2020 TOPNOTCH MEDICAL BOARD PREP HANDOUT PATHO‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT (03/2020) BY KEVIN ELOMINA, MD For inquiries visit www.topnot: ::/ www. face 9k. COF yotchmedicalboardpret CELL INJURY. PATHOLOGY ee Seve uy ___] Kevin) Eloming MD + Oxygen deprivation Tone eS hye agens Ti celine Reapagenta Sep * Chemical agents and Drugs Resear Sra Zinflammation and Repair Infectious agents S Henodanis Bhetes é ¢ Immunologt reactions Genet Dida € { Geneti derangements 5: Ducne ofthe inne 7a 0 {Nutritional imbalances chase a 7 ates Damas 7 ] ‘8. Environmental and Nutritional Pathology 20 PATTERNS OF REVERSIBLE CELL INJURY 9. Diseases of Infancy and Childhood 24 CELLULAR SWELLING destin 3 7 Firstmanifestation of almostal forms ofan tol ita 4 {Influx of ions (and water) due to flare of energy-dependent 12. Wits Na Speen and Tama 3 ion pumps (aKa Pase) 15 Hed asd CelssdBeed Duara 3 « Haamplaeyttoic edema in merce ie ingen Piss ra 45. Head and Neck 48. FATTY CHANGE ie Cone 30 =a 3 Seen in calls dependent on atimetabalim (ver ear) 2 Gerad alba SS 1 Sinan of tonne iplavaceole ibe st TPES OF CELL DEATH 20: ewer ty Tac ad ae Gea thie Gael he $e FEATURES NECROSIS ‘APOPTOSIS 22 reat 78 7 Reduced ndocrine System 7 Cellsize — Enlarged (swelling) (yrinkage) (shrinkage) Fists er 35 Sones [and Tae i oFyincsis > + Fragmentation ito 26. Peripheral Nerves and Skeletal Nusdlex 2 Nucleus _Karyorthexis > nucleosome-sized 37 cena Nervous Sst <6 | ianoya fragments, ie 95 © Intact; altered Plasma pjrupted structure, especially 1. CELLULAR RESPONSES TO STRESS membrane orientation of lipids. CELLULAR RESPONSES TO STRESS AND Cellular . coma me . Beds maybe gestion; maylesk "released in INJURIOUS STIMULI contents Oe apoptotic bodies car oe - eiveane ‘dace, prenu - inflammation * Frequent No Physiologic invariably ++ Often physiologic; orpatoletle *Secologe may be pathologic OUTLINE CELLULAR ADAPTATIONS ‘ADAPTATION | _ DEFINITION ‘STIMULUS MECHANISM EXAMPLES HYPERTROPHY |«Organ/cell + ‘Functional demand “+ Protein synthesis » PHYSIOLOGIC SIZE + Hormonal stimulation ‘© Myometrial hypertrophy in gravid uterus (hormonal stimulation) © Muscle of bodybuilders (functional demand) + PATHOLOGIC ‘LVH inhypertensive heart disease HYPERPLASIA [+ NUMBER of — + Hormonal + Growth factor” + PHYSIOLOGIC cells + Compensatory driven proliferation _o Pubertal breast changes (hormonal) ofmature cells oro Liver regeneration (campensatory) : + NOutputofnew —» PATHOLOGIC cellsfrom tissue __ Endometrial hyperplasia (hormonal) stem cells ‘ATROPHY [+ Vincallsize + Workload + VProtein synthesis » PHYSIOLOGIC AND number + Denervation + NProtein ‘© Embryonic atrophy (notochord and * Ischemia degradation thyroglossal duct) + Malnutrition + Autophagy + PATHOLOGIC + Loss of endocrine stimulation co Senile atrophy of brain + Pressure METAPLASIA |» Differentiated + Stress + Reprogramming of » Squamous (Columnar to squamous; most cell ype replaced stem cells common) Vitamin A deficiency by another cel * Columnar: Barrett esophagus ‘ype + Connective tissue: Myositis ossificans after intramuscular hemorrhage TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inauiries visit www tannntehhnardnran enm nh nett Page 1 of 98NECROSIS + Unregulated form of cell death * Common morphologic changes: © Increased eosinophilia (pink) © Myelin figures (From da (from damaged cell es; can undergo saponitioua ged cell membranes; can underg © Nuclear changes: { Karyolysis: decreased basophilia of chromatin ‘ Pyknosis: nuclear shrinkage with increased basophilia Karyorrhexis: fragmentation of pyknotic nucleus —_] PATTERNS OF NECROSIS Coagulative necrosis, * Architecture of dead tissues preserved ("acidophilic on 5 preserved ("acidophili * Ischemic necrosis in all organs, EXCEPT brain * Infarct: localized area of coagulative necrosis, Liguefactive necrosis * Digestion of dead cells, resulting in transformat ion ofthe tissue into a liquid viscous mass (pus) ‘ Infections (usually bacterial; some fungal) « Ischemic necrosis in BRAIN Gangrenous necrosis * Ischemic coagulative necrosis ofthe limbs (dry gangrene) + May have superimposed bacterial infection > liquefactive necrosis (wet gangrene) Caseous necrosis "Cheese-like” « Architecture NOT preserved ‘Tuberculous infections «Part of a tuberculous granu Joma Enzymatic fat necros|s «+ Fatty acids from triglyce ride breakdown comb'me with Ca anu form soaps (saponificat ion) '* Pancreatitis * Shadowy outlines of t ecrotic fat cells + bas ophilic Ca deposits + surrounding inflamrr jation Fibrinoid riecrosis: ‘+ Immune reactions involving blood vessels ‘+ Fibrin + immune ¢ omplexes = pink, arnorphous material (fibrin-like”) c ME CHANISMS OF ‘CELL INJURY met 2 tar Op meg toe Danage 9 itachi! Actenion oanere am ‘oipee —'eemeasity Smalls "tes Proters. ‘ala ona oraynes Pama Lysosomal memrere — nonbeane | 4 Ens c : amo! “agente alder ote ar ‘TOPNOTCH MEDICAL BOA.RD PREP PATHOLOGY HA\ Ene inmiirine visit ww ‘eannntchhaardoren.com. oh \NDOUT BY KEVIN ELOMINA, MD ih or httos://www. facebook, com/topnatchmedicalboardoreo/ a TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT (03/2020) BY KEVIN ELOMINA, MD For inquiries visit www.topnotchboardprep.com,ph or https: /www. facebook, com/topnotchmedicalboardprep/ ATP DEPLETION * Fundamental cause of necrotic cell death ‘Effects (at $-10% of norma levels); © Nav-K--ATPase failure > cellular swelling © Altered cellular metabol! sm -> anaerobic glycolysis > lactic acidosis 0 Ca pump failure > Ca2* influx > activation of cellular ‘eonaymes, © Reduction in protein synthesis © Misfolded proteins > unfolded protein response ‘© Membrane damage > necrosis APOPTOSIS + Regulated cell death “programmed” ‘© Can be physiologic (embryogenesis); or pathologic (viral Infections) + Two pathways: += Two phases: co Intrinsic (Mitochondrial) o Initiation © Extrinsic (Death receptor) _o Execution APOPTOSIS: INITIATION PHASE INTRINSIC EXTRINSIC MITOCHONDRIAL) DEATH RECEPTOR) ~ Activation of death receptors by appropriate ligands > Activation of. ~ Tnactivation of BCL2 (anti- apoptotic) > Activation of BAX/BAK channel > leakage ofeytochromeC> Activation initiator caspases > of initiator caspases > Apoptosis Apoptosis, — APOPTOSIS: EXECUTION PHASE ‘aspases 9 Cysteine proteases that cleave proteins after asparate residues + Initiator caspases ‘Intrinsic: Caspase 9 ‘Extrinsic: Caspases Band 10 + Executioner caspases © Caspases 3 and 6 AUTOPHAGY = Process in which a cell eats its own contents + Survival mechanism under various stress conditions (Le. nutrient deprivation) INTRACELLULAR ACCUMULATIONS MECHANISMS 11, Abnormal metabolism ofa normal endogenous substance (Steatosi 2, Accumulation of an abnormal endogenous substance (mutated at-antitrypsin) 43, Enzyme deficiencies (storage diseases) 4. Accumulation of an exogenous substance (anthracotic pigments) Lupiws + Triglycerides « Steatosis (in liver (most common), heart and kidney) + Cholesterol esters c Atherosclerosis (blood vessels) 6 Xanthomas (subepithelial connective tissue and tendons) 6 Cholesterolosis (macrophages in lamina propria of gallbladder) ‘o Niemann-Pick Disease Type C PROTEINS ‘MECHANISM ‘CONDITION ~ Reabsorption dropletsi , wephrotic syndrome proximal renal tubules. Nephiotie syndro ‘> Multiple myeloma: Plasma cells actively producing Igs (Russell bodies) «# Excess of normally-secreted proteins Defective intracellular transport and secretion ~ Accumulation of cytoskeletal proteins + el-antitrypsin deficiency + Alzheimer disease (neurofibrillary tangles) Aggregation of abnormal gyoidoss [_protelns Page 2 of 98u TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT (03/2020) BY KEVIN ELOMINA, MD For inquiries visit www,topnotchboardprep.com.ph or httos://www.facebook, com/tepnotchmedicalboardoren/ [HYAUINECHANGE, + Homogeneous, glassy, pink appearances NOT specifi Intracellular hyaline * Example: a1-antitrypsin deficiency (PAS-positive, diastase: ‘resistant cytoplasmic hyaline globules; composition misfolded proteins) © Extracellular hyaline ‘+ Example: hyaline arterioloscleross in Hypertension and DM (composition: protein and basement membrane components) GLYCOGEN * Abnormalities in glucose and glycogen metabolism Diabetes mellitus . z slycogen granules in hepatocytes, renal tubular epithelium, and cardiac myocytes © Glycogen storage diseases += Glycogen granules in cells due to inherited defects in glycogen metabolism PIGMENT EXOGENOUS ENDOGENOUS = Carbon * Lipofuschin © Anthracosis: © *wear and tear pigment” asymptomatic + Melanin © Coal worker's + Homogentisic acid pneumoconiosis: with © Alkaptonuria | associated interstitial (echronosis) Tung disease + Hemosiderin (heme) = Tattooing © Old hemorrhage; hemochromatosis, CALCIFICATIONS. FEATURE ‘DYSTROPHIC METASTATIC ‘oftissue_ Necrotic = Viable ‘Serum calcium Nofmal = Increased * Basophilic, amorphous granular, clumped ‘= Response of vascularized tissues to infections and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed, in order to eliminate the offending agents + Generally a beneficial response, but can be harmful n autoimmune diseases and allergies + Components (2) © Vascular Cellular ‘= Both activated by mediators (can be cell- or plasma-derived) CAUSES * Infections « Tissue necrosis + Foreign bodies + Immune reactions CARDINAL SIGNS * Rubor (Redness) + Calor (Warmth) ‘= Dolor (Pain) ‘= Tumor (Swelling) « Functio Laesa (Loss of function) GENERAL STEPS: SRS © Recognition ofthe injurious agent « Recruitment of leukocytes + Removal ofthe agent ‘© Regulation (control) ofthe response + Resolution (repair) RECOGNITION OF THE INJURIOUS AGENT = Cellular receptors for microbes ‘Toll-like receptors (TLRs) > production of molecules: involved in inflammation Histology” appearance; either intro extracel, hetbrotopic bone may be formed * Sensors ofcelldamage | 7 ene heptotoni hone may be formed Oia ora. ATP) aca nannasome (sabe ke (respiratory + Fereceptrsin leukocytes init ——_Tanellated compromise: | ae ae importance _coveretions);—» nephocacnosis | ——_, © Resneize opsonized mira sseehinapilary (renal Strang preeing cancers dysfunction) ‘© Mannose-binding lectin (activates complement) CELLULAR AGING GENERAL TYPES OF INFLAMMATION ‘Rest ofa progretsive decline in cellular function and vabliny FEATURE ACUTE ROME Cause by genetic abnormalities andthe accumulation of eRe aes sae cellar and molecular damage de tote elects of exposure to set Rare minutes «Slows days exogenous influences calldar Wainy + Wionoayies/macrophog infitrate__" neutrophils _” es and lymphocytes Tissueinjury, * ULAlY PE open severe and fibrosis ane progressive Tovaland eiicaland = Prominent + Less ACUTE INFLAMMATION MECHANISMS THAT PROMOTE AND COUNTERACT CELLULAR AGING ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries visit wrw.topnotchboardorep,com,ph or https://wwnu, face tcty + Components (3): 6 Dilation ofsmall vessels 6 Increased microvascular permeability ‘© Emigration of leukocytes and their activation DILATION OF SMALL VESSELS = Increase in caliber of blood vessels ‘ First involves the arterioles followed by new capillary beds ‘© Results in increased blood flow and stasis of blood > sxythema o Stasis > accumulation of leukacytes along endothelium + One of earliest manifestations of acute inflammation + Histamine: most notable mediator that produces vasodilation Page 3 of 98 Iboardpren/JA. ToPNoTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT (03/2020) BY KEVIN ELOMINA, MD For inquiries visit www.topnotchboardprep.com,ph or, INCREASED MICROVASCULAR PERMEABILITY * Mechanisms: _ © Endothelial cell contraction (Mast common) © Endothelial injury © Increased transport of substances across endothelial cells (transcytosis) ‘* Results in edema _; RECRUITMENT oF LEUKOCYTES TO SITES OF INFLAMMATION + Mediated by adhesion molecules and chemokines (chemoattractant cytokines) + Steps (5): © Margination Rolling © Adheston © Transmigration (Diapedesis) © Migration in the tissues toward a chemotactic stimulus MARGINATION + More leukocytes assume a mor peripheral postion along the endothelial surface a 7 ° LEUKOCYTE-ENDOTHELIAL INTERACTIONS FEATURE ROLLING ‘ADHESION * Transient binding» Frm adhesion of Definition aMddetachment of leukocytes to the efnition jeukocytes tothe endothelium endothelium Strength of| inrenath of Weak «Strong Duration of Duration oF Transient # Permanent a Po cha and P) 5 + Ligands on endothelium: Cytokine + expressionof _‘rexpression (INFandIL-1) —selectinsand—_ Leukocyte integrins: effects ligands activation from low- affinity to high- affinity state DIAPEDESIS Migration of adherent leukocytes across the endothelium ‘+ Mainly occurs in postcapillary venules '* Adhesion molecule: CD31/PECAM-1 (immunoglobulin) CHEMOTAXIS '* Movement of leukocytes toward the site of injury influenced by a chemical stimulus +» Most common exogenous: bacterial products (N- formylmethionine, lipids) ‘ Endogenous: cytokines (IL-8), complement (C5a), arachidonic acid metabolites (LTB4) + Chemoattractants activate GPCRs “> cytoskeletal changes > ‘movernent Cellular infiltrates in inflammation TYPE INEILTRATE ieite + PHN usually replaced by monoges after 24-48 hours) Prolonged + Monocytes Pseudomonas PMNs (for several days) Viral + Lymphocytes (usually first to arrive) ‘Allergic + Eosinophils (main infiltrate) Gelkmedisted «mp ain irate) JOVALOF THE AGENT © Leukocyte activation > phagoaytods > inacailar ng {Brysiolog consequence) 0 ROS and NO (intracellular) ‘Lysosomal enzymes (through phagolysosome formation) ‘o Neutrophil extracellular traps (NETS) « Killing mechanisms can also damage normal tissues (pathologic consequence) ‘© ROS, NO, and enzymes can be released into extracellular space ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD :chmedical REGULATION (CONTROL) OF THE RESPONSE * Inflammatory mediatars have generally short half-lives + Neutrophils have short half-lives and die by apoptosis ‘* Anti-inflammatory cytokines AA metabolites: lipoxin oTGF-B, and IL-10 MEDIATORS OF INFLAMMATION '* Substances that initiate or regulate inflammatory reactions + Can be cell-derived or plasma-derived ‘* Active mediators are produced only in response to various stimu ‘+ Most mediators are short-lived ‘© One mediator can stimulate release of other mediators VASOACTIVE AMINES «Histamine (from Histidine) ‘0 Masteelis (richest source), platelets, basophils. ‘o Release triggered by physical injury, immune-mediated (allergies), anaphylatoxins (C3a, C5a), cytokines (IL-1 and 8), neuropeptides (Substance P) + Serotonin (from Tryptophan) Platelets and neuroendocrine cells © Vasoconstrictor ARACHIDONIC ACID METABOLITES ‘* Fromarachidonic acid (20:4(«-6)) + Cyclooxygenase > Prostanoids and thromboxanes + Lipooxygenase > Leukotrienes and lipoxins ‘ACTION. EICOSANOIDS Vasocilation ~ PGh (Prostacyclin), PGE:, POEs, PCD: Vasoconstriction» TKA, LTCx, Ds Ee ‘vascular peectlity ——_¢ ETC Da Es Chemotaxis, leukocyte» LTB,, Hydroxyeicosatetraenoic adhesion acid (HETE) ‘CYTOKINES AND CHEMOKINES «Cytokines: proteins produced by activated lymphocytes, ‘macrophages, and dendritic cells, endothelial, epithelial, and connective tissue cells that mediate and regulate immune and ‘inflammatory reactions 0 See systemic effects of inflammation ‘+ Chemokines: small (8 to 10 kD) proteins that act primarily as ‘chemoattractants for specific types of leukocytes (Can be constitutively expressed (homeostatic) or inducible (inflammatory) COMPLEMENT SYSTEM + Soluble proteins that function mainly in host defense against ricrobes and in inflammatory reactions + 3athways differ in mechanisms of C3 cleavage: Classical, alternative and lectin + 3 functional outcomes: inflammation, opsonization and Phagocytosis, and cell isis + Regulated by cell-associated and circulating proteins NOTEWORTHY COMPLEMENT COMPONENTS ‘= C1: complexes with Ig-Ag complex (In classical pathway); activated by mannose-binding lectin complexed with bacterial surface CHOs (lectin pathway) ‘+ C3: most abundant component; lysis gives rise to C3a (anaphylatoxin) and C3b (opsonin) + C5: cleaved to CSa (anaphylatoxin) and CSb (part of MAC) '* C6-C9: late components of complement system (part of MAC) ANAPHYLATOXINS # (3a, C5a, and C4a « Promote histamine release from mast cells (same with anaphylaxis) > vasodilation and increased vascular permeability + CBa: chemoattractant to neutrophils, monocytes, eosinophils, ‘and basophils; activates LOX in PMNs and monocytes > inflammatory mediators Page 4 of 98For inquiries visit w COMPLEMENT-RELATED DISEASES + Cl inhibitor deficiency: hereditary angioedema * Decay accelerating factor (DAF) and CD59 deficiency 'aroxysmal nocturnal hemoglobinuria (PNH) * Deficiency in at components: suscepti to Nesseria infections. ponents panty OTHER MEDIATORS OF INFLAMMATION © Vaso- and bronchoconstriction (high concentrations); histamine-like effects (low concentrations) + Kinins © Bradykinin: increased vascular permeability, contraction of uo TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT (03/2020) BY KEVIN ELOMINA, MD stopnotchboardorep,com,ph or https://www.facebook,com/topnotchmedicalboardorep/ SYSTEMIC EFFECTS OF INFLAMMATION o Eevei LPS from bacteria > IL-Land TNE > Increased PG production (PGE2) ~> elevates temperature set point © Ike6 > Increased synthesis of CRP fibrinogen, and serum amyloid A Cytokines -> Colony stimulating factors > WBC proliferation ‘High levels of cytokines > hypotensive shock, DIC, insulin resistance, and hyperglycemia sasha acason dp ("RESOLUTION (REPAIR) ] _ ‘¢ Restoration of tissue architecture and function after and injury © Substance: pain, increased vascular permeabilty, BP *Genealgpes “ we ‘regulation, and endocrine cell hormone secretion ‘© Regeneration (generally happens in labile and stable tissues: MORPHOLOGIC PATTERNS OF ACUTE INFLAMMATION Connective Use depsion (happens chron severe . ae CLASSIFICATION OF TISSUES BY REGENERATIVE CAPACITY Svat exudation of cl-poor fu STSSUE DESCRIPTION Sens © Purulent: ps: exudate consisting of PMNs, Nquefed necrotic labile proliferation of residual ePhnElM phe fells or maturation of | * Hematony 0 Ulcer: excavation on organ surface from sloughing of | stem cells sem cel {inflamed necrotic tissue Cells are quiescent (in tiyey OUTCOMES OF ACUTE INFLAMMATION 2 cscapactyto KiStEY + Resolution seeraceacepe Fanereas + Pus formation (abscess) Stable ey (except. Endothelium loss cells CHRONIC INFLAMMATION ' Terminally '¢ Neurons ‘* Response of prolonged duration in which inflammation tissue Permanent differentiated and * Cardiac and injury, and attempts at repair coexist, in varying combinations nonproliferative skeletal myo ues ee 3 perscntiy tases (autelmmune diseases) ae 0 Prolonged exposure to potentially toxic agents + Principal celis involved: ‘0 Macrophages Lymphocytes MACROPHAGES + Basically, monocytes ih tissues (monocytes are circulating) «Functions in chronic inflammation: 0 Phagocyte o Initiate tissue repair 0 Secrete inflammatory mediators © Antigen-presenting cells LYMPHOCYTES: '* Activated lymphocytes (by microbes and environmental antigens) propagate and amplify chronic inflammation 0 GD4- T-celle: secrete cytokines, thus promote inflammation ‘and influence nature of inflammatory actions © Activated B-cells and antibody-producing plasma cells GRANULOMATOUS INFLAMMATION > Granuloma: collections of activated macrophages, often with T lymphocytes, and sometimes associated with central necrosis, + Activated macrophages > epithelioid cells (hallmark) or giant cells losis) ‘TUBERCULOUS GRANULOM: ‘TTOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD 35: / www facebook, com/topnotch For inquiries visit www. topnotchboardprep.com.ph or h ‘Angiogenesis: formation of new blood vessels from existing ones; growth factor: VEGE ‘© Formation of granulation tissue: fibroblasts + Joose CT. (ECM) + angiogenesis + inflammatory cells; hallmark of repalr ‘9 Remodeling ofthe scar: formation of fibrous scar; balance between ECM degradation (metalloproteinases) and synthesis (Tissue inhibitor of metalloproteinases (TIMPs) + Macrophages: central cells in repait o Produce PDGF, FGF-2, and TGF-8 + Deposition of CT happensiin 2 sequential steps: © Migration of broblasts © Deposition of ECM CHONS by fibroblasts + IGE: most important cytokine for synthesis and deposition of or FACTORS THAT IMPEDE REPAIR * Infections + Diabetes mellitus + Vitamin C deficiency + Glucocorticoids (inhibit TGF-) + Pressure + Poor perfusion + Foreign bodies ABNORMALITIES IN TISSUE REPAIR. ‘Wound dehiscence and ulcers: from inadequate granulation tissue formation « Keloids and hypertrophic scars: from excessive formation of repair components + Proud flesh: from exuberant granulation tissue + Contracture: from excessive wound contraction Page 5 of 98 icalboardoreo/i For inquiries visit TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT (03/2020) BY KEVIN ELOMINA, MD \h or https: /www. facebook, com/topnotchmedicalboardprep/ HEMOSTASIS ‘Bdema/Effusion + Formation of blood clots at sites of endothelial injury * Hyperemia and congestion «Three elements: ‘* Hemostasis and thrombosis. Platelets + Embolism © Coagulation cascade '* Shock o Endothelium ‘SUMMARY OF HEMOSTASIS. Asam EDEMA/EFFUSION. ‘STEP IMPORTANTEVENTS OUTCOME \ccumulation of fluid in tissues (edema) or Body cavities (effusion) © Reflex neurogenic Transient + Four main mechanisms achat” mechanimsand decease © iydrostatic pressure (Hear failure) endothelin flow 9 ¥Oncote pressure (Nephrotic syndrome) Exposure of © Vascular permeability (Burns, infections) * Expos Primary Lymphatic obstruction (post- MRM) purimary | subendothelia| ECM “> pemostatic = tanaaawereraae wemostasis _ platelet adhesion an Lt activation > aggregation ‘TRANSUDATE Vs, EXUDATE + Facor Xl andexposure ary aT SUDA EDA oftissue factor (VI) socom Pchoniraaieg ns Secondary coagulation cascade _* Secondary -athophysi nk =_h * ar jostasis fibrin n> al Physiology Starling forces permeability Ce Gt Nee aie plug. a additional pla permeability __* Normal Increased Searesaton as - a * Permanent plug ee Absent + Present os resorption by n et sn counterregulatory * Tissue iE Otei Content Of Maem! © High scabilissto ‘mechanisms (fibrinolysis: repair fluid. and resorption tissue plasminogen ‘Specific gravity + <.072 => 1012 activator (tPA)) Fibrin + Absent = Present Tnflammatory cells —» Absent = Present ‘THROMBOSIS ~ Pathologic counterpart of hemostasis MORPHOLOGY * Caused by conditions under Virehow triad ~ Clearing and separation of EOM and subtle cell swelling co Endothelial injury ‘+ Most common sites: subcutaneous tissue, lungs, and brain ‘© Abnormal blood flow (Stasis) + Inenal dysfunction, edema usually occurs in areas with loose ‘oHypercoagulable state CT (periorbital area) MECHANISMS HYPEREMIA AND CONGESTION VIRCHOW MECHANISMS OF THROMBOSIS '* ® Blood volume within tissues TRIAD. Endothelial injury _* NoFmal antithrombotic endothelium FEATURE VPEREMIA ‘CONGESTION ‘becomes prothrombotic on injury Process Adve + Passive = Turbulent injury can injure = Anke inion + Radel ow Abnormal bod, isthe > preirombots ininflammationand of blood ina aoe «+ Stasis: maximizes platelet contact a ae ‘oxygen demand) tissue (localized Psa Re leitiaeaaaind _or systemic) Tissue color + Red = Dusk © Genetic oracquired sonal at Hemoglobin + Oxygenated + Deoxygenated Hypercongubiiy Pesepoweso thrombosis, MORPHOLOGY [___ (resistant toactivated Proteinc) _| ‘ORGAN ROUTE CHRONIC, res ‘ung Engorged alveolar Thickened and fibrotic — — Seolurs ned FEATURE _yyiRoMBosIs__ THROMBOSIS « Alveolar septal edema» Hemosiderinladen THOM 4 Focalintra-alveolar macrophages (Heart sites Turbulent tae hemorrhage failure cells) 5 endothelial injury. ~ Centrilobular regions eclusive + Frequently = Almost awa “ are grossly red-brown + More enmeshed and slightly depressed + RBCsand platelets ly depres Appearance «(+)LinesofZannt (BCsane Ba + Distended central _—_ contrasted with tan fora veinand sinusoids surface (Nutmeg liver) romb) + Centrilobular + centrilobular © amet eemty ischemic necrosis hemorrhage Common sites + Coronary> 7a (008): ‘+ Periportal fatty» Hemosiderin-laden af involvement cerebral femoral * ™DVTimost change macrophages ramos dep S + Variable degrees of vein hepatocyte dropout and *-Taminatlons composed pale platelet and fibrin deposits mre alternating with darker red ellrih layers; signify formation of ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD thrombus in flowing biood = ‘ANTEMORTEM POSTMORTEM Fea’ ‘THROMBOSIS __ THROMBOSIS ‘Mitachedto vessel Yes = No wall Tines of Zahn» Yes No Page 6 of 98 For inauiries visit www.tonnotchboardorep,com.oh or httos://www.f k.com/topnotchmedicalboardpreygis TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD ‘+ Heart valves For inquiries visit www.topnotchboardprep.com.ph or https: /www. facebook. cor notchmedicalboardprey THROMBOSIS IN THE HEART OTHER FORMS: FEATURE MURAL THROMB! VEGETATIONS EMBOLISM CLINICAL PICTURE FINDINGS sites Heart chambers + Long bone fractures, ~ Recurrent thrombosis repeated miscarriages, cardiac valves, ar aortic lumen trauma > Pulmonary ex lobu Tala ray aang? * Fatt « Abnomal topreviously Marrow neurologicsymptoms Pulmonary Can damaged valves or | anemia, and myncardial ig destruction of thrombocytopenia Sciemyecial mere = Poreparam 9+ Fel san agp infective Dyspnea, cyanosis, hair, vernix caseosa, sexing eiear) fmmiose hegre, radian : + Hypercoagulable coma, pulmonary pulmonary steroease e ea pel ee eeaueand thrombotic 7 Gas bubbles in dation endocarditis) + Divers wh did skeletal muscle and + SLE (Libman-Sacks rapidascent > pain joints (Bends) endocarditis) Air onjoints, + Gas bubbles in 100ce: respiratory pulmonary FATES OF THROMBUS symptomatic insufficiency Yasculature (Chokes) FATE an DEFINITION (Decompression + Calsson disease on ® Thrombr accumulate addtional platelets sickness) {ischemia of femoral Exsraart ahd fibrin ® head, tibia, & humerus cation ® Thfombi dislodge and wavelto other Embolization "sites in the vasculature INFARCTION Diswohagon » Rid shrinkage and total disappearance ‘Area oflschemic necrosis caused by occlusion of either the of recent thrombi arterial supply or the venous drainage ‘Organization Thrombl become incorporated in the ‘* Most common cause: and vessel wall with formation of new recanalization _capilary channels that restore blood flow MORPHOLOGY : FEATURE REDINFARCT WHITE INFARCT -ANTIPHOSPHOLIPID ANTIBODY SYNDROME(APAS)_ 7, Venous occlusion 1. Solid organs 2. Loose, spongytissues 2. End-arterial TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD and thrombocytopenia (dung) circulation + Antibody-mediated interference with trophoblast growth and 3. Organs with dual blood (heart, spleen, differentation - failute of placentation ae supply (lung&bowel) kidney) « Antiphospholipid antibodies (anti-cardolipin lupus jetting 4, Tissues previously anticoagulant) induce thrombosis congested 5. Reperfusion of site of EMBOLISM peevioasarierals = « Detached intravasculat solid liquid, or gaseous mass that is CATE is taried by the blood fom ts paincof origin toa distant ste, Gras + Wedge-shaped, with occluded vessel at apex ‘where it often causes tissue dysfunction or infarction ang periphery of organ at base _ 4 Most common type: Pulmanary embolism 7 Ischemic, coagulative necrosis (EXCEPT in Microscopie Pain: liquefactive necrosis) MAJOR TYPES PIC, Most are ultimately replaced by scar tissue SYSTEMIC (EXCEPT in septic infarcts: abscess formation) FEATURE Sd ‘THROMBO- EMBOLISM SHOCK Moo = Mural thrombi « State in which diminished cardiac output or reduced effective + Deep venous (60%); mostarise circulating blood volume impairs tissue perfusion and leads to common "thrombosis inthe setting of cellular hypoxia source LVinfarcts «General morphology: Hypoxic injury (Ischemic coagulative = Pulmonary necrosis) vasculature + Changes generally reversible if patient survives EXCEPT in + Pulmonary artery neurons, myocytes bifurcation: saddle + Lower Sitesof embolus (Sudden extremities ‘MAJOR TYPES OF SHOCK. involvement death) (75%) ‘SHOCK SETTING MECHANISM. + Paradoxical embolism: « Brain (10%) = Myocardial 7 {in systemic circulation infarction spumpresulting from ‘through an interatrial/ ‘Ventricularrupture Intrinsic myocardial ventricular defect Cardiogenic archythmia damage, extrinsic inicaly silent ‘ Cardiactamponade compression, or + (60-80%) Act + Pulmonary embolism obstruction to outflow} + Pulmonary a + Fluid loss (eg. Clinical —_—_—hemorvhage (more enone Hypovolemic bemorthage, + Inadequate blood or findings common,duetodual « S2DPO a typovolemic vomiting diarrhea, plasma volume blood supply) organ ischemia burns oF trauma) + Acutecor pulmonale "8 7 Acihation af (260% obstruction) ‘cytokine cascades Shock + Overwhelming _» Peripheral associated microbial infections vasodilation and lwith systemic.» Superantigens pooling of blood inflammation » Trauma + Endothelial (Septic + Burns shock) _« Pancreatitis activation/injury « Leukocyte-induced damage Dic Page 7 of 98 Fr inauiries visit www.topnotchboardprep,com,ph or https:/ww. facebook, com/topnotchmedicalboardprep/i ‘sing TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries visit www, topnotchboardprep,com,ph or httpsi//mww facebook, com/topnotchmedicalboardorepy OTHER CLINICALLY IMPORTANT TYPES rua - = TisORDER ‘so Tatagin sese Systemic vasodilation and increased vascular permeability ¢ Netrftromatens fr ‘ediator: histamine) secondary to an IgE-mediated Nervous ‘* Myotonic dystrophy a ioPerserty chon Tuberous sceran ene ‘ Tuburows serous ‘© Anesthetic accident or spinal cord injury with resultant loss rim Polya Mey disease (ADPKD) of vascular tone and peripheral pooling of blood STAGES Gastrointestinal :milial polyposis col * Hereditary spherocytosis + Von Willebrand disease Hematopoletic STAGE DESCRIPTION * Marfan syndrome” “egNOt,_ © Reflex compensatory mechanismsareacuvated Skelea __* Ebler-Danlos syndrome (some vartants)* rogressive and perfusion of vital organs is maintained + Osteogenesis imperfecta * Tissue hypoperfusion and onset of worsening = Achondroplasia Progressive circulatory and metabolic imbalances, Metaboue * Familial hypercholesterolemia {including lactic acidosis + Acute intermittent porphyria * Cellular and tissue injury so severe thateven Irreversible ifthe hemodynamic defects are corrected, MARFAN SYNDROME [__survivalisnotpossibie | « Fibrillinel gene defect © Loss of support in microfibei-rich connective tissue ‘TYPES OF SHOCK: PHYSIOLOGIC PARAMETERS + Manifestations: skeleton, eye, heart TYPEOF PCWP ‘Skeleton: tal stature, arachnodactyly, doichocephaly, SHOCK {PRELOAD) a svR hyperextensible joints, kyphoscoliosis, chest wall anomalies * n 0 Ocular: bilateral ectopia lentis (outward, upward) Cardiogentc _(impalred ¥ 7 displacement of lens Sutfow of (pump fallure) (Compensatory Heart: Mitral valve prolapse, Aortic insufficiency, aortic blood) mechanism) aneurysms and dissection ¥. * Hypovolemic (ow intra- v coe EHLER-DANLOS SYNDROME vce Glows) Gompensaieny + Hageopneus rosy of sores emon dete n Abia Distributive at * v «Ether defects in structural proteins or enzymes for post: Septic, Gerber! (compensatory __(lossof. translation modification of collagen ‘eurogenic) blood) mechanism) vascular tone) '* Clinical manifestations : © Skin, joints and ligaments: hyperextensible skin, MORPHOLOGY hypermobile joints ‘oncan MORPHOLOGIC “unicat 6 Visceral involvement: rupture of colon and large arteries ‘CHANGE PRESENTATION (vascular EDS), diaphragmatic hernia (classic EDS) © Aldosterone and 0 Ocular: corneal rupture and retinal detachment (ocular EDS) cortisol effects © Poor wound healing Adrenals» Cortical ipl depletion (Neurohormonal compensatory [AUTOSOMAL RECESSIVE DISORDERS mechanisms) wo recessive alleles produce phenotype Kidneys —~ Acute tubular necrosia > Acute kidney injury + Usually parents are phenotypically normal, but there are * Rese roe siblings affected in injury in hypovolemic —, ,aps © Ina cross of two heterozygous parents: "shocks ifseptic shock: = 25% chance of having the trait diffuse alvelar damage ‘© More uniform expression: ‘© Complete penetrance and early onset Leal O Lee © Usually, enzyme defects ‘Mendelian disorders 6 Autosomal dominant SvSTEM DISORDER © Autosomal recessive 2 Cyc Rbrosis X-linked disorders + Phenylketonuria + Chromosomal disorders * Galacosemia © Autosomal + Homocystinarta © Sex chromosomes Metabolic © Lysosomal storage diseasest + Trinucleotide repeat disorders + c-L-antirypsin deficiency '* Mitochondrial disorders + Wilson disease ‘¢ Disorders of genomic imprinting ‘ ‘s Memechromalosis + Giycogen storage diseases MENDELIAN DISORDERS: Hematopoietic 7 Hei Cellanemla «Single gene defects that have large effects a et as * Basic patterns of transmission: dominant, recessive, and X-linked Seieciee > une ace et ‘* Co-dominance: both alleles contribute to phenotype Skeletal allaptonuria © Examples: histocompatibility and blood group antigens ‘> Neurogenic muscular trophies Nervous Friedrich ataxia Spinal muscular atrophy ‘One parents usually affected ‘ln some cases, no parent is affected; due to newly acquired. ‘mutations + Variable expression © Penetrance: proportion of those who inherit the gene and express its phenotype o Expressivity: variability in phenotypic expression among those who inherit the gene * Usually, Key structural proteins/receptor defects ‘TTOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD Far inontiries visit wow tannatehhaardnran ram mh nr httne:/hanins farahanl ram iinnnatchm adinatnsedne ‘SPHINGOLIPIDOSES ‘Tay-Sachs disease © Defect: a-subunit of hexosaminidase A > accumulation of Guz {ganglioside (most prominent: in neurons and retina) © Neurons: ballooned with cytoplasmic vacuoles with ganglioside (+) for fat stains (oil red 0, Sudan Black B) = EM: cytoplasmic inclusions, whorled (onion-skin) configuration ‘© Retina: ganglion cells distended by ganglioside vacuoles: (+) cherry-red spotin retina Page 8 of 98ar a ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MB For inquiries visit www,topnotchboardprep.com.ph or https://www. facebook com/topnotchmedicalboardorep/ SULFATIDOSES + Niemann-Pick disease (Types A and B) © Defect: sphingomyelinase deficiency -> accumulation of sphingomyelin © Clinically, hey cherry-red spot in macula * EM: membranous cytoplasmic inclusions of lamellated ‘myelin figures (zebra bodies) + Gaucher disease ‘© Most common lysosomal storage disorder © Defect: glucocerebrosidase deficiency (B-glucosidase) © Gaucher cells * Distended phagocytic cells in spleen, liver, BM, LNs, tonsils, thymus, and Peyer patches * Fibrillary cytoplasm (“crumpled tissue paper" appearance) X-LINKED RECESSIVE DISORDERS + Usually males express phenotype (duo heminygosy fore ‘Females may express the phenotype (because of random activation of one X chromosome) * Affected males do not transmit the disease to their sons (hecause they get their from their dads}; butal of thelr daughters are carriers (because they get one X from their dads) +# Ina cross of heterozygous female and an affected male © 50% of sons and 50% of daughters (+) ‘SYSTEM. DISORDER Musculoskeletal + Duchenne Muscular Dystrophy ‘* Hemophilia Aand B Blood * Chronic granulomatous disease 0 + G6PD deficiency ‘ Agammaglobulinemia + Wiskott-Aldrich syndrome * Diabetes insipidus + Lesch-Nyhan syndrome Nervous « Ffagile X syndrome X-LINKED DOMINANT DISORDERS Ina cross of heterozygbus female witha normal male 0 50% of sons and 50% of daughters (+) ‘* Ina cross of affected male with a normal female ‘All daughters (+), all ons (-) + Examples: Alport syndrome and Vitamin D-resistant rickets ‘CHROMOSOMAL DISORDERS ‘» Normal karyotype: 2% pairs of autosomes and 1 pair of sex chromosomes (46XX or 46XY) (Euploid) ‘+ Abnormalities in number (Aneuploidy) or structure « Can involve autosomes or sex chromosomes Immune Metabolic ANEUPLOIDY > Errors in gametogenesis, oNondisjunction * Failure of homologous chromosomes or sister chromatids to separate during cell division * One gamete has an extra chromosome; the other gamete lacks chromosome Anaphase lag * One homologous chromosome (meiosis) or one chromatid is left out of the cell nucleus * One gamete is normal; one gamete lacks a chromosome « Errors post-fertilization 0 Mosaicism * Two or more populations of cells with diferent chromosomal complement in one individual = Examples: Autosomal mosaicism in Trisomy 21 046 X(K/¥), 47 X(X/¥), #21 + Sex chromosome mosaicism in Turner syndrome ASX, 47K TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries visit www, topnotchboardprep,com.ph or h DISORDERS OF AUTOSOMES TRISOMY 21 * Most common of the chromosomal disorders; leading cause of MR ‘+ Advanced maternal age: strong influence of accurrence # Causes: Nondisjunction (95%) © Robertsonian translocation (496) o Mosaicism (19) ‘Advance maternal age: strong influence of occurrence « Diagnostic clinical features: at facial profile oblique palpebral fissures, and epicanthic folds + Notable associations: Cardiac: Endocardial cushion defect, ostium primum defect, ASDs, AV valve malformations, VSDs © GIT: Hirschsprung disease, duodenal atresia ‘Acute leukemia: ALL or AML (Myeloid; acute mmegakaryoblastic leukemia, most common) © Neuronopathologic changes: Alzheimer disease ‘© Abnormal immune responses: serious infections ‘TRISOMY 18 AND 13, «= Trisomy 18 (Edward syndrome) and Trisomy 13 (Patau syndrome) ‘* More severe than Trisomy 21; most die within first year of life ‘© Most common cause: nondisjunction of chromosome during. meiosis + Common features: MR, cardiac and renal defects, rocker-bottom feet « Cleft lip and palate, and umbilical hernias: distinguish Patau syndrome CHROMOSOME 2211.2 DELETION SYNDROME + DiGeorge syndrome: CATCH22 (Cardiac anomalies, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia) + High-risk for schizophrenia and bipolar disorders DISORDERS OF SEX CHROMOSOMES, ‘* More common and better tolerated than autosomal chromosomal disorders ‘© Subtle, chronic problems regarding sexual development and Tertity, « Difficult to diagnose at birth: Usually detected at puberty ‘The more number of X chramasomes, the higher the likelihood of MR Page 9 of 98 com/topnotchmedicalboari KLINEFELTER SYNDROME * ® 2X chromosomes and 2 1 Y chromosomes © Most common: 47XXY (90%) * One of the most common genetic diseases involving sex chromosomes and male hypogonadism ‘© Important cause of reduced spermatogenesis and male Infertiity * Clinical characteristics © Eunuchoid body habitus © Testicular atrophy, micropenis, absence of secondary sex characteristics © Type 2 DM, metabolic syndrome ‘Mitral valve prolapse (50%) © Gynecomastia ‘© Low IQ, but MR is uncommon ‘TURNER SYNDROME * Complete or partial monosomy of X chromosome; female hypogonadism in phenotypic females ‘+ Most common abnormality: lack of entire X chromosome (45X0) (57%) ‘Single most important cause of primary amenorrhea ‘© Clinical characteristics © Ovarian streaks: * Accelerated loss of oocytes due to loss of other X chromosome © Absence of secondary sex characteristics o Short stature ‘Cystic hygromas of neck > regress -> webbed neck © Cardiovascular: preductal CoA, bicuspid aortic valve ‘+ Most important cause of increased mortality in children ‘with Turner syndrome HERMAPHRODISM AND PSEUDOHERMAPHRODISM ‘© True hermaphrodism ‘Presence of both avarian and testicular tissue ‘« Pseudohermaphroditm ‘© Disagreement between phenotypic and gonadal sex * Genotypically mdle with female phenotype (Androgen insensitivity syndrome) * Genotypically fentale with male phenotype (Androgenital syndromes) ‘TRINUCLEOTIDE REPEAT DISORDERS + Timpartant genetic caiise of human disease, especially neurodegenerative disorders ‘* Proclivity to expand depends on sex of transmitting parent (Female: Fragile X; Male: Huntington disease) « Mutations may cause loss-of-function (Fragile X) or gain-of| function (Huntington) «+ Anticipation: disease worsens with each successive generation FRAGILE X SYNDROME ‘Second most common cause of MR after Trisomy 21 ‘© OGG expansion in FMR1 gene in X chromosome + Clinically, ong face, large mandible, large everted ears, and macro-orchidism © Macro-orchidism: most distinctive feature (90%) HUNTINGTON DISEASE + Autosomal dominant; CAG expansion on HTT gene on Ch « Clinically, progressive movement disorders and dementia due to degeneration of striatal neurons oRelentlessly progressive; uniformly fatal MITOCHONDRIAL DISORDERS « Distinctive feature: maternal inheritance Usually, defects in electron transport chain stroke (MELAS) o Leber hereditary optic neuropathy (LHON) DISORDERS OF GENOMIC IMPRINTING «= Imprinting: silencing of one copy of gene from either parent synthesis of immunoglobulins ‘against the pathogen of interest (active immunity) ‘ Administration of immunoglobulin > immediate neutralization ‘of the antigen/pathogen of interest (passive immunity) DISEASES OF THE IMMUNE SYSTEM. «Excessive, unregulated activity ‘© Hypersensitivity: injurious immune reactions; basis for autoimmune diseases © Clinically, end-organ damage due to immune-mediated injury ‘© Decreased or absent activity ‘Immunodeficiency syndromes © Clinically, susceptibility to infections, especially opportunistic Page 10 of 98 Fae innniriae vieit wurw tanantchhnardnren enm nhar httne:/fowu! farahaal: ram/tannntchmadicalhnardnran!Sheng TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries visit www, topnotchboardprep.com,oh or https://www.facebook,com/topnotchmedicalboardorep/ HYPERSENSITIVITY REACTIONS (MMEDIATE (TYPE 1) HYPERSENSITIVITY { Commonly known as allergies (exogenous trigger3) * Key traits: Rapid occurs in previously sensitized individuals; IgE-mediated * Two phases (with different effects and mediators) © Immediate phase: vascular changes © Late phase: leukocytic infiltration and tissue damage + Eosinophils: main cells * IS: most potent eosinophil activating cytokine kno from Tx2 cells * * First exposure toallergen © Tu2 cell activation and production of IgE that binds to basophils and mast cells * Subsequent exposure to allergen ‘© Antigen binds to IgE on basophils and mast cells > mast cell degranulation: mediators * Vasoactive amines (Histamine), Arachidonic acid metabolites > Immediate response = Cytokines and chemokines > Late response * Morphology © Vascular dilation, edema, smooth muscle contraction, mucus production, tissue injury, inflammation + Examples © Anaphylaxis © Bronchial asthma © Allergic rhinitis, sinusitis (hay fever) © Food allergies ANTIBODY-MEDIATED (TYPE Il) HYPERSENSITIVITY. EFFECT MECHANISM CONDITIONS © Antbodies activate Transfusion complement;¢3b "reactions so (opsoniny + Heroic iease Opsonization Phagocytods ofnewbera * Ditect lysis: antibody- * AIHA, hagocytosis one mediated cytotoxicity agranulocytosis, and (trough NKcelsand thrombocytopenia dcrophages) + Drugreactions o Reactive arthritis © Serum sickness © Arthus reaction ‘T-CELL-MEDIATED (TYPE IV) HYPERSENSITIVITY * CD4"-mediated: cytokines induce inflammation © Antigen exposure: CD4* differentiation to Tw1 and Ty17 cells © On subsequent exposure: ‘Tul: secretes IFN-y: activates macrophages to secrete cytokines: inflammation += Ty17: produces IL-17 and other cytokines: leukocyte recruitment: inflammation * CDB> (cytotoxic T-cell)-mediated: direct killing by perforins and granzymes in lysosome-like granules © Perforins: helps release granzymes © Granzymes: cleave and activate caspases (apoptosis) © Cytotoxic cells: express Fas ligand (apoptosis) ‘Also secrete IFN-y * Morphology Perivascular cellular infiltrates Edema © Granuloma formation Cell destruction ‘+ Examples Rheumatoid arthritis o Multiple sclerosis © Type I Diabetes Mellitus © Inflammatory bowel disease ‘0 Psoriasis ‘Contact sensitivity, AUTOIMMUNE DISEASES + Chronic, sometimes with relapses; damage often progressive « Clinical and pathologic manifestations determined by nature of the underlying immune response * More common in women ‘= Usually associated with other autoimmune diseases. ‘SYSTEMIC LUPUS ERYTHEMATOSUS. Antibodies activate cothplement:C3a + Glomerutonephrts Intammation Sn C5a vascular rejection in (anaphylatoxins): ——organgrafts inflammation * Anlibodies bind to i FeGeptorsandaer — siyasthenia gravis nea cellular function; no Seema lysfunction inflammation or cell injury + Morphology o Inflammation + Examples © Autoimmune hemolytic anemia © Immune thrombocytopenic purpura © Pemphigus vulgaris © ANCA-vasculitis ‘© Goodpasture syndrome ‘Acute rheumatic fever © Myasthenia gravis, o Graves disease 6 Insulin-resistant diabetes © Pernicious anemia IMMUNE COMPLEX-MEDIATED (TYPE Ill) HYPERSENSTIVITY = Immune complex deposition in tissues (common: kidneys, joints and small blood vessels) + Subsequent inflaminatory response (by complement activation) and tissue destruction + Diseases tend to be systemic (EXCEPT Arthus reaction: local) + Morphology © Inflammation, Necrotizing vasculitis (ibrinoid necrosis) + Examples oSLE ‘oPSAGN © Polyarteritisnodosa TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries visit www.topnotchboardorep,com,ph or https://www.facebook.com/topnotchmedicalboardoren/ * Autoimmune disease affecting multiple organ systems © Failure of the mechanisms that maintain selfolerance + Immune complex mediated and antibody-mediated © Most of the systemic lesions are caused by immune complexes (Type It} ‘oematologic manifestations are usually antibody-medlated (type, opsonization and phagocytosis) + Hallmaric: production of autoantibodies ‘© Most common: ANA (989) best screening test; but does NOT correlate with disease activity © Specific for SLE: anti-Sm (Smith) and anti-dsDWA; ant- cell death > phagocytosis of free ‘nuclear material ‘* DROPPED from the 1997 ACR SLE criteria Ruiz-Arguelles A, et al. Novel facts about an old marker: LE cel. Scan} Clin Lab invest ‘TART CELL. ‘+ Morphologically similar to LE cell Found in patients with lymphoblastoma/metastatic carcinoma © Chromatin preserved (vs.fine, homogeneousin LE cell) Hepburn AL. The LE cell. Rheumatology, 40(7). 2001: 826-827 Page 11 of 98Doves TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries visit wwrw,topnotchbeardorep.com,ph or https:/Awww, facebook, com/topnotchmedicalboardorep/ CLINICAL MANIFESTATIONS OF SLE 1. Male Fae be ft redo ral erace, ta ape eats 2 Ort 3 Pesematy 4 al veo 5 hme Socata 2. Rv rae {Nec iene ees tg 2 tin ee ep he ci Prenat St own agen, ta oe ‘9 reraoge derar ~ “Won nais—wh icon of ulapnie—<40 1% a (0 aa) talon to or scasng, ‘ane 1 it er en ‘Trentnopaie—<10 > 10 cl (00 10 cela ne sen of tng ge 10. tna Orr AON ogy rate OA in bor er, Sogn fwd Se wg, Fete tng of anhoegotp ates tee (1) a aberal sane oto atcarslp atoses, (2) pon wt wp antogut ang wand te or) se otve sw tt esis en © be {a at ar ete oan Tarren ncn are opr ony 1, Aetrce:antoty 7 srama i richard by iets el am a any fl ie an ibe bene ot ‘gr mon be omocted pnd a oe _ ‘0 Extensive lymphocytic infiltration > germinal centers ‘ORGAN ‘MORPHOLOGY ‘© May be at risk of B-cell lymphoma Blood + Acute necrotizing vasculitis (fibrinoid necrosis) vessels __> fibrosis with luminal narrowing (chronic) Kidney» La hritis (6 classes) ‘+ Epidermis: Vacuolar degeneration of basal layer Skin» Dermis: Variable edema and perivascular {inflammation Joints + Non-erosive synovitis with lite deformity + Acute serosts:fbrinous exudate on serosal surface + Chronic: thickening of serosal surface > obliteration of serosal cavity + brfusiais Body cavities Cardio- + Libmati-Sacks endocarditis: 1-3 mm warty vascular deposits on any heart valve, on either surface of the leaflets CLASSES OF LUPUS abuts CLASS Tg Minimal 3 mesangial + Norsial + Nestn mesanguen (lass) + Mesangial cel 7 Granular mesangial Mesangial” proliferation; ofen and complement w/o PRETTY’ With mesangial matrix involvemeatot secumulation glomerular calles 7 PMNs, necrosis crescent roca and hyaline trombt + Wizelnap annsarance of (assim * Wisloan * subendothelia ic + <50% of glomerull deposits Diffuse» Type lll with 25096 of (Class 1V)__glomerull Late: acinar atrophy, fibrosis, hyalinization © Secondary changes due to lack of secretions: inflammation, erosion, ulceration __SYSTEMIC SCLEROSIS (SCLERODERMA) __ Triad 1. chronic infiammation (autoimmunity; 2, widespread damage to small blood vessels; 3. progressive interstitial and perivascular fbrosis in the skin and multiple organs ‘© T-cell-mediated and activation of humoral immunity (and production of antibodies) + Diffuse cutaneous systemic sclerosis (deSS¢} widespread skin {nvolvementat onset with early visceral involvement + Limited cutaneous systemic sclerosis (IeSSc) limited skin Involvement with late visceral Involvernent OCREST syndrome * Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyy,Telanglectasia + Mostare directed against RNA polymerases and topoisomerases + Sets ofautoantibodies associated with different clinical presentations © Diffuse scleroderma: anti-DNA topoisomerase | (ant-Scl 70) (most common, 30-70%; highly specifi) o Limited scleroderma: anti-centromere SYSTEMIC SCLEROSIS: MORPHOLOGY ‘ORGAN MORPHOLOGY * Diffuse, sclerotic atrophy of skin « Increased collagen, thinning of the epidermis, loss Skin of rete pegs, atrophy of the dermal appendages, «and hyaline thickening of the walls of dermal vessels ‘Membranous + Diffuse capllary _» Subepithelial To (ClassV)__ thickening deposits ‘Advance sterasing Seto of 90% {Caseviy__Somerul SJOGREN SYNDROME + Triad: Dry eyes (keratoconjunctivitissioca), dry mouth (xerostomia), autoimmune-mediated destruction of lacrimal and salivary glands «T-cells (CD4+) (Type 1V) and B-cells + Diagnosis: lip biopsy (minor salivary glands) ‘* Notable autoantibodies anti-Ro (S5-A) and anti-La (SS-B) (90%) ‘© Most important and most common autoantibodies detected (o High-titers of anti-Ro: more likely to have early disease onset, longer duration and extraglandular manifestations + Morphology co Earliest: periductal and perivascular lymphocytic infiltration in glands ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, AD WW, For inquiries visit wow topnotchboardorep,com.ph or ‘* Progressive atrophy and collagenous fibrous replacement of the muscularis GIT» Esophagus: Rubber-hose-like inflexibility > GERD ‘+ Small bowel: Villiand microvilli loss > malabsorption * Intimal thickening (deposition of collagenous ‘material} of interlobular arteries and concentric Renal intimal proliferation «Scleroderma renal crisis: Arteriolar fbrinoid necrosis with thrombosis and infarction * Interstitial fibrosis and secondary pulmonary ‘hypertension + Pericarditis with effusion, myocardial fibrosis, and thickening of intramyocardial arterioles Lung Heart Page 12 of 98. hmedicalboardorJoe. TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries visit www, topnotchboardorep.com. ph or https: /ww. facebook, com/topnotchmedicalboardorep/ TRANSPLANTATION IMMUNOLOGY = MHC Class I: CD4 T-cells > Tul and Ty17 effector cells Rejection: Cell-mediated or antibody-mediated graft co Indirect pathway: donor Ags presented by recipient APCS to destruction recipient T-cells * Differences in HLA alleles: major: in seers ee eles: major antigenic difference leading to ee + Allorecognition pathways * Acute cellular rejection, Chronic rejection ‘© Direct pathway: donor APCs present Ags to recipient T-cells ce Anitbody mediated ‘* MHC Classi: CD8 T-cells active CyrotonieT cells * Hyperacute rejection, Acute humoral rejection PATTERNS OF KIDNEY REJECTION REJECTION ONSET CLINICAL FINDINGS MICROSCOPIC FINDINGS Hyperacute ~ Cyanotic, mottled, and |» Thrombotic occlusion ofthe capillaries (pre-formed anti- | Minutes orhours |, "#ecidkidney « Fibrinold necrosis in arterial walls donor antibodies) ‘+ May excrete few drops of bloody urine 1 Tubulointerstital (Type Ij: Tubulontersttil ymphooytic {nfitrate (tubulitis) Acutecellular | ¢ Days, months or 2. Vascular (Type I): swollen endothelial cells with focal years after Iymphocytic infiltration (endothelitis), with vascular wall cessation of * Clinical and biochemical | necrosis (Type til) Tews antiboly-] imenune signs of renal failure mediated suppression + Inflammation of glomeruli and peritubular capillaries; (igs produced after focal thrombosis of smal vessels {transplantation} * Vascular lesions: 4. Intimal thickening with inflammation ; « Monthsater «ise inserum creatinine |? Slomerulopathy, wih duplication ofthe basement Chronic overa period of 4to 6 nephrane ‘transplantation | vera 3.Peritubular capillartis with multllayering of peritubular capillary BM aienchyma HEMATOPOIETIC STEM CELL TRANSPLANTATION DEFECTS IN LYMPHOCYTE ACTIVATION AND FUNCTION * Indications: hematologic malignancies, bone marrow failure + Immature B-cells must differentiate into mature B-cells that syndromes, inherited HSC defects have different membrane Igs (leM, IgA 1gG,and IgE) ‘+ Abolishment of immurie system prior to transplantation (by + Blocks in maturation pathways > hypogammaglobulinemia chemo- or radiotherapy) necessary (cither isolated or multiple) ‘+ Complications: Graft vs. host disease (GVHD) and ‘Clinically, suscpetibility to pyogenic organisms (because they're immunodeficiency Killed primarily by opsonization) GRAFT VS, HOST DISEASE FEATURE, ISOLATED IGA DEFICIENCY + Setup; immunologically competent cells + Inheritance * Familial, or acquired: Toxoplasmosis, ‘mmunocompromised recepients Measles, o some other viral infection ‘+ Morphology: Epithelial injury (acute); Abrosis with end-organ Feaureg® Decreased serum and secretory igh > failure (chronic) impaired mucosal defense + Usual organs affected: skin, GIT, HBT, Immune system (in Clinical» Recurrent respiratory, GIT and GUT chronic GVHD) findings infections + Acute or chronic © Acute: cell-mediated Treatment reactions ‘asan antigen to those who © Chronic: cell-mediated with antibody mediated (possible) sacra tases a ec IMMUNODEFICIENCY SYNDROMES WISKOTT-ALDRICH SYNDROME © Primary or secondary « Xlinked: triad: + Defects in either innate or adaptive immunity 1. Thrombocytopenia; © Clinteally: susceptbility to infections; depending on the arm of 2. Infections (Immunodeficiency); the immune system affected 3. Eczema + T-cells in thymus are normal but depleted in other areas (CMI) DEFECTS IN INNATE IMMUNITY: LEUKOCYTE FUNCTION ‘+ VigM, normal IgG, ‘eA and IgE (paradoxical) (humoral ‘+ Inherited defects in leukocyte adhesion immune abnormalities) © Leukocyte adhesion deficiency ‘+ Treatment: HSC transplantation + Impaired phagolysosome function © Chediak-Higashi syndrome ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) + Inherited defects in microbidal activity ‘+ Most common secondary immunodeficiency Chronic granulomatous disease + Hallmark: profound immune deficiency # Atrisk groups: DEFECTS IN ADAPTIVE IMMUNITY (see Table in p. 15) © Homosexual, bisexual men (largest) (most common mode of + Disorders referable to blocks in lymphocyte maturation, transmission in males) ‘activation and lymphocyte lV drug users ‘© Beeline blocks: depressed humoral immunity ‘oHemophiliacs {+ T-eellline blocks: depressed cel mediated immunity ‘Recipients of blood components «Earlier locks: depressed activity of both arms of immunity ‘o Heterosexual contacts (most common mode of transmission + Blocks in immunoglobulin class switching: deficiency of some infemales) Jaeunoglobulins OHV infection of the newborn ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD Page 13 of 98 For inquiries visit 1tchboardprep,com,ph or https: //www. facebook. hmedicalboardora1 Nyy TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD “For inquiries visit www, topnotchboardprep.com,ph or https://www, facebook. com/topnotchmedicalboardprep/ DEFECTS IN ADAPTIVE IMMUNITY FEATURE 3a. BRUTON AGAMMAGLOBULINEMIA DIGEORGE SYNDROME Inheritance X-linked (more common), AR + X-linked: mutation in the common y Defect _ chain (yc) subunit of cytokine receptors: * AR: Adenosine deaminase (ADA) deficiency = X-linked recessive + Bik gene = Not familial in most cases + Failure of development of third ‘and fourth pharyngeal pouches due to deletion of Ch22 or TBX1 ‘+ Xolinked: disturbance of early T- lymphocyte development due to loss of * Btk ig needed for signal transduction for B-cell + Absence of thymus > decreased production is W due to loss of T-cell help (secondary humoral immunodeficiency) Mechanism function of cytokine receptors development; defect arrests T-cell > Impaired cell mediated ‘AR: impaired DNA synthesis due to al epmene chain accumulation of deoxyadenosine > toxic eugehment absent gh cha ame to rapidly dividing lymphocytes (T-cells) + ¥ cell-mediated and humoral immunity; + V numbers of T-lymphocytes in *« Abseit germinal centers in lymph x Features T-2ells more W than B-cells butantibody * Doves Peyer patches tonsils and peripheral blood and lymphoid appendix; absent plasma cells organs | NtoV levels of igs ‘+ Prominent thrush (oral candidiasis), Clinical extensive diaper rash, and failure to thrive; morbifillorm rash due to GVHD + Symptomatic atabout 5-6 months of age due to maternal antibody depletion + Most common: bacterial infections + Increased susceptibility to FUNGAL and VIRAL infections + Cardiac anomalies, abnormal findings of the respiratory tract (H. facies, thymic hypoplasia cleft (loxmunocompotent maternal T-cells vs. Tnnvenze, pneumoniae, S aureus; p/paat, hypocalcemia utlunocompromsed baby) viral infections (most common: (catcH22) enteroviruses); Glardia lamblia ® HSC transplantation (both cases) gene 1 . ‘+ Immunoglot cement reaunent_” agente Cn Immunoglobulin replacement av Kapas sarcoma + Nonsransforming tetrovius (family Retroviridae), Genus Rayos sarcoma herpesvirus (KSHY) or human herpesvirus Lentivirus 8(HHV-8) IV (more commén) and HWV-2 + NS disease + Two major targets of HIV: Immune system and CNS + Sexual (most comrion), parenteral, and vertical (mother to Infant) co Sexual: can be enhanced by coexisting STDs ‘Parenteral: 1V drug users (largest), hemophiliacs (because of transfusion), and random recipients Vertical: 1. in uterb; 2. intrapartum; 3. postpartum via breast rik; Intrapartum and peripartum are more common ‘Sexual: initially infects dendritic cells > dendritic cells transported to lymph nodes and spleen -> both organs act as reservolr of infection « Parenteral: direct indcutation of virus into the blood HIV life cycle: important events # gp120: Attaches to CD4 ~ conformation change > new recognition site for CXCR4 and CRS -> gp120 binds to CKCR4 and CCRS + gp41: Fusion protein > integrates itselfinto hostcell ‘membrane > facilitates fusion and delivery of viral genome ‘+ HIV ineffectively infects unactivated T-cells; T-cell activation of latently infected cells completes life cycle (cell lysis) HIV-induced changes in the immune system and CNS + CD4T-cell depletion: many mechanisms; most common: Infection and direct cytopathic effect + Polyclonal B-cell activation > germinal B-cell hyperplasia, bone ‘marrow plasmacytosis, hypergammaglobulinemia and immune complex deposition ‘oUsually due to infection with viruses that induce B-cell proliferation eg. EBV « CNS infection of macrophages and microgtia (0 Usually rom infected monocytes AIDS-defining ilInesses + Infections © Canuidiasis: most common fungal infection = Other fungal infections: Pneumocystis iroveci and Cryptococcus neoformans 0 Taxoplasma gondit responsible for >50% ofall mass lesions, ines ‘0 CMY chorloretintis: occurs in CD4 count < 50/L '» Neoplasms ‘olymphomas ‘© Most common type: B-cell iymphoma + Becell hyperplasia occurs in HIV infection + EBV or KSHV-associated (HHV-8), or not ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD Far innnirias visit www fonnntchhnardaran eam nh or httns://www.facebook.com/tonnotchmedicalboardoreo/ ‘0 Common and important manifestation of AIDS ‘6 Most common: progressive encephalopathy (HIV-associated neurocognitive disorder HIV: LYMPH NODE MORPHOLOGY. EARLY LATE + Breellfollcle hyperplasia» Burned-out lymph nodes (Colices enlarged with ‘Hyalinized germinal serpiginous reas) centers «= Attenuation of mantle * Depleted lymphocytes zones Disrupted dendritic cell ‘ Impingement of network interfollicular T-cell zones» Spleen and thymus depleted of lymphocytes AMYLOIDOSIS ‘+ “Starch-like” misfolded proteins that accumulate extracellularly + Can cause disease by pressure atrophy on adjacent cells * Mechanisms Excessive production of protein prone to misfolding and aggregation ‘Genetic defects Impaired removal Morphology ‘ Grossly, enlarged organ with gray, waxy, firm consistency ‘* Amyloid deposition is ALWAYS extracellular and begins between cells ‘* Congo red: pink to red under ordinary light; apple green ‘© Due to B-sheet confirmation of amyloid «Kidney: most common and mast serious form of organ involvement «Spleen: amyloid in lymphoid follicles: tapioca-like granules (sago spleen); coalescence of deposits: map-like areas (lardaceous spleen) «Liver: deposition usually starts at space of Disse with extensfon to parenchyma and sinusoids Page 14 of 98.Generalities + Nomenclature + Characteristics of benign and malignant tumors *+ Cancer epidemiology + Cancer hallmarks * Carcinogenic agents * Clinical aspects of neoplasia TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries vistt wasw.tapnotchboardprep,com.ph or https://www. facebook, chmedicalboaré METASTASES ‘ Spread of a tumor to sites that are physically discontinuous with the primary tumor + Uneguivacal marker of malignancy * Routes: © Direct seeding of body cavities and surfaces ‘Lymphatic: primary route for CARCINOMAS © Hematogenous: primary route for SARCOMAS ‘0 Some carcinomas (liver, lung, kidney) usually disseminate via inflammatory cells * Desmoplasia: formation of abundant collagenous stroma + Benign or malignant ‘TUMOR-LIKE CONDITIONS CHORISTOMA FEATURE — HAMARTOMA HECTOPIA) ‘Appearance of « Benign but + Cytologically and tissue disorganized architecturally normal Location of tissue + Indigenous» Ectopic Examples Peutz-Jegher _ Ectopic gastric issue hi polyp Meckel diverticulum NOMENCLATURE + oma; usually connotes a benign tumor, EXCEPT: seminoma, lymphoma, melanoma, hepatoma * Carcinoma: malignant neoplasm of EPITHELIAL origin + Sarcoma: malignant neoplasm of MESENCHYMAL origin + Leukemia/Lymphoma: malignancies of HEMATOLYMPHOID origin « ized tumors: umd ofmorethan online of iferentation ‘0 Pleomorphicadenoa, Teratoma ‘CHARACTERISTICS OF BENIGN AND MALIGNANT TUMORS DIFFERENTIATION AND ANAPLASIA DIFFERENTIATION ‘ANAPLASTA ‘* Extent to which neoplastic + Lack of differentiation parenchymal cells + Considered a hallmark of resemblethe ‘malignancy corresponding nora parenchymal cells, Both morphologically and functionally ‘MORPHOLOGIC FEATURES ASSOCIATED WITH ANAPLASIA FEATURE, ‘DEFINITION Pleomorphism __« Variation in size of cells and nuclel ‘bnormal nuclear + Nuclear pleomorphism morphology» 'nuclear:cytoplasmic (NC) ratio + Hyperchromasia (more darkly stained nucleus) ‘© Coarse chromatin pattern ¢ Prominent nucleoli Mitoses ¢ Amitotie figures Toss of polarity « Disoriented arrangement of tumor cells Other features Necrosis, due to tumor outgrowing its blood supply. DYSPLASIA * Disordered growth; encountered principally in epithelia + Basically, cytologic and architectural atypia ‘ Carcinoma-in-situ: Ful-thickness dysplasia without invasion of the basement membrane «= Invasive carcinoma: invasion of the basement membrane LOCAL INVASION > Progressive infiltration, invasion, and destruction of the surrounding tissue benign tumors ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD .com,ph or https: //wrvnw. For inquiries visit www.topnotchboar: pp hematogenous route GENERALITIES = 1 Rela aFowa new growth aed eo5m CANCER EPIDEMIOLOGY amor basic component + Tneidencer ‘oParenchyma: composed of neoplastic cells 1m) > CNS tumors » Bur © Males: Prostate (most common) > Lung > Colorectal 0 Females: Breast (most common) > Lung > Colorectal + Mortality: . (© Males: Lung (most common) > Prostate > Colorectal © Females: Lung (most common) > Breast > Colorectal (“cancer watimarks » Self:sufficiency in growth signals 1 Altered cellular metabolism ¢ Bvaslon of apoptdi + Limits epieave potential (immortal) ® Sustaled anglogeness 2 Abit invade and metastasize 2 Abli9yt evade the host immune response SELF-SUFFICIENCY IN GROWTH SIGNALS * Proto-oncagenes: normal cellular genes whose products promote cell proliferation ‘+ Oncogenes: mutated or overexpressed versions of proto- ‘oncogenes that function autonomously, having lost dependence on normal growth promoting signals + RAS: most common type of abnormality involving proto- ‘oncogenes in human tumors COMMONLY MUTATED PROTO-ONCOGENES AND ASSOCIATED CANCERS PROTO- ae REPRESENTATIVE EXAMPLES EGFR Lung, HERZ + Breast * Polycythemia vera, jake + Essential thrombocytosis, + Primary myelofibrosis ABL + Chronic myelogenous leukemia RAS = Many cancers BRAF + Hairy cell leukemia ae * Burkitt lymphoma (¢M¥C), ‘+ Neuroblastoma (NMC) COKE Glioblastoma INSENSITIVITY TO GROWTH-INHIBITORY SIGNALS + Tumor-suppressor genes © Apply brakes to cell proliferation, and abnormalities in these genes ead to failure of grout inhibition, another fundamental hallmark of earcinogenesis + Two important tumor suppressor genes ‘Rb: "Governor ofthe cel cycle" © p83: "Guardian ofthe genome” Rb: “Governor of the cell cycle” ‘« Hypophosphorylated Rb binds to E2F -> cells cannot pass G1-S cell cycle checkpoint + Growth signals > hyperphosphorylated Rb > transcription occurs Rb in cancers : + Loss-of function mutations affecting RB + Gene amplifications of CDK4 and cyclin D genes + Loss of cyclin-dependent kinase inhibitors (p16/INK4a) + Viral oncoprotein that bind and inhibit RB (E7 protein of HPV) Page 15 of 98 jotchmedicalboardorep/i aye TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOKINA, MD For inquiries visit www.topnotchboardprep.com,ph or i fi PS8: “Guardian ofthe genome” * Central monitor of stress inthe cll, activated by anoxia, inappropriate signaling by mutated oncoproteins, or DNA damage * p53 synthesizes p21, cyclin dependent kinase inhibitor; Causes arrest at G1-S checkpoint to repair DNA ‘+ IFDNA is too damaged to be repaired, cell undergoes apoptosis PS3 in cancers ** Majority of human cancers have loss-of-function mutations in p53 © Li-Fraumeni syndrome: increased susceptibility to many cancers « Inactivation of p53 by £6, a viral oncoprotein of HPV COMMONLY MUTATED TSGS AND ASSOCIATED CANCERS TSG REPRESENTATIVE EXAMPLES Rb + Retinoblastoma p53» Many cancers, i-Fraumeni syndrome ‘APC « FAP, Colorectal cancer (adenoma-carcinoma sequence) E-cadherin Diffuse type gastric carcinoma, Invasive - Jobular breast carcinoma PTEN + Breast Endometrium hhttps://www, facebook, com/topnotchmedicalboardorep/ CLINICAL ASPECTS OF NEOPLASIA «Cancer cachexia « Paraneoplastic syndromes ‘« Tumor grading and staging ‘« Tumor lysis syndrome (CANCER CACHEXIA © Characteristics: © Equal loss of both fat and muscle © Elevated basal metabolic rate (Evidence of systemic inflammation (increase in acute phase reactants) «TNE (originally, cachectin): released from immune cells; primary suspect « Proteolysis-induciag factor: released by tumor cells; implicated {in oss of muscle mass PARANEOPLASTIC SYNDROMI ‘Signs and symptoms not referable to the a of the tumor ‘+ May involve ectopic hormone production by tumor cells, ‘© Importance: Initial manifestation of occult neoplasm 0 May cause significant clinical problem * Napsopharyngeal Ca NF1__+ Neurofibromatosis 1 © May mimic metastatic disease NFZ___ + Neurofibromatosis 2 WT + Wilms tumor SYNDROME, ‘CANCERS, ‘MECHANISM. PTCHI_« Gorlin syndrome ‘VEL + Von Hippel-Lindau disease ‘+ Small cell lung a + ACTH or ACTH- ‘CARCINOGENIC AGENTS. Cushing syndrome + Pancreatic like substances = Tnfections carcinoma ‘« Physical and chemical exposures + eum 4 = Small cell ung INFECTION ER” __ETIOLOGIC AGENT oy ‘cancers « antidiuretic a = Squamous cell + Intracranial hormone or ANP. V infection * Sas + HPV 16,18,31,33 | ______eoplasms_-_ ~ Clonorchis si «Sa el Liver uke» Cholangio Se carcinomas infection carcinoma ee Hypercalcemia * Breast + PTHrP, TGF-a, Ste per carcinomas ‘TNE, IL-l Peptic ulcer ddenocarcinoma _* Helicobacter peeled disease « Gastric MALT pylort corepomes ‘Wawhons, = Renal cell + Hepatocellular yeythemia — , carcinoma + Erythropoi Hepatiis _* Hepatocelul + HBV, HCV Lk + Cerebellar Erythropoietin hemangioma [psc Mononucleosis TSMEOPESOTHL egy Bronchogenie ¢ Burkitt lymphoma Myasthenia — « Immunologic Thymic Adult Tell HTLV waumbane Jeukemia se la '* Primary CNS +Hv aA aos” iymphoma moe na _* HAUS (KSHY) Acanthos — ,SCMOMEE 4 immuno ‘Chronic '* Schistosoma nigricans a secretion of EGF + Bladder SCA Uterine cysts hoematobtum toe) PHYSICAL AND CHEMICAL EXPOSURES EXPOSURE ‘ASSOCIATED CANCERS ontearhropahy ” eacnones 7 Oral cavity, pharynx, larynx, esophagus Srdaene Tie + Unknown smoki (ScCA} lung (SCCA and small ce), fingers neoplasms ing pancreas (adenoCA), kidney (Renal cell CA) Wid ——— 7 Hepatcoiar carcinoma glengas + Fane or products ‘Alcohol Synergistic with smoking in causing cancers that activate ofupper airways and digestive tract, coeearay eroenogenie clotting Targa > easels ane) archos “Arsenic Skin (SCA), Liver (Angiosarcoma) Disseminated promyelocytic» Tumor products Asbestos. + Lung, pleura (Malignant mesothelioma) intravascular. Jeukemia that activate ae coagulation (DIC) Promatie clotting Gitpecne + eeiagurerd eke carcnoma Caimi = Predate ns ning + Blader [Uroeay Redetlapiasis "neoplasms * Unknown Tigh corde Liver (Angosareama) Radiation _ Skin (SCA), Melanoma “TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD Page 16 of 98 lene innusieine lett wnanus tannntehhaardnran enm ph ar hitos: //www.facebook.com/topnotchmedicalboardorep/NA, MD PNQICH TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY ‘KEVIN ELOMINA, . De eee i caindcneabontaes TUMOR GRADING AND STAGING DNA VIRUSES ~ FEATURE ‘GRADE ‘STAGE Herpes» Pinkto arp inranear inclusion bodies > Degree of + Size ofthe primary Simplex (Cowdry Type ) differentiation lesion, its extent of (HSV) _+ Multinucleated s) tia with Inclusions 8 (well-differentiated _spread to regional © Clinically, Seca rose petal” sis low-grade: Iymph nodes, & (intraepithelial vesicles poorly: presence/absence Nartcla«faranuclear incon cols at vei ase differentiated = of metastases “Foster shingles: Radiculoneuritis (painful) wit }__highegrade)__| (ZY) * mononuclear infiltrates, and cells with herpetic * Gleason scoringfor » TM staging for inelusion bodies Examples Prostatic most tumors Large cells with atypia adenocarcinoma ytome. ¢ ntramilear basophilic incisions surrounded Clinical © Of less clinical More reflective of sary) byaclear halo “Owl's eye value value than stage biologic behavior (CMV). Serology: (-] heterophile (Monospot) test Transforming vitus: causes mononucleosis, ‘TUMOR LYSIS SYNDROME nasopharyngeal Ca, and Iymphomas ‘* Chemotherapy leads to lysis of tumor cells with release of thelr Epstein 1 ymphocytosis; atypical lymphocytes (in contents Barr peripheral blood and tissues) « Abmormallies hyperialemia, hyperphosphateia, Virus Pymph nodes: paracoecl hyperplasia hyperuricemia hypocalcemia ey oy ‘* Clinical consequence: Acute kidney injury (urate nephropathy) l + Serology: (+) heterophile (Monospot) test eRe ee ‘General pattern of respon: BACTERIA MORPHOLOGY to infections «Fungal diseases, “GRAM-POSITIVE, i Viral diseases Parasitic diseases «+ Pseudomembrane: coagulated exudate wit © marked vascular congestion, interstitial GENERAL PATTERN OF RESPONSES TO INFECTIONS diphtheriae edema, and fibrin exudation in the RESPONSE. FINDINGS ‘ORGANISMS, lunderlying tissue 7 Exudative inflanimation with numerous = vascular + Exeracellular G(*) Lmono ” eutophils Suppurative _ Permeability cocci, {-} rods qytogenes + G(s) intracellular bacill in CSF: in paras sPuinzates (pyogenic satatomatossnfantzepen Pur organisms) i * Tissue necrosis and exudative inflammation * Lymphoplasmacytie + Chronic infections rich in neutrophils and macrophages fella gee vata anthracs_, emorrhagelesions duc to vasculitis Mononuclear» Lytiphocytes: Viral intracellular ‘GRAM-NEGATIVE « Platta cells: bacteria + Laryngotracheobronchidis: bronchial syphilis parasites mucosal erosion, hyperemia, and copious Granulo- * Grafiulomas with or «Mtb, fungi, Bordetell mucopurulent exudate (severe) matous joutcaseation _ schistosome e fordetella peripheral lymphocytosis, with ou wtout caveat piscneos are hypercellularity and enlargement of mucosal + Inclusion bodies Jymph follicles and peribronchial lymph nodes| Gytopathic/ » Multinucleated giant + Fleur-de-lis pattern of necrotizing cyto: cell + Viruses | pneumonia (pale necrotic centers with red, proliferative + Host cell | hemorchagic periphery) proliferation (HPV) Pseudo- « Coagulative necrosis due to vasculitis ; * Clostridia, ‘monas (perivascular infltration of pseudomonads: ‘Severe gangrenous diphtheria, E “perivascular blue haze”) ae tissue necrosis histolytica (colon, + Echthyma gangrenosum: Well-demarcated necrosis Ulcers liver), HBV (liver), necrotic and hemorrhagic oval skin lesions Herpesvirus (brain = Lymph node enlargement (buboes), Yersinia Pneumonia, Sepsis (neutrophilia) fe oa + HBV pestis « Proteinand polysaccharide-rich effusions a * Schistosoma + Tissue and vascular necrosis VIRAL DISEASES. “Klebsiella VIRUS. MORPHOLOGY FEATURE Haemophilus ducreyi granulomatis BNA VIRUSES si Chaneroid Granuloma inguinale «+ Rash: Dilated sin vessels, edema, mononuclear > Painful, with perivascular infiltrate shaggy, + Beefy red ulcer with + Warthin-Finkeldey cells: MNGC with Genital nonindurated indurated borders Measies _ °0sophilicmuclear and cytoplasmic Inclusions Involvement borders with + Strictures (in lymph nodes, ung, and sputum) yeliow-gray exudate (untreated) + Koplik spots: Necrosis, PMNs, and Sebase neovascularization (near opening of Stensen Lymphinode + Prominent: buboes> , 4, duct) involvement erosion > sinuses__° Not Prominent + Parotid/Testis/Brain: Edema and mononuclear Layers (superficial infltrates deep) + Marked epithelial + Parotid: PMNs and necrotic debris with duct ‘Neutrophil debris hyperplasia at the 2-0 nga una samupnea-> shot and fibrin uleer borders + Testis: Swelling against tunica albuginea istologic « Granulation tissue G(-) coccobacill in Mampt* farcoon’> carting seoply > sory Teaures "itnnecocsand —" mecrophages + Fanreats: secondary tonfestionof acinar thrombosed vessels (Donovan bodies) ls ‘* Mononuclear (Giemsa/Warthin- «Brain; Perivascular infiltrates, perivenular infiltrate with G(-) Starry stain) destination coccobacilli ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD For inquiries visit vnww.topnotchboardprep.com.ph or https://MwW.t Vtopnotchmedicalboardarep/ Page 17 of 98. j ‘vgs. TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMIMA, MD. For inquiries visit yoww,topnotchboardorep.com.ph or https://www. facebook, notchmedicalboardpr MYCOBACTERIUM TUBERCULOSIS FEATURE TUBERCULOID LEPROMATOUS + Tuberculosis Peripheral nerVe —< Asyenmetric _» Symmetric ++ Intact cell-mediated immunity: chronic, granulomatous involvement “en {inflammation anemia a ~ Lipid-aden macrophage ©leL2: produced by APCs, for Tat differentiation Morphology * Cram (Lepra cells) with globs © EN-Y: produced by Tw, to activate macrophages (to become {ar8) bactericidal) and to form granulomas and caseation necrosis AFB olparsl + Many (mulibaclary) Tal response: usually A weeks (2-4 weeks) postinfection LB tpauetbactary) _* Many (multbacilany) | * Depressed CMI; paucity of granulomas; macrophages filed with At euch paiecemctapge Hed TREPONEMA PALLIDUM © Depressed CMI ({.e. HIV, all stages) increases risk of TB * Syphilis TUBERCULOSIS: CLINICOPATHOLOGIC FORMS FORM. LESIONS SEQUELAE * Ghon focus + Healing by fibrosis (consolidation ‘ther fower pare (Ra bapens = ofupperlobe or upper‘ immune- Primary partof lower lobe) ihren + Ranks compler: CF» ith an Dumonaryhiar node thant involvement * Healing by fibrosis ‘Localized caseating destructive lesions + Progressive secondary + Simmon focus Secondary (consolidation) apical © Spread into adjacent parenchyma * Erosion into bronchi or Progressive — vessels ‘Miliary pulmonary Pulmonary + Pleural involvement: TB effusions, empyema, blterative brous pleuritis 7 Scattered small foc itary SERRE SRATCE Tina pulmonary throughout lung Lee eeand parenchyma other organs) EXTRAPULMONARY TUBERCULOSIS + Kidneys * Adrenals ; * Bones: Osteomyelitis (Pott disease vertebrae) = CNS: Meningitis: * Lymph nodes: Sofa ‘© Most common form of extrapulmonary TB san " 0 Most common segmént affected: ileum 6 Rare; due to decreade in consumption of nected milk ‘MYCOBACTERIUM AVIUM INTRACELLULARE (MAC) © Four stages (Primary, Secondary, Latent, and Tertiary) (© Congenital form * Characteristic plasma cell-predominant inflammatory infiltrate STAGE LESIONS. ‘MORPHOLOGY * Ghancre Painless» Plasma cell-rich inflate, lesion in penis macrophages, Primary (males), vulva, and Iymphocytes, cervix (females proliferative endarteritis > Mucocutaneous (oral cavity, palms» Same as chancre; less Secondary and soles) inflammation + Condyloma tata > doreitis: obliterative endarteritis of vasa vasorum > loss of elasticity (medial scarring): aortic « Aortits regurgitation and + Neurosypbilis(in aneurysms Tertiary” cS module) + Gumma: central + Gumma » coagulation necrosis, surrounded by palisading ‘macrophages and fibroblasts, plasma cell- rch infiltrate, few treponemes ‘CONGENITAL SYPHILIS ‘ORGAN MORPHOLOGY * Osteochondritis and periostitis Bones + Tibia: Saber shins (excessive new bone growth) + Nose: Saddle nose (destruction of vomer) Liver» Fibrosis, mononuclear infiltrates, vascular changes * Interstitial pneumonia Ly °F _« Pale, airless tung (pneumonia alba) in stiborn infants “Triad of late manifestations others’ * Interstitial keratitis ‘= Hutchinson teeth (screw driver or peg-shaped) L. + Bight nerve deafness aa ‘CONDYLOMAS OF STDs ‘CONDYLOMA + Disseminated disease inpatients with profound FeaTune (upnioM ‘CONDYLOMA LATA ‘Immunodeficiency (AIDS and transplant patients) Hoteaie ‘ATA * Histologically, macrophages filled with acid-fast bacilli; rare agen HPV Gand 11 +7 pallidum granulomas Flori, cali B ® s necesa as ross Povid, cauliflower + Broad based, elevated Intact CMI{s necessary for granuloma format G like grows ping * Papillary fronds» Psoriasiform hyperplad = fonacrmane SEPRAE covered with (Cest tubes ina rack) * Affects skin and peripheral nerves Wirwscopie Sgummour eden TY Sema * Tw forms; maifestaons ated by host ell mediated spithetum * (ee Syphilis: im + Kollocyticatypla_ Morpholo 0 Tuberculoid (pauelbacillary) _ a © Lepromatous (multibacillary) SEROLOGIC DIAGNOSIS OF SYPHILIS © Borderline (intermediate) FEATURE NON-TREPONEMAL "TREPONEMAL > Sereenin LEPROSY: CLINICAL FORMS Cink Monitoring response ¢ Confirmation FEATURE TUBERCULOID LEPROMATOUS “to therapy clSereening Celimediated ne, + Fluorescent immunity _* Intact _lDenreseed ‘Treponemal antibody Tepromin silt poate» Negauve “teeny emtReatin—brorption (FTA-ABS) opens ¢ TH #T2> Tet Research Laboratory _*SS4V for Abs of 7 + (not protective; may ‘ause GN and vasculitis (Type tlt sR) Antibodies + () TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD rdore OF httos://www.farebonk ram/tanantrhmartcsihnsein. For inquiries visit pallidum (MH-T ony + Tatum pace _agglutination (TPPA) © Ant 7 pallidum antibodies (specific) Deweas ° Anticardiolipin antibodies Page 18 of 98it }OPNQICH TOPNOTCH MEDICAL BUARU Fé FatiULVGT Faiwuut BY Net ELUmiy HAD ~ For inquiries visit www,topnotchboardorep.com.ph or bi 5: wow f LIMITATIONS OF SEROLOGIC DIAGNOSTICS FOR SYPHILIS [PARASITIC DISEASES ————«d + Falsepesve reat PARASITIC DISEASES ] 0 Pregnancy autoimmune diseases nections eter hen PROTOZOANS o Falon-nogative resi PLASMODIUM AND BABESIA SPeaerskeaeeen ‘FEATURE Plasmodium Babesta, * Too many antibodies prevent antibody-antigen complex Species a cone G formation - no visible flocculation > read as negative aA _ eens Can also happen in other assays (pregnancy test) Diagnosis ‘+ Glemsa-stained peripheral blood smear ~ Asexual stages of + Parasite WITHOUT ANAEROBIC INFECTIONS. Morphology parasite WITH hemozoin, Maltese {= Abscess formation: morphologically similar with that of hhemozoin cross pattern pyogenic organisms + Cerebral malaria © Usually polymicrobial Vessels plugged with ‘= Clostridia Spedal infected RBCS © Usually cause disease through toxins lesions perivascular ring a hemorrhages (Durck sM_ CLINICAL granulomas) AND TOXIN DISEASE peoersoL cy, y clostridiay » CasbUBbIES LEISHMANIASIS Coperfringens * “stidial severe myanecrosis ‘TYPE ‘MORPHOLOGY 1 celts Eprensive hemolysis 7 Gai Elerged macrophages ied lecithinase «© Marked vascular injury Visceral with leshmania gangrene * with thrombosis ‘isceral skin: Hyperpigmentation (South Asian C difficile ancestry; kala-azar) Toxind: © Pseudo- © Granulomatous with many giant cells and chemokine membrano_° Mucopuruient exudate Cutaneous few leishmania Toxin B: uscolitis _"eméniscent ofa voleano 7 Mixed mononuclear infiltrate + EE ani ee uae aE EOE ESET macrophages filled with leishmania > Mucocutaneous granulomatous (few leishmania) > (CHLAMYDIA TRACHOMATIS scarring ® Genital infection: Most common sexually transmitted bacterial, # May reactivate disease in the world Diffuse + Foaray macrophages filled with co Urethritis: cutaneous ___leishmania * Purulent like gonorrhea, but NO ORGANISMS ‘oLstrains: Lymphogranuloma venereum (LGV) ‘TRYPANOSOMIASIS * Chlamydial inchisions in cells (active lesions) FEATURE “AFRICAN ‘AMERICAN, * Lymph nodes: granulomatous inflammation with tregular os 2 Febracel var gambiense 7 eye) {oid of necrosis cintaining PMNs (stellate abscesses) reanisms and rhodisiense * Chronic: non-spetific chronic inflammation and fibrosis, © Chanere: at bite site , numerous parasites "FUNGAL DISEASES surrounded by YEASTS. mononéclears z ‘Gryptococcus + Hemolymphatic: + Dilated FEATORE Corda albvenns neoformans Splenomegaly and cardiomyopathy sree = Yocst with prominent Lymphadenopathy; + Megacolon and Morphology concentration of ‘megaesophagus s ae, lysaccharide capsul Forms —_stiidehyeh or eeeera parasites in capillary (No organisms in hyphae oT Toops (choroid pense gangliaot e mucicarmine(+) and glomerull) ‘uerbach plexus) 7 Thrush: gray-white, Immunocompetent: + Cerebral: dirty-looking Granulomatous Leptomeningtis > pseudomembrane, + Immunocompromise demyelinating Morphology with underlying soap-bubble panencephalltis mucosal hyperemia lesions (in CNS) and inflammation METAZOANS ‘MOLDS NEMATODES FEATURE Aspergillus ‘Mucor ‘STRONGYLOIDES STERCORALIS 7 Septate hyphae, + Non-septate + Larvae penetrate skin > lungs > GIT Morphology branchingatacute hyphae, branching + Autoinfection: larvae hatched in GIT invade colonic mucosa > angles (40°) at right angles Jungs = Necrotizing + Hemorrhagic FORM, ‘MORPHOLOGY Pneumonia with pneumonia, = Larvae in duodenal erypts with Puimonary gray foci and vascular Mild strongyloidiasis _eosinophil-rich infiltrate in lamina involvement —_hemorchagic thrombosis, and propria and mucosal edema orders (target distal infarcts Hivperintection® ae lesions) invastnaflrvaetno. 7 Mononuclear infites ‘Angioinvasion a7 oloie submucosa, * Mer a eps nce art = Yes (Fhinocerebral forms) lymphatesandblood Warm ofl stages in skin Ls TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD sl For inquiries visit www. topnotchboardorep,com.ph or. ‘"TTnereased worm burden In immunosuppressed patients ‘TRICHINOSIS + Trichinella spiralis ‘ Commonly encyst in striated muscles with richest blood supply ‘© Diaphragm, EOMs, laryngeal, deltold, gastrocnemius, intercostals + Skeletal muscle cells > "Nurse cells” ‘Loss of striations, formation of collagenous capsule, development of new blood vessels Page 19 of 98 rw facet not chi ardorep/Forms ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY Wynw.topnotchboardprep,com,ph or For inquiries vist LYMPHATIC FILARIASIS ia. ban ‘ORGAN ‘MORPHOLOGY > Persistent Iymphedema extremities, scrotum, penis, vulva) ‘© Hydroceles (testis) > thickening of tunica vaginalis « Adult worms (in LNs and vessels), surrounded by: 1. Mild or no inflammation 2 Intense eosinophilia with hemorrhage and fibrin (recurrent flarial funiculoepididymtts) 3.Granulomas + Elephantiasis: subcutaneous Nbross, epithelial hyperkeratosis + Eosinophilia * Dead worms surrounded by hyaline, lung eosinophil precipitates embedded in small - epithelioid granulomas (Meyers-Kouwenaar bodies) Lymphaties ‘ONCHOCERCA VOLVULUS + Leading cause of preventable blindness in sub-Saharan Africa ‘ORGAN ‘MORPHOLOGY ‘Skin « Onchocercoma (subcutaneous nodule): fibrous capsule surrounding adult worms, with {inflammatory infiltrates ‘© Leopard, lizard or elephant skin: Epidermal atropiy and elastic ber breakdown, alternating with Hyperkeratosis; Hyperpigmentation with pigment incontinence, dermal atrophy & fibrosis. Bye» Sclerosing keratitis (limbus) ‘¢ Mazzotti reaction: Accentuation of keratitis with antifilarial treatment + Anteridr chamber: Iridocyclitis and Glaucoma + Choroill and retina: Atrophy and loss of vision TREMATODES ScHISTOSOMA SSS '*S. japonicum, mangon, and haematobium 6 Dioecious wormt + Cercariae: infective stage; elicit minimal skin reaction ‘© Eggs: elicit inflamthation; inflammatory response allows transport to bowel (Japonicum and mansoni) and bladder wall (haematobium) > shedding ‘Granulomatous inflammation and fibrosis + Morphology 0S japonicum and S. mansoni * Granulomas, fibrosis, and portal enlargement (without regenerative nodules); pipestem fibrosis 0S haematobium * Granulomatous cystitis * Increased risk of bladder squamous cell CA * Ureters: Inflammation and fibrosis of ureteral walls (most ‘common complication) cesropes FEATURE Taenia solium_ ‘Echinococcus granulosus Pathologic © Cysticercl ‘ Hydatid cysts (Hydatid lesions (Cystercosis) disease) (Disease) 7 Ovoid, white» Mononuclear & eosinophilic toopalescent, infiltrates: on larvae grape-sized, + Cysts with inner contain rminative, and outer non- Morphology jnvaginated __germinativelaye, with scolexbathed surrounding fibrosis with clear cyst « Hydatid sand: Degenerating fluid scolices ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD Far innuiries visit www.toonotchboardorep.com.oh or htt © Air pollution ‘Heavy metals © Tobaceo co Alcohol Thermal injuries ‘ Blectrical injury c lonizing Radiation + Nutritional diseases ‘0 PEM (Marasmus and Kwashiorkor) Cachexia ‘o Anorexia and Bulimia nervosa o Vitamin disorders ‘Obesity ENVIRONMENTAL PATHOLOGY ‘AIR POLLUTION Most common organ system affected: lungs (especially those ‘with depressed lung function) + Can affect multiple organ systems +» Common pollutants ‘6 Outdoor: Ozone, nitrogen dioxide, sulfur dioxide, aerosols and soot Indoor: Wood smoke, bioaerosols, radon, formaldehyde OZONE (02) ‘Injury to Type I pneymocytes via free-radical formation Clinically, respiratory symptoms; more detrimental to patients with decreased lung function (patients with obstructive lung diseases) «Usually in Combination with $02 and others © Detrimental even to those with intact lung function SOOT (PARTICULATE MATTER) ‘+ Engulfment of soot by alveolar macrophages > inflammatory response ‘© Common pathogenesis of Pneumoconioses (see Lungs) « Fine or ultrafine particles (<10 ym): more dangerous ‘Can travel to distal alr spaces to alveolar macrophages > inflammation CARBON MONOXIDE (CO) « Systemic asphysiant; important cause of accidental and suicidal death Non-irrtating colorless and odorless gas « Also present in cigarette smoke + Causes injury by two major mechanisms: 0 Voxygen delivery: CO has 200x more afinity to hemoglobin, > hypoxia > hypoxic changes in organs 0 VATP: CO is an inhibitor of Complex IV in ETC > decreased ATP > cell death # CO poisoning ‘Systemic hypoxia: 20-30% CO saturation ‘© Coma and death: 60-70% CO saturation Acre ‘CHROMIC * Cherry-red discoloration of —* CNS: hypoxic changes skin.and membranes particulary in basal ganglia. + Nomorphologic changes in and enticular nuclei patients who quickly expired + Increased levels of # CNS:edematous brain with carboxyhemoglobin in the punctate hemorrhages and blood (COHgb) hypoxic changes INDOOR POLLUTANTS. CLINICAL orca ‘COMMON INDOOR POLLUTANTS + Wood smoke, bloaeros0l (containing Pulmons Pulmonary" pathogenic organisms, eg, Legionella, viruses) © Bioaerosols (pet dander, dust mites Fangland Alleges * Boner Cancer * Wood stoke (polyeycic hydrocarbons), Radon (in uranium miners), Formaldehyde Page 20 of 98 notchmPowe ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD “=== For induiries visit www.toonotchboardorep.com.ph or https: 100k, otchmedicalboar« HEAVY METALS ‘TOBACCO SMOKE COMPOUNDS a EFFECT ‘COMPOUNDS * Interfeves with Ca metabolism oTar © Gets deposited into bones and teeth (12 = 20-30 years) « Polycyclic aromatic hydrocarbons © Impairs fracture healing Carcinogenesis, Benzo(a)pyrene * CNS involvement is more prominent in children + Nitrosamine ‘© Higher intestinal absorption (increased burden) and more * Nicotine permeable BBB Tumor promotion 7 you © Inadutts, peripheral neuropathies are more common ‘Inhibits ALA dehydratase and ferrochelatase © Microcytic hypochromic anemia LEAD POISONING ‘ORGAN, MORPHOLOGY Ring sideroblasts(iron-laden mitochondria) | (Prussian Blue stain) Hematologic + Microcytic, hypochromic anemia with hemolysis + Punctate basophilic stippling of red cells * Children: Brain involvement (learning disabilities, blindness, psychoses) CNS * Adults: peripheral demyelinating neuropathy sally present with wrist drop, then foot irop) GIT + Lead colic (poorly-localized abdominal pain) _| '* Proximal tubular damage (intranuclear ‘inclusions: protein aggregates) Kidney» Chronic: interstitial fibrosis and CKD ‘Impaired uric acid excretion > gout "Saturnine gout” MERCURY i ‘Primary targets: Kidheys and CNS * Forms: © Metallic: Elemental Hg ‘Inorganic: Mercurie chloride * Metallic and Orgahic: Highly lipophilic > CNS damage (clinically, motor, behavioral and cognitive dysfunction) ‘0 Organic: Methylmetcury + Minamata disease: cerebral palsy, blindness, mental retardation, major CNS defects (in utero exposure) ‘= Developing brait highly sensitive to methylmercury ARSENIC ‘= "Poison of kings’, “King of potsons” « Interferes with cellular metabolism ‘s Primary targets: CVS, GIT, CNS + Trivalent compounds are toxic: Arsenic trioxide, Na arsenite, ‘Arsenic trichloride + Neurologic: 2-8 weeks post-exposure (neuropathy: paresthesias, numbness, pain) «Skin: chronic; hyperpigmentation and hyperkeratosis, + Can cause lung, bladder and skin cancers ‘CADMIUM + Proferentially toxic to kidneys by ROS production '* Other targets: Lungs, Bones co Lungs: obstructive lung disease, increased risk of lung cancer ‘0 Bones: Skeletal abnormalities associated with calcium loss « Ital-itai disease: osteoporosis and osteomalacia with associated renal disease TOBACCO ‘Smoking: most readily preventable cause of death in humans ‘+ >2,000 compounds in cigarette smoke © Nicotine: addictive + One ofthe four coronary risk factors += Passive smoking: same effects 0 Cotinine: metabolite of nicotine; measure of passive smoking (blood levels) ‘TOPNOTCH MEDICAL BOARD PREP PATHOLOGY HANDOUT BY KEVIN ELOMINA, MD 95: / www. fe For inquiries visit wow, toonotchboardorep,com,ph or. » Formaldehyde ‘= Nitrogen oxides + Phenol ‘+ Formaldehyde + Nitrogen oxides =o Mucosal irritation Toxicity to cilia Tmpaired Oa transport ‘and utilization Ganglionic stimulation» Nicotine and depression EFFECTS ‘ORGAN, EFFECT. Lung + Bronchitis, emphysema (centriacinar) * Atherosclerosisand MI © Aplatelet aggregation (0.VO2 supply (pulmonary disease and CO) # Vthreshold for VAb + ASpontaneous abortions, preterm births and Obstetric * NPP Others + Cancersin different organs cvs ALCOHOL —— 7 Most commonly abused substance ‘+ Metabolism by CYP2E1 (MEOS), alcohol dehydrogenase (ADH)* and catalase > acetaldehyde ‘+ Acctaldehyde is metabolized to acetic acid by aldehyde dehydrogenase (ALDH)* ‘+ * produces NADH co Simulates energy excess > metabolism shifts to lipogenesis > hepatic steatosis EFFECTS Acute ‘Acute toxicity: CNS, GIT and liver ‘© GIT and liver changes: reversible ‘© CNS: CNS depression * Reticular formation (consciousness center) * Lower medullary centers (respiratory center) > respiratory arrest o Liver: steatosis ‘0 Stomach: acute gastritis and ulceration ORGAN EFFECTS gr» Liver Alcoholic steatohepatitis 5 Cirthosis > HCC + Pancreas: Acute and chronic pancreatitis + Massive bleeding from gastritis, ulcers and GIT esophageal varices ~ Wernicke and Korsakolf syndrome (See ONS) + Peripheral neuropathy qs * Alcoholic cardiomyopathy (Dilated cardiomyopathy + Dyslipidemia (LHDL) with liver disease + Fetal alcohol syndrome: microcephaly, growah Obstetric retardation, facial abnormalities, reduction in mental function * Cancers in oral cavity, esophagus liver, and possibly breast + Malnutrition (empty calories) and vitamin deficiencies (Thiamine) ‘THERMAL INJURIES ‘THERMAL BURNS ‘* Most common thermal injury ‘* Most common cause: fire or scalding + Factors that determine outlook of burns Depth ‘© BSA (Recall BSA computation in Surgery) © Internal injuries (from toxic fume inhalation) © Promptness of efficacy of therapy Nervous Others Page 21 of 98 hmedicalboardorey