophied.

Answer 94

* lie **just above pelvic brim or within the pelvis**. * normal or slightly small kidneys. * **kinking or tortuosity of ureters ⇒ obstruction to urinary flow ⇒ ↑ risk bacterial infections**.

Answer 95

* **fusion of upper or lower poles of kidneys ⇒ horseshoe-shaped structure** continuous **across midline anterior to great vessels.** * most fused at lower pole (90%).

Answer 96

* **persistence in the kidney of abnormal structures**: cartilage, undifferentiated mesenchyme, and immature collecting ductules: **and by abnormal lobar organization**. * associatead with **ureteropelvic obstruction, ureteral agenesis or atresia, and anomalies of lower urinary tract.** * dysplasia is uni or bilateral and cystic. * **enlarged, irregular, and multicystic**. * cysts vary in size and **lined by flattened epithelium**. * **presence of islands of undifferentiated mesenchyme with cartilage and immature collecting ducts.** * **unilateral dysplasia** discovered by **appearance of flank mass**, opposite kidney is normal. * **bilateral multicystic renal dysplasia** will go to **renal failure**.

Answer 97

* **autosomal dominant**. **multiple expanding cysts of both kidneys** that destroy renal parenchyma and cause renal failure. systemic disease = cysts happen in other organs. * 1/400-1000 births. **need mutation of both alleles of PKD gene**. * **bilateral**. initially involve **portions of nephrons** ⇒ renal function good until 30-50yrs. * mutations of chromosome **16p13.1 (PKD1) and 4q21 (PKD2)**. * **PKD1 is 85%. severe disease, end-stage renal disease or death by age 53**. * age 69 for PKD2. * PKD1 encodes **polycystin-1** an integral membrane protein **in tubular epithelial cells in distal nephron**. * PKD2 encodes **polycystin-2**, integral membrane protein in **all segments of renal tubules and some extrarenal tissues**. functions as **Ca-permeable cation channel** so a defect ⇒ disrupted intracellular Ca level regulation. * **defects in mechanosensing, Ca flux, and signal transduction underlie cyst formation.** * polycystin 1 and 2 are located on primary cilium of tubular cells. bending cilia allows Ca channels to open. * defect ⇒ no opening of Ca channels ⇒ changes in cellular proliferation, basal levels of apoptosis, interactions with ECM, and secretory function of epithelia. * **↑ proliferation and ↑ intraluminal fluid from ↑ secretion ⇒ cyst formation** * _morphology_: bilaterally enlarged kidneys. ** mass of cysts with no obvious parenchyma btw**. * cysts filled with **clear, serous fluid or turbid, red-brown hemorrhagic fluid**. * arise from tubules and move toward calyces and pelvis ⇒ **pressure defects**. * lining of epithelium. * _presentation_: **asymptomatic** until renal insufficiency. * or **pain from hemorrhage or dilation of cysts, hematuria, urinary tract infection, renal stones, HTN.** * dragging sensation. * sometimes insidious onset hematuria with progressive chronic kidney disease (proteinuria, polyuria, HTN). * progression **accelerated in blacks, males, and pts with HTN**. * **40% have polycystic liver disease**. * also can have intracranial **berry aneurysms, mitral valve prolapse** * 40% die of coronary of HTN heart disease, 25% of infection, 15% ruptured berry aneurysm or HTN intracerebral hemorrhage.

Answer 98

* **autosomal recessive**. perinatal, neonatal, infantile, and juvenile forms. * **perinatal and neonatal** most common * caused by mutations of **PKHD1 gene** encoding **fibrocystin**. highly expressed **in adult/fetal kidney and liver and pancreas.** * localized to primary cilium of tubular cells * _morphology_: **kidneys enlarged with smooth surface**. numerous **small cysts** in cortex and medulla, looks **spongelike**. * dilated elongated channels perpendicular to cortical surface. **cylindrical dilation of collecting tubules.** * **cysts have uniform lining of cuboidal cells**. * **liver has cysts with portal fibrosis** and **proliferation of portal bile ducts**. * survive infantile or juvenile form may ⇒ hepatic fibrosis with bland periportal fibrosis and proliferation of well-differentiated biliary ductules = **_congenital hepatic fibrosis_**. * may develop portal HTN with splenomegaly

Answer 99

* restricted to lesions consisting of **multiple cystic dilations of collecting ducts in medulla**. * in **adults**, incidental finding or **from secondary complications**: **calcifications in dilated ducts, hematuria, infection, urinary calculi**. renal function normal. * _gross inspection_: **papillary ducts in medulla dilated**, **small cysts** present. * cysts **lined by cuboidal epithelium or transitional epithelium**. * **cortical scarring absent** unless have pyelonephritis. * _features_: **hematuria, UTI, recurrent renal stones**.

Answer 100

* variable number of **cysts in medulla, concentrated at corticomedullary junction**. * **cortical tubulointerstitial damage** causes renal insufficiency. * **most genetic cause of end-stage renal disease in children and young adults**. * **juvenile form - NPH1, NPH2, NPH3 mutated**. * present in **primary cilia, basal bodies of the cilia, or centrosome organelle**. * NPH1, NPH3-NPH6 = **nephrocystins** * **NPH2 = inversin**, mediates left-right patterning during embryogenesis * 3 forms: * 1. sporadic/nonfamilial * 2. **familial juvenile nephronophthisis = most common.** * **autosomal recessive**, manifest in childhood or adolescence. * 3. renal-retinal dysplasia = as ocular lesions. * _morphology_: **small kidneys** with **contracted granular surfaces** and cysts in medulla (corticomedullary junction). small cysts in cortex. * lined by **flattened or cuboidal epithelium**, surrounded by **inflammatory cells or fibrous tissue.** * **widespread atrophy and basement membrane thickening of proximal and distal tubules** in cortex. interstitial fibrosis. * in **children or adolescents** with unexplained chronic renal failure, family history, and chronic tubulointerstitial nephritis. * _features_: **salt wasting, polyuria, growth retardation, anemia**. defect in concentrating ability, tubular acidosis. can have ocular motor abnormalities, retinal dystrophy, **liver fibrosis**, and cerebellar abnormalities. **terminal renal failure in 5-10 yrs**.

Answer 101

* variable number of **cysts in medulla, concentrated at corticomedullary junction**. * cortical tubulointerstitial damage causes renal insufficiency. * **autosomal dominant**. mutation in **MCKD1 and MCKD2**. progresses to end-stage kidney disease in adult life. * _morphology_: **small kidneys with contracted granular surfaces** and cysts in medulla (corticomedullary junction). small cysts in cortex. * **lined by flattened or cuboidal epithelium**, surrounded by **inflammatory cells or fibrous tissue.** * **widespread atrophy and basement membrane thickening of proximal and distal tubules** in cortex. interstitial fibrosis. * _features_: **salt wasting, polyuria**.

Answer 102

* pts have **end-stage renal disease**, are on **dialysis**, and show **numerous cortical and medullary cysts**. * contain **clear fluid, lined by hyperplastic or flattened tubular epithelium**, contain **calcium oxalate crystals.** * form from **obstruction of tubules by interstitial fibrosis or oxalate crystals**. * _presentation_: **mostly asymptomatic**. may have **hematuria**. 7% develop **renal cell carcinoma**.

Answer 103

* **multiple or single** cortical cystic spaces usually 1-5cm in diameter. * **translucent, lined by gray, glistening, smooth membrane, filled with clear fluid. single layer of cuboidal or flattened cuboidal epithelium. can be atrophic**. * **usually post mortem findings**. * if hemorrhage ⇒ **sudden distension and pain**, and bizarre radiographic shadows. * have **smooth contours, are avascular, and show as fluid** on ultrasound.

Answer 104

* ⇒ ↑ susceptibility to infection and stone formation. * unrelieved ⇒ hydronephrosis/obstructive uropathy = **permanent renal atrophy**. * can be sudden/insidious, partial/complete, uni/bilateral. * common causes: * **congenital anomalies**: posterior urethral valves and structures, meatal stenosis, bladder neck obstruction, ureteroplevic junction narrowing, vesicoureteral reflux. * **urinary calculi** * **benign prostatic hypertrophy** * **tumors** * **inflammation** * **sloughed papillae or blood clots** * **pregnancy** * **uterine prolapse and cystocele** * **functional disorders**: spinal cord damage, diabetic nephropathy, abnormalities or ureter or bladder. * **_hydronephrosis_** = **dilation of renal pelvis and calyces** associated with **progressive atrophy of kidney** from obstruction to outflow of urine. * **high pressure in pelvis** causes renal atrophy and causes **dimunition in inner medullary blood flow.** * also get **interstitial fibrosis**. * GFR decreases later on, have impaired concentrating ability. * _morphology_: **_sudden and complete obstruction_** ⇒ **↓ GFR, mild dilation of pelvis/calyces, atrophy of renal parenchyma. ** * **_subtotal/intermittent_** ⇒ normal GFR, progressive dilation. * kidney enlargred. interstitial inflammation * **_chronic_** = cortical tubular atrophy with **diffuse interstitial fibrosis**. progressive **blunting of apices of pyramids, become cupped**. * **_advanced_** = kidney thin-walled cystic structure with **parenchymal atrophy, total obliteration of pyramids, thinning of cortex.** * _presentation_: * **_acute_** = **pain** from distention, **renal colic**, prostatic enlargment ⇒ **bladder symptoms**. * **_unilateral complete/partial hydronephrosis_** = **silent**. diagnose by ultrasound. * **_bilateral partial obstruction_** = **inabiity to concentrate urine, polyuria, nocturia, distal tubular acidosis, salt wasting, secondary renal calculi, chronic tubulointerstitial nephritis with scarring and atrophy of papilla and medulla. HTN.** * **_complete bilateral obstruction_** = **oliguria or anuria** ⇒ death. if relieved can have **postobstructive diuresis** (lose lots of sodium chloride).

Answer 105

* **men**\>women, ages **20-30**yrs. **family predisposition**. * 4 types: * 1. **calcium stones** (70%) * 2. **triple stones/struvite stones (**15%) * 3. **uric acid stones** (5-10%) * 4. **cystine stones** (1-5%) * **mucoprotein matrix** in all stones. * could also be caused by **deficiency in inhibitors of crystal formation in urine**: pyrophosphate, diphosphate, citrate, glycosaminoglycans, osteopontin, nephrocalcin. * determinant = **↑ urinary concentration of constituent, supersaturated.** can have **low urine volume** as well. * _morphology_: **80% unilateral**. usually in **renal calyces and pelves and bladder**. * renal pelvies - **small stones, smooth or jagged**. * _presentation_: **smaller stones** produce colic with **intense pain** and ureteral obstruction. * **larger stones** remain silent in renal pelvis. * manifest by **hematuria**

Answer 106

* 70% of calculi * **calcium oxalate** or mixed with calcium phosphate * 5% have **hypercalcemia and hypercalciuria**; **55% have hypercalciuria without hypercalcemia**; 20% have **hyperuricosuric calcium nephrolithiasis** (↑ uric acid secretion). * 5% have **hyperoxaluria** from ↑ absorption; **hypocitraturia with acidosis and chronic diarrhea** ⇒ stones. * **radiopaque**

Answer 107

* 15% of all calculi * **Magnesium ammonium phosphate**. * from bacteria (**Proteus**) which convert urea to ammonium ⇒ **alkaline urine ⇒ precipitation**. * forms large stones = **staghorn calculi**. take up **large part of renal pelvis**.

Answer 108

* 5-10% of calculi * common with **hyperuricemia** (gout). * 50% have neither hyperuricemia nor ↑ uric acid secretion. have **urine pH \<5.5 ⇒ precipitate uric acid**. * **radiolucent**.

Answer 109

* 1-5% of calculi * from **genetic defects in renal absorption of amino acids ⇒ cystinuria**. * get stones at **low urinary pH**.

Answer 110

* small adenoma **arising from renal tubular epithelium**. * **benign**, usually found at autopsy. * usually papillary * _morphology_: **\<0.5cm** in diameter, in cortex, **pale yellow-gray, discrete, well-circumscribed nodules**. * made of complex, branching, **papillomatous structues with complex fronds**. * can grow as tubules, glands, cords, and sheets. * **cuboidal to polygonal cells** in shape, regular **small central nuclei, scanty cytoplasm, no atypia.** * have **trisomy 7 and 17**. * **3cm is cutoff for metastases**.

Answer 111

* **benign**, made of **vessels, smooth muscle, and fat**. * in **25-50% pts with tuberous sclerosis** = loss of function mutation in TSC1 or TSC2 tumor suppressor genes. * lesions of cerebral cortex ⇒ **epilepsy, mental retardation, skin abnormalities, and benign tumors**. * susceptible to **spontaneous hemorrhage**.

Answer 112

* **benign epithelial tumor** of **large eosinophilic cells** with small round nuclei and **large nucleoli.** * **numerous mitochondria**. * _gross_: **tan or mahogany brown, homogeneous, well encapsulated**. up to 12cm in diameter. * can be familial = multicenteric.

Answer 113

* in **older people (50-70yrs**), **2:1 men**:women. * **arise from tubular epithelium**. * _risk factors_: **tobacco**\*\*, obesity, HTN, estrogen therapy, asbestos, petroleum, heavy metals, tuberous sclerosis, acquired cystic disease, chronic renal failure. * usually **sporadic** but **can be autosomal dominant**. * **_Von Hippel-Lindau syndrome_** - in familial and sporadic clear cell tumors. * **_Familial clear cell carcinoma_** * **_Hereditary papillary carcinoma_** -**multiple bilateral tumors** with papillary histology. **mutated MET.** * types: * **clear cell carcinoma** (70-80%) * **papillary carcinoma** (10-15%) * **chromophobe renal carcinoma** (5%) * **collecting duct (Bellini duct) carcinoma** (\<1%) * _morphology_: usually at the **poles**. tendency to _invade the renal vein_ and grow as solid column of cells in vessel. can **extend to right side of heart.** * _presentation_: **costrovertebral pain, palpable mass, and hematuria** seen in 10% of cases. hematuria most reliable. * general symptoms: fever, malaise, weakness, weight loss. * **paraneoplastic syndromes**: polycythemia, hypercalcemia, HTN, hepatic dysfunction, feminization or masculinization, Cushing syndrome, eosinophilia, leukomoid rxn, amyloidosis. * tendency to **metastasize widely before have symptoms**. * metastasizes to: **lungs, bones**, regional lymph nodes, liver, adrenal, and brain. * _prognosis_: 5 year survival 45%. 15-20% with renal vein invasion. 70% without distant metastases. * _tx_: nephrectomy.

Answer 114

* 70-80% renal cell carcinomas * **nonpapillary cells**, clear or granular cytoplasm. **95% sporadic**. associated with VHL on chromosome 3 (deletion or **somatic mutation or hypermethylation**) * **VHL** encodes protein in ubiquitin ligase complex, mutation ⇒ ↑ HIF-1 ⇒ ↑ VEGF, PDGF, TGF-alpha, TGF-beta. upregulation of insulin-like growth factor 1. * arises from **proximal tubular epithelium**. * **solitary unilateral lesion, spherical. bright yellow-gray-white tissue, distorts renal outline**. yellow = **prominent lipid accumulation** in tumor cells. * large areas of **ischemic, opaue, gray-white necrosis** and foci of hemorrhage. * margins sharply defined and **confined in capsule**. * growth pattern can be **trabecular or tubular**. * **tumor cells rounded or polygonal** shape with **clear or granular cytoplasm** (glycogen and lipids). * **branching vasculature, cysts, and solid areas**. * most are **well differentiated** but some have nuclear atypia with bizarre nuclei and giant cells.

Answer 115

* 10-15% renal cell carcinomas * **papillary growth pattern**, familial and sporadic. * _sporadic_ = **trisomies 7, 16, 17, and loss of Y** in males * _familial_ = **trisomy 7**. * **MET** on chromosome 7 = receptor for hepatocyte growth factor. * **multifocal** in origin, **bilateral**. * from **distal convoluted tubules**. * hemorrhagic and cystic. * **most common type in those with acquired cystic disease**. * **cuboidal or low columnar cells** in papilary formations. * **interstitial foam cells** in papillary cores. **psammoma bodies**. * little stroma but **highly vascularized**.

Answer 116

* 5% renal cell carcinomas * made of cells with **prominent cell membranes** and **pale eosinophilic** cytoplasm with **halo around nucleus**. * **arranged in solid sheets with concentration of largest cells around blood vessels**. * multiple chromosome losses and **extreme hypodiploid**y. * grow **from intercalaed cells of collecting ducts**. * **good prognosis**. * hard to **distinguish from oncocytoma**.

Answer 117

* \<1% renal cell carcinomas * from **collecting duct cells in medulla**. * characterized by **nests of malignant cells enmeshed within prominent fibrotic stroma** (medullary). * **irregular channels lined by atypical epithelium** with **hobnail pattern**.

Answer 118

* 5-10% of renal tumors come **from urothelium of renal pelvis**. * **produce hematuria** quickly, **small when discovered.** * block urinary outflow and **cause palpable hydronephrosis and flank pain**. * can involve pelvis, ureters, bladder. * **50% have preexisting bladder urothelial tumor**. * **foci of atypia or carcinoma in situ in urothelium remote from renal pelvis and bladder** in pts with **analgesic nephropathy and Balkan nephropathy**. * **infiltration of pelvic wall and calcyes** is common. * _presentation_: **flank pain, hydronephrosis, hematuria**. * poor prognosis.