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-Gross appearance - odor, color, clarity
-RBCs make urine opaque
-Protein (e.g. albumin) will make urine foamy
-Tubular disorders - protein is not reabsorbed (< 1-1.5 g/day)
-Glomerular diseases - protein > 3-3.5 g/day must be from glomerulus
-Overflow states - as in light chains from multiple myeloma
-Contamination - semen, mucus, etc.
-Basic chemistries, pH, specific gravity
-6-dipstick test: blood, bilirubin, ketone, glucose, protein, pH (BBKGPP)
-10-dipstick test - also specific gravity, urobilinogen, nitrite, leukocyte esterase
-Microscopic exam - cells, crystals, casts, organisms
-Squamous cells appear polygonal w/ small nuclei
-Indicate contamination
-Transitional cells are rounded w/ slightly larger nuclei
-Dysmorphic RBCs come from the glomerulus
-They are traumatized by the variable tonicity of the nephron tubule
-Oval fat bodies - shed tubular cells containing lipid
-Lipid accompanies protein in the urine; tubular cells absorb it
-Polarized light gives them a cross or 4-leaf clover appearance
-Normal values
-0-2 RBCs per high power field
-0-5 WBCs/hpf
-Oxalate - like the backs of envelopes, seen in acid urine
-Triple phosphate - like coffin lids, assoc w/ infection, seen in alkaline urine
-Cystine - hexagonal
-Cylindrical-shaped elements of urinary sediment molded by the renal tubule
-Tamm-Horsfall protein, made by the TAL, acts as "cement"
-Hyaline cast
-Does not contain a cellular component - mostly Tam-Horsfall protein
-May be seen in small numbers normally
-RBC cast
-RBCs are trapped within a proteinaceous matrix (e.g. T-H protein)
*Indicates glomerulonephritis (glomerular inflammation)
-WBC cast
-WBCs trapped within a proteinaceous matrix
-Seen in acute inflammatory processes – glomerulo- & pyelonephritis
-Renal tubular cast
-Renal tubular epithelial cells are trapped in a proteinaceous matrix
*Imply tubular damage - e.g. nephrotoxin, pyelo- or interstitial nephritis
-Granular cast
-Unidentifiable degenerated cells in a proteinaceous matrix
-Large numbers are seen in acute tubular necrosis
-Waxy cast
-Broad, translucent cast representing severe, long-standing renal disease
-Are contaminants unless accompanied by inflammatory cells


-Other tests must be ordered separately
-Measuring GFR (the best overall indicator of renal function)
-Requires measurement of a substance meeting the following criteria:
-Constantly produced/infused, freely filteres, not secreted/reabsorbed
-Creatinine is the best endogenous compound
-Creatinine clearance (CCr)
-CCr = (urine [creatinine]) * (urine flow rate) / (plasma [creatinine])
-CCr = UCr * V / PCr
-Yields volume of blood cleared of creatinine per unit time
-Creatinine is secreted by the tubules, so it overestimates GFR
-In addition, the PCr-GFR relationship is not linear
**Hence s[Cr] should NOT be the sole means of assessing kidney fxn
-Other variables must be considered when calculating GFR
-Assume steady state, so these eqns don't work for an acute condition
*Cockcroft-Gault (know)
-Men: Cr Cl = (140-age) * (weight) / (sCr*72)
-Women: Cr Cl = (140-age) * (weight) * 0.85 / (sCr*72)
-Modification of Diet in Renal Disease (MDRD)
-GFR = 186 * [sCr]^-1.154 * age^-0.203 * 0.742 if female * 1.21 if AA
-Results given as ml/min/1.73m^2
-Cytology, eosinophils & electrolytes, protein, or creatinine quantification
*Proteinuria may be the only indication of renal disease
-GFR & sCr may be normal
-Protein is the most important factor for future loss of kidney fxn
-CKD - proteinuria is an independent risk factor for CV disease & death
-Measuring protein excretion
-Dipstick is useful for screening, but imprecise (scale 0-4+)
-Misses small amounts of albumin, seen in early DM
*Send a separate urine sample for microalbumin testing
-Untimed, random "spot" urine for protein & creatinine
-Is as accurate as a 24 hr timed specimen
-[protein (mg/dL)]/[creatinine] = grams protein excreted per 24 hrs

-Chronic Kidney Disease Stages (according to NKF)
-1 - kidney damage w/ normal or increased GFR (>/=90 ml/min/1.73m^2)
-2 - kidney damage w/ mildly decreased GFR (60-89)
-3 - moderately decreased GFR (30-59)
-4 - severely decreased GFR (15-29)
-5 - kidney failure (< 15 or dialysis)

-Never do a 24 hour urine collection - it's not reliable. Just use equations.


-Eipithelial Tumors
-Benign tumors
-Tubulopapillary (fimbria-like) tumor of the renal cortex – often incidental find
-Same genetic findings as RCC, but smaller size (< 5mm)
-Responsible for 5% of adult kidney tumors; majority are asymptomatic
-Derived from intercalated cells of collecting ducts
-Circumscribed, brown (cortex-colored), possibly w/ central scar
-May be multifocal and/or bilateral
-Histopathology - uniform sheets or nests of pink cells
-EM reveals numerous mitochondria
-Renal cell carcinoma
-Clear cell
-Comprise 70% of epithelial kidney tumors; 75% five year survival
-Associated w/ Von Hippel-Lindau disease
-Mutated/inactive VHL gene results in overactive HIV & VEGF
-Sx: angiomatosis & hemangiomas, polycythemia
-Hemangioblastoma in the cerebellum
-Pheochromocytoma & renal clear cell carcinoma
-Derived from the proximal tubule; usually a solitary, unilateral tumor
-Gross pathology (same for Papillary & Chromophobe)
-Solid or cystic; bright yellow appearance
-Variable hemorrhage/necrosis - pts may present with hematuria
-Tendency to grow into the renal vein & inferior vena cava
-Histopathology - islands of cells w/ round nuclei
-Clear cytoplasm b/c high lipid content has been washed out
-Intervening capillary network may separate islands
-Remember: "CC'd emails by Proxy, VHS images are Clear"
-Associated with acquired cystic kidney disease; 95% five year survival
-Caused by trisomy 7, 16, or 17; or loss of Y chromosome in men
-Derived from distal tubule
-Histopathology - cuboid-ish cells in papillary formations
-Papillary cores are often filled w/ foamy macrophages
-Remember: "take 3 (trisomY) Pills Distilled in Foam"
-100% 5-yr survival; caused by monosomy 1,2,6,10,13, or 17 (chroMo = mono)
-Derived from intercalated cell of collecting duct
-Histopathology - eosinophilic cells w/ a perinuclear halo
-Granular, pink cytoplasm may be outside of the perinuclear halo
-Remember: "Chromo & onCo = Collecting"
*Prognosis correlates strongly with nuclear grade & stage of cancer
-pT1/2 - tumor confined to kidney - 95% five yr survival -1/2-kidney
-pT2 is > 7cm
-pT3a - invading perinephric fat or adrenal - 75% -3a-fat
-Tumor has not gone through Gerrota's fascia
-pT3b - invading renal vein - 40% -3b-vein
-pT4 - invading adjacent structures - 20% -4-Gerrota's


heart *Renal angiomyolipoma and cardiac rhabdomyoma are associated -Clinical features -Sporadic .forming glomeruli-ish or tubular structures -Mesenchymal .hamartoma formation in skin.small blue cells w/ little cytoplasm. & mesenchymal elements -Blastemal .spindle-shaped fibroblasts -Anaplastic features indicate a worse prognosis -We won't have to identify the histo -Secondary Tumors -Lymphoma -Metastases 4 .female predominance. smooth muscle. GI obstruction -Genetics -Often a component of WAGR syndrome & Denys-Drash syndrome -WT1 gene is implicated . may result in renal failure -Histopathology -Hemorrhage & necrosis -Composed of fat. abdominal pain.presents at younger age. smaller -Often detected as part of work-up. can present w/ acute sx from hemorrhage -Tuberous Sclerosis . brain.-Mesenchymal Tumors -Angiomyolipoma -Benign mesenchymal tumor -Often seen in pts w/ Tuberous Sclerosis (~40%) -AD disorder . in sheets -Epithelial . solitary. kidney. often detected by the mother -Presents as large abdominal mass. & blood vessels -Cartwheel pattern of SM can be seen coming off of vessel walls -Remember: "Angio & Rhabdo fed Tubers to their children" -Embryonal Tumors -Wilms tumor -Most common pediatric (age < 5) kidney neoplasm. multiple/bilateral.critical for normal renal & gonadal formation -Histopathology -Triphasic w/ blastemal. epithelial. larger -Often incidental finding. eye.

GLOMERULAR PATHOLOGY -Nomenclature: -Refer to # of glomeruli: -Diffuse is > 50% -Focal is < 50% -Refer to a single glomerulus: -Segmental-portion is involved -Global-all involved -Glomerular Anatomy -Membrane: cap endothelial cell. MCD. glom basement membrane (GBM).5 g/day) -Peripheral edema due to hypoalbuminemia -Hyperlipidemia & lipiduria . MPGN. membranous GN -2o causes: SLE (rare) -Adults: FSGS (24%).negative. diabetes.anticoag's & Ab's in urine -Age influences the differential diagnosis -Children: MCD (65%). FSGS. (also IgA nephropathy. MPGN) -Secondary causes (40%): diabetes.0-3.) -Immunofluorescence (IF) . open capillaries.increase flow & pressure -HTN & hyperfiltration cause further injury . nml cellularity.vicious cycle -Microscopy -LM . 2nd leading cause in children -Protienuria isn't selective -Tx w/ transplant drugs (not steroids). etc. epithelial podocyte feet -Mesangium supports glomerular capillary loops -Nephrotic Syndrome -Features -Marked proteinuria (> 3.transferred serum induces it -Secondary causes result from conditions of significant nephron loss -Unilateral renal agenesis -Chronic renal disease of any kind when pt is "close to the end" -HTN. membranous GN (23%). tubule will atrophy & fibrose -IF . vascular disease. SLE.podocyte injury resulting in lost foot processes -Focal segmental glomeruloscerosis (FSGS) -Clinical -Most common cause in African Americans. immune complexes (IC's) or antibodies -Electron microscopy (EM) .to compensate for low protein? -Hypercoagulability & increased propensity for infection .generally following URI or vaccine -Incidence is increased in Hodgkin lymphoma patients -Injury reduces the (-) charge on the GBM → albumin lost -Microscopy -Light microscopy (LM) . podocyte foot process effacement 5 . also important to adults -Albumin is the predominant protein in urine -Responds well to steroids -Etiology -Primary podocyte injury of unknown cause .begins w/ < 50% of glomeruli showing partial sclerosis -Over time all capillary loops collapse resulting in global sclerosis -Other glomeruli begin to show segmental followed by global sclerosis -Once glomerulus is scarred. progresses to chronic renal failure (yrs) -Etiology -Idiopathic resulting in primary podocyte injury -Due to a non-antibody circulating factor . amyloidosis -Minimal change disease (MCD) -Clinical -Most common cause of nephrotic syndrome in MCD. -Remaining glomeruli try to compensate . no immune deposits -EM .normal (capsule.

*Hepatitis B -Autoimmune diseases . important cause of nephrotic syndrome in white adults (30s-40s) -Renal failure is associated w/ -High levels of proteinuria at diagnosis -Older age at onset. syphilis.don't attract -IF .-Nephrotic Syndrome (cont. & increased incidence in African Americans **HIV-associated nephropathy (HIVAN) -Collapsing glomerulopathy in HIV-infected patients -Assoc w/ AA polymorphism in myosin heavy chain (MYH9/CD2AP) -HIV infection in podocytes causes dedifferentiation -Etiology . uniform thickening of the GBM -Deposits don't stain differently w/ H&E. coarse. remain static. podocyte foot process effacement -Membranous glomerulopathy (MG) -Clinical -Like FSGS. & GBM grows between them -Secondary causes (15%) are largely treatable *Chronic infections .idiopathic -Microscopy -LM . of onset -Associated w/ HIV. male sex.) -Collapsing glomerulopathy (CG) -Clinical -Considered a heroin users.SLE.innumerable dense subepithelial IC deposits -Digitating "hair like" GBM progections & podocyte foot effacement 6 .diffuse. increased BUN & Cr at diagnosis -May resolve. so it looks like one big GBM -Trichrome stain (red) differentiates b/t GBM & IC's -Jones stain (black) shows GBM finges & bubbly holes -Glomerulus is not hypercellular (only 1-2 nuclei in the mesangium) -Anaphyactatoxins are washed into the urine .malaria. rapidly progressive form of FSGS -Massive proteinuria & end-stage kidney disease w/in 13 mo. or slowly progress to renal failure -Tx w/ transplant drugs (not steroids) -Etiology -Mostly idiopathic autoimmune disease -Auto-Ab's react with podocyte phospholipase A2 receptor (PLA2R) -IC's shed into SUBEPITHELIAL MCD. rheumatoid arthritis -Paraneoplastic syndrome associated with cancer -Medications .regular. granular GBM w/ IgG & C3 -EM . penicillamine -Microscopy -LM collapse of glomerular tufts -Hypertrophy & hyperplasia of podocytes overlying the capsule -Nuclei are increased & "lined up" around the exterior -IF . not due to IC's -EM .

more than 2-3 nuclei -Endocapillary proliferation . &/or evidence of renal failure (inc Cr) -Clinical course -Idiopathic is usually progressive with poor prognosis -Reversal is possible if secondary causes are treated -Etiology -Idiopathic .IC's seen in subendothelial space & mesangium -Mesangial cells can be seen between GBM layers 7 . etc. cryoglobulinemia -Paraneoplastic syndrome associated with malignancy -Microscopy -Light microscopy -Mesangial hypercellularity .misnomer. -Immune disorders . & evidence of renal failure (increased Cr) -Also assoc w/ asymptomatic hematuria/proteinuria & acute nephritic syndrome -Suspect in pts with nephrotic range proteinuria who also have -Many RBC's in urine. PMN margination in the lumen -Combined changes give glomeruli a lobated "cauliflower" appearance -Special stains show duplicated GBM . *Hep C.) -Membranoproliferative glomerulonephritis type I (MPGN) -Clinical -Affects primarily children & young adults -Nephrotic range proteinuria -Hypocomplementemia .SLE.decreased serum C3 & C4 -HTN.capillary loops & mesangium stain for IgG & C3 -EM .IC's deposit in MESANGIUM & SUBENDOTHELIAL space -Activate complement & attract inflammatory cells -Mesangial cells spread along GBM b/t original & new layer of GBM -Hence IC's cause endothelial cell injury & GBM reduplication -Secondary causes **Chronic infection . *bacterial endocarditis. persistent hematuria.-Nephrotic Syndrome (cont.Hep B."train tracks" -IF .

C3."starry night" or "lumpy bumpy" capillary loop deposits .hematuria. tissue may necrose *Membranous glomerulopathy is seen in SLE -Treatment .-Acute Nephritic Syndrome -Features -Hematuria .IgG.a misnomer -IF . 8 . IgM. etc.deposits in capillary loops.corticosteroids.subendothelial deposits damage GBM -Inflammatory cells marginate -GBM's may rupture. -Think "Starry Strep" -EM .mild to moderate (not in nephrotic range) -Hypertension -Poststreptococcal glomerulonephritis is the prototypic cause -Clinical-Onset 1-3 wks after Grp A Strep throat infection. C4. but especially in mesangium -"Full house" . IgA. still significant) -Proteinuria . oliguria. azotemia. etc.gross or microscopic (but if microscopic.capillary loops occluded by marginated inflammatory cells (PMNs) -Called "diffuse endocapillary proliferation" . 3-6 wks after skin infection -Features suggestive of renal inflamm/edema .IgG. -Titers of anti-Streptolysin O or anti-DNAse B from Strep pyogenes -Decreased complement levels early during disease (indicates glomerular cause) -Immune complexes formed from Ab's to pyrogenic exotoxin B -Prognosis -95% children recover spontaneously or w/ minimal treatment -60% adults recover. 40% develop rapidly progressive GN or chronic RF -Microscopy -LM . etc. C3. cytotoxic agents like cyclophosphamide -Do renal biopsy to confirm disease before treating young women -Microscopy -IF .large randomly spaced SUBEPITHELIAL "humps" of IC deposits -Lupus nephritis -Seen in 2/3 of pts at diagnosis -Renal biopsy is almost always indicated to guage activity & make diagnosis -Clinical manifestations -Nephrotic syndrome (membranous glomerulopathy) -Acute nephritic syndrome -Asymptomatic hematuria/proteinuria -Acute renal failure due to severe glomerular damage -Etiology -Autoimmune disorder mediated by IC's -Mesangial proliferation & deposits -Endocapillary proliferation .

IC's deposit in the glomerulus -Membranoproliferative GN .no deposits.the biochemical abnormalities that lead to symptoms (increased Cr. uncommon in African Americans -Most cases are idiopathic.linear pattern (like crumpled paper) -EM .-Acute Renal Failure -Features -Anuria or oliguria -Occurs over short time (days-weeks) -Azotemia .Anti-GBM disease -Anti-GBM Ab's. C') leak and stimulate formation -Cells are derived from monocytes & epithelial cells lining Bowman's space -Pathogenesis -Type I .clinical term) / Crescentic GN (path term) -Caused by various diseases that severely damage the glomerulus -The crescent .PR3 -Myeloperoxidase & PR3 expression usually follows infection -PMN-Ab complexes stick to glomerular endothelium -Potential causes ANCA Vascuitis Granuloma Asthma Comments *Microscopic polyangiitis p&c yes no no *Wegener’s granulomatosis c yes yes no Highly associated w/ lung & ENT Churg-Strauss syndrome p no yes yes Often involves lungs. etc.) -Caused by Rapidly progressive GN (RPGN . malaria. idiopathic) -Predominates at ages > 40 -ANCA(+) in > 90% of patients . severe glomerular damage -Type II .anti-neutrophil cytoplasmic antibody -Antibodies to myeloperoxidase & proteinase-3 components of granules -Perinuclear (p-ANCA) ."full house" on IF -IgA nephropathy .non-immune deposit diseases (PAN. influenza A2. hx of Strep infection -Type III . eos are seen Pauci-immune crescentic GN p Renal involvement only 9 . coag factors. but many patients have HLA-DR2 haplotype -Also assoc w/ hydrocarbon solvents.proliferation of cells w/in Bowman's space cause glomerulus to collapse -Plasma proteins (fibrin.also attack against pulm capillary BM (hemoptysis) -Microscopy -LM .immune complex-mediated diseases -Seen mostly in ages 10-40 -Diagnose with kidney biopsy . Wgener's."Starry night" by IF.myeloperoxidase -Cytoplasmic (c-ANCA) .IgA deposition by IF w/o vasculitis -HS Purpura if vasculitis is seen *Post-Strep GN .subendo deposits & "tram tracks" -Lupus nephritis .GBM's fluoresce for IgG .crescents! also areas of necrosis w/ nuclear debris (karyorrhexis) -IF . & Hodgkin -Goodpasture's syndrome .

hematuria/proteinuria -Relatively benign clinical course -Etiology .thick GBM w/ irregular borders & "basket-weave" appearance -GBM looks eroded like dirt after a hard rain -Thin basement membrane disease *Clnical . Nat Americans -Hx of associated upper respiratory or GI infection (inflamed mucosa) -Hx of intermittent macro hematuria. polyuria.nonspecific (open loops.IC's containing IgA & C3 (not C1 or C4) in the mesangium -EM . eye lens -X-linked .especially the mesangium -Microscopy -LM .most glomeruli look normal.negative with conventional study.fever. -IF .-Asymptomatic Hematuria / Proteinuria -A variety of diseases present this way. or hematuria/proteinuria on urinalysis -Prognosis . episodic gross.characteristic thin GBM -Other Glomerular Disorders -Chronic Renal Failure .benign disease or progressive to chronic renal failure (10-50%) -Etiology -Genetic & environmental components -Genetic mutation → IgA Ab's w/ d/c # of galactose moieties at hinge regions -Environmental trigger causes production of Ab's against abnormal IgA's -IC's lodge in glomeruli .symptomatic support. cochlea.negative -EM .glomerulus. high incidence in SE Asians. & nocturia -Urinary Tract Infections . 2-3 cells in mesangium).AR defect in GBM production -Microscopy -LM .manifests as electrolyte disturbances. flank pain -Nephrolithiasis (kidney stones) 10 . persistent micro -High frequency hearing loss -Myopia & other visual changes -Variable progression to end-stage renal disease -Tx . pyuria. but capillary loops remain open -IF . mesangial hypercellularity -Basement membrane disorders -Alport's disease -Clinical -Hematuria . some of which are not related to the glomerulus -IgA nephropathy (Berger's disease) -Clinical -Mostly children & young adults. renal transplant (may cause anti-GBM) -Etiology -Hereditary defect in type IV collagen .missing alpha-3 or alpha-4 isoforms -Microscopy -LM . some may be sclerosing -IF . must look for collagen isoforms *EM .most common presentation.mesangial hypercellularity.deposits in the mesangium.missing alpha-5 isoform of type IV collagen -Autosomal (AD/AR) .marked by progressive increase in Cr & BUN -Renal Tubular Defects .

TGF-beta -Renal biopsy is rarely indicated -DIsease has a natural history -Exceptions -Early onset proteinuria (< 10 y/o in T1DM) -Lack of other diabetic changes when renal disease develops -Atypical features . but no IC's -Myeloma cast nephropathy -Associated with multiple myeloma & light chain production -Chemical reaction between light chains & Tamms-Horsfall protein produces casts -Casts can obstruct cortical and medullary tubules & cause renal failure -Pathology -LM . -Clinical features -Microalbuminuria progressing to proteinuria.ECM in mesangium forms Kimmelstiel-Wilson nodules -Mesangium compresses capillary lumens & leads to glomerulosclerosis -Other changes *Hyaline arteriolosclerosis . unusual pace -Pathology -Gross . often cracked or fractured -Casts may appear lamellar (concentric rings) -May be ringed by Mphages & multinucleated giant cells -Treatment -Reduce light chain production w/ chemotherapy -Decrease light chain & TH protein aggregation -Drink more water. even thickening of GBMs & mesangium -Nodular .enlarged kidneys due to ECM & growth factors *LM . but tubules are clogged -Large.BOTH afferent & efferent arterioles -Fibrin "caps" in the glomeruli & "drops" in Bowman's capsule -Tubular atrophy & sclerosis following gomerular failure *Accelerated atherosclerosis in all arteries -IF . favoring formation -Increased synthesis of TIMPs & decreased MMPs -Disturbance involves growth factors .diagnostic lesion for DM renal dz -Diffuse .SYSTEMIC / HEREDITARY / VASCULAR RENAL DISEASES -Systemic Renal Diseases -Diabetes mellitus *Diabetic nephropathy (DN) is leading cause of ESRD in the U. etc.unexplained nephrotic syndrome -Decreased GFR & hypertension -Other manifestations of DM .linear deposition of IgG & albumin along GBM & TBM -Hypothesized that proteins stick to the abnormal GBM -EM . irregular casts w/in tubules.diffuse & nodular glomerulosclerosis .retinopathy.uniformly thickened GBMs.S. -Pathogenesis *Primary lesion is excess ECM accumulation in the kidney -Formation/degradation is disturbed. avoid nephrotoxins (radiocontrast) 11 . alkalinize urine. expanded mesangium -Podocyte foot process effacement.glomeruli are normal.

Rheumatoid arthritis -Chronic infections .an acute phase reactant -Inflammation increases its serum levels -Normally metabolized by monocytes/macrophages -Hereditary defect in metabolism may result in abnormal processing -Associated w/ chronic inflammatory conditions -Autoimmune diseases . SAA -EM .identifies light chains. TB. non-branching fibrils 12 . mainly in glomeruli & vasculature -Glomerulus: amyloid deposits first in mesangium → d/c capillary lumen -Subsequent deposition in GBM → protein loss -Vasculature: amyloid compromises artery & arteriole lumens -Congo Red + polarized light identifies amyloid -IF .-Amyloidosis -Abnormally synthesized or processed proteins are deposited in tissue -Results in proteinuria in the kidney -Renal insfficiency also develops ~ 60% of pts have i/c Cr at time of dx -Characteristics of amyloid -Can be made from 21 different proteins -All deposit as a beta-pleated sheet and stain w/ Congo Red -Polarized light reveals characteristic apple-green birefringence -Forms of amyloid -AL .g.e.Primary amyloidosis -Most common type. results from Ig light chains (multiple myeloma) -Malignant plasma cells produce monoclonal Ig's & light chains -Lambda light chains > kappa -Detected as a monoclonal spike in SPEP -Bence Jones proteinuria = free light chains in urine -AA .e.g.masses of thin.Secondary amyloidosis -Serum AA protein (SAA) .amorphous pink material. osteomyelitis -Pathology -LM .

hematuria. pre-eclampsia.) -Note: diarrhea is occasionaly present. etc. eclampsia. associated w/ hereditary C' disorder of Factors H & I -Thrombotic thrombocytopenic purpura (TTP) -Most commonly seen in adult women -Clinical -Fever.antiphospholipid syndrome (lupus anticoagnulant) may cause TM -Renal transplant . tacrolimus -Other .mesangial cell interposition & new GBM formation -Similar to membranoproliferative GN .-Vascular Renal Diseases (Thrombotic Microangiopathies) -TMs cause direct damage to endothelium resulting in increased platelet aggregation & adherence -Acute changes -LM . aphasia.GBM reduplicates .thrombi in capillaries -Results in bloody diarrhea & acute renal failure -Diarrhea negative (D-) or Atypical -Smaller # of cases. but not necessarily -CNS encephalopathy . etc. focal IC's -Hemolytic uremic syndrome (HUS) -Diarrhea positive (D+) or Typical *Most common cause of acute renal failure in children -E. scleroderma.Platelet/fibrin thrombi in glomerular capillaries & arterioles -IF .anti-endothelial antibodies may develop -Drugs . bleeding. proteinuria.minocycline (antineoplastic). paraneoplastic syndrome 13 . azotemia (elevated Cr.HA. cyclosporin. seizure.radiation. coli that produce Shiga toxin (O157:H7) are ingested -Shiga toxin damages epithelium of gut & kidney -Endothelial cells swell & detach -Platelets activate & aggregate . confusion. -Other organ systems like heart & lungs often hemorrhage as well -Pathogenesis -Hereditary or acquired deficiency in ADAMTS13 -Enzyme normally cleaves vWF pre-protein -Defect leads to vWF multimers that favor platelet aggregation -slide 48 -Malignant hypertension .glomerulus stains for fibrin deposition -Chronic changes -EM .direct barotrauma to endothelium triggers TM -SLE .

support and transplant are the only treatment -In utero renal failure leads to oligohydramnios -Insufficient amniotic fluid .may become infected. & abnormal ECM -Cyst epithelium produces cytokines . fluid secretion.may compress porta hepatis structures of IVC -Pancreatic cysts -Cysts in various organs -Pathology -Gross -Markedly enlarged kidneys .compresses face & arms -Respiratory hypoplasia due to compression by kidneys -Pathology -Gross -Large kidneys filling the abdominal cavity *Cut kidney surface shows radially oriented tubular cortical cysts -Microscopic -Cortical area filled with cysts -Compressed intervening glomeruli & proximal nephron elements 14 . HTN.provoke interstitial inflamm & fibrosis -Associated with berry aneurysm .ion channel closely associated with polycystin 1 -Characterized by progressive development & enlargement of cysts in both kidneys -Cysts balloon out of the nephron . acute & chronic pain -Decreased ability to concentrate urine -Cardiovascular -Intracranial saccular aneurysms that may rupture and bleed -Aneurysms of other vascular beds -Cardiac valvular abnormalities -Other extrarenal -Liver cysts . hemorrhage -Hyperproliferation of tubular epithelial cells. & UTI's -ESRD may occur at any time .fibrosis.membrane glycoprotein for cell & matrix interactions -PKD2 (polycystin 2) .defects in basement membrane & ECM? -Clinical manifestations -Renal -Hypertension. rupture. cysts -Large number of variably sized cysts distributed throughout parenchyma -Micro -Cysts lined by simple cuboidal epithelium -Cysts may arise from any portion of the nephron -Autosomal recessive Polycystic kidney disease (ARPKD) -Much less common disorder -Mutation in gene w/ unknown function on chromosome 6 *Cysts only arise from the collecting duct . hematuria.-Hereditary Renal Diseases -Autosomal dominant Polycystic kidney disease (ADPKD) -Inherited defect in either PKD1 or PKD2 gene -PKD1 (polycystin 1) .radial distribution -Liver undergoes a variable amount of fibrosis -Clinical manifestation -Pts usually diagnosed < 1 y/o -Present w/ palpable abdominal mass.

less cylindrically shaped.most cells are simply injured -If the tubular basement membrane remains intact. gentamicin). diptheria.results from ischemia (usually 2o to pre-renal cause) -Acute tubulo-interstitial nephritis . -Bladder outlet obstruction . -Tubulo-toxic injury . tumor. radiocontrast dye -Histopathology -Normal histology -Proximal tubule .due to shock or hypotension caused by sepsis. diuretics -Also associated with systemic infections where antigens deposit in the tubulo-interstitium -Group A Strep. etc.g. cancer -Acute Tubular Necrosis (ATN) -Results from injury and/or destruction of renal tubular epithelium -Impaires synthetic fxn (low ATP) & activates destructive processes -"Necrosis".hemorrhage. mercury. etc. however.RPGN/Crescentic GN -Vasculature *Interstitial/Tubule -Acute tubular necrosis .penicillin. diuresis -Relative decrease in peripheral resistance . less nuclei per x-section -Pink line around lumen indicates brush border -Distal tubule . fibrosis. more nuclei. prostate. rarely occurs .mitoses indicate regeneration -Acute Tubulo-Interstitial Nephritis (ATIN) -Probably an immunological phenomenon . pulmonary embolism. then regeneration is possible -Two categories of cause -Ischemic injury .MI.related to drugs.calculi. anaphylaxis. d/c CO. *Renal (intrinsic) events -Glomerular .tumor. no brush border -Indicators of damage -Vacuoles inside of the tubular epithelial cells -Absent brush border in the proximal tubules -Necrotic material filling tubule lumens -Tubular epithelial cells may form casts & obstruct the tubule lumen -Obstruction effectively decreases GFR -Naked tubular basement membranes . contrast) -Principal Causes of ARF -Pre-renal events -Absolute decrease in effective blood volume . toxoplasmosis. etc.sepsis. etc. CFH -Post-renal events (obstruction) -Ureteral obstruction of one or both kidneys . nephrotoxic drugs (diuretics. GI loss. Legionnaire's disease 15 . -Sulfonamides.occurs in pts w/ clinical hx of hypersensitivity *T-cell mediated hypersensitivity (type IV) is the most likely explanation *Drug probably acts as a haptan & incites an immune reaction -Beta-lactam antibiotics .TUBULO-INTERSTITIAL DISEASES & ACUTE RENAL FAILURE -Development of Acute Renal Failure -Oliguria (< 400 mL urine/day) is the earliest warning sign -Most cases develop inside the hospital -Causes: hypovolemia. shock -Reduced cardiac output . infection. NSAIDs. hemorrhage.due to a substance that is toxic to tubular cells -Ex: aminoglycosides (e. ampicillin. surgery & anesthesia.cuboidal epithelium.

& pelvis -Commonly seen in patients with chronic reflux. rash. -Histopathology -Interstitial nephritis .papillae degenerate into the renal pelvis -Chronic Pyelonephritis -Due to recurrent.bilobed nucleus -ATIN vs. repeated bouts of acute pyelonephritis -Leads to severe scarring of renal parenchyma. eosinophilia + - -Acidosis.incomplete bladder emptying (DM).secondary to prostatic hypertrophy -Complications -Pyonephrosis . etc. inflammation of bladder wall -Instrumentation of GU tract .kidney is a bag of pus -Perinephric abscess .many "seeded" areas in the cortex -Ascending infection . etc.AIDS.asymmetric. diabetes. Enterobacter. Enterococcus -5% of cases due to hematogenous spread via bacteremia -Predisposing factors for UTI -Obstructed urine flow at any level .due to congenital anomalies -Age 1-50 yr . WBC casts in the urine -Papillary necrosis .infection escapes the kidney *Papillary necrosis .women more likely . + -Nephrotic syndrome . numerous UTIs.catheter -Pregnancy . calyces. Klebsiella.has 3 requirements -Acute pyelonephritis -Obstructed urine flow -Vascular compromise -Histopathology -Hematogenous spread . hyperkalemia + - -Hypertension . + -Renal Signs -Papillary necrosis + - -Calyceal abnormality + - -Urinary sediment Eos RBCs & RBC casts -Proteinuria (g/day) <2 >2 -Acute Pyelonephritis -Actual infection of the renal parenchyma -Usually due to ascending UTI (95% of cases) -Hence organisms are usually GI-related: more likely .Lcytes in the interstitial tissue & attacking tubular BM *Eosinophils in the interstitial tissue and urine .male infants more likely . & acute pyelonephritis -Histopathology . contraction closes the ureters -Interference with this mechanism predisposes to reflux -Congenital defect. scarred kidneys w/ markedly thickened & scarred calyces 16 . GN -Clinical Signs ATIN GN -Fever.spread through papillae into the medulla & cortex -Tubules filled with PMN's.uterus obstructs ureters -Immune dysfunction . intercourse trauma. -Vesico-ureteral reflux -Ureter normally enters bladder at an acute angle. coli. -Age > 50 yr . BPH.short urethra. steroids -Age & sex are important -Age < 1 yr .

secretes surfactant & DPPC -Surfactant -Type 2 pneumocytes become functional ~ 7 mo.columnar ciliated cells. a healthy lung is compliant . which have no cartilage -Acinus is composed of respiratory bronchiole.type I & type II penumocytes -Type I pneumocyte . arterioles -Elasticity allows for recoil after expansion -Surface epithelium -Bronchus .keeps lung "dry" -Production decreases in hypoxic states -Collateral airflow maintains V/Q match.dipalmitoyl phophatidylcholine. & alveoli -Pulmonary arteriole runs adjacent to the bronchiole -3-30 acini form a lobule. -Interstitial tissues .LUNG PATHOLOGY OVERVIEW -Lung Anatomy -Lobes – 3 on Right. of gestation -Hyaline membrane disease . 2 on Left – each lung has 10 bronchopulmonary segments -Airways -Conductive zone . which is the smallest gross compartment -Negative intrapleural pressure keeps airways open -Tissue compartments -Airspaces .surfactant deficiency of newborn -DPPC . alveolar ducts. Bronchiole .stem cell.air enters -A low lung volume. no mitosis -Component of blood-air barrier w/ capillary endothelium -Type II pneumocyte .cartilagenous airways such as trachea & bronchi -Respiratory zone . lymphatic & blood vessels.area where gas exchange occurs -Includes the bronchioles.openings in interalveolar septae -Respiratory Mechanics -Compliance -Change in volume produced by a change in pressure -Thoracic expansion decreases intrapulmonary pressure to negative .connections between alveolar ducts & terminal bronchioles -Pores of Kohn . etc.squamous epithelial cell lining alveolar wall.expands w/ little change in P -Compliance decreases with increasing volume -Disease states -Emphysema increases compliance (more volume for a given pressure change) -Fibrosis decreases compliance (less volume for a given pressure change) -Elasticity -Ability of the lung to recoil to resting volume after being stretched -Facilitated by elastic tissue in lung & chest that supports small airways during expiration -Emphysema decreases lung elasticity 17 . but also allows infection to spread -Canals of Lambert . main component of surfactant -Reduces surface tension & hence alveolar collapse -Laplace: surface tension increases w/ radius -Hence DPPC decreases the work of breathing -Interrupts bonds between liquid molecules .primarily elastic tissue -Located in the interstitial space between alveoli & bronchioles. fibroblasts.contain alveolar macrophages -Interstitial space .cuboidal cells w/ decreasing cilia -Alveolus .contain supporting tissue -These surround airways & alveolar walls -Contain lymphoid cells.

protein-rich fluid leakage through altered capillary barrier -Causes .pneumonia.visceral & parietal -Visceral .increases systemic hydrostatic pressure -Liver disease & nephrotic syndrome .-Pulmonary Vasculature -Lungs receive a dual blood supply -Pulmonary artery terminates in an anastomosing network of vessels around alveoli -Bronchial artery supplies respiratory bronchioles -Pulmonary lymphatics .inflammation of the pleura -Pneumonia is the most common cause.impaired lymphatic drainage -Pneumonia . pain intensifies w/ breathing 18 .lung is collapsed centrally against the mediastinum -Pleuritis . & cells to enter -Pleural Tissue -Continuous membrane covering lungs & inner chest wall . since pt already has compromised fxn -X-ray . exceeds lymphatic drainage -Classification .damage to alveoli allows fluid. malignancy.increased vessel permeability -Lung appears smaller on X-ray -Differential diagnosis is narrowed by distinguishing transudate from exudate -Transudate .in/c hydrostatic pressure (CHF). cystic fibrosis.air in the pleural space -Caused by communication between alveoli & pleural space -Negative pressure of pleural space causes air to enter until pressures equalize -Causes of secondary pneumothorax -COPD .cardiogenic (pump failure) or non-cardiogenic (in/c permeability) -Cardiogenic . etc. d/c oncotic pressure -Exudate .elastic tissue & connective tissue underlying mesothelial cells -Vascular supply is continuous w/ lung parenchyma -Parietal .decreased oncotic pressure -Pleural lymphatic tumor .increased hydrostatic pressure creates protein-poor infiltrate -Non-cardiogenic .composed of superficial pleural plexus & deep bronchovascular plexus -Both drain → to intrapulmonary & hilar lymph nodes → mediastinal & tracheal LN's -Pulmonary edema -Defined as fluid accumulation in the alveolar space.protein-poor fluid leakage through intact capillary -Causes . PE. asthma.abnormal accumulation of lung in the pleural space -Due to increased flow into space & decreased fluid exit -CHF . -Pneumothorax .mesothelial cells w/ stomata -Vascular supply is continuous w/ pleural space -Pleural fluid fills the pleural space -May contain transudative fluid in CHF -Is continuous w/ interstitial fluid of parietal pleura through mesothelial cell stoma -Fluid from systemic vessels leaks into interstitium of parietal pleura -Fluid enters pleural space & is absorbed across visceral pleura into lymphatics *Effusion .most common cause -Penumocystis jiroveci (PCP). protein. mechanical ventilation *2o pneumothorax is worse than 1o.

entire lobe is grossly white -Bronchopneumonia . S.K. Klebsiella pneumoniae.patchy gross appearance -Etiology drives choice of therapy *Histopathology -Lobar . etc.airspaces diffusely involved with acute inflammation.LUNG INFECTIONS -Injury to Defense Mechanisms Increases Risk for Infection -Tracheobronchial clearance (cough. immune supp) -Also prior pneumonia. surfactant. L-cytes. foul-smelling sputum -Histopathology . diffuse alveolar damage. fibrin.generally manifests w/ worsening cough. lobar.located in distal airspaces (bronchioles.often terminal -Tissue response -Acute -Bacteria & fungi .defined area of confluent PMNs. -Smoking. mucociliary elevator).) or etiology (bacterial. cavitation -Superinfection & death are possible -Bacterial Pneumonia -Disease of the distal airspaces -Symptoms . & underlying lung disease -Cystic fibrosis . etc. etc. poor oral hygiene. aspiration. alcohol.*Pseudomonas. Mphages -Chronic -Successful therapy leads to resolution & reorganization -Presents as abscess. fungal. PMNs. exudate -Risk factors . granulomas. post-obstructive pneumonia -Pathology -Anaerobic infection mix w/ oral flora .exudate & bacteria spread along lumen of broncus -Inflammation confined by lobar barrier . hemorrhage. and/or necrotic material 19 . hemorrhage. altered LOC.) -Key points -One type of pneumonia predisposes to another -Inhalation is most often the portal of entry (hematogenous seeding can also occur) -Many hospitalized patients acquire pneumonia . fibrin. fibrous capsule -Cavity may form in the lung. granulation tissue. Haemophilus influenzae -Lung Abscess -Local suppurative process with tissue necrosis -Causes/risk factors . etc.airspaces consolidate & fill w/ PMNs.damage to normal defense mechanisms -Smoking. necrosis -Viruses & mycoplasma .located in proximal airways & interstitium -Present as bronchial epithelial necrosis.patchy distribution of inflammation (adjacent areas are normal) -Associated w/ Staph aureus. can impair these mechanisms -Pneumonia -Definition . Staph aureus *Classification -Lobar pneumonia . surrounded by granulation/fibrous tissue -Clinical course . viral pneumonia. etc. Mphages. aeruginosa. proteinaceous exudate -Associated w/ Strep pneumoniae. etc. alveoli. aureus -Liquefactive necrosis.) -Present w/ L-cytes. alveolar Mphages. -Bronchopenumonia .inflammation of the lung -Classified by morphology (bronchial.inflammatory exudate originates in bronchioles & damages walls -Pores of Kohn provide spread to adjacent alveoli . pneumoniae.aspiration is most common (altered LOC. P.

at least 3 wks after exposure -Does NOT differentiate infection from disease -Infection . Hodgin lymphoma. Hodgkin. young age. etc.pts may have (+) PPD test -Interferon-gamma release assay is more specific for MTB infection -Risk factors -Primary infection . recent live virus vaccine -False positive . malnutrition.-Tuberculosis -Airborne infectious disease caused by Mycobacterium Tuberculosis (MTB) -Even talking can aerosolize the bacteria -Symptoms -Weight loss. old TB. homelessness -Secondary disease .g. low fever. migrant worker).poverty. homeless.DM.seen in pts w/ sardoidosis. head & neck cancer 20 . cough w/ bloody sputum. overwhelming TB.organisms present w/ or w/o clinical sx -Disease . immunosuppression. but CDC says to take it as actual infection -BCG is used to tx bladder CA . chronic lung disease.infection by atypical mycobacteria.clinical symptoms of infection -False negative (anergy) . -Tuberculin skin test -Purified protein derivative (PPD) is MTB culture precipitate -Mantoux test .prepared from Mycobacterium bovis -Administered after birth in countries w/ high TB prevalence -Protection is variable 5-80% -PPD test may be (+). viral inf. adenopathy -Imaging may reveal a lung nodule -Generally seen in foreign-born persons (e.usually in left arm (give in the arm you don't shake hands with) -Any induration after 48-72 hrs = positive -Size of induration is specific to population -Tests delayed hypersensitivity (type IV) . alcoholism. BCG vaccine pts -BCG vaccine . night sweats. overcrowded living. debilitating disease. CKD.

most common extrapulmonary site. kidney. usually w/o cavitation -Generally seen in middle & lower lobes -Erosion of bronchial tree & spread to adjacent lung → tuberculous pneumonia *May involve blood vessels → hematogenous dissemination (Milary TB) -Secondary disseminated disease -Reactivation of asymptomatic primary infection or re-infection -Occurs at time of decreased immune function -Pts may be asymptomatic or have insidious sx (malaise. vertebrae -Lymphadenitis . but can't do drug testing -Other manifestations -Isolated sx of dissemination . but fibrosis & calcification in 90% of pts -Progressive primary disease *Seen mostly in immunosuppressed individuals -Ghon focus undergos caseous enlargement. wt loss.likes the reticuloendothelial system (spleen) -Massive dissemination leads to Miliary TB (immunosuppressed pts) -Differential diagnosis -Fungal infection. good for drug susceptibility test -PCR is faster. multinucleated giant cells -Sheets of histiocytes in immune suppressed individuals (can't form granuloma) -Acid-fast baccilli w/ special stains -Diagnosis -Culture . etc. adrenals.nodule/mass in the lung w/ or w/o lymph node enlargement -Microscopic .due to swallowing coughed-up infected material PPD & Granuloma (what it looks like) will be on the exam 21 . -Pathology -Gross . -Classification -Primary infection -Develops in unsensitized person *Ghon complex . aspiration.1 cm focus of granulomatous inflammation in the lung -Usually subpleural w/ granulomatous lesion in corresponding LN -Clinical course -Usually asymptomatic.) -Increasing sputum & hemoptysis are more overt sx -Lung "mass" is malignancy until proven otherwise *Typically occurs in apical or posterior segments of upper lobes -Oxygen tension is higher in these areas -Forms a cavitory lesion -Clinical course is variable -Fibrosis & calcification can stop the infection -Can spread beyond lungs .gold standard. sarcoidosis.meninges. often cervical -Intestinal . vasculitis (Wegener). etc.granulomas w/ central caseous necrosis. but takes 3-8 weeks.

SM constriction. exacerbation.8 -Restrictive lung disease is characterized by FEV1/FVC ~ 0. catarrhalis. -Pathogenesis -Innate defense system damage .increased submucosal glands -Clinical disease *Small airway obstruction leading to V/Q mismatch -Post-obstruction alveoli do not participate in gas exchange -Hypercarbia & hypoxemia result .present on inspiration & expiration -Histopathology -Gross . NOT fully reversible.FEV1/FVC < 0.coal workers. welders."blue bloater" -Emphysema . S.small airway obstruction -Cigarette smoke & other irritants influence epithelial cells -Submucosal glands undergo hyperplasia & increase mucus production -Irritants injure epithelium and impair ciliary mucus clearance -Bronchiolar basement membrane thickens due to collagen deposition -Bronchoconstriction in response to irritant exposure -Small airway obstruction is structural . fumes) .decreased FEV1 & FVC -FRC (=ERV + RV) and RV increase -TLC increases over time -Chronic Obstructive Pulmonary Disease (COPD) -Preventable & treatable disease characterized by irreversible airflow limitation -Airflow limitation is progressive.mucus plugging -Micro . etc. remodeling -Decreased outflow pressure due to loss of parenchymal elasticity -Alveolar walls are disrupted -Etiology -Cigarette smoking -Occupational exposures (dust.may lead to erythrocytosis -Pulmonary vascular constriction → pulmonary HTN."pink puffer" -Diagnosis via spirometry . cytokines -Chronic bronchitis . fire fighters.7 follwoing bronchodilator -Normal FEV1/FVC ~ 0. leads to progression & worsening sx -Acute exacerbation generally brings a patient to see the physician -50% of cases are related to bacteria .epithelial cell damage. -Each infection.H.9 -Chronic Bronchitis -CLINICALLY defined by a productive cough for 3+ months for 2 consecutive yrs -Diagnosed by excluding other causes -Early disease may be mild . & edema -Decreased chemoreceptor sensitivity to CO2 prohibits normal hyperventilation -Body "chooses" hypercarbia over work of breathing → blue bloater 22 . flu. infection. pneumo -Pathogenesis . etc. cor pulmonale. M. fibrosis.OBSTRUCTIVE LUNG DISEASE -Obstructive Lung Disease -Is defined by spirometry values .slightly worse during the winter. & assoc w/ noxious gas/particles -Causes -Increased airflow resistance in small airways -Mucus hypersecretion.

barrel chest -X-ray .initially affects the respiratory bronchiole -Due to cigarette smoking .initially affects the acini -Related to α-1-antitrypsin deficiency (an anti-protease).-COPD (cont. IV drug abuse -A1AT deficiency permits overactive PMN elastase activity -Pathogenesis -Overactive elastase activity results in destruction of airspace walls -Enlarged airspaces coalesce to form bullae & blebs -Rupture may lead to pneumothorax -Elastase activity on capillary beds may compromise perfusion of ventilated areas -Increased dead space -Inflammation around bronchi & bronchioles -Histopathology -Massive airspaces .) -Emphysema -PATHOLOGICALLY defined by permanent airway distension distal to term. accessory muscle use.flat hemi-diaphragm (hyperinflated lung) & thin mediastinum -Types of emphysema -Centriacinar -Proximal . bronchiole -Due to destruction of airspace walls.hyperventilation.centriacinar is worse in upper lobes -Clinical disease -Parenchymal destruction causes a dynamic outflow obstruction to expiration -It's hard to breathe against the already expanded space -Scaffolding that holds lungs open at low volume is lost -Forced expiration causes airways to collapse → air trapping -V/Q mismatch due to ventilation of areas that are not perfused → hypercarbia -Hypoxemia may be mild. but chemoreceptors are sensitive to CO2 -Body "chooses" the increased work of hyperventilation → pink puffer -Hence these patients expend enormous energy and are thin -Try to breathe at a higher RV to decrease airway resistance -Increasing RV & FRC resculpts the chest into a "barrel shape" Age SOB Cough Infection Blood gas Chest XR Appearance Chronic bronchitis 45 late early common hypoxemia large heart overweight Emphysema 65 early scant occasional ~normal hyper-inflated emaciated 23 .leads to PMN & MΦ recruitment -PMN’s & MΦ’s release elastase -Free radicals in smoke inhibit anti-proteases -MΦ elastase is not normally inhibited by A1AT -Panacinar -Distal . obvious fibrosis is NOT noted -Results in decreased lung elasticity / increased lung compliance -Sx . pursed lips.

type I hypersensitivity rxn to extrinsic antigen -Atopy .obstruction followed by infection -Pathology -Gross . fever.hyperplasia of mucus glands & smooth muscle -Bronchiectasis -Characterized by permanent dilation of bronchi & bronchioles -Due to destruction of muscle & elastic tissue associated w/ necrotizing infections -Now uncommon w/ antibiotics -Sx: cough. IgE's bind to mast cells -IL-3. mucus plugging -Clinical disease -May progress to bloody sputum & life-threatening hemorrhage -Obstructive pattern can lead to profound cyanosis & dyspnea -Also cor pulmonale. chest tightness.aspirin -Occupational .enlarged airways. etc.tumor. influenza. filled w/ mucopurulent secretion -Big. Pseudomonas -Viral .genetic predisposition to develop IgE response to common allergens -Ex: dust mites. exercise.dilated airways can be traced to pleura. → vascular permeability & bronchoconstriction -Leukotrienes have been implicated -PMN's are recruited & cause endothelial damage and mucus production -Pathogenesis of intrinsic asthma -Viral URTI is the most common trigger .5 -IL-4 causes IgE class switching in B-cells.4. dilated holes in the lungs -Micro . -Pathology is similar to chronic bronchitis -Gross . brain abscess. flu. cat dander -Intrinsic .) -Clinical -Spirometry before & after bronchodilators to determine if obstruction is reversible -Pathogenesis of atopic asthma -Allergen is presented to Th2 cell → IL-3.MTB.adenovirus.mucus plugging -Micro . H.aspergillus -Bronchial obstruction . cough . foreign body -Pathogenesis .worst in morn & evening -Variable bronchoconstriction & airflow limitation due to hyperreactivity -REVERSIBLE spontaneously or w/ therapy -Classification helps guide therapy -Extrinsic . infection. amyloidosis 24 .lowers threshold of vagal receptors to irritants -Drug-induced . Staph. dust. HIV -Fungi . copious foul-smelling purulent sputum -Associated conditions -Congenital .5 recruit eosinophils & stimulates release of mediators -Allergen binds & cross-links IgE's on mast cell → mediator release -Mediators stimulate vagus n.diverse non-immune mechanisms (cold.cystic fibrosis (predisposed to Pseudomonas) -Post-infectious -Necrotizing bacteria .-Asthma -Chronic inflammatory disorder of the airways -Recurrent wheezing. etc. breathlessness. stress.fumes.

9 (normal = 0. lung carcinomas. *does not respond to steroids -Known causes -Collagen vascular diseases . & endothelium -Gas exchange occurs through it -Chronic Interstitial Lung Disease -Overview -Constitute 15% of non-infectious lung diseases seen by pulmonologists -Fibrosis around pulmonary vessels may cause R-sided HF 2o to pulmonary HTN -Diseases are progressive -Distinctive pathology becomes generic "honeycomb" in end-stage lung -Usual Interstitial Pneumonia (UIP) -Clinical .breast CA. men > women. obstructive -Obstructive .age > 50.characterized by reduced expansion of lung parenchyma -Decreased total lung capacity & loss of lung compliance (in/c recoil) -FEV1/FVC ~ 0. patchy. can hear end-inspiratory crackles (like velcro) -Prognosis . amiodarone -Environmental .8) -Diffuse & chronic involvement of the interstitium -Interstitium = fused epithelium. along w/ Mphages secrete proteases -Fibroblast recruitment leads to fibrosis -Pathology -Gross .bleomycin. Hodgkin disease -Drugs .RESTRICTIVE (INTERSTITIAL) LUNG DISEASE -Restrictive Lung Diseases -Heterogenous group of lung diseases -Both known and idiopathic etiologies -Classified by clinical syndrome or histology -Pathology = diffuse interstitial disease -Restrictive vs. systemic sclerosis -Radiation .asbestos *Idiopathic cause is most common -Pathogenesis -Lung injury leads to macrophage activation & cytokine release -PMN's are recruited. SLE.rheumatoid arthritis. fibrotic disease -Fibrosis gives pleural surface a "cobblestone" appearance -Lesions seen predominantly in lower lobes -Progresses to honeycomb lung -Micro . BM.3-5 yr survival.*subpleural-based.*"temporally heterogenous fibrosis" -Old collagenous scarring & loose new fibrosis right next to each other 25 .characterized by an increase in resistance to airflow -Restrictive .

do not respond to either Candida test or PPD test -Prognosis . dyspnea. pet bird. Mphages fill the airspaces 26 . steroids may be used -Pathology -Micro .S.Lcytes. humidifier -Immune complexes & delayed type IV (T-cell) hypersensitivity -Involves alveoli. multinucleated giant cells -Calcifications may also be seen -Hypersensitivity Pneumonitis -Immunologically mediated interstitial lung disease due to prolonged exposure to Ag’s -Occurs in genetically predisposed individuals -Takes weeks to months of exposure for sensitization to occur -Bizarre etiology .20-40 y/o. black > white ."desquamative" is a misnomer -Mononuclear cell infiltrate (Mphages) w/o prominent fibrosis or honeycombing -Clinical . 70% recover fully w/ minimal manifestation -Pathogenesis -CD4+ cells accumulate → IL-2 & IFN-gamma → T-cell & Mphage prolif -TNF. silo. pleura -Hilar & mediastinal lymphadenopathy -Cross-section of lung reveals bronchioles surrounded by granulomas -Micro . & MIP recruit T-cells to form a granuloma -Main pathology . IL-8.-Sarcoidosis -Multi-organ system disease of unknown etiology -Clinical .varied progression & spontaneous resolution *Responds to steroids.40-50 y/o.full recovery if pt stops smoking.recognize early & prevent -Clinical -Acute attacks of fever. women > men.granulomas along lymphatics. usually incidental finding on CXR -Pts tend to be anergic . not airways (compare to asthma) . vessels. SOB) takes weeks-months to develop -Prognosis . & couch 4-6 hrs after exposure -Chronic exposure leads to progressive respiratory failure due to fibrosis -Remove offending antigen and lung will recover -Pathology -Micro .diffuse nodules centered around bronchioles -Non-caseating epitheliod granulomas.*young black woman *Predominantly in southeast U. plasma cells..non-caseating granulomas -Lungs are most common site -Gross . men > women -Subacute illness (cough. bronchioles.hypercellular lung. & Mphages in a loose non-caseating granuloma -Granulomas are centered around bronchioles -Para-bronchiolar fibrosis occurs late -Desquamative Interstitial Pneumonia (DIP) *Interstitial lung disease in current/former smokers .

avoid infection. white.impedes gas exchange -Pathology -Micro . surfactant disruption. C-section -Sx w/in hours of birth . TGF-beta -Sx . increased cellularity.tachypnea. IL-10.dramatically thickened alveolar walls -Looks like holes in tissue instead of alveoli -Acute Interstitial Pneumonia (AIP) -Same as DAD both histologically & clinically.-Acute Restrictive Lung Disease -Overview -Spectrum of pulmonary lesions initiated by numerous factors -Causes include bacteremia.treat w/ empiric antibiotics but doesn’t respond -No organism is ever identified -Clinical . 50% w/ fever. congestion. but IDIOPATHIC cause -Ex: pt thought to have CA pneumonia . respiratory failure -Clinical .hyaline membranes. exogenous surfactant therapy -Pathology -Gross . subcostal retractions. IL-6.evolves in days-weeks. stiff lungs -Micro . atelectasis -Diffuse Alveolar Damage (DAD) -Rapid. treat hypotension -Pathogenesis -Damage to alveolar epithelial & capillary endothelial cells allows leakage -May be a result of G(-) bacteremia & LPS -Cells & fluid leak into alveoli . sudden onset in pt usually hospitalized for profound dyspnea w/ cyanosis. DIC. recruit fibrobasts -Reorganization forms a hyaline membrane . may lead to death -Prognosis .100% present w/ cough.Mphages phagocytose debris.prevent premature birth. etc. multiorgan failure. IL-1. condensed. nostril flaring. gestational diabetes.50% overall mortality (sepsis.pulmonary edema.heavy. cyanosis -Expiratory grunting to open airways .alveolar collapse increases work of breathing -Cases may be mild or severe -Treatment .maintain O2. & many more -Genetic susceptibility contributes -Mediated by cytokines .TNF. male. & thickened alveolar walls 27 . hypoxemia.premature birth (< 28 wks).) -Provide supportive tx . may lead to acute respiratory failure -Only tx is mechanical ventilation -Survival ~50% -Hyaline Membrane Disease *Most common cause of respiratory distress in the newborn -Responsible for 1/3 of neonatal deaths -Child makes insufficient surfactant due to prematurity or lung insult -Hyaline membranes form as a result of hypoxemia & CO2 retention -Hypoxemia & hypoperfusion lead to endothelial & epithelial damage → leakage -Clinical *Risk factors .

Nodules of fibrosis. little dust. stone engraving. effective mucociliary elevator -Size & shape of particles . *Increases susceptibility to tuberculosis -Nodules may undergo necrosis w/o epithelioid granulomatous rxn -Necrosis + granulomatous rxn in a nodule = TB until proven otherwise -Diagnosis . particularly asbestos -Only a small % of those exposed go on to develop pneumoconiosis -Process -Particles activate alveolar Mphages → release cytokines & proteases -Generates inflammation & fibrosis -Reaction patterns -Inorganic particulate dust . but dust is polarizable* -Progressive parenchymal nodules & fibrosis after inhaling silica crystals -Risky occupations . exclusion of other causes 28 .hypersensitivity pneumonitis.dust may overwhelm capacity. upper lobes -Pulmonary function test (PFT) is normal -Histopathology -Numerous bilateral nodules throughout lungs -Carbon macules (dust-filled Mphages).causes sarcoid-like granulomas -Vapors.1-5um particles can reach the terminal air sacs -Alveolar Mphages .quarrying.asymptomatic or chronic cough w/ black-tinged sputum *Coal nodules . vapors -Pathogenesis -Depends on -Amount of dust retained in airways -Irritant conc.only tx is prevention -Silicosis . chemical fumes .worsens the effects of inhaled irritants.based on clinical hx & radiologic findings -In absence of smoking. etc. dust > fibrosis -Treatment . in air. radiologic findings. findings may overlap (silicosis .but exam is 1:1) -Diagnosis .black Mphages border bronchioles. acute lung injury -Organic dusts (animals.PNEUMOCONIOSES & PULMONARY HYPERTENSION -Pneumoconioses -Definition . etc. but little fibrosis -Complicated CWP . does not in/c CA risk.harmless accumulation of carbon in lymphatics -Simple CWP .cause DAD.dyspnea & productive cough -Rare .hx.Nodules with lots of dust & less fibrosis than other dz’s -Interstitial lung disease caused by coal dust -Since coal is not dz after SCWP. aspestos cause fibrogenesis -Carbon/coal is not fibrogenic -Fine dusts (beryllium) . bronchiololitis.non-neoplastic lung reaction to inhalation & retention of dust. sandblasting.silica.) . duration of exposure. Mphage rxns can injure cells -Tobacco smoke . even w/o continued exposure -PFT shows a restrictive pattern -Histopathology -Large zones of scarring & anthracosis -Dense fibrosis w/ anthracotic pigment-laden Mphages -However. no increased susceptibility to TB -Types of CWP -Anthracosis . fumes. granulomas -Classification of Pneumoconioses -Coal Workers Pneumoconiosis .

bilateral nodules . or acute depending on exposure -Acute .sx develop decades after exposure -Restrictive pattern via PFT. cor pulmonale -Radiology -Bilateral. asbestos bodies -Risks . insulation.Diffuse fibrosis. floor tiles -Types of fibers -Chrysotile . demarcated. most common manifestation -Pathognomonic for exposure."eggshell calcification" -Peritoneum & pleura may experience fibrosis -Gross cavitation may be seen in fibrotic nodules -Asbestosis . mainly in lower lobes -May appear similar to UIP -Pleural involvement is a hallmark & sets it apart from other dz's -Pathology -Fibrosis beginning at bronchioles & spreading peripherally *Subpleural fibrosis & diffuse interstitial fibrosis -Asbestos bodies seen microscopically 29 .flexible. failure. but not required for dx of asbestos exposure -Asbestos exposure -Increases the risk of lung carcinoma . ship-yards. textile nodules of dense. due to heavy exposure as in sandblasting -Sx develop w/in 3 yrs -Chronic (classical) is the most common form -Sx develop decades after exposure to low levels of dust -Accelerated experience disease after 3-10 yrs -Can be simple or complicated (like CWP) -Lung nodules are present (like CWP). gets caught in the URT -Amphibole .rare. aligns w/ air to reach LRT -Can penetrate epithelial cells & reach interstitium -Amphibole exposure correlates with mesothelioma -Asbestos bodies -Asbestos fibers coated w/ iron by macrophages (ferruginous body) -Appear straight w/ clubbed ends & beaded shaft -Diagnostic for asbestosis.mining. symmetric. diffuse interstitial fibrosis.circumscribed plaques of dense collagen -Asymptomatic. dyspnea.5x in non-smoker. bodies need not be present -Asbestosis -Bilateral diffuse interstitial fibrosis of the lungs due to fiber inhalation -Requires heavy exposure -Diagnosis .straight & stiff. non-productive cough -Disease may be static or progress to resp. asbestos bodies -Clinical .Mphages cause fibrosis -Radiology can't distinguish CWP from silicosis -Histo . -Clinical may be chronic.hx of exposure. 55x in smokers -Increases relative risk of mesothelioma by 1000x *Bronchogenic carcinoma is more common than mesothelioma -Pathology: Pleural plaques . accelerated. but more obvious fibrosis -Predominantly in upper lobes -Histopathology -Firm. linear opacities. lamellar fibrosis **Birefringent silicates & collagen fibers -Anthrocotic pigment may be seen -Lymph nodes often calcify .

RVH due to lung disease -80% generally die in 2-5 years 30 . due to structural conditions -Etiology -COPD/interstitial lung disease (hypoxia) + destruction of alveolar capillaries -Increases pulmonary arterial resistance & hence pressure -Congenital or acquired heart disease -Recurrent thromboemboli . portal HTN. cyanosis. thrombocytosis.causes vasoconstriction in pulmonary vessels -Anorexigens (appetite suppressants) -CNS stimulants . methamphetamine -HIV infection.-Pulmonary Arterial Hypertension (PAH) -General -Pulmonary circulation is a low resistance system (pressure is 1/8 of systemic) -Pressure increases due to increased blood viscosity or decreased vessel radius -Secondary -Most common cause of PAH.primary PAH & R→L shunts -Capillary formation in the arteriole lumen (recanalization?) -Clinical -Dyspnea.cocaine. respiratory distress. fatigue. hemoglobinopathies *Pathogenesis is similar to atherosclerosis -Endothelial cell dysfxn -Vascular constriction & platelet adhesion -Decreased prostacyclin & NO.cause inflammation & fibrosis of pulmonary vessels -Ex: systemic sclerosis -Obstructive sleep apnea *Clinincal associations -Hypoxia . increased endothelin -Vascular remodeling .concentric rings of SM cells -Atheromatous changes .reduce x-sectional area of pulmonary vascular bed -Autoimmune disorders .migration & proliferation of SM & production of ECM -Primary (familial / idiopathic) -Diagnosis of exclusion.histologic lesions are not specific to PAH -Marked medial hypertrophy in vessels . 6% familial AD w/ incomplete penetrance -Most common in children & women age 20-40 -Mutations in the BMPR2 signaling pathway -Normally inhibits proliferation & favors apoptosis in vascular SM -Morphology .arterioles & small arteries are most affected -Plexogenic pulmonary arteriopathy .

etc. dry mouth. HA. or may present w/ sx -Sx . genetic alterations.hyponatremia from SIADH. -Metastases may cause the first sx . bone pain/fracture -Adrenals.seizure.rapid cell turnover -Squamous cell carcinoma -Generally preceeded by metaplasia. head. ptosis -LEMS often develops before diagnosis of cancer -Small cell carcinoma -Derived from dispersed neuroendocrine system.lower prox muscle weakness. brain -Pericarditis . radon. arm. -Strong association with smoking -Slower to spread outside of the thorax compared to other types of carcinoma -However.LUNG AND PLEURAL TUMORS -Carcinomas -Overview -Pathogenesis -Stepwise accumulation of genetic abnormalities in bronchial epithelium -Smoking. etc. carcinoma in situ.cough.hypercalcemia from PTH-related peptide (PTHrP) -Associated with bone resorption -Lung cancer (mostly small cell) . intercellular bridges 31 . possible chemo/radiation -Pathogenesis -Smoking causes squamous metaplasia of the respiratory epithelium -Evolves to squamous dysplasia & squamous cell carcinoma in situ -Eventually becomes invasive .extends into stroma -Histopathology -Nests of polygonal cells w/ glassy pink cytoplasm.central mass -Commonly associated with paraneoplastic syndromes . dyspnea. paraneoplastic syndrome. etc. edematous face. brain.CA may extend to pericardium & restrict cardiac filling -Pleural effusions. & bone are most common sites of metastasis -Overall 5-year survival is 15% -Secondary pathology -Bronchial obstruction can cause atelectasis. ADH *Almost never associated with hypercalcemia -Aggressive . strong association w/ smoking -Usually found in the hilum .surgery isn't possible due to metastases -Histopathology -Sheets of "small" cells with scant cytoplasm -Finely granular "salt & pepper" chromatin -Frequent mitotic figures & necrosis . liver. Cushing from ACTH -SCC . pleuritis -Paraneoplastic syndrome .any tumor can secrete hormone-like substances -SmCC . fatigue. -Presentation -Pts are generally 40-70 y/o -May be an incidental finding.ACTH. post-obstructive pneumonia -Superior vena cava syndrome – compression or invasion of SVC (emergency) -Sx .Lamber-Eaton Myasthenic Syndrome -Sx .generally metastasized widely at diagnosis -Tx: chemotherapy . locoregional recurrence is more common than w/ other types **Strongly associated with paraneoplastic Hypercalcemia -Tx: surgery. demoplastic stroma -Keratin pearls. wt loss. dysplasia.venous congestion. fatigue.

atypical (necrosis. & large cell -Less frequently associated with smoking (only 75%) -Generally appear peripherally.patterns vary. squamous. possible chemo/radiation -Histopathology . or a multiple "buckshot" lesion -Many lesions of various sizes is indicative of mets from a distant primary -Malignant Pleural Tumors -Metastases are also the most common tumor of the pleura -Often obstruct lymphatics & cause a pleural effusion -Other causes include lung CA.diagnosis of exclusion -Tends to be large at diagnosis -Usually peripheral location. breast CA.polyploid mass protruding into the bronchial lumen -Nests of homogenous cells with round nuclei -Hamartoma -A mature indigenous tissue in a disorganized mass -Appears in lung as lobule of disorganized cartilage w/ clefts lined by epithelium -Usually incidental . but rare overall . ugly cells -Nuclei have open chromatin & prominent nucleoli -Other Cancers of the Lung & Pleura -Carcinoid -Low grade malignant epithelial neoplasm w/ neuroendocrine differentiation -Arises from dispersed NES in bronchogenic epithelium. 2-10 mitotic fig’s) -Sx . ~3% of lung tumors -Types . may present w/ cough & hempotysis -Histopathology -Gross appearance . -Adenocarcinoma -Most common histologic carcinoma -Generally seen in women & non-smokers . smaller size than other carcinomas -Earlier metastasis outside of thorax than SCC -May appear in pleura or chest wall since they are peripheral -Symptoms may appear before the primary tumor is identified -Tx: surgery. may appear like an orange rind 32 . chest wall pain -20% of pts have concurrent asbestosis -However.diffuse pleural thickening.peripheral. glandular structures lined by a single layer of epithelium -Large cell carcinoma -Undifferentiated malignant epithelial tumor .usually an incidental finding.carcinomas. looks like a "coin" -Tx: excision is curative -Lung Metastases -Lungs are most common site for mets .pleural effusion.EGFR(+) -EGFR is a TK that signals kRas to regulate proliferation & apoptosis *NSmCC's with somatic EGFR mutations may respond to TK inhibitors -EGFR mutations are extremely rare in small. circumscribed. sarcomas. < 2 mitotic figures). necrosis is seen -Tx: surgery. possible chemo/radiation -Histopathology -Sheets of cells with large nuclei & moderate cytoplasm . & lymphoma -Survival 3-6 months -Mesothelioma -Most common 1o pleural CA. lymphomas -May be a single "cannonball" lesion.big. breathlessness. asbestos is more likely to cause lung CA than mesothelioma -Histopathology .typical (no necrosis. melanomas.very aggressive (2yr survival) -Sx . solitary.

LUNG LAB -Smoker w/ Shortness of breath -Bronchopneumonia .stiff. jagged orientation of spaces -Well-formed cartilage indicates the cancer obstructed a bronchus → bronchopneumonia *Panacinar emphysema -Correlates with A1AT deficiency -Upper lobes are affected worse .pink material. Pseudomonas -If alcoholic vomits & aspirates. giant cells. pleural effusion -Diffuse pleural thickening (rind-like).overactive elastases -Panacinar .acute respiratory distress syndrome from chlorine exposure -Tuberculosis -Caseating granuloma . full of something besides air -Hypercellular lungs .smoking -Causes of DAD -Something damages epithelium or endothelium .asbestos bodies.most likely mestastases -Pathogenesis of emphysema .LUNG CASES -Asthma -Airway remodeling in bronchioles . & outer layer of lymphocytes -Other Points -HA pneumonia occurs > 48 hrs after hospital admission .mucus appears this way on a slide -Charcot-Leyden crystals .fibrosis & SM proliferation -Also mucus gland proliferation & mucus plugs -Curschmann sprial .Enterobacteriaceae. central necrosis -Surrounded by macrophages. most common primary tumor of the pleura -Change in history – rapidly progressive dyspnea -Differentiate from carcinoma -Mesothelioma: Calretinin(+). can get Klebsiella pneumonia -Multiple lung lesions .dilated airspaces -Migrant Worker -Diffuse Alveolar Damage (DAD) -Hyaline membranes made of proteinacous debris & pneumocytes -Clinical .remnants of eosinophil proteins -Hyaline Membrane Disease & GBS Pneumonia (infant) -Lungs look like liver .chemicals. exotoxin (sepsis) -Proteinacous fluid leaks & accumulates in alveoli.don't see airspaces or alveoli -Hyaline membrane lining alveolar spaces -Asbestos Exposure . acellular fibrosis -Mesothelioma .A1AT deficiency -Centriacinar .lower lobe infiltrates.PMN infiltrate in a PATCHY pattern -Adenocarcinoma .single layer of cells lining a space. pneumocytes are damaged -Debris forms hyaline membranes 33 .