1

SSG
Pathoma
Chapter Page
1 Growth, Cells 2
2 Inflammation, Wounds 4
3 Neoplasia 6
4 Hemostasis & related 9
5 RBC disorders 13
6 WBC disorders 17
7 Vascular Pathology 22
8 Cardiac Pathology 25
9 Respiratory Tract Physio 30
10 GI pathology 36
11 Pancrease, Gallbladder, Liver 42
12 Kidney & UG 45
13 Female 49
14 Male 53
15 Endocrine 55
16 Breast Path 60
17 CNS 62
18 NMS 67
19 Skin 71
 2
Ch 1.1 Growth Adaptations Ch 1.2 – Cellular Injury Ch 1.3 – Cell Death
Hyperplasia ↑ stress on organ → ↑ organ size via Injury Stress > cells ability to adapt Cell Death (!) Loss of Nucleus = morphological hallmark of cell death.
& • ↑ cell size = Hypertrophy Factors that 1. Type of Stress - eg. Inflammation vs infarction 1. Pyknosis – nucleus shrinks down into “ink-dot”
Hypertrophy o ↑ protein synth, gene expression, organelle synth determine injury 2. Severity – eg. Atherosclerosis vs embolism 2. Karyorrhexis – breakup of nucleus into pieces
• ↑ cell # = Hyperplasia 3. Type of Cell effected – neurons are ↑ susceptible to hypoxia 3. Karyolysis – pieces broken down into basic building blocks
o ↑ stem cell divisions Causes of Injury Inflammation - Nutritional Deficiency or excess - Hypoxia - Trauma - Genetics Mechanisms Necrosis – “murder” of cells/tissue from outside
o ∅ stem cells in permanent tissues → can only hypertrophy Hypoxia Low O2 delivery to tissue • Large group of cells affected → followed by acute inflammation
permanent Permanent tissues → ∅ stem cells → HYPERTROPHY ONLY O2 is final e- acceptor in electron transfer chain → ↓ OxPhos → ↓ ATP → Injury • Due to underlying pathologic process (never normal physiologic)
tissues 1. Cardiac Myocyte Ischemia ↓ blood flow through an organ via. Apoptosis – “suicide”, energy dependent, genetic, Single cells or small groups of cells
2. Skeletal m.m • Blockage in arterial flow (eg atherosclerosis of coronary → angina) • Eg: endometrial shedding, embryogenesis, CD8+ killing virus infected cells
3. Nerves • ↓ venous flow → backup & ↓ flow across organ bed • Dying cell shrinks (becomes eosinophilic)→nucleus condenses →
Pathologic Pathologic hyperplasia → ↑ risk of dysplasia → ↑ risk of cancer o Budd-Chiari – thrombosis of hepatic v → liver infarction apoptotic bodies “fall from cell” & are removed by macrophage
Hyperplasia (!) Exception: BPH – ∅ ↑ risk of cancer
Polycythemia Vera is most common cause • ∅ followed by inflammation
Atrophy ↓ stress on organ (↓ hormonal stimulation, ↓ use, ↓ nutrients) → atrophy via
Lupus anticoagulant → hypercoagulable state Necrosis types
• ↓ cell size • Shock - ↓ perfusion of vital organs Coagulative necrotic tissue that remains film
o Ubiquitin-Proteasome Degradation o Cardiogenic • hypovolemic • Analphactic • Septic Necrosis Cellular shape & organ structure remains via coagulation of proteins

ubiquitin tags proteins to be removed Hypoxemia ↓ PaO2 < 60 mmHg → SaO2 < 90% via.. ∅ nucleus in cells
o Autophagy – • ↓ FiO2 – eg High altitude Occurs @ ischemic infarction in every organ (except brain)

cellular components→vacuoles→ fuse w/ • ↓ PAO2 – eg. Anything that ↑ PACO2 – hypoventilation, COPD Area of infarction is usually WEDGE shaped & PALE
lysosomes • Transfer from A→a – interstitial fibrosis of lung • Tip of wedge points to area of vessel occlusion
• ↓ # of cells - Apoptosis • V/Q mismatch Red Infarct Blood re-enters a loosely organized tissue (eg hemorrhagic infarct)
Metaplasia ∆ stress on organ → ∆ cell type ↓ O2 carrying Anemia - ↓ RBC mass w normal PaO2 & SaO2 Liquefactive Tissue liquefied by enzymatic lysis of cells & proteins
Most commonly involves surface epithelial layers capacity CO poisoning – CO binds Hb more avidly than O2 → normal PaO2, ↓ SaO2
Necrosis • Brain Infarction – bc microglial cell enzymes
• Squamous – keratin/non-keratin • Smoke, fires, car exhaust, gas heaters • Abcess – mediated by PMN enzymes
• Columnar – (gut) • Clinical: (!) CHERRY RED SKIN & HA → confusion → coma, death • Pancreatitis – parenchymal destruction via enzymes
• Transitional – (UG tract) Methemoglobinemia Gangrenous coagulative necrosis that resembles mummified tissue (dry)
New cells better equipped to handle stress • Iron in heme in oxidized Fe+3 form (normal = Fe+2 binds O2) Necrosis • (!) Ischemia of Lower limb & GI
eg: Barrets • PaO2 normal, ↓ SaO2 • If dead tissue becomes infected → liquefactive necrosis → Wet Gangrene
• Normal Esophagus – Squamous • Normal Stomach – Columnar • Seen w oxidant stress (sulfa & nitrate drugs) Caseous soft friable necrotic tissue with cottage-cheese like appearance
• GERD → lower esophagus converts → • Newborns - ↓ amount of reducing “machinery” → ↑ oxidation Necrosis • Combination of coagulative & liquefactive necrosis
o columnar non-ciliated mucinous epithelium • Clinical: (!) Chocolate-Colored Blood & Cyanotic • Characteristic of granulomatous inflammation due to TB or fungus
(!) Mechanism of Metaplasia = Reprogramming of Stem cells • Tx: IV Methylene Blue – reducing agent → reduce Fe to Fe+2 Fat Necrosis Necrotic adipose tissues w chalky-white appearance
• Remove stress → REVERSALE of metaplasia Consequences of ↓ OxPhos → ↓ ATP Calcium deposits on fatty acids → saponification → chalky appearance
Metaplasia can progress to cancer (eg. Barrets → Adenocarcinoma) Hypoxia • ↓ Na/K pump → ↑ Na in cell → H2O follows → cell swells • Dystrophic calcification – dead tissue is nidus for Ca deposition
• (!) Exception: Apocrine Metaplasia (fibrocystic ∆ of breast) - ∅ ↑ risk for • ↓ Ca+2 pump – ↑ Ca+2 cytosol → activate enzymes • (vs Metastatic calcification - ↑ serum Ca or PO4→precipitates)
cancer o Normal cell – tries to keep Ca+2 in cytosol very low Characteristic @
Vit A deficiency can result in metaplasia
• ↑Anerobic rxn → ↑ Lactic Acid → ↓ pH → DNA & protein precipitation • Trauma to fat (Breast) → can present as
• Night blindness • ↓ immune-system o mass w giant cells
Initial Phase of (!) Reversible
• 15-17 translocation @ Vit A receptor → Promyelocytic Leukemia (PML) o calcifications – on mammogram may be benign
Injury (!) Cell Swelling = hallmark
o (Tx: Altra) • Pancreatitis-mediated peripancreatic fat necrosis
• Loss of microvilli – swelling “covers up” microvilli
• Vit A maintains specialized epithelium (eg: Squamous epithelium lining Fibrinoid Necrotic damage to blood vessel wall → leaking of proteins from blood vessel into
• membrane blebbilng – cell “blebs” out of cytoskeleton
conjunctiva)
• RER swelling – ER fills w H2O → ribosomes pop off → ↓ protein synth
Necrosis wall → BRIGHT PINK staining
o ↓ vit A → ↓ specialization → thickening → KERATOMALACIA Characteristic @
Later phase of (!) Irreversible
Mesenchymal Tissues can undergo metaplasia (bone, connective tissues, fat)
Injury (!) Membrane Damage = hallmark Malignant HTN • Vasculitis • Pre-eclampsia → placenta
• (!) Myositis Ossificans : trauma → skeletal m.m inflammation Apoptosis Mediated by Caspase
• Plasma Membrane damage
o → metaplasia@ healing • Activate proteases (breakdown cytoskeleton)
o cell products into blood (eg. Troponin)
o Bone produced within skeletal m.m • Activate endonucleases (breakdown DNA)
o Ca2 can rush into cell
Dysplasia Disordered cellular growth → refers to proliferation of precancerous cells • Mitochondrial Membrane Caspase activated by pathways
EG: CIN – cervical intraepithelial neoplasia (I, II, & III)
o ETC in on INNER mitochondrial membrane → ↓ ETC • 1. Intrinsic mitochondrial pathway
Arises from longstanding pathologically hyperplasia or metaplasia o Cytochrome C mediate in response to…

↓ ETC → ↓ ATP → irreversible, ∅ able to fix
(!) Dysplasia is REVERSIBLE by removing stress
Cellular injury
o Cytochrome C leaks into cytoplasm → activate apoptosis
• If progresses to carcinoma → IRREVERSIBLE
DNA damage,
• Lysosome Membranes
Aplasia Failure of cell production during embryogenesis
↓ hormonal sSmulaSon → inactivated BCL2
o Enzymes into cytoplasm → destroy cell
(eg: unilateral renal agenesis) o Cytochrome C moves from mito→cyto→activate caspases
o These enzymes futher activated by influx of Ca+2
Hypoplasia ↓ cell production during embryogeneses → small organ • 2. Extrinsic Receptor Ligand Pathway
End result of Cell Death!
Eg: streak ovary in Turners o FAS-ligand binds FAS-death receptor (CD95) on target cell
Injury
• 3. Cytotoxic CD8+ T-cell Pathways
o Perforins create pore in membrane of target cell
o Granzyme enters pore → activates caspases
 3
Ch 1.4 Free Radical Injury CH 1.5 Amyloid
Free Radical Chemical speciese w unpaired electron in outer orbit Amyloid Misfolded protein deposited in EXTRAcellular space
Physiologic Occurs normally during Ox Phos Results in damaged tissue – tends to deposit around blood vessels
generation Cytochrome C oxidase transfers e- → O2 during OxPhos Multiple proteins can deposit as amyloid
Partial reduction → O2• , H2O2, & • OH radicals • β pleated sheet configuration
Pathologic Ionizing Radiation → • OH from splitting up H2O → • OH free radical is most damaging Congo Red staining
Generation Inflammation – Oxidative burst (NADPH oxidase) Apple Green birefringence @ polarized light
Metals (Cu & Fe) – Fe → Fenton reaction → OH radical (Wilsons & Hemochromatosis) Systemic 1° - AL-amyloid - amyloid derived from Ig Light Chain
Drugs & Chemicals (acetaminophen → hepatotoxicity) & CCl4 Amyloid • associated w Plasma Cell Dyscrasia → overproduced light chain
Free Radical Peroxidation of Lipids 2° - AA-Amlyoid – amyloid derived from SAA (Acute phase reactant)
Damage Oxidation of DNA & Proteins • inflammatory states (RA, IBD, etc),
• Oxidation of DNA implicated in oncogenesis • malignancy → inflammatory states
Elimiation Antioxidants • Family Mediterranean fever – genetic AR dysfunction of PMN
of Free Enzymes o PMN activated → episodes of inflammation
Radicals • Super Oxide Dismutase (SOD)– handles O2• o Episodes of fever & acute serosal inflammation
• Glutathione Peroxidase – handles • OH Classic Clinical Nephrotic Syndrome – Kidney is MOST COMMONLY involved organ
• Catalase – handles H2O2 Findings Restrictive Cardiomyopathy
Metal Carrier Proteins - Transferrin, Ferratin, etc → prevent free metals Tounge enlargement, malabsorption & hepatosplenomegaly
O2 → O2• → H2O2 → OH → H2O Dx Tissue Biopsy required
Free Radical CCl4 – classically used in DRY CLEANING industry • Abdominal fat pad & rectum are easily accessible targets
Injury • converted in body to CCl3- in P450 system Tx Damaged organs must be transplanted → amyloid ∅ able to be removed
• initial reversible damage (cell swelling) → ↓ ribosome → ↓ protein synth Localized Amyloid
• fat gets stuck in liver → can’t be exported in Lipoprotein → FATTY LIVER Senile Cardiac Non-mutated serum Transthyretin deposits in heart
Reperfusion Injury Amyloidosis Usually asymptomatic
• ischemia → cell injury → enzymes leak out into blood Present in 25% > 80 y.o
• blood returned to organ → inflammatory cells & O2 & dead tissue Familial Amyloid Mutated serum Transthyretin deposits in heart
→ free radical production Cardiomyopathy Leads to restrictive cardiomyopathy
5% of blacks carry mutated gene
NIDDM Type II Amylin deposits islets of pancreas
• derived from insulin production
Alzeimers dz Aβ amyloid deposits in brain → forms amyloid plaques
• derived from β-amyloid precursor protein (Chrm 21)
<downs syndrome patients have early onset alzhemiers>
Dialysis β2-microglobulin deposits in JOINTS in patients on dialysis
Associated • β2-microgloublin from MHC-I is not well removed from blood
Amyloidosis
Medullary Calcitonin deposits within tumor
carcinoma of • C-cells
thyroid “Tumor cells in an amyloid background”
 4
Ch 2.1 Acute Inflammation Pt 1 – Fluid & Edema Hageman Factor Inactive Proinflammatory protein, produced in liver Step 7 PMN undergo APOPTOSIS within 24 hrs after resolution of inflammatory stimulus
Inflammation Move PMN & Lymphocyte, plasma protein, fluids from blood → interstitial Activated @ exposure to subendothelial or tissue collagen → activates Resolution
• PMNs = acute • Coagulation & fibrinolytic systems → (!) role in G- sepsis & DIC
• Complement Stage 3 of Mφ stage
• Lymphocyte = chronic
• Kinnin system – cleave HMWK → bradykinin → vasodilation, vascular inflammation Days 2-3 after inflammation begins
Acute Inflammation
perm, & pain Mφ Monocyte in blood → arrive via margination/rolling/adhesion/transmigration
Characterized by 1) Edema & 2) PMN Cardinal Signs of Redness (rubor) & warmth (calor) Ingest via phagocytosis → destroy using enzymes in 2ndary granules
Response to 1) Infection → eliminate pathogen Inflammation • Relax arteriolar smooth m.m → Vasodilation → ↑ blood flow • Lysozyme is (!) enzyme
2) Tissue Necrosis → clear necrotic debris • Mediators: Histamine > PGs (I2,D2,E2) & bradykinin Manage the next step of inflammation
Timing Immediate response → limited specificity Swelling (tumor) • Resolution & Healing → IL-10 & TGF-β → ↓ inflammatory process
• Leakage of fluid from postcapillary venule → interstitial space • Continue acute inflammation → IL-8 → Mφ recruit more PMN
Innate immunity – epithelium, mucous, complement, mast cells, Mφ, PMN, etc
• Mediators: Histamine & Tissue Damage • Abscess formation – area of fibrosis around area of infection
Ch 2 Acute Inflammation Pt 1 – Fluid & Edema Pain (dolor) • Chronic Inflammation
TLR Present on cells innate immune system (Mφ & Dendritic cells) • Sensitization of sensory nerve endings Ch 2.2 Chronic Inflammation
Toll-Like Recognize PAMP (pathogen associated molecular pattern) • Mediators: Bradykinin & PGE2 General Lymphocytes & Plasma cell in tissue
Receptor eg. CD-14 on Mφ recognizes LPS on G- bacteria → activates immune system Fever Delayed response but ↑ specific (adaptive)
TLR → ↑ NF-κ κB → turns on acute inflammatory response → ↑ immune mediators • Pyrogens cause Mφ → IL-1 & TNF release → hypothalamus Stimuli Persistent infection – most common cause
• → ↑ COX acSvity @ perivascular cells of hypothalamus → Viral, mycobacterial, parasites, fungi, autoimmune dz, foreign material, some cancers
TLR also mediate chronic inflammation
• → ↑ PGE2 → raises temperature set point @ hypothalamus → fEEver T-lymphocytes Produce in marrow as “Progenitor T-cell” → Thymus for education
Arachidonic Acid Released from phospholipid cell membrane via Phospholipase A2
Ch 2 Acute Inflammation Pt 2 – PMN arrival & function (~24hr) • TCR (T-cell Receptor) undergoes rearrangement
Acted on by COX or 5-Lipoxygenase Step 1 Vasodilation → slows bloodflow in postcapillary venules • Become CD4+ helper or CD8+ cytotoxic
COX path Produces PGs Margination Cells marginate from center of flow → periphery TCR-complex used to survey antigens presented on MHC (TCR & CD3)
PGI2, PGD2, PGE2 Step 2 Endothelial SELECTINs upregulated → act as “speedbump” when PMN rolling over • CD4+ → MHC Class II • CD8+ → MHC Class I
• ↑ arteriolar vasodilation Rolling • P-selectin – from Weibel-Palade bodies nd
Activation of T-Cell requires 1. Binding of Ag/MHC complex & 2. Additional 2 signal
• ↑ post capillary vascular permeability o Mediator: Histamine CD4+ activation APC take extracellular Ag → phagocytosed→processed→present on MHC II
PGE2 also mediates fEEEEver & pain o Weibel-Palade Bodies also have vW factor APC B7 → CD28 on CD4+ T cell (mnemonic: 28/7 = 4)
• E-selectin – induced by TNF & IL-1 Activated CD4+ T-cells secrete cytokines → help B-cells or CD8+ T-cells
5-lipooxygenase LTB4 – attracts/activates PMN
Selectins bind Sialyl-Lewis X on WBC → interaction slows down WBC • Th1 – help CD8+
• (!) (things that attract PMN – LTB4, C5a, IL-8, bacterial products) Step 3 Binding of WBC to vessel wall o IL-2 – T-cell growth factor & CD8+ T cell activator
LTC4, LTD4, LTE4 – contract smooth muscles Adhesion Endothelium: TNF & IL-1 → ↑ Cellular Adhesion Molecules (ICAM & VCAM) o IFN-y – Mφ activator
• mediate vasoconstriction, WBC: C5a & LTB4 → ↑ integrins • Th2 – helps B-cells
• bronchospasm, CAMs & Integrins interact → firm adhesion o IL-4 – class switching to IgG & IgE
• ↑ vascular permeability (!) Leukocyte Adhesion Deficiency – AR defect of integrins CD18 subunit o IL-5 – eosinophil chemotaxis & activation/maturation of
Mast Cells Widely distributed throughout CT • delayed separation of umbilical cord, B-cell → plasma cell & class switching to IgA
• ↑ circulaSng PMN - ↓ marginated PMN in lungs → ↑ in blood o IL-10 – inhibits Th1 phenotype
(!) Activated by
• recurrent infections that lack pus formation CD8+ activation INTRACELLULAR antigens processed & presented on MHC-I
• Tissue Trauma
Step 4 WBC transmigrate across endothelium of postcapillary venules IL-2 from CD4+ Th1 cells provides 2ndary activation signal
• Complement (C3a & C5a) Chemotaxis Chemotaxis towards IL-8, LTB4, C5a, & bacterial products Activated CD8+ → kill cells with Ag of choice of MHC
• Cross-linking of cell-surface IgE by an antigen Step 5 Consumption of pathogens or necrotic tissue • Secretion of Perforins & Granzymes → induce Apoptosis (caspase)
Immediate Response Phagocytosis Enhanced by opsonins (IgG & C3b) • Expression of FasL → bind Fas on target cells → activated apoptosis
• Release preformed histamine granule → Pseudopods from leukocytes extend → form phagosomes B-lymphocytes Immature B-cell produced in marrow
• Arterial vasodilation & ↑ postcapillary venule vascular perm Phagosomes internalized → merge w lysosomes → form phagolysosomes → undergo Ig rearrangement to become naïve B-cell w IgM & IgD
Chediak-Higashi Syndrome – AR B-cell Activation 1.Ag binds surface IgM (or IgD) → become IgM secreting plasma cell
Delayed Response
• protein trafficking defect (↓ microtubules for movement) 2.B-cell Ag presentation to CD4+ via MHC II
• Produce arachidonic acid metabolites → especially LTs • ↑ risk of pyogenic infecSon, neutropenia, giant granules in leukocytes • CD40-r on B-cell binds CD40L on helper T-cell → 2nd activation signal
Complement Proinflammatory serum proteins that “complement” inflammation • Defective primary hemostatsis, albinism, peripheral neuropathy • IL-4 & IL-5 from T-cell → B-cell isotype switch, mutation, & maturation
Circulate as inactive precursors → must be activated by various pathways Step 6 O2-depended killing – MOST effective o Now produces IgM, IgD, IgG, IgA
Classic Pathway: C1 binds to IgG or IgM that is bound to antigen Detruction •
 
  
  
 Granulomatous Subtype of chronic inflammation
• “GM makes classic cars” Phagocytosed

  
   
 
Inflammation Granuloma
Alternative pathway – microbial products directly activate complement • HOCl generated by oxidative burst in phagolysosome
material • (!) Epitheloid histiocytes – Mφ w abundant pink cytoplasm = DEFINING
Chronic Granulomatous Disease
Mannose-binding Lectin Pathway(MBL) – MBL binds mannose on microorganism → • Other optional features Surrounded by giant cells & rim of lymphocytes
bound MBL activates complement • ↓ O2 depended killing due to ∆ NADPH oxidase (X-linked or AR)
• Cat+ organisms – • Subtypes → Caseating & Non-caseating
Result of all 3 pathways
o S.aureus, • (!) Pseudomonas cepacia Noncaseating ∅ central necrosis
• C3 convertase generated : C3 → C3a & C3b
o S marcescens, • Nocardia, • Aspergillus granuloma • rxn to foreign material • Sarcoidosis • Beryllium
• C5 convertase generated : C5 → C5a & C5b
• Nitroblue Tetrazolium Test – (NBT Test) - tests NAPDH oxidase • Crohns dz • Cat Scratch Dz – stellate shaped
• C5b joints C6-C9 → formation of Membrane Attack Complex (MAC)
o If reaction is intact → dye will turn blue Caseating Central Necrosis
Key Products of complement
o If ∅ reaction (CGD) → dye will stay clear Granuloma • (!) TB & Fungal infection → AFB stain for TB & GMS (silver) stain for
• C3a & C5a – trigger mast cell degranulation
MPO deficiency – usually asymptomatic, but ↑ risk Candida infecSons, normal NBT fungi
• C5a – chemotactic for PMN
O2 – independent killing – less effect Granuloma Mφ → present Ag via MHC-II to CD4+
• C3b – opsonin for phagocytosis
• Occur via enzymes in leukocyte 2ndary granules formation Mφ secreted IL-12 → induce CD4+ into Th1 subtype
• MAC – lyses microbes by creating holes in cell membrane
• Lysozyme • Major Basic Protein (both types) Th1 cells secrete IFN-y → converts Mφ to Epithelioid Histiocytes
 5
Ch 2.4 Primary Immunodeficiency
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
DiGeorge Failure of development of 3rd & 4th pharyngeal pouch 22q11 microdeletion T-cell deficiency ( ∅ thymus) → ↓ immune to virus Cardiac Abnormality (especially tetralogy of Fallot)
Hypocalcemia (∅ parathyroids) Abnormal facies
Abnormal heart, great vessels & face Thymic aplasia Chromosome 22
Cleft palate
Hypocalcemia.
SCID Defective cell-mediated & humoral immunity CK-receptor defects ↑ susceptibility to fungal, viral, bacterial & protozoal infection Sterile isolation – Bubble Boy
“severe combined” (!) Adenosine deaminase deficiency Stem cell transplant
• Build up adenosine→ toxic to lymphocyte ↑ opportunisSc infecSons • Generate normal T & B cells
MHC Class II deficiency ∅ give live vaccines
• CD4+ ∅ able to activate → ↓ B-cell & T-cell function
X-linked Lack of immunoglobulins X-linked mutation @ BTK ↑ presentaSon a\er 6 months of life (a\er moms Abs gone) <The Brute Tyrant on the X chromosome takes
agammaglobulinemia Disordered B-cell maturation • Bruton Tyrosine Kinase (!) ↑ recurrent bacterial, enterovirus & Giardia infections away your Ab’s>
Naïve B-cell ∅ able to mature to Plasma Cell Avoid Live vaccines

CVID ↓ immunoglobulin bc B-cell or helper T cell defect Present late in childhood

“common variable” ↑ bacterial, enterovirus & Giardia infections
(!) ↑ risk for autoimmune dz & lymphoma
IgA deficiency Low serum & mucosal IgA ↑ risk for mucosal infecSons (esp viral) <IgA in musosA>
Hyper-IgM syndrome Elevated IgM Mutated CD40L or CD40-receptor Recurrent pyogenic infections
↓↓ IgA, IgG, IgE  ∅ IL-4 or IL-5→ ∅ class switching of B-cell Mucosal infections
Wiskott Aldrich X-liked mutation in WASP Thrombocytopenia – bleeding, petechiae
Eczema
Recurrent infections (↓ humoral & cellular immunity)
Complement ↓ C5b-C8 → ↑ risk for Neisseria infecSon <you better complement neiserria 5 to 9 times, or
Deficiency ↓ C1 inhibitor – hereditary angioedema of skin & mucosa it will infect you>
• Periorbital edema is classic finding <C1- – if you see (some) one w periorbit edema>
Ch 2.5 Autoimmune Loss of self-tolerance ↑ in women, esp @ childbearing age
Disorders • ∅ apoptosis of self-reactive lymphocyte Environmental triggers in genetically susceptible individual
General • Self-reactive lymphocytes ∅ anergic ↑ incidence in twins & association w certain HLA subtypes
Name Desc Cause Clinical Patho Dx/Tx
SLE Systemic autoimmune dz Type II (Cytotoxic) hypersensitivity Fever & weight loss ANA ANA – sensitivity test - screening
Antibodies vs host → damage multiple tissue Type III (Ag-Ab complex) Hypersensitivity Malar “butterfly” rash w photosensitivity Anti-dsDNA Anti-dsDNA – specific test
Arthritis Pleuritis & pericarditis CNS psychosis Anti-Smith → core protein of snRNPs
Renal damage – common cause of death in SLE Antiphospholipid Syndrome – associated w SLE
• (!) Diffuse Proliferative GN = most common -antibody against proteins bound to phospholipids (Note:
• Can have other lesions -anticardiolipin → false+ for syphilis AntiHISTONE Ab = drug-induced SLE
Heart – can affect any layers -lupus anticoagulant – falsely elevated PTT Drugs: Hydralazine, procainamide, INH
• Endocarditis, Myocarditis, Pericarditis • Ptnt is actually hypercoagulable Tx: remove drug
• Libman-Sacks endocarditis – vegetations on both • DVT • Stroke
sides of valves <”Leaflet stacks” on both sides> • Hepatic Vein thrombosis – budd chairi
Anemia, TCP, Leukopenia – ↓ blood products • Placental thrombosis → loose babies
• Infections – common cause of death • Tx: Lifelong anticoagulation
Sjogren Snydrome Autoimmune destruction of lacrimal & salivary gland Dry eyes → “dirt in my eyes” ANA
Dry mouth → “can’t chew a cracker” Anti-Ribonucleoprotein antibody <Sjogren = “Stoner”
Recurrent dental carries • Anti-SS-Α • Anti-SS-B • Dry eyes, cotton mouth
Associated w other AI dz – esp RA • Dental carries – from junk food
(!) ↑ risk for B-cell lymphoma – UNILATERAL enlargement of • Anti Studying Stuff to get an A or B
parotid late in disease course • B-lymphoma – Bowl, Brownies>
Scleroderma Autoimmune activation of fibroblasts Diffuse – skin & visceral involvement Diffuse -
Collagen deposition into skin • Esophagus commonly affected → dysphagia Anti-DNA topoisomerase I antibody (Scl-70)
Localized Scleroderma → CREST syndrome Localized
• Calcinosis & anti-Centromere Anti-centromere antibody
• Raynaud’s
• Esophageal dysmotility
• Sclerodactyly
• Telangiectasias of skin
Mixed CT disease Mixed – features of SLE, scleroderma, polymyositis U1-ribonucleoprotein antibody
 6
Ch 2.6 Wound Healing Ch 3.1 Neoplasia
General Healing is initiated when inflammation begins General Neoplasia - New tissue growth that is unregulated, irreversible & monoclonal
Combination of Regeneration & Repair (scar) • Monoclonal = neoplastic cells are derived from a single mother cell
Regeneration Replace damaged tissue with native tissue Clonality (!) Can be determined by G6P-DH enzyme isoforms
Depends on regenerative capacity of tissue → 3 types of capacity • Multiple isoforms exist (G6PDA,G6PDB, G6PDC, etc)
1.Labile Tissues – constantly cycle tissues, stem cells in tissue • 1 isoform inherited from each parent onto X- chromosome
• Bowel/crypts, skin/basal layer, marrow/hematopoietic stem cell (CD34) o In females → 1 isoform is inactivated by Lyonization
2.Stable Tissues – quiescent but can renter cell cycle • Normal ratio of active forms is 1:1 (50% of each isoform)
• Liver – compensatory hyperplasia after partial resection o Hyperplasia is Polyclonal → 1:1 ratio maintained
• Proximal Renal Tubule – o Neoplasia is monoclonal → ∆ ratio of isoforms
3.Permanent Tissues – lack significant regenerative potential → repair w fibrous scar Clonality can also be determined by adregen-r isoforms (also on X chromosome)
• Myocardium • Skeletal m.m • Neurons (!) Clonality of B-lymphocyte determined by immunoglobulin (Ig) light chain phenotype
Repair permanent tissues & trauma/lesion that removes stem cells • Each B cell has light chain→ either • κappa or • lambda
Granulation Tissues = initial phase of repair • Normal κappa::lambda ratio = 3:1
Eventually Type III collagen replaced w Type I collagen o Reactive Hyperplasia (Polyclonal) → ratio maintained
• (!) Collagenase removes Type III collagen & requires Zn co-factor o (!) Lymphoma (monoclonal) → ratio reverses & is 6:1
Mediated by paracrine signaling via growth factors
κappa::lambda ratio = 1:6 → lambda:: κappa ratio = 6:1
• Factors bind receptors → ∆ gene expression & cellular growth Neoplastic Remember: both types are monoclonal!
• TGFα – epithelial & fibroblast growth factor Tumor Benign Tumors – remain locations → ∅ mets
• TGFβ – fibroblast growth factor, inhibit inflammation
Malignant Tumors (cancer)– invade locally & have potential to mets
• Platelet Derived GF – endothelium , smooth m.m, & fibroblast growth
Tumor Lineage Benign Malignant
• Fibroblast GF – angiogenesis, skeletal development
• VEGF – angiogenesis Nomenclature Epithelium Adenoma - glands Adenocarinoma – glands
Granulation Fibroblasts → deposit Type III collagen Papilloma – fingerlike Papillary Carcinoma – fingerlike (Epithelium, CT core, vessel)
Tissues Capillaries – provide nutrients Mesencyhme Lipoma, Osteoma, etc Liposarcoma, Osteosarcoma, etc
Myofibroblast – contract wound Lymphocyte ∅ exist Lymphoma/Leukemia
Cutaneous Primary Intention – wound edges brought together → minimal scar Melanocyte Nevus (mole) Melanoma – mass of cells
Healing Secondary intention – edges ∅ approximated → granulation tissue fills in defect Epidemiology Cancer is #2 cause of death in both adult & children
• Myofibroblast → can cause retraction of wound/scar • Adults 1) Cardiovascular Dz 2) Cancer 3) Cerebrovascular Dz
Delayed Wound Infection – most common cause • Children 1) Accidents 2) Cancers 3) Congenital Defect
Healing ↓ Vit C - ↓ hydroxylation of Proline or Lycine → ∅ pro-collagen cross-linking Most common cancers in adults (excluding skin)
↓ Cu - ↓ Lysyl oxidase → ∅ crosslinking of collagens Most common (by Incidence) Mortality (# deaths)
Zn deficiency - ↓ Collagenase → ∅ able replace Type III → Type I 1. Breast/Prostate 1. Lung – ∅ really good screen
Other: foreign body, ischemia, DM, malnutrition 2. Lung 2. Breast/Prostate – mammogram, PSA
Dehiscence Rupture of wound 3. Colorectal 3. Colorectal - colonscopy
Most commonly seen @ abdominal surgery Screening Cancer starts as single cell
Hypertrophic Scar Scar is in excess of the wound (!) 30 divisions needed before earliest symptoms arise
Type I • Every division → increased mutations
Keloid Excess scar tissue way out of proportion to wound • Cancers that are detected late have a poorer prognosis
Type III collagen Goal of Screening
↑ in African Americans • Catch dysplasia before it becomes carcinoma
↑ @ earlobes, face & upper extremity +6 • Detect carcinoma before clinical symptoms arise
Pap smear – identify cervical dysplasia (Cervical Intraepithelial Neoplasia or CIN) before it becomes carcinoma
Mammography – detect breast cancer before clinical symtpoms
• Ductal Carcinoma in Situ – pick it up before tissue invades → Look for calcifications
• Average size when detected by patient 2 cm Average size when detected by mammography = 1 cm
PSA & DRE
• Prostate cancer tends to grow @ posterior peripheral prostate (∅ urinary symptoms till late)
• (remember BPH is periurethral→ urinary symptoms)
Hemoccult Test & Colonoscopy → Colonic adenoma before it becomes carcinoma or carcinoma before it spreads
 7
3.2 Carcinogenesis -
Chemicals 3.2 – part 2 Carcinogenesis 2
Carcinogenic Agent Associated Cancer Comments Carcinogens → DNA DNA mutations → disruptied regulatory systems
Aflatoxin Hepatocellular Carcinoma Derive from Aspergillus → contaminates grains mutations 1.Protoncogenes
Alkylating Agents Leukemia/Lymphoma Side effect of chemotherapy 2. Tumor Surpressor Genes
Alcohol Squamous Cell carcinoma of oropharynx 3.Regulators of Apoptosis
Squamous Cell carcinoma of upper esophagus Proto-oncogenes Essential for cell growth & differentiations
Pancreatic carcinoma Mutation of proto-oncogene → Onco-gene → unregulated growth
Hepatocellular carcinoma Categories of proto- oncogenes
Arsenic Squamous Cell Carcinoma of Skin Arsenic also present in cig smoke • Growth Factors • Growth Factor Receptors
Lung Cancer • Signal Transducers • Nuclear Regulator • Cell Cycle Regulator
Angiosarcoma of Live Genes
Asbestos Lung Cancer (!) more likely to get lung cancer than Function Mechanism Tumor
Mesothelima mesothelioma Growth Factors
Cig Smoke Carcinoma of Oropharynx & Esophagus Most common carcinogen worldwide PDGFB Platelet-Derived Growth Factor ↑ PDGF expression → ↑ astrocyte divisions Astrocytoma
Lung Cancer (Squamous Cell & Small Cell) (!) Polycyclic hydrocarbon – most important • Autocrine loop (cell signals self)
Kidney & Bladder cancer carcinogen in cig smoke
Growth Factor Receptors
Nitrosamines Stomach carcinoma (intestinal type) ↑ in smoked food → ↑ in Japan
Her2/neu Epidermal Growth Factor Receptor Ampliation Subset of breast cancers
Naphthylamine Urothelial Carcinoma of bladder Derived from cig smoke ERBB2 • trastuzumab
Vinyl Chloride Angiosarcoma of Liver Occupational Exposure RET Neural Growth factor receptor Point mutation Medullary Carcinoma of Thyroid
Used to make PVC pipes
• MEN 2A & 2B
Nickel, Chromium, Lung cancer Occupational exposures
KIT Stem cell growth factor receptor Point Mutation Gastrointestinal Stromal Tumor
Beryllium, Silica
Signal Transducers
Oncogenic Viruses
RAS gene family GTP-binding protein Point mutation Carcinoma,
Bug Associated Cancer Comments
RAS-GTP → work @ nucleus . RAS can normally inactivate GTP melanoma,
EBV Nasopharyngeal Carcinoma – Asians, male Presents as neck mass → mets to regional LN • ∆ GAS lymphoma
Burkitt Lymphoma – in Africa
ABL Tyrosine Kinase t(9:22) with BCR CML & some types of ALL (adult ALL)
CNS lymphoma in AIDS
• Philadelphia chromosome (Ph+)
HHV-8 Kaposi Sarcoma -Eastern Europeans Male→ excise to treat
Nuclear Regulators
• Tumor of endothelial cells -AIDS patients → Anti-Retroviral (HAART)
c-MYC Transcription factor t(8:14) involving IgH Burkitt lymphoma
-Transplants → ↓ immunosuppressive drugs
• Immunoglobulin heavy chain
HBV & HCV Hepatocellular Carcinoma
coded on Chrm 14
HTLV-1 Adult T-cell leukemia/lymphoma
N-MYC Transcription factor Amplification Neuroblastoma
HPV 16, 18, 31,33 SCC of vulva vagina, anus, cervix
L-MYC Transcription factor Amplification Lung Small Cell Carcinoma
Adenocarcinoma of Cervix
Cell Cycle Regulator
Radiation
CCND1 (cyclin D1) Cyclin t(11:14) involving IgH Mantle cell lymphoma
Type Associated Cancer Comments
• G1 phase → S phase • Expansion of LN mantle
Ionizing Papillary Carcinoma of Tyroid Radiation → Hydroxyl free radicals
CDK4 Cyclin-Dependent Kinase Ampliation Melanoma
(Nuclear Reactors) AML
CML
Non-Ionizing Basal Cell Carcinoma of skin Form pyrimidine dimers in DNA
(UVB sunlight) SCC of skin Normally excised by restriction endonuclease
Melanoma of skin • Xeroderma Pigmentosum
 8
3.2 – part 3 – Carcinogenesis (Part 3) 3.3 Tumor Progression 3.4 Clinical Characterisics of Cancer
Tumor Regulate cell growth Tumor Invasion Accumulate mutations Tumor Benign Malignant
Suppressor • P53 • Invasion • spread Characteristics Slow Growing Rapid growing
Genes • Rb Characteristics to ↓ regulation of E-cadherin Well Circumscribed Poorly circumscribed
p53 Regulates G1 → S phase ↑ spread Distinct Infiltrative
• p53 examines DNA E-cadherin Normally: keep epithelial cells attached to each other Mobile Fixed to surrounding tissue
DNA injured → p53 triggers DNA repair mechanism Tumors need to be able to dissociate from neighbors Biopsy/Excision Required to classify a tumor w certainty
↑↑↑ mutations → p53 triggers BAX → BAX destroys BCL2 • ↓ regulated E-cadherin Histo Features Benign Malignant
• BCL2 normally stabilizes mitochondrial membrane dissociated Tumor cell will bind to Laminin in BM Differentiated ↓ differentiation
• ↓ BCL2 → Cytochrome C release → Caspases → Apoptosis • Eventually destroy BM via Collagenase IV→ spread to ECM Organized Growth Disorganized growth
Both copies of p53 must be knocked out for tumor formation In ECM → bind to Fibronectin → local spread → lymph or blood Uniform Nuclei Nuclear pleomorphism w hyperchromasia
• “Knudson’s Two-Hit Hypothesis” Lymph Spread (!) Carcinoma → Lymphatic Spread Low Nuclear/Cytoplasm ratio High nuclear to cytoplasmic ratio
• Loss is seen in >50% of cancer (Carcinoma) • Initial Spread: Regional draining lymph nodes Minimal mitotic activity High mitotic activity
Li-Fraumeni Syndrome – germline mutation → 1 bad copy of p53 ∅ invasion Invasion
Heme spread (!) Sarcomas → Hematogenous Spread (and some carcinomas)
• ↑ risk of carcinomas & sarcomas ∅ metastatic potential (!) Metastatic potential = hallmark
(Sarcomas) • Characteristic spread to lungs
Rb Hematogenous spreading Carcinomas Immuno-Histo- Useful to characterize malignant tumors that are difficult to classify histologically
Regulates G1→S
• Renal Cell Carcinoma → Renal Vein → mets Chemistry
(retinoblastoma) • Rb normally binds E2F
• Hepatocellular Carcinoma → Hepatic vein → mets Intermediate Filaments
• Phosphorylate Rb → release E2F → cell cycle progression
o Phos by CyclinD/CD4 complex • Follicular Carcinoma of Thyroid Keratin Epithelium → carcinoma
↓ Rb → ↑ free E2F → uncontrolled progression of cell cycle • Choriocarcinoma (placenta, Trophoblast) Vimentin Mesenchyme → sarcoma
Both Rb must be damaged (Two Hit Hypothesis) Seeding of Body (!) Ovarian Carcinoma Desmin Muscle Cell
• Sporadic mutation → Unilateral Retinoblastoma Cavities • Seed to omentum → “Omental Caking” GFAP Neuroglia
• Germline Mutation → Bilateral Retinoblastoma + Neurofilament Neurons
Osteosarcoma Other
Regulators of Prevent apoptosis in normal cell, promote apoptosis in mutated cells PSA Prostate
Apoptosis • BCL2 Estrogen R Breast epithelium
BCL2 Stabilizes mitochondrial membrane → prevent cytochrome c Thyroglobulin Tyroid Follicular cell
Overexpressed in Follicular Lymphoma Chromogranin Neuroendocrine cells
• t(14,18) moves BCL (18) → IgH locus (14) • Small cell carcinoma of Lung – worst differentiated neuroendocrine
• ↑ BCL2 expression in B-cell → ∅ apoptosis in B-cell in follicle • Carcinoid Tumor – best differentiated neuroendocrine
Other important regulators S-100 Melanoma
Telomerase Necessary enzyme for cell immortality Serum Tumor Proteins released by tumor
Normal: telomere shortening w cell divisions → senescence Markers • 1.screening,
Cancers – upregulated telomerase → preserves telomeres • 2.monitors Tx response,
Angiogenesis FGF & VEGF – commonly produces by tumor cells • 3.monitor recurrence
Avoiding Tumor cells evade immune response by ↓ expression of MHC I ∅ used for diagnosis → Tissue Biopsy needed for dx
Immune • Immunodeficiency → ↑ cancer risk Grading of Look @ architectural & nuclear features
Surveillance Cancer Well differentiated -resembles parent tissue→ better prognosis
Poorly differentiated - ∅ resemble parent tissue → worse prognosis
Staging of Based on Size & Spread
Cancer (!) Staging is key prognostic factor (more important than Grading)
Final staging is determined after resection of tumor
TNM
• Tumor – size & depth of invasions (tubular organs)
• Nodes – spread to regional lymph nodes - #2 prognostic factor
• Metastasis – (!) most important prognostic factor
 9
Ch 4.1 – Primary Hemostasis
Intro Blood vessels Hemostasis = Repair to damage wall of vessel Primary Hemostasis – goal is to form a weak Platelet Plug 2ndary Hemostasis – goal is to stabilize platelet
• Endothelial cells on a BM • Forms a Thrombus/Clot Mediated by coagulation cascade
• Mediated by endothelium/platelet
1° Hemostasis
1. Transient caused by: 2. vWF binds Platelet Adhesion: Platelet - GPIb –binds to→ vWF 3.Platelet Adhesion to vWF → platelet shape change → dumping of mediators 4 Platelet Aggregation via GP2b3a
Vasoconstriction • Neural stimulation/reflex subendothelial vWF comes from Degranulation Mediators Aggregation (!) Fribinogen = linking molecule
of damaged • Endothelial cells release Endothelin → collagen → vWF • endothelial cells → Weibel-Palade bodies • ADP – induces platelets to express GP2II/IIIa End Result – Weak Platelet Plug
vessels vasoconstriction links to platelets • Platelet α granules o GP2II/IIIa is important for aggregation (step 4)
Weibel-Palade bodies - in endothelial cells hold vWF Factor • Thromboxane A2 – derived from platelet cox
• vWF factor both stored in WP bodies promotes aggregation
• P-selectin

Name Desc Cause Clinical Labs/Dx Tx & Notes

Disorders of 1° • Abnormality in platelet Mucosal Bleed Labs o
hemostasis (general) • quantitative • (!) Epistaxis • Hemoptysis • Platelet Count (Normal: 150k-
• Qualitative • GI Bleed 400k)
• Hematuria • Menorrhagia • Bleeding Time (Normal 2-7 min)
• (!) complication @ severe TCP → Intracranial bleed • Blood Smear
Skin Bleed o # of platelets
• Petechiae – sign of TCP (↓ quantity) o Size of plateles
o ∅ seen w qualitative disorder • Bone Marrow Biopsy
• Ecchymoses • Purpura Megakarytocytes
• Easy Bruising
ITP (!) most common cause of TCP in childrens & adult Autoimmune IgG → platelet antigens Thrombocytopenia Corticosteroid
Acute Form – Children • eg. IgG against Gp2b3a • Platelets <50k/uL • Children respond well
• TCP weeks after vial infection or immunization Spleen → Plasma Cells → Antibodies Normal PT • Adults – respond but often relapse
• (!) self-lmiting – resolves in few weeks Ab-covered platelets travel to spleen Normal PTT IVIG - can raise platelet count in symptomatic
Chronic Form – Adults → consumed by splenic macrophages Hyperplasia of Megakarytocytes @ Biospy bleeding
• ↑ in women of childbearing age • Slpeenic Mφ focuses on consuming
o IgG can cross placenta and cause short IVIG
period of TCP in offspring • Short period of ↑ platelets
• Primary – cause unknown Splenectomy
• 2ndary – associated w SLE, others • (!) Elimate site of Antibody
• (!) Eliminate site of destruction
Microangiopathic Pathological formation of platelets microthrombi in small RBC crossing across Platelet Microtrhombi gets sheared <pic of schistocyte>
Hemloytic Anemia vessels • Hemolysis → Schistocytes 2 points at both end
• Causing Hemolytic Anemia Platelets are consumed in formation of microthrombi • Look like “helmet cell”
2 classic disorders → TTP& HUS
Thrombotic Microthrombi due to ↓ ADAMSTS13 Plasmapharesis – remove autoAb against ADAMS
Thrombocytopenic • Genetic Deficiency Corticosteroid - ↓ autoAb production
Pupura • Autoantibody to ADAMSTS13 in adult female Skin & Mucosal Bleeding TCP w ↑ bleeding time
ADAMSTS13 normally chop up polymeric vWF precursor Microangiopathic Hemolytic Anemia Normal PT/PTT
∆ platelet adhesion Fever Anemia w Schedistocytes
Hemolytic endothelial damage by drugs or infection Renal Insufficiency – predominant in HUS ↑ megakaryocytes @ bone marrow biopsy
Uremic Platelet microthrombi formed CNS Abnormalities – predominant in TTP
Syndrome • E Coli 0157:H7 (EHEC)→ Verotoxin
• Verotoxin damages endothelial cell
• Undercooked beef → Dysentery
Bernard-Soulier Genetic GP1b deficiency → ↓ platelet adhesion Bleed Mild TCP – platelets destroyed earlier (Big Suckers (platelets) in Bernard Soulier)
Syndrome Enlarged Platelet
Glanzmann Genetic GpIIb/IIIa deficiency Glands often come in two or 3s
Thrombasthenia • ↓ platelet aggregation • Gp 2 or 3
ASA ASA irreversibly inactivates COX
• ↓ TXA2 → impaired platelet aggregation
Uremia ↓ kidney → buildup of nitrogenous waste products
• ∆ platelet Adhesion & Aggregation
 10
4.2 2ndary Hemostasis – goal is strengthen plug w Coagulation Cascade
Name Desc Cause Clinical Labs/Dx Tx & Notes
2ndary Hemostasis Stabilizes weak plug via Coagulation Cascade Factors of Cascade are produced by Liver→ produced in an Inactive state <Coagulation Cascade> PT – extrinsic & common pathway
• Coagulation cascade → thrombin → Activation of Factors requires 12 – activated by subendothelial collagen • Best for monitoring wafrain dose
fibrinogen2fibrin → fibrin cross linked • Exposure to Activating Substance – 11 Intrinsic PTT – intrinsic & common pathway
o Tissue Thromboplastin 9 7 – activated by tissue thromboplastin • The side with more numbers
→ activate Factor VII (extrinsic) 8 Extrinsic • Best for monitoring HEParin dose
o Subendothelial Collage X o <“HEP” is clinic slang for heparin
→ activate Factor XII (intrinsic) 5→2→1 and has 3 letters, like PTT>
• Phospholipid Surface of Platelet
• Calcium
Disorder of 2ndary usually due to Factor Abnormalities Deep Tissue Bleeding → into muscle & joints PT – extrinsic & common pathway
Hemostasis Rebleeding after Sx procedures PTT – intrinsic & common pathway
Hemophilia A Factor VIII Deficiency <call it Hemophilia 8> Deep tissue, Joint bleeding ↑ PTT Recombinant Factor VIII
Xlinked-Rec → ↑ in Males Postsurgical Bleed Normal PT
Can arise from de novo mutation without family hx ↓ Factor VIII
Normal Platelet Count & Bleeding Time
Normal PTT @ mixing study (vs Factor Inhibitor)
Hemophilia B <B for Bear Factor IX deficiency Deep tissue, Joint bleeding ↑ PTT
“Christmas Dz” • Santa bear → Christmas Postsurgical Bleed Normal PT
• Deep bleeds from bear ↓ Factor IX
bites Normal Platelet Count & Bleeding Time
Coagulation Factor Antibody against coagulation factor Deep tissue, Joint bleeding Same as Hemophilia A except…
Inhibitor • Anti-Factor VIII is most common → similar to hemophilia A Postsurgical Bleed (!) ↑ PTT in Mixing Study (vs Hemophelia A)
vonWillibrand Dz Most common inherited coagulation disorder Genetic vWF deficiency - many reasons exist (qualitative & quantitate) Mild mucosal & skin bleeding ↑ bleeding time – poor platelet adhesion (!) Demopressin
Autosomal Dominat w ↓ vWF - Most common type ↑ PTT – vWF needed to stabilize factor VIII • ↑ vWF release from
• Not severe enough for clinical signs Weibel-Palade bodes of
Normal PT endothelium
(!) Abnormal Ristocetin test – platelets ∅ aggregate
Vit K Deficiency Dirupts multiple coagulation factors
<Vit K epoxide normally activates Vit K in liver Deficiency in ↓ gut flora
Vit K → Gamma Carboylate 2, 7, 9, 10, C, S> • Newborns • Long-term antibiotic
• Malaborption – Vit A,E,D, & K are fat soluble
Liver Failure ↓ coagulation factors Measure liver failure effect by monitoring
↓ activation of Vit K by epoxide reductase • PT
Large Volume Dilutes coagulation factors → relative deficiency
Transfusion
4.3 Other Hemostatic Disorders
Heparin-Induced TCP Heparin forms complex w Platlet Factor 4 (PF4) Complication – platelet fragments ∅ give coumadin → ↑ risk of skin necrosis
• IgG antibody against Heparin-PF4 complex → activate more platelets → thrombosis Protamine Sulfate?
DIC Widespread microthrombi → ischemia & infarction Pathologic activation of coagulation cascade Ischemia & Infarction ↓ platelet coutn Tx underlying cause
Exhaustion of platelets & factors → bleed Microthrombi in vessel → ischemia & infarction Bleed ↑ PT & PTT Tx patient supportively
Consumption of platelets & factors → ↑ bleed @ IV sites & mucosa ↓ Fibrinogen • Blood products
Almost always 2ndary to some other dz Microangiopathic Hemolytic Anemia • Cryoprecipitate
• OB complication – aminiotic fluid w Thromboplasin • Thrombi sheer RBC → schitocytes
• Sepsis – endotoxin or Mφ → IL-1 & TNF (!) ↑ Fibrin Split Products (D-Dimer)
• Adenocarcinoma → mucin actiates • Best screening test for DIC
• Acute Promyelocytic Leukemia – granules/auer rod
• Rattlesnake Bite
Disorders of Plasmin overactivity → excessive cleavage of fibrinogen Resembles DIC ↑ PT & PTT Aminocaproic Acid
Fibrinolysis • ↓ coag factors, ↓ fibrinogen, ↓ platelet function ↑ Bleeding Time – w normal platelet coutn • Blocks Plasminogen activation
Plasmin ↑ fibrinogen split products
• cleaves linked fibrin AND cleaves serum fibrinogen • without D-dimer
• cleave factors • ∅ fibrin to split → only fibrinogen
• block platelet aggregation
α2-antiplasmin – normally inactivates plasmin
Examples
• Radical Prostatectomy – urokinase released→activate plasmin
• Cirrhosis of Liver - ↓ production of α2-antiplasmin
 11
4.4 – Thrombosis
Thrombosis Pathologic formation of an intravascular blood clot (!) 3 risk factors for Disruption in Blood Flow
Basic Principles • In artery or vein thrombosis Endothelial Cell Damage
• Most common location – Deep Vein of leg ((DVT) BELOW THE KNEE (Virchows Triad) Hypercoagulable State
Optional #4 – Iatrogenic – Dr Siew – “The Siew Quatrad”
Thrombus 1. lines of Zahn – alternating layers of RBC → platelet fibrin → RBC → Fibrin Disruption in Normal Stasis or turbulence
Characteristics 2. Attachment to Vessel Wall – Mural Thrombi Blood Flow Examples
• Immobilization – post-op
**remember to distinguish b/t post-mortem clot • Cardiac Wall Dysfunction –
→ ∅ lines of zahn or attachment o a-fib
o MI
• Aneurysm – stasis & turbulent flow in aneurysm

Name Desc Cause Clinical

Endothelial Cell Endothelium is normally protective against thrombosis Examples:
Damage • blocks exposure of subendothelial collagen • produces PGI2 • produces NO .Atherosclerosis,
• secretes Heparin-Like molecules → activate AntiThrombin-III → ↓ thrombin & coagulation factors .Vasculitis,
• secretes tPA → converts Plasminogen → Plasmin .↑ Homocysteine
o Plasmin works @ 1. Fibrin 2. Fibrinogen 3. ↓ Platelet Aggregation 4.Destroy Coag Factors • b12/folate deficiency
• Thrombomodulin – modulates Thrombin activity • CBS deficiency
o Normally: Thrombin ( Factor II) coverts Fibrinogen → Fibrin
o @ Thrombomodulin: Thrombin modulated → Activates Protein C

Protein C→ inactivate Factor V & VIII
B12 or Folate ↑ homocysteine Mildly elevated homocysteine levels
deficiency ∅ able to convert homocysteine → methionine
Cystathionine β ∅ able to convert homocysteine → cystathionine ↑ homocysteine → Homocystinuria
Synthase (CBS) • Vessel Thrombosis
Deficiency • Mental Retardation
• Lens Dislocation
• Long Slender Features
Hypercoagulable State ↑ Procoagulants and/or ↓ Anticoagulant Proteins Recurent DVT or DVT @ young age
Inherited or Acquired Other sites – Hepatic & Cerebral
Protein C or S Normal : Protein C & S → Inactivate Factor V & VIII (!) ↑ risk for Wafarin Skin Necrosis
deficiency ↓ Protein C & S → ↑ coagulation risk • Warfarin blocks Epoxide Reductase in Liver → ↓ activated Vit K
• ↓ 2,7,9,10,C,S activations
• Old factors start to degrade → C & S degrade first
→ ↑ risk of thrombus formation
Factor V Leiden Normal: C & S inactivate Factor V by cleaving it Mutated form of Factor V
Mutated form → ∅ able to be cleaved by C & S
Most common inherited cause of hypercoabule state
Prothrombin 20210A Inherited point mutation in Prothrombin
• ↑ gene expression → ↑ thrombus formation
AntiThrombin III ↓ protective effect of heparin-like molecules from Heparin @ standard does will ∅ have increased PTT
Deficiency endothelium → ↑ thrombus risk formation • ∅ antithrombin III to bind
Use high does of heparin → will bind what it can
.Coumadin given to maintain anticoagulated state → wean off heparin
OC E→ ↑ production of coagulation factors OC – Estrogen → ↑ production of coagulation factors
 12
4.5 Embolism
Embolism Intravascular Mass that travels → occludes downstream blood vessels
General ∆ symptoms depending on vessel involved
Most common cause (>95%) – Thromboembolism
Thromboembolism Thrombus dislodges
Atherosclerotic Embolus Plaque that dislodges
(!) Cholesterol Clefts in embolus

Fat Embolus Associated w bone fracture, trauma

Develops while fracture present or shortly after repair
(!) Dyspnea & Petechiae in skin overlyin chest
• Dyspnea bc fat emboli classically travel to lung

Gas Embolus Decompression sickness

• Scuba divers rapidly ascend → Nitrogen gas precipiates out of blood
• Join & Muscle Pain → “the bends”
• Respiratory Symptoms → “the chokes”
Caissons Dz – Chronic gas embolism
• Infarct bone → Multifocal Ischemic Necrosis of Bone
Laparoscopic Sx
• Air pumped into abdomen → some can get into vessels
Amniotic Fluid Embolus Amniotic fluid enters maternal circulation → Lung & CNS
↑ occurance @ delivery/labor
(!) Dyspnea, Neurological Symptoms,
(!) Amniotic Fluid has Thromboplastin → DIC
Squamous cells & Keratin debris (from fetal skin)

PE Usually due to Thromboembolism

DVT of lower extremity
• Femoral v • Iliac v •Popliteal v
Often clinically silent
• Lung has dual blood supply (Pulmonaries & Bronchioles)
• Most are small→ self-resolve & lyse
Pulmonary Infarction – only ~10% of PE cause infraction
Sudden Death – w massive eboli
o Large Saddle Embolus
o PEA
Pulmonary HTN – chronic emboli → reorganized over time
Pulmonary Infraction • Need Obstruction of large or medium sized arteries
• Need pre-existing cardiopulmonary compromise
• SOB, hemoptysis, pleuritic chest pain, pleural effusion
• V/Q mismatch → ↓ perfusion
• Spiral CT – vascular filling defect in lung
• CXR – hamptons hump
• Dopler US to lower extremity → identify DVT
• ↑ D-Dimer – remember this is not the best test
• Gross Specifimin: Hemorrhagic Wedge-Shaped Infarct
o Hemorrhage – 2nd blood supply entering loose tissue
Systemic Emboli Usually thromboembolism from L heart
Most common site of occlusion → Lower Extremities

CH 5 Red Blood Cell Disorders
Name Desc
Anemia ↓ circulating RBC mass
Microcytic Anemias MCV < 80
Iron Deficiency Most common anemia
Anemia Fe deficiency – most
common nutritional
deficiency in the world
Plummer-Vinson Fe deficiency anemia
Esophageal Web
Atrophic Glossitis
Anemia of Most common anemia in
Chronic Dz hospitalized patients
Sideroblastic ∆ protoporphyrin synthesis
Anemia
α thalassemia ↓ synthesis of globin chain
↑ in asians
β thalassemia ↓ synthesis of globin chain
Cause Clinical
Hypoxia
• Weakness • Fatigue • Dyspnea
Pale Conjunctiva & Skin
HA & Lightheadedness (hypoxia to CNS)
Anginal pains – especially if preexisting CAD
↓ Fe → ↓ Hb → microcytic anemia → Fe Deficiency Anemia Hemoglobin
Fe ∅ able to be utilized (Stored in Mφ) → Anemic Chronic Dz • Heme – Fe & Protoporphyrin
↓ Protoporphyrin → Sideroblastic Anemia • Globin
∆ ↓ Hb chains production → Thalassemia
Dietary lack or Blood loss Storage Fe depleted
Infants – breast feeding (breast milk has ↓ Fe) • ↓ Ferritin & ↑ TIBC
Children – poor diet • Liver is ↑ TIBC to try to get more Fe
Adults Serum Fe depleted
• Peptic Ulcer Dz (male) • ↓ serum iron & ↓ % saturation
• Menorrhagia/Pregnancy (female) Normocytic Anemia – initial stage of Fe anemia
Elderly – • BM initially ↓ RBC production
• colon polyps/carcinoma (Western World) Microcytic, hypochromic anemia
• Hookworms – Necator, Ancylostoma (3rd world) • ∅ able to make normal RBC
Malnutrition, Malabsorption, • ↓ size (extra division) hypochromic (↓ Hb)
Gastrectomy – acid convert Fe+3 → Fe+2 → Fe+2 inTO the body • Anemia
• Koilonychia – think, spoonshaped nails
• Pica – chew on dirt, ice
Anemia
Dysphagia
Beefy-Red Tongue
Chronic Disease or Cancer → inflammation Starts as normocytic → progress to Microcytic
Congenital
• Defect in ALAS (most common congenital cause)
o Rate limiting enzme
Acquired
• Alcoholism – mitochondrial poison → ↓ production
• Lead Poisoning – denature ALAD & ferrokelatase
• Vit B6 deficiency - ↓ ALAS
o INH can cause ↓ B6
Normally 4 α alleles present on Chromosome 16 1 gene deleted → asymptomatic
• Gene Deletion of 1→4 genes 2 genes deleted → Mild Anemia w slightly ↑ RBC count
Carriers are protected from Plasmodium falciparum malaria 3 genes deleted → Severe Anemia
4 genes deleted → Lethal in Utero (Hydrops fetalis)
2 β genes present on Chromosome 11 β thalassemia minor (β/β+) – mildest form of dz
+
• Gene Mutation → Absent β° or ↓ production β • Usually asymptomatic, ↑ RBC count
β thalassemia major (β° /β° ) – most severe form
. Severe anemia within a few months
. HbF is temporarily protective
. Massive Erythroid Hyperplasia
• Hematopoesis in skull & facial bones
• Extramedually hematopoesis → HSM
• Risk of Aplastic Crisis w Parvovirus B19
13
Patho & Pics Dx/Tx & Notes
Classify Anemia based on MCV (size of RBC) ∅ able to measure RBC mass
• Microcytic (MCV < 80) • use Hb, Hct, RBC count as surrogates
• Normocytic (MCV = 80-100) • concentration dependent –
• Macrocytic (MCV > 100) pregnancy, bleeds
Definition of Anemia
• M: Hb < 13.5 g/dL
• F: Hb < 12.5 g/dL
RBC formed from progenitor Erythroblast (EB) MCV < 80
large EB → divides many times → many small RBCs Serum Iron – measure Fe in blood
Microcytosis occurs due to an “extra” division TIBC – total # of transferrin (bound or unbound)
• Due to ↓ production of Hb % saturation - # bound transferrins (Normal =33%)
• RBC is trying to keep [Hb] ok → to keep the level of “pinkness” Serum Ferritin – measure amount Fe stored
constant RDW - red blood cell distribution width
FEP – free erythrocyte protoporphyrin
Heme-form – Meat → ↑ absorbed MCV < 80
∅ heme – Vegetable Hypochromic anemia
Absorption in duodenum @ enterocyte ↑ RDW – some normocytic, some microcytic
• Ferroportin –channel for Fe transfer from enterocyte ↓ ferritin → ↑ TIBC
→ blood (if needed) ↓ serum iron → ↓ % saturation
Fe is always bound – otherwise forms free radiacals ↑ FEP - ∅ Fe to bind protoporphyrin
• Transferrin (blood) –transported to→ Liver & BM Mφ →storage
• Ferratin (intracellular) – storage Tx
Microcytic, hypochromic anemia • Supplimental Iron (Ferrous Sulfate)
• Expandend center rof pallor • Tx underlying causes
o Colon Ca, bleeds, etc
Chronic Dz → Inflammation → ↑ Acute Phase Reactants (!) ↑ ferratin, ↓ TIBC
• Hepcidin → sequesters Fe in storage sites ↓ serum iron & ↓ % saturation
• Limit Fe transfer from Mφ to erythroid precursor ↑ FEP
• ↓ EPO production • Tx underlying cause - ↓ inflammation
<trying to hide Fe from bacteria> • Exogenous EPO – esp in cancer ptnt
Protoporphyrin synthesized by rxns in erythroblast Cytoplasm & Mitochondria Prussian Blue stain – stains Fe
1. succinyl CoA – ALA synthase (ALAS) → ALA
• Rate limiting step • Vit B6 cofactor (Fe loaded cell dies → iron leaks out)
2. ALA –ALA-D → porphobilinogen →→→ protoporphyrin ↑ ferritin, ↓ TIBC
Fe enters via Mφ → Erythroid precursor …. Fe → mitochondria ↑ serum iron, ↑ % saturation
Final:. Ferrochelatase – bind Fe & protoporphyrin – occurs in MITROCHONDIA
∅ protoporphyrin → Fe-loaded mitochondria in a ring around nucleus
• RINGED SIDEROBLST
↓ globin → ↓ Hb → microcytic anemia HbBarts seen on electrophoresis
2 genes deleted can be HbH seen on electrophoresis
• 2 on same side = cis-deletion
• ↑ risk of severe thalassemia in offspring. ↑ in Asian < HbF – α2γ2 HbA – α2β2 HbA2 – α2δ2>
• 2 on opposite sides = trans-deletion. ↑ in Africa
3 deleted: β chains form tetramer (HbH) → RBC damage
4- genes deleted - γ chain tetramer (Hb Barts) → RBC damage
↓ globin → ↓ Hb → microcytic anemia Crew Cut – skull xray
Thalasemia Minor – microcytic hypochromic RBC & target cells Chipmunk cheeks
• (!) ↑ HbA2
Thalsemia Major - α tetramers aggregate → RBC damage ↓ or –∅ HbA @ electrophoresis
• Ineffective erythropoieses • Extravascular hemolysis ↑ HbA2 & HbF
• Microcytic hymochromic target cells
• Nucleated RBCs Tx: Chronic Transfusions
• Side Fx: 2ndary Hemochromatosis
 14
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Macrocytic Anemia MCV > 100 Folate or B12 deficiency (Megaloblastic anemia) Megaloblastic anemia Megaloblastic Anemia → large cells (Less division occurs bc ↓ DNA precursors) MCV > 100
Other causes (Macrocytic, ∅ megaloblastic) • (!) Hypersegmented PMNs ( > 5 lobes)
• EtOH • Liver Dz • Drugs (5-FU) • Megaloblastic changes in all dividing cells (eg gut)
Folate Deficiency Poor Diet – alcoholics & elderly Glossitis Folate normally obtained from green veggie & some fruit MCV > 100
↑ Demand – pregnancy, cancer, hemolytic anemia • (!) Absorbed @ Jejunum Glossitis
Folate Antagonists (methotrexate→ ↓ DHF-R) • Minimal body stores → deficiency in months Hypersegmented PMN
↓ serum folate, ↑ serum homocysteine
Normal methylmalonic acid
Vit B12 Deficiency Pernicious Anemia – most common cause of B12 deficiency Glossitis B12 is complexed to animal-derived proteins → enters bound to protein MCV > 100
. Autoimmune destruction of parietal cells → ↓ IF Subacute Combined Degeneration of Spinal Cord B12 cleaved from protein → binds “R-binder” in mouth (salivary gland enzyme) Hypersegmented PMN
rarer causes • ∅ methylmalonic acid→succinyl CoA R-binder cleaved @ small bowel via Pancreatic proteases Glossitis
Pancreatic Insufficiency - ∅ proteases • Methylmalonic acid builds up in spinal B12 binds IF small bowel – (IF produced by parietal cells in stomach) Subacute Combined Degeneration of Spinal Cord
Ileum damage cord → ↓ myelin B12-IF absorbed @ Ileum ↓ serum B12, ↑ serum homocyteins
• Crohns dz Large hepatic stores → Years to develop deficiency
• Diphyllobothrium lactum (fish tapeworm) (!) ↑ methylmalonic acid
Rare with diet → large stores in liver
• only in Vegans
<parietal cells are the “P” cells>
• Pink • proton pump • pernicious anemia
 15
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Normocytic Anemia MCV 80-100 Peripheral RBC hemolysis Peripheral Reticulocytes – young RBC released from BM RCcorrected
• Extravascular – destroyed by RES • Anemia w good BM response (↑ retic) • Larger cells w bluish cytoplasm (RNA)
• Intravascular – destroyed in vessel Retic Count – (Normal = 1-2%)
Or • Anemia → Retic Count > 3%
Underproduction (RC < 3%) • Will be falsie elevated in anemia bc
↓ total RBC
• Correct by calculating
RCcorrected= RCmeasured*Hct/45
Normocytic Anemia RBC destruction by RES Anemia Mφ consume RBC → break down Hemogloblin
w predominant • Mφ of spleen, liver, & LN Splenomegaly • Globin → Amino Acids
Extravascular Jaundice – due to UC • Heme → Fe & Protoporphyrin
Hemolysis ↑ risk for bilirubin gallstones - CB • Protoporphyrin → UC bilirubin →
Marrow hyperplasia w RCcorrected > 3% UC binds albumin → liver→ CB → bile
Hereditary Inherited defect of cyto-skeleton membrane tethering proteins Splenomegaly – work hypertrophy ↓ central pallor (bc ∅ biconcave shape) Spherocytes w loss of central pallor
Spherocytosis • Spectrin • Ankyrin • Band 3.1 Jaundice – UC billiruben Range in size of cell - ∆ amount of membrane ↑ RDW
↓ tethering of → Blebs on RBC → blebs removed by spleen ↑ risk of bilirubin gallstones – CB • ↑ RDW (!) ↑ MCHC - ↑ Hb/cell
↓ amount of membrane → spherocyte (round) shape ↑ risk for aplastic crisis w Parvovirus B19 infection Osmotic Fragility Test-fragile in hypotonic solution
Eventually get stuck in splenic sinusoids → consumed by spleen Howell-Jolly bodies – extra fragment of DNA material Tx: Splenectomy
Also consumed RES • Normally removed by spleen • Anemia resolves
• Remain in RBC if asplenia • Spherocytes persist
• Howell-Jolly bodies on blood smear
Sickle Cell Anemia Gene carried by 10% of Africans AutoRec mutation of β chain of Hemoglobin ↑ risk of sickling HbS REVERSIBLY polymerizes when deoxygenated ↓ haptoglobin
• Protective against falciparum malaria • Glutamic Acid → Valine (hydrophilic → hydrophobic) • Hypoxemia • Dehydration • Acidosis • Aggregate to needle-like structure → Sickle Cells
2 abnormal genes → > 90% HbS in RBC → polymerize Anemia results in sickle cell formation Target Cells
Capsulated organisms – common death in SCA kids Jaundice – UC bilirubin • Target Cells Howell-Jolly Bodies - autosplenectomy
Acute Chest Syndrome – common death in SCA adult ↑ risk for bilirubin gallstones • Sickle→desickle every pass through body Crew cut X-Ray & chipmunk facies
Minimal amount of Intravascular hemolysis → ↓ haptoglobin • RBC membrane damage - ↓ flexible → Metabisulfite screen – causes sickling
Massive Erythroid Hyperplasia → expansion of skull/facial hemolysis HB electrophoresis
Extramedullary Hematopiesis w Hepatomegaly HbF protects against sickling • > 90% HbS, ∅ HbA
↑ risk for aplastic crisis w Parvovirus B19 infection • Protective for first months • Some HbF & HbA2
Dactylitis – swelling hands/feet due to infract of bones • SCA presents @ 6 months
• (!) common presenting sign in Infant (6 month) Irreversible Sickling Tx:
Autosplenectomy – shrunken/fibrotic spleen from infarcts • → vasocclusion → Infarcation of tissue • Hydroxyurea → ↑ HbF levels
• ↑ infect w encapsulated organisms → death
• ↑ Salmonella paratyphi osteomyelitis
Acute Chest Syndrome – occlusion in pulmonary circulation
• Chest pain, dyspnea, lung infiltrates
• Often precipitated by pneumonia
Pain Crisis – vasoocclusion anywhere
Renal Papillary Necrosis – gross hematuria & proteinuria
Sickle Cell Trait Gene carried by 10% of Africans 1 abnormal gene → HbA > HbS (< 50% HbS) Asymptomatic except @ renal medulla > 50% HbS needed to sickle → ∅ sickling except kidney ∅ sickle cells or target cells
Protective against falciparum malaria Renal Medulla - has hypoxia & Hypertonicity • renal medulla Metabisulfite screen – causes sickling
• Microinfraction → microscopic hematuria HB electrophoresis
• ↓ ability to concentrate urine • < 50% HbS, > 50% HbA
• Some HbF & HbA2

Hemoglobin C Less common than Sickle Cell Auto Rec mutation in β chain of hemoglobin Hb Crystals on blood smeer
• Glutamic Acid → Lysine (HbC has lyCEEine)
<HbC → LyCCCCine → Hb CCCrystals>
 16
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Normocytic Anemia MCV 80-100 Peripheral RBC hemolysis Peripheral Reticulocytes – young RBC released from BM RCcorrected
• Extravascular – destroyed by RES • Anemia w good BM response (↑ retic) • Larger cells w bluish cytoplasm (RNA)
• Intravascular – destroyed in vessel Retic Count – (Normal = 1-2%)
Or • Anemia → Retic Count > 3%
Underproduction (RC < 3%) • Will be falsie elevated in anemia bc
↓ total RBC
• Correct by calculating
RCcorrected= RCmeasured*Hct/45
Normocytic Anemia RBC destruction in Blood Vessel Hb released into blood → bound by Haptoglobin ↓ free serum haptoglobin
w Predominant • Hb passed directly into blood • Haptoglobin → Spleen to save Fe Hemoglobinemia
Intravascular ↑↑↑ Hb → Hemoglobinemia → Hemoglobinuria Hemoglobinuria
Hemolysis Hb→ renal tubule cell → binds hemosiderin→Cells Hemosiderinuria
slough into urine → Hemosiderinuria
Paroxysmal Acquired defect in myeloid stem cells → ↓ GPI Episodic Intravascular Hemolysis @ night RBC has membrane particles to inhibit complement Sucrose Test – activates C’ → RBC destruction
Nocturnal Thrombosis – main cause of death • ∅ GPi in RBC, platelets, or WBC Hemoglobinemia → Hemoglobinuria DAF (CD55) – decay accelerating factor Acidify Serum – confirmatory test
Hemoglobinuria • Cells susceptible to Complement destruction Hemosiderinuria – after a few days MIRL – membrane inhibitor of reactive lysis Flow Cytometry → detect lack of CD55 (DAF)
(PNH) Sleeping → ↓ breathing → mild acidosis → ↑ C’ activation Thrombosis – main cause of death DAF & MIRL anchored to membrane by GPI
• ↑ complement damage to cells @ night • Destroyed platelets → induce thrombosis
Complication
• Fe deficiency anemia
• AML – in 10% of patients
G-6-P DH deficiency X-Linked Recessive disorder → ↓ t½ of G6PD Oxidative Stresses GSH protects against oxidate stress in RBC Heinz Peperation → Heinz Bodies
• ↑ susceptibility to oxidative stress • Infections • H2O2 + GSH → GS-SG Bite Cells
(G6PD) African Variant – mild ↓ t ½ → only old cells affected • Drugs – primaquine, sulfa, dapsone GS-SG needs NADPH to returns to GSH Enzyme Studies confirm disease
Protective against falciparum malaria Mediterranean Variant - ↓↓↓ t ½ → younger cells affected • Fava Beans ∅ G6PD → ↓ NADPH → ↑ oxidative damage to RBC • Do enzyme studies after acute stress
Hemoglobunuria – hours after exposure to oxidative stress Precipitated Hb → Heinz Body
Back Pain – Hb is nephrotoxin Heinz Body removed by spleen → Bite Cells
Immune Hemolytic Antibody (IgG or IgM) destruction of RBC Coombs Test
Anemia -Direct – confirm presence of IgG-coated RBC
• test w Anti-IgG
-Indirect – confirm presence of serum IgG Ab
• Anti-IgG & test RBC mixed w serum
IgG IgG bind RBC in warm central body (Warm Agglutanin) Associated w SLE, CLL Spherocytes • ↓ take drugs
Ab coated RBC membrane consumed by splenic Mφ Drugs • Steroids
• Extravascular hemolysis Drug attach to RBC → Ab binds drug (PCN) • IVIG – delays RBC destruction
• Drug ↑ Ab production (Metyldopa) • Splenectomy
IgM IgM bind RBC in cold extremities (Cold Agglutinin) Wear mittens in the
• Fixes complement cold
Associated w Mycoplasma pneumonia & Infectious Mono
Microangiopathic Small blood vessel w thrombus Sheared RBC → Schistocyte (Helmet cells) Schistocytes
Hemolytic Anemia TTP & HUS → platelet thrombi
DIC – many causes → platelet + fibrin thrombi
Hemolysis Elevated Liver Enzymes & Low Platelets (HELP) - prego
Prosthetic Valves & Aortic Stenosis
Malaria Infctn of RBC & Liver w Plasmodium Some extravascular → splenomegaly Plasmodium life cycle → RBC rupture & Fever
• Transfer via Anopheles mosquito P falciparum – daily fever
P vivax & ovale – fever every other day
Anemia Due to ↓ RBC production ↓ RCcorrected
Underproduction Causes of microcytic & macrocytic anemia
Renal Failure - ↓ EPO
Damage to BM precursors
Parvovirus B19 Infects progenitor red cells → ↓ erythropoiesis ↑ aenmia if existing marrow stress Supportive treatement – virus is self limited
Aplastic Anemia Damage to hematopoietic stem cell → pancytopenia & ↓ RC (!) Empty marrow Cessation of drugs, Transfusions, Immunosurpress
Cause: drugs, chemical, viral, Autommune • ↑ Adipose in in bone Marrow Stimulating Factor (EPO, GM-CSF, G-CSF)
BM transplant – last resort
Myelophtihisc Pathological process that replaces BM → Pancytopenia
Process • eg. Cancer Mets
 17
6.1 Leukopenia & Leukocytosis
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Basic Principles • Hemotopoetin Stem cell – CD34+ → 2 divisions Normal WBC 5000-10,000
-Lymphoid Stem Cell → B & T lymphoblasts → B & T cell WBC < 5000 = Leukopenia
-Myeloid Stem Cell → Erythroblast, Myeloblast, WBC > 10000 = Leukocytosis
Monoblast, Megakaryocyte
•
Leukopenia Neutropenia = ↓ PMN
• Drug Toxicity (chemo) → Tx GM-CSF & G-CSF
• Severe infection – PMNs out of blood→in tissue
Lymphopenia - ↓ lymphocytes
• Immunodefieiciency (DeGeorge)
• ↑ cortisol (Cushings) → ↑ lymphocyte apoptosis
• Autoimmune (SLE)
• Whole Body Radiation – lymphocytes most sensitive
Leukocytosis Neutrophilic Leukocytosis - ↑ PMN Neutrophilic Leukocytosis → Leftward shift
• Bacterial infection • ↓ CD16 = ↓ Fc receptors on PMN
• Tissue necrosis
• High cortisol state – dislodge Marginal PMN
Monocytosis
• Chronic Inflammatory State
• Malignant
Eosinophilia
• Allergic Rxn
• Parasitic Infection
• Hodgkin Lymphoma – mediated by IL-5
Basophilia
• CML
Lymphocytic Leukocytosis
• Viral Infection
• Bordetella pertussis – lymphocytosis promoting fctr
o Prevents lymphocytes from exiting blood
Infectious EBV → lymphocytic leukocytosis w Reactive CD-8+ T-cell Oropharnynx → soar throat CD8+ T-cell response Screen w Monospot Test
Mononucleosis • Saliva → kissing dz in teenages Liver → hepatitis Generalized lymphadenopathy • detects IgM heterophile Ab
CMV is less common cause B-Cell • Paracortex Hyperplasia • eg.IgM against animal RBC
Complications Splenomegaly – white pulp expansion • usually + 1 wk after EBV infection
• ↑ risk of splenic rupture • Periarterial Lymphatic Sheath (PALS) • CMV → negative monospot
• avoid contact sports for 1 yr ↑ white count w atypical lymphocyte Definitive diagnosis
• Rash if exposed to PCN • Large n.n & abundant nucleus • EBV viral capsid Ag testing
• Dormancy of virus in B-cells → • Look like Monocyte → “mononucleuosis”
o ↑ risk of recurrence
o ↑ risk of Lymphoma, esp in
immunodeficiency/AIDS
 18
6.2 Acute Leukemia
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Acute Leukemia Disruption in ability to mature Neoplastic proliferation of blasts Acute Anemia, TCP, neutropenia signs Hematopoetic stem cell → LB & MB TDT polymerase→ + in Lymphoblast
Basic Principles • Blast precursor buildup • > 20% blasts in BM • fatigue, bleeding, infection -MB → Erythro, Mono, Myelo, Megakaryo Myeloperoxidase → + in myeloblsats
Blasts “crowd-out” normal hematopoesis -LB → B, T • Can crystalize into auer rod
• anemia, TCP,neutropenia Blasts → hard to tell bt LB & MB
Blasts enter blood → high WBC • Large WBC
• Immature - ↓ cytoplasm
• Nucleololus present – “punched out”
Acute Lymphoblastic Neoplastic Acute accumulation of lymphoblast Neoplastic Acute accumulation of lymphoblast Tdt – is a DNA polymerase Tdt+ in nucleus
Leukemia (ALL) Most common in children Subclassify based on surface markers
• Down syndrome after 5 y.o Associated w Down syndrome after 5 y.o • B-ALL or T-ALL
B-ALL Most common type of ALL t(12:21) – good prognosis, ↑ in kids CD10, CD19, CD20 CD10, CD19, CD20
Acute Lymphoblastic t(9:22) – poor prognosis, ↑ in adults ∆ prognosis based on cytogenetic abnormalities Excellent response to Chemotherapy
Leukemia • Ph+ ALL (!) Requires prophylaxis to scrotum & CSF
T-ALL Thymic mass (mediastinum) in Teenage CD2, CD3, CD4, CD5, CD6, CD7, CD8
Acute Lymphoblastic Lymphoma – malignant cells forming a mass ∅ CD10
LYMPHOMA
Acute Myeloid Acute accumulation of myeloblast precursor Neoplastic Acute accumulation of myeloblast precursor Auer Rod – crystalized myeloperoxidase Tdt-
Leukemia (AML) ↑ in older (average age = 50 years) Subclassification Myeloperoxidase+ staining
• Cytogenic Abnormalities Auer Rods – crystal aggregate of myeloperoxidase
• Lineage of Myeloblasts
• Surface Markers
Acute Promyelocytic t(15:17)→ ∆ Retinoic Acid Receptor (RAR)→ promyelocyte accumulation Risk of DIC → Medical Emergency Auer Rods → can activation coagulation (!) ATRA – all-trans retinoic acid
Leukemia (APL) • Cause blasts to mature
Acute Monocytic Proliferation of monoblasts → Infiltrate gums (!) Involvment of Gums Usually lack MPO
Leukemia
Acute Proliferation of Megakaryoblasts Lack MPO
Megarkaryoblastic associated w down syndrome< 5 y.o
Leukemia Preexisting dysplasia – exposure to alkylating agents or radiotherapy
• Myelodysplastic syndromes
Myelodysplastic Preexisting dysplasia – exposure to alkylating agents or radiotherapy Cytopenias w hypercellular bone marrow ↑ blasts (<20%)
Syndrome Most die from infection or bleeding
May progress to acute leukemia (if blasts > 20%)
6.3 Chronic Leukemia
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Chronic Leukemia Insiderious onset Neoplastic Proliferation of mature lymphocytes ↑ WBC count
(basic principles) ↑in older adults
Chronic Lymphocytic Neoplastic proliferation of Naïve B-cells Generalized lymphadenopathy Co-express CD5 & CD20 CD5 + CD20
Leukemia (CLL) • Small Lymphocytic Lymphoma ↑ lymphocytes Smudge cells
Hypogammaglobulinemia - ∅ producing many Ab Smudge Cells
• Most common cause of death = infection
Autoimmune hemolytic Anemia
• may produce anti-RBC Ab
Transformation to Diffuse Large B-Cell Lymphoma
• Enlarging lymph node or enlarging spleen
Hairy Cell Leukemia <TRAP+, trapped in Red Pump, Trapped in BM, Neoplastic proliferation of mature B-cell Splenomegaly – enlargement of red pulp Hairy cytoplasmic process Hairy cells
can’t go to lymph node because they are Bone Marrow Aspiration – Dry Tap Tartrate Resistant Acid Phosphatase (TRAP+) TRAP+
trapped, grow a hairy beard while trapped> Absent lymphadenopathy Tx: 2-CDA - Adenosine deaminase inhibitor
• Adenosine builds to toxic levels
Adult T-Cell Neoplastic proliferation of mature CD4+ T-cell Rash → skin rash (∅ found in mutple myeloma)
Leukemia/Lymphoma Associated w HTLV-1 virus Generalized Lymphadenopathy & Hepatosplenomegaly
(ATLL) • Japan & Carribean (!) Lytic bone lesions w Hypercalcemia
(d/dx Multiple Myeloma)
Mycosis Fungoides Neoplastic proliferation of mature CD4+ T-cell Rash, Plaques, Nodules @ skin Pautrier Microabscess
Aggregates of neoplastic T-cell in epidermis Sezary Syndrome – cerebriform nuclei (look like brains)
• Pautrier Microabcesses
Spread to blod → Sezary Syndrome
 19
6.4 Myeloproliferative Disorders (MPDs)
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
MPD basic principles ↑ in late adulthood Neoplastic accumulation of mature Myeloid cells ↑ risk of hyperuricemia & gout (cell turnover→purine) All the myeloid cells are increased ↑ WBC count (Granulocytes)
Progression to Marrow Fibrosis • Named based on predominant cell hypercellular marrow
• Spent phase / Burnt out phase
Transformation to Acute Leukemia
Chronic Myeloid Neoplastic proliferation of mature myeloid cells t(9:22) → BCR-ABL function → ↑ Tyrosine Kinase Activity Chronic Phase - Splenomegaly is common ↑ granulocytes Imatinib – blocks tyrosine kinase activity
Leukemia (CML) • ↑ Granulolytes Accelerated phase – Enlarging spleen Basophilia
• ↑↑ basophils Transformation – transforms to acute leukemia
• AML (2/3rds) or • ALL (1/3rd) Must differentiated CML vs Leukomoid Reaction
• Stem cell mutation • CML granulocytes are
• Leukocytealakaline Phosphate– (LAP-)
• ↑ basophils
• t(9;22)
Polycythemia Vera Neoplastic proliferation of mature myeloid cells JAK2 kinase mutation Hyperviscocity symptoms Must distinguish PV vs Reactive Polycythemia Phlebotomy
(PV) • ↑↑ RBCs Blurry Vision & HA • PV – SaO2 normal & ↓ EPO • Or death would occur
↑ risk of venous thrombosis → Budd-Chiari syndrome • Reactive due to Lung Dz - ↓ SaO2, ↑ EPO Hydroxyurea – 2nd like treatment
Flushed face – due to congestion • Reactive due to Ectopic EPO (RCC)
(!) Itching after bathing – extra mast cells ↑ EPO, normal SaO2
Essential Neoplastic proliferation of mature myeloid cells JAK2 kinase mutation ↑ risk of bleed or thrombosis d/dx – Fe deficiency anemia
Thrombocythemia • ↑↑ Platelets • Patelets functioning or nonfunctioning
(ET) Rarely progress to marrow fibrosis or acute leukemia
∅ significant risk for hyperuricemia or gout
• ∅ nucleus in platelets → ∅ DNA turnover
Myelofibrosis Neoplastic proliferation of mature myeloid cells Splenomegaly – extramedullary hematopoesis ↑production of PDGF → marrow fibrosis
• ↑↑ Megakaryocytes Leukoerythroblastic Smear - ∅ reticulin gate in spleen Pink collagen/fibrosis deposited in BM
• ↑ Immature cells in blood
• Nucleated RBCs Teardrop cells – some blood cells developed in fibrosis
↑ risk of infection, thrombosis, & bleeding • “stretched” as they leave into blood
• Spleen ∅ as effective as BM
 20
6.5 Lyphadenopathy (LAD)
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
LAD basic principles Enlarged lymph node Painful LAD – Acute Infection Inflammation → hyperplasia of different regions Cortex – B cells
Painless LAD – -Follicles – RA or early HIV (follicular cells CD4+) Paracortex – T-cells
• chronic inflammation, -Paracortex – viral infection Medulla – Sinus Histocytes
• metastatic Ca, or -Sinus Histiocytes – LN draining tissue w cancer
• lymphoma

6.6 Non-Hodgkins Lymphoma

Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Lymphoma basic Neoplastic proliferation of lymphoid cells that forms Classifiy based on May arise in LN or in extranodal tissue
principles a mass • Cell type • cell size • pattern of cell growth Can be divided into
• Expression of surface markers • NHL – 60% & • Hodgkins (40%)
• Cytogenetic translocations Small B-Cell
• LN has follicle→mantle → margin
Small B-cell
lymphomas
Follicular Lymphoma Neoplastic proliferation of small B-cells (CD-20+) t(14:18) Late adulthood Folicle-like nodules Realtively asymptomatic
In follicle • BCL2 on Ig Heavy Chain chain locus → ↑ BCL2 Painless generalized LAD Tx
• BCL2 prevents apoptosis in LN follicle Complication – d/dx - Follicular Hyperplasia (infection) • Low dose Chemotherapy
(where we want apoptosis to occur) • Progression to Diffuse Large B-cell lymphoma Folliicular lymphoma will have the abnormal findings: • Rituximab – anti-CD20 Ab
• Present as 1 enlarging lymph node • Disruption of normal LN architecture
• ∅ Tingible Body Mφ in germinal center
• BCL2 expression in follicles
• Monoclonality – ∆ Kappa/Lambda ratio (>5:1)
Mantle Cell Neoplastic proliferation of small B-cells (CD-20+) t(11:14) Late adulthood Expansion of mantle (adjacent to follicle)
Lymphoma Expands mantle zone • Cyclin D on Ig Heavy chain locus → ↑ Cyclin D Painless generalized LAD
• ↑ Cyclin D → promote G1/S transition
Marginal Zone Neoplastic proliferation of small B-cells (CD-20+) Associated w chronic inflammatory states Marginal zone formed by post-germinal center B-cells
Lymphoma Expands marginal zone • Hashimotos Thyroiditis Formed in chronic inflammatory state
• Sjogren Syndrome MALToma → tx the H pylori
• H pylori gastritis → MALToma
Burkitt Lymphoma Neoplastic proliferation of intermediate sized B-cells Translocations of c-myc (chromosome 8) Extranodal mass in child or young adult High mitotic rate
(CD-20+) t(8:14) = most common African form – jaw mass • “Starry Sky appereance”
• Translocation of c-myc to Ig Heavy Chain locus Sporadic form – abdominal involvement • Blue tumor sky,white Mφ stars
• ↑ c-myc → ↑ cell growth
associated w EBV

Diffuse Large B-cell Neoplastic proliferation of large sized B-cells Sporadically Present in late adulthood
Lymphoma (!) Most common form for Non-Hodgkins Transformation of Follicular lymphoma Enlarging LN or extranodal mass
Clinically aggressive

6.7 Hodgkins Lymphoma

Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Hodgkins ∅ all cells are neoplastic Reid Sterberg cells → secrete cytokines RS → CK release Reid Sternberg Cells
Rare neoplastic cells (Reid Sternburg Cells) secrete -B-symptoms – fever, chill, night sweats • Large B-cell w Multilobed nuclei &
inflammatory mediators → ↑ inflammatory cells Subtypes – characterized by inflammatory cell types -↑ lymphocytes, plasma cell, Mφ & eosinophils → mass prominent nucleoli
• Produces mass -Nodular Sclerosis – most common subtype -May lead to fibrosis • (!) CD15+ & CD30+ (∅ CD20)
• Enlarging neck or mediastinal LN, young female • Mutilobed nucleus → Owls-Eye
-Lymphocyte-rich – best prognosis Reactive inflammatory cells make up mass of tumor
-Mixed cellularity – RS → ↑ IL-5→ ↑ eosinophils & eosinophilia
-Lymphocyte-depleted – worst prognosis, ↑ in old & HIV+ Nodular Sclerosis
• Lymph node divided by bands of sclerosis
• RS cells present in “lake-like” spaces
• Lacunar Cells
 21
6.8 Plasma Cell Dyscrasias
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Multiple Myeloma Malignant proliferation of plasma cell in BM Osteoclast Activating factor → bind RANK receptor M-spikes Punched-Out lesions
Most common 1°malignancy of bone ↑ IL-6 sometimes present • Punch out lesions of bone Bence Jones Proteins
• (most common overall =mets) • Bone pain Myeloma Kidney Serum Protein Electrophoresis (SPEP)
• Hypercalcemia Infections • Normal: albumin is highest & γ is
• ↑ risk of fracture wide and not as tall as albumin
↑ immunoglobun → ↑ serum protein • Myeloma → ↑↑ IgG or IgA = M-spike
• M-spike on spep M-spike = monoclonal Ig
• Most commonly IgG or IgA
↓ antigenic diversity
• infection is most common cause of death
Rouleaux Formation on blood smear
• ↓ charge on blood cell→ cells overlap
↑ light chain production → 1° AL amyloidosis
• Free light chain circulates→deposit in tissue
Proteinuria – light chain excreted in urine
• Bence-Jones Proteins – light chain in urine
Light Chain Deposit in kidney tubal → renal failure
• Myeloma kidney
Monoclonal ↑ serum protein w M-spike on SPEP Complication
Gammopathy of ∅ other myeloma features • 1% develop multiple myeoma
Undetermined • ∅ BJ protein, ∅ AL amyloid, etc
Significance (MGUS) ↑ in eldery (5% > 70)
Waldenstrom B-cell lymphoma w monoclonal IgM production Generalized LAD IgM in pentamer → “Macro” Plasmapheresis – remove IgM from serum
Macroglobulinemia ∅ lytic bone lesions • For acute complications
↑ serum protein w M-spike due to IgM
↑ IgM → hypervisocity
• Retinal hemorrhage, Stroke
Bleeding - ∆ platelet aggregations
6.9 Langerhans Cell Histiocytosis
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Langerhans Cell Neoplastic proliferation of Langerhans Cells Mnemonic: Langerhan cells are APC in skin Immunohistochem: CD1a+ & S100+
Histocytosis (general names = malignant → skin involvement • CD1a+ & S100+
principles) 2 names = children < 2 Birbeck (tennis racket) Granules @ EM
3 names – children > 3
Letterer-Siwe 2 names → Skin Rash Rapidly fatal
Disease Malignant Cystic skeletal defects in infant (<2 y.o)
Children < 2 y.o Multiple organs may be involved
Eosinophilic ∅ names → benign Pathologic Fracture of bone Biopsy
Granuloma ↑ in adolescence • Langerhans Cell w Mixed inflammatory cell
• ↑ eosinophils
Hand-Schuller- Malignant proliferation of Langerhands cells Scalp rash
Christian Disease Lytic skull defects
In children > 3 Diabetes Insipidus
Exophthalmos
 22
Ch 7.1 – Vasculitis
General Inflammation of blood vessel wall Etiology of Vasculitis Usually unknown
• Can be anywhere → We focus on arteries Infection is NOT the #1 cause
Layers of Vessel Intima – dark blue – endothelial cells on BM Clinical Nonspecific Symptoms – fatigue, weight loss etc
Media – smooth m.m Symptoms of Organ Ischemia
Adventitia – connective tissue • Thrombosis: endothelial damage → activate coagulation in subendothelial tissue
• Fibrosis: Healing after infection → fibrosis of vessel → tissue damage

Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Large-Vessel Vasculitis – involves aorta & major branhes
Temporal (Giant Cell) Granulomatous vasculitis (!) Headache <temporal> Inflamed vessel wall Biopsy – need a long piece & need to examine the
Arteritis • involves branches of carotid Visual Disturbances <ophthalmic> Giant cells – from granulomatous rxn whole vessel bc of segmental involvement
Older (>50 yo) ; ↑ in females Jaw Claudication Intimal Fibrosis • (-) biopsy doesn’t not rule out disease
Polymyalgia Rheumatica - Flu-like symptoms. Joint & m.m Segmental Involvement - (!) Tx – Corticosteroids
↑ ESR (>100) • Risk of blindness without early Tx
• Tx even before confirming biopsy

Takayasu Arteritis Granulomatous vasculitis Visual & CNS symptoms Similar to & overlaps Temporal Arteritis Corticosteroids
• Involves aortic arch @ branch points Weak/absent pulse in upper extremity
Adults (<50 yo), ↑ in asian females • “Pulseless disease”
↑ ESR
Medium Vessel Vasculitis - Involves muscular arteritis
Polyarteritis Nodosa Necrotizing Vasculitis Renal a. → HTN Early associated w serum HBsAg
• Involves most organs Mesenteric a. → Abdominal Pain w melena • Transmural Inflammation with
• (!) Lungs are spared CNS disturbance (!) Fibrinoid Necrosis (!) Corticosteroids or Cyclophosphamide
Skin Lesions Later – • Fatal if ∅ treated
• Fibrous Nodes
• (!) “String of Pearls” on imaging
Kawasaki Dz Asian Children < 4 y.o (!) Erythematous rash of palms & soles Coronary a.a involvement → ↑ complicaSons (!) Aspirin
Fever • Thrombosis → MI • Unique for childhood dz
Conjunctivitis • Aneurysm → rupture IVIG
Strawberry Tounge Disease is self-limited
Cervical Lymphadenopathy
Later complications – thrombosis & aneurysm of vessel
Buerger Necrotizing Vasculitis (!) SMOKING – highly associated Ulceration (!) Quit Smoking
Dz • Involves Digits Gangrene
↑ associaSon w Raynaud Autoamputation of fingers & Toes
,….shocking
Small Vessel Vasculitis – involves arterioles, capillaries, & venules
Wegener’s Necrotizing Vasculitis Sinusitis or nasopharyngeal ulceration Large Necrotizing Granulmona w adjacent Cyclophosphamide & Steroids
Granulomatosis • (!) involves Nasopharynx, Lungs & Kidney • Saddle-Nose deformity necrotizing vasculitis • Relapse common
Middle ages Males • Strawberry Gum ↑ C-ANCA correlate w dz severity
Hemoptysis w bilateral nodules lung infiltrates bilateral nodules lung infiltrates “WeCners” – remember the ‘C”
Hematuria – due to rapidly progressive GN Rapidly Progressive GN – see renal notes • C – distribution • C-ANCA • Cyclophosphamide

Microscopic Necrotizing vasculitis Similar to Wegeners but P-ANCA correlates w dz severity Cyclophosphamide & Steroids
Polyangiitis • Involve multiple organ → esp lung & kidney ∅ nasopharyxnx invovled, ∅ C-ANCA, ∅ Granulomas • Relapse common
∅ granulomas, ∅ asthma, ∅ periph eosinophilia
Churg-Strauss Necrotizing granulomatous vasculitis w Eosinophils Asthma Granulomas
• Involve multiple organ → esp lung & heart Peripheral Eospinophelia
P-ANCA correlates w dz severity
Henoch-Schonlein Most common vasculitis in kids IgA immune complex deposition Palpable purpura on buttocks & legs Self-limited but my reoccur
Purpura (HSP) Usually follows URT-infection GI pain & bleeding Steroids to treat symptoms (if needed)
Hematuria – IgA nephropathy
 23
7.2 HTN
General ↑ BP via pulmonary or systemic circuit 2ndary Due to identifiable cause – 5% of cases HTN can also be classified as Benign vs Malignant
• We are focusing on systemic for this section HTN • Renal a. Stenosis Benign Mild-moderate elevation
HTN Clinically silent → vessels & organs damaged overtime
Systemic > 140/90 mmHg Renal ↑ plasma renin → ATII → Malignant Severe elevation in BP (>200/120 mmHg)
HTN • Most have both (systolic & diastolic) but either can be use to qualify artery • ↑ aldosterone → ↑ Na @ DCT → ↑ plasma volume HTN Cause
Normal < 120/80 stenosis • Direct contraction of arteriolar smooth m • Preexisting benign HTN
Primary Unknown etiology – 95% of cases Unilateral atrophy of affected kidney • De novo
HTN Risks: Age, Race-↑ in black, ↓ in Asian; Obesity, Stress, ↓ exercise,↑ Na Causes Clinical
• Atherosclerosis – elderly males • Acute Renal Failure • HA • Papilledema
Fibromuscular Dysplasia – young females Medical Emergency
7.3 Arteriosclerosis – thickening of vessel walls
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Atherosclerosis Thickening of INTIMA of medium & large vessel (!) Modifiable Risk Factors Stenosis of Medium vessel → Symptoms @ >70% stenosis Fatty Streak – Mφ takes up cholesterol
• Intimal Plaque → obstructs blood flow • HTN • Abdominal aorta → ischemic bowel dz • Gets inflamed → healed
Medium & large vessel • Hypercholesterolemia • Coronary → angina Plaque
• Smoking • Popliteal → peripheral vascular dz • Necrotic Lipid Core – Cholesterol
• DM • Internal Carotid • Fibromuscular Cap
Non-modifiable Risk Factors Plaque Rupture w Thrombosis
• Age • Coronary → MI
• Gender ( ↑ in M & Postmenopause) • MCA → Stroke
• Genetics Plaque Rupture w Embolization → atherosclerotic emboli Atherosclerotic Embolus → Cholesterol clefts
Weakening of Vessel Wall - ↓ blood to wall → atrophic wall
• ↑ risk of aneurysm
Hyaline Thickening of walls of small blood vessels via protein leaking (!) Protein across wall → 2 causes ↓ vessel caliber → end-organ ischemia Proteins leak into wall
Arteriolosclerosis • Benign HTN – proteins pushed into vessel • Glomerular Scarring - Arterionephrosclerosis Pink thickening of wall
• DM – after nonenzymatic glycosylation &
damage to BM → allow protein leak

Hyperplastic Thicken of small blood vessels via hyperplasia of smooth m.m (!) Malignant HTN ↓ vessel caliber → end-organ ischemia Onion skin appearance
Arteriolosclerosis Fibrinoid necrosis of vessel wall
Acute Renal Failure (ARF) → flea-bitten kidney

Moenckeberg Medial Calcification of media ∅ clinically significant

Sclerosis ∅ obstructive → ∅ clinically significant Incidental finding on radiology (X-Ray & Mammography)
7.4 – Aortic Dissection & Aneurysm
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes
Aortic Dissection Tear in intima → blood tears through media HTN Sharp tearing chest pain
Occur @ proximal 10 cm of aorta w • hyaline arteriolosclerosis of vasovasorum → Radiates to back
preexisting weakness of media (HTN, CT disorder) ↓ blood flow to outer portion of vessel → Complications
weakened media • Pericardial Tamponade – most common death
Inherited defects of connective tissue • Direction → Renal a.a → compress renal a.a
• Marfan’s • Ehlers Danlos • Rupture into mediastinum
Thoracic Aneurysm Ballon-like dilation of thoracic aorta Weakness in wall Complications Syphilis – “tree-bark” appearance of aorta
• 3° syphilis – endarteritis of vasovasorum • (!) Dilation @ aortic valve root → aortic insufficiency
• Compression of Mediastinal Structure
• Thrombosis/Embolism

Abdominal Aortic Ballon-like dilation below renal a & above bifurcation of aorta Weakness in wall Pulsatile Abdominal Mass
Aneurysm (AAA) • Atherosclerosis • Grows with time
o thickened wall → ↓ O2 diffusion Complication
o ↑ in M, smoker, >60 yo, HTN • Rupture → esp when > 5 cm diameter
• Rupture Triad
o hypotension,
o pulsatile abdomen mass,
o flank pain
 24
7.5 Vascular Tumors
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Hemangioma Benign tumor comprised of blood vessels Commonly present @ birth Most often involves d/dx bt Pupura → apply pressure
→ (!) often regresses during childhood • Skin • Hemangioma will blanch
• Liver • (vs Purpura - will not blanch)

(!) Often regresses during childhood

• avoid surgery, especially on face
Angiosarcoma Malignant proliferation of endothelial cells Associated w Skin
Highly aggressive • (!) PVC Breast
• Arsenic Liver
• Thorotrast
Kaposi Sarcoma Low-grade malignant proliferation of endothelial cells (!) HHV-8 infection of endothelial cells Purple patches/plaques/.nodules on skin Will not blanch → blood is not in a vessel
3 patients Involve skin & visceral organ
• Older eastern European males - ↑ in skin Eastern European w Skin only – Sx removal
• HIV HIV + HHV8 – Antiretroviral Tx (HAART)
• Transplant Patients Transplants - ↓ immunosuppressive drugs
 25
Ch 8.1 Ischemic Heart Dz
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Ischemic Heart Dz Usually atherosclerosis in coronary a.a
(General) Risk factors – similar to atherosclerosis risk factors
↑ incidence w age
Stable Angina Reversable Chest Pain @ exertion Atherosclerosis in coronary a.a Chest pain (<20 min) → radiates to left arm & jaw (!) Reversible Injury to myocytes EKG – ST depression
• 70% stensosis needed Diaphoresis • Hallmark – Swelling • Subendcardial ischemia
↓ blood to myocardium → Injury to myocytes Dyspnea Subendocardial Ischemia Rest
Nitroglycerine – vasodilate veins → ↓ preload
Unstable Angina Reversable Chest Pain @ rest Rupture of atherosclerotic plaque w thrombosis Incomplete Occlusion EKG – ST depression
• (!) Incomplete Occlusion Reversible Injury to Myocytes • Subendcardial ischemia
(!) High risk of progression to MI Nitroglycerine – vasodilate veins → ↓ preload
Prinzmetal Angina Episodic chest pain UNRELATED to exhertion Vasospasm of coronary artery Reversible Injury to myocytes EKG – ST elevation
• Transmural ischemia
Nitroglycerine
Ca-Channel Blockers
Myocardial Common Cause - Rupture of atherosclerotic plaque Severe crushing chest pain → radiates to left arm or jaw Death after 20 minutes Labs
Infarction • complete occlusion of coronary • > 20 minutes necrosis of cardiac myocytes Troponin I – most sensitive & specific
LAD – anterior LV & anterior IV septum Diaphoresis Usually involves ventricles • Rise 2-4 hrs → peak @ 24hr
RCA – Posterior LV & posterior IV septum Dyspnea • Atria generally spared • →normal in 7-10 d
L circumflex – Lateral wall of LV Symptoms ∅ relieved by nitro Initial Phase – Subendocardial Necrosis CK-MB
• ST depression • Rise 4-6 hr→Peak @ 24 hr
Other: vasospasm, emboli, vasculitis (kawaski) Progresses → Transmural Infarction • → normal by 72 hr
• ST-elevation • Good for detecting 2nd infarction
Drugs Tx
After returning blood flow • ASA/heparin – limit thrombosis
-Contract Band Necrosis –Ca+ returns to dead tissue • O2 - ↓ ischemia
• Pink Bands • Nitrates -dilate v & a → ↓ preload
-Reperfusion Injury – O2→free radicals→more • β blocker - ↓ arrhythmia
myocardial damage • ACE – inhibitor - ↓ LV dilatation
• Cardiac enzymes continue to rise o ↓ constriction of
peripheral arterioles
1d – coagulative necrosis o Aldosterone → ↓ volume
1 wk – inflammation (PMN → Mφ ) → granulation Fibrinolysis or Angioplasty
1 month → scar formed •
Time Gross Change Microscopic Change Complication
<4 hr ∅ ∅ Cardiogenic shock , CHF, arrhythmia
3-24 hr Dark discoloration Coagulative Necrosis → Pink Bamds Arrythmia
1-3 d Yellow Pallor Inflammation Fibrinous Pericarditis – in transmural infraction
PMN • Chest pain & friction rub
• Shaggy appearance – (“bread & Butter”?)
4-7 d Yellow Pallor Macrophages Rupture of
• Ventricular free wall → tamponade
• Interventricular suptum → shunt
• (!) RCA → Papillary m.m → insufficiency
1-3 wk Red border emerges from edge of infract Granulation tissue –
• Granulation tissue on edge of infarction • Plump Fibroblasts, Collagen, Blood vessels
1 Month White Scar Fibrosis Weakened wall, ↓ movement, stasis
Anyeursm → balloon dilatation
Mural Thrombus, - on wall of scar or in anyeurism
Dressler Syndrome – anti-pericardial antibody
• Autoimmune pericarditis 6-8 wkafter infraction
Sudden Cardiac Unexpected death due to cardiac dz Usually due to fatal ventricular arrhythmia
Death Acute Ischemia
- Most commonly bc Preexisting atherosclerosis
-also: Mitral valve prolapse, cardiomyopathy, cocaine
Chronic Ischemic Poor myocardial damage Due to chronic ischemic damage Can progress to CHF
Heart Dz
 26
8.2 – Congestive Heart Failure
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
L-side Heart Failure L pump failure Ischemia → myocardial damage Pulmonary Congestion Rupture of engorged capillaries
HTN → concentric LVH → harder to get O2 to wall • Pulmonary Edema w Dyspnea Mφ consumed blood
Dilated Cardiomyopathic –↓ contraction • Paroxysmeal Nocturnal Dyspnea & Orthopnea • Hemociderin laden Mφ
MI • Crackles • “Heart Failure Cells” ACE inhibitor
Restrictive Cardiomyopathy - ↓ filling ↓ perfusion
• ↑ RAAS → AT-II → constrict arteriole & ↑ aldosterone
• ↑ peripheral resistance → worsten CHF
R-side Heart Failure Most common cause – Left-sided HF JVD
L-R shunt Painful Hepatosplenomegaly → cardiac cirrhosis Liver – congested central vein
Chronic Lung Dz (Cor Pulmonale) Dependent Pitting Edema • Nutmeg Liver
• Hypoxia → Reactive Pulmonary vasospasm
8.3 – Congenital Defects
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Ventricular Septal Division bt R & L ventricle Associated w Fetal Alcohol Syndrome L→R shunt → ↑ pulmonary blood volume → Pulmonary HTN Spontaneous healing
Defect (VSD) • L-R shunt RVH, reversal of shunt to R→ L shunt & Cyanosis Surgical – if large
Most common congenital heart defect • Eisenmenger Syndrome
• Clubbing, cyanaosis, polycythemia
Atrial Septal Defect Defect in wall bt L & R atrial septa Most common – Ostium Secundum L→R shunt → delayed closure of pulmonic valve
(ASD) ()! Ostium Primium – associated w Downs Snydrome • Split S2
DVT emboli can cause lodge in systemic circulation
• Paradoxical Emboli
Patent Ductus PDA –∅ Failure of PDA to close L→R shunt Indomethacin - ↓ PG-E
Arteriosis (PDA) (!) Associated w Congenital Rubella Holosystolic Machinelike mumur • PG-E kEEEps PDA open
Pulmonary HTN → shunt reversal
Cyanosis in Lower Extremity
• Remember PDA branches after major asecending a.a
Tetralogy of Fallot • Stenosis of RV outflow tract R→ L shunt (!) Bloot shaped heart @ CXR
• VSD • early Cyanotic
• Overriding aorta • Squat to reverse cyanosis (↑ pressure to lung)
• RVH
Transposition of Aorta branches of RV (!) Associated w Maternal Diabetes 2 separate circuits of blood Tx
Great Vessels Pulmonary trunk branches of LV • Baby survives to term via PDA • Maintain PDA with PG-E
Early Cyanosis • Create Surgical Shunt
Truncus Arteriosus Trunk fails to divide Blood from RV & LV mix
1 large trunk arising from both ventricles Early Cyanosis
Tricuspid Atresia Tricupsid valve orifice fails to develop Associated w ASD Early Cyanosis
• RV hypoplastic • RA → LA → LV → Systemic
Coarctation of Aorta Narrowing of aorta Infantile ↑ collateral circulation across intercostal a.a Infant
• Infantile • Associated w PDA • Notching of vessel against ribs • Coaraction distal to aortic arch &
• Adult • Associated w Turners Syndrome Infantile proximal to PDA
Adult • Coaraction distal to aortic arch & proximal to PDA Adult
• ∅ relation to PDA • Lower Extremity Cyanosis •Coarctation is distal to aortic arch
• Associated w Bicuspid Aortic Valve Adult
• HTN in upper extremities
• Hypotension in lower extremities
 27
8.4 – Valvular Disorders
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Acute Rheumatic Group A β hemolytic strep pharyngitis Mitral Regurg Pancarditis Jones Criteria
Fever • 2-3 wk after strep throat, ↑ in children -Endocarditis – vegetations on endocardium • Evidence of GAS infection
• M-protein → “Molecular Mimicry” Myocarditis – most common cause of death in acute RF • ↑ @ mitral valve → regurgitation o ASO titer
• If another valve involved – aortic o Anti-DNAase B titer
-Myocarditis • Minor Criteria – fever, ↑ esr
• Ashoff Bodies - giant cells & fibrinoid • Major Criteria
material w Anitschkow cells • J – joints – migratory polyartheritis
• Anitschkow cells – histiocytes w slender • O – O looks like a heart → pancarditis
wavy nuclei – “Caterpiller nucleus” • N - Nodules
-Pericarditis – friction rub • Erythema Marginatum – annular rash
• Sydenham’s chorea
Chronic RF Heart Dz Repeat exposure to GAB → relapse of acute phase Chronic rheumatic valvular disease Scarring, thickening of chordae → Mitral Stenosis
Mitral Stenosis Aortic Valve involvement – Fusion of Commistures
Aortic Stenosis
Complication - Endocarditis
Aortic Stenosis Narrowing of aortic valve orifice Fibrosis & Calcification – “wear & tear” (#1 cause) Compensation Tx
• Normal – 4 cm2 → stenosis is < 1 cm • ↑ in late adulthood (>60 y) • Prolonged asymptomatic stage • Valve Replacement
↑ risk w Bicuspid aortic valve → earlier onset of dz • Systolic Ejection Click & after onset of complications
Chronic Rheumatic Valve disease – fused commisures crescendo-decresendo mumur
Complication
• Concentric LVH
• Angina & Syncome w Exercise
• Microangiopathic Hemolytic Anemia
Aortic Regurgitation Backflow of blood from aorta into LV during diastole Isolated Aortic Root Diliation (#1 cause) Early blowing diastolic mumur LV-dilation Tx
Syphilitic aneurysm → aortic root dilation (!) Hyperdynamic Circulation - ↑ systolic, ↓ diastolic • Eccentric Hypertrophy • Valve Replacement
Damage to valve (eg. Infectious Endocarditis” • Bounding pulses, pulsating nail bed when LV dysfunction develops
• Head bobbing
LV-dilation
• Eccentric Hypertrophy
Mitral Valve Prolapse Valve flops into atria @ systole Degeneration of valve (!) Mid-systolic click Tx
Regurgitation Mumur • Valve Replacement
Some asssociation w marfans or Ehlers danlos Complcations – rare
• Infectious endocarditis
• Arhythmia
• Severe Mitral Regurgitation
Mitral Regurgitation Reflex of blood from LV → LA @ systolie Complication of Mitral Valve Prolapse (common) (!) Holosystolic “Blowing” murmur
LV dilatation – spread apart leaflets • Radiate to axilla
Infective Endocarditis, Acute Rheumatic Heart Dz, Louder @ squatting or expiration
Papillary m.m rupture after MI
Mitral Stenosis Narrowing of mitral valve orifice Chronic Rheumatic Valve Dz (!) Opening Snap → Diastolic Rumble
Complications
• Volume overload of LA
• Pulmonary congestion → Pulmonary HTN
• Pulmonary Edema & Hemorrhage
• Atrial Fibrillation → stasis → ↑ risk thrombi
o Calcified mitral annulus
 28
8.5 - Endocarditis
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Bacterial Inflammation of endocardium Bacterial Infection – common Fever Subacute + Blood Culture
Endocarditis • Lines surface of valves Strep viridans – most common cause & subacute Mumur .damaged valve → thrombotic vegitations Anemia of Chronic Dz
• Low virulence → only infects damaged valves Septec Emboli – from vegetations off valve .transient bacteremia (eg dental trauma) • Microcytic
• Small vegetations that will not destroy valve • Janeway Lesion – erythematous nontender . bacteria trapped @ vegetation Hepcidin→ ↑ iron trapping → ↑ ferratin
Staph aureus → Acute lesions on palms/sole ↓ TIBC → ↓ [iron]serum
• ↑ in IV drug abuse → Tricuspid Valve • Osler Nodes – Painful lesion @ finger/toe Janeway Lesions
• High-virulence organism o Ouch → Osler Osler Nodes TEE – detect lesions on valves
• Large vegetations → destroy valve • Splinter hemorrhage in nailbed
Staph epi – prostethic valves Anemia of Chronic Dz
(!) S bovis – endocarditis in patient w underlying
colorectal carcinoma
HACEK organism – endocarditis w negative blood culture
.hemophilus, acinobacillus, Cardiobacterium, Eikenella, Kingella
Nonbacterial Sterile vegeations Hypercoagulable state Vegetations on Mitral Valve along lines of closure Vegetations on Mitral Valve along lines of closure
Thrombotic Underlying adenocarcinoma • Regurgitation • Regurgitation
Endocardtiis
Liebman Sacks Sterile vegeations associated w SLE SLE Vegeations on BOTH SIDES of valve (!) Vegetations on BOTH SIDES of valve
Endocarditis Mitral valve commonly involved → regurg

8.6 - Cardiomyopathies
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Dilated Dilation of all 4 chambers Idiopathic – most common cause Systolic Dysfunction Transplant
Cardiomyopathy Most common type of cardiomyopathy Genetic – Auto Dom Biventricular CHF
EtOH abuse Complications
Myocarditis – Coxsackie A & B • Mitral & Tricuspid Regurg
• Lymphocytic infiltration in myocardium • Arrhythmia – stretching conduction system
Drugs – Doxirubicin, Cocaine
Pregnancy – late in 3rd or postpartum
Hypertrophic Massive hypertrophy of LV Genetic mutations in Sarcomere – Auto Dom Syncope w exercise Myofiber hypertrophy with disarray
Cardiomyopathy Common cause of sudden death in young atheletes ↓ Cardiac Output
Sudden Death due to Ventricular Arythmia
Restrictive Restricted filling ↓ compliance Present as CHF Low Voltage EKG
Cardiomyopathy • Amyloidosis Diminished QRS amplitudes
• Sarcoidosis Low Voltage EKG
• Hemochromotosis Diminished QRS amplitudes
• Endocardial Fibroelastosis (children)
• Loefflers syndrome – eosinophilic infiltrate
o Fibrosis of endomyocardium
 29
8.7 – Cardiac Tumors – combined w Dr Siew
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Mxyoma Most common primary cardiac tumor in adults Mesenchymal Proliferation w Gelatinous appearance Mitral valve obstruction → Syncope Mesenchymal proliferation
• ↑ in L-atria ↑ ground substance
• Peduculated mass
Carneys Complex 18% chance of malignancy NAME syndrome: Associated w Endocrinopathies & pigmentary changes Reoccuance of myxoma after surgery – 18%
(Syndrome of Auto Dom Chrm 17 mutation, PKAR gene • Nevi, Atrial myxoma, Myxoid Neurofibroma, Ephelides
Myxoma) Mutiple Tumors, involving more than just LA LAMB syndrome
Age: 20 • Lentigenes, Atrial Myxoma, Blue Nevi
Rhabdomyoma Most common primary cardiac tumor in children Benign Hamartoma of Cardiac m.m
• ↑ in Ventricle
(!) associated w Tuberous Sclerosis
AV Node Smallest tumor capable of causing death Origin – endodermal tumor
Mesothelioma Acini
Gray, firm, partially cystic nodules near AV node, usually
<15mm
Angiosarcoma (!) Most common 1° cardiac sarcoma Rapid Progression & Poor prognosis Malignant tumor of blood vessels
aka most common malignany tumor of heart Large cavernous spaces → + for Factor VIII
M > F, ↑ @ R side of heart Factor VIII present = Endothelium present
Genetic cause: polysomy chr8
Lipoma ↑ at epicardium (↓ at myocardium) LHAS Non-ecapsulated adipocytes
May be associated w tuberous sclerosis
Sarcomas 25% of heart tumors, 75% of malignant hrt tumors R-heart – Subtypes
nd
• bulky & infiltrative → Early mets • Rhabdomyosarcoma – 2 most common primary
• Complication: Grow outward→ obstruction → HF sarcoma of heart
L Heart – o Strands within cytoplasm
• Solid & ↓ infiltrative → Later Mets • Fibrosarcoma
Complication – Common in LA → block flow→HF Malignant Fibrous Histocytoma
Lymphoma Primary Lymphoma can occur in Heart Dyspnea, arrhythmia, tamponade Echo – large mass on right side
∆ presentation than systemic lymphoma Burkits – african baby w jaw swollen shut, B-cell, poor prognosis
Mets to heart Epicardium – most commonly involved More common than primary tumor Clear cell renal Renal v. → IVC → RA
Lung tumors Pulmonary v. → LA
May be invaded from local (heart/lung) Myosarcoma Systemic system → RV
May have traveled Breast cancers
• Carcinoma – lymphatic spread Melanoma
Sarcoma – blood spread → ↑ @ RA Lymphoma
Common Involvement of pericardium
• Pericardial Effusion
 30
9.1 – Nasopharynx
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Rhinitis Inflammation of nasal mucosa Adenovirus – most common Sneezing, congestion, common cold
• Respiratory type epithelium Allergic Rhinitis – due to Type I hypersensitivity (pollen)
• Inflammatory infiltrate w eosinophils
• Associated w Atopy → asthma & eczema
Nasal Polyp Repeated bouts of Rhinitis Protrusion of edematous inflamed nasal mucosa
(!) Cystic Fibrosis – child with nasal polyp
(!) Aspirin Intolerance Asthma → Samter’s Triad
• ASA intolerance • Asthma • Nasal Polyp
Angiofibroma Benign Tumor of Nasal Mucosa composed of Only in adolescent males Present w Profuse epistaxsis
Large blood vessels & fibrous tissue
Nasopharyngeal Malignant tumor of nasopharyngeal epithelium Associated w EBV Commonly present w enlarged cervical lymph nodes Pleomorophic keratin+ epithelial cells in background
Carcinoma Classically seen in African Children & Chinese young adults of lymphocytes
Larynx
Acute Epiglottitis H flu Type B – most common in immunized & non-immunized Fever, sore throat
Drooling w Dysphagia
Muffled voice
Inspiratory strido
Complication – Acute Airway Obstruction → emergency
Laryngotracheo- Parainfluenza Virus (most common) Hoase barking cough
bronchitis
“Croup”
Vocal Cord Nodule Nodules that arise on vocal cord Excessive use Hoarseness Degenerative (Myxoid) Connective Tissue
• Usually bilateral • Resolve w rest
Laryngeal Papilloma Benign papillary tumor of vocal cord HPV 6 & 11 Hoarseness
Single in adults & Mutiple in children
Laryngeal Carcinoma SCC arising from lining of vocal cord Risk factors – EtOH & Tobacco Hoarsness
Rarely – can come from HPV 6 & 11 (remember they are LOW risk) Cough & Stridor
 31
Pulmonary Infections
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Pneumonia Infection of lung parenchyma Normal defenses impaired Fever & Chills 3 patterns CXR
• Mucociliary escalator damage, Mucus Plug Cough – yellow-green or rusty sputum • Lobar – consolidated in lobe Sputum Gram stain & Culture
Tachypnea w pleuritic chest pain • Bronchopneumonia – pathy @ small airways Blood Culture
↓ breath sounds w dullness to percussion • Interstitial – in CT of alveolar air sac
↑ WBC count o Atypical
Lobar Pneumonia Consolidation of entire lobe Bacterial Air sacs full of PMN & pink frothy exhudate
• S. pneumonie (95%) - community, ↑ in middle aged adults 4-pases
• Klebsiella pneumonia (5%) – aspirated enteric flora • Congestion
o Elderly & Alcoholics Klebsiella • Red Hepatization - RBC & solid
o Thick Mucoid capsule → currant jelly sputum • Currant jelly sputum • Grey Hepatization – RBC brokedown & solid
• Complication - Abcess • Resolution - ↓ exhudate & regenerate lung
o Type II Pneumocyte is stem cell
Bronchopneumonia Scattered patchy consolidations around bronchiles Bacterial Scattered patchy consolidations around bronchiles
• Often multiple or bilateral Staph a – most common cause of 2ndary infection Often multiple or bilateral
• Often complicated by abcess or empyeme
H flu. – common cause of 2ndary pneumonia &
pneumonia superimposed on COPD
Pseudomonia – pneumonia in CF
Moraxella catarrhailis – community acquired pneumonia &
pneumonia superimpored on COPD (exacerbation of COPD)
Legionella – community acquired pnueomnia, superimposed on
COPD, or pneumonia in ↓ immune
• Transmission via H2O • Intracellular- silver stain
Interstitial (Atypical) Diffuse interstitial infiltrates Mycoplasma Mild upper respiratory symptoms Diffuse interstitial infiltrates
Pneumonia • Interstitia = Connective tissue of alveolar air sac • Young adults – military recruit, dorm college student • Minimal sputum, cough, low fever
• Autoimmune hemolytic anemia – IgM – Cold Aglutinin
• ∅ cell wall
Chylmdia Pneumonia - 2nd most common cause in young adult
RSV – atypical in infants
CMV – atypical in posttransplant immosurpressive therapy
Influenza - ↑ in eldery, immunocompromised & preexisting lung dz
• ↑ risk for S aureus or H flu superinfection
Coxiella burnetti - ↑ in farmers & vets
• Spores from cattle via ticks OR cattle placenta
• Rickettsiae-like - ∅ arthropod, ∅ rash, causes pnueomnia
Aspiration Patient @ risk for aspiration Right Lower Lobe
Pneumonia • EtOH-holic • Comatose patient RLL abcess
Anerobic Bacteria
• Bacteroides
• Fusobacterium
• Peptococcus
Tuberculosis (TB) Inhalation of aerosol Mycobacterium TB Fever, 1° TB Acid Fast stain – AF Bacilli
night sweats Focal caseating necoris in lower lobes & hilar lymph n
Cough Focia undergo fibrosis & calcification → Gohn Complex
Hemoptsis • Gohn Complex frequently Subpleural
2° Recativation of TB
• Reactivated via AIDS, aging
• Occur @ apex of lung – highest O2 tension
• Foci of caseous necrosis
• Miliary Pulmonary TB or TB bronchopneumonia
Systemic Spread
• Meninges & granulomas @base of brain
• Cervical LN
• Kidneys – sterile pyuria
• Lumbar spine → Potts Dz
 32
COPD – from live presentation @ school
Name Desc Patho Clinical Dx/Tx
COPD ↓ FVC, ↓↓ FEV1
↓ FEV1/FVC ratio
↑ TLC (air trapping)
Chronic Chronic productive cough of 3 mnths over 2 yr ↑ thickenss of mucous glands Cough - productive
Bronchitis • Cough up cups/buckets of mucous (!) Reid Index > 50% Cyanosis → blue bloater
↑ w Smoking • (normal Reid index ≈ 40%) • ↑ PACO2 → ↓ PAO2 bc limited maximum pressure in
• Hyperplasia of mucin glands in lung alveolar sacks
↑ risk of infection & corpulmonale
Emphysema Destruction of alveolar air sac .Imbalance of Proteases & Antiproteases Dyspnea & Cough w MINIMAL SPUTUM
↓ elastic recoil & collapse of small airway .α1-antitrypsin normally protects against low-level inflammation (!) Prolonged expiration w pursed lips
• Air trapping @ exhalation from alvelolar Mφ • Pursed lips → ↑ backpressure
• “suck” walls closed . ↑ ↑ ↑ inflammation > α1-antitrypsin ability → keeps walls opened
• Smokers • “Pink-puffer”
Subtypes of Emphysema . α1-antitrypsin deficiency → ↓ protease deficiency Weight-loss – bc exercising to breath
• Centriacinar - ↑ in upper lobes • Co-morbid w liver cirrhosis ↑ AP diameter of chest (“barrel-chest”)
o Smoker o Problem is w Export of protein • ↑ FRC
• Panacinar - lower lobes o A1AT builds up in hepatocyte E.R • “Reset of FRC”
o A1AT o PAS+ globules in liver
o PiZ/PiZ • PiM is normal allele Late Complications
• PiZ – most common clinically relevant mutation • Hypoxemia – eventually blood vessels are destroyed
o Heterozygote – ok unless they smoke along with walls
o PiZ/PiZ – ↑ severity + cirrhosis • Cor Pulmonale – later (vs bronchitis)
Asthma Reversible airway bronchoconstriction CD4+ Th2 cells → Il-4, Il-5, Il-13 Dyspnea & Wheezing
Often bc Allergy (Type I HSR) • Il-4 → class switching of plasma cell Productive Cough
o IgG → IgE • Chrocot-Leyden crystal – M.B.P derived from
Cause: • Il-5 → calls eosinophils eosinophils
• Exercise • Il-10 → ↓ Th1 & ↑ Th2 • Curshmann Spiral – mucous plugs
• Viral Infection Allergen → IgE mediated mast cell release ↑ in childhood
• ASA • Step 1: Histamine • Assoc w other Atopy
o Nasal polyp (d/dx CF in kids) • Step 2 : LT Severe Unreleting cough w/o resove
o Rhinitis Inflammation by Major Basic Protein • Status Asthmaticus → death
o Bronchoconstriction
• Occupation exposure
Bronchiectasis Permanent dilation of bronchioles & bronchi (!) Large caliber airways @ PERIPHERY of lung Coughing
• ↓ airway tone → ↓ outflow → airtrapping Dyspnea
Necrotizing Inflammation of Wall Foul smelling cough → necrotized material
• CF Hypoxemia & Cor Pulmonale
• Kartanger Syndrome - ↓ dynein arm of cilia
o Associated w sinusits, infertility & (!) 2ndary amyloidosis
situs invertus • 2° - SAA → AA
• Tumor/Foreign body – inflammation behind block o SAA is acute phase reactant
• Necrotizing Infection o ↑ SAA @ inflammation
• Allergic Bronchopulmonary Aspergillosis (ABPA)– o AA deposited throughout body
hypersensitivity rxn to aspergillis • Remember 1° amylosis is Light Chain
o CF & Astmatics
 33
Restrictive Dz
Name Desc Patho Clinical Dx/Tx
General ↓ TLC & ↓ FVC Causes
FEV1:FVC normal or ↑ (>80%) • commonly due to fibrosis of interstitium
• • other: ↑ pressure @ chest wall (skeletl/obease)

Idiopathic Fibrosis of interstitium Progressive Dyspnea Transplant

Pulmonary Idiopathic Fibrosis on lung CT
Fibrosis Related to cyclical lung injury • (!) starts Subpleural
• (!) TGFβ from pneumocytes → ↑↑ repair • Later: Honeycomb lung
May be 2° to chem drugs(Bleo, Amioderone)/radiation
Pneumoconioses Interstitial fibrosis due to occupation exposure
• Chornic exposure to small fibrogenic particle •
• Particles must be small enough to pass mucous
• Particles must have chronic exposure
Coal Workers Exposure – Carbon • Worst Case: Black Lung – fibrotic/shrunk lung
Pneumoconiosis o Associated w R.A (“Caplan Syndrome”)
• Benign Case : Anthracosis – carbon in Mφ via pollution
o Asymptomatic, in everyone

Silicosis Exposure – Silica – in sandblaster & silica miners • Fibrotic nodules in Upper lobe
• (!) Only pneumoconiosis w ↑ risk of TB
 ↓ ability of Mφ to form phagolysosome
Berylliosis Exposure – Beryllium • (!) Aerospace industry (NASA, Boeing)
• Noncasteating granuloma in lung/hilar lymph nodes &
systemic organs
o d/dx: sarcoidosis
• ↑ risk of lung cancer

Asbestos Exposure – constriction, pulmbers, shipyard workers • Fibrosis of lung, Fibrosis of pleura
• Cancer of lung, Cancer of pleura (mesothelioma)
• Lung cancer > mesothelioma
• Asbestos bodies w Iron on top
Sarcoidosis ↑ in african american bc CD-4+ response Granuloma → “epitheloid histocyte” Dyspnea cough Steroid
Noncaseating = non-necrotic ↑ ACE
Asteroid body Hypercalcemia

Hypersensitivity Exposure → resolved after a few hours of removing exposure Interstitial Fibrosis w chronic exposure
Pneumonitis • Pigeon Breeder
 34
Pulmonary HTN
Name Desc Cause Patho Clinical Dx/Tx
General MAP > 25 mmHg (!) Aterosclerosis of pulmonary trunk Exertional dyspnea
• Normal = 10 Smooth m.m hypertrophy of pulmonary a.a RHF
• Intimal fibrosis
(!) Plexiform Lesions – group of capillaries that arise together
RVH → Co-pulmonary
Primary ↑ in young adult mutations Unknown cause
Pumonary HTN (!) Familial Form – inactivation of BMPR2
• Proliferation of vascular smooth mm
2ndary Hypoxemia → ↑ pulmonary vasoconstriction
pulmonary HTN ↑ volume in pulmonary circuit (congenital heart dz)
Recurrent PE
ARDS
Name Desc Cause Patho Clinical Dx/Tx
ARDS Diffuse damaged to aleveior-capillary interface Etiology – many many causes PMNs make too much protease-mediate & Free-radical mediated Hypoxemia & Cynaosis w/o respiratory distress Tx underlying cause
Leakage of protein-rich fluid into alveolar space • Anything damaging alveolar/capillary membrane damage to Type I & Type II pneumocytes Diffuse “White-out” on CXR
• Lines alevolar space • Pancreatitis → enzymes into blood • ↓ Type II → only way left to heal is fibrosis • Lung white & full of fluid Vent w PEEP
• Forms HYALINE MEMBRANE in alveoli • Shock, Trauma, Aspiration, DIC, hypersensitivity, • (!) Recovery may be complicated by fibrosis (Positive end-expiratory
• pressure)
Hyaline membrane in alveoli – dense pink hyaline membrane
• ↓ O2 & CO2 diffusion → Hypoxemia & Cynaosis ↑ survival → ↑ fibrosis
• (!) ↑ surface tension of lung → collapsing alveoli
↑ risk of death
Neonatal Resp distress due to inadequate surfactant levels ↓ Surfactant Produced in lung by Type II pneumocytes Surfactant ↓ the amount of pressure needed to inflate alveoli ↑ resp effort after birth
Respiratory • ↑ stretch on lung → damage • Phosphatidylcholine/(Liectin) Tachypnea w use of resp mm CXR
Distress alveoli/capillary inrfce Associated w prematurity • Screen w L:S ratio (Lechtin:sphingomyelin) Grunting -Diffuse Granularity
Syndrome • ↑ effort of breathing • Surfactant starts @ 28 → peak @ 32 wk o S is set (!) diffuse granularity @ CXR
• Screen with L:S ratio (Lecithin:Surfactnat) > 2 o L increases with duration of gestation) • Ground glass appearance on lung Corticosteroid
• ↑ L after 28 wk, S stays constant o L:S > 2 = adequate . ↑ surfactant release
• Lecithin = Phosphatidyl choline Complication
Associated C-section delivery • Hypoxemia → ↑ persistence of PDA
• ∅ steroid release • Necrotizing Enterocolitis – infraction/death of gut
→ ∅ increased surfactant production
• ∅ steroid release @ birth stress
→ ∅ surfactant release Complication of O2 → ↑ free radicals
Associated Maternal DM • Retinal Damage → blindness (common)
• ↑ blood sugar in baby → ↑ baby insulin • Bronchopulmonary Dysplasia – lung ∅ developing in
• Insulin acts as anti-steroid → ↓ surfactant release • face of free radicals

9.9 Pleura
Name Desc Cause Patho Clinical Dx/Tx
Pneumothorax Air in pleural space Spontaneous – rupture of bullae (↑ in young adults) Tension
Tension Pneumothorax – chest wall trauma • Tracheal deviation Tension
• Medical emergency • Pressure on heart → PEA -needle decom & chest tube
Mesothelioma Malignant neoplasm of mesothelial cells Asbestos Tumor encases lung Pleural Effusions
Dyspnea
Psomomma body formation Chest Pain
 35
9.8 Lung Cancers
Name Desc Cause Patho Clinical Dx/Tx
General ↑ cause of mortality via cancer #1 - Smoking Imaging – solitary nodule Cough & Hemoptysis T – size
∅ screening mechanism • Polycyclic Hydrocarbons • “coin lesion” – 2-5 cm single nodle N – spread to LN
• Related to pack-years & o Benign or malignant Imaging – solitary nodule • hilar
#years • (!) Next step after CXR → compare to old CXR • “coin lesion” – 2-5 cm single nodle • mediastinal
#2 - Radon Exposure o Benign or malignant M – mets
• Uranium-derived exposure of • (!) Next step after CXR → compare to old CXR • (!) adrenal gland is a
non-ionizing radiation Biopsy – needed for cancer Dx frequent location for
#3 – Uranium Miners • Benign – more common in younger patient w coin lesion lung mets
o Granuloma (Histoplasmosis);
o Bronchial Hamartoma – disorganized lung tissue + cartilage + calcified
• Malignant Overall 5 yr survival – 15%
o Small → SCC → Tx w Chemo
o Non-Small → Tx w Sx

Keratin Pearls or Intracelllar Bridges → Squamous Cell
• Intracellular bridges = Desmosomes

Glands and/or mucous → Adenocarcinoma

∅ keratin, ∅ bridges, ∅ glands, ∅ mucus → Large Cell

5% - carcinoid
Small Cell Carcinoma Central Tumor Male, Smoking associated Poorly differentiated neuroendocrine (Kulchitsky) cells Treat with Chemotherapy
Central Tumor
Paraneoplastic Syndromes <Tumor starts with S → Smoking, Sentral (central), Syndromes>
• ADH
• ACTH
• Eaton Lambert – presynaptic Ca-channel autoAb
Squamous Cell Central Tumor Male, Smoking associated Central Tumor <Tumor starts with S → Smoking, Sentral (central), Syndromes>
carcinoma • Metaplasia → Dysplasia → (!) Keratin Pearls Paraneoplastic PTH → hypercalcemia
carcinoma (!) Intercellular Bridges (desmosomes) Superior Vena Cava syndrome
Horners syndrome – ptosis, miosis, anhdrosis
Involvement of recurrent laryngeal or phrenic n
Adenocarcinoma Peripheral Tumor ↑ in non-smokers (!) Glands & Mucous ∅ paraneoplastic syndrome
↑ in female smokers ∅ paraneoplastic syndrome Peripheral tumor → pleural involvment

Large Cell Poorly differentiated large cells Smoking associated ∅ keratin, ∅ bridges, ∅ glands, ∅ mucus
Peripheral or Central
Bronchiololalveolar Columnar cell that grow along ∅ related to smoking Peripheral tumor May present w pneumonia-like consolidation on imaging Excellent prognosis
Carcinoma preexisting bronchioles & alveoli (!) arises from clara cells Excellent prognosis
Carcinoid Central or peripheral ∅ related to smoking Well differentiated neuroendocrine cells Low grade malignancy
(!) Polyp-like mass in bronchus • (!) Chromogranin + Rarely can cause Carcinoind Syndrome
Nests of cells
Mets to Lung Mets is more common than primary Multiple cannon ball nodules @ imaging Sources
tumor • Breast
• Colon
 36
Ch 10.1 – Oral Cavity
Name Desc Cause Patho Clinical Dx/Tx
Cleft Lip & Palate Full thickness defect of lip or palate (!) Failure of facial prominences to fuse
• Often occur together
Aphthous Ulcer Painful superficial ulceration of oral ucosa Stress → resolve spontenously Greyish base surrounded by eryethema
Grey base = granulation tissue
Behcet Syndrome Recurrent aphthous ulcers + Genital Ulcers + Uveitis Immune complex vasculitis involving small vessels
May be post-viral infection
Oral Herpes Vesicles involving oral mucosa → rupture → shallow painful red ulcer HSV-1 1° infection early → virus dormant in Trigeminal Ganglia
Reactivated @ stress/sun → vesicles on lips
Squamous Cell Malignant neoplasm Tobacco & EtOH – major risk factors Leukoplakia & Erythroplakia – precursors lesions
Carcinoma Floor of mouth is most common location • Biopsy to rule out carcinoma d/d of Leukoplakia
• Erythroplakia is more suggestive of dysplasia Oral Candidiasis – plaque can be scraped off
Hairy Lukoplakia –plaque on lateral tounge EBV
CH 10.2 – Salivary Gland
Name Desc Cause Patho Clinical Dx/Tx
General Salivary glands – exocrine glands
• 3 Major – Parotid, Submandiular, Sublingua
• 1000s of minor glands
Mumps Mumps Virus Bilateral inflamed parotid glands → ↑ amylase
Orchitis → sterility
Pancreatitis → ↑ serum amylase
Meninges → aseptic meningitis
Sialadenitis Inflammation of salivary gland Sialoitiasis (obstructing stone)
Unliateral Staph a infection
Pleomorphic Adenoma Most common tumor of salivary gland Pleomorphic – many tissues Mobile painless circumscribed mass @ angle of jaw (!) ↑ rate of recurrence
• Stromal tissue • Epithelial tissue Usually arises @ parotid - Bc Irregular margins
Rarely transforms into carcinoma hard to remove w Sx
• Present w Facial Nerve Damage If progression to carcinoma → CN VII damage
Warthin Tumor Benign cystic tumor w ↑ lymphocytes & germinal centers Benign cystic tumor Almost always in Parotid
2nd most common tmor of salivary gland ↑ lymphocytes & germinal centers → lymph node tissue

Mucoepidermoid Malignant tumor w mucinous & squamous cells Usually in Parotid

Carcinoma • Commonly involves CN VII
 37
Ch 10.3 – Esophagus
Name Desc Cause Patho Clinical Dx/Tx
Tracheoesophageal Connection bt esophagus & trachea Congenital defect Proximal esophageal atresia Polyhydramnios
Fistula Distal esophagus connects to trachea Food consumed → blind pouch → vomiting
Abdominal distension
Aspiration → aspiration pneumonia
Esophageal Web Mucosal protrusion → partial obstruction Thin protrusion of esophageal mucous Dysphagia especially poorly chewed food

↑ risk for SCC of esophagus Plummer Vinson

• Fe deficiency anemia
• Beefy red tounge - atrophic glossitis
Zenker Diverticulum Outpouching of pharyngeal mucosa through acquired Acquired defect Arises aove upper esophagea spincter Dysphagia
“False Diverticulum” defect in muscular wall - @ junction of esophagus & pharynx Obstruction
“False” – only part of wall protruded Halitosis
Mallory-Weiss Longitudinal laceratin of mucosa @ GE unction Severe vomiting PAINFUL hematemesis
Syndrome/Tear • EtOH • Bulemia risk of Boerhaave Syndrome – rupture of esophagus
• Air in mediastinum → subcutaneous emphysema
• Air bubbled beneath skin → crepetance
Esophageal Varices Dilated submucosal veins in lower esophagus Portal HTN Asymptomatic but risk of rupture
Most common cause of death in cirrhosis Backup to→ L gastric vein → Esophagus Rupture → PAINLESS Hematemesis
• Hypoliver → ↓ coagulation factors
Achalasia ∅ able to relax LES Damage to Ganglia cells @ Myenteric Plexus Dysphagia for solids & liquids Birds Beak @ barium swallow
Disordered esophageal motility Idiopathic or 2ndary to Chagas (T cruzi) ↑ risk for SCC of esophagus Putrid breath ↑ LES pressure @ esophageal manometry

GERD Reflux of acid from stomach ↓ LES tone Metaplasia of Esophageal cells Heartburn – mimics cardiac chest pain
Risks: EtOH, tobacco, obesity, fat-rich diet, Normal – non-keratinizing squamous epithelium Asthma & Cough → Adult Onset Asthma
caffeine, hiatal hernia Metaplasia – non-ciliated columnar epitlium w goblet cells Damage to enamel of teeth
Complications
• Ulceration → ↓ stem cells → fibrosis→ stricture
• Barrett Esophagus - metaplasia
Esophageal Malignant proliferation of glands GERD → Barrets Must have metaplasia first → glands Progressive dysphagia, weight loss, pain, hematemesis
Adenocarcinoma Most common type of esophageal carcinoma in west • Has to be in lower 1/3rd
Mets of Lower 1/3rd → Celiac & Gastric Nodes
Esophageal Malignant proliferation of squamous cells Risk factors – Irritation Arises in upper or middle third of esophagus Progressive dysphagia, weight loss, pain, hematemesis
Squamous Carcinoma Most common esophageal cancer worldwide • EtOh, Tobacco, very hot tea, Mets of Upper 1/3rd → cervical nodes
• Achalasia, Esophageal web (Plummer V), Mets of Middle 1/3rd – mediastinal or tracheobronchial nodes Hoarseness → recurrent laryngeal nerve
• Esophageal injury (lye ingestion) Cough → trachea
 38
10.4 Stomach
Name Desc Cause Patho Clinical Dx/Tx
Gastroschisis Wall splits → Exposure of abdominal contents Congenital malformation of abdominal wall Contents of abdomen are clearly visible
Failure of wall formation
Omphalocele Persistent herniation of bowel into umbilical Failure of herniated intestines to return to body cavity Contents are covered by peritoneum &
cord amnion of umbilical cord
Pyloric Stenosis Congenital hypertrophy of pyloric smooth m.m Projectile non-bilious Vomiting
• Normal @ birth → develops after birth Peristalsis visable on abnomen
• Present @ 2 wk after birth Palpabale Olive-like mass Myotomy to treat
Acute Gastritis Acidic damage to mucosa ↑ acid production Acid damage results in
↓ protection of mucosa 1.Superficial Inflammation
• Foveolar/Epithelium – secrete stuff 2.Erosion (loss of epithelium)
• Mucous, bicarb, blood supply/nutrients 3. Ulcer (loss of mucosal layer)
Risk Factors
• Severe Burn – Curling Ulcer
o Hypovolemia → ↓ blood/nutrients <remember Parietal cell has ACh, Gastrin, & H2
• NSAID - ↓ PG → ↑ acid, ↓ mucous, ↓ bicarb, ↓ blood flow receptor → all can ↑ acid production>
• Heavy EtOH – directly toxic to mucosa
• Chemotherapy - ↓ cell turnover <remember Parietal cells are ↑ in body & fundus>
• (!) ↑ ICP (Cushing Ulcer) → ↑ CN X → ↑ Ach @ Parietal
o Ach → ↑ acid production
Shock - ↓ blood supply to stomach → Stress Ulcers
Chronic Chronic inflammation Autoimmune destruction of Parietal cells @ Body & Fundus T-cell mediated Type IV hypersensitivity Mucosal Atrophy Anti-Parietal or Anti-IF antibodies
Autoimmune T-cell mediated Type IV hypersensitivity As a result of damage → Anti-Parietal Ab or Anti-IF Ab Achlorhydria → ↑ Gastrin
Gastritis Most common cause of B12 deficiency • ∅ the source of damage, but a consequence • G-cell hyperplasia @ antrum
(!) ↑ risk for Gastric Adenocarcinoma Megaloblastic pernicious anemia
• Chronic inflammation→Intestinal Metaplasia • bc of ↓ IF
• Goblet cells in stomach
Chronic Chronic inflammation H pylori → urease & protease @ Antrium H pylori Epigastric Pain
H pylori • Ureases & Proteases ↑ risk for
Gastritis Most common form of gastritis (90%) • Bug is on epithelium, ∅ in mucosa • Ulceration Triple Therapy
• Gastric adenocarcinoma • Confirm w - Urea Breath Test
• MALT lymphoma • Confirm w ↓ HpyloriAg in stool

Peptic Ulcer Dz Solitary mucosal ulcer involving H pylori (most common) Ulcer w Hypertrophy of Brunner Glands Epigastric pain → improve @ meal Duodenal ulcers are almost never cancer
• Proximal Duodenum (90%) ZE syndrome – gastrinoma Complication → Rupture
Duodenal Ulcer • Distal Stomach (10%) • Bleed from gastroduodenal a. or
Acute pancreatis (posterior ulcer)

Peptic Ulcer Dz Solitary mucosal ulcer involving H pylori (70%) Commonly @ lesser curvature of antrum Epigastric pain → worse @ meal d/dx – Cancer
• Proximal Duodenum (90%) NSAIDs (20%) Benign Ulcer Commonly @ lesser curvature of antrum • Gastric ulcer can be caused by
Distal Stomach Distal Stomach (10%) Bile Reflex • small, Complication → Rupture gastric carcinoma
• punch-out lesions, • Bleeding from L gastric artery • Irregular lesion & space w
• smooth margins on the borders of ulcer piled up mucosa @ border
Gastric Carcinoma Malignant proliferation of surface epithelium Intestinal Type – risk factors Intestinal Type Presents late in life
(Gastric • Columnar cells → adenocarcinoma • Intestinal metaplasia (Chronic gastritis) • Large, irregular ulcer w heaped up margin Abdominal pain
Adenocarcinoma) • Nitrosamines – in smoked foods (Japan) • ↑ @ lesser curvature of antrum Anemia
• Blood Type A Diffuse Type Early satiety – esp in Diffuse
(!) Diffuse Type • Signet Ring Cells – nucleus pushed to side by mucous
• ∅ related to H pylori, intestinal metaplasia or nitrosamines • Signet ring cells → diffusely infiltrate gastri wall Rare presentation
• Desmoplasia – thickening of stomach wall are reaction • Acanthosis Nigricans
to invasion (Linitis Plastica) • Leser-Trelat Sign – seborrhac keratosis
• all over skin
Lymph Spread
• L supraclavicular node (Virshow Node)
Mets
• Liver – most common
• Periumbilical Region – Intestinal Type
(Sister Mary Joseph nodule)
• Bilateral Ovaries – Diffuse Type
(Krukenburg Tumor)
 39
10.5 Small Bowel
Name Desc Cause Patho Clinical Dx/Tx
Duodenal Atresia Blind pouch duodenum Congenital Failure of small bowel to canalize Polyhydramnios
(!) associated w Downs Syndrome Distension of stomach & duodenum
• Double-Bubble Sign
Bilious Vomiting
Meckel Diverticulum Outpouching of ALL 3 layers of bowel wall Failure of vitelline duct to involute (Persistence of Vitelline Duct) Outpouching of all 3 layers (vs Zenker’) Most are asymptomatic Palpation of umbilical area
• “True Diverticulum” • feel like poopy
Rules of 2 <if ∅ involution at all → Passing meconium via umbilicus> May present by 2 yrs of life
-Seen in 2% of population • Bleeding – acid produced
• most common GI congenital • Volvulus
-2 inches long & 2 feet from iliocecal valve • Intussesception
Volvulus Twisting of bowel along mesentery Elderly → Sigmoid Colon obstruction of bowel
Younger → Cecum distruption of blood supply
Intussusception Telescoping of proximal segment of bowel into Leading Edge obstruction of bowel
a distal segment of bowel • Children – Lymphoid Hyperplasia (infection) disruption of blood supply
o Terminal ileum → cecum (!) Currant jelly stools
• Adults - tumor
Small Bowel Infarction Infarction of small bowel Small bowel is highly susceptible to ischemic injury Infarction Abdominal Pain
-Transmural Infraction – thrombosis/emboli of SMA or mesenteric v Bloody diarrhea
-Mucosal Infraction – marked hypotension ↓ bowel sounds
Lactose Intolerance ↓ Lactase Enzyme in Brush Border of Enterocytes Abdominal Distension & Diarrhea
• Congenital - rare @ consumption of Milk products
• Acquired
o ↓ enzyme w aging (onset @ 10-20 y.o)
o after GI infection – temporary intolerance
Celiac Disease Immune-Mediated damage of small bowel vili Gluten Exposure → autoimmune damage to Villi Gliadin – pathogenic compment of grains/wheat Children IgA against
• due to gluten exposure associated w HLA DQ2 & DQ8 Gliadin -- deamidated by tTG • Abdominal distension • Endomysium
associated w IgA deficiency Deamidated Gliaden – presented by APC via MHC II • Diarrhea • tTG
Helper T-cells mediate damage • Failure to Thrive • Gliadin
<Dairy Queen combo # 2 & # 8 come with cereals & bread> Adults Use IgG antibodies if patient IgA deficient
Biopsy • Chronic Diarrhea & Bloating
• Flattening of Villi, Dermatitis Herpetiformic Biopsy – Flat Villi, Hyperplasia of Crypt
• Hyperplasia of Crypts
(!) Damage is mostly @ duodenum Long-term complications – symptoms returns Tx – Gluten-Free Diet
• Jejunum & ileum are less invovled • Small Bowel Carcinoma
• (!) T-cell Lymphoma (EATL)
Dematitis Blister/vesicle @ tip of dermal papillae IgA deposited at tips of dermal papillae Blister/vesicle @ tip of dermal papillae Tx – Gluten-Free Diet
Herpetiformis Associated w Celiac Dz
Tropical Sprue Damage to small bowel villi Unknown organism in Tropical Region (!) Damge is mostly @ Jejunum & Ileum → nutrition deficiencies Similar to celiac
Arises after Infectious Diarrhea • Duodenum is less involved
Responds to antibiotics • Folic Acid deficiency
• B12 deficiency
Whipple Disease Mφ w T whippelii Tropheryma whippelii organisms (!) Damage @ Small Bowel Lamina Propria Fat Malabsorption
Partially destroyed & present in Mφ lysosomes • Foamy Mφ in lamina propria Steatorrhea
• PAS + Systemic
Mφ build up → compress lacteals • Synivium of joints – arthritis
• Fat Malabsorption • Cardiac valves
• Steatorrhea • Lymph Nodes - • CNS
Abetalipoproteinemia Auto Rec deficiency of
• B-48 → ↓ chylomicron production
• B-100 → ↓ VLDL & LDL
Carcinoid Tumor Malignant proliferation of neuroendocrine cell Malignant proliferation of neuroendocrine cell Malignant proliferation of neuroendocrine cell Initially – no presentation ↑ 5-HIAA in urine
Low grade malignancy Can arise anywhere along the gut • Submucosal Polyp-like nodule
• Small Bowel is most common sit • Chromogranin + Carcinoid Syndrome – tigger by EtOH & stress
Secrete 5-HT into Hepatic a.a • Bronchospasm
• MAO processes it liver →5-HIAA excreted in the urine • Diarrhea
mets to liver → Secrete 5-HT into Hepatic v.v • Flushing of Skin
• 5-HT → systemic circulation Fibrosis of Heart Valves (R-Heart)
• Carcinoid Heart Dz @ R-lung • Carcinoid Heart Dz
• 5-HT destroyed by MAO @ lungs → ∅ L heart fibrosis • Tricuspid Regurg→ Pulm Stenosis
 40

10.6 & 10.7 Appendix & IBD

Name Desc Cause Patho Clinical Dx/Tx
Acute Appendicitis Acute inflammation of appendix wall Obstruction of appendix by Periumbilical Pain
Most common cause of acute abdomen • Lymphoid hyperplasia (child) • Starts diffuse → localize to RLQ
• Fecalith ( adults) Fever
Nausea
Complication → Rupture
• Peritonitis
• Guarding & rebound tenderness
Complication → Periappendiceal Abcess
Inflammatory Bowl Chronic relapsing inflammation of bowel Possibly due to abnormal immune response to enteric flora Recurrent diarrhea Diagnosis of Exclusion
Disease Abdominal Pain • Rule of infection,
Classically Young adult female w ischemia, etc
• Recurrent bloody diarrhea & abdominal pain
↑ in Caucasian, Jewish, & western decent
Ulcerative Colitis Associations Mucosal & submucosal ulcers LLQ pain – where rectum is Lead-pipe sign
• Primary Sclerosing Cholangitis (!) Crypt Abcess – PMN in crypts = histologic hallmark Bloody Diarrhea
• + p-ANCA Begins @ rectum → continuous involvement through colon → cecum
• Remained of GI tract is unaffected Complications
Smoking is PROTECTIVE against UC Gross • Toxic Megacolon → risk of rupture
• Pseudopolyps • (!) Carcinoma – risk based upon
• ↓ haustra → lead pipe sign o Extent of colon invlvmnt
o Duration of dz
Crohns Disease Associations Full-thickness inflammation w Knife-life Fissures RLQ pain String-sign
• Ankylosing spondylitis Lymphoid aggregates w Granulomas Non-bloody diarrhea
• Sacroiliitis Skip Lesions – anywhere from mouth to anus
• Migratory polyarthritis • Terminal ileum – most common Complication
• Erythema nodosum • Rectum – least common • Malabsorption, ↓ nutrition
• Uveitis Gross • CaOxalate Nephrolithiasis
• Cobblestoning of Mucosa o Inflammation → ↑ GI oxalate
Smoking ↑ risk for Crohns Dz • Creeping fat – fat pulled close to lesion by myofibroblast entering blood
• Strictures - ↓ lumen of wall→ string sign • Fistula Formation
• (!) Carcinoma – if colon affected
 41
10.8 Colon
Name Desc Cause Patho Clinical Dx/Tx
Hirschsprung Dz ↓ relaxation & peristalsis of rectum & distal Congenital failure of ganglion cells to descend ∅ Ganglion cells Failure to pass meconium (!) Rectal suction biopsy
sigmoid colon Associated w Downs Auer Bachs Plexus in Muscularis Proprius Empty rectal vault on DRA • ∅ ganglion cells
– peristalsis & relaxation Massive dilation of bowel proximal to obstruction
Meisners submucosal plexus • Risk of rupture Tx: Resection of involved bowel
– blood flow & secretions

Colonic Diverticula Outpouching of mucosa & submucosal through Wall Stress → ↑ risk Arise where Vasa Recta travese Muscular Propria Usually asmymptomatic
muscularis propria Constipation, Low Fiber diet • Weak point in colon wall Complications
• False outpouching Common in older adults Sigmoid Coon - Most common location • Bleeding – occurs adjacent to veins
 Hematochezia
<high stress in L colon> • Diverticulitis – “L sided appendicitis”
• Colovesicular fistua → air or stool in urine
Angiodysplasia Acquired malformation of mucosal & Arise in cecum & R colon due to ↑↑ wall tension Hematochezia in an older adult
submucosal capillary beds <high stress in R colon>
Hereditary GI, skin, & nose bleeds from thin vessels Auto Dom disorder Telanictasisa – dialted thin wall capillary Vessels rupture → Bleeding
Hemorrhagic ↑ @ nasopharynx & GI tract
Teleangiectasia
Ischemic Colitis Ischmic damage to colon Atherosclerosis of SMA ↑ @ splenic flexure Postprandial Pain & Weight Loss
• Post-meal = ↑ energy demand
• Angina of the gut
Infarction → Pain & Bloody diarrhea
Irritable Bowel Relapsing abdominal pain Related to disturbed intestinal motility ∅ biopsy finding Bloating & Flatulence Fiber may improve symptoms
Syndrome ↑ in middle aged females ∆ bowel habits (diarrhea, conspitation, or alternating)
Improves w defecation
Hyperplastic Raised prorusions of colonic mucosa Hyperplasia of Glands Hyperplasia of glands
Colonic Polyps Most common type of polyp Usually in L colon (rectosigmoid) “Serrated” appearance on microscopy
Benign - ∅ malignant potential
Adenomatous Polyp 2nd most common type of colon polyp Neoplastic proliferation of glands Benign but Premalignant Screen for Polyps
Colonic Polyps • May progress to adenoma via Adenoma-Carcinoma sqnc -Heme-occults & Colonoscopy
(!) Adenoma-Carcinoma sequence -Remove polyps before carcinoma
• APC mutations (sporadic or germline) → ↑ risk of polyp -↑ risk polyp
o Chromosome 5 • > 2 cm size
• K-ras mutation → formation of polyp • Sessile growth – flat
• p53 mutation & ↑ COX expression → progress to carcinoma • Villous histology
o ASA protects against this sequence by ↓ COX
Familial Adenomatous Autodom Germline APC mutation 100s-1000s of adenomatous colonic polyps 100s-1000s of adenomatous colonic polyps Prophylactically remove
Polyposis (FAP) • Chromosome 5 Progress to carcinoma by 40 y.o – colon & rectum

Gardner Syndrome FAP & Fibromatosis & Osteoma Fibromatosis – fibroblast proliferation → destructive
Osteoma - tumor bone, ↑ in skull
Turcot Syndrome FAP + CNS tumors
• Medullobalstoma & Glial Tumors

Juvenile Polyp Sporadic hamartomatous (benign) Polyp
Arises in Children < 5 yo
Juvenile Polyposis Multiple juvenile polyps in stomach & colon
Peutz-Jeghers Hamartomatous polys throughout GI tract
Syndrome Mucocuataneous hyperpigmentation of lips,
oral mucosa & genital skin
Colorectal Carcinoma Carcinoma arising from colon or rectal mucosa
Peak incidence @ 60-70 y.o
HNPCC
Autosomal Dmoinat
1.Adenoma-Carcinoma Sequence – most common cause (~80%)
2.Microsatellite Instability (MSI)
• Repeating segments of non-coding DNA
• Damage in MSI → other damage to DNA
Inherited mustaion in DNA mismatch repair enzymes (MSI)
Solitary rectal polyp May prolapse & bleed
↑ # of polps → ↑ risk of progression to carcinoma
Hamartomatous polys throughout GI tract
Mucocuataneous hyperpigmentation of lips, oral
mucosa & genital skin
↑ risk for colorectal, breast, & GYN cancer
Other Risk Factors L –sided Screening – Colonscopy & FO blood
• Ulcerate Colits • Peutz Jahgers • ↓ stool caliber • LLQ pain -Screen @ 50
Cancer develop anywhere • Blood Streaked Stool -Goal – Remove polyps before cancer
• L Sided - Napkin-Ring lesions (usually Adenoma Carcinoma) R – sided - Detect cancer early
• R sided – grows as raised lesions (usually MSI) • Fe-deficiency-bleed • Vauge pain Staging – TNM staging
o (!) ↑ risk for Streptococcus Bovis endocarditis -Most common mets → liver
Colorectal carcinoma arises de novo at an early age ↑ risk for colorectal, ovarian & endometrial carcinoma CEA – asses treatment response &
• Usually Right sided recurrence → ∅ screening!
 42
11.1 Exocrine Pancreas
Name Desc Cause Patho Clinical Dx/Tx
Annular Pancreas Pancrease forms ring around duodenum Developmental malformation Risk of duodenal obstruction
Acute Pancreatitis Inflammation/hemorrhage of pancrease Autodigestion of pancrease by pancreatic enzmes Liquifactive necrosis of pancreas w Hemorrhage Epigastric abdominal pain ↑ serum lipase & amylase
Premature activation of Trypsin → activation of other enzymes Fat necrosis of peripancreatic fat • Radiates to back • Lipase is ↑ specific
2 most common causes Nausea & VOmitting Hypocalcemia
• EtOH – contraction of sphincter or Oddi Perumbilical & Flank hemorrhage
• Gallstones – block ampulla Complications
Other causes • Shock
• trauma (auto accident in children) • Pancreatic pseudocyst
• hyperCalcemica, hypreLipidemia, • Pancreatic abcess
• Drugs, Scorpion stings, Mumps, • DIC & ARDS – pancreatic enzymes in
• Rupture of posterior duodenal ulcer blood → trigger C’ & alveoli
Chronic Pancreatitis 2ndary to recurrent acute pancreatitis Fibrosis of pancreatic parenchyma Epigastric abdominal pain Amylase & lipase are POOR markers
Most common • EtOH – adults • CF – children • Radiates to back • These stay low
Pancreatic Insufficiency
• Malabsorption & steatorrhea
• Fat soluble Vit deficiency (↓ A,E,D,K)
Complication
• Dystrophic calcification of pancrease
• 2ndary DM (late finding)
• Pancreatic Carcinoma
Pancreatic Carcinoma Adenocarcinoma from pancreatic ducts Chronic Pancreatitis Epigastric abdominal pain Serum tumor marker
Smoking Weight loss • CA-19-9
↑ in eldery 2ndary DM – in body or tail Tx
• Thin elderly w new onset DM -Whipple Procedure
Pancreatitis -Remove head, neck of pancreas &
Migratory Thrombophlebitis duodenum
@ Head Of Pancreas
• Obstructive jaundice 1 yr survival - < 10%
• Pale stools & Palpable gallbladder
11.2 – Gallbladder & Biliary Tract
Name Desc Cause Patho Clinical Dx/Tx
Billiary Atresia Failure to form or early destruction of Congenital - failure to form Biliary obstruction within first 3 months Conjugated bilirubin
extrahepatic biliary tree Early destruction – via infection Jaundice
→Cirrhosis
Cholelithiasis Precipitation of cholesterol or bilirubin in bile Cholesterol Stone – most common in west Usually asymptomatic
(Gallstones) • Supersaturation -( cholestyramine → ↑ cholesterol) • Radiolucent Complications -see belw
• ↓ phospholipids/bile acids – • Grossly: Yellow color
• Statsis • Risks – Age, Estrogen/Female gender, Clofibrate,
Native america, Chrons Dz-ileum damage, Cirrhosis
Bilirubin Stone
• Radiopaque
• Extravascular hemolysis → ↑ unconjuaged bilirubin
• Biliary Tract Infection – E coli, Ascaris, Clonorchis
Biliary Colic Gallbladder push against stone in cystic duct waxing/waning RUQ pain

Acute Cholecystitis Inflammation of gallbladder Compression → ↓ blood to GB → infctn RUQ pain radiating to R-scapula ↑ WBC, N+V, ↑ Alk-Phos
Risk of Rupture if ∅ treated
Chronic Cholecystitis Chronic inflammation of galbladder Long standing cholelithiasis Rokitansky-Aschoff sinus Vague RUQ pain – especially after eating Tx – Cholecystectomy
Chemical irritation • Herniation of gallbladder mucosa into muscular wall • Especially if porcelin
Porcelain Gallblader – late complication Porcelain Gallblader – late complication gallbladder
• Shrunken, hard, fibrosed gallbladder due to chronic
inflammation, firbosis, & dystrophic calcification
Ascending Cholangitis Bacterial infection of bile ducts Ascending Infection w Enteric G- bacteria Sepsis
↑ incidence w choledocholithiasis Jaundice
Abdominal Pain
Gallstone Ileus Gallstone enters/obstructions small bowel Cholecystitis → fistula bt gallbladder & small bowel
Gallbladder Carcinoma Adenocarcinoma of gallbladder gland epithlum Gallstones – major risk facor → esp porcelain gallbladder New onset Cholecystis Poor prognosis
• esp in eldery woman
 43

11.3 – Liver Jaundice

Name Desc Cause Patho Clinical Dx/Tx
Jaundice Yellow discoloration of skin ↑ serum bilirubin Bilirubin Metabolism Scleral Icterus – earliest sign
• > 2.5 mg/dL • RBC live for ~ 120d → Mφ of RES remove old RBC+ Yellow skin
hemoglobin (↑ in spleen)
• Globin → proteins → aminoacid
• Heme
• Protoporphyrin→UCB→ UCB+albumin → Liver→CB
→ bile caniculi → bile duct → gallbladder → excreted
@ digestion
• CB + gi flora → Urobilinogen
• Urobilinogen makes poop brown & pee yellow
Extravascular Hemolysis ↑ RBC destruction → ↑ UCB → overwhelm liver UCB floats in blood until liver gets a chance Dark Urine ↑ [UCB]serum
Ineffective erythropoiesis • ∅ water soluble → ∅ able to enter urine • ↑ urobilinogen from CB ↑ [CB]bile → ↑ urobilinogen
↑ risk for pigmented gallstones
Physiology jaundice of Low conjugating ability in new liver UCB is fat soluble → deposit in brain → Basal Ganglia Neurological deficicits ↑ [UCB] serum
newborn • ↓ UGT enzyme activity • Kernicterus → neurodaamge Death Phototherapy – makes UCB water soluble

Gilbert Syndrome Auto Rec mildly ↓ UGT activity Jaundice @ stress (eg infection) ↑ [UCB]serum
Otherwise - ∅ clinically significant
Crigler-Najjar Syndrome ∅ UGT UCB is fat soluble→ deposit in brain→ Basal Ganglia → Kernicterus Kernicterus → fatal <the evil version of Gilbert>
Dubin-Johnson Auto Rec deficiency of Bilirubin canalicular transport Dark liver ∅ clinically signification ↑ [CB] serum
Rotor Syndrome –same as DJ but ∅ liver discoloration (!) liver is pitchblack
Biliary Tract Obstruction Gallstones, pancreatic carcinoma, cholangiocarcinoma CB is water soluble → pass into urine Pruitis – bile acid deposit in skin ↑ [CB], ↑ plasma bile acids, ↑ cholesterol
Obstructive Jaundice Parasites, liver fluke (Clonorchis sinensis) Xanthomas – hypercholesterolemia ↓ urine urobilinogen
Steatorrhea & malabsorption of Fat soluble vitamin
Dark urine – due to CB
Pale stool
Viral Hepatitis Inflammation of hepatocyte ^ small bile Dark Urine ↑ [CB] & ↑ [UCB]
ductures Normal urine urobilinogen
Hepatits Hepatitis section – see SSG Bug Parade Acute hepatitis Acute
EBV or CMV Acute • Jaundice – CB & UCB • ↑ ALT > ↑ AST
• CB – from destroying ductule • Dark Urine – from CB •
• UCB – from detstroying hepatocytes • Nausea, fever, malaise
Chronic • Symptoms < 6 months
• Involves portal tracts Chronic Hepatitis
• Symptoms > 6 months
• Risk of cirrhosis
Hep A & E F-O
A – travelers
E – F-O or undercooking cseafood
Hepatitis section – see
SSG Bug Parade
 44
11.4 – Liver Cirrhosis & tumors
Name Desc Cause Patho Clinical Dx/Tx
Cirrhosis End-stage liver damage Disruption of normal hepatic parenchyma Portal HTN
Bands of Fibrosis & regenerative nodules of hepatocytes • Ascites
(!) Stellate Cell - mediates fibrosis • Congestive splenomegaly→hypersplenism
• TGFβ → mediate fibrosis • Potosystemic shunts →
• Lie beneath endothelial cells lining sinusoids esophagus varices, hemorrhoids, caput madusea
• Hepatorenal syndrome
↓ blood detoxification/clearace of substance
• Mental status change → asterixis → come
• Gynecomastia, Spider angiomata, palmar erythema
• Jaundice
↓ protein synth
• Hypoalbuinemia –↓ osmotic pressure → edema
• Coagulopathy - ↑ PT & PTT (track w PT like warfarin)
EtOH-related Liver dz Most common cause of liver damage in west EtOH → damage parenchyma Fatty Liver Painful hepatiomegaly AST > ALT
• Accumulation of fat in hepatocytes→ greasy liver • AST > ALT
• Reversible w Abstinence • AST is in mitochondria → EtOH damages mito
Alcoholic Hepatitis
• Chemical injury to hepatocytes @ binge drinking
• Damage via acetylaldehyde
• Ballooning/swelling of hepatocytes
• Mallory Bodies – damaged intermediate fillaments
Cirrhosis - Chronic EtOH inuduced liver damage
Non-Alcoholic Dx of Exclusion Fatty change, Hepatitis, or Cirrhosis ALT > AST
Fatty Liver Dz Associated w obesity • w/o EtOH
Hemochromatotsis Fe deposition Hemosiderosis – deposit → Hemochromtosis = damage Present in late adulthood ↑ ferritin
1° ↓ enterocyte regulation of Fe (!) Damage via generation of Free Radicals Cirrhosis ↓ TIBC
• C282Y mutation @ HFE gene 2ndary DM – Bronze Diabetes ↑ serum iron
• all Fe goes into blood → Fe overload Biopsy Bronze Skin ↑ percent saturation
2° - complication of transfusions • Brown pigment in hepatocytes Cardiac arrhythmia Biopsy – brown hepatocyte, Prussian Blue+
• Fe accumulate as RBC turnover in 120d • Prussian Blue stain + ( helps d/dx Fe via lipofuscin) Gonadal dysfunction
↑ risk of Hepatocellular Carcinoma Tx – multiple transfusions
Wilsons Disease Auto Rec defect in ATP7B gene Cu accumulates into hepatocytes → serum → tissues Cirrhoism ↑ [Cu]urine
ATP-mediated hepatocyte Cu transport (!) Cu-mediated production of Hydroxyl free radiacls many CNS –dimentia, chorea, ∆ behavior, Parkinson-like, etc ↓ serum ceruloplasmin
• ↓ Cu into bile Kayser-Fleisher rings ↑ [Cu] @ liver biopsy
• ↓ Cu into ceruloplasmin ↑ risk of Hepatocellular Carcinoma
Tx – D-penicillamine
• Cu chelator
Primary Biliary Cirrhosis Autoimmune granulomatous destruction of Obstructive jaundice (!)Antimitochondrial antibody
intrahepatic bile ducts Cirrhosis – late complication
• Antimitochondrial antibody
Primary Sclerosing Inflammation & firbosis of intrahepatic & Unknown Periductal fibrosis w onion-skin appeance Obstructive jaundice
Cholangitis extrahepatic bile ducts Associated w Ulcerative Colitis Uninvolved regions are dilated → Beaded apperance Cirrhosis – late complication
p-ANCA is often positive ↑ risk for cholangiocarcinoma
Reye Syndrome Fuminant liver failure & encephalopathy in Virus + ASA Hypoglycemia
children w viral illness who take ASA Mitrochondrial damage of hepatocytes ↑ liver enzymes
<remember Kawaski – vasculitis that needs ASA to treat> N+V
May progress to coma & death
Hepatic Adenoma Benign tumor of hepatocytes Associated w OC → regress w cessation Subcapsular Benign
Risk of rupture → intraperitoneal hemorrhage
• esp @ pregnancy
Hepatocellular Carcinoma Chronic Hepatits Invade Hepatic v → ↑ risk of Budd-Chiari Budd-Chiari – painful hepatomegaly & acites Poor prognosis – late detection
Cirrhosis – any cause αFP
Aflatoxins from Aspergillus (p53 mutations) αFP
Mets to Liver More common than primary Colon ca, pancreas ca, lung, breast ca Multiple nodules in lvier Hepatomegaly w nodular free edge of liver
 45
12.1 Congenital Renal Dz
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Horseshoe Kidney Conjoined Kidney → usually connected at lower pole Located in lower abdomen → caught on IMA root
Most common renal congenital anomalie

Renal Agenesis Absent kidney Unilateral → Hypertrophy of remaining Kidney Incompatible w life
• Unilateral • Hyperfiltration → risk of renal failure
• Bilateral Bilateral Agenesis
• (!) Oligohydramnios → Potter Sequence
o Lung Hypoplasia,
o Flat face w low set ear,
o ↓ development of extremities
Dysplastic Kidney Unilateral in real life Noninherited congenital malformation of renal parynchma Noninherited → ∅ genetic
Often presented Bilaterally on Exam Cysts w abnormal tissue (cartilage)
• Must distinguish from inherited PKD
Polycystic Kidney Dz Bilateral enlarged kidneys Inherited defect Bilateral enlarged kidneys w cysts in
(PKD) renal cortex & medull
Auto-Rec PKD Auto Rec PKD ↑ in infants <cysts in kidney & cysts in liver>
Newborns may present w Potters Sequence
Associated w Congenital Hepatic Fibrosis & Hepatic Cysts → Portal HTN
Auto-Dom PKD Auto Dom PKD HTN – from ↑ renin Berry anyeurism is a common cause of death
Mutation in APKD1 or APKD2 → cysts develop over time Hematuria
Worsening renin failure <cysts in liver, brain, & kidney>
Associated w Berry Aneurysm, Hepatic Cysts, Mitral Valve Prolapse a
Medullary Cystic Inherited Auto Dom defect Worsening renal failure Cyts in Medullary Collecting Ducts
Kidney Dz • Cysts in medullary collecting ducts (!) Shrunken kidneys
12.2 – Acute Renal Failure
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
ARF (General) ↓ renal function Azotemia - ↑ BUN & creatinine BUN/creatinine ratio – Normal = 15
Oliguria - ↓ production of urine
PreRenal Azotemia ↓ renal a.a blood flow ↓ GFR (!) Serum BUN/creatinine ratio : >15
• CHF • Renal a.a emboli/occlusion Azotemia FENa <1%
Tubular function intact/normal Urine Osm > 500
Oliguria
PostRenal Azotemia ↓ ureter outflow → backpressure in kidney → ↓ GFR ↓ GFR, Azotemia, Oliguria Early Stage
Early Stage • Pressure forces BUN into blood →
• Pressure forces BUN into blood → Serum BUN/Cr ratio : >15
• Serum BUN/Cr ratio : >15 • Tubular function intact –
• Tubular function intact – FENa<1% & Urine Osm >500 FENa<1% & Urine Osm >500
Long-standing Obstruction → tubular damage Long-standing Obstruction → tubular damage
• ↓ BUN reabsorption → BUN:Cr < 15
• ↓ BUN reabsorption → BUN:Cr < 15
• ↓ Na reabsorption → FENa > 2%
• ∅ able to concentrate urine → Urine OSM < 500 • ↓ Na reabsorption → FENa > 2%
• ∅ concentrate→ Urine OSM < 500
Acute Tubular Most common cause of ARF Ischemic ATN Oliguria w brown granular casts (!) Dirty Brown granular casts in urine
Necrosis Injury & Necrosis of tubular epithelial cells • ↓ blood supply → PreRenal → necrosis Azotemia BUN:Cr < 15
Necrotic cells block tubule → ↓ GFR • ↑ risk @ proximal tubule & medullary TAL ↓ reabsorption : FENa > 2%
Nephrotoxic ATN – due to toxic agents Hyperkalemia & metabolic acidosis
• ↑ risk @ proximal tubule • ↓ renal excretion of K Reversible
• Aminoglycosides, Heavy Metals (Pb), • ↓ renal excretion of H → ↑ anion gap • Requires supportive dialysis
Myoglobinuria (crush injury), Ethylene Glycol, • Oliguria can persist for 2-3wk before
Radiocontrast dye, Urate (tumor lysis) recovery → tubular cells take time to
renter cell cycle
Acute Interstitial Inflammation of interstitial (connective) tissues Hypersensitivity a drug Oliguria, FEVER, RASH that begins days/weeks after starting drug (!) Eosinophils in Urine
Nephritis • Tubules are ok • NSAID • PCN • Diuretics Complication – Renal Papillary Necrosis Remove Drug → resolves
Renal Papillary Necrosis of renal papillae Chronic analgesic abuse Gross Hematuria & flank pain
Necrosis DM
Sickle Cell
Severe Acute Pyelonephritis
 46
12.3 Nephrotic Syndrome
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Nephrotic Syndrome Proteinuria > 3.5 Edema Endothelial Cell→BM→Podocytes
(general) • Hypoalbuminemia → ↓ Edema Podocytes = epithelial cells
• Hypogammaglobulin → ↑ infection risk Foot processes
• Loose ATIII → hypercoagulable
• Hyperlipidemia & Hypercholesterolemia
o Liver ↑ production - “blood is “thin”
Minimal Change Dz Most common cause of nephrotic syndrome in children Cytokines → damage podocytes Effacement of Podocytes on EM Selective Proteinuria
(MCD) usually Idiopathic Normal Glomeruli on H&E stain • Loss of albuinm but ∅ immunoglobulin)
(!) may be associated w ∅ immune complex→ (-) Immunofluorescence
• Hodgkins Lymphoma (!) Steroids – excellent response → ↓ CK
↑ CK production by Reed-Sternberg Cells
Focal Segmental Most common cause of neprhrotic in Hisplanics & Blacks Usually Idiopathic Dense deposition of collagen in glomerulus Poor response to steroids
Glomerulosclerosis (!!) may be associated w Focal – only involves a few glomeruli
(FSGS) <its kinda like a progression of a MCD that doesn’t respond to • HIV Segemental – of the glomeruli involved, only certain Will progress to Chronic Renal Failure
steroids> • Heroin use portions effected, not the whole thing
• Sickle Cell Effacement of Podocyte on EM
∅ immune complex → (-) Immunofluorescence
Membranous Most common cause of nephrotic in Caucasian adult ImmuneComplex Deposition Thick glomerular BM on H&E
Neuropathy Usually idiopathic IC Deposition → Granular immunofluorescence we<note:
May be associated w Subepithelial deposits w “spike & dome” appearance • SLE – most common renal disorder is
<membranous = • HBV, HCV, solid tumors, on EM Diffuse proliferative GN but if
immune complex • SLE Membranous is the nephropathy they
deposition> • Drugs - Nasids, penicillin get
>
Membranoproliferative Mesangial cell grows/proliferates Type I - associated w HBV & HCV (!) Can produce nephrotic synd, nephritic synd or both Thickening of capillary membrane
Glomerulonephritis → seperates deposits → tram track • Subendotheial deposits • Tram-Track appearance
• ↑ formation of Tram-Tracks IC Deposition → Granular immunofluorescence
Type II – C3-nepritic factor • Type I - Subendothelial deposit
• C3 nephritic factor (C3 convertase antbody • Type II – BM deposits
that stabilizes enzmye→ activate C3 → ↑ C’)
• Basement membrane deposits
DM NEG of BM → protein leak → hyaline arteriolosclerosis ↑ glucose → non-enzymatic glycosylation of vascular BM Sclerosis of Mesangium ACE inhibitor - ↓ AT-II @ efferent arteriole
• ↑ @ efferent arteriole → ↑ GFR → hyperperfuse → Kimmelsteil-Wilson Nodules
Hyperperfusion
• Begins as microalbuminuria → progresses to
sclerosis of mesangium → nephrotic syndrome
Systemic Amyloid Kidney is most commonly involved organ in Amyloid Amyloid deposit in mesangium Congo Red w Apple-Green Bifringence
 47
12.4 Nephritic Syndrome
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Nephritic Syndrome Glomerular Inflammation & Bleeding = hallmark Hypercellular Inflamed Glomeruli
• Immune-complex → C’ → C5a → PMN
• RBC casts & dysmorphic RBC in urine
Oliguria & Azotemia
Limited Proteinuria (<3.5g/d)
Na retention→ periorbital edema & HTN
PostStrep GN ↑ in children but can occur in adults too Group A β Heme infection of Skin & Pharynx Hematuria (cola colored) Hypercellular inflamed glomeruli Deposits will self-resolve → tx is supportive
• M-protein virulence factor Oliguria Immunecomplex → Granular IF Adults – have risk of progression to RPGN
Can occur from non-strep organisms too Periorbital Edema Subepithelial Hump @ EM
• Lumpy-Bumpy
Rapidly Progressive Nephritic syndrome → Renal Failure in weeks to months Crescents in Bowmans Space
GN • Made from Fibrin & Mφ
Immunofluorescence
• Linear → Anti-BM = Goodpasture
• Granular
o PSGN (more common)
o Diffuse Proliferative - SLE
• Negative – Pauci-Immune → ANCA
o c-ANCA → Wegner’s
o pANCA

Microscopic Polyangitis

Churg-Strauss
IgA Nepropathy Most common nephropathy worldwide IgA-immune complex deposition in MESANGIUM Episodic gross or microscopic hematuria IgA complex deposition on mesanguium → Granular IF
(Begers Dz) ↑ in childhood following mucosal infection • RBC casts
Complication → progression to Renal Failure
Alports Syndrome Defect in Type IV collagen Isolated Hematuria Thinning/splitting of glomerular BM <Air-ports – gotta make your flight @ 4 of clock,
• Most common type – X-linked Sensory Hearing loss with your family. But the airport is so busy that
• Family Hx of clinical symptoms →→ Ocular disturbances you went to the bathroom (hematuria) you
couldn’t see or hear your family afterwards>
12.5 UTI
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
UTI (General) Most often ascending but can also come via blood
• Sex • Catheters • Urinary Stasis
Cytitis Infection of Bladder E.coli (80%) Dysuria Culture - >100,000 CFU (Gold Standard)
Staph saprophyticus - ↑ in young sexually active F Urinary Frequency/Urgency ↓ systemic signs Urinalysis: Cloudy urine w >10 WBC/hpf
Klebsiella pneumoniae Suprapubic pain Dipstick: + Luekocyte Esterase & NitrItes
Proteus mirabilis – alkaline urine w ammonia smell
Enterococcus fecalis
Sterile Pyuria Burns when you pee but urine is clean think about Urethritis Pyuria w negative culture Pyuria w negative culture
Chlamydia trachomatis & N. gonorrhea
Pyelonephritis Infection of kidney Ascending Infection Flank pains – infection makes kidney capsule tender WBC casts
• ↑ risk w vesicouteral reflex Fever Leukocytosis
E coli (90%), Klebsiella, Enterococus Symptoms of cystitis
Chronic Interstitial Fibrosis & Atrophy of kidney Multiple bouts of Acute Pyelo Cortical Scarring , Blunted Calyces
Pyelonephritis • ↑ rin Children w Vesicouteral reflux (VUR) Scarring @ upper & lower poles – characteristic of VUR
• ↑ risk in Obstruction (BPH) Thyroidization of Kidney – atrophic tubules contain eosinophilic
proteinaceous material → resembles thyroid follicles
12.6 Precipitation of urinary solute as stone Risks Colicky pain Ca-Oxalate or Ca-PO4 – most common types If ∅ passed → Sx may be needed
Nephrolithiasis • ↑ [solute] • ↓ urine volume Hematuria • Idiopathic calciuria – most common cause
Ca-Ox or Ca-PO4 – idiopathic calciuria Flank tenderness • Rule out hypercalcemia Calcium Stone – HCTZ
AMP – proteus • Crohn’s – bowel damage → ↑ oxalate absorption
Uric Acid – gout, hyperuricemia, myeloproliferative dz AMP (Ammonium-Mg-PO4) – Staghorn AMP – Surgery
Cystein – children w cystinuria • urease+ organisms → Proteus & Klebsiella
• Staghorn stones in calyces → 2ndary infection Uric Acid –
Uric Acid - ↑ in gout, hyperuricemia, & myeloproliferative dz • hydration,
• Radiolucent - ∅ show up on KUB • alkalinization of urine - bicarb
• ↑ in hot climate, ↓ urine volume, acidic pH • allopurinol
Cysteine – rare, ↑ in children w Cystinuria Cysteine – hydration, alkalinzation of urine
• Can also produce Staghorn in kid
 48
12.7 Chronic Renal Failure
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
End-Stage Kidney Any lesion Uremia Shrunken kidney Dialysis
Failure -Glomerular or Tubular • Nausea • Anorexia • Pericarditis • @ dialysis → Cysts can develop on • (!) ↑ risk of renal cell carcinoma
-Inflammatory or Vascular • Platelet dysfunction shrunken kidney Renal Transplant
Common causes – HTN, DM, glomerular dz • Encephalopathy w asterixis
• Urea crystals deposit in skin
Na/H2O retention → HTN
Hyperkalemia w Metabolic Acidosis (anion -gap)
(!) Anemia - ↓ erythropoietin
• ↓ Renal peritubular interstitial cells
Hypocalcemia
• ↓ 1α hydroxylation of Vit D @ Prox Renal Tub
• ↓ PO4 excretion → hyperphosphatemia → binds Ca
Renal Osteodystrophy – 3 components
• Osteitis Fibrosa Cystica – hypocalcemia → ↑ PTH → bone
reabsorption → fibrosis & cyst formation in bone
• Osteomalacia - ∅ able to mineral osteoid
• Osteoporosis – leach mineral from bone → trying to buffer
metabolic acidosis → leach Ca
12.8 – Renal Neoplasia
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Angiomyolipoma Hamartoma w blood vessel, smooth m.m & adipose ↑ in Tuberous Sclerosis
Renal Cell Malignant epithelial tumor arising from tubule Loss of VHL (3p) tumor suppressor (!) Triad: Hematuria, Palpable Mass, Flank Pain Grossly - Yellow mass Stageing
Carcinoma • ↑ IGF-1 & HIF • ∅ all present at same time Clear Cytoplasm T – size & involvement of renal vein
• HIF → ↑ VEGF & PDGF Fever or Weight Loss N – spreads to retroperitoneal lymph nodes
1.Sporadic – single tumor, upper pole, adult Mutiple Paraneoplastic Syndrome
• smoker • EPO → Polycythemia • Renin → HTN
2.Hereditary – younger, bilateral • PTHrP → Hypercalcemia • ACTH → Cushing
• Von Hipple Landau Dz → ↓ VHL L-sided Varicocele – rare presentation
→ also @ risk for hemangioblastoma of • Block L-renal vein → block L spermatic vein
cerebellum • R spermatic vein drains into IVC so R-side ∅ affected
Wilm’s Tumor Most common malignant renal tumor children WT1 mutations Large unilateral flank mass Comprised of
(average age = 3yo) WAGR syndrome Hematuria • (!) Blastema
Beckwith Wiedemann Syndrome HTN – due to renin • Primitive glomeruli, tubules, stroma
WAGR Mutation/deletion on chromosome 11 • Wilms Tumor
syndrome • 11p13 → PAX6, WT1 • Aniridia
• Genital Anomaly’s
• Mental/Motor Retardation
Beckwith Sporadic (85%) or Familial (15%) • Wilms Tumor & Hepatoblastoma
Dactinomycin
Wiedemann Chromsome 11 short arm involved (11q15) • Neonatal hypoglycemics
Syndrome • Muscular Hemihypertrophy
• Organomegaly – esp @ tounge (macroglossia)
Denys-Drash Abnormal WT1 • gonadal dysgenesis – pseudohermaphrodism Mesangial renal scloris Progresses to renal failure (usually by 3 y.o)
Syndrome • nephropathy
• Wilms tumor
12.9 – Lower Urinary Tract Carcinoma
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Urothelial Malignant tumor from urotehial lining of lower UT #1 risk = Cigarrete Smoke – polycyclic hydrocarbons Painless Hematuria Flat – associated w early p53 mutations Tumors often multifocal & reoccurring
(transitional cell) Most common type of lower UT cancer • Napthylamine – also in cigs - High grade tumor → invade • Field Defect – entire uretelial
carcinoma • Most common location = bladder Azo Dyes Papillary field is impacted/mutated →
↑ in older adults Long-term cyclophosphamide or phenacetin • Papillary growth - starts as low grade more tumors will develop
• low grade → high grade → invade
Squamous Cell Malignant proliferation of squamous cells Chronic Cystitis
Carcinoma • Usually involves bladder (!) Schistosoma haematobium - ↑ in middle eastern boys
Arises after Squamous metaplasia → dysplasia Long-standing nephrolitiasis
Adenocarcinoma Malignant proliferation of glands Urachal remnant – lined by glandular cells Urachal origin - @ dome of bladder
• Usually involves bladder • (!) Present @ DOME of bladder
urachal reminant, cystitis glandularis, exstrophy Cystitis Glandularis – columnar metaplasia of bladder
Bladder Exstrophy - ∅ form caudal portion of bladder wall
 49
13.1 Vulva – external skin & mucosa (external to hymen) → lined by squamous epithelium
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Bartholin Cyst Cystic dilation of Bartholin Gland Inflammation/Obstruction of Bartholin Gland Unilateral painful cyst Complication - Abcess
Women of reproductive age – can have hx of STD Located in lower vestibule, adjacent to vaginal canal

Condyloma Warty neoplasm of vulvar skin HPV 6 or 11 – most common cause Can infect vulva, vaginal canal, & cervix, Koilocytic Change HPV classification based on DNA sequencing
Warty neoplasm • Crinkled “raisin-like” nucleus
Low risk to progress to carcinoma Rare complication – Progression to Carcinoma

Lichen Sclerosis Thinning of epidermis Most common in postmenopausal Leukoplakia w Parchment-like vulvar skin
Fibrosis of dermis Benign but associated w ↑ risk for Squamous Cell Ca

Lichen Simplex Hyperplasia of vulva squamous epithelium Chronic Irritation & Leukoplaskoa w thick,leather, vulvar skin
Chronicus Scratching Benign & ∅ increased risk of cancer

Vulvar Carcinoma Rare – accounts for a small % of female genital cancers HPV-related (16,18,31,33) [in female 40-50 y.o] Leukoplakia
Arise from squamous epithelium lining vulva • VIN dysplasia → vulvar carcinoma • Biopsy used to distinguish from other diagnosis
Non-HPV related [in post-menopausal woman >70 y.o]
• Long standing Lichen Sclerosis→ progresses
Extramammary Malignant epithelial cell in Epidermis of vulva Erythematous, pruritic, ulcerated skin Pagets cells in epithelium D/Dx
Paget Disease Pagets –
(Pagets Dz of Vulva) Pagets dz of nipple → underlying cancer • PAS+, Keratin+, S100-
Pagets dz of vulva → ∅ underlying cancer Melanoma –
• PAS-, Keratin-- , S100+
13.2 Vagina
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Adenosis Focal persistence of columnar epithelium in May occur in normal population Adenosis → ↑ risk for Clear Cell adenocarcinoma Upper 1/3rd of vagina derived from mulerrian duct DES is ∅ in use
upper 1/3rd of vagina ↑ in females exposed to DES in utero • Malignant proliferation of glands w clear cytoplasm • Columnar epithelium anymore
• Old anti-abortion drug • Rare complication of DES-associated adenosis Lower 2/3rd derived from Urogenital Sinus (UGS)
• Squamous Epithelium
Normally Squamous grows → covers upper 1/3rd
Embryonal Malignant mesenchymal proliferation of immature Bleeding Grape-Like mass Rhabdomyoblast
Rhabdomyosarcoma skeletal muscle protruding from vagina/penis of child • Cytoplasmic cross-striations
Very rare • +IHC stain → desmin & myoglobin
• Indicate muscle tissue
Vaginal Carcinoma Carcinoma arising from squamous epithelium lining High-Risk HPV (16,18,31,33) Regional LN spread
vaginal mucosa VAIN → Carcinoma • Lower 2/3rd → inguinal nodes
• Upper 1/3rd → regional iliac nodes
13.3 Cervix -
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Cervix (general) “neck” of uterus Exocervix – squamous epithelium
Transformation Zone
Endocervix – columnar epithelium
HPV infection Infects lower genital tract Sexually transmitted DNA virus CIN – High-Risk – 16,18,31,33 Pap Smear – most successful cancer screen
• esp cervix @ transformation zone Most HPV is cleared but can become persistant • koilocytic change, nuclear atypia, ↑ mitosis • E6 - ↑ destruction of p53 → ∅ apoptosis -Catch dysplasia before progression
Persistent infection → ↑ risk for CIN • CIN 1 • E7 - ↑ destruction of Rb → free E2F -Dysplasia - ↑ N/C ratio, ↑ nucleus size, blue
• CIN 2 potential to reverse Low-Risk – 6,11 -Limitation –
• CIN 3 - • Must be @ transitional zone
• CIN 4 – Carcinoma in Situ → invasive CIN - koilocytic change, nuclear atypia, ↑ mitosis • ↓ efficacy for adenocarcinoma
• Progresses stepwise. I → III → Carcinoma • ∅ ∆ incidence for Adenocarcinoma
Cervical Carcinoma Invasive carcinoma that arises from cervical epithelium High-Risk HPV → progression of CIN → CIS Present as Vaginal Bleeding (!) HPV can cause both Colposcopy & Biopsy – confirmatory test
↑ in middle ages women (40-50 y.o) 2ndary risk factors – • May be post-coital bleeding • Squamous Cell Cervical Carcinmoa
• Smoking Advanced Tumors - ↑ local symptoms, ↓ mets • Cervical Adenocarcinoma Immunization
• ↓ immune HPV frequently resolved in • Invade through anterior uterine wall → bladder • Quadrivalent vaccine – 6,11,16,18
Immunocompetent • Block ureters → hydronephrosis → • Protection last 5 yrs
• postrenal failure (frequent cause of death) • Pap smear still necessary – other strains
 50
13.4 Endometrium & Myometrium
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
General Endometrium – hormonally sensitivity Functionalis – layer that grows & sheds
• Grown (proliferation) via Estrogen Basalis – stem cell layer
• Prepared (secreatory) via Progesterone
• Shed when ↓ E & P
Asherman Syndrome 2ndary Amenorrhea due to loss of Basalis & scarring Overaggressive dilation & curettage (D&C) <the stem cells in the basalis were burnt to ashes>
(∅ regenerative layer)
Anovulatory Cycle Lack of ovulation Menarche Dysfunctional uUterine bleeding Overgrowth of endometrium past blood supply
• ∅ progesterone driver secretory phase Menopause •
Acute Endometritis Bacterial infection of endometrium Due to retained productions of conception Fever
• eg. piece of placenta left behind Abnormal uterine bleeding
Pelvic pain
Chronic Chronic inflammation of endometrium Retained production of conception Abnormal uterine bleeding Characterized by Plasma Cells
Endometritis Chronic PID – chlamydia Pelvic Pain • PMN are normal cells
IUD Infertility If Tb → granuloma
TB
Endometrial Polyp Hyperplastic protrusion of endometrium Can be side effect of Tamoxifen Abnormal uterine bleeding
• weak Pro-estrogen effects @ endometrium
Endometriosis Endometrial glands & stroma OUTSIDE endometrial lining 3 theories Dysmenorrhea – tissue grows/shed in abnormal location Glands & Stroma
-Retrograde Menstruation → tissue emplants Pelvic Location of Involvement
• #1 theory Scarring of fallopian tube Ovary → Chocolate Cyst
-Metaplastic Theory – Mullerian duct tissue metaplasia • ↑ risk of infertility Soft Tissues → Gun-powder lesions
-Lymphatic Dysemenation - endometrial tissue spread via • ↑ risk of ectopic pregnancy Uterine Ligament → Pelvic Pain
lymph → lungs, GI, etc Pouch of Douglas → Pain @ Defecation
↑ risk of Carcinoma @ site of endometriosis Bladder Wall → Pain @ Urination
• especially @ Ovary Bowel Serosa → Abdominal Pain & adhesions
Fallopian tube mucosa → Scarring → infert +ectopic
Adenomyosis Endometriosis into myometrium
Endometrial Hyperplasia of endometrial glands Unopposed Estrogen Postmenopausal Uterine Bleeding ↑ glands (relative to stroma)
Hyperplasia • ∅ progesterone Classified Histologically
• Based on architectural growth & cellular atypia

Most important prediction for progression to

carcinoma is Cellular Atypia
Endometrial Malignant proliferation of endometrial glands 2 pathways Postmenopausal Bleeding Hyperplasia Aggressive tumor
Carcinoma Hyperplasia - ↑ in 50-60 y.o • Endometrioide cancer
• Unopposed estrogen → growth→ • Looks like disorganized normal
• Endometrioid carcinoma endometrial tissue
Sporadic - ↑ in eldery (> 70 y.o) Sporadic
• Cancer from Atrophic Endometrium • p53 mutation
• Associated w p53 mutations • Papillary Serous histology
• Calcification of papilla → Psomoma Body
Leiomyoma Benign proliferation of smooth m.m from myometrium Estrogen Dependent Usually asymptomatic – most common finding (!) Multiple well defined white whorled masses
↑ in premenopausal women If symptoms present
• ↑ @ pregnancy • Abnormal uterine bleed ∅ progress to leiomyosarcoma
• ↓ @ menopause • Infertility
• Pelvic amss
Leiomyosarcoma Malignant proliferation of smooth m.m arising from Arises DeNovo Single lesions w hemorrhage/necosis
myometrium Disease of post-menopausal women (>70) Necrosis
Mitotic acitivity
Cellular atypia
 51
13.5 Ovary
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Ovary (normal) LH → Theca → Androgen Follicle – functional unit
↓ Layers:
FSH → Granulosa --------→ Estradiol → egg maturation • Oocyte → Granulosa → Theca
• Estrogen matures egg Corpus Luteum – is very large – almost size of ovary
• Estrogeen matures endometrium
Ovulation of egg – Secretory phase Degeneration of Follicle – result in follicular cyst
• Left overs “Corupus Leutum → progesterone • Normal to have a few
• Prepare endometrium for implantation
Hemorrhagic Leuteal Hemorrhage into corpus leuteum
Cyst
Polycystic Ovarian Many fibrotic cysts in ovary ↑ LH & ↓ FSH Obese woman
Dz (PCOD) • LH:FSH > 2 • Associated w Type 2 DM
↑ LH → ↑ theca cells → ↑ androgen Infertility
• Androgen@ Adipose → converted to estrone Oligomenorrhea
• Estrone → Pituitary → ↓ FSH Hisutism – excess androgen
• ↓ FSH → ∅ estrogen → follicle degeneration ↑ estrone → ↑ risk of Endometrial Carcinoma
13.6 Ovarian Tumors → on the next page
13.7 Gestational Pathology
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Ectopic Implantation of fertilized ovum @ site that’s not uterine Risk Factors Lower Quadrant Abdominal Pain weeks after missed period Pregnancy Test
Pregnancy wall • Scarring Surgical Emergency - may rupture
• Most common @ Fallopian Tube • Endometriosis
Spontaneous Miscarriage of fetus @ < 20 wks Chromosomal anomalies – most common Vaginal Bleeding
Abortion Occurs in up to ¼ of recognizable pregnancys Hypercoagulable state (SLE) Cramp-like pain
Congenital infections Passage of fetal tissue
Teratogen exposure – depends on dose & exposure
Placenta Previa Implantation of placenta in lower uterine segment 3rd trimester bleed “preview of placenta” C-section
Placenta overlies cervical os
rd
Placenta Placenta seperates from decidua/uterus prior to delivery 3 trimester bleeding Blood & clots on maternal surface of placenta
Abruption Common cause of still birth Fetal insufficiency & risk of still birth
Placenta Improper implantation of placenta into myometrium Difficulty delivering placenta Often require hysterectomy
Accreta • ∅ decidua Post-partum bleeding
Preeclampsia Pregnancy-induced HTN, proteinuria, & edema Abnormality of maternal-fetal vascular interface in placenta ↑↑ HTN → headaches, ∆ eyes Fibrinoid Necrosis HTN resolved by removing placenta
rd
Arise in 3 trimester Fibrinoid Necorisis in vessels in placenta
Eclampsia Pre-Eclampsia+ Seziures Must remove placenta
HELLP Hemolysis Elevated Liver Enzyme & Low Platelts Preeclampsia w Thrombotic Microangiopathy involving liver Hemlyosis, ↑ liver enzymes, ↓ platelets Platelet thrombi in Liver Hemolysis,
Platelet thrombi in liver ↑ liver enzymes
↓ platelets
Sudden Infant Sudden death of healthy infant (1 month → 1 year) Risk factors
Death Die in sleep • Sleeping on Stomach
Syndrome • Smoking in Household
Hydatidiform Abnormal conception → grow abnormal placental tissue Partial Mole Complete Mole Uterus expands as if pregnant Swollen & Edematous villi ↑↑↑ β hCG
Mole Genetic Normal Ovum, 2 Empty ovum, 2 • Uterus will be larger than expected Prolifertion of trophoblasts Ultrasound – grapes & snow-storm
sperm sperm • β hCG will be higher than expected
69 chromosomes 46 chromosomes Woman will pass Grape-Like masses Grape-like Masses = large edematous villi Tx
nd
Fetal Present ∅ • Usually present @ 2 trimster if ∅ prenatal care • D&C
Tissue Prenatal Care → Ultrasound < • Follow up w β hCG
• Grape-like masses on Ultrasounds Complete mole is Completely from dad •
Villous Some hydropic Most are hydropic
• “Snow-Storm” appearance on Ultrasound Partial mole is partially dad Also screen for choriocarcinoma w β hCG
Edema Some normal
>
Trophoblastic Focal proliferation Diffuse circumfertial
2 sperms make a mole Proliferation around hydropic villi proliferation around
↑ β hCG hydropic villi
↑↑↑ β hCG
Risk for Minimal 2-3%
choriocarcinoma
Chorio- Tumor of trophoblast 2 pathways ∅ villi → only Trophoblast 2 outcomes
carcinoma • Arise as complication of gestation (molar preg) Gestation pathway – responds well to chemo
• Spontaneous germ cell tumor Germ Cell Pathway – poor response to chemo
 52
13.6 Ovarian Tumors
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Normal Surface epithelium – Coelomic epithelium Ovary – 3 categories
• Can form ∆ cell types Oocyte → Germ Cell Tumors
• 2 most common are Serous & Mucinous Granulosa Theca& Stroma cells → Sex Cord Stroma
Surace Epithelium → Surface Epithelial tumors
Surface Epithelial Most common type of ovarian tumor 4 types Present later → poor prognosis Can also be classified based on benign/malignant CA-125 – serum tumor marker
2 most common → Serous & Mucinous Present w vague symptoms Benign – cystadenoma • Monitor treatment response
• Both usually cystic Spread locally → especially into peritoneum Malignant – cystadenocarcinoma • Screen for recurrence
Borderline – features in bt benign/malignant • ∅ good for initial screen
• Have malignant potential but better
prognosis?
Benign Most common in premenopsaul women Single simple cyst
Cystadenoma • Age 30-40 y.o Single flat lining – single epitheliul layer
Can be serous or mucinous
Malignant Most common in post menopausal women Multiple complex cysts
Cystadenocarcinoma • Age 60-70 y.o Thick shaggy lining
Can be serous or mucinous
Invasion of cells → into connective tissue
BRCA1 mutation BRCA1
carriers • ↑ risk for Serous Carcinoma
• in ovary & fallopian tube
Endometrioid Malignant surface epithelial tumor associated w Endometriosis
Tumor 15% of patietnt w endometrioid carcinoma of ovary will
have endometrial carcinoma in endometrium
Brenner Tumor contains Urothelium
Germ Cell Tumors 2nd most common type of ovarian tumor (15% of case) Fetal Tissues → cystic teratoma Tumor subtypes mimic tissues normally produced by
Women of reproductive age Embroynal Carcinoma germ cells
• Age 15-30 y.o Yolk Sac → Yolk Sac Tumor
Germ Cells → Dysgerminoma
Placenta → Choriocarcinoma
Cystic Teratoma Cystic tumor comprised of fetal tissue derived from 2 or 3 (!) Bilateral in 10% of cases Contains hair, teeth, glands, bone, skin, etc
embryonic layers Benign
Most common germ cell tumor in females Indicators of Malignant potential
Struma Ovarii – cystic teratoma composed of thyroid tissue • Immature Tissue (neuroectoderm)
• Hyperthyroid symptoms in patient + ovary mass • Somatic Malignancy (SCC of skin)
Dysgerminoma “Mass of egg cells” Large cells w Clear cytoplsam <counterpart in Male – Seminoma>
Most common MALIGNANT germ cell tumor ↑ LDH
Good prognosis, Response well to radio therapy
Endodermal Sinus Tumor mimcks yolk sac Produces αFP ↑ α FP
Tumor Most common germ cell tumor in children Schiller-Duval Bodies – “glomeruloid”
• “5 yo with ovarian mass”

Choriocarcinoma Malignant proliferation of placenta-like tissue Small hemorrhageic tumor Normal placenta- Villus + blood vessels ↑ β hCG
Early hematogenous spread • Cytotrophoblast & Syncitiotrophoblast Poor response to chemo
• This tumor was desgined to invade blood vessels Choriocardinoma
∅ villi → malignant proliferation of Trophoblasts
Embryonal Composed of large primitive cells Aggressive w early metasisis
Carcinoma
Sex Cord Stromal Resemble sex-cord stroma tissue of ovary
Tissue
Granulosa-Theca Neoplasm of granulosa & theca cells Produce Estrogen → Estrogen Excess
cell tumor • Precoious puberty, ∆ menses, postmenopausal bleeding
Sertoli-Leydig Mimic sex-cord stromal element of testicle Produce Androgen Sertoli cells → tubules
Tumor • Hirsutism or Virilization Leyddig cells – contain Reinke Crystals
Fibroma Benign Tumor of Fibroblasts (!) associated w Pleural Effusion & Ascites
• Meig’S Syndrome
Kruckenberg Mucinous carcinoma → bilateral mets 1° tumor – Diffuse Gastric Carcinoma, Breast, Colon Ca Signet Ring Cells – mucous pushes nucleus to side (d/d if unilatera→ Surface Mucionus Epithelial)
Pseudomyxoma Abundent amount of mucin in periotenum - “Jelly Belly” Mucinous Carcinoma in Appendix → mucinous product “
peritonei Mets to Ovary
 53
14.1 Penis
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Hypospadias Opening of urethra on inferior surface of penis Failure of urethral folds to close
Epispadias Opening of urethra of superior surface of penis Abnormal positiontion of Genital Tubercle
Less common than hypospadias associated w Bladdery Exstrophy
Condyloma Benign warty growth on genital skin HPV 6 & 11 Koilocytic change
Acuminatum

Lymphogranuloma Necrotizing granulomatous inflammation of inguinal Chlamydia trachomatis L1-L3 Granulomatous inflammation of inguinal lymphatic & LN
Venerum lymphatic & lymph nodes Evetually heals w fibrosis
• May rest in Rectal Strictures
Squamous Cell High risk HPV (66% of cases) Precursor Lesions – carcinomas in situ
Carcinoma Lack of Circumcision • Bowens Dz – leukoplakia on shaft
• Eryhtoplasia of Queyrat – erythroplasia on glans
• Bowenoid Papulosis – reddish papules & carcinoma like
Bowenz but ∅ invasion
14.2 Testicle
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Cryptorchidism Failure of testicle to descend into scrtal sac Complication – Most resolve spontaneously
Most common congenital male reproductive abnormality Testicular Atrophy & infertility If ∅ resolve by 2 y.o → Surgery
↑ risk of Seminoma
Orchitis Inflammation of Testicle Chlamydia trachomatis (D-K) - STD
Neisseria Gonorrhea - STD
E coli & Pseudomonas – in older, from UTI AutoImmune
Mumps • Granulma of Testicular Tubule
Autoimmune Orchitis → granuloma @ tubule • d/dx – TB → necrotizing & AcidFast+
Testicular Torsion Twisting cord → hemorrhagic infecation Twisting of spermating cord Hemorrhagic infraction of testicle
• vein gets occluded
Adolescent w sudden testicular pain • artery stays patent
& absent cremasteric relfex Congenital failure of testes to attaching to inner
lining of scrotum
Varicocele Dilation of Spermatic vein Impaired drainage Scrotal swelling → bag of worm appearance L spermatic vein → L renal vein → IVC
↑ in infertile males Usually L-sided • ↑ risk of varicocele
associated w Left Sided Renal Cell Carcinoma R spermatic vein → IVC
Hydrocele Fluid collection within tunica vaginalis Associated w Scrotal Swelling Tunica Vaginalis
-incomplete closure of processus vaginalis (infants) • Can be transluminated ( light passes through)
-Blockage of lymphatic drainage (Adults)
 54
14.3 Testicular Tumors
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Normal Film, painless testicular mass 2 types ∅ biopsy
• Cannot be transilluminated • Germ Cell
(!) ∅ Biopsy → risk of seeding scrotum & most are germ cell • Sex Cord Stroma Remove via Radial Orchiectomy
Germ Cell Tumors Most common testicular tumor (>95%) Risk factors All are malignant
Occur bt 15-40 years of age • Cryptorchidism Seminoma
• Klinefelter Syndrome • late mets, good radiation response, good prognosis
Non- seminoma
• variable response, early mets
Seminoma Malignant tumor of large cells w clear cytoplasm & central Homogenous mass w ∅ hemorrhage or necrosis large cells w clear cytoplasm & central nuclei Responds to radiotherapy
nuclei Rarely produce β hCG Good prognosis
<analogous to dysgerminoma>
Non-Seminomas
Embryonal Malginant tumor of immature primitive cells Hemorrhagic mass w necrosis (!) tumor may form Glands (!) Chemo may cause differentiation
Carcinoma Aggressive w Early hematogenous spread May produce AFP or β hCG
Remember normall - (AFP-yolk sac β hCG- chorioccnma)
Yolk Sac Tumor Most common testicular tumor in children (!) α FP is elevated
Schiller-Duval body aka “Glomeruloid” structure
Choriocarcinoma Malignant tumor of synctiotrophoblasts & β hCG can activate TSH or FSH receptors Syncitiotrophoblasts produce β hCG
crytotrophoblasts • HyperThyroidim
• Gynecomastia
Early spread via blood
Teratoma Tumor of mature fetal tissue (!) Malignant in males May produce –β hCG or AFP
Derive from 2 or 3 embryoinc layers • Even though Benign in Female
Mixed Germ Cell Germ cell tumors are usually mixed Pr
Tumor onogisis based on worst type of tumor
Sex-Cord Stromal Resemble sex-cord stromal tissues
Tissues Usually Benign
Leydig Cell Tumor Produce androgen Sertoli cells – Reinke Crystals
• Precocious Puberty in children
• Gynceomastia in adult
Sertoli Cell Tumor Clinically silent Comprised of Tubules
Lymphoma Most common cause of testicular mass in male > 60 Lymphoma
• Often bilateral • Diffuse Large B-cell Type
14.4 Prostate
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
General Prostate sits anterior to rectum, urethra pass through it Glands – functional unit → Alkaline Milky secretion
• Inner lumen Layer
• Out Basal Cell Layer
Stroma - CT
Acute Prostatitis Acute inflammation of prostate Young Adult- Chlamydia & Gonorrhea Dysuria Prostatic secretions show WBC
Older Adults– E coli & Pseudomonas Fever & Chills Culture shows Bacteria
“Tendery & Boggy” prostate @ DRE
Chronic Prostatitis Chronic inflammation of prostate Dysuria Prostatic secretions show WBC
Pelvic or Low Back pain Culture negative
Benign Prostate Hyperplasia of Prostatic Stroma & Glands Age-related change Compression of Urethra → Urinary Obstruction Occurs @ Periurethral Zone of Prostate α1-antagonist(terazosin) – relax smooth m.m
Hyperplasia (BPH) Related to DHT Problems starting/stopping stream ∅ ↑ risk for cancer • Also treats HTN
Impaired bladder emptying & Dribbling Slight elevation PSA (4-10) α1A selective (tamsulosin) – normotensive patient
Hypertrophy of bladder smooth m.m or Diverticuli of bladder wall 5α reductase inhibitor
Microscopic Hematuria • Slow onset → months for results
complication – Hydronephrosis
Prostate Malignant proliferation of prostatic glands Risk Factors Clinically silent Occur @ Posterior Periphery of Prostate Screen @ age 50
Adenocarcinoma Most common cancer in men • ↑ in age • ∅ urinary symptoms • ∅ urinary symptoms early in course • DRE
2nd mose common cause of cancer death • ↑ in black>white>Asians Biopsy • PSA: > 10 ng/dL is concerning
• ↑ in diet w ↑ saturated fats Complication • Small glands infiltrating tissue ↓ %free-PSA → suggest cancer
• Spread to Lumbar Spin – osteoblastic metises • (!) Dark Nucleoli in nuclei Prostatic Biopsy – required to make diagnosis
• Low back pain Gleason Grading System Tx
• ↑ alkaline phosphatase, ↑ PSA, ↑ PAP • Based on ARCHITECTURE (∅ atypia) Prostatectomy (local disease)
• Score many regions of prostate GnRH analogs (Leuprolide) - ↓ GnRH → ↓ androgens
Androgen-R inhibitors (Flutamide)
 55
15.1 & 15.2 Pituitary Gland
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Anterior Pituitary
Pituitary Adenoma Benign tumor of anterior pituitary cells Functional – produces ∆ hormones → ∆ features
• May be functional or non-functional Non-Functional → Mass Effect
• Bitemporal Hemianopsia
• Hypopituitarism
• HA
Functional Prolactinoma – most common Dx
• Galactorrhea & Amenorrhea (females) GH adenoma - ↑ GH & IGF-1 & ∅ glucose surpression
• ↓ libido & HA (males) Tx
GH adenoma → Giantism (kid) & Acromegaly (adult) Prolactinoma
• Enlarged tongue, 2ndary DM, heart dz • DA-agonists (Bromocriptine)
ACTH → cushings • Surgery
TSH, LH, & FSH – are rarer GH Adenoma
• Octerotide – Somatostatin analog
• GH-receptor anatgonists
Non-Functional Mass Effect
• Bitemporal Hemianopsia
• Hypopituitarism
• HA
Hypopituitarism Insufficiency production of hormones Pituitary Adenoma (adults)
• Symptoms @ > 70% loss Craniopharyngioma (children)
Sheehan Syndrome – pituitary infarct @ birth Sheehan - Amenorrhea & ↓ pubic hair
Empty Sella Syndrome
• Congenital herniation of CSF into sella
• 2ndary trauma
Posterior Pituitary – ADH & Oxytocin produced in hypothalamus → stored/released @ posterior pituitary
Central Diabetes ADH deficiency Hypothalamic or Posterior Pituitary pathology Polyuria → Polydipsia Dx - H2O deprivation tests – fails to ↑ urine osmolality
Insipidus Hypernatremia & ↑ serum osmolality Tx – Desmopressin (ADH analog)
↓ urine osmolality & ↓ specific gravity
Nephrogenic Impaired renal response to ADH Inherited Mutations Polyuria → Polydipsia ∅ response to desmopressin
Diabetes Insipidus Drugs Hypernatremia & ↑ serum osmolality
↓ urine osmolality & ↓ specific gravity
SIADH ↑↑ ADH Ectopic Production (small cell carcinoma) Hyponatremia & ↓ serum osmolalaity
CNS trauma Cerebral Edema → Mental Status change & Seizures Tx
Pulmonary Infection & pathologies • Free Water Restriction
Drugs ( eg. Cyclophosphamide) • Demeclocylcine
 56
15.3 – 15.7 Thyroid
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Thyroglossal Duct Cystic dilation of thyroglossal duct remnant Congenital – thyroid duct ∅ involute Anterior Neck Mass
Cyst
Lingual Thyroid Persistent thyroid tissue @ base of tounge ∅ movement of thyroid glass Base of Tongue mass
Hyperthyroidism ↑ circulating thyroid hormone ↑ basal metabolic rate → ↑ synthesis of Na/K ATP-ase
(general) ↑ SNS activity → ↑ expression of β1 receptors
Weight loss despite ↑ appetite
Heat intolerance & sweating
Tachycardia & ↑ C.O → Arryhtmia (esp A-fib in elderly)
Tremor, anxiety, insomnia, heightened emotions
Staring gaze w lid lag
Diarrhea w malabsorption
Oligiomenorrhea
Bone resorption & hypercalcemia
↓ m.m mass w weakness
(!) Hypocholesterolemia & Hyperglycemia
Graves Dz Most common cause of hypertrhyroid IgG → TSH-receeptor Hyperthyroidism Large follicles ↑ total & free T4
↑ in women of reproductive age • ↑ thyroid hormoe synthesis & release Diffuse Goiter Scalloping of colloid ↓ TSH
Exophthalmos – fibroblasts have TSH-R → ↑ GAG production • Colloid ∅ fill the whole follicle Hypocholesteremia & hyperglycemia
Pretibial Myxedema – fibroblasts have TSH-R → ↑ GAG production Tx:
• “doughy” appearance/texture • .β blocker
Complication – Thyroid Strom • .Thioamides – block peroxidase → ↓ T3/T4
• ↑ caechoamines & massive hormone excess (stress) • .Radioiodine ablation
• Arryhtmia, hyperthermia, vomiting Tx for Thyroid Storm
• Hypovolemic shock • PTU, β blocker, Steroids
Multinodular Enlarged thyroid w multiple nodules Iodine Deficiency Usually non-toxic (Euthyroid)
Goiter Regions may become TSH-independent → Toxic Goiter
Hypothryroidism
Creatinism Hypothyroidism in neonates & infants Maternal hypothyroid during early pregnancy Mental retardation
Tyroid agenesis Short stature w Skeletal abnormalities
Dyshormonogenic Goiter Coarse facial features
• ∅ able to produce thyroid hormore Enlarged tounge
• ∅ Thyroid Peroxidase – most common Umbilical hernia
Iodine deficiency
Myxedema Hypothyroid in older children & adults Iodine Deficiency Myxedema
Hashimotos Thyroiditis • Especially @ larynx & tounge → deeper voice
• most common if sufficient iodine Weight gain w normal appetitie
Drugs – Lithum Slowing of mental activity
Surgical removal/Radioablation of thyroid Muscle weakeness
Cold intolerance w ↓ sweating
Bradiacardia & ↓ CO
Oligomenorrhea
Hypercholesterolemia
Constipation
Thyroiditis
Hashimoto’s Autoimmune destruction of Thyroid Gland Associated w HLA-DR5 Initial hyperthyroid → euthyroid → Hypothyroid Antithyroglobulin Ab & Antimicrosomal Ab can be ↓ T4 & ↑ TSH
Thyroiditis most common cause of hypothryroid w sufficient I • present as marker of Thyroid damage
↑ risk for B-cell lymphoma (Marginal Zone) Chronic inflammation w formation of germinal center
• Present as enlarging thyroid late in course of dz Hurthle Cells – eosinophilic metaplasia lining follicles
Subacute Granulomatous thyroiditis following viral infection Follow Viral Infection Tender/Painful thyroid w transient hyperthytroid
Granulmoatous Self-limited → ∅ progress to hypothyroid
(DeQuervains)
Reidel Fibrosing Chronic inflammation/fibrosis of thyroid Hypothyroid
Thyroiditis ↑ in young female (!) Hard as wood, nontender thyroid gland
• (vs anaplastic carcinoma in elder ptnt) Fibrosis my extend to local struction → Airway
(d/dx – Anaplastic carcinoma – will present in older people)
 57
15.7 continued Thyroid Neoplasia
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
131
Basics More likely to be benign (vs malignant) Presents as distinict, solitary nodule I radioactive uptake study
• ↑ in grave/nodular goiter
• ↓ uptake in adenoma & carcinoma → biopsy
(!) FNA biopsy – (fine needle aspiration)
Follicular Adenoma Benign proliferation surrounded by Surrounded by Fibrous Capsule FNA biopsy
fibrous capsule • ∅ invasion through capsule → ∅ able to distinguish follicular adenoma vs carcinoma
Papillary Carcinoma Most common type of Thyroid Carcinoma (80% Major Risk factor Papillary projections
• Exposure to ionizing radiation in Complication → Spread to cervical nodes • Calcification → Psammoma Body
childhood • Still excellent prognosis Orphan Annie nuclei – white clearing in nucleus
Nuclear grooves
Follicular Carcinoma Malignant proliferation of follicles Surrounded by Fibrous Capsule FNA biopsy
Hematogenous Mets • Invasion through capsule → ∅ able to distinguish follicular adenoma vs carcinoma
Medullary Malignant proliferation of parafollicular C cell Familial Cases ↑↑↑ calcitonin produced by tumor → Hypocalcemia Malignant cells in Amyloid stroma Detection of RET mutation
Carcinoma • MEN 2A & 2B Calcitonin can deposit in tumor as Amyloid (local amyloidosis) • warrants prophylactic thyroidectomy
• Mutation of RET oncogene
Anaplastic Undifferentiated malignant tumor of thyroid Invades local structures Very undifferentiated (anaplastic) Poor prognosis
Carcinoma ↑ in eldery Dysphagia
Respiratory compromise
(similar to Reidels but –∅ in young)
15.8 Parathyroid Gland
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Basic PTH Chief cell – regulate serum FREE (ionized)
• osteoblast activation → ↑ bone osteoclast activity calcium
• Activate Vit D → ↑ small bowel absorption of Ca & PO4 • 60% of Ca is protein bound
• ↑ renal calcium reabsorption & ↓ phosphate reabsortion
1° hyperPTH Excess PTH due to parathyroid disorder 1. Parathyroid Adenoma (most common) Usually astmpyomatic ↑ serum PTH
-benign If symptoms - ↑ PTH & Hypercalcemia symptoms ↑ serum Ca
2.Sporadic Hyperplasia • Nephrolithiasis (Calcium-Oxalate) ↓ serum PO4
3.Carcinoma • Metastatic Calcification → Nephrocalcinosis (!) ↑ urinary cAMP
→ renal insufficiency w polyurea • PTH → Gs → adenylate cyclase → ↑ cAMP
• CNS disturbances – depression, seizures ↑ serum alkaline phosphatase
• Constipation, peptic ulcer dz • Alkaline environment necessary to lay down bone
• Acute Pancreatitis – “Ca activated pancreatic enzems” • PTH activates osteoblasts → alkaline phose
• Osteitic fibrosa Cystica Tx:
• Surgical Removal of effected gland
2ndary HyperPTH ↑ PTH due to extrinsic cause Chronic Renal Failure – most common cause ↓ kidneys ↑ PTH
↓ PO4 excretion → ↑ serum PO4 → binds Ca++ ↓ serum calcium
↓ free calcium → stimulate all 4 parathyroids ↑ serum phosphate
• ↑ PTH → bone resoprtion ↑ alkaline phosphatase
Hypoparathyroidism ↓ PTH Autoimmune destruction of Thyroid Numbness & Tingling – especially perioral ↓ serum calcium
Surgical Excession Muscle Spasm/ Tetany ↓ PTH
Parathyroid hyperplasia • Trousseaus Sign – bp cuff → arm spasm
DiGeorge Syndrome • Chvostek sign – tap on CN VII → facial spasm
Pseudohypo Signs & symptoms of hypocalcemia but ↑ PTH End-organ Resistance to PTH Hypocalcemia symptoms Hypocalcemia
parathyroidism • Defect in Gs-protein (GPCR) ↑ PTH
AutoDom form – associated w Auto Dom form – short stature & short 4th & 5th digits
Short Stature & short 4th & 5th digits
 58
15.9 Endocrine Pancreas
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Basics Insulin Islets of Langerhans
• ↑ GLUT4 → ↓ serum glucose • β cells in center of islets → Insulin
• ↑ glycogen, protein synthesis & lipogenesis • α cell → glucagon
Glucagon → glycogenolysis & lipolysis
Type 1 DM Insulin Deficiency → metabolic disorder w Type IV hypersensitivity ↑ serum glucose ↑ serum glucose
hyperglycehmia Destruction of β cell by T-lymphocyte
Inflammation of islets ↓ weight, Tx: Life-long insulin
Associated w HLA-DR3 & DR4 ↓ muscle mass with polyphagia
May have autoantibodies against insulin Polyruia, polydipsia, & Glucosuria

DKA ↑ serum ketoacids Arise w stress/infection Hyperglycemia (> 300 mg/dL) Fluids
Epi → ↑ glucagon → ↑ lipolysis → ↑ FFA Anion gap metabolic acidosis Insulin – counter glucagon effect
• FFA go to liver → Ketone Bodies Hyperkalemia Replacement of electrolytes (especially K+ )
• ∅ insulin to drive K+ into cell
• K+ pushed out of cell to buffer H+
Kussmaul Respirations
Dehydration,N+V, Mental Status Changes
Fruity Smell Breath – acetone
Type 2 DM End-organ insulin resistance Arise in middle-ages, obese adults Polyuria & Polydipsia ↑ insulin early in disease → β cell burn out → Random Glucose > 200 mg/dL
Most common type of diabetes Obesity → ↓ number of insulin receptors Hyperglychemia ↓ insulin Fasting Glucose > 126 mg/dL
Strong genetic predisposition (stronger than type 1) Often clinically silent (!) Amyloid in Islets 2 hrs after Glucose Tolerance Test > 200 mg/dL
Complications: Tx
-Hyperosmolar Non-Ketotic Coma Weight Loss & Exercise
• ↑ glucose level (>500 mg/dL) → life threatening diuresis Drugs Therapy
• Hypotension & Coma Insulin @ later stage
• Ketones are absent (small amount of insulin present)
-NEG of Vascular BM
• NEG of large & medium vessels → Atherosclerosis
• NEG of small vessels → Hyaline Arteriolosclerosis
• Diffuse Glomerculosclerosis → Chronic renal failure
• NEG of hemoglobin → HbA1C
-Osmotic Damage to cetain cells (that take up sugar w/o insulin)
• Schwann Cells • Pericytes of Retinal Blood vessel • Lens
• ↑ glucose in cells → Aldose Reductase → Sorbitol
• Sorbitol cause damage
• ↓ schwann cell → neuropathy
• ↓ retinal pericytes → anyerism in retina → hemorrhage →
retinopathy → blindness
• Lens → cataracts
Pancreatic Tumors of Islets cells Often associated w MEN1 MEN1 – parathyroid hyperplasia,
Endocrine Tumors pituitary adenoma & pancreatic tumor
Insulinoma Episodic hypoglychemia w mental status change Dx: ↓ glucose, ↑ insulin, ↑ C-peptide
• If ∅ ∆ c-peptide → munchausen w insulin
Tx: Glucose
Gastrinoma ↑ parietal cell acid production Can be multiple tumors
ZOLLINGER ELLISON Treatment-resistant Peptic Ulcer Can extend into jejunum
Stomatostatinoma ↓ parietal cell acid production
• Achlorhydria
↓ cholecystokinin
• Cholelithiasis & Steatorrhea
VIPoma ↑ VIP
Wattery diarrhea
Achlorhydria
Hypokalemia
 59
15.10 – Adrenal Cortex
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Basic Cholesterol Derived Hormones Glomerulosa
Glomerulosa →Mineralocorticoids/ Aldosterone Fasciculata
Fasciculata → Cortisol Reticularis
Reticularis → Sex Steroids
<gets sweeter as you get deeper…salt→sugar→sex>
Hypercortisolism Excess Cortisol Exogenous Corticosteroids – most common cause m.m weakness & thin extremities (breaking down m.m for sugar) ↑ 24 hour urine cortisol level
Cushings Syndrome • Both adrenals will be atrophic Moon facies, buffalo hump, truncal obesity ( ↑ GNG→↑ adipose)
Primary adrenal adenoma/hyperplasia/carcinoma Abdominal striae (↓ collagen synthesis)
• 1 adrenal will be large/overactive HTN (cortisol → upregulate α-receptor on arterioles) Dexamethasone Suppression Test
• Other adrenal will be atrophic Osteoporosis • Able suppress pituitary adenoma ACTH
ACTH-secreting pituitary adenoma Immune suppression • ∅ able to suppress ectopic ACTH
• Both adrenals will be large • Inhibits Phospholipase A2 → ∅ arachidonic metabolites • Follow effect of test by measuring Cortisol levels
Paraneoplastic ACTH secretion • Inhibit IL-2
• Classically Small Cell Carcinoma • Inhibit release of histamine from Mast Cells
• Both adrenals will be large
Hyperaldosteronism Excess aldosterone Hypernatremia Aldosterone works @
Conn Syndrome Hypokalemia Principle Cells
Metabolic alkalosis • ↑ Na reabsorption, dump K
α intercalated cell
HTN – water follows solute • Dump H
Primary Benign Adrenal Adenoma – most common ↑ aldosterone
Hyperaldosterone Sporadic hyperplasia – less common ↓ renin
Carcinoma – less common
2ndary Activation of RAAS ↑ renin
Hyperaldosterone • Fibromuscular dysplasia of renal a.a (F) ↑ aldosterone
• Atherosclerosis of renal a.a (M)

Congenital Adrenal Excess sex steroids w hyperplasia of both adrenals Congenital defect ↑↑ sex steroids 11-hydroxylase deficiency <blackjack
Hyperplasia 21-hydroxylase deficiency – most common cause • Clitoral Enlargement (F) • Less mineralocorticoid problems 21 – get excited (sex) & adrenalin
• Required for Mineralocorticoid & • Precocious Puberty (M) • ∅ hyponatremia & hyperkalemia >
Cortisol production ↓ Cortisol –Life threatening Hypotension 17 – hydroxylase deficiency
• ↑↑ Sex Steroid production • Hypotension • ∅ Cortisol or Sex Steroid
• • ↑↑ ACTH → adrenal hyperplasia • ↑↑ Mineralocorticoids
↓ mineralocorticoids
• Salt wasting → Hyponatremia & Hypovolemia
• Hold K → Hyperkalemia
Acute Lack of adrenal hormones Acute – Waterhouse-Friderichsen Syndrome Meningitis → DIC → bilateral necrosis of adrenal glands
Adrenal Insufficiency ↓ Cortisol → Hypotension
Chronic Adrenal Progressive destruction of adrenal glands Autoimmune destruction – most common in west Hypotension
Insufficiency TB – most common in developing world Hyponatremia, Hypovolemia, Hyperkalemia
Mets Carcinoma to both adrenals Weakness
• Especially Lung Cancer Hyperpigmentation – ACTH derived from POMC
• POMC → also creats Melanocyte Stimulating Hormone
Vomiting & Diarrhea
15.11 – Adrenal Medulla
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Basics Composed of neural crest-derived chromaffin cells Main physiologic source of catecholamines (epi & norepi)
Pheochromocytoma Tumor of Chromaffin cells Rule of 10’s Episodic HTN (!) Brown Tumor of Adrenal ↑ serum Metanephrins
• Epi & NE release • 10% bilateral HA ↑ 24 hr Urine Metanephrines & VMA
• 10% familial Palapatations E → metanephrin
• 10% malignant (90% benign) Tachycardia VMA Tx: Surgical Removal of Tumor
• 10% located outside of adrenal medulla Sweating NE → normetanephrin • Pretreat w Phenoxybenzamine (irrev α antagonist)
o Bladder (If @ bladder → HTN @ urination)
Associations
• MEN2A & 2B
• Von Hipple Landau disease
• NF type 1
 60

Ch 16 – Breast
Embryo Breast is a modifying skin gland Hormone Sensitive to Estrogen & Progesterone Note: Things that can show up on biopsy
Breast tissue can develop anywhere along milk line (axilla→vulva) Sensitivity Development @ menarche
• Extra nipples • Extra breast tissues • Extra Breast Ca (!) Highest density of breast tissue – Upper Outer Quadrant of breast • Apocrine Metaplasia, Fibrosis, Cysts → benign
breast tenderness @ menstruation • Apocrine Metaplasia – metaplasia w
hyperplasia @ pregnancy ∅ ↑ cancer risk
atrophy @ menopause •Ductal Hyperplasia - ↑ # of duct cells → ↑ Ca risk 2x
Terminal Duct Lobular Lobules make milk → drains to ducts → Terminal Duct → Nipple Galactorrhea Milk produced OUTSIDE of lactation (∅ recently pregnant) •Sclerosing Adenosis - ↑ # of glands w fibrosis → ↑ Ca risk 2x
Unit “functional unit” of breast ∅ a symptom of breast cancer • Often present as calcified lesion
Causes: • Atypical Hyperplasia – atypical cells w ↑ # → ↑ Ca risk 5x
Lobules & Ducts have 1.Luminal Cells • Nipple Stimulation – Risk factoring is for Invasive Carcinoma in BOTH breasts
2.layers of epithelium • Protective in Duct • Milk producing in Lobule • Prolactinoma of Ant Pituitary
2.Myoepithelial Cells – contract to push milk forward • Drugs
16.2 – Inflammatory Conditions
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Acute Mastitis Bacterial Infection of Breast Breast feeding → stress skin (fissures) → Warm, erythematous breast Can progress to abcess → mass Continue Drainage – keep breast feeding or pump
• Usually Staph aureus Staph aureus enters & infects Purulent nipple discharge Antibiotic: Dicloxicillin
Periductal Mastitis Inflammation of subareolar duct ↑ in smokers → relative Vit A deficiency → Mass in subareoral region Squamous Metaplasia
Squamous metaplasia of lactiferous duct → Fibrosis/Granulation tissue – Myofibroblasts Keratin Plug
Keratin plugs duct → inflammation behind block • (!) nipple retraction Fibrosis/Granulation Tissue

Mammary Duct Inflammation of wall of subalverolar duct Inflammation of wall of subalverolar duct → dilatation of duct (!) Green/brown nipple discharge Chronic inflammation w Plasma Cells
Ectasia → dilatation of duct→ green/brown nipple discharge Classily in multiparous postmenopausal women Mass in post menopausal women (d/dx Breast Ca)
Fat Necrosis Necrosis of breast fat usually Trauma related Mass @ physical exam Necrotic Fat w associated
• trauma often not described in vignette Calcification @ mammography (Saponification → Calcium) • calcifications
• can be mild damage (“playing baseball, got hit”) • giant cells
16.3 Benign Tumors & Fibrocystic Change
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Fibrocystic Change Cystic change/enlargement of lobules Most common change in premenopausal women Vague irregularity to breast tissue (“Lumpy Breast”) Gross: Blue Domed Cysts
• fibrosis occurs as connective tissue stretches Variation of normal ↑ occurance at upper/outer quadrant
Benign & ∅ increase cancer risk

Intraductal Papilloma Benign fingerlike Tumor in duct Fingerlike projection w fibrovascular core (!) Bloody nipple discharge 2 standard cell types in duct
↑ in premenopausal women • epithelial cells d/dx – papillary carcinoma
• myoepithelial • ↑ in older
• ∅ myoepithelial cells
Fibroadenoma Tumor of fibrous tissue & glands Most common tumor in premenopausal females Well circumscribed, mobile, marble-like mass Benign → ∅ increased risk for cancer Benign & ∅ increased cancer risk
Estrogen sensitivity → ∆ @ pregnancy, menstruation, etc Most common benign neoplasm of breast Estrogen sensitivity

Phyllodes Tumor Fibroadenoma-like tumor w fibrous tissues & glands Postmenopausal women (!) Leaf-like projections May be malignant
• (!) Overgrowth of fibrous components →
• Causes leaf-like projections of tissue

16.4 Breast Cancer
Epidemiology
Staging
Name
Ductal Carcinoma
in Situ (DCIS)
Paget’s Dz of Nipple
Invasive Ductal Carcinoma
4 subtypes
Tubular Carcinoma
Mucinous Carcinoma
Medullary Carcinoma
Inflammatory Carcinoma
Lobular Carcinoma in Situ
(LCIS)
Invasive Lobular Carcinoma
Hereditary Breast Cancer
Male Breast Cancer
Most common carcinoma in women (by incidence, excluding skin)
2nd most common cause of cancer mortality in women
TNM
• Metastasis – most important factor
• Spread to axillary lymph notes – most useful factor (bc mets isn’t a common presentation)
o Test w Sentile Lymph Node Biopsy – inject breast w dye/tracer → follow to LN in axilla
o If 1st layer of LN are (-) → assume all LN are (-) • If (+) → remove all LN
Desc
Malignant proliferation of cells in ducts
- bound by basement membrane
Tumor @ skin of nipple
Most common type of invasive carcinoma
Malignant cells in lobules
-bound by basement membrane
Low risk of progression to invasive
Lobular carcinoma that breaks BM
10% of cases
Rare
Older males
61
Risks Female Gender – #1 risk 99% are in women Obesity – adipose can create estrone
Age - ↑ in postmenopausal → unless Hereditary Atypical Hyperplasia – on previous biopsy
Early menarche/Late menopause - ↑ E exposure 1st degree relative w breast cancer (sister, mother,
daughter)
3 Predictive EsterogenR & ProgesteroneR – Triple-Negative - ∅ ER, PR, or Her2
Factors • ↑response to anti-estrogen agents (tomixifen) -poor prognosis
(ER, PR, Her2/nu amplification -↑ in african american
Her2/nu) • Her2/nu is a growth factor receptor on cell surface
• Tx – Trastuzuman/Herceptin (Her2 antibody)
Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
∅ mass → detect on mammogram Dystrophic calcification of dead cells Calcification on Mammography
• calcification on mammography
If spread to skin of nipple → Paget’s Dz
Comedo-Type: If breaks basement membrane → Invasive ductal
• high grade cells w necrosis & dystrophic If invades lobules → Invasive Lobular
calcification in center of duct
DCIS spreads to skin of nipple Nipple ulcerations Associated w underlying carcinoma
Erythema
Mass Duct-like structure in desmoplastic stroma Mammography or Physical Exam
• detect > 2 cm @ Physical Exam • CT growing around tumor
• detect ~ 1 cm @ Mamography
Dimpling of skin
Retraction of Nipple
Well differentiated tubules → May look normal Good prognosis
∅ myoepithelial cells
Desmoplastic Stroma – blue/grey CT
↑ in elderly women Malignant cells floating in pools of mucous Good prognosis
↑ in BRCA1 mutations High grade malignant cells
inflammatory cells in background
Cancer in lymphatics Erythematous, swollen breast Cancer within dermal lymphatics Dx – must see clinical presentation + patho finding
• d/dx Mastitis→ ∅ Tx by antibiotics Poor Prognosis – tumor is already in lymph
∅ mass, ∅ calcifications Dyscohesive cells → cells are separate Usually incidental finding
(!) Often multifocal & Bilateral • ∅ E-cadherin between cells
Tamoxifen & close-follow up
• Goal - ↓ risk of progresion to invasive
carcinoma
(!) Single file pattern (∅ duct formation)
• ∅ E-cadherin
BRCA1 - ↑ risk of break & ovarian carcinoma Be suspicious (!) may elect Prophylactic Mastectomy
• ↑ risk of medullary (but ∅ most common type) →Multiple 1st degree relatives w breast cancer • Some Risk still remains in axillary tail
• Ovarian – serous carcinoma & fallopian tube risk →Tumor @ premenopausal age of spence or extra breast tissue
BRCA2 – breast carcinoma in males →Multiple tumors
BRCA2 mutation Subareolar mass under nipple Usually DCIS
↑ risk in Klinefelter’s May produce discharge • ↑ ducts in males , ↓ lobules

17. 1 CNS developmental Abnormalities
Name
Neural Tube Defect
Cerebral Aqueduct Stenosis
Dandy-Walker Malformation
Arnold-Chiarai Malformation
(Type II)
17. 2 Spinal Cord Lesions
Name
Syringomyelia
Poliomyelitis
Werdnig-Hoffman Disease
Amyotrophic Lateral Sclerosis
(ALS) aka Lou Gehrig Dz
Friedreich Ataxia
17.3 Meningitis
Name
Basic Principles
Desc
Failure of neural tube closure
Congenital stenosis of Aqueduct
Desc
Cystic degeneration of spinal
Damage to Anterior motor horn
Inherited degeneration of anterior horn
Deneration of UMN & LMN
Degeneration of cerebellum & spinal cord
Desc
Inflammation of leptomeninges
62
Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Associated w low Folate PRIOR TO CONCEPTION Anencephaly – failure to close @ top of tube Neural crest → PNS Detect during prenatal care
• Absence of skull/brain Wall of tube → CNS • ↑ α FP in maternal blood
• Frog-like appearance of fetus Lumen of tube → ventricles & spinal cord canal • ↑ α FP in amniotic fluid
• Maternal polyhydramnios - ↓ swallowing
Spina Bifida – failure to close @ bottom of tube Folate supplement before pregnancy
• Failure of Posterior Vertebral Arch closure
• Complication: Meningocele or
meningomyelocele
• Spina Bifida occulata – dimple or patch of
hair @ defect
Congenital ↓ aqueduct → ↑ CFH in ventricles hydocephalus
Enlarging head circumference
Congenital failure of cerebellar vermis to develop Massivly dilated 4th ventricle
Absent cerebellum
Often accompanied by hydrocephalus
Congenital extenstion of cerebellar tonsil Obstruction of CSF flow → Hydrocephalus
through foramen magnum Associated w Meningomyelocele & Syringomyelia
Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Degeneration @ White commisure Usually @ C8-T1 Occur
Trauma ↓ Pain & Temp @ upper extremity
Associated w Arnold Chiarai • spares MVP in Upper extremity
Complication – expansion of syrinx
• → can lesion anterior horn → ↓ LMN
• → can lesion lateral horn → ↓ SNS
o Horner Syndrome
Polio Virus Lower Motor Neuron signs Lesion @ anterior horn
• FO route → small bowel &oropharynx → CNS • Flacid paralysis • ↓ tone • ∅ babinski
Auto Rec ↓ LMN → “Floppy Baby”
Death occurs with a few years after birth
Most are Sporadic & in middle age adults Early – atrophy & weakness of hands
• ∅ ∆ pain & temp (vs syringomyelia)
Zinc-Copper Superoxide Dismutase mutation → familial ↓ Anterior horn → LMN signs
↓ corticospinal tract → UMN signs
Mixed UMN & LMN sighns
Auto Rec – Unstable Trinucleotide repeat (GAA) Ataxia
• Frataxin Gene → ↓ mitochondrial Fe regulation→ ↓ MVP, ↓ P & T, ↓ LMN
↑ Fenton reaction → ↑ free radicals Present @ early childhood
Can have associated Hypertrophic Cardiomyopathy
Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Infections (!) Triad - HA, Neck stiffness, Fever Pia – Arachnoid – Dura (PAD in bt brain & skull) Lumbar Puncture - bt L4-L5 → spinal cord end @ L2
Neonate – Group B strep (B is for baby), E coli, Listeria Photophobia – especially viral Pia & Arachnoid = leptomeninges • ∅ pierce pia @ LP
Kids & Teens – N meningitidis (Nasopharnx→blood→CNS) Vomiting Bacterial – PMN & ↓ glucose, + gram stain & culture
Adults & Eldery – Strep Pneumo ∆ mental status Viral – Lymphocytes & normal CSF glucose
Nonvaccinated infajt – H flu Complications - ↑ in bacterial meningitis (↑ space) Fungal – lymphocytes & ↓ CSF glucose
Coxsackie – most common virus • Death – from ↑ ICP
Fungi – in imminocomprimised • Repair fibrosis →
Hydrocephalus, Hearing loss, seizure

17.4 Cerebrovascular Disease
Name
Basic Principles
Global Cerebral Ischemia
Ischemic Stroke
Intercerebral Hemorrhage
Subarachnoid Hemorrhage
17.5 Trauma
Name
Epidural Hematoma
Subdural Hematoma
Herniation
Desc
Neuro defiecit due to ↓ blood flow
Global ischemia
Regional ischemia → Focal deficit
Bleeding into brain parynchema
Bleeding into subarachnoid space
Desc
Blood on top of dura
Blood beneath dura
Displacement of brain tissue
63
Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Ischemia (85%) or Hemorrhage (15%)
↓ perfusion (atheroscleorsis of large vessel) Mild → Transient confusion
Acute ↓ blood flow (shock) • complete recovery
Chronic Hypoxia (anemia) Moderate
Repeated episode of hypoglycemia (insulinoma) • infarcts in watershed areas
• Damage to vulnerable regions
Pyramidal layer of cortex Layer 3, 5, 6
Corticolaminar Necrosis
Pyramidal neurons of hippocampus
↓ memory
Purkinje layer of cerebellum
Severe → Diffuse necrosis of brain
• death or coma
Thrombotic – ruptured plaque → thrombus → infarct Focal neuro deficiets Thrombotic → Pale Infarct
• ↑ @ branch points of artery • < 24 hr → T.I.A Embolic → Hemorrhagic Infract
• Pale Infarction • >24 hr → Ischemia Stroke Lacunar →
Embolic stroke - clot from L heart → lysis → hemorrhage small cystic lesions/”lakes”
• ↑@ MCA Liquefactive necrosis
Lacunar Stroke – vessels undergoing Hyaline Arteriolosclerosis • (!) Red Neurons – earliest change – 12 hr
• DM or Benign HTN • PMN, microglial → Granulationish tissue
• ↑ @ lenticulostriate artery • 1m later – fluid filled cyst lined by gliosis
Rupture of Charcot-Bouchard microaneurysm HA, N+V
• Complication of HTN Coma
• Basal Ganglia = most common sit
Rupture of Berry Anyerism Sudden HA – “Worst HA of my life” Bleed on bottom of brain LP – Xanthochromia
• associated w Marfan Nuchal Rigidity Berry Anyeurism • Yellow tinged CSF
• asociated w Auto Dom Adult Polycystic Kidney • Thin wall saccular outpouching • Billrubin breakdown
• ↑ @ circle of Willis…especially @ products
branch point of Anterior communicating a.
↓ media @ branch points → weak wall
Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Fracture skull → Middle Meningeal a.a Lucid Interval - ∅ neuro signs, asymptomatic Dura & skull tightly bound (!) Lens-Shaped lesion @ CT
Dura separated from skull → some parts of dura tightly attached Complication: Sudden Expansion→herniation → • High pressure artery needed
• Death
• “Talk & Die”
Rupture of bridging vein @ Trauma Progressive neurological signs Pia & arachnoid are loose
Rupture of bridging vein @ Atrophy of Brain Herniation – lethal complication • Low pressure vein will do the trick
Mass effect/ ↑ ICP 1.Tonsillar – cérébralar tonsils through foramen magnum
• Compress brainstem → cardiopulmonary arrest
2. Subfalcine – singular gyrus under falx cerebri
• compress Anter Cerebral a → infract
3. Uncal Herniation: uncus → tentorium cerebelli
• ↓ CN III → eyes down & out w dilated pupil
• *compress posterior cerebral a
• *pull on perimedian a.a → hemorrhage

17.6 Demyelinating Disorders
Name
Basic Principles
Leukodystrophies
Metachromatic
Leukodystrophy
Krabbes
Adrenoleukodystrophy
Multiple Sclerosis
Subacute Sclerosing
Panencephalitis
Progressive Multifocal
Leukoencephalopathy
Central Pontine Myelinolysis
Desc
Problem @ White Matter
Most common leukodystrophy
Most common chronic CNS dz of adults
↑ in regions away from equator
Progressive debilitating PAN -Encephalitis
• Grey & white matter
Encephalopathy of white matter
Focal demyelination of Pons
64
Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Destruction of myelin OR oligodendrocyte Myelin - ↑ conduction CNS – oligodendrocyte
• Axons preserved but ↓ conduction PNS - schwanncell
Inherited mutation in enzmes necessary for production or maintance
↓ arylsulfatase → ∅ myelin degradion
• Myelin accumulates in lysosomes
↓ galactocerebroside β galactosidase
Galactocerebroside accumulates in Mφ
Impaired addition of CoEnzyme A to Long Chain Fatty Acid
Fatty Acid accumulate → damage adrenals & white matter
Autoimmune destruction of CNS myelin & oligodestrocytes CN II → blurred vision in one eye MRI – plaques
Associated w HLA-DR2 Brain stem → vertigo & scanning speech LP
• Speech sounds like drunk • Lymphocytes
MLF → Internuclear Ophthalmoplegia • (!) ↑ Ig w oligoclonal Ig bands
White Matter – Hemiparesis • Myelin basic protein
Spinal Cored - ↓ LE sensation or weakness Tx
ANS – bowel, bladder & sexual dysfunction • High Dose streoids @ acute attack
• IFN-y
Slowly progressing, persistent infection of brain by Measles Neuro symptoms – years after infection Viral Inclusions in gray matter & white matter
• Infection @ infancy Death
JC infection of oligodendrocyte Rapidly progressive neuro signs
• Immunosuppression→reactivate latent virus Death
Rapid IV correction of Hyponatremia Acute Paralysis - except eyes
• Esp in malnourished patient or EtOH patient • Locked-In syndrome
 65
17.7 Dementia & Degenerative Disorders
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Alzheimer’s Disease Degeneration of cortex Sporadic – most common cause Dementia Diffuse cerebral atrophy Dx
(AD) Most common cause of dementia • Age is major risk factor Slow-onset memory loss – starts @ recent memories • Narrowing of gyri & Widening of sulci • Presumptive clinical dx after excluding
• (!) β secreatse → extracellular Aβ amyloid deposition Progressive disorientation • Hydrocephalus Ex Vacuo all other causes of dementia
• ↑ risk with ε4 allele of ApoE → ↑ conversion of APP to β ↓ learned motor skills & language skills Neuritic Plaque • Confirm dx @ autopsy
• ↓ risk w ε2 allele of ApoE Behavior & personality change • Aβ amyloid w neuron processes trapped
Early onset form Eventually become Mute & bedridden Cerebral Amyloid Angiopathy – Aβ amyloid@ vessels
• Seen in younger patients (!) ∅ focal deficits (early in course) • ↑ risk of hemorrhage
• Presenilin 1 & 2 mutation Neurofibrillary Tangles (NFT) of hyperPO4’d Tau
• ↑ risk in Downs Syndrome – APP is on Chrm 21 • Neuron w fibers → flame shaped edge
• (!) tau protein – microtubular protein
• Tau is hyperphophylated → ∆ tubules
nd
Vascular Dementia 2 more common cause of dementia HTN, atherosclerosis, vasculitis Multifocal infraction & injury
• Moderate global cerebral ischemia
Pick Disease Degenerative dz of frontal & temporal Frontal → ∆ behavior Round aggregates of tau protein in neuron & cortex
• Spares parietal & occipital Temporal → ∆ language
Dementia
Parkinson Disease Degeneration of DA neurons Unknown Etiology Tremor – pillrolling tremor → ↓ @ movement Normal Nigrostriatal Pathway:
@ substantia nigra pars compacta Rare cases – related to MPTP (drug contaminant) Rigidity DA causes ↑ stimulation & ↓ inhibition of cortex
• Part of Basal Ganglia Akinesia/bradykinesia – expressionless face • ↑ movement
Postural instability & shuffling gate (!) Lewy Bodies - composed of α-synuclein
Dementia – seen late into course of disease
Lewy Body Dimentia Early onset dementia – within 1 yr Cortical Lewy Bodies
Hallucinations
Parkinsonian features
Huntington Disease Degeneration of GABA neurons Auto Dom Chorea
@ caudate nucleus of basal ganglia Expansion of CAG trinucleotide repeat in Huntingtin Gene Athetosis
shows Anticipation – due to expansion of repeat @ spermatogenesis ↓ caudate → hydrocephalus ex vacuo
Progression to dementia & depression
• Suicide is common cause of death
Normal Pressure ↑ CSF → dilate ventricles Usually idiopathic Stretch of Corona Radiata CSF formed by choroid Lumbar Puncture – improve symptoms
Hydrocephalus • ↓ absorption into arachnoid granulations • Urinary incontinence CSF drained by arachnoid granulations → venous sinu VP shunt – definitive treatment
• Gait instability • Ventricle → peritoneum
• Dementia <wet wacky wobbly>
Spongiform Accumulation of abnormal Prion Protein CJD Normal prion is in α configuration (PrPC) CJD
Encephalopathy • Sporadic, Inherited, or Transmitted • Rapidly progressive dementia Pathogenic prion Is in –β configuration (PrPSc) • Spike-wave complex @ EEG
CJD • Ataxia & startle myoclonus • Converts normal prion → pathologic form
• Sporadic or rarely transmitted via infected human tissue • Spike-wave complex @ EEG • ∅ degradeable → damage neuron & glia
vCJD - ↑ in younger patients, linked to cow BSD (mad cow) • Death usually < 1 yr Accumulation → spongy degermation of parenchyma
Familial Fatal insomnia – inherited form Familial Fatal Insomnia – insomnia & ↑ startle response
 66
17.8 CNS tumors
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Basic Principles Mets (50%)– multiple, well circumscribed lesions Glia = astro, oligodendrocytes, ependymal cells Mets – multiple, well circumscribed lesions (tumors in adults→ usually above tentorium
• Lung, Breast, Kidney Neurons • Lung, Breast, Kidney Tumors in kids → usually below tentorium)
Primary – 50% Meningeal cells 1° tumors are locally destructive, ↓↓↓ mets from brain
Glioblastoma Multiforme Malignant tumor of astrocytes (!) Crosses corpus callosum (!) Crosses corpus callosum
(GBM) Most common malignant brain tumor in adults Necrosis with Pseudo-palisading cells on edge
Endothelial cell proliferation
Derived from glial cell
• (!) GFAP is intermediate filament
Meningioma Benign tumor of arachnoid cells Round mass attached to dura → compress cortex Expresses Estrogen receptor
Most common benign tumor in adults (!) Seizures Whorled appearance of cells
• ↑ in F • Calcify → Psammoma bodies
Schwannoma Benign tumor of Schwann Cells Involve CN or Spinal N S100 positive
(!) ↑ @ CN VIII @ cerebellopontine angle
Associated w NF2 – bilateral schwannoma • ↓ hearing & tinnitus
Bilateral in NF2
Oligodendroglioma Malignant tumor of oligodendrocytes Calcified tumor in white matter Fried-egg appearance
• ↑ @ frontal lobe
• Seizures
Pilocytic Astrocytoma Benign tumor of astrocytes ↑ @ Cerebellum Cystic lesion w mural nodule
Most common CNS tumor in children Rosenthal Fibers – astrocyte w thick eosinophil process
GFAP+
Medulloblastoma Malignant tumor derived from granular cells of Poor prognosis Small-round blue cells
cerebellum (Neuroectodermal origin) Tumor grows & Spread via CSF → spinal cord Homer-wright rosettes
Neuroectodermal tumor in kids • “Drop Metastasis) • Blue cells around nerve proceses
Ependymoma Malignant Ependymal tumor in kids Block 4th ventricle → Hydrocephalus Perivascular pseudorosettes
• Common @ 4th ventricle
Craniopharyngioma Tumor from epithelial remnants Preset as supratentorial mass in child/young adult Rathkes pouch → forms anterior pituitary from mouth Calcified @ imaging
of Rathke’s pouch Compress optic chiasm → Bitemporal Hemianopsia
Benign but recurring • (d/dx – pituitary adenoma) ↑ recurrence after resection
 67
18.1 Skeletal System
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Achondroplasia Impaired cartilage proliferation @ growth plate Auto Dom Short extremities
• ↑ w paternal age • ↓↓ Endochondral bone formation
• Most mutations are sporadic Normal sized head & chest
Activation mutate in FGFR3 • Intramembranous bone formation is ok
• Fibroblast Growth Factor Receptor 3 •
• Activated receptor → inhibit growth Mental function, life span, & fertility are not effected

Osteogenesis Imperfecta Congenital defect of bone formation Auto Dom defect Multiple fractures of bone
→ weak bone ↓ Type I Collagen Synthesis (!) Blue sclera –
• ↓ Type I collagen→expose choroidal veins
Hearing loss – fracture of bones in ear
Osteopetrosis Thick bone w frequent fractures ↓ osteoclast function Abnormally thick, heavy bone (!) Bone Marrow Transplant
Inherited defect of bone resorption • Multiple causes Bone Fractures • Normal hematopiesis → normal mφ
• Carbonic Anhydrase (CA) II mutation –(common) Anemia, TCP, Leukopenia → normal monocyte
→ ∅ acid to resorb bone • Bone growth → ↓ medullary space → normal osteoclasts
• “Myeloschisis process” → pancytopenia
Vision & Hearing impairment – compress CN @ skull
Hydrocephalus – thicken @ foramen magnum
Renal Tubular Acidosis – ∅ CA → ↓ bicarb
Rickets/Osteomalacia Defective mineralization of osteoid ↓ Vit D Rickets – in children → deposition of osteoid ↓calcium, ↓ PO4, ↑ PTH, ↑ alkaline phosphate
• Vit D works @ bone, kidney, intestine -Pigeon Breast Deformity
• Resorb Ca & PO4 -Frontal Bossing – prominent forehead
↓ sun exposure, poor diet, malabsorption, liver & renal failure -Rachitic Rosary – bead @ costochondral junction
-Bowing of Legs
Osteomalacia – in Adults → Weak bone & ↑ fracture
-↑ risk @ weight bearing area (Hip, Vertebrae)
-↓calcium, ↓ PO4, ↑ PTH, ↑ alkaline phosphate
-(!) AlkPhos is necessary for osteoblast deposition
Osteoporosis Loss of trabecular bone mass Based on Bone Pain & Fractures @ weight bearing areas Monitor density w DEXA scan
Porous bone w ↑ risk of fracture -Peak Bone mass (@ ~ 30 y.o) • Vertebra (!) serum Ca, PO4, PTH & alk phos are NORMAL
• Diet, Exercise, & Vit D receptor • Hip ∅ Glucocoricoids – contraindicated
More common in senile & postmenopausal -Rate of loss after peak bone mass • Distal radius Tx:
• Determined by diet & exercise -Exercise, Vit D, Ca → limit bone loss
• Estrogen is protective → ↑ loss @ menopause -Bisphosphonates → osteoclast apoptosis
-Estrogen replacement is debated (DVT risk)
Paget’s Dz of Bone Imbalance bt osteoclast & osteoblast function Unknown etiology – possibly viral? Thick sclerotic bone that fractures easily Localized process – involving 1 or more bones (!) ↑ alk phos only
↑ @ late adulthood ↑↑↑ osteoclast function → ↑↑↑ osteoblast function rapidly Bone pain – microfracture • ∅ involve the whole skeleton • Everything else normal
Eventually osteoclast burns out → osteoblast keeps going ↑ hat size – skull effects Stages Tx
• Osteoblast does a poor job of deposition because Hearing Loss – imping CN • Osteoclastic • Calcitonin
its “in a rush” Lion-like facies – thickened facial bones • Mixed osteoblastic-osteoclastic • Bisphosphonates
(!) Isolated elevated Alkaline phophataste • Osteoblastic
Complication Mosaic pattern of Lamellar bone – “puzzle pieces”
• High-output Cardiac Failure
Remodeling → ↑ pressure
• Osteosarcoma (in elderly)
Osteomyelitis Infection of marrow space & bone Bacterial – hematogenous spread Bone pain w fever & leukocytosis Lytic focus Lytic focus @ xray
↑ in children → metaphysis (kids) & epiphysis (adults) -Liquefactive necrosis surrounded by sclerosis on Blood Culture
X-Ray
Bugs of S. aureus - overall most common TB – Pots Dz @ lumbar vertebrae Pseudomonas – IV drug use
Osteomyelitis N gonorrhoeae – sexually active young adult Salmonella – sickle cell Pasteurella – dog or cat bite/scratch
Avascular (Aseptic) Ischemic Necrosis of bone & bone marrow Ischemia Complication:
Necrosis • Trauma or Fracture • Osteoarthritis
• Steroids • Fracture
• Sickle Cell - dactylitis
• Caissons Dz – gas emboli (N2) precipitates in bone
 68
18.2 Bone Tumors
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Osteoma Benign tumor of bone Most common @ surface of facial bone
Gardner’s Syndrome
• FAP
• Fibromatosis in retroperitoneum
• Osteoma of facial bone
Osteoid Osteoma Benign tumor of osteoblast → lay down osteoid Bone pain → RESOLVES w ASA @ cortex of long bones (femur) Xray- Bony Mass w Radiolucent (osteoid) core
• surrounded by rim of reactive bone • usually @ diaphysis
↑ in young adults < 26 y.o
Osteoblastoma Similar to osteoid osteoma Bone Pain → ∅ respond to ASA Larger than osteoid osteoma ( > 2cm)
@ vertebrae
Osteochondroma Benign tumor of bone w overlying cartilage cap Complication Arise from lateral projection of growth plate
Most common benign tumor of bone • overlying cartilage transforms
→ Chondrosarcoma

Osteosarcoma Malignant tumor of bone Risks Bone Pain w Swelling @ metaphysis of long bones Xray – drag periosteum off bone
Malignant proliferation of osteoblasts • Familial retinoblastoma → teenage Pathological Fracture • Distal femur or proximal tibia • “Codman’s Angle”
↑ in teenagers → also seen in elderly • Pagets Dz of Bone • Sunburst
• Radiation Pleomorphic cells producing osteoid

Giant Cell Tumor Tumor comprised of @ epiphysis of long bones X-ray –

• multinucleated giant cells Locally aggressive tumor → may recur • Distal femur & proximal tibia • Soap Bubble
• Stromal cells Appearance
↑ in young adult

Ewing Sarcoma Malignant Proliferation of poorly differentiated cells 11:22 translocation Some patient my present w fever Small round blue cells – resemble lymphocytes X-Ray
• Derived from neuroectoderm • d/dx – osteomyelitis • d/dx – lymphoma or chronic osteomyelitis • Onion Skin
• Patrick EWING was #33 on the knicks • These cells have 11:22 tranlocation appearance
↑ in male children • 11 + 22 = 33 Aggressive → often present as mets
• Basketball → onion skin @ diaphysis of long bone is this an onion or a
• Blue cells – NY Knicks Jersey color Grows inside medullary cavity → push on bone surface basketball?? →→→
• Layering of new bone by periosteum Responds well to chemo
Chondroma Benign tumor of cartilage @ medulla of small bones of hand & feet
Chondrosarcoma Malignant tumor of cartilage @ medulla of pelvis & central skeleton
Mets More common than primary Osteolytic (Punch-out) Lesions
(!)Exception
• Prostate Carcinoma → osteoblast lesion

18.3 Joint
Name
Basic Principles of Joint
Degenerative Joint
Disease
(Osteoarthritis)
Rheumatoid Arthritis
Seronegative
Spondyloarthropathies
Ankylosing
spondyloarthritis
Reiter’s Syndrome
Psoriatic Arthritis
69
Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Connective bt 2 ones Solid joints – tight connection → structural strength Bone – Articular Cartilage (Type II) – Joint Capsule →
Synovial joints – allow motions Synovium → secretes Synovial Fluid w Hyaluronic Acid
Progressive degeneration of articular cartilage Wear & Tear Joint stiffness @ morning → WORSTEN during day @ hip, lumbar spine, knees, DIP & PIP
Risk factors – age, obesity, trauma Occur @ hip, lumbar spine, knees, DIP & PIP Disruption of cartilage lining articular surface
-Bone chips fall into joint → Joint Mice
-Bone against bone → Eburnation of subchondral bone
-Osteophyte formation - ↑ @ DIP & PIP
• Heberden’s & Bouchard’s Nodes
Chronic Systemic Autoimmune Dz associated w HLA-DR4 Synovitis → leads to formation of Panus Panus (!) IgM Ab against Fc portion of IgG
↑ in middle aged women Morning stiffness → IMPROVE w activity • Inflamed Granulation tissue • “Rheumatoid Factor”
Joint space narrowing, loss of cartilage • Myofibroblast in granulation tissue • Marker of tissue damage & dz activity
Osteopenia, Fever, malaise, weight loss, myalgia  Joints move together or apart PMN & protein in joints
Rheumatoid Nodules, Vasculitis Bilaterally @ PIP, finger, wrist, elbow, ankles, & knees
Bakers Cyst, Pleural Effusion, LAD, interstitial lung fibrosis • (!) DIP spared
Complications Rheumatoid Nodules – central necrosis surround w
• Anemia of Chronic Dz - epithelioid histiocytes
• 2ndary amyloidosis –( SAA → AA )
∅ rheumatoid factor Associated w HLA-B27 Axial skeletal involvement @axial skeleton
Young adults, often male Low Back Pain @ SI joint & spin
Fusion of vertebrae – Bamboo spine
Uveitis – red eye, blurry vision → blindness
Aortitis - ↑ risk of aneurysm & aortic regurg
Young males Weeks after infection Arthritis “cant see, cant pee, cant climb a tree”
• GI infection Urethritis
• Chlamydia Conjunctivitis
Seen in 10% of psoriasis Axial involvement @ axial & peripheral joints
involve DIP of hands/feet
→ Sausage Finger/ Toe

Infectious Arthritis Arthritis due infectious agent – usually bacteria N gonorrhoeae – young adults, sexually active
• Most common
S aureus – older children & adults
Gout Depositing of Monosodium Urate (MSU) in tissues Hyperuricemia
• Especially joint • ↑ uric acid into blood (diet)
• ↓ filtration @ kidney
1° Gout – exact cause unknown, most common form
• Adult males
2° Gout – associated w
• Leukemia, MPD – cell turnover
• Lesch-Nyhan - ↓ purine salvage (HGPRT)
• Renal insufficiency
Pseudogout Deposition of calcium pyrophosphate
Usually involves single joint (↑ @ knee)
Warm, erythematous joint w ↓ R.O.M
Fever, ↑ WBC, ↑ ESR
Acute Gout
• MSU → activate PMN inflammation rxn
• Painful arthritis @ great toe (Podagra)
• Triggers: EtOH & Meat consumption
Chronic Gout
• Tophi – uric acid crystal aggregate in soft
tissue joints
• Renal Failure – uric acid deposit in kidney
Clinically resembles gout
Tophi – white chalky deposit of uric acid Hyperuricemia
• Surrounding fibrosis Needle-shape crystals w Negative Birefringence
under polarized light
Joint Aspiration
• Needle-shape crystals w Negative
Birefringence under polarized light
• “yellow” under parallel light
Rhomboid shaped crystals w weak positive
birefringence under polarized light
 70
18.4 Skeletal Muscle
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Dermatomyositis Inflammatory disorder of skin & skeletal mm Unknown etiology Bilateral proximal m.m weakness Perimysial inflammation (CD4+) ↑ creatine kinease
some associated w carcinoma (gastric carcinoma) • Can’t comb hair, can’t climb stairs • perifascicular atrophy ANA + (d/dx SLE)
• Late in disease → can involve distal m.m Anti-Jo-1 antibody
Rash of Upper Eylids w purple color <perimysium is closer to the skin (dermato)>
Malar Rash – (d/dx SLE) Tx – Corticosteroids
Red Papules on elbow, knuckes, knees – Gratin lesion
Polymyositis Inflammatory disorder of skeletal m.m Resembles dermatomyositis → ∅ skin involvement Endomysial Inflammation (CD8+)
Bilateral proximal m.m weakness • Necrotic m.m fibers
• Can’t comb hair, can’t climb stairs

X-Linked Muscular Degenerative disorder characterized by m.m wasting Deletions of Dystrophin Proximal m.m weakness @ 1 y.o (!) Replacement of skeletal m.m by adipose tissue ↑ Creatine kinase
Dystrophy • Mutations are frequent (large genes) • Progress to distal m.m • Calf is full of adipose tissue
(Duchenne’s) • Dystrophin anchors m.m filament to ECM (!) Calf-Pseudohypertrophy <duchenees is a deletion in the gene>
Death – Cardiac or Respiratory failure
Becker Muscular Mutated Dystrophin m.m weakness Replacement of skeletal m.m by adipose tissue
Dystrophy Clinically milder than Ducheenes <beckers is a booboo in the gene>
18.5 NMJ
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Myasthenia Gravis completes for ACh-R Autoantibody against Postsympatic ACh-R @ NMJ Muscle Weakness @ activity Anti-Cholinesterase (Acetylchoinesterase inhibitor)
↑ in women • Recovery @ rest • ↑ [ACh]
(!) Associated w thymic hyperplasia or thymoma Involvment of eyes → Ptosis & Dyplopia If thymoma → Thymus Sx can help
Lambert-Eaton Autoimmune m.m dz Paraneoplastic – Small Cell Carcinoma Proximal m.m weakness ∅ improved by anti-cholinesterase
Syndrome Autoantibody against presynaptic calcium channel @ NMJ • Improves @ activity
• ∅ ACh release Eyes spared Tx the cancer
18.6 Soft Tissue Tumors
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Lipoma Benign tumor of adipose tissue
Most common benign soft tissue tumor in adult
Liposarcoma Malignant tumor of adipose Lipoblast = characteristic cell
Most common malignant soft tissue tumor in adults
Rhabdomyoma Benign tumor of skeletal m.m (cardiac rhabdomyoma associated w tuberus sclerosis)
Rhabdomyosarcoma Malignant tumor of skeletal m.m ↑ @ head & neck Rhabdomyoblast = characteristic cell
Most common malignant soft tissue tumor in kids (!) Vagina is classic site @ young girls • Desmin+
 71
19.1 Inflammatory Dermatoses
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Skin (General) Barrier against outside world & fluid loss Stratum Basales – contains stem cells BM separated epidermis/derm
Stratum Spinosum – spiny layer Epidermis
• “spines” = desmosomes • Keratinocytes in multiple layers
• Cytoplasmic bridges between cells Dermic
Stratum Granulosum – granules in keratinocytes • Adnexal structures – sweat, hair,
Stratum Corneum – pink keratin, ∅ nucleus • Blood vessels
Atopic Dermatitis Pruritic erythematous oozing rash Type I hypersensitivity Often @ face & flexor surfaces Topical Steroids
aka Eczema w vesicles & edema Atopy – Asthma, Allergic Rhnitis
↑ @ face & flexor surfaces

Contact Dermatitis Pruritic erythematous oozing rash Allergens/Irritants → Inflammatory response Remove offending agent
w vesicles & edema • Poison Ivy – Type IV hypersensitivity Topical Steroid
• Nickle – watchs, jeans– Type IV hypersensitivity
• Irritant chemicals – detergents
• Drugs -PCNs

Acne Vulgaris Chronic inflammation of hair follicles & sebaceous gland Comedones – whiteheads/blackheads Benzoyl peroxide – antimicrobial
↑ in teenage → ↑ hormones → • Clogged sebaceous gland → whitehead/blackhead Pustules – pimples Vit A derivative (Isotretinoin) - ↓ keratin production
↑ keratinization @ hair shafts & ↑ sebum • Infection w Propionibacterium acnes Nodules - scarring
• Lipases → breakdown sebum → Pro-inflammation CKs
• Scarring of pimple → nodules
Psorasis Well circumscribed salmon-colored plaques w silvery scale Excessive keratinocyte proliferation Well circumscribed salmon-colored plaques Acanthosis - Epidermal Hyperplasia Corticosteroids
↑ @ extensor surfaces & scalp Possibly autoimmune → environmental trigger my by Trauma silvery scale Parakeratosis – hyperkeratosis w retention of nuclei PUVA = UV-A light w Psoralen
Nails - pitting Genetic associate w HLA-C ↑ @ extensor surfaces & scalp @ stratum corneum Immune mediating therapy
Nails - pitting Collection of PMN @ stratum corneum
• Munro Microabcess
Thin epidermis above elongated dermal papillae
• Bleeding when scare is picked off
• Auspitze Sign
Lichen Planus Pruritic, planer, polygonal, purple papules Unknown Pruritic, planer, polygonal, purple papules Infammation @ dermal/epidermal junction
Often w reticular white lines on surface Associated w chronic HCV Often w reticular white lines on surface @ mucosa • Sawtooth dermal/epidermation junction
• Wickham striae • Wickham striae
↑ @ wrists, elbows, & oral mucosa ↑ @ wrists, elbows, & oral mucosa

19.2 Blistering Dermatosis – separation of basal layer & BM OR separation bt layers of epithelium
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Pemphigus Vulgaris Autoimmune destruction of desmosome IgG against Desmoglian Thin wall bullae → rupture easily Blister b/t Basal cells → rest of epidermis Immunoflourescence
• Shallow erosions w dry crust Basal cells attached to BM via hemodesmosome • IgG surrounding keratinocytes
• Tombstone apperance • “Fish-net appearance”
Can involve Skin & oral mucosa Acantholysis – separation of keratinocytes
Thin Epidermis → thin wall blister → rupture
Bullous Pemphigoid Autoimmune destruction of hemidesmisome IgG against Epidermal Basement membrane Tense Bullae → ∅ rupture easily Subepidermal blisters of skin Linear immunoflouresence
Oral mucosa spared Blister bt dermis & epidermis

Dermatitis Pruitic vesicles resembling herpes Autoimme deposition of IgA @ tips of dermal papillae Puritis vesicles & Bullae that are grouped IgA @ just the tip of dermal papillae → blisters Control Celiac
Herpetiformis (!) strong association w Celiac Dz • Gluten-free diet
• Antibody against Gluten → x-rxn w reticulin fibers
Erythema Hypersensitvity → tergetoid rash & bullae Hypersensitivity Multiple red rash/lesion
Multiforme (EM) Associated w White in center – necrosis @ center of lesion
• (!) HSV • Targetoid appearance
• mycoplasm, drugs, autoimmune (SLE), malignancy
Steven Johnson EM + Oral mucosa involvement + Fever Adverse drug rxn
TEN Severe form of SJS Adverse drug rxn Diffuse sloughing of skin Slough @ dermal/epidermal junction Medical emergency
Toxic Epidermal
Necrolysis
 72
19.3 Epithelial Tumors
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Seborrheic Keratosis Benign squamous proliferation Normal in aging Raised discolored plaque Raised lesions
↑ in eldery Leser-Trelat Sign – sudden onset of multiple seborrheic keratosis • “Stuck-On appearance” Pseudocyst - Circular spaces w abundant pink keratin
• Suggests underlying GI carcinoma
Acanthosis Nigracans Epidermal hyperplasia w darkening of skin Associated w Epidermal hyperplasia w darkening of skin
• Insulin Resistance (Type II DM) • “Velvety skin”
• Malignancy (Gastric Carcinoma)
Basal Cell Carcinoma Malignant proliferation of basal cells Risk Factors Elevated nodule w central ulceration Tumor nodules w ” Peripheral Palisading” Sx excision
↑↑ UV-B → dna damage → ↑ pyrimidine dimers Surrounded by dilated blood vessels Very rare mets → excellent prognosis
• Sunlight • Albinism • Telangiectasias
• Xeroderma Pigmentosum – ↓ nucleotide excision ↑ occurance @ upper lip
Squamous Cell Malignant proliferation of squamous cells Risk Factors : Ulcerated nodular mass Keratin pearls Sx excision
Carcinoma ↑↑ UV-B → dna damage ↑ @ face Very rare mets → excellent prognosis
• Sunlight • Albinism ↑ occurance @ lower lip
• Xeroderma Pigmentosum – ↑ pyrimidine dimers
Immunosuppressive Therapy – transplants
Arsenic Poisoning
Chronic Inflammation
Actinic Keratosis Dysplasia → Rare progression to SCC Sunlight Hyperkeratotic scaly plaque
@ face, back, & neck
Keratoacanthoma Well differentiated Squamous cell carcinoma Develops rapidly (weeks) Cup-shaped tumor
Regresses spontaneously Keratin debris
19.4 Disorders of Pigmentation & Melanocytes
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Melanocytes Responsible for skin pigmentation Tyrosine → Melanin @melanosome Present in basal layer
(general) melanosome→ passed to keratinocytes Derived from neural crest
Vitiligo Localized Autoimmune destruction of melanocyte Autoimmune Localized loss of skin pigmentation Easy to see in dark skinned
In light skined – some areas don’t tan right
Albinism Congenital lac of pigment Enzyme defect → impaired melanin production Complication: ↑ risk of skin cancer Involving eyes only = Ocular form
• ↓ Tyrosinase Eyes + Skin = Oculocutaneous form
Freckle (Ephelis) Small tan brown macule ↑ # of melanosomes
Darken when exposred to sunlight • ∅ increased melanocytes
Melasma Mask-like hyperpigmentation of cheeks Associated w Pregnancy & Oral Contraceptive
Nevus (mole) Benign neoplasm of melanocytes Congenital – present @ birth, associated w hair growth on it Congenital – hair growing from it = benign Junctional
Acquired -grow @ dermal/epidermal junctional
Junctional – most common in kids •Junctional – most common in kids Complication – Dysplasia → precursor to melanoma Compound – extend into dermis
Intradermal – most common in adults • Compound Intradermal - in dermis only (last stage of junctional)
Melanoma Malignant neoplasm of melanocytes Risk Factors : Mole-like growth w ABCD 2 growth phases
Most common cause of death from skin cancer ↑↑ UV-B → dna damage Asymmetry 1.Radial – horizontal along epidermal/superficial dermis
• Sunlight • Albinism Borders – irregular 2.Vertical – grows into deep dermis
• Xeroderma Pigmentosum – ↑ pyrimidine dimers Color - ∅ uniform • worst prognosis @ vertical phase
Dysplastic Nevus syndrome – AutoDom Diameter - > 6mm
Lentigo Lentiginous proliferation (radial growth only) Good prognosis
Maligna melanoma grows around dermal/epidermal junction
Superficial Most common subtype Dominant early radial phase Good prognosis
Spreading Melanoma
Nodular Melanoma Creats nodule/bump on skin Early vertical phase → push epidermis up Poor prognosis
Acral Lentiginous ↑ in dark skin individuals ∅ related to UV light exposure ↑ @ palms & soles
 73
19.5 Infectious Dz of Skin
Name Desc Cause Clinical Patho & Pics Dx/Tx & Notes & Pics
Impetigo Superficial bacterial skin infection Staph a & Strep p Erythematous macules → Pustules
↑ in children Erosion w dry crusted, honey-colored serum
↑ @ face
Cellulitis Deeper, dermal infection Staph a & Strep p Tender, red swollen rash w Fever
Risks
• Recent Sx Necrotizing Faciitis = complication
• Trauma • Necrosis of subcutaneous tissue via anerobic bugs
• Insect Bite • CO2 → crepitus
• Surgical emergency
Staph Scaled Skin Staph infection → Exfoliatin A & B Toxin Staph a Diffuse soughing of skin → significant skin loss Separation @ Stratum Granulosum
Syndrome Erythematous rash & fever (d/dx – TEN is @ dermal/epidermal junction)
Verruca (wart) Flesh-color papuled w rough surface HPV infection of keratinocytes ↑ @ hands & feet
Molluscum Firm, pink umbilicated papule Poxvirus Molluscum Bodies in affected keratinocytes
Contagiosum ↑ in children • Viral inclusions
Can also occur in sexually active &/or ↓ immune