Review of Renal Anatomy and Histology with Introduction to ...



Review of Renal Anatomy and Histology with Introduction to Renal Pathology (Robbins pp. 931-936)

Renal anatomy

Renal Histology Distribution of glomerular damage

Pattern of glomerular injury

|Injury |Presentation |Description |

|capillary wall alterations |proteinuria |may be thickened due to immune complexes |

|GBM alterations |proteinuria (permeable to albumin) |may be thickened due to accumulation of structural proteins |

|proliferation |hematuria |( in cells either intrinsic (e.g., mesangial cells) or extrinsic (e.g., e.g., |

| | |inflammatory), may have deposits |

|necrotizing | |necrosis usually w/ disruption of capillary wall & fibrinoid change |

|cellular crescents |dysmorphic rbcs w/ rbc casts in urine, acute |defn – 2 cellular layers occupying min 1/3 of circumference |

| |renal failure |( in cells in Bowman’s space (parietal epithelial cells & m(), often see fibrin, if |

| |clinically “RPGN” |>80% glomeruli w/ crescents ( “crescentic GN” |

|fibrocellular crescent | |same as above but w/ fibrosis |

|fibrous crescent | |fibrous scar which may or may not have arisen from cellular/fibrocellular crescents |

|hyalinosis |proteinuria |acellular, structureless material located in capillary lumen consisting of |

| | |glycoproteins & sometimes lipids |

|sclerosis | |( in mesangial matrix or fibrosis w/ glomerular collapse or occlusion ( glomerular |

| | |scar; possible final pathway |

IF patterns

• granular – due to discrete deposits of immune complexes, best seen on capillary loops

• linear – smooth, global staining of GBM

• mesangial – w/in mesangial matrix

EM patterns

• epithelial cell injury – effacement of foot processes and microvillous transformation

• subepithelial deposits – btw epithelial cells and GBM

• subendothelial deposits – btw endothelial cells and GBM

• mesangial matrix deposits – in mesangium

Immune complex deposition

In situ deposition

• antibodies to GBM deposit on GBM itself (linear IF pattern) (e.g., anti-GBM GN)

• antibodies to intrinsic glomerular antigens (granular IF pattern) (e.g., Heymann’s nephritis, , membranous GN)

• nonglomerular antigens bind to GBM, antibodies bind to planted antigen

Circulating immune complex deposition

• complexes trapped in glomerular filter ( incite inflammatory response

Progression of renal injury

• end stage renal disease ( compensatory hypertrophy, ( glomerular pressure, systemic HTN

Clinical manifestations of renal disease

• acute nephritic syndrome – hematuria, mild to moderate proteinuria, HTN

• nephrotic syndrome – heavy proteinuria (> 3.5 g/d), hypoalbuminemia, severe edema, hyperlipidemia, lipiduria

• asymptomatic hematuria or proteinuria – subtle/mild glomerular abnormalities

• acute renal failure – oliguria or anuria, recent onset of azotemia

• chronic renal failure – prolonged symptoms and signs of uremia

• renal tubular defects – polyuria, nocturia, electrolyte disorders

• urinary tract infection – bacteriuria, pyuria

• nephrolithiasis (renal stones) – renal colic, hematuria, recurrent stone formation

• urinary tract obstruction and renal tumors – varied manifestations

Renal failure

• diminished renal reserve – GFR 50% of normal, serum BUN and Cr values normal, pts asymptomatic

• renal insufficiency – GFR 20% to 50% of normal, azotemia appears, anemia, HTN, polyuria, nocturia

• renal failure – GFR less than 20% to 25% of normal, edema, metabolic acidosis, hypocalcemia, overt uremia

• end-stage renal disease – GFR less than 5%, end stage of uremia

Medical Renal Disease (Robbins pp. 942-968)

Nephrotic Syndrome – proteinuria > 3.5 g/d, hypoalbumenia (< 3.5 g/dL), edema, hyperlipidemia/hypercholesterolemia, little or no hematuria

|Disease |Epi |Path |Clinical/Rx |

|Minimal Change Dz |children (most) |cause: unknown |nephrotic syndrome, but nl renal |

|(Lipoid Nephrosis, Nil Dz) |also adults |LM: nl glomeruli, lipids in tubular cells |fx |

| | |IF: no staining |diagnosis of exclusion |

| | |EM: diffuse effacement of epi foot processes, microvillous transformation |rx w/ steroids, sometimes |

| | |of epi cell |spontaneous remission |

| | |protein & lipid in prox tubule | |

|Focal & Segmental GN |uncommon in children|cause: 1o (idiopathic)/2o (HIV, morbid obesity, ( renal mass) |nephrotic syndrome, renal |

|(Focal Sclerosis, FSGS) |freq in adults |LM: segmental sclerosis (( mesangial matrix), hyalinosis, atrophy of prox |insufficiency, HTN, hematuria |

| |African Americans |tubule |can progress to renal failure |

| | |IF: passive trapping of IgM, C3 |recurs in transplants at |

| | |EM: diffuse effacement of epi foot processes, separation of epi cells from|relatively high freq |

| | |GBM (vacuolization), cell swelling, proliferation |rx w/ steroids somewhat helpful |

| | |mech includes circulating factor, hemodynamic injury, glom hypertrophy, | |

| | |hyperlipidemia, 1o injury or dysfxn of glom cells | |

|Membranous Nephropathy |adults |cause: 1o (idiopathic)/2o (HBV, SLE, gold therapy); immune-complex |lower extremity edema, mild renal |

| |leading cause of |mediated |insufficiency |

| |nephrotic syndrome |LM: uniform thickening of the GBM on H&E or PAS stains, silver stain will |chronic GN can occur |

| | |see spikes |rx w/ steroids, sometimes |

| | |IF: granular capillary-loop of IgG, C3 |spontaneous remission, sometimes |

| | |EM: subepi electron dense deposits (spikes = GBM rxn to deposits), |nothing works |

| | |effacement of epi foot processes, microvillous transformation | |

| | |little glom cell prolif or inflam exudate | |

|Diabetic Nephropathy |adults 10-20 yrs |cause: poor metabolic control, hyperfiltration, genetic factors, HTN |microalbuminuria progressing to |

| |after onset of |LM: marked uniform thickening of GBM & ( of mesangial matrix w/o ( cells, |nephropathy (nephrotic syndrome & |

| |diabetes |periph spherical accumulations (Kimmelstiel-Wilson nodules), hyaline |mild renal insufficiency) |

| | |arteriosclerosis (aff and eff arterioles) |rx w/ good metabolic & HTN control|

| | |IF: linear Ig, albumin |(slow progression) |

| | |EM: homogenous thickened GBM w/o deposits | |

|Amyloid |adults w/ multiple |cause: deposition of light chains, chronic infxns, chronic dialysis, |no rx |

| |myeloma |familial | |

| |familial in others |LM: amorphous pink material in all 4 compartments, stains positively w/ | |

| | |Congo red & shows circular dichroism under polarized light | |

| | |IF: kappa or lambda chains | |

| | |EM: microfibrils | |

| | |manifestation of plasma cell dyscrasias | |

Nephritic Syndrome – inflamm damages glom capillaries ( hematuria (rbc casts/smoky, brown urine), oliguria, azotemia, HTN, mild proteinuria, mild edema

|Disease |Epi |Path |Clinical/Rx |

|IgA Nephropathy |young adults |cause: unknown; ( synthesis of IgA by gut, errors of IgA processing by liver |viral illness 1-2 d before |

|(Berger’s Dz) |> in males |LM: mild to moderate diffuse proliferation of mesangial cells & matrix, |recurrent microscopic or gross |

| |Asia, W. Eur, |cellular crescents rare |hematuria & proteinuria |

| |Mexico |IF: granular IgA deposits in mesangium |slowly prog HTN & renal insuff ( |

| | |EM: mesangial electron dense deposits, focal or no foot process effacement |20% lose renal fxn |

|Post Infectious GN |common in children |cause: serum sickness (Ag-Ab complexes ( trapped in glom ( accumulate & |no rx, but usually no sequelae |

|(Post Strep GN) | |stimulate C’ ( inflamm | |

| | |LM: ( in mesangial cells & varying numbers of inflamm cells (PMNs) w/ endo | |

| | |cell swelling, cellular crescents, inflamm & edema in interstitium | |

| | |IF: diffuse granular IgG, C3 (IgA, IgM) around cap loops | |

| | |EM: electron dense material ( “humps” subepi | |

| | |strep common; also staph, pneumo, others | |

|Lupus Nephritis (LN) |young women |cause: SLE (autoimmune immune complexes) |rx w/ steroids, other |

| |renal dz imp cause |LM/EM: |immunosuppressive |

| |of morbidity, death|normal glomeruli | |

| |in SLE |mesangial proliferative (nl/( cells) – LM shows ( matrix, EM shows mesangial | |

| | |deposits | |

| | |focal proliferative – segmental ( cells < 50%, EM shows deposits in | |

| | |mesangium, subendo space | |

| | |diffuse proliferative – same as above, but > 50% | |

| | |membranous – spikes, subepi deposits, mesangial deposits | |

| | |IF: full house mesangial or cap, IgG, IgA, IgM, C3, C1q | |

| | |EM: tubuloreticular inclusions in endo cells | |

|Membranoproliferative GN |older children & |cause: complement, 2o causes (Hep C) |type II worse prognosis |

|(MPGN) |young adults |LM: diffuse global thickening of capillary loops accompanied by ( numbers of | |

|Type I |relatively rare |mesangial cells & accumulation of mesangial matrix, double contours on silver| |

|Type II – Dense Deposit Dz | |stain (GBM split) | |

|(DDD) | |IF: granular C’ (C3) in mesangium, periph cap loops | |

| | |EM: Type I – excess matrix containing deposits, mesangial cells extend to | |

| | |subendo space, subendo deposits, endo cells make GBM ( double contours, foot | |

| | |process effacement, microvillous transformation | |

| | |EM: Type II – massive, very electron dense deposits in lamina densa of | |

| | |capillary GBM, GBM appears scalloped | |

|Anti-GBM Dz |> in young men, but|cause: circulating IgG Ab ( interacts w/ Goodpasture’s Ag (subunits of NC1 |pulmonary hemorrhage followed by |

|(Goodpasture’s Dz) |at any age |domain of collagen IV), viral infxn, smoking, hydrocarbons |ARF |

| |2nd peak in elderly|LM: crescentic GN |rx w/ steroids, cytotoxic drugs, |

| | |IF: linear IgG, C3 in GBM |plasmaphoresis |

| | |EM: collapse of cap loops, frag of GBM, no GBM deposits | |

|GBM Dz: |females mild |cause: lack Goodpasture’s Ag - ( mech fragility & breakage of GBM(micro/macro|penetrance important |

|Alport’s Hereditary Nephritis |males CRF by 40 |hematuria; COL4A5 gene |deficits in hearing, mental |

|(AHN) | |LM: early nl, later focal sclerosis or proliferative GN, foam cells |retardation, platelet |

| | |(glomeruli, interstitium) |abnormalities |

| | |IF: no staining |renal transplants for AHN pts ( |

| | |EM: (diagnosis) – segmental thickening & splitting of GBM ( layered, other |anti-GBM nephritis |

| | |segments show marked thinning | |

|GBM Dz: |children & adults |cause: unknown |no rx |

|Thin Basement Membrane |familial |LM/IF: unremarkable | |

|Disorder | |EM: marked thinning of GBM | |

Nephrotic Syndromes

Nephritic Syndromes

Crescents

Male Reproductive System (Robbins pp. 1011-1034)

Prostate

Inflammations

• acute bacterial prostatitis – minute, dissemin’ abscesses; large necrotic areas; or diffuse edema, congestion, suppuration

• chronic prostatitis – aggregation of lymphocytes, plasma cells, macrophages, PMNs

Benign Prostatic Hypertrophy (Hyperplasia)

• epidemiology

• common in men over 50

• ( w/ age (90% in 8th decade)

• pathology/pathogenesis

• large hyperplastic nodules in central, periurethral region of prostate

• composed of glandular & stromal proliferation

• may be caused by testosterone (DHT) or advancing age

• clinical

• arise when nodules compress and narrow urethra ( dysuria

• usually no rx, but 5-10% need surgery if serious urinary tract obstruction

• finasteride (anti-androgen) somewhat helpful

Carcinoma

• epidemiology

• 3rd leading CA death in men (11% of CA deaths)

• ( w/ age (peak in 8th decade)

• Af-Am > Caucasians > Asians

• occult CA common (9/10 remain undetected & clinically unimportant)

• pathology/pathogenesis

• most lesions adenocarcinoma (back-to-back acini w/ little stroma), in peripheral zone of gland

• gritty and firm tissue, felt best by palpation

• prostatic intraepithelial neoplasia (PIN) may be precursor to frank carcinoma (many of the same features)

• Gleason grade

• 1 = well-differentiated (small to medium glands closely spaced)

• 3 = moderately differentiated (cribiform patterns)

• 5 = poorly differentiated (cords, nests, solid sheets, individual cells w/ anaplastic features)

• Gleason score

• sum Gleason grades from 2 most prevalent types

• score < 4 = well differentiated, rx is conservative

• score > 5 = moderately to poorly differentiated, rx is aggressive

• Staging – spread occurs by direct local invasion, lymphogenous spread, or hematogenous spread

a. occult or clinically unsuspected

b. palpable by rectal, but confined to prostate

c. local extension beyond prostate (seminal vesicles, bladder, lymph nodes)

d. metastases

• clinical

• PSA = 4-10 (stage a/b) ( localized prostate CA; PSA > 10 (stage c/d) ( invasive/metastatic prostate CA

• virtually diagnostic if find osteoblastic metastases in bone

• rx w/ orchiectomy, radiation, or estrogen therapy

Testes

Cryptorchidism

• epidemiology – 0.3-0.8% of males, unilateral 75%, bilateral 25%

• pathology – congenital anomaly characterized by incomplete descent of one or both testes into scrotal sac

• clinical

• sequelae – 1.) infertility (( in interstitial stroma, Leydig cell hyperplasia), 2.) 10x-40x ( risk of testicular CA

• rx w/ orchiopexy (surgical repositioning) at around 2 yrs of age

Torsion

• twisting of spermatic cord resulting in altered blood supply ( hemorrhage/infarction ( requires emergency surgery

Atrophy

• due to atherosclerosis, end stage inflamm orchitis, cryptorchidism, hypopituitarism, malnutrition/cachexia, obstruction to semen outflow, irradiation, estrogen rx to prostate CA, Klinefelter’s syndrome (XXY)

Inflammation

• epididymitis > orchitis

• in children, epididymitis associated w/ congenital genitourinary abnormalities

• in sexually active men, epididymitis associated w/ Chlamydia trachomatis & Neisseria gonorrhoeae infxn

• syphilis first affects the testis

• mumps orchitis unilateral & self-heals

Tumors

• Germ Cell Tumors (95% of testicular CA) ( factors 1.) cryptorchidism, 2.) genetics, 3.) testicular dysgenesis

• Seminoma (30% of germ cell tumors)

• typical variant (85% of seminomas)

• sheets of uniform cells w/ infiltration of septa by lymphocytes

• large individual cells, well-defined membranes, clear cytoplasm, large nuclei, prominent nucleoli

• anaplastic variant (5-10% of seminomas)

• greater cellularity, nuclear irregularity

• spermatocytic variant (4-6% of seminomas)

• slow growing that affects men > 65, does not metastasize, excellent prognosis

• not seen in children

• chemo and radiotherapy works for pure seminomas

• most AFP & HCG negative, but may see PLAP on tissue by immunoperoxidase staining

• Embryonal carcinoma (3% of germ cell tumors in pure form, 45% of germ cell tumors in mixed form)

• has glandular, alveolar, tubular, or sheet-like growth patterns

• individual cells have indistinct borders, marked variation in cell and nuclear size and shape

• see AFP on immunoperoxidase staining or in serum

• Yolk sac tumor (infantile embryonal carcinoma, endodermal sinus tumor)

• most common in infants and children

• contain AFP

• Choriocarcinoma

• highly malignant arising from placenta, ovary, or totipotential cells in mediastinum or abdomen

• contains 2 cell types

• syncytiotrophoblast – large, multinucleate, contains HCG

• cytotrophoblast – regular, polygonal cells w/ distinct cell borders

• Teratoma

• derivatives from more than one germ layer (ectoderm, mesoderm, endoderm)

• ectodermal only (skin, hair, sebaceous glands) – cystic, filled w/ sebaceous material & hair (dermoid cysts)

• benign (collection of mature tissue) usually occur in children

• malignant (contain embryonic tissue) usually occur in adults – lack of malignant cytologic features

• when contains areas of adenocarcinoma, squamous carcinoma, sarcoma ( “teratoma w/ malignant transformation”

• Mixed tumors

• 60% of testicular cancer is mixed

• most common mixture (14%) is teratoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma

• if seminoma part of MCGT (mixed cell germ cell tumor), then prognosis better than NS-MGCT (non-seminomatous mixed cell germ cell tumor)

• Staging

• Stage I – tumor confined to the testis

• Stage II – tumor confined to the retroperitoneal nodes below the diaphragm

• Stage III – tumor outside the retroperitoneal nodes above the diaphragm

• Sex Cord-Gonadal Stromal Tumors (4-6% of testicular CA)

• Leydig cell tumors

• epi – 2% of testicular CA

• path – cell cytoplasm may contain lipid granules, vacuoles, lipochrome pigment & characteristic rod-shaped crystalloids of Reinke, most benign

• clinical – boys ( precocious puberty; men ( nothing or gynecomastia

• Sertoli cell tumors (androblastoma) – most benign, freq in cryptorchid testes

Germ Cell Tumors

Seminoma showing poorly demarcated lobules and clear cells

Embryonal carcinoma showing sheets of undifferentiated cells and glandular elements

Choriocarcinoma w/ clear cytotrophoblastic cells w/ central nuclei and syncytiotrophoblastic cells w/ multiple dark nuclei

Neoplastic Disease of the Urinary Tract (Robbins pp. 991-994, 999, 1003-1008)

Neoplasms of the Urothelium

normal histology – 5-7 layers thick (>7 abnl), lined by superficial “umbrella” cells (w/ asymmetric unit membrane)

Epithelial Tumors of the Bladder

• classification – based on pattern of growth, cell type, cytologic abnormalities, papillary vs. non-papillary, carcinoma-in-situ

• etiologic agents

• cigarette smoking is the most important factor

• industrial chemicals – β-naphthylamine & biphenyl compounds (both in dyes of textiles, paints, plastics, rubber, cable)

• environmental exposure – artificial sweeteners, Schistosoma may cause squamous bladder tumors

• genetic – chromosome 9 deletions (also 17 and 14)

• grading – based on epithelium thickness, mitosis, polarity, presence of umbrella cells, nuclear chromatin abnormalities

• Grade 0 – urothelial papilloma 100% 5-yr survival

• Grade I – urothelial neoplasm, low malignant potential >90% 5-yr survival

• Grade II – urothelial carcinoma, low grade >50% 5-yr survival

• Grade III – urothelial carcinoma, high grade ................
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