Goljan Path Review: High Yield o steal e- from molecules

Cell Injury o damage membrane & DNA

 FR Neutralization: SOD, GSH & Vitamins C & E
Tissue Hypoxia  Vitamin C: best hydroxyl FR neutralizer
 Hypoxia: inadequate tissue oxygenation  Acetaminophen: FR injury liver & kidneys
 O2 Content: (Hb x 1.34) x SaO2 + PaO2 x 0.003  N-acetylcysteine: generates GSH
 Pulse Ox: falsely ↑ SaO2 w/ metHb &COHb  Reprofusion Injury: superoxide FRs & ↑cytosolic Ca
 Ischemia: ↓arterial blood inflow or venous outflow  Excess Fe & Cu: hydroxyl FR damage of tissue
 Hypoxemia: ↓PaO2
 ↑ Alveolar PCO2 = ↓Alveolar PO2 = ↓PaO2 = ↓SaO2 Cell Organelle Injury
 Ventilation Defect: perfused but NOT ventilated—intrapulmonary shunt  SER Hyperplasia: ↑ drug metabolism
 Perfusion Defect: ventilated but NOT perfused—dead space  SER Inhibition: ↓drug metabolism
 Diffusion Defect: interstitial fibrosis or pulmonary edema  1° Lysosomes: derive from Golgi Apparatus
 Anemia: normal PaO2 & SaO2  Phagolysosomes: contain lysosomal enzymes
 MetHb: Heme Fe3+ & ↓SaO2  I-Cell Disease: defect in post-translational modification of lysosomal
o Tx w/ IV methylene blue enyzmes
 CO Poisoning: normal PaO2 & ↓SaO2  Lysosomal Storage Disease: ↓lysosomal enzymes
o Tx w/ O2 via nonbreather mask  CHS: giant lysosomal
 High Altitude: ↑ 2,3-BPG synthesis & Respiratory ALKALOSIS  Defect Tublin Synthesis G2 Phase: Etoposide & Bleomycin B
 CO & CN: inhibit Cytochrome Oxidase  Mitotic Spindle Defects: Vinca Alkaloids, Colchicine & Paclitaxel
o Poisoning—house fires  Ubiqutin: marker for intermediate filament degradation
o Tx CN poisoning w/ Amyl Nitrite & Thiosulfate
 Uncouplers: Theromgenin & Dinitrophenol Intracellular Accumulations
 Mitochondrial Toxins: Alcohol & Salicylates  *Alcohol = most common cause of FATTY Δ*
 Watershed Areas: Cerebral Vessels & Mesenteric Arteries  Fatty Liver: ↑TG synthesis & ↓TG secretion
 ST Segment Depression: Subendocardial Ischemia  G3-P: substrate for TG synthesis
 Kidney Cortex: Proximal tubule most susceptible to hypoxia  Fatty Δ in Cardiac Muscle: anemia & diphtheria
 Kidney Medulla: thick ascending limb most susceptible to hypoxia  Serum Ferritin: ↓in Fe deficiency anemia
 Neurons: most adversely affected cell in tissue hypoxia  Hemosiderin: Ferritin degradation product
 Zone III Hepatocytes: most susceptible to hypoxia  Dystrophic Calcification: calcification of NECROTIC tissue
 Anaerobic Glycolysis: 1° source ATP in hypoxia—Lactic Acidosis  Metastatic Calcification: calcification of NORMAL tissue
 ↑ Ca in Cytosol: “point of no return”—activates enzymes
Adaptation to Cell Injury: Growth Alterations
Free Radical Cell Injury  Atrophy
 Cytochrome C in Cytosol: activates APOTOSIS o ↓size/weight of tissue or organ
 Hydroxyl Free Radicals: most destructive Free Radicals o Autophagic vacuoles
 Oxidase Rxns: produce superoxide FR o ↑lipofuscin in cells
 Acetaminophen: Drug FRs formed in liver  Hypertrophy: ↑cell size & workload
 Fe & Cu: generate hydroxyl FRs  Hyperplasia: ↑# of cells
 Free Radicals  Labile/Stable Cells: can divide
  Permanent Cells: cannot divide  Delayed Separation Umbilical Cord: selection or CD11a:CD18 def
 Metaplasia: 1 cell type replaces another  Chemostaxis: directed migration of neutrophils
 Barrett’s Esophagus: glandular metaplasia gastric reflux  Opsonins: IgG & C3b
 Metaplasia/Hyperplasia: in some cases may progress dysplasia  Bruton’s Agammaglobulinemia: opsonization defect
 Dysplasia: disordered cell growth & may progress to cancer  Chediak-Higashi Syndrome: cannot form phagolysosomes
 O2 Dependent MPO System: most potent microbicial system
Cell Death  End-Product O2 Dependent MPO System: bleach
 Coagulation Necrosis: preservation of structural outlines  Chronic Granulomatous Dz: absent NADPH Oxidase & Respiratory Burst
 Infarctions: pale & hemorrhage types  MPO Deficiency: normal respiratory burst
 Dry Gangrene: predominately coagulation necrosis  ↓NADPH: microbicidal defect
 Infarction LESS likely w/ dual or collateral blood supply  Histamine: most important chemical mediator of acute inflammation
 Cerebral Infarction: LIQUEFACTIVE necrosis—NOT coagulative  Chemical Mediators: short ½ lives
 Wet Gangrene: predominantly LIQUEFACTIVE necrosis  S aureus: most common cause of SKIN ABSCESS
 Tuberculosis: most common cause of CASEOUS necrosis  Pseudomembranous Inflammation: Diptheria, Clostridium difficle,
 Enzymatic Fat Necrosis: Acute Pancreatitis noninvasive bacteria
 Traumatic Fat Necrosis: NOT enzyme-mediated  FEVER IS GOOD
 Fibrinoid Necrosis: necrosis of IMMUNE-mediated dz  Clearance of Neutrophils in AI: apoptosis
 Apoptosis: programed cell death
 Extrinsic Pathway of Apoptosis: requires TNF Chronic Inflammation
 BCL2 Gene: ANTI-apoptosis gene  Infection: most common cause of chronic inflammation
 TP53 Suppressor Gene: “guardian” of cell  Monocytes & Macrophages: 1° leukocytes in chronic inflammation
 BAX Gene: apoptosis gene  Granulation Tissue: converted to scar tissue
 Caspases: group of cysteine proteases—activation INDUCES apoptosis  Fibronectin: key adhesion glycoprotein in ECM
 Apoptotic Δs: deeply EOSINOPHILIC cytoplasm & PYKNOTIC nucleus  Cell Types in Tuberculous Granuloma: macrophages & CD4 T helper
 Epithelioid Cells: macrophages activated by γ-interferon from CD4 T
Inflammation & Repair helper cells
 TNF-α: important in formation & maintenance of granulomas
Acute Inflammation  G1 Phase: most variable phase in cell cycle
 AI: chemical, vascular & cellular responses—NOT synonymous w/  G1-S Phase: most critical phase in cell cycle
infection  Genes Controlling G1-S Phase: RB & TP53 suppressor genes
 Rubor, Calor, Tumor—histamine mediated  BAX Gene: activation by TP53 initiates apoptosis
 Mast Cells: release PREFORMED histamine  Laminin: Key adhesion glycoprotein in BM
 Neutrophils: 1° leukocytes in acute inflammation  Granulation Tissue: essential for normal CT repair
 Selectins: responsible for neutrophil rolling  Lysyl Oxidase: cross-links ↑ tensile strength
 β2 Integrins: neutrophil/endothelial adhesion molecules—firm  Ascorbic Acid: hydroxylates proline & lysine
adherence  Copper: cofactor in lysyl oxidase
 Neutrophil Leukocytosis: Catecholamines, Corticosteroids & Lithium  Ehlers-Danlos Sydrome: defects in Type I & III collagen
 Neutropenia: Endotoxins  Zinc: cofactor in collagenase
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  Infections: most common cause of impaired wound healing  Myasthenia Gravis & Graves Disease: antibodies against receptors—type
 Vitamin C Deficiency: ↓cross-linking of tropocollagen  ↓tensile II HSR
strength  Type III: complement activation by circulating antigen-antibody
 Glucocorticoids: prevent scar formation complexes
 Keloids: excess Type III collagen  Antibody Mediated HSR: Type I, II, & III
 Severe Injury Liver: regenerative nodules & fibrosis  Type IV: cellular immunity—Delayed Rxn Hypersensititivity CD4 cells
 Lung Injury: Type II penumocyte is repair cell interact w/ macrophages, TB granuloma
 Brain Injury: Proliferation of astrocytes & microglial cells  Contact Dermatitis
 Peripheral Nerve Transection: Schwann Cell key cell in reinnervation o activated CD4 (1°mediator) + CD8 cells
 IgM: predominant immunoglobulin in acute inflammation o Poison Ivy, Nickel
 IgG: predominant immunoglobulin in chronic inflammation
 Corticosteroid Effect in Blood: ↑neutrophils, ↓eosinophils & Transplantation Immunology
↓lymphocytes  ABO Blood Group Compatibility: most important requirement for
 ↑ESR: ↑fibrinogen, anemia successful transplantation
 CRP: necrosis marker & disease activity  Autograft: best survival rate
 SPE Acute Inflammation: ↓albumin, NO alteration in γ-globulin peak  Fetus: allograft NOT rejected by mother
 Polyclonal Gammopathy: sign of chronic inflammation  Hyperacute Rejection: irreversible, type II HSR
 Acute Rejection: most common type, type IV & II HSR
 Chronic Rejection: irreversible
Immunopathology
 Immunosuppressive Therapy: danger of Squamous Cell Cacrinoma
 GVH Rxn: jaundice, diarrhea, dermatitis
Immune System Cells
 Corneal Transplant: best allograft survival rate
 Innate Immunity: 1st defense against pathogens
 Natural Killer Cells: large granular lymphocytes in peripheral blood
Autoimmune Diseases
 TLRs: recognize non-self antigens on pathogen
 Organ-Specific Disorders: Addison’s Dz & Pernicious Anemia
 NFκβ: master switch to nucleus
 Serum ANA: antibodies against DNA, histones, acidic protein, nucleoli
 IgM & IgG Synthesis: begin AFTER birth
 Anti-dsDNA: SLE w/ glomerulonephritis
 Rim Pattern: associated w/ anti-dsDNA antibodies
MHC
 SLE: genetic + environmental factors
 APCs: B cells, macrophages, dendritic cells
 Most Common Cardiac Finding in SLE: fibrinous pericarditis w/ effusion
 HLA-B27: anklyosing spondylitis
 Procainamide: most common drug associated w/ drug-induced lupus
Hypersensitivity Rxns  Drug Induced Lupus: Anithistone Antibodies
 Type I: IgE activation of mast cells  Screen for SLE: serum ANA
 Mast Cell Activation: allergens cross-link allergen-specific antibodies  Confirm SLE: anti-dsDNA & anti-Sm antibodies
 Mast Cells: early & late phase rxns  LE Cell: neutrophil w/ phagocytosed, altered DNA
 Anaphylactic Shock: potentially fatal Type I hypersensitivity rxn  Systemic Sclerosis
 Type II: antibody-dependent cytotoxic rxns o excess collagen deposition & digital vasculitis
o anti-topoisomerase antibodies

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  Raynaud’s Phenomenon: most common initial sign of systemic sclerosis  Compartment Sizes: ICF > ECF & Interstitial > Vascular
 CREST Syndrome: Calcinosis/Centromere Antibody, Raynaud’s  Na & K: major ECF & ICF cations respectively
Phenomenon, Esophageal Dsyfxn, Sclerodactyly, Telangiectasia  EOsm = 2 (serum Na) + serum glucose/18
 Dermatomyositis & Polymyositis  Osmosis: H2O moves between ECF & ICF—controlled by serum Na
o heliotrope eyes & Gottron Patches  Serum Na ≈TBNa/TBW
o ↑serum creatine kinase  ↓TBNa: signs of vol depletion
 Mixed Connective Tissue Dz: anti-ribonucleoprotein antibodies  ↑↑TBNa: pitting edema, body cavity effusion
 Starling Pressure Alterations: control water movement in ECF
Congenital Immunodeficiency Disorders compartment
 IgA Deficiency: most common congenital immunodeficiency  Isotonic Loss: ↓TBNa/↓TBW, loss whole blood, secretory diarrhea
 AIDS: most common acquired immunodeficiency dz worldwide  Isotonic Gain: ↑TBNa/↑TBW, excessive infusion isotonic saline
 Pediatric AIDS: most dt vertical transmission  Isotonic Loss or Gain: normal serum Na
 Risk per unit of blood = 1 per 2million units transfused  Hypotonic Disorders: hypoNa always present, ICF expansion
 HIV: cytoxic to CD4 T helpr cells—loss of cell mediated immunity  Gain in Fluid: ECF always expands
 Anti-gp120: detected in ELISA tes screen  Loss in Fluid: ECF always contracts
 Western Blot: confirms HIV  Hypertonic Loss: ↓↓TBNa/↓TBW, loop diuretics, Addison’s Dz, 21-
 Reservoir Cell for HIV: follicular dendritic cells in lymph nodes hydroxylase def
 Most Common Malignancy in AIDS: Kaposi Sarcoma  Central Pontine Myelinolysis: rapid correction of hypoNa w/ saline
 CMV: most common cause of blindness in AIDS  Hypotonic Gain of Water: TBNa/↑↑TBW
 Death in AIDS: disseminated infection  Pitting Edema States: right-sided heart failure, cirrhosis, nephrotic
 C3a & C5a: anaphylatoxins syndrome, ↓CO
 C3b: opsonization  Hypertonic Disorder: hyperNa or hyperglycemia, ICF contraction
 C5a: activate neutrophil adhesion molecules, chemotaxis  Hypotonic Loss Na + Water: ↓TBNa/↓↓TBW, osmotic diuresis,
 C5-C9: cell lysis, MAC sweating
 Hereditary Angioedema: deficiency C1 esterase inhibitor  Hypotonic Loss of Water: TBNa/↓↓TBW, diabetes insipidus, insensible
 Decay Accelerating Factor: deficient in PNH water loss
 Classical Pathway Activation: ↓C4 & C3, normal factor B  Hypertonic Gain: ↑↑TBNa/↑TBW, excess NaHCO3, infusion of Na
 Alternative Pathway Activation: ↓factor B, C3 & normal C4 containing antibiotic
 Diabetic Ketoacidosis: hypertonic state w/ dilutional hypoNa, osmotic
Amyloidosis diuresis
 Amyloid:  Proximal Tubule: reabsorb Na, reclaim HCO3, ↓EABV  ↑FF  Po>Ph
o apple green birefringence in polarized light  Ph>Po
o abnormal folding of protein  Carbonic Anhydrase Inhibitor: causes proximal renal tubular acidosis
 β-Amyloid: associated w/ Alzheimer’s in Down Syndrome  Heavy Metal Poisoning: produces Fanconi Syndrome
 Na/K/2Cl Symporter: generates free water
Water, Electrolyte, Acid-Base & Hemodynamic Disorders  CL Binding Site in Na/K/2Cl Symporter: inhibited by loop diuretics
 Loop Diuretic: hypoNa, hypoK, metabolic alkalosis
Water & Electrolyte Disorders  Thiazides:

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 o inhibit Cl site in Na/Cl symporter  Respiratory Alkalosis: PaCO2 <33mmHg
o HypoNa, hypoK, metabolic alkalosis, hyperCa  Tetany: commonly occurs in acute respiratory alkalosis
 HypoK: ↑ risk of metabolic alkalosis  Metabolic Acidosis: HCO3 <22 mEq/L
 Amiloride & Triamterene: diuretics w/ K sparing effects  ↑AG Metabolic Acidosis: anions of acid replace buffered HCO3
 Spironolactone: aldosterone inhibitor, K sparing  Lactic Acidosis: most common ↑AG metabolic acidosis, anaerobic
 Addison’s Disease: hypoNa, hyperK, metabolic acidosis glycolysis in shock
 1° Aldosteronism:  Normal AG Metabolic Acidosis: Cl anions replace HCO3
o hyperNa, hypoK, metabolic alkalosis  Loop & Thiazide Diuretics: most common causes of metabolic alkalosis
o low plasma renin type hypertension  Metabolic Alkalosis: HCO3 > 28 mEq/L
o absence of pitting edema  Clues for Mixed Disorder: normal pH, extreme pH Δ
 Bartter’s Syndrome: normotensive, hypoK, metabolic alkalosis,  Salicylate Intoxication: often mixture of 1° Metabolic Acidosis & 1°
↑aldosterone & PRA Respiratory alkalosis, nl pH
 +CH2O: indicates dilution, absence of ADH  pH defines what is the 1° disorder vs what is the compensation
 SIADH:  Edema: excess fluid in interstitial space
o small cell carcinoma of lung most common  Transudate: protein-poor & cell-poor fluid
o serum Na <120 mEq/L, dilution disorder  Pitting Edema:
o Tx: restrict water o transudate, ↑hydrostatic pressure &/or ↓oncotic pressure
 Serum Na usually <120 mEq/L—136-145 mEq/L o right-sided heart failure dt ↑hydrostatic pressure, cirrhosis dt ↓
 -CH2O: concentration, presence of ADH oncotic pressure
 oCH2O: chronic renal failure, no concentration or dilution  Exudate: protein rich & cell rich fluid
 CDI & NDI: hyperNa, polyuria, concentration disorder  Lymphedema: lymphatic obstruction after modified radical mastectomy
 CDI: desmopressin ↑UOsm (concentration) & radiation
 NDI: desmopressin no significant ↑UOsm  Myxedema: excess hyaluronic acid in interstitial tissue
 pH Δs: may cause shift of K into or out of ICF
 Insulin, β2-Agonist: may shift K into cell, hypoK Thrombosis
 Digitalis, β-Blocker, Succinylcholine: may shift K out of cells  Endothelial Cell Injury: arterial thrombi
 HyperK, Loop & Thiazide Diuretics: most common cause of hypoK  Stasis of Blood Flow: venous thrombi
 HypoK: EKG shows U wave  Most common site for venous thrombosis: deep vein in lower extremity
 Renal Failure: most common cause of hyperK BELOW knee
 PseudohyperK: RBC hemolysis from difficult venipuncture  Venous Thrombi Composition: entrapped RBCs, platelets, WBCs
 HyperK: EKG shows peaked T waves  Heparin & Warfarin: anticoags that prevent venous thrombosis
 Arterial Thrombus Composition: fibrin clot composed of platelets
Acid-Base Disorders  Aspirin: prevents formation of arterial thrombi
 Chronic Bronchitis dt Smoking: common cause of respiratory acidosis  Mixed Thrombus: prevented by aspirin along w/ anticoag therapy
 Respiratory Acidosis: PaCO2 >45mmHg
 Full Compensation: rarely occurs Embolism
 Formulas: help recognize single vs multiple acid-base disorders  Pulmonary Thromboemolism: majority originate in femoral veins
 Anxiety: most common cause of respiratory alkalosis

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  Pulmonary Infarction: uncommon dt dual blood supply—pulmonary o most involve enzyme deficiencies
arteries, bronchial arteries  PKU: ↑phenylalanine, ↓tyrosine
 Systemic Embolism: majority originate in Left side of heart  Von Gierke’s Dz: G-6-Pase Deficiency (gluconeogenic enzyme), fasting
 Fat Embolism: hypoglycemia, hepatorenomegaly
o long bone frx  Most Common AR Disorder: hemochromatosis
o dyspnea, petechial over chest/UE  AD Inheritance: heterozygotes w/ dominant mutant gene express dz
 Amniotic Fluid Embolism: abrupt onset dyspnea, hypotension, bleeding  Reduced Penetrance: individual w/ mutant gene does NOT express dz,
(DIC) transmits to children
 Decompression Sickness: N gas bubbles occlude vessel lumens  Most Common AD Disorder: von Willebrand Dz
 Pneumothorax, Pulmonary Embolism & Aseptic Necrosis: complications
of scuba diving X-Linked Recessive Disorders
 XR Inheritance: asymptomatic female carrier transmits mutant gene to
Shock 50% sons
 Hypovolemic Shock:  Most Common X-Linked Disorder: Fragile X Syndrome
o most often caused by blood loss  XD Inheritance: female carriers are symptomatic
o ↓CO2, ↓LVEDP, ↑PVR, ↓MVO2
 MVO2: best indicator of tissue hypoxia Chromosomal Disorders
 Cardiogenic Shock:  Barr Body:
o most often caused by acute MI o inactivated X chromosome
o ↓CO2, ↑LVEDP, ↑PVR, ↓MVO2 o # of Barr Bodies = #X chromosomes - 1
 Septic Shock:  Nondisjunctional: unequal separation of chromosomes in meiosis
o most often caused by sepsis dt E. coli  Mosaicism: nondisjunction in mitosis
o initial phase: ↑CO2, ↓LVEDP, ↓PVR, ↑MVO2  Cri du Chat Syndrome: deletion short arm chromosome 5
 Multiorgan Dysfxn: most common cause of death in shock  Down Syndrome:
o most cases dt nondisjunction
Genetic & Developmental Disorders o most common cause of mental retardation
o duodenal atresia, Hirschsprungs
Mutations o Alzheimers dz at young age
 Missense Mutation: Sickle Cell Dz/Trait  Advanced Maternal Age: ↑ risk for bearing offspring w/ trisomy
 β-Thalassemia Major: nonsense mutation w/ stop codon syndromes
 Frameshift Mutation: Tay-Sachs Dz  Edward Syndrome: trisomy 18
 Anticipation: additional trinucleotide repeats ↑ dz severity in future  Patau Syndrome: trisomy 13
generations  Turners Syndrome:
o 45 X
Mendelian Disorders o Menopause before menarche
 Most common type of medialian disorder—autosomal recessive o Most common cause of 1° amenorrhea
 AR Inheritance:  Webbed Neck: Cystic Hygroma
o both parents must have mutant gene  Klinefelters Syndrome: ↓ testosterone & inhibin, ↑LH & FSH
 XYY Syndrome: paternal nondysjxn, aggressive behavior
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 o Maternal factors most often responsible in SGA infants
Other Patterns of Inheritance o Often have oligohydramnios
 Polygenic Disorders: more common than mendelian & chromosomal
disoders Genetic & Developmental Disorder Dx
 Mitochondrial DNA: associated w/ maternal inheritance, ova have  Open Neural Tube Defects: Folate deficiency prior to conception, ↑AFP
mutant gene  Triple Marker for Down Syndrome: ↓AFP, ↑hCG, ↓urine estriol
 Genomic Imprinting: inheritance depends on whether mutant gene is on
maternal or paternal origin Aging
 Prad-Willi Syndrome: microdeletion on paternal chromosome 15  Age-Dependent: inevitable w/ age—↓GFR & prostate hyperplasia
 Angelman Syndrome: microdeletion on maternal chromosome 15  Age-Related: common but NOT inevitable w/ age—Alzheimers Dz,
systolic htn
Sex Differentiation Disorders
 Y Chromosome: determine genetic sex of individual Environmental Pathology
 Testicular Feminization:
o most common cause of male pseudohermaphroditism Chemical Injury
o vagina ends as blind pouch  Smoking: most important preventable cause of dz & death in US
 Cotinine: metabolite of nicotine, used for screening
Congenital Anomalies  Nicotine Patch: effective in txing ulcerative colitis
 Malformation:  Alcohol Metabolism: ↑NADH is key to lab abnormalities
o disturbance in morphogenesis in embryonic period  Women: less gastric alcohol dehydrogenase than men
o open neural tube defect, cleft lip/palate
 Alcohol Abuse: most common cause of thiamine deficiency
 Deformation:
 ↑Anion Gap Metabolic Acidosis in Alcohol Abuse: lactic acid & β-
o Extrinsic disturbances in fetal development
hydroxybutyric Acid
o Oligohydramnios causing Potter’s Facies, clubfeet
 Alcohol Liver Dz: Aspartate aminotransferase > Alanine
 Congenital Abnormalities: genetic + environmental factors
aminotransferase, ↑ γ-glutamyltransferase
 Maternal Diabetes: macrosomia—hyperinsulinemia ↑ muscle mass & fat
 Hepatitis B: most common systemic complication of IVDU
 Alcohol: most common teratogen—fetal alcohol syndrome
 Salicylate Poisoning: danger of hyperthermia
 CMV: most common pathogen causing congenital infection
 Both acetaminophen & aspirin cause fulminant hepatitis
 TORCH Syndrome: Toxoplasmosis, Other Agents, Rubella, CMV, HSV
 Unopposed Estrogen: thrombogenic, carcinogenic, cholestasis
 Retinoic Acid in Pregnancy: disrupts HOX gene fxn, craniofacial, CNS &
 Oral Contraceptives:
cardiovascular defects
o ↓risk for endometrial & ovarian cancer—only surface type
o Most common cause of htn in young women—↑
Selected Perinatal & Infant Disorders
angiotensinogen
 Stillbirth: most often caused by abruption placentae
 Spontaneous Abortion: frequently caused by trisomy 16 Physical Injury
 SIDS: majority of deaths occur before age 6mo  Bee/Wasp/Hornet Sting: most common cause of death dt venomous bite
 Large for Gestational Age (LGA): most often dt maternal diabetes  Contact Gunshot Wound: fouling
 Prematurity: most common cause of neonatal death/morbidity  Intermediate Range Wound: powder tattooing
 Intrauterine Growth Retardation (IUGR):
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  Motor Vehicle Collisions: most common cause of accidental death in o Pancreas  bile salts/acid  intestinal cells
people ages 1-39
 Shaken Baby Syndrome: retinal hemorrhages Protein-Energy Malnutrition
 1st & 2nd Degree Burns: no permanent scarring  Kwashiorkor:
 Most common cause of death in burn pts—sepsis caused by o inadequate protein intake
pseudomonas o pitting edema
 Heat Exhaustion: <40°C, no anhidrosis/no mental status Δs o fatty liver—↓apoB synthesis & ↑VLDL synthesis
 Heat Stroke: >40°C, anhidrosis, impaired conscioiusness  Marasmus:
 AC electricity more dangerous than DC o total calorie deprivation
 Most Common Drowning: Wet drowning o extreme muscle wasting
 High Altitude:
o O2 [ ] 21%, ↓atmospheric pressure Eating Disorders
o Respiratory alkalosis, right shifted O2 Binding Curve  Anorexia:
 Ionizing Radiation: damage to DNA o Distorted body image
 Lymphoid Tissue: most sensitive to radiation o 2° amenorrhea, osteoporosis
 Bone: least sensitive tissue to radation o Most common cause of death—ventricular arrhythmia
 Total Body Radiation: lymphopenia 1st hematologic sign  Vomiting in Bulimia Nervosa: produces hypoK metabolic alkalosis
 Ultraviolet Light B: ↑pyrimidine dimers distorts DNA helix  BMI: weight in kg/height in m2
 Basal Cell Carcinoma: most common UVB light-related skin cancer  Obesity:
o abdominal visceral fat most important
o ↑adipose causes ↓synthesis insulin receptors
Nutritional Disorders  Leptin: hormone, maintains energy balance—intake & output
 3500 Calories = 1lb
Nutritional & Energy Requirements in Humans  Leptin Gene: often defective in obesity
 BMR:
o most important factor in determining daily energy expenditure Fat Soluble Vitamins
o ↓hypothyroidism & ↑hyperthyroidism
 β-carotenemia: yellow skin, white sclera
 Vitamin A: vision, cell differentiation, growth/reproduction
Dietary Fuels
 Night Blindness: 1st sign of vitamin A deficiency
 Carbohydrate Digestion: begins in mouth, 4kcal/g
 Vitamin A in tx: acne, acute promyelocytic leukemia
 Disaccharides:
 Vitamin A Toxicity: consumption of bear liver
o lactase, maltase, sucrose
 Sunlight: major source of Vitamin D
o produce glucose, galactose, fructose
 Vitamin D
 Amino Acids: substrates for gluconeogenesis
o Liver & kidney hydroxylation
 Protein Digestion: begins in stomach, pepsin & acid
o Bone mineralization, maintain serum Ca & P
 Essential Fatty Acids: linolenic, linoleic acids
 Renal Failure: most common cause of Vitamin D deficiency
 Fat Digestion
 Vitamin E:
o Begins in small intestine
o Cell membrane antioxidant
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 o Toxicity: ↓synthesis vitamin K-dependent coagulation factors  Copper Excess: Wilson’s Dz
 Vitamin K  Iodide Deficiency: multinodular goiter
o Majority synthesized by colonic bacteria  Chromium: useful in diabetics
o Γ-carboxylates, II, VII, IX, X  Selenium: antioxidant
 Broad Spectrum Antibiotics: most common cause of vitamin K deficiency  Fluoride:
in hospital o component of Ca hydroxyapatite
 Newborns: require vitamin K injection o Deficiency: dental caries
 Rat Poison contains coumarin derivatives
Dietary Fiber
Water-Soluble Vitamins  Fiber Types: insoluble, soluble
 Thiamine:  Soluble: lowers cholesterol
o present in outer shell & seed of grains  Fiber: ↓ risk for sigmoid diverticulosis, certain cancers & heart dz
o important in ATP synthesis  Na Restriction: htn, heart failure, chronic liver/kidney dz
 Chronic Alcoholism: most common cause of thiamine def in US  Protein-Restricted Diet: chronic renal failure, cirrhosis
 Riboflavin: FAD & FMN in citric acid cycle
 Niacin: NAD & NADP cofactors Neoplasia
 Corn Based Diets: deficient in tryptophan & niacin
 Tryptophan: Nomenclature
o used to synthesize niacin  Benign Tumors: epithelial or CT origin
o deficiency—Hartnup Dz& Carcinoid Syndrome
 Epithelial Tissue Origin: ectoderm or endoderm
 3 Ds of Pellagra: dermatitis, diarrhea, dementia
 CT Origin: mesoderm
 Pyridoxine: heme synthesis, transamination, neurotransmitters
 Teratoma: derives from ectoderm, endoderm, & mesoderm
 Isoniazid Therapy: most common cause of pyridoxine def
 Carcinomas: derive from squamous, glandular (adenocarcinoma),
 Vitamin B12: transitional epithelium
o Only in animal products
 Sarcomas: derive from CT
o DNA synthesis, odd-chain fatty acid synthesis
 Hamartoma: non-neoplastic overgrowth of tissue
 Pernicious Anemia: most common cause of vitamin B12 def
 Choristoma: normal tissue where it should not be
 Folic Acid: DNA synthesis
 Goat Milk: lacks folate & pyridoxine
 Alcohol Excess: most common cause of folate def Properties of Benign & Malignant Tumors
 Biotin Deficiency: eating raw eggs  Parenchyma: neoplastic component
 Ascorbic Acid:  Grade of Cancer: does the cancer resemble its parent tissue or not
o collagen synthesis, antioxidant, reducing agent  Malignant Tumors:
o cofactor conversion dopamine to norepinephrine o ↑nuclear/cytoplasmic ratio, abnormal mitotic spindles
o Scurvy—def of ascorbic acid o 30 doubly times before detected
 Benign & Malignant Tumors: monoclonal
 Malignant Tumors: upregulation telomerase activity
Trace Elements
 Basal Cell Carcinomas of Skin: invade tissue but do NOT metastasize
 Zinc Deficiency: poor wound healing, dysgeusia, perioral rash
8
  Invasion: 2nd most important criterion for malignancy  Rx GERD: ↓ risk for distal adenocarcinoma of esophagus
 Resist Invasion: cartilage, elastic tissue
 Loss of intercellular Adherence  Cell invasion Carcinogenesis
 Point Mutations: most common type of mutation in cancer
Metastasis  Proto-oncogenes: involved in normal growth & repair
 Extranodal Metastasis: has greater prognostic significance than nodal  Suppressor Genes: protect against unregulated cell growth
metastasis  BCL2 Gene Family: antiapoptosis genes
 Lymph Nodes:  BAX Gene: apoptosis gene
o 1st line of defense in carcinomas  Repair Genes: correct errors in nucleotide pairing, excise pyrimidine
o Most common tissue metastized to dimers
 Route of Metastasis: lymphatic, hematogenous, seeding of body cavities  Enzymes Involved in Dimer Excision: endonuclease, exonuclease,
 Seeding: common w/ surface-derived ovarian cancers polymerase, ligase
 Bone Metastasis: vertebra most common site, paravertebral venous
plexus Carcinogenic Agents
 Osteoblastic Metastasis: ↑serum alkaline phosphatase  Chemical Carcinogenesis: initiation  promotion  progression
 Osteolytic Metastasis: potential for hyperCa, pathologic frx  Pathogens & Cancer: viruses > bacteria > parasites
 Bone Metastasis: osteoblastic (radiodense) or ostelytic (radiolucent)  Leukemia: most common cancer dt ionizing radiation
 Basal Cell Carcinoma: most common cancer dt excessive UV light
Cancer Epidemiology exposure
 Cancer is 2nd most common cause of death in US
 Lifetime risk of cancer: MEN > women Clinical Oncology
 Blacks: greater overall risk for cancer  Cytotoxic CD8 T Cells: most effective host defense against cancer
 Most common cancer in children: Acute Lymphoblastic Leukemia  ↓ Prognosis: Extranodal Metastasis > Lymph Nodes > Tumor Size
 Cancer in Men: prostate, lung & colorectal  Anemia of Chronic Dz: most common anemia in cancer
 Cancer in Women: breast, lung & colorectal  Hemostasis in Malignancy: thrombogenic
 Gynecologic Cancer: endometrium, ovary, cervical  Gram – Sepsis: most common cause of death in cancer
 Most common cause of cancer death in adults: lung cancer  HyperCa: most common paraneoplastic syndrome
 Malignant Melanoma: most rapidly ↑ing cancer  Acanthosis Nigricans: may be associated w/ stomach cancer
 Actinic (solar) Keratosis: precursor of squamous cell carcinoma  Signs of Ectopic Hormone Production: hyperCa, hypoNa, hypoglycemia,
 Cessation of is most important factor in ↓ing risk for cancer hypercortioslism, polycythemia
 HBV Immunization: ↓risk for hepatocellular carcinoma  Hormone Tumor Marker: calcitonin—medullary carcinoma of thyroid
 HPV Immunization: ↓risk for cervical cancer
 Cervical Cancer: least common gynecologic cancer in US
 Cervical Pap Smear: most responsible for ↓ incidence/mortality rate for
cervical cancer
 PSA: more sensitive than specific Vascular Disorders
 Rx H. pylori Infection: ↓ risk for developing gastric
lymphoma/adenocarcinoma Lipoprotein Disorders

9
 Chylomicron:  Oral Contraceptives
o diet-derived triglycerides o Estrogen ↑TG synthesis in liver
o absent during fasting o Variable effects on LDL & HDL
o turbid supranate  Type V
 Capillary Lipoprotein Lipases—CPL o ↑VLDL + Chylomicrons
o Located in adipose, muscle, & myocardium o Hyperchylomicronemia syndrome
o Induced by insulin  ApoB Deficiency: ↓chylomicrons, VLDL & LDL
o Activated by apoCII
o VLDL  IDL  LDL Arteriosclerosis
 VLDL:  Medial Calcification: dystrophic calcification in muscular arteries
o liver-derived triglyceride  Atherosclerosis: endothelial cell injury, platelets/macrophages pivotal
o TG/5 rules
 Hypertriglyceridemia: causes turbidity in plasma  Fibrous Cap: pathognomonic lesion of atherosclerosis
 LDL  C-Reactive Protein: excellent marker of disrupted fibrous plaques
o Transports cholesterol  Abdominal Aorta: most common site for atherosclerosis, no vasa
o (CH –HDL-TG)/5 vasorum
 Serum CH: fasting NOT required  Complications of Atherosclerosis: aneurysms, thrombosis, ischemia
 HDL  Hyaline Arteriosclerosis: diabetes mellitus & htn
o good CH
o source of apolipoproteins CII & E Vessel Aneurysms
o removes cholesterol from plaques for disposal in liver  Abdominal Aortic Aneurysm: most common aneurysm in men >55yo
 ↑VLDL causes ↓HDL  Rupture Triad: left flank pain, hypotension, pulsatile mass
 Type I: ↓CPL or ↓apo CII  Fungal Vessel Invaders: B. fragilis, P. aeruginsos, Salmonella
 Type II:  CNS Berry Aneurysms: jxn communicating branch w/ main vessel
o ↑LDL dt ↓LDL receptors  Aortic Arch Aneurysms: tertiary symphilis, vasa vasorum vasculitis
o ↑CH synthesis  Syphilitic Aneurysms: produces aortic regurgitation, bounding pulses
o ↓CH excretion in bile  Aortic Dissection
 Achilles Tendon Xanthoma: pathognomonic for familial o cystic medial degeneration
hypercholesterolemia o pain radiates into back
 Type III: o absent pulses
o deficiency in apoE o most common cause of death in Marfans & EDS pts
o ↑cylo remnants & IDL o cardiac tamponade—most common cause of death
o Palmar santhomas
 Type IV: Venous System Disorders
o ↑VLDL  Superficial Varicosities: valve incompetence
o most common lipid disorder  Phlebothrombosis: stasis of blood flow most common cause
o Alcohol Excess—most common cause  Stasis Dermatitis: sign of DVT
o Eruptive xanthomas  Thrombophlebitis: pain & tenderness overlying vein
o Rx: ↓carb & alcohol intake  SVC Syndrome: compression of SVC by primary lung tumor
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  Thoracic Outlet Syndrome: common among weight lifters, tight scalene  Afterload: resistance ventricle contracts against to eject blood in systole
muscles  Preload: equivalent to LVEDV &/or RVEDV
 Acute Lymphagitis: S. pyogenes cellulitis  Ventricular Hypertrophy
 Turner’s Webbed Neck: lympathic abnormality o ↑afterload causes CONCENTRIC hypertrophy
o ↑preload causes ECCENTRIC hypertrophy
Vascular Tumors & Tumor-like Conditions  Consequences of Hypertrophy: Heart Failure, S4, Angina (LVH)
 Bacillary Angiomatosis: Bartonella henselae, common in AIDS  S4: blood entering noncompliant ventricle

Vasculitic Disorders Congestive Heart Failure

 ANCA: antibodies against components of neutrophils  Left-Sided Heart Failure = forward failure  pulmonary edema
 Small Vessel Vasculitis: palpable purpura  Systolic Dysfxn
 Medium-Sized Vessel Vasculitis: thrombosis, aneurysm formation o most common type of LHF
 Large Vessel Vasculitis: absent pulse, stroke o ↓ventricular contraction, ↓EF
 Diastolic Dysfxn
Hypertension o most common cause of HTN
 Systolic Blood Pressure o ↑resistance to filling ventricle, normal EF
o Correlates w/ SV, aorta compliance  Dyspnea: cannot take full inspiration
o ↑SBP: ↑preload & contractility  Pulmonary Edema: hydrostatic pressure > oncotic pressure
o ↓SBP: ↓preload & contractility, ↑afterload  Kerley’s Lines: septal edema
 Diastolic Blood Pressure  Heart Failure Cells: alveolar macrophages w/ hemosiderin
o Correlates w/ tonicity of TPR arterioles  S3 Heart Sound: 1st cardiac sign of LHF
o ↑DBP: vasoconstriction peripheral resistance arterioles  Paroxysmal Nocturnal Dyspnea/Orthopena: ↑ venous return to right
o ↓DBP: vasodilation peripheral resistance arterioles side of heart at night
 Pathogenesis HTN: renal retention of Na commonly involved  Brain Natriuretic Peptide: useful in confirming/excluding LHF
 Most common type of HTN—essential htn  Right-Sided Heart Failure = backward failure  ↑in venous hydrostatic
 Renovascular HTN pressure
o most common cause of 2° htn  LHF: most common cause of RHF
o atherosclerosis in men  RHF
o fibromuscular hyperplasia in women o ↑venous hydrostatic pressure
 Plasma Renin Activity: ↑ in involved kidney & ↓ in unaffected kidney o Neck vein distention, hepatomegaly, dependent pitting edema,
 Fibromuscular Hyperplasia: beaded appearance of renal artery ascites
 Complications of HTN: acute MI, stroke & renal failure  ACE-I: ↓afterload, ↓preload
 β-Blockers: ↓myocardial O2 consumption, ↓HR
 TPR = Viscosity/Radius of Vessel
Heart Disorders  Causes of high output failure: ↑SV, ↓TPR, arteriovenous fistula

Ventricular Hypertrophy Ischemic Heart Disease

 Tachycardia: ↓diastole & filling of coronary arteries
 Wall stress ↑ gene controlled sarcomere duplication

11
 LAD: most common site of coronary artery thrombosis  Fibrinous Pericarditis: early—acute inflammation & late complications—
 Angina Pectoris autoimmune
o most common manifestation of coronary artery dz  Ventricular Aneurysms: CHF most common cause of death
o age most important risk factor  RV AMI: hypotension, RHF, preserved LV fxn
o MALES > females  Reinfarction: reappearance of CK-MB after 3 days
 Stable Angina  cTnl, cTnT: cannot dx reinfarction
o Most common type of angina  EKG Findings in AMI: inverted T waves, elevated ST segment, Q waves
o Exercise-induced substernal chest pain
o Subendocardial ischemia w/ ST-segment depression Congenital Heart Disease
 Prinzmetal’s Angina  Chorionic Villus: primary site for O2 exchange
o vasospasm w/ transmural ischemia  Umbilical Vein: highest PO2 in fetal circulation
o ST-segment elevation  Fetal Circulation: foramen ovale & ductus arteriosus are patent
o Ca Channel Blockers vasodilate coronary arteries  Single Umbilical Artery: ↑risk congenital abnormalities
 Unstable Angina: angina at rest,multivessel dz, disrupted plaques  Ductus Arteriosus: become ligamentum arteriosum
 Chronic Ischemic Heart Dz: replacement of muscle by fibrous tissue  Newborn: foramen ovale & ductus arteriosus are CLOSED
 Sudden Cardiac Death  Congenital Heart Dz: ↑risk w/ ↑maternal age
o unexpected death w/in 1 hr after symptoms  CHD Shunts: L-R & R-L—often cyanoic
o coronary artery thrombosis NOT usually present  L-R Shunts: danger of shunt reversal if uncorrected
 Mitral Valve Prolapse Sudden Death: arrhythmias from mitral  Ventricular Septal Defect
regurgitation or CHF o most common CHD in children
 Acute Myocardial Infarction o defect in membranous septum
o most common cause of death in US  Atrial Septal Defect
o Q wave type transmural o Most common CHD in adults
o Non-Q wave type subendocardial o Patent foramen ovale
o Coagulation Necrosis w/in 24hrs o Fixed splitting of S2
o Heart softest 3-7—danger of rupture  Patent Ductus Arteriosus
o Retrosternal pain, radiation to left arm/shoulder, diaphoresis o Closed w/ indomethacin
 Rupture of disrupted plaque  platelet thrombus  AMI o Machinery murmur
 Cocaine: AMI w/ normal coronary arteries  Tetralogy of Fallot
 Reperfusion: ↑short/long-term survival o Most common cyanotic CHD
 Contraction Band Necrosis: reperfusion, hypercontraction myofibrils dt o Degree of Pulmonary Valve stenosis correlates w/ presence or
Ca absence of cyanosis
 Q Wave AMI: ↑early mortality rate  Cardioprotective Shunts: ASD & PDA
 Non-Q Wave AMI: ↑risk for sudden cardiac death  Tet Spells: squatting, ↑systemic vascular resistance, ↑PaO2
 Ventricular Fibrillation: most common cause of death in acute MI  Transposition: aorta empties RV, pulmonary artery empties LV, atria
 Myocardial Rupture: most common at 3-7 days normal
 Posteromedial Papillary Muscle Rupture: RCA thrombosis, mitral  Infantile Coarctation: associated w/ Turners Syndrome
regurgitation
 Mural Thrombus: danger of embolization
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  Adult Coarctation: disparity between upper/lower extremity blood o No ↑intensity w/ deep held inspiration
pressure > 10mmHg  Calcific AV Stenosis: most common cause in pts >60yo
 Hypertension: dt activation of Renin-Angio-Aldosterone system  AV Stenosis
 Coarctation Collaterals: Anterior Intercostal Arteries – Posterior o Ejection murmur
Intercostal Arteries to aorta, Superior Epigastric Artery-Internal Thoracic o S4
Artery to external iliac artery o ↓intensity w/ ↓preload
o ↑intensity w/ ↑preload
Acquired Valvular Heart Disease o Most common valvular lesion causing syncope & angina w/
 Acute Rheumatic Fever exercise
o After group A strep pharyngitis o Microangiopathic hemoly anemia w/ schistocytes
o Immune-mediated type II hypersensitivity rxn o Hemoglobinuria
o Cell-mediated immunity Type IV  Isolated AV Root Dilation: most common cause of aortic regurgitation
o Migratory polyarthritis most common initial presentation  AV Regurgitation
o Myocarditis most common cause of death o ↑pulse pressure
o Mitral Valve most often involved followed by Aortic Valve o Early diastolic murmur
o Dx w/ Jones Criteria o Bounding pulses
o Carditis, Arthritis, Chorea, Erythema Marginatum, SubQ Nodules o S3 & S4
o ↑ASO & DNase B titers o No ↑intensity w/ inspiration
 Rheumatic Fever o Hyperdynamic circulation
o Mitral regurgitation in acute attack  Austin Flint Murmur: sign for AV replacement
o Mitral stenosis in chronic disease  Tricuspid Valve Regurgitation
 Mitral Valve Stenosis o functional most common cause adults
o most common cause is recurrent Rheumatic Fever o infective endocarditis
o pulmonary venous htn o carcinoid heart disease
o RHF o pansystolic murmur
o Opening snap followed by an early to mid-diastolic rumble o S3/S4
 Atrial Fib: common cause of mitral stenosis o ↑intensity w/ deep held inspiration
 Mitral Valve Prolapse  Pulmonary Valve Regurgitation: pulmonary htn
o most common cause of mitral regurgitation  Carcinoid Heart Disease: PV stenosis or TV Regurgitation
o association /w Marfans’ & Ehlers-Danlos syndromes  Strep viridans: most common cause of infective endocarditis
o myxomatous degeneration  Staph aureus: most common pathogen producing infective endocarditis
o excess dermatan sulfate in IV drug use
o Systolic click followed by murmur  Strep bovis: most common pathogen producing infective endocarditis in
o Preload alters click & murmur relationship to S1/S2 ulcerative colitis/colorectal cancer
 Symptomatic Mitral Valve Prolapse: β-Blockers  TV regurgitation in IV drug abusers is dt infective endocarditis

 Mitral Valve Regurgitation  Infective Endocarditis

o pansystolic murmur o fever most consistent sign
o S3/S4 o microembolization
13
 o immuncomplex vasculitis o ↓ventricular compliance
o + blood culture majority of cases
 Libman-Sacks Endocarditis: associated w/ SLE, Mitral Valve involved Heart Tumors
 Marantic Endocarditis: sterile vegetations, paraneoplastic syndrome  Heart Tumors: metastasis > primary tumors
 Cardiac Myxoma
Myocardial & Pericardial Diseases o most common in LEFT atrium
 Coxsackievirus: most common cause of myocarditis & pericariditis o myxomas occur in adults
 Chaga’s Disease: most common cause of myocarditis leading to CHF in  Rhabdomyomas: occurs in children
Central/South America
 Drugs: Doxorubicin & Daunorubicin Red Blood Cell Disorders
 Myocarditis: ↑CK-Mb, troponins I & T
 Pericarditis Erythropoiesis
o coxsackievirus most common cause  EPO
o precordial rub o synthesized by interstitial cells in peritubular capillary bed
o pain relieved by leaning forward o stimuli for EPO—hypoxemia, left-shifted OBC, high altitude
 Young woman w/ peridcarditis & effusion—most likely has SLE  Reticulocyte Count
 Pericardial Effusion on Inspiration: JVD, ↓systolic blood pressure > o measure of effective erythropoiesis
10mmHg o Correction: Hct/45 x Reticulocyte Count
 Constrictive Pericarditis o Corrected Reticulocyte Count: <3% ineffective erythropoiesis &
o incomplete filling of chambers >3% effective erythropoiesis
o pericardial knock o Polychromasia: divide original reticulocyte correction by 2
 Extramedullary Hematopoiesis
Cardiomypoathy o most often occurs in LIVER & SPLEEN
 Cardiomyopathy: dilated, hypertrophic, restrictive o heaptosplenomegaly
 Dilated Cardiomyopathy  Anemia Prematurity: loss of iron from mother & blood loss from
o Most common cardiomyopathy venipuncture
o Myocarditis most common cause  Fetal Hb: left-shifts OBC causing an ↑ in Hb
o Doxorubicin & daunorubicin  Children: more right-shifted OBCs than adults
o Global enlargement of heart  Anemia in Children: <11.5 g/dL
 Hypertrophic Cardiomyopathy  Anemia in Adults: <13.5 g/dL
o Most common cause of sudden death in young individuals  Anemia in Nonpregnant: <12.5 g/dL
o Obstructive BELOW aortic valve  Pregnancy: 2x greater ↑ in plasma vol than RBC mass
o Preload changes on murmur intensity opposite of those for AV  Thalassemia: ↓Hb & Hct, ↑RBC count, MCV/RBC <13
stenosis
 Anemia:
o Sudden cardiac death dt V Tachy/Fib
o O2 sat & arterial PO2 normal
o Tx w/ β-Blockers
o Sign of disease
 Restrictive Cardiomyopathy o Not a specific dx
o Least common cardiomyopathy o ↓O2 content
o Low-voltage EKG
 MCV: classification of anemia
14
  MCHC: ↓in microcytic anemia & ↑ in spherocytosis o most common anemia in hospitalized pts
 RDW: measure of size variation of RBCs o most common anemia in malignancy
 Fe Deficiency: ↑RDW o alcohol excess
 Mature RBC: anaerobic glycolysis, lactic acid end-point o ↓Fe, TIBC, % saturation, ↑Ferritin
 Cori Cycle: lactic acid converted to glucose in liver  glucose to RBC  Hepcidin: antimicrobial peptide synthesized/released by liver
 GSH: neutralizes peroxide & other free radicals  Blacks: can have α or β-thalassemia
 MetHb Reductase: reduces Fe3+ to Fe2+  α-Thalassemia: dt gene deletions
 2,3BPG: product of glycolytic cycle  α-Thalassemia Trait
 Unconjugated Bilirubin: end-porduct of heme degradation in o 2 gene deletions
macrophages o ↓HbA, HbA2, HbF—normal electrophoresis
 Ferritin: synthesized in bone marrow macrophages o ↑RBC count
 Serum Ferritin: ↓Fe Deficiency, ↑Anemia of Chronic Dz, Fe Overload Dz  HbH: 4 β chains
 Serum Fe: ↓Fe Deficiency, Anemia of Chronic Dz, ↑Fe Overload Dz  Hb Bart: 4γ chains
 Total Fe Binding Capacity (TIBC)  β-Thalassemia
o ↓TIBC = ↓Transferrin o mild—DNA splicing defect
o ↑TIBC = ↑Transferrin o severe—stop codon
 ↓Ferritin Stores: ↑TIBC, Fe Deficiency,  β-Thalassemia Minor
 ↓Ferritin Stores: ↓TIBC, ACD, Fe Overload o β/β+
 ↓Fe Saturation: Fe deficiency, ACD, ↑Fe saturation, Fe Overload Dz o ↓HbA, ↑RBC count, HbA2, HbF
 HbA: 2α/2β or 2α/2δ  β-Thalassemia Major
 HbF: 2α/2γ o β0/β0
o no HbA, ↑HbA, HbF
Microcytic Anemia  Sideroblastic Anemia
 Microcytic Anemia: defects in Hb synthesis—Heme + Globin Chains o defect in heme synthesis in mitochondria
o ringed sideroblasts
 Types of Fe: Reduced—Fe2+ heme Fe in meat & Oxidized—Fe3+
o alcohol most common cause
nonheme Fe in plants
o ↑serum Fe, Fe saturation, Ferritin
 Oxidized Fe3+: must be reduced to Fe2+ for reabsorption in duodenum
o ↓MCV & TIBC
 Fe: majority stored in marrow macrophages
 Pyridoxine Deficiency: Isoniazid Therapy most common cause
 Ascorbic Acid: reduces nonheme Fe3+ into Fe2+
 Pb Poisoning
 Fe Deficiency
o paint, batteries
o most commonly caused by BLEEDING
o denatures ferrochelatase, ALA dehydrase, ribonuclease
o ↓Fe, % saturation, ferritin
o coarse basophilic stippling
o ↑TIBC & RDW
o Pb deposits in epiphyses
o Stages: all lab studies abnormal before anemia is present
o Rx: chelation therapy
 Koilonychia: spoon nails, sign of Fe deficiency
Macrocytic Anemia
 Thrombocytosis: common finding in chronic Fe deficiency
 Vitamin B12
 Rx Fe Deficiency: ferrous sulfate o only present in animal products
 Anemia of Chronic Dz o reabsorbed in terminal ileum
15
 o odd chain fatty acid metabolism  Anemia Malignancy: ACD, blood loss, metastasis to marrow,
 Parietal Cells: synthesize intrinsic factor (IF) & HCl immunologic
 Vitamin B12 Deficiency
o pernicious anemia most common cause Normocytic Anemia—Corrected Reticulocyte Count or Index: <3%
o posterior columns, lateral corticospinal tract, dorsal  Types of Hemolytic Anemia: intrinsic—RBC defect or Extrinsic—factors
spinocerebellar tract outside RBC
o causes macrocytic anemia neurologic dz  Extravascular Hemolysis: macrophage phagocytosis, unconjugated
 Intestinal Conjugase: inhibited by phenytoin hyperbilirubinemia
 Monoglutamate Reabsorption: inhibited by alcohol & oral contaceptives  Intravascular Hemolysis: ↓serum haptoglobin, hemoglobinuria
 Folate Deficiency: alcohol most common cause  Hereditary Spherocytosis
 Vit B12/Folate Deficiency o intrinsic defect
o delayed nuclear maturation o extravascular hemolysis
o megaloblasts o black, Ca bilirubinate gallstones
o pancytopenia, apoptosis, macrophage phagocytosis o ↑ RBC osmotic fragility
 ↑Homocysteine: folate (most common) & vitamin B12 deficiency  Aplastic Crisis: parvovirus induced
 Thymidylate Synthase: irreversibly inhibited by 5-Fluorouracil  Hereditary Epliptocytosis: >25% elliptocytes in peripheral blood
 Dihydrofolate Reductase: inhibited by methortrexate (reversible) &  Paroxysmal Nocturnal Hemoblgobinuria
Trimethoprim o loss of anchor for decay accelerating factor (DAF)
 Pernicious Anemia: o intrinsic defect
o ↑incidence gastric cancer o intravascular hemolysis
o Type II hypersensitivity o pancytopenia
o ↑antibiodies & gastrin levels o screen—sucrose hemolysis tests
 ↑Methlymalonic Acid: most sensitive test for Vit B12 deficiency o confirm—acidified serum test
 Hypersegmented Neutrophil: marker for folate or B12 def  Trait x Trait: 25% normal, 50% trait, 25% disease
 Schilling Test: defines the cause of B12 def  Sickle Cell Anemia
 ↓Maternal Folate Intake: ↑risk for open neural tube defect o Intrinsic defect
 RBC Folate: best indicator of folate stores o Extravascular hemolysis
 Alcohol Liver Dz: round macrocytic target cells o Missense mutation
o Substitution of VALINE for GLUTAMIC acid
Normocytic Anemia—Corrected Reticulocyte Count or Index: <3% o Sickling: ↑HbS & ↑deoxyHb
 Acute Blood Loss: external or internal o Severe hemolytic anemia
 Signs of Vol Depletion: ↓BP & ↑pulse o Vasoocclusive crises
 Aplastic Anemia  Irreversible Sickle Cell: ↑ adherence to endothelial cells
o most cases idiopathic  Dactylitis: most common presentation in infants w/ sickle cell
o drugs most common known cause  Acute Chest Syndrome: most common cause of death in adults w/ sickle
o fever, bleeding, fatigue cell
o pancytopenia  Howell-Jolly Bodies: sign of splenic dysfxn in sickle cell
 Anemia Chronic Renal Failure: ↓EP most common cause  Pathogens associated w/ Sickle Cell: Streptococcus pneumonia sepsis,
 Chronic Renal Failure: platelet dysfxn Salmonella paratyphi osteomyelitis
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 Sequestration vs Aplastic Crisis: reticulocytosis for sequestration & o Extrinsic, intravascular hemolysis
reticulocytopenia for aplastic crisis o P. vivax—most common type w/ fever every 48hr
 Sickle Cell Trait: no anemia, microhematuria o P. falciparum—most lethal type w/ fever quotidian
 HbAS: HbA 55-60%, HbS 40-45% o P. malaria—fever every 72hr
 HbSS: HbS 90-95%, HbF 5-10% & no HbA o Chloroquine prevention
 Target Cells: excess RBC membrane, sign of hemoglobinopathy or alcohol o Rx P. vivax/ovale—chloroquine + primaquine
excess o Rx P. falciparum: chloroquine sensitive—chloroquine alone,
 G6PD Deficiency resistant—quinine sulfate + doxycycline
o most common enzyme deficiency causing hemolysis
o intrinsic defect White Blood Cell Disorders
o primarily intravascular hemolysis
o oxidant damage with Heinz Bodies & Bite Cells Benign Qualitative WBC Disorders
o O2-dependent MPO system dysfxn  Qualitative WBC Defects
o Lack of NADPH cofactor o Defects in structure & fxn
o Active hemolysis screen w/ Heinz Body Prep o Unusual pathogens, “cold” abscesses, frequent infections
o Enzyme analysis—confirmatory test  Job’s Syndrome: defect in chemotaxis, ↑IgE
 Drugs causing G6PD Def: primaquine, dapsone, sulfonamides  Absolute Count = %leukocytes x total WBC count
 PK Deficiency  Leukemoid Reaction: benign, exaggerated leukocyte response
o Intrinsic defect  Leukoerythroblastic Rxn in Woman >50yo: usually dt breast cancer
o Extravascular hemolysis metastatic to bone
o ↑2,3BPF right shifts OBC
o Offsets clinical effects of anemia Benign Quantitative WBC Disorders
 Immune Hemolytic Anemia: Autoimmune warm type (IgG) most  Neutrophilic Leukocytosis: neutrophil count >7000 cells/mm3
common cause  Neutropenia: neutrophil count <1500 cells/mm3
 Drug-Induced: drug adsorption—penicillin, immuncomplex—quinidine,  Eosinophilia
autoantibody—methyldopa o eosinophil count >700 cells/mm3
 IgG-Mediated: extravascular hemolysis, spherocytosis o Type I hypersensitivity
 Complement-mediated: intravascular or extravascular hemolysis o Invasive helminthes
 IgM-Mediated: intravascular (most common) or extravascular hemolysis o Hypocortisolism
 Direct Antihuman Globulin (DAT): most important marker of immune  Eosinopneia: hypercortisolism
hemolytic anemia  Basophilia: consider myeloproliferative disease
 Micro/Macroangiopathic Hemolytic Anemia  Lymphocytosis
o Aortic stenosis—most common cause o Adult: lymphocyte count >4000 cells/mm3
o Extrinsic o Child: lymphocyte count >8000 cells/mm3
o Intravascular hemolysis  Atypical Lymphocytes
o Schistocytes—sign of MHA o angtigenically stimulated
 Malaria o EBV, CMV, Viral Hepatitis, Phenytoin
o Anopheles mosquito  B Cells have CD21 receptor sites for EBV
o Intravascular hemolysis correlates w/ fever spikes  Infectious Mono: rash develops if pt placed on ampicillin
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  Heterophile Antibodies: IgM antibodies directed against horse, sheep, o only polycythemia w/ ↑PV & ↓EPO
bovine RBCs o phlebotomy ↓ viscosity-induced thrombosis
 Anti-VCA-IgG/IgM: excellent test if screening test is negative—mono  RBC Count = RBC mass/PV
 Lymphopenia  Relative Polycythemia: ↑RBC count, ↓PV, normal RBC mass, Sao2, EPO
o Adult: lymphocyte count <1500 cells/mm3  Appropriate Absolute Polycythemia: ↑RBC mass, EPO, normal PV,
o Child: lymphocyte count <3000 cells/mm3 ↓Sao2
 Lymphopenia in HIV: CD4 helper T cell lysis by virus  Inappropriate Absolute Polycythemia
 Corticosteroids: produce neutrophilic leukocytosis, eosinopneia & o Ectopic Secretion EPO: ↑RBC mass, EPO, normal PV, normal
lymphopenia Sao2
 Monocytosis: chronic infection, autoimmune dz, malignancy o PRV: ↑RBC mass, ↓EPO, ↑PV, normal Sao2
 PRV
Leukemias o mutation of JAK2 gene
 Leukemia o thrombotic events
o malignant transformation of marrow stem cells  CML: t9:22 translocation ABL proto-oncogene
o arises in the marrow & disseminates  Philadelphia Chromosome = chromosome 22 w/ translocation
 ALL  CML Blast Crisis
o most common leukemia & cancer in CHILDREN o myeloblasts or lymphoblasts
o CNS o no Auer Rods
o Testicle involvement o only leukemia w/ thrombocytosis
 AML: 15-60yo  BCR-ABL Fusion Gene: most sensitive & specific test for CML
 CML: 40-60+yo  Myelofibrosis & Myeloid Metaplasia (MMM)
 CLL: most common overall type of leukemia o JAK2 gene mutation
 Acute Leukemia o Extramedullary hematopoiesis
o abrupt onset o Marrow fibrosis
o key finding of blasts >20% in bone marrow o Massive splenomegaly
 Skin Involvement: T cell leukemias o Tear drop RBCs
 Bone Marrow Exam: most important test for diagnosing leukemia o Leukoerythroblastic smear
 Chronic Leukemia  Essential Thrombocythemia (ET)
o Insidious onset o Dysplastic/nonfxnal platelets
o Key finding of blasts <10% in bone marrow o ↑platelets
 Acute vs Chronic Leukemia: bone marrow aspirate w/ blast count o JAK2 gene mutation
 Myelodysplastic Syndromes (MDS)
o Cytopenias
o Hypercellular marrow
Neoplastic Myeloid Disorders o >30% progress to acute leukemia
 Myeloid Disorders: neoplastic stem cell disorders  Acute Promyelocytic Leukemia: t(15:17)
 Polycythemia Vera  Acute Monocyte Leukemia: gum infiltration
o most common chronic myeloproliferative disorder  AML: Auer rods in cytoplasm of myeloblasts
o serum EPO best initial test  Auer Rods: only in AML & NOT in CML
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  Toxoplasmosis: mononucleosis-like syndrome w/ painful cervical
Lymphoid Leukemias lymphadenopathy
 ALL  Tularemia: rabbits, ulceroglandular type most common
o Most common cancer & leukemia in children
o CD10 & TdT positive, most common type Non-Hodgkin’s Lymphoma
o T(12:21) offerst favorable prognosis  Sinus Histiocytosis Axillary Nodes: favorable sign in breast cancer
 Adult T-cell Leukemia  NHL
o association w/ HTLV-1 o majority B-cell origin
o skin lesions o most common malignant lymphomas adults/kids
o lytic bone lesions w/ hyper Ca  Extranodal Sites: stomach (most common), CNS, Peyer’s Patches
 TAX gene: inhibits TP53 suppressor gene  Epstein-Barr Virus: Burkitt’s Lymphoma, CNS lymphoma
 CLL  H. pylori: malignant lymphoma of stomach
o Most common leukemia  Lymphoma in Autoimmune Dz: Sjorgren’s Syndrome, Hashimoto’s
o Most common cause of generalized lymphadenopathy in those Thyroiditis
>60yo  Mycosis Fungoides: CD4 T helper cells neoplasm, skin involvement
o Hypogammaglobulinemia  Sezary Syndrome: mycosis fungoides in leukemic phase
o Smudge cells
 Hairy Cell Leukemia (HCL) Hodgkin’s Lymphoma
o Spleen primary site for neoplastic cells  Nodular Sclerosing HL
o Absence of lymphadenopathy o female dominant
o Positive TRAP stain o most common type of HL
o Dramatic response to purine nucleosides  EBV: association w/ mixed cellularity HL
 Reed-Sternberg Cell
Lymphoid Tissue Disorders o neoplastic cell of HL
o CD15+, CD30+
Lymphadenopathy o Required to make HL dx
 B Cells: germinal follicles  HL
 T Cells: paracortex, thymus o Pel-Ebstein Fever
 Histocytes: sinuses, skin, Langerhans cells o Prognosis—stage more important than type of HL
 Nodal Enlargement: <30 usually benign, >30 usually malignant  Nodular Sclerosing HL: anterior mediastinal mass + single group of nodes
 Painful Lymphadenopathy: infection above diaphragm
 Painless Lymphadenopathy: metastasis or 1° malignant lymphoma  Rx for HL: ↑risk for 2nd malignancies
 Left Supraclavicular Node Metastasis: stomach or pancreatic carcinoma
 Hilar Nodes Metastasis: lung cancer
 Para-aortic Node Metastasis: testicular cancer Langerhans Cell Histiocytoses
 Follicular Hyperplasia: prominent germinal follicles  Histiocytes: CD1+, contain Birbeck granules
 Dermatopathic Lympadenitis: melanin pigment in macrophages  Malignant Histiocytoses: skin involvement common, lytic bone lesions
 Hand-Schuller-Christian Dz: lytic skull lesions, diabetes insipidus,
exophthalmos
19
  Eosinophilic Granuloma: benign histiocytosis, unifocal lytic lesions in  ATIII: neutralizes activated serine protease coagulation factors
bone  PGI2: vasodilator, inhibits platelet aggregation
 Proteins C & S: inactivate factors V & VIII, enhance fibrinolysis
Mast Cell Disorders  tPA: activates plasminogen to release plasmin
 Mast Cell Dz: pruritus, swelling, hyperpigmentation  TXA2: vasoconstrictor, enhances platelet aggregation
 Urticaria Pigmentosum: dermatographism, lesions remain  vWF
hyperpigmented o platelet adhesion molecule
 Mast Cells: metachromatic granules o synthesized in Weibel-Palade bodies in endothelial cells
o ↓ vWF causes ↓VIII:c
Plasma Cell Dyscrasias o Platelet adhesion
 Plasma Cell Dyscrasia: monoclonal spike, usually IgG o Prevents degradation of VIII:c in plasma
 Bence Jones Protein: light chains in urine  Factor VIII: c synthesized in the liver + reticuloendothelial cells
 Myeloma  Tissue Thromboplastin: activates factor VII in extrinsic coagulation
o Rare <40yo system
o Normal plasma cell  MGUS  myeloma  Platelet Receptors: GpIb binds to vWF & GpIIb-IIIa binds to fibrinogen
o Sepsis & renal failure common causes of death  Ticlopidine, Clopidogrel & Abciximab: interfere w/ GpIIb-IIIa receptor fxn
 Bone Findings in Myeloma: lytic lesions, pathologica frx, hyperCa  Important Platelet Storage Proteins: ADP, vWF, fibrinogen
 BJ Renal Dz in Myeloma: proteinaceous casts w/ multinucleated giant  Platelet Fxn: stabilizes intercellular adherens jxns in venular endothelial
cell rxn cells
 MGUS: most common monoclonal gammopathy  Extrinsic System: factor VII, activates factors IX & X
 Intrinsic System: factors XII, XI, IX, VIII
Spleen Disorders  Factor XIIa: activates kininogen system
 Red Pulp: fixed macrophages  Final Common Pathway: factors X, V, II, I
 White Pulp: B & T cells  Factor XIII: cross-links insoluble fibrin monomers
 Malaria: most common cause splenomegaly in developing countries  Vitamin K Dependents Factors: procoagulants II, VII, IX, X, anticoagulants
 Gaucher’s Dz: ↓glucoerebrosidase, ↑glucocerebroside protein C&S
 Massive Splenomegaly: infarcts common w/ pain, friction rub, & Left-  Vitamin K: liver-activated by epoxide reductase
sided pleural effusion  Calcium: binds γ-carboxylated vitamin K-dependent factors
 Splenomegaly in Cirrhosis: “sugar coated” spleen  Factors Consumed in Clot to Produce Serum: I, II, V, VIII
 Hypersplensim: destruction of hematopoietic cells producing cytopenias  Plasminogen Activators: tPA, streptokinase, urokinase
 Splenic Dysfxn: ↑ risk for strep pneumo sepsis  Aminocaproic Acid: inhibits plasminogen
 Mechanisms: ↓IgM, ↓Tuftsin, ↓splenic macrophages  D-Dimers: cross-linked fibrin monomers
 Platelet Sequence in Hemostasis: adhesion, release rxn, synthesis TXA,
temporary plug
Hemostasis Disorders  TXA2: enhances fibrinogen attachment to GpIIb-IIIa receptors
 Temporary Platelet Plug: held together by fibrin
Normal Hemostasis & Hemostasis Testing  BT: test of platelet fxn to formation of temporary plug
 Heparin-like Molecules: enhance ATIII activity  Ristocetin Cofactor Assay: test of vWF fxn

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 o AD inheritance
Coagulation Tests o Associated w/ MVP, Marfan Syndrome, angiodysplasia
 PT: evaluates factors VII, X, V, II & I o Most common hereditary coagulation disorder
 INR: standardizes PT for warfarin therapy o Combined platelet & coagulation factor disorder
 PTT: evaluates factors XII, XI, IX, VIII, X, V, II, I o ↑PTT, bleeding time
o ↓VIII:c, vWF
Fibrinolytic System Tests o Rx: desmopressin acetate, OCP
 Fibrinogen Degradation Products: ↑ w/ lysis of fibrinogen & fibrin in  Circulating Anticoagulant: PT &/or PTT NOT corrected w/ mixing study
fibrin thrombi  Vitamin K Dependent Factors: II, VII, IX, X, protein C&S—activated by γ-
 D-Dimer Assay: specific for lysis of fibrin thrombi (clots), detects cross- carboxylation
links  Newborns: lack bacterial colonization in bowel, no synthesis vitamin K
 Vitamin K Deficiency in Hospitalized Pts: dt antibiotic therapy
Platelet Disorders  Rat Poison: contains warfarin
 TTP/HUS: platelet consumption + hemolytic anemia w/ schistocytes  Warfarin: inhibits epoxide reductase, vitamin K is nonfxnal
 Thrombocytosis: chronic Fe deficiency, malignancy, splenectomy  Cirrhosis
 Aspirin: most common cause of qualitative platelet defect o ↓synthesis of Vit K dependent factors, ↓ activation of Vit K
 Petechiae: only w/ thrombocytopenia o Multiple hemostasis abnormalities
 Senile Purpura: vessel instability  Sepsis: most common cause of DIC
 Platelet Dysfxn: bleeding from superficial scratches, easy bruising, ie  DIC
aspirin o Consumption of coagulation factors
 Thrombocytopenia: petechial, bleeding from superficial scratches, easy o Thrombohemorrhagic disorder
bruising o Lab Findings: ↑PT, PTT, D-dimers, BT, ↓platelets
o Rx: treat underlying dz most important, component replacement
Coagulation Disorders  D-Dimers: most sensitive screen for DIC
 Coagulation Disorders
o ↓production, inhibition, consumption Fibrinolytic Disoders
o Late rebleeding  Primary Fibrinolysis
o Hemarthroses—severe deficiency o Open heart surgery
 Hemophilia A o Prostatectomy
o X-linked recessive o Diffuse liver dz
o % VIII:c never changes o +test for FDPs, - test for D-dimers, nl platelet count, ↑PT & PTT
o Correlates w/ severity of dz  Secondary Fibrinolysis
o ↓ VIII:c o D-dimer & FDPs
o ↑PTT o ↓platelet count
o ↑PT & PTT
 Hemophilia B Thrombosis Syndromes
o X-linked recessive  Acquired Thrombosis Syndromes: anticardiolipin, antibody, lupus
o Factor IX deficiency anticoagulant
 vWD  Antiphospholipid Syndrome
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 o thrombosis syndrome  CMV: most common pathogen transmitted by transfusion
o spontaneous abortions, strokes, DVTs, hepatic vein thrombosis  Newborn Transfusion: must irradiate blood to destroy lymphocytes
 Anticardiolipin Antibody: false + syphilis serologic test  Major Crossmatch: pt serum + donor RBCs
 Other Thrombosis Syndromes: post-op state, malignancy, OCPs,  A negative antibody screen ensures that a major crossmatch will be
↓folate/B12, hyperviscosity compatible
 Factor V Leiden: most common hereditary thrombosis syndrome  Blood Group O: universal donors
 ATIII Deficiency: normal PTT after standard dose of heparin  Blood Group AB: universal recipients
 Hemorrhagic Skin Necrosis: associated w/ warfarin therapy in protein C  Allergic Transfusion Rxn: IgE Mediated
deficiency  IgA Deficient Pts: must receive IgA deficient blood products
 Febrile Transfusion Rxn: anti-HLA antibodies against donor leukocytes
Immunohematology Disorders  Anti-HLA Antibodies: come from previous exposure to HLA antigens—
blood transfusion, transplant
ABO Blood Group Antigens  Acute Hemolytic Transfusion Rxn (HTR)
 Blood Group O o dt blood group incompatibility or presence of an atypical
o Most common blood group antibody
o Anti-A-IgM, anti-B-IgM, anti-A & anti-B-IgG o intravascular or extravascular hemolysis
 M Cells: transport A & B antigens in Peyer’s patches to B lymphocytes  Suspected HTR: keep IV open w/ normal saline, d/c transfusion
 Group A: anti-B-IgM
 Group B: anti-A-IgM Hemolytic Dz of Newborn (HDN)
 Group AB: no natural antibodies  ABO HDN
 Newborns: lack natural antibodies o most common HDN
 Elderly People: frequently lose natural antibodies o mother group O, fetus blood A or B
 Blood Group AB Parents: cannot have O child o positive direct Coomb’s test on fetal cord RBC
 Blood Group O Parents: cannot have AB, A or B child  Jaundice in 1st 24hrs: most common cause is ABO HDN
 Forward Typing: identifies blood group antigen  Rh HDN
 Back Typing: identifies natural antibodies o mother Rh negative, fetus Rh postive
o anemia & amount of unconjugated bilirubin > ABO HDN
Rh & Non-Rh Antigen Systems o unconjugated bilirubin is free—not bound
o positive direct Coombs test on fetal RBCs
 5 Rh Antigens: D, C, c, E, e
 Kernicterus: free unconjugated bilirubin deposits in basal ganglia
 Rh Positive: D antigen positive
 ABO Incompatibility: protects mother from Rh sensitization
 Alloimmunization: antibodies develop against foreign antigens
 Prevention of Rh HDN: Rh immune globulin—anti-D globulin
 Atypical Antibodies: may produce Hemolytic Transfusion Rxn
 Bilirubin Absorbance: 450nm
 Individual with an atypical antibody must receive blood lacking the
antigen  Δ OD 450: bilirubin wavelength in amniotic fluid, degree of ↑ correlates
w/ severity of hemolysis
 Fy Antigen Negative RBCs: protection against P vivax malaria
 Blue Fluorescent Light/Sunlight: converts bilirubin in skin to water-
Blood Transfusion Therapy soluble dipyrrole
 Autologous Transfusion: safest transfusion

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 Upper & Lower Respiratory Disorders o most on true vocal cords
o squamous cancer
Pulmonary Fxn Tests
 ↑A-a Gradient: hypoxemia of pulmonary origin Atelectasis
 Normal A-a Gradient: hypoxemia of extrapulmonary origin  Resorption Atelectasis
o most common cause of fever 24-36hr after surgery
 PAO2 = % O2 (713) – arterial PCO2/0.8
o absent vibratory sensation, dullness to percussion, absent breath
 Medically Significant: A-a ≥30 mmHg
sounds
 Hypoxemia + ↑ A-a: ventilation, perfusion, diffusion defects, R-L cardiac
 Compression Atelectasis: air under pressure or fluid in pleural cavity
shunts
 Surfactant
 Hypoxemia + normal A-a: depression of respiratory center, upper airway
o Synthesized by type II pneumocytes
obstruction, chest bellows dz
o Cortisol ↑s synthesis
 Volumes not directly measured by spirometry: TLC, FRC, RV
o Insulin inhibits synthesis
 Normal FEV1sec/FVC: 4/5L = 80%
o ↓ surface tension
 FRC - ERV = RV
 RDS
 TLC & RV: TLC end of maximal inspiration, RV end of maximal expiration o dt a ↓ in surfactant
 Obstructive Pattern: nonuniform empyting, expiratory curve shift to left o prematurity, diabetes, C-section
of normal curve o intrapulmonary shunting
 Restrictive Parenchymal: expiratory curve shifted to right of normal o grunting, tachypnea, intercostal retractions
curve o O2 complications, blindness, bronchopulmonary dysplasia
 Fetal Surfactant: ↑ w/ maternal intake of glucocorticoids
Upper Airway Disorders  Hypoglycemia in Newborn: dt excess insulin in response to fetal
 Choanal Atresia: newborn cannot breathe through the nose, cyanosis hyperglycemia
when breast-feeding
 Allergic Polyp: most common polyp, adults Acute Lung Injury
 Triad Asthma: aspirin, nasal polyp, asthma  Left-sided Heart Failure: most common cause of pulmonary edema
 Obstructive Sleep Apnea  ARDS
o excessive snoring w/ periods of apnea o noncardiogenic pulmonary edema
o apnea causes respiratory acidosis & hypoxemia o risk: sepsis, gastric aspiration, severe trauma
o risk for developing cor pulmonale o acute alveolar-capillary damage, sepsis—most common cause
 Polysomnography: confirmatory test for obstructive sleep apnea o neutrophil damage to Type I & II pneumocytes
 Sinus Infection: most common cause of sinusitis o severe hypoxemia, PA wedge pressure <18 mmHg, ↑A-a gradient
 Srep pneumo: most common bacterial pathogen causing sinusitis  Alveolar Macrophages: cytokines chemotactic to neutrophils
 Sinusitis
o blockage of sinus drainage in nasal cavity
o CT scan most sensitive
 Nasopharygneal Carcinoma: association w/ EBV Pulmonary Infections
 Laryngeal Carcinoma  Strep pneumo: most common cause of typical community-acquired
o cigarette smoking—most common cause pneumonia
23
  Bronchopneumonia: acute bronchitis w/ local extension into  Main Cause of 2° Pulmonary HTN: respiratory acidosis & hypoxemia
parenchyma  Pulmonary HTN
 Typical Pneumonia: signs of consolidation—alveolar exudate o Exertional dyspnea—most common symptom
 Chest Radiograph: gold standard for diagnosing pneumonia o Tapering of pulmonary arteries on CXR
 Positive Gram Stain: more useful than culture  Cor Pulmonale: PH + RVH
 Mycoplasma pneumonia: most common cause of atypical pneumonia
 Atypical Pneumonia: interstitial pneumonia, no signs of consolidation Restrictive Lung Dz
 Water Loving Bacteria: Pseudomonas & Legionella pneumophila  Goodpasure Syndrome: hemoptysis followed by renal failure
 Pseudomonas: nosocomial pneumonia, contracted from respirators  Alveolitis  interstitial fibrosis
 Pneumocystis jiroveci: most common pathogen in AIDS pneumonia  Restrictive Lung Dz
 TB o ↓compliance, ↑elasticity
o acid-fastness dt mycolic acid o ↓ volumes/capacities, normal to ↑FEV/FVC ratio
o cord factor = virulence factor  Pneumoconiosis: inhalation of mineral dust
o PPD—does NOT distinguish active from inactive TB  Particle Size 1-5μm: bifurcation respiratory bronchioles & alveolar ducts
o Primary TB—upper part lower lobes, lower part of upper lobes,  Particle Size <0.5μm: alveoli
Ghon complex  Coal Workers Pneumoconiosis
o Reactivation TB—upper lobe cavitary lesions o Anthracotic pigen
o Drenching night sweats, fever, weight loss o Also element of obstructive lung dz
o Kidneys most common extrapulmonary site o Complicated CWP: black lung dz
o Pott’s Disease—TB in vertebra o No risk for lung cancer or TB
o MAC: most common TB in AIDS  Dust Cells: alveolar macrophages w/ anthracotic pigment
 Lung Abscesses  Caplan Syndrome: pneumoconiosis & cavitating rheumatoid nodules
o Most often dt aspiration of oropharyngeal material  Silicosis
o Mixed aerobic/anaerobic infection o most common occupational dz
o Chest Xray shows cavitation & fluid level o opacities contain collagen & quartz
 Superior Segment Right Lower Lobe: most common site for aspiration o “egg0shell” calcification in hilar nodes
o ↑risk lung cancer & TB
Vascular Lung Lesions  Asbestos Fibers deposit in respiratory unit
 Source of Pulmonary Thromboemoli: femoral veins  Ferruginous Bodies: Fe coated asbestos fibers
 Bronchial Arteries  Benign Pleural Plaques: most common lesions in asbestos-related dz
o protect lungs from infarction  Bronchogenic Carcinoma: most common asbestos-related cancer
o arise from aorta & intercostal arteries  Malignant Mesothelioma: arises from serosa of pleura, encases lung
 Saddle Embolus: sudden death  Asbestos: not risk for TB
 Pulmonary Infarctions  Berylliosis: risk for lung cancer
o dyspnea & tachypnea most common S&S, respiratory alkalosis,  Sarcoidosis
hypoxemia o most common noninfectious granulomatous dz of lungs
o normal ventilation scan, abnormal perfusion scan o CD4 T helper cells interact w/ unknown antigen
o ↑D-Dimers o Noncaseating granulomas
 Dx of Pulmonary Embolism: V/Q scan, spiral CT o Skin nodules have granulomas on biopsy
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 o Most common noninfectious granulomatous dz of liver  Paraseptal Emphysema: risk for spontaneous pneumothorax
o ↑ACE  Irregular Emphysema: scar emphysema
o HyperCa dt hypervitaminosis D  Chronic Bronchitis
o Dx of exclusion—r/o other granulomatous dz o Productive cough at least 3mo for 2 consecutive yrs
 Idiopathic Pulmonary Fibrosis: alveolitis leading to interstitial fibrosis, o Cigarette smoking—most common cause
honeycomb lung o Hypersecretion of mucous glands
 Collagen Vascular Dz w/ Interstitial Fibrosis: systemic sclerosis, SLE, RA o Blue bloaters, retain CO2 & develop cyanosis
 Pleural Effusion in Young Woman: consider SLE o Stocky & obsess
 Farmers Lung o Horizontally oriented heart
o antigen is thermophilic actinomyces in moldy hay o Chronic respiratory acidosis & hypoxemia
o type III & IV hypersensitivity o Hypoxemia early in CB
 Silo Fillers Dz: inhalation of gases—oxides of Nitrogen  Asthma
 Byssinosis: contact w/ cotton, line, hemp products, “Monday Morning o episodic & reversible airway dz
Blues” o wheezing
 Drug associated w/ Interstitial Fibrosis: amiodarone, bleomycin, o ↑AP diameter
cyclophosphamide, methotrexate  Extrinsic Asthma: type I hypersensitivity rxn
 Radiation-induced Lung Dz: cause of interstitial lung dz  IL-4: isotype switching to IgE production
 IL-5: production & activation of eosinophils
Obstructive Lung Dz  Eosinophils: major basic protein & cationic protein damage epithelial
 Emphysema cells
o Targets respiratory unit  LTC-D-E4: potent bronchoconstrictors
o Cigarette Smoking—most common cause of emphysema  Curschmann Spirals: shed epithelial cells
o ↑ compliance, ↓elasticity  Bronchial Asthma
o ↑TLC, RV o Initially present w/ respiratory alkalosis
o ↓FEV/FVC o Normal pH or respiratory acidosis indicates need for intubation
o Normal to ↓arterial PCO2—respiratory alkalosis  Intrinsic Asthma: nonimmune
 Cigarette Smoke: chemotactic to neutrophils, inactivates AAT &  O3: free radical, O2 combining w/ oxides of nitrogen & sulfur
Glutathione  Bronchiectasis: permanent dilation of bronchi & bronchioles
 Destruction of Elastic Tissue: loss of radial traction  Cystic Fibrosis
 Air trapping behind collapsed distal terminal bronchioles o most common cause of bronchiectasis
 Centriacinar Emphysema: destruction of distal terminal bronchioles & o autosomal recessive
RBs, upper lobe o 3 nucleotide deletion chromosome 7 coding for phenylalanine
 Panacinar Emphysema o Defective CFTR CL- is degraded in golgi apparatus
o targets distal terminal bronchioles & entire respiratory until, o Loss of NaCl in sweat, loss of NaCl in luminal secretions
lower lobe (dehydrated)
o loss α1-globulin peak on SPE o Respiratory Infections—most common cause of death in CF
 Emphysema: pink puffers, blow off CO2 o Chronic pancreatitis producing malabsoprtion & type I diabetes
 Chest Xray in Emphysema: hyperlucency, ↑AP diameter, vertically o Males infertile > females
oriented heart, depressed diaphragms o Meconium ileus, rectal prolapse
25
  Primary Ciliary Dyskinesia: absent dynein arm in cilia  Cleft Lip/Palate
 Bronchiectasis o most common congenital disorder of oral cavity
o dilated bronchi extend to periphery o failure of fusion of facial processes
o productive cough, hemoptysis  Pre-AIDS-Defining Lesions: thrush, hairy leukoplakia, apthous ulcers
 Horner Syndrome: lid lag, miosis, anhydrosis  Kaposi Sarcoma: hard palate, HHV-8
 Eaton-Lambert Syndrome: muscle weakness, antibody against Ca  Dental Caries: caused by Strep mutans
channel  Fluoride: prevents dental caries
 Behcet’s Syndrome: recurrent apthous ulcers, uveitis, genital ulcers
Mediastinum Disorders  Melanin Pigmentation in Oral Mucosa: Addison’s Dz, Peutz-Jeghers
 Anterior Compartment: most common site for mediastinal masses Syndrome
 Neurogenic Tumors: most common mediastinal mass, located in  Tooth Discoloration: tetracycline, ↑fluoride erythropoietic porphyria
posterior mediastinum  Macroglossia: myxedema, Down Syndrome, Acromegaly, Amyloidosis,
 Symptoms in Thymomas: most often associated w/ Myasthenia Gravis MENIIb
 Glossitis: deficiency of Fe, B12, Folate, Vitamin C, niacin, scarlet fever,
Pleural Disorders hairy leukoplakia
 Pleural Fluid Movement: parietal pleura to pleural space to lungs  Leukoplakia/Erythroplakia
 Congestive Heart Failure: most common overall cause of pleural effusion o smoking & alcohol—major risk factors
 Pleural Fluid Exudate o biopsy to r/o squamous dysplasia or cancer
o acute inflammation, infarction, pneumonia, metastasis  Wickham’s Stria: association w/ squamous dysplasia or cancer
o tuberculosis & malignancy most common cause  Dentigerous Cyst: association w/ 3rd molar & amelobiastoma
 Chylous Effusion: lymphatic fluid, malignancy most common cause  Squamous Papillomas: most common benign tumor in oral cavity
 Pseudochylous Effusion: pleural effusion in RA  Ameloblastoma: most common odontogenic tumor, “soap bubble”
 Pleural Effusion: blunting costophrenic angle, obscure diaphragm appearance in mandible
 Spontaneous Pneumothorax  Squamous Cell Carcinoma
o commonly seen in tall, thin, young men o Smoking products most common risk factor
o rupture of apical subpleural bleb o Lower lip—most common site
o loss of negative intrathoracic pressure  Basal Cell Carcinoma: upper lip—most common site
o sudden onset of dyspnea & pleuritic chest pain  Sjogren’s Syndrome: dry eyes, dry mouth
 Tension Pneumothorax  Parotid Gland: most common site for salivary gland tumors
o penetrating trauma to lungs  Pleomorpic Adenoma: most common salivary gland tumor
o check valve type of pleural tear  Warthin’s Tumor: heterotopic salivary gland tissue in lymph node
o ↑ in pleural cavity pressure w/ each breath  Mucoepidermoid Carcinoma: most common malignant salivary gland
o Trachea deviates to contralateral side tumor

GI Disorders Esophageal Disorders

 Dysphagia for Solids: obstructive lesion
Oral Cavity & Salivary Gland Disorders
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 Dysphagia for Solids & Liquids: motor disorder o nocturnal regurg
 TE Fistula o Barium Swallow—dilated aperistalic esophagus, beak-like
o Proximal esophagus ends blindly, distal esophagus from trachea tapering distal end
o Polyhydraminos  Leiomyoma: most common BENIGN esophageal tumor
 VATER Syndrome: vertebral abnormalities, anal atresia TE fistula, renal  Distal Adenocarcinoma: most common esophageal cancer
dz & absent radius  Squamous Cell Carcinoma
 Plummer-Vinson Syndrome: associated w/ chronic Fe deficiency o cigarette smoking most common cause
 Zenker’s Diverticulum: most common esophageal diverticulum o dysphagia for solids + weight loos
 Hiatal Hernia o symptoms often relate to LOCAL invasion
o ↑s w/ age
o Sliding type most common Stomach Disorders
o Proximal stomach in thoracic cavity  Peptic Ulcer Dz
o Acid reflux most common symptom o most common cause of hematemesis & melena
 Paraesophageal Hernia: gastroesophageal jxn at level of diaphragm o duodenal ulcers NEVER malignant
 GERD o Gastric ulcers—small % malignant
o Relaxed lower esophageal sphincter  Melena: hematin, sign of upper GI bleed
o Nocturnal cough/asthma  Gastric Analysis: measures BAO & MAO (Basal Acid Output & Max Acid
o Acid injury to enamel Output)
o Barrett’s esophagus  Congenital Pyloric Stenosis:
o Atypical presentation—esophageal pH monitoring, endoscopy, o Hypertrophy of pyloric sphincter muscles
manometry o Vomiting of non-bile stained fluid
 Barrett’s Esophagus Complications: distal adenocarcinoma, stricture  Gastroparesis
 AIDS-related Esophagitis: HSV, CMV, Candida o sign of autonomic neuropathy—ie diabetes
 Corrosive Esophagitis: strictures, perforation, squamous cancer o early satiety
 Left Gastric Vein drains from distal esophagus & proximal stomach into o vomiting undigested food
the portal vein  Hemorrhagic Gastritis: NSAIDs most common cause, alcohol 2nd
 Esophageal Varices: portal htn dilates left gastric vein  Type A Chronic Atrophic Gastritis: body & fundus, pernicious anemia
 Ruptured Esophageal Varices  Type B Chronic Atrophic Gastritis: antrum & pylorus, H. pylori
o most common cause of death in CIRRHOSIS  H. pylori
o endoscopy most important diagnostic procedure o Urease producer
 Mallory-Weiss Syndrome: mucosal tear of distal esophagus o Colonizes mucous layer, noninvasive
 Boerhavve’s Syndrome: rupture of distal esophagus o Intestinal metaplasia precursor for cancer
 Pneumomediastinum: air in subQ tissue, crunching sound on physical o Stool Antigen Tests Results: + infection, - infection
 Achalasia o Urea Breath Test/Serology: do NOT distinguish active vs old
o most common neuromuscular disorder of esophagus infection
o autoimmune destruction ganglion cells myenteric plexus o Rx: ↓risk of gastric cancer & lymphoma
o loss of smooth muscle motility  Menetrier’s Dz: giant rugal folds, ↑mucus w/ protein loss, achlorhydria
o destruction NO synthase producing neurons causes incomplete  Zollinger-Ellison Syndrome
relaxation lower esophageal sphincter o ↑gastrin, acid
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 o Malignant islet cell tumor  Serum Immunoreactive Trypsin: ↓in chronic pancreatitis
o single or multiple ulcers  Chronic Pancreatitis: CT scan dystrophic calcification
o Peptic Ulcer Dz + Diarrhea  Tests Bile Salt/Acid Def: serium bile acids, bile breath tests
o Association w/ MEN I Syndrome  Clinical Malabsorption: steatorrhea, fat-/water-soluble vitamin def,
 Gastric Polyps: complication chronic gastritis, achlorhydria anemia, ascites
 Leiomyoma: most common BENIGN stomach tumor  Celiac Dz
 Gastric Cancer o immune dz directed against gluten
o ↑ incidence in Japan o greatest associationg w/ dermatitis herpetformis
o Lesser curvature pylorus & antrum most common sites o tTG has pivotal role
o Virchow’s Left supraclavicular node metastasis o ↑anti-tTG, anti-EMA, anti-gliadin antibodies
o Acanthosis nigricans o Steatorrhea, weight loss
o Leser Trelat Sign o Flattened villi, hyperplastic glands
 Diffuse Gastric Cancer: “linitis plastic”, not related to H. pylori o Gluten free diet
 Intestinal Metaplasia: precursor lesion for gastric adenocarcinoma  Whipple’s Dz
 Krukenberg Tumor: metastatic signet-ring cells to BOTH ovaries o Caused by Tropheryma whippelii
 Gastric Lymphoma: H pylori—most common cause o Foamy macrophages
 Small Bowel Obstruction
Small & Large Bowel Disorders o Bowel distention, air/fluid levels
 Colicky Pain: symptom of bowel obstruction o Colicky Pain—pain w/ alternating w/ pain free intervals = sign of
 Bowel Obstruction: small bowel > large bowel SM obstruction
 Dysentery: bloody diarrhea w/ mucus o Adhesions from Previous Surgery: most common cause
 Melanosis Coli: black bowel from laxatives  Indirect Inguinal Hernia: most common hernia
 Hematochezia: sigmoid diverticulosis, angiodysplasia  SMA & IMA Jxn: watershed area
 Types of Diarrhea: osmotic, secretory, invasive  Occlusion of SMA: most common cause of small bowel infarct
 Fecal Smear for Leukocytes: screen for invasive diarrhea  Atrial Fib: most common arrhythmia associated w/ systemic
 Secretory Diarrhea: loss of isotonic fluid embolization
 Osmotic Diarrhea: loss of hypotonic fluid  Small Bowel Infarct
 Stool Osmotic Gap: distinguishes secretory from osmotic diarrhea o sudden onset diffuse abdom pain, bloody diarrhea
 Lactase Deficiency: disaccharidase deficiency in brush border, avoid dairy o distention, absent bowel sounds, no rebound tenderness
products  Ischemic Colitis: mesenteric angina after eating  fear of eating &
 Causes of Malabsorption: pancreatic insufficiency, bile salt/acid weight loss
deficiency, small bowel dz  Angiodysplasia
 Pancreatic Insufficiency: malabsorption of fat & proteins—NOT carbs o dilation cecal submucosal venules, hematochezia
 Bile Salts/Acids: required to micellarize monoglycerides & fatty acids o 2nd most common cause hematochezia
 Small Bowel Dz: loss of villous absorptive surface o Association w/ vWD & calcific aortic stenosis
 General Malabsorption Screening Tests: stool for fat, serum beta  Newborn w/ Fecal Material in Umbilical Area: persistence of vitelline
carotene duct
 D-Xylose: ↓ reabsorption indicates small bowel dz  Meckel Diverticulum
o bleeding most common complication
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 o mimics acute appendicitis  Familial Polyposis: auto dom, ALL pt develop colon cancer, complete
 Small Bowel Diverticula: duodenal most common site, diverticulitis, penetrance
bacterial overgrowth  Turcot’s Syndrome: auto rec, colon cancer, brain tumors
 Sigmoid Diverticular Dz  Colon Cancer
o constipation most common cause o 3rd most common cancer in men & women
o diverticulitis most common complication o 3rd most common cause of mortality dt cancer
o “left-sided” appendicitis  Rectosigmoid: most common site for colon cancer
o CT scan best for dx  Fecal Occult Blood Test: most tests do NOT distinguish hemoglobin from
o Most common cause hematochezia & fistulas myoglobin
 Ulcerative Colitis: mucosal/submucosal ulcerations  Left Sided Colon Cancer: tend to obstruct, small diameter
 Crohn’s Dz: transmural inflammation  Right Sided Colon Cancer: tend to bleed, large diameter, Fe deficiency
 IBS  Colon Cancer Prevention: aspirin, FOBT, dietary alterations, stop smoking
o Intrinsic colonic motility disorder  Acute Appendicitis
o Most common fxnal bowel disorder o most common abdom surgical emergency
o Alternating bouts of constipation/diarrhea o pain precedes nausea & vomiting
o ↑mucus in stool o periappendiceal abscess most common complication
o Mainstay is adequate fiber intake o Dx: spiral CT or plain CT w/ rectal contrast
 Small Bowel: least common site for malignancy in GI tract  Acute Diverticulitis & Appendicitis: initially periumbilical & shifts to RLQ
 Carcinoid Tumors  C Fibers: refers to midline
o malignant neuroendocrine tumors  Aδ Fibers: localize pain
o terminal ileum—metastasis to liver causes carcinoid syndrome  Retrocecal Appendicitis: sentinel loop
o bright yellow  Pyelophlebitis: portal vein inflammation
o Carcinoid Syndrome—liver metastasis is necessary  Subphrenic Abscess: persistent fever post-op
o Flushing, diarrhea, wheezing, ↑urine 5-HIAA  Anorectal Bleeding: internal hemorrhoids most common cause
 Bowel Primary Lymphoma: usually in Peyer’s Patches in terminal ileum  Internal Hemorrhoids
 Sigmoid Colon: most common site for GI polyps, diverticula, cancer o straining at stool, painless bleeding
 Hyperplastic Polyp: most common polyp in adults o commonly prolapse out of rectum
 Juvenile Polyp: most common polyp in children o anal pruritus, soiling of underwear
 Hyperplastic & Juvenile Polyps: NO malignant potential  External Hemorrhoids: painful thrombosis inferior hemorrhoidal veins
 Peutz-Jeghers Polyposis  Rectal Prolapse
o predominance small intestine polyps o In kids <2yo: whooping cough, trichuriasis, cystic fibrosis
o ↑ risk colorectal, breast, gynecologic cancer o Elderly: straining at stool
 Vermiform Appendix: most common site for carcinoid tumor  Pilonidal Sinus/Abscess: painful mass in deep gluteal fold
 Tubular Adenoma: most common neoplastic polyp  Pruritus Ani: internal hemorrhoids, diabetes, pinworm
 Anorectal Fistula: Crohn’s Dz, Cryptoglandular infection
 Villous Adenoma  Anal Fissure: most are posteriorly located, anal tag marks location
o may cause hypoproteinemia & hypoK  Anal Carcinoma
o greatest risk for developing colon cancer o Basaloid carcinoma most common

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 o Squamous cancer has HPV 16 & 18 relationship
Other Inflammatory Disorders
Hepatobiliary & Pancreatic Disorders  Autoimmune Hepatitis
o type I most common in US
Lab Eval of Liver Cell Injury o +serum ANA, +anti-smooth muscle antibodies
 Unconjugated Bilirubin  Neonatal Hepatitis: multifactorial, biopsy shows multinucleated giant
o End-product of heme degradation in splenic macrophages cells
o Lipid soluble  Rye Syndrome
o 20% recycled to liver & kidneys o association w/ aspiring & infection—chickenpox, flu
 Conjugated Bilirubin: glucuronic acid makes bilirubin water soluble o encephalopathy, fatty Δ in liver, ↑transaminases
 Intestinal Bacteria: convert CB  UBC o sleepy but respond  stuporous  obtundation  coma
 Urobilin: color of stool & urine o ↓transaminases, bilirubin, PT, ammonia
o ↓glucose
 Viral Hepatitis: most common cause of jaundice
 Fatty Liver of Pregnancy: dysfxn in β-oxidation fatty acids, deliver baby
 Gibert’s Dz: 2nd most common cause of jaundice, fasting unconjugated
hyperbilirubinemia  Preeclampsia: periportal triad liver cell necrosis, HELLP syndrome
o HELLP: hemolytic anemia w/ schistocytes, elevated serum
Viral Hepatitis transmainases, low platelets
 Phases Acute Hepatitis: prodrome, jaundice, recovery  Fulminant Hepatic Failure
o viral hepatitis most common overall cause
 Transminases: peak before jaundice
o ↑transaminases, ↑PT & Ammonia
 Hepatitis A: most common viral cause of jaundice
 Fulminant Hepatitis: acetaminophen most common drug cause
 Hepatitis A Virus: anti-HAV-IgM indicates infection, anti-HAV-IgG
indicates recovery/vaccination
Circulatory Disorders
 Extravascular Hemolysis: ↑↑ UBG, no UB
 Hepatic Artery Infarct
 Hepatitis B
o Uncommon dt dual blood supply
o HBsAg: 1st antigen to arrive & last to leave w/ recovery from Hep
o Liver transport rejection, Polyarteritis Nodosa
B
 Portal Vein Thrombosis: ascities, portal htn, no hepatomegaly, air in
o HBeAg & HBV-DNA: infective particles
portal vein
o Anti-HBc-IgG: present after 6mo
o Anti-HBs: protective antibody, immunization or recovery from  Intrahepatic Obstruction to Blood Flow: cirrhosis most common cause
past infection  Centrilobar Necrosis
o HBsAG > 6mo defines chronic HBV o Combined LHF & RHF
o Health Carrier: HBsAG, anti-HBc-IgC o “nutmeg” liver
o Infective Carrier: HBsAg, HBeAg, HBV-DNA, anti-HBc-IgG o May progress to cardiac cirrhosis
 Hepatitis C & D  Peliosis Hepatis: anabolic steroids, Bartonella henselae
o HCV Testing: screens w/ EIA, confirm w/ RIBA & HCV RNA  Polycythemia Vera: most common cause of hepatic vein thrombosis
o HCV RNA: gold standard test  Hepatic Vein Thrombosis: hepatomegaly, portal htn, ascites
o HCV, HDV: no protective antibodies  Veno-Occlusive Dz: complication of bone marrow transplant
 Viral Hepatitis: urine UBG++, urine bilirubin++  Hematobilia: blood in bile from liver trauma
 Serum ALT: last enzyme to return to normal
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Alcohol-Related & Drug/Chemical Induced Liver Disorders  Portal HTN & Shunts: shunts that bypass the liver can precipitate
 Alcohol Liver Disease: fatty Δ, hepatitis cirrhosis encephalopathy
 Alcoholic Hepatitis  Splenorenal Shunt: does NOT bypass lier, most physiologic shunt
o acetaldehyde damages hepatocytes  Transjugular Intrahepatic Portosystemic Shunt: ↓portal vein pressure,
o fatty Δ, neutrophil infiltration, Mallory Bodies connects portal vein w/ hepatic vein
 Intrahepatic Fibrosis: methotrexate, amiodarone  Ascites
o Transudate dt alterations in Starling Pressures
Obstructive (Cholestatic) Liver Dz o Secondary aldosteronism
 Intrahepatic Cholestasis: Oral Contraceptive Pills, anabolic steroids o Liver vs peritoneal: serum albumin—ascitic fluid albumin,
 Extrahepatic Cholestasis: Stone in common bile duct—most common >1.1g/dL liver origin & <1.1g/dL peritoneal origin
cause  Hepatorenal Syndrome
 Cholestasis o Reversible renal failure w/out parenchymal dz
o urine UBG o, urine bilirubin++ o Liver transplantation only curative tx
o pregnancy: effect of estrogen on intrahepatic bile secretion  Hyperestrinism in Males: gynecomastia, spider telangiectasia
 Extrahepatic Biliary Atresia: jaundice in newborn  Postnecrotic Cirhosis: chronic hepatitis HBV & HCV
 Primary Sclerosing Cholangitis  Primary Biliary Cirrhosis
o Obliterative fibrosis intrahepatic & extrahepatic bile ducts o Autoimmune destruction of bile ducts in triads
o Strong association w/ ulcerative colitis > Crohn’s Dz o Damage to mitochondrial proteins in bile duct epithelium in
o Cirrhosis, cholangiocarcinoma triads, destruction by CD8 T cells
o ERCP diagnostic “beading” of bile ducts o Antimitochondrial antibodies
o Pruritis before jaundice
Cirrhosis o Jaundice is late finding
 Cirrhosis: irreversible fibrosis, regenerative nodules o ↑serum ANA, AMA, IgM
 Regenerative Nodules: produce intrasinusoidal htn  Secondary Biliary Cirrhosis: cystic fibrosis
 Alcoholic Liver Dz: most common cause of cirrhosis  Hemochromatosis
 Hepatic Encephalopathy o Unrestricted reabsorption of Fe
o reversible metabolic disorder o Missense mutations HFE gene on chromosome 6
o ↑false neurotransmitters, ↑serum ammonia o Bronze diabetes
o Alternations mental status, somnolence, asterixis o Malabsorption, restrictive cardiomyopathy, infertility
 Ammonia o ↑serum Fe, % saturation ferritin, ↓TIBC
o derives from amino acid metabolism & urease-producing bacteria o % saturation best screen
in bowel o Serum ferritin—used to follow therapy
o ↓Ammonia: ↓protein intake, antibiotics, lactulose  Fe initiates synthesis hydroxyl free radicals
 Encephalopathy Precipitating Factors: ↑protein, alkalosis, sedatives,  Hemosiderosis: acquired Fe overload dz
portasystemic shunts
 Portal Vein  Wilson’s Dz
o Splenic vein superior mesenteric vein o ↓incorporation Cu into ceruloplasmin, ↓excretion Cu into bile
o Htn: dt intrasinusoidal htn from regenerative nodule o Ceruloplasmin: enzyme synthesized in liver that contains Cu
compression
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 o Kayser-Fleischer Ring: excess Cu in Descemet’s membrane of  Cystic Diseases: ↑risk for cholangiocarcinoma
cornea  Caroli Disease: association w/ juvenile polycystic kidney dz
o Lenticular degeneration in CNS, movement disorder, dementia  Primary Sclerosing Cholangitis: most common cause of
o Hemolytic anemia cholangiocarcinoma
o Renal dz  Bile: bile salts/acid, phospholipid protein, CB, free cholesterol,
o ↓total serum Cu, ↑serum/urine free Cuf electrolytes, bicarb
o Rx: penicillamine—Cu chelator  Cholesterol Gallstones
 α1-Antitrypsin Def o most common stone
o M is normal allele o ↑cholesterol in bile, ↓bile salts & lecithin
o Z & S are deficiency variant allels o Female, fat, forty, fertile
o Cirrhosis—homozygous ZZ variant, ATT not secreted properly &  Estrogen: ↑HDL & delivery cholesterol to liver, ↑LDL receptors & HMG-
accumulates in liver CoA reductase activity
o Cirrhosis—↓serum BUN, ↑serum ammonia  Black Pigment Gallstone: sign of extravascular hemolysis, Ca bilirubinate
 Hypoglycemia in Cirrhosis: ↓gluconeogenesis, ↓glycogen stores  Brown Pigment Gallstone: sign of common bile duct infection
 Cirrhosis: lactic acidosis, hypoNa, HypoK  Stone Complications: cholecystitis, common bile duct obstruction,
 Severe Liver Dysfxn: ↓serum albumin, ↑PT cancer, acute pancreatitis
 HypoCa in Cirrhosis: ↓serum albumin, ↓25(OH)-Vit D  Stage 1: stone lodges in cystic duct, midepigastric colicky pain
 Stage 2: stone impacts in cystic duct, pain shift to RUQ, radiation to right
Liver Tumors scapula/shoulder
 Focal Nodular Hyperplasia: central stellate scar w/ radiating fibrous  Stage 3: bacterial invasion gallbladder wall, +Murphy Sign, subsides if
septae stone falls out
 Cavernous Hemangioma: most common benign tumor, potential for  Stage 4: perforation
intraperitoneal hemorrhage  Stone Pain Radiation: right scapula/shoulder
 Liver Cell Adenoma: Oral contraceptive pills, intraperitoneal hemorrhage  Ultrasound: gold standard for stone dx
 Metastasis: most common liver cancer, lung most common 1° site  HIDA Scan: identifies stone in cystic duct & common bile duct
 Hepatocellular Carcinoma  Jaundice: indication for common bile duct exploration
o Pre-existing HBV or HCV cirrhosis most common risk factors  Pain in Cholecystitis: merperidine NOT morphine
o Pre-existing cirrhosis  Chronic Cholecystitis
o Bile in neoplastic cells o Most common symptomatic disorder of gallbladder
o Pain, ↑ascites, fever, blood in ascetic fluid o Chemical inflammation
o ↑serum α-fetoprotein—AFP
 Cholesterolosis: excess cholesterol in bile, speckled yellow mucosal
o Rapidly ↑ing bloody ascites
surface
 Ectopic Hormones: PTH-related protein, insulin-like factor, EPO
 Hydrops: chronic cystic duct obstruction
 Liver Angiosarcoma: exposure to vinyl chloride (plastic pipes)
 Gallbladder Cancer
o Association w/ stones
o Porcelain gallbladder—↑risk for gallbladder cancer, immediate
Gallbladder & Biliary Tract Dz
surgery
 Choledochal Cyst: most common biliary tract cyst in kids, pain w/
intermittent jaundice Pancreatic Disorders
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 Major Pancreatic Duct: empties into terminal part of common bile duct, Kidney Disorders
stone blocking CBD causes acute pancreatitis
 Alcohol Abuse: most common cause of acute pancreatitis Important Lab Findings in Renal Dz
 Seat Belt Trauma: most common cause of pancreatitis in kids  Second Hydroxylation of Vitamin D: 1-α-hydroxylase in proximal tubule
 Pancreatitis: pain radiates into the back, described as knife-like pain  Renal Stone: most common upper urinary tract cause of hematuria
 3rd Space Fluid: fluid unavailable for maintenance of vol in vascular  Infection: most common cause of lower urinary tract hematuria
compartment  Transitional Cell Carcinoma Bladder: most common noninfectious cause
 Hypoxemia: circulating phospholipase destroys surfactant of lower urinary tract hematuria
 Grey-Turner Sign: flank hemorrhage  Benign Prostatic Hyperplasia: most common cause of microscopic
 Cullen’s Sign: periumbilical hemorrhage hematuria in adult males
 Persistent ↑ in Serum Amylase: consider pancreatic pseudocyst  Anticoagulants: most common drugs causing hematuria
 Pancreatic Abscess: higher fever from gram – sepsis, ↑amylase, CT  Persistent Proteinuria: usually indicates intrinsic renal dz
shows bubbles
 Pancreatic Ascites: leaking pseudocyst Renal Fxn Tests
 Amylase: NOT specific for pancreatitis  Urea: some extrarenal loos (ie skin) w/ high serum [ ]
 Acute Pancreatitis: ↑clearance of amylase in urine  Congestive Heart Failure: most common cause of ↑serum BUN
 Serum Lipase: more specific & lasts longer than amylase in acute  Creatinine
pancreatitis, excellent screen for acute pancreatitis o End-product of creatine metabolism
 Serum Immunoreactive Trypsin o Filtered, not reabsorbed or secreted
o excellent newborn screen for cystic fibrosis  Azotemia: ↑serum BUN & creatinine
o ↑ acute pancreatitis, ↓chronic pancreatitis  Urea: filtered, partly reabsorbed in proximal tubules
 CT Scan: gold standard for pancreatic imaging  Prerenal Azotemia: ↓GFR, ratio >15
 Plain Radiograph: sentinel loop, left-sided pleural effusion  Renal Azotemia: intrinsic renal dz, extrarenal loss of urea, ratio ≤15
 Chronic Pancreatitis  Postrenal Azotemia: obstruction behind kidneys, initially ratio >15, ≤15 if
o Adults: alcohol abuse most common cause obstruction persists
o Kids: cystic fibrosis most common cause  Nephrotoxic Drugs in Elderly: must adjust dose & interval for normal ↓
o Malabsorption, type I diabetes mellitus in CCr
o CT scan shows dystrophic calcification  CCr: normally ↓s with age
o Tests pancreatic insufficiency: secretin stimulation, bentiromide  ↑CCr: normal pregnancy, early diabetic glomerulopathy
 Pancreatic Carcinoma  Urinalysis: gold standard test to evaluate renal dz
o smoking most common cause, chronic pancreatitis
o CT scan best test Clinical Anatomy of Kidney
 Carcinoma in Head of Pancreas: jaundice, light-colored stool, palpable  Renal Medulla: relatively ischemic
gallbladder  Renal PGE2: vasodilation afferent arteriole
 ATII: vasoconstriction of efferent arterioles
 Pancreatic Cancer  Glomerular Basement Membrane: size & charge determine protein
o metastasis left supraclavicular node
filtration
o CA19-9 gold standard tumor marker
 Albumin: negative charge, repelled by negatively charged GBM

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  Fusion of Podocytes: sign of nephrotic syndrome  ACE-I/Receptor Blockers: slow progression of nephropathy in type
 Crescents: proliferation of parietal epithelial cells 1/type 2 diabetes
 Alport’s Syndrome: hereditary nephritis, sensorineural hearing loss,
Congenital Disorders & Cystic Dz of Kidneys ocular defects
 Horseshoe Kidney: association w/ Turner Syndrome  Thin Basement Membrane Dz: persistent hematuria
 Renal Dysplasia: most common cystic dz in kids  Rapidly Progressive GN & Focal Segmental Glomerulosclerosis: most
common cause of chornic glomerulonephritis
Glomerular Disorders
 Linear Immunofluorescence: anti-GBM diz—ie Goodpastures Disorders Affecting Tubules & Interstitium
 Granular Pattern: immunocomplex type of glomerulonephritis  Acute Tubular Necrosis
 Electron Microscopy: immunocomplex deposits are e- dense o most common cause of Acute Renal Failure
 Immunocomplex o BUN:creatinine ratio ≤15
o most common mechanism causing glomerulonephritis o hyperK, metabolic acidosis
o activate complement  C5a produced  attracts neutrophils   Ischemic ATN: most common type of ATN
damage tissue  Prerenal Azotemia: most common cause of ischemic ATN
 Nephritic Syndrome  Renal Tubular Cell Cast: key cast of ATN
o Neutrophil-related injury to glomeruli  Aminoglycosides: most common cause of nephrotoxic ATN
o Moderate proteinuria  Acute Pyelonephritis
o dysmorphic RBCs, RBC casts o most common cause of Tubulointerstitial Nephritis (TIN)
 Pitting Edema: does NOT distinguish nephritic from nephrotic syndrome o women > men
 Nephrotic Syndrome o E. coli most common cause
o Cytokine injury to podocytes  Vesicoureteral Reflux: urine refluxes into ureters during micturition
o Loss of negative charge on GBM  Ascending Infection: most common mechanism for upper/lower UTIs in
o Proteinuria >3.5 g/24hr females
o Fatty casts  Findings in APN & NOT Lower UTIs: fever, flank pain, WBC cases in urine
o Less glomerular inflammation than nephritic syndrome  Causes of Chronic Pyelonphritis
 Diabetic Glomerulopathy: type 1 > type 2 diabetes o vesicoureteal reflux in young girls, chronic hydronephrosis
 Minimal Change Dz: most common nephrotic syndrome in children o cortical scars overlie blunt calyces
 Focal Segmental Glomerulosclerosis: most common nephrotic syndrome o visible w/ intravenous peylogram
in adults o glomerular scarring, tubular atrophy (thyroidization)
 Diffuse Membranous Glomerulopathy: HBsAg association  Reflux Nephropathy: htn in children
 Type 1 MPGN: HBV, HCV (most common) association  Drugs Causing TIN: methicillin, NSAIDs, rifampin, sulfonamides
 Diabetic Glomerulopathy: poor glycemic control—most common cause  Acute Drug Induced TIN: abrupt onset fever, oliguria, eosinophilia
 Nonenzymatic Glycosylation: ↑vessel/tubular permeability to protein  Analgesic Nephropathy: acetaminophen + aspiring, renal papillary
 Osmotic Damage: ↑sorbitol necrosis
 Hyaline Arteriolosclerosis of Efferent Arteriole: ↑GFR producing  Prevention of Urate Nephropathy: allopurinol BEFORE aggressive cancer
hyperfiltration injury therapy
 Microangiopathy: ↑deposition type IV collagen  Chronic PB Poisoning: proximal tubule w/ nuclear acid-fast inclusions
 Microalbuminuria: 1st lab sign of diabetic glomerulopathy  Bence Jones Proteinuria: casts incite foreign body giant cell rxn
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 o Prevention—hydration is very important
Chronic Renal Failure o Rx for Ca stones: hydrochlorothiazide
 Chronic Renal Failure  HyperCa: most common metabolic abnormality causing Ca stones
o normocytic anemia, qualitative platelet defect  Thiazides: ↑ reabsorption of Ca out of urine
o htn, pericarditis, CHF, atherosclerosis  Struvite Stone: Mg Ammonium phosphate, urease producers, alkaline
o ↑anion gap metabolic acidosis urine pH
o ↑serum phosphorus/K  Ultrasound: detects hydronephrosis, not stone
o ↓serum Ca
o Free water clearance: 0 Kidney & Renal Pelvis Tumors
o Waxy casts—sign of CRF  Angiomyolipoma: hamartoma associated w/ tuberous sclerosis
 Renal Osteodystrophy: dt 2° hyperparathyroidism, osteomalacia,  Renal Cell Carcinoma
osteoporosis o yellow tumor w/ renal vein invastion
 Cystatin C: biomarker of kidney fxn o derives from proximal tubule cell
o smoking most common cause
Vascular Disorders o invades renal vein, poor prognosis
 Benign Nephrosclerosis: kidney of essential htn, dt hyaline o Triad: hematuria, flank pain, abdominal mass
arteriolosclerosis o Ectopic secretion EPO & PTH-related peptide
 Malignant HTN  Transitional Cell Carcinoma Renal Pelvis: smoking—most common cause
o pre-existing benign nephrosclerosis most common cause  Wilm’s Tumor
o ≥210/120 mmHg o Most common primary renal tumor in kids
o Encephalopathy, renal failure o Kids w/ unilateral flank mass & htn
o IV nitroprusside o Htn dt renin secretion
 Renal Infarctions
o Embolization most common Lower Urinary Tract & Male Reproductive Disorders
o Hematuria & flank pain
 Sickle Cell Trait/Dz: hematuria, loss concentration, renal papillary Common Ureteral Disorders
necrosis, APN
 Congenital Megaloureter: association w/ Hirschsprung’s Dz
 Diffuse Cortical Necrosis: anuria followed by ARF in pregnant women
 Ureteritis Cystica: risk factor bladder adenocarcinoma
 Hydronephrosis: most common complication of retroperitoneal fibrosis
Obstructive Disorders
 Transitional Cell Carcinoma: most common cancer of ureter
 Hydronephrosis: most common complication of upper urinary tract
obstruction
Urinary Bladder Disorders
 Renal Stones
 Exstrophy
o most common cause of upper urinary tract obstruction
o developmental failure anterior abdominal wall & bladder
o Ca oxalate most common, Ca phosphate
o risk factor for bladder adenocarcinoma
o Ipsilateral colicky pain in flank radiating to groin
 Urachal Cyst Remnants: most common cause of bladder
o Hematuria
adenocarcinoma, drainage of urine from umbilicus
o Plain films: 80% stones radiopaque
 Indwelling Catheters: most common cause sepsis/UTIs in hospital
o Spiral CT: best overall sensitivity & specificity
 Cyclophosphamide: hemorrhagic cystitis, prevented w/ mesna
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  Schistosoma hematobium: egg w/ large TERMINAL spine Penis Disorders
 E. coli: most common uropathogen, sepsis in hospital  Hypospadias
 S. saprophyticus: lower urinary tract infection in young sexually active o abnormal opening on ventral surface of penis
female, coagulase negative o most common malformation of urethral grove
 C. trachomatis: most common cause of acute urethral syndrome in o faulty closure urethral folds, androgen dysfxn
women & nonspecific urethritis in men  Epispadias: abnormal opening on dorsal surface of penis, defect of
 Lower Urinary Tract Signs: dysuria, ↑frequency, urgency genital tubercle
 ≥105 CFUs/mL: gold standard for lower urinary tract infection  Phimosis: orifice of prepuce cannot retract over head of penis
 Asymptomatic Bacteriuria: tx pregnant women w/ amoxicillin, no tx for  Balanoposthitis: infection of glans & prepuce
healthy elderly women  Peyronie’s Dz: fibromatosis, lateral curvature of penis, infertility
 Sterile Pyuria: neutrophils in urine, negative standard culture  Priapism: persistent painful erection
 Malacoplakia: Michaelis-Gutmann Bodies  Risk Factors for Invasive Squamous Cell Carcinoma: Bowen’s Dz,
 Acquired Bladder Diverticula: most common cause is BPH, chronic E. coli erythroplasia of Queyrat
infection  Bowenoid Papulosis: HPV 16, no invasive cancer
 Cystocele: bladder wall protrudes into vagina  Penis Cancer: squamous cell carcinoma
 Cystitis Cystica/Glandularis: risk of bladder adenocarcinoma  Circumcision: Protects against developing cancer of penis, HPV 16, 18
 Retain Urine: ↑ sympathetic activity—relax detrusor muscle, contract relationship
internal sphincter muscle  Testes Transabdominal Phase: mullerian inhibitory factor
 Void Urine: ↑parasympathetic activity—contract detrusor muscle, relax  Testis Inguinoscrotal Phase: androgen & hCG dependent
internal sphincter muscle  Cryptorchid Testis
 Transitional Cell Carcinoma o most common GU disorder in male kids
o Most common bladder cancer o risk for seminoma & infertility of cryptorchid testis + normally
o Smoking cigarettes—most common cause descended testis
o Multifocal tumor, recurrences are the rule  Orchitis: mumps, syphilis, HIV
o Painless hematuria—most common sign  Epididymitis
 Squamous Cell Carcinoma of Bladder: S. hematobium infection o <35yrs old—consider STD, >35yo—E. coli, Pseudomonas
 Bladder Squamous Cancer: S. hematobium o Scrotal pain w/ radiation into spermatic cord
 Killing Helminth Eggs: type II hypersensitivity rxn involving eosinophils  Prehn’s Sign: elevation of scrotum ↓pain
 Embyronal Rhabdomyosarcoma: most common sarcoma in kids, boys  Varicocele
protrude from urethra o most often left-sided, spermatic vein empties into left renal vein
 Cancers Invading Bladder: cervical & prostate cancer o smoker w/ sudden onset of left varicocele, consider renal
carcinoma invading renal vein
o “bag of worms” appearance

Urethral Disorders  Torsion of Testicle

 STD Urethritis: Chlamydia trachomatis & Neisseria gonorrhoeae o violent movement or trauma—most common
 Reiter’s Syndrome: Chlamydial urethritis, conjunctivitis, HLA-B27 arthritis o absent cremasteric reflex, testis high in inguinal canal
 Urethra Cancer: squamous cell carcinoma—most common cause  Hydrocele
o most common cause of scrotal enlargement
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 o persistent tunica vaginalis, inguinal hernia also present o Prognosis: markedly improved bc of early detection & improved
 Seminoma: most common testicular cancer tx
 Testicular Cancer
o seminomas & nonseminomas Male Hypogonadism
o cryptorchidism—most common risk factor  FSH: stimulates spermatogenesis
o Unilateral, Painless Testicular Mass  LH: stimulates testosterone synthesis in Leydig cells
o Markers: AFP, hCG  Testosterone: enhance spermatogenesis, libido
 Testicular Cancer Metastasis: para-aortic nodes NOT inguinal nodes  Sex Hormone Binding Globulin (SHBG)
o Synthesized in Sertoli cells & liver
Prostate Disorders o ↑SHBG causes ↓free testosterone
 Dihydrotestosterone: embryologic development of prostate o ↓SHBG causes ↑free testosterone
 Prostatitis: chronic > acute  Impotence: most common manifestation of male hypogonadism
 Acute Prostatitis: <35yo—consider Chlamydia, Neisseria  ↓testosterone causes ↓libido
 Chronic Prostatitis  Hypogonadism: impotence, female 2° sex characteristics, osteoporosis
o majority are abacterial  1° Hypogonadism
o can radiate to lower back, perineum, suprapubic area o ↑LH, ↓testosterone
 BPH o Leydig Cell Dysfxn: ↓testosterone & sperm count, ↑LH, nl FSH
o Most common cause of enlarged prostate in men >50yo o Leydig Cell + Seminiferous Tubule Dysfxn: ↓testosterone &
o Periurethral/transitional zones sperm count, ↑LH & FSH
o 30%-50% have ↑PSA  2° Hypogonadism
o Most common cause of bladder diverticula o ↓LH, ↓testosterone
o NOT risk factor for prostate cancer o Causes: constitutional, Kallmann’s Syndrome, Hypopituitarism
o Rx: α-adrenergic blockers of smooth muscle o Kallmann’s Syndrome/Hypopituitarism: ↓testosterone, sperm
o Surgery: Transurethral Resection of Prostate count, ↓LH & FSH
 DHT: primary mediator for developing BPH, estrogen co-mediator
 Obstructive Uropathy: most common complication of BPH, produces Male Infertility
bladder diverticula  Seminiferous Tubule Dysfxn: accounts for ≈90% of cases of male
 Prostate Infarct: pain on DRE, ↑PSA infertility
 Prostate Cancer  End-organ Dysfxn: obstruction of vas deferens
o Most common cancer in men  Semen Analysis: gold standard test for infertility
o Peripheral in location
o Advanced aging—greatest risk factor Erectile Dysfxn
o DHT-dependent  Impotence + Preserved Nocturnal Penile Tumescence: psychogenic
o Generally silent until advanced stage cause of impotence
o Osteoblastic metastases, lumbar spine, pelvis  Vascular Insufficiency: most common cause impotence men >50yo
 PSA  Parasympathetics for Erection: S2-S4
o More sensitive than specific in prostate cancer  Sympathetic for Ejaculation: T12-L1
o ↑free PSA consider BPH, ↑bound PSA consider prostate cancer  Neurologic Causes Erectile Dysfxn: multiple sclerosis, diabetes
o Dx: transrectal needle core biopsies  Drugs Erectile Dysfxn: leuprolide, methyldopa, psychotropics
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  Endocrine Dz Erectile Dysfxn: diabetes, 1° Hypothyroidism, prolactinoma  Cervical Polyp
 Sildenafil: ↑cGMP—causes vasodilation in corpus cavernosum o non-neoplastic
 Yohimbe: vasodilation o postcoital bleeding, vaginal discharge
 Cervical Intraepithelial Neoplasia: most cases associated w/ HPV,
Female Reproductive Disorders & Breast Disorders smoking = risk factor
 Koilocytosis: HPV effect in squamous cells
Vulva Disorders  Cervical Dysplasia: precursor for squamous cancer
 Lichen Sclerosis: thin epidermis, parchment-like skin  Cervical Cancer
 Lichen Simplex: leukoplakia (hyperplasia) o least common gynecologic cancer, important of Pap smear
 Papillary Hidradenoma: painful apocrine gland tumor o abnormal vaginal bleeding most common sign
o renal failure—common cause of death
 Vulvar Intraepithelial Neoplasia: HPV 16 association
 Extramammary Paget’s Dz: intraepithelial adenocarcinoma, PAS +
Reproductive Physiology & Selected Hormone Disorder
(Periodic Acid-Schiff)
 Sequence to Menarche: breast budding, growth spurt, pubic hair,
 Melanoma: PAS –
axillary hair, menarche
 Proliferative Phase: estrogen-mediated, most variable phase
Vagina Disorders
 Ovulation: estrogen surge  LH surge  ovulation
 Rokitansky-Kuster-Hauser Syndrome: absence of upper vagina/uterus
 Subnuclear Vacuoles: sign of ovulation
 Gartner’s Cyst: woffian duct remnant
 Secretory Phase: progesterone-mediated, least variable phase
 Embryonal Rhabdomyosarcoma: grape-like mass protruding from vagina
 Arias-Stella Phenomenon: exaggerated secretory phase—occurs in
 Diethylstilbestrol (DES): inhibits mullerian differentiation
pregnancy
 Vaginal Adenosis: red superficial ulcerations
 Menses: drop in hormones initiates apoptosis
 Clear Cell Adenocarcinoma of Vaginia/Cervix: association w/ DES
 Newborn Girls: may have vaginal bleeding
exposure, adenosis precursor lesion
 FSH: prepares follicle, aromatase synthesis, LH receptor synthesis
 Other DES Abnormalities: incompetent cervix, abnormal uterine shape
 LH Proliferative Phase: testosterone synthesis for conversion by
Cervix Disorders aromatase into estradiol in granulosa cells
 Transformation Zone: site where squamous dysplasia & cancer develop  LH Secretory Phase: synthesize 17-OH-progesterone
 Acute Cervicitis  hCG
o vaginal discharge—most common complaint o LH analogue
o C. trachomatis & N. gonorrhoeae >50% of cases o Maintains corpus luteum of pregnancy for 8-10wks
 Follicular Cervicitis: caused by C. trachomatis  Oral Contraceptives: prevents LH surge & ovulation, progestins cause
gland atrophy
 Reticulate Bodies: produce elementary bodies—infective particle of
Chlamydia  Estradiol: estrogen of a nonpregnant woman
 Cervical Pap Smear: screen for dysplasia/cancer, evaluates hormonal  Estrone
status o estrogen of a postmenopausal woman
o androstenedione from adrenal converted by aromatase to
 Superficial Squamous Cells: adequate estrogen
estrone
 Intermediate Squamous Cells: adequate progesterone
 Estriol: estrogen of pregnancy
 Parabasal Cells: lack of estrogen & progesterone
 DHEA-Sulfate: almost exclusively synthesized in adrenal cortex
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 Testosterone: synthesized in ovary & adrenals o Ovulatory: inadequate luteal phase, ↓progesterone, irregular
 Sex Hormone-Binding Globulin shedding of endometrium, persistent luteal phase
o synthesized in liver  1° Amenorrhea
o higher binding affinity for testosterone than estrogen o most cases dt constitutional delay
o ↑SHBG, ↓Free Testosterone o Turner’s Syndrome—1° Amenorrhea + poor female 2° sex
o ↓SHBG, ↑Free Testosterone characteristics
 Pregnancy  2° Amenorrhea: most cases dt pregnancy
o ↑RBC mass/↑↑plasma vol = ↓Hb & RBC count (dilutional  Hypothalamic/Pituitary Cause Amenorrhea: ↓FSH, LH, estrogen
effect)  Ovarian Cause Amenorrhea: ↑FSH, LH & ↓estrogen
o ↑↑plasma vol causes ↑GFR & CCr  End Organ Defect: normal FSH, LH, estrogen
o Respiratory alkalosis  Asherman Syndrome: removal of stratum basalis by curettage
o Estrogen/progesterone stimulation of respiratory center
o ↑serum T4/cortisol—dt ↑ in binding proteins Uterine Disorders
 Menopause  Acute Endometritis
o No menses for 1 yr after age 40 o Uterine infection following delivery or abortion
o Hot flushes, night sweats, mood swings o Group B strep—common path
o ↑FSH best marker, absence of menses for 12mo  Intrauterine Device: Actinomyces infection
 Hirsutism  Chronic Endometritis: presence of plasma cells in biopsy
o excess hair in normal hair-bearing areas  Adenomyosis: glands & stroma in myometrium
o polycystic ovary syndrome—most common cause  Endometriosis
o Ovarian Cause: ↑testosterone o Fxning glands & stroma outside the confines of the uterus
o Adrenal Cause: ↑DHEA-S, testosterone o Reverse menses—most common cause
 Virilzation: hirsutism + male 2° sex characteristics o Coelomic metaplasia, vascular/lymphatic spread
 Hirsutism & Virilzation: hyperandrogenicity of ovarian, adrenal, or drug o Ovaries—most common site of implantation
origin o Triad: dysmenorrhea, dyspareunia, infertility
 Polycystic Ovary Syndrome  Rectal Pouch of Douglas: site for collection of blood, malignant cells, pus,
o ↑estrogen & androgens endometrial implants
o Oligomenorrhea—most common complaint  Endometrial Polyp: common cause of menorrhagia, no risk for
o ↑LH, ↓FSH, LH:FSH ratio >2 endometrial cancer
o Rx: low-dose oral contraceptives or medroxyprogesterone  Endometrial Hyperplasia
 Menorrhagia: loss >80mL per period o Prolonged estrogen stimulation
 1° Dysmenorrhea: dt PGF2α, ↑uterine contractions o Atypical hyperplasia greatest risk for endometrial cancer
 2° Dysmenorrhea: endometriosis—most common cause o Postmenopausal bleeding
 Dysfxnal Uterine Bleeding  Endometrial Carcinoma: most common gynecologic cancer
o abnormal bleeding unrelated to an anatomic cause  Oral Contraceptives: ↓risk for endometrial cancer
o occurs most often after menarche & in perimenopausal period  Endometrial Cancer: postmenopausal bleeding—most common finding
o Anovulatory: most common type of DUB, excessive estrogen  Leiomyoma: most common benign connective tissue tumor in women
stimulation  Leiomyoma Clinical: menorrhagia, obstructive delivery
 Leiomyosarcoma: most common sarcoma of uterus
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  Carcinosarcoma: association w/ previous irradiation  Sex Cord Stromal Tumors
o hormone producing tumors, most are benign
Fallopian Tube Disorders o ↑estrogen/androgen
 Hydatid Cysts: cystic mullerian remnant, may undergo torsion  Surface Derived Tumors: ↑CA125
 Pelvic Inflammatory Dz
o most common cause of female infertility & ectopic pregnancy Gestational Disorders
o most common cause is N. gonorrhoeae & C. trachomatis—both  Fetal Surface: chorionic plate
present in 45% of cases  Maternal Surface: cotyledons
o cervical motion, adnexal, uterine tenderness, highly predictive of  Chorionic Villi: extract O2 from maternal blood
PID  Trophoblast: lines villi, syncytiotrophoblast—synthesizes hCG, HPL, &
o Rx: ceftriaxone (N. gonorrhoeae) + doxycycline (C. trachomatis) cytotrophoblast
 Salpingitis Isthmica Nodosa (SIN): tubal diverticulosis  HPL: directly correlates w/ placental mass, anti-insulin activity
 Ectopic Pregnancy  Umbilical Cord: 2 arteries, 1 vein, umbilical vein has most O2
o most common cause is previous PID  Placenta Infections: group B strep most common
o Triad: vaginal bleeding, pelvic pain, adnexal mass  Chorioamnionitis: infection fetal membranes, danger neonatal
o most common cause of death in early pregnancy sepsis/meningitis
o most common cause of hematosalpinx  Placenta Previa
o implantation over cervical os, previous C-section risk factor
Ovarian Disorders o painless vaginal bleeding
 Follicular Cyst: most common ovarian mass, non-neoplastic o do NOT perform pelvic exam, dx by ultrasound
 Corpus Luteum Cyst: most common ovarian mass in pregnancy, non-  Abruptio Placentae
neoplastic o retroplacental clot
 Oophoritis: complication of mumps or PID o most common cause of late pregnancy bleeding
 Stromal Hyperthecosis: hirsutism/virilization, htn, insulin resistance o HTN greatest risk factor
(metabolic syndrome) o Triad: painful vaginal bleeding, tetanic contractions, fetal
 Ovarian Cancer compromise
o risk ↑ w/ age  Placenta Accreta: implanation into muscle, danger of hemorrhage at
o genetic factors, excess estrogen exposure delivery
o abdominal enlargement dt fluid most common sign  Velamentous Insertion: cord inserts away from placental edge, danger of
o palpable ovaries in postmenopausal women is cancer until tearing vessels
proved otherwise  Accessory Lobe: ↑ risk for hemorrhage if detached
 Oral Contraceptives/Pregnancy: ↓risk for surface derived ovarian  Enlarged Placenta: Rh HDN, congenital syphilis, diabetes mellitus
cancers  Monochorionic Twin Placentas: identical twins, single fertilized egg
 Surface-Derived Tumors: most common group of ovarian tumors  Dichorionic Twin Placentas: identical or fraternal—separate fertilized
 Serous Cystadenocarcinoma: most common ovarian cancer, bilaterality, eggs
psammoma bodies  Preeclampsia
 Malignant Surface-Derived Cancers: commonly seed abdom cavity o usually occurs during 3rd trimester
 Germ Cell Tumors: teratoma (benign) & dysgerminoma (malignant)— o placental hypoperfusion, vasoconstriction overrides vasodilation
most common o premature aging of placenta, placental infarctions
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 o HTN, proteinuria, pitting edema  Atypical Ductal Hyperplasia: ↑risk for breast cancer
o Rx: delivery is tx of choice, Mg sulfate for seizures  Mammary Duct Ectasia: common in menopause, greenish brown nipple
 Complete Mole discharge
o Whole placenta is neoplastic, no embryo, 46XX *both male Xs)  Traumatic Fat Necrosis: usually painless indurated mass, associated w/
o Ultrasound w/ “snowstorm” appearance, too large for gestational trauma to breast tissue
age  Silicone Breast Implant Rupture: foreign body giant cell rxn
 Partial Mole: part of placenta neoplastic, embryo present 69  Fibroadenoma:
chromosomes o most common breast tumor women <40yo
 Choriocarcinoma o commonly develop in women taking cyclosporine
o malignancy of trophoblastic tissue, no chorionic villi o benign tumor derived from stroma
o complete mole—50%, spontaneous abortion—25%, normal  Phyllodes Tumor: benign, borderline, or malignant, depends on stromal
pregnancy—25% cellularity
 Amniotic Fluid: high salt content causing ferning when dried on glass  Intraductal Papilloma: most common cause of blood nipple discharge in
slide women < 50yo
 Polyhydramnios: TE fistula, duodenal astresia, maternal diabetes—fetal  Breast Cancer
polyuria o most common cancer in women
 Oligohydramnios: juvenile polycystic kidney Dz o risk: prolonged estrogen stimulation, genetically susceptible
 ↑AFP in Pregnancy: open neural tube defect, inadequate folate prior to background
pregnancy o genetic basis <10%
 L:S Ratio >2: adequate surfactant o Risk Factors: unopposed estrogen, recent use of oral
 Estriol: derived from fetal adrenal gland, placenta, maternal liver contraceptives
 ↓ Estriol: fetal-maternal-placental dysfxn o Factors ↓ing Risk: breast-feeding, exercise, health body weight
 Down Syndrome Triad: ↓urine estriol, ↓serum AFP, ↑serum hCG o Clinical: painless mass skin/nipple retraction
o Most common cancer metastatic to lungs & bone
Breast Disorders o Extranodal spread has greater significance than nodal metastasis
 Outer Quadrant Cancer: axillary node involvement alone
 Inner Quadrant Cancer: internal mammary node involvement o Sentinel Node: initial node draining the tumor
 Galactorrhea  Mammography: detect nonpalpable masses
o mechanical stimulation of nipple most common physiologic cause  Initial Management of Breast Mass: fine needle aspiration
o primary hypothyroidism, ↑TRH stimulates prolactin release  Microcalcifications: DCIS, sclerosing adenosis
o drugs very common cause  ERA-PRA Receptor Assays: positive assay confers better prognosis for
 Prolactinoma: most common pathologic cause of galactorrhea breast cancer
 Bloody Discharge: intraductal papilloma, ductal cancer  ERBB2 Oncogene: if positive in breast tissue—poor prognosis for breast
 Purulent Discharge: acute mastitis during breast feeding cancer
 Breast Pain: most common cause is fibrocystic change  Winged Scapula: damage to long thoracic nerve
 Fibrocystic Change: most common breast mass in women <50yo  Breast conservation therapy has similar survival rate as modified radical
 Cysts & Fibrosis: “lumpy bumpy” feeling on breast exam mastectomy
 Slcerosing Adenosis: often contain microcalcification seen on  Gynecomastia
mammogram o Benign glandular proliferation of male breast tissue
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 o Normal in newborn, adolescence, elderly  Rathke’s Pouch: develops anterior pituitary
o Cirrhosis (hyperestrinism)—most common pathologic  Sheehan’s Pospartum Necrosis: sudden cessation of lactation, pituitary
o Genetic Causes: Klinefelter’s Syndrome, testicular feminization infarction 2° to shock
o Drug Causes: spironolactone, ketoconazole, DES, Digoxin,  Pituitary Apoplexy: hemorrhage into preexisting adenoma
Flutamide, Leuprolide  Lymphocytic Hypophysitis: autoimmune destruction, occurs during or
o Cancer Causes: choriocarcinoma after pregnancy
 Estrogen Sources: peripheral aromatization of androgens, Leydig cells in  Empty Sella Syndrome: subarachnoid space extends into sella, ↑CSF
testis pressure compresses gland
 Breast Cancer in Men: Klinefelter’s BRCA2 suppressor gene inactivation  Posterior Pituitary: storage of ADH & release of oxytocin
 Prolactinoma
Endocrine Disorders o most common pituitary tumor
o 2° amenorrhea + galactorrhea
Overview of Endocrine Dz o In Men: impotence dt loss of libido, headache
 Negative Feedback: ↑Ca, ↓PTH or ↓Ca, ↑PTH o Rx: dopaime analogues, surgery
 Endocrine Gland Hypofxn  Growth Hormone: gluconeogenesis, ↑amino acid uptake in muscles,
o use stimulation tests stimulate IGF-1 in liver
o autoimmune dz—most common cause  IGF-1: stimulates bone, cartilage, soft tissue
 Endocrine Gland Hyperfxn  Gigantism: ↑linear/lateral bone growth in children, epiphyses NOT fused
o Use suppression tests  Acromegaly
o Pituitary Cushing Syndrome & prolactinoma can be suppressed o ↑lateral bone growth only—epiphyses NOT fused
o Benign adenoma—most common cause o Organomegaly, hyperglycemia
 Hypothalamic Dysfxn: 2° hypopituitarism, Central Diabetes Insipidus, o Comparing old vs new photo—valuable diagnostic tool
↑prolactin, precocious puberty, visual field defects, mass effects— o Heart failure from cardiomyopathy—common cause of death
hydrocephalus
 Precocious Puberty: true if CNS origin, pseudo if peripheral cause Thyroid Gland Disorders
 Thyroid Hormone: iodide attached to tyrosine
Pineal Gland Disorders  TSH: mediates trapping organification & proteolysis
 Pineal Gland: midline above quadrigeminal plate  FT4: prohormone, metabolically active by outer ring deiodinase (FT3)
 Melatonin: chemical messenger of darkness  FT4/FT3: negative feedback w/ TSH
 Pineal Gland  Total Serum T4: T4 bound to TBG + FT4
o Commonly undergoes dystrophic calcification  Estrogen: ↑TBG which ↑total serum T4, but NOT FT4
o Majority are germ cell tumors  ↓TBG: ↓ total serum T4, no effect on FT4 & TSH
 Pineal Gland Tumors: paralysis of upward gaze—“setting sun” sign  Serum TSH: best screening test for thyroid dysfxn
 123I Uptake: evaluates synthetic activity of thyroid gland
Pituitary Gland Disorders  ↑123I Uptake: ↑synthesis of thyroid hormone, Grave’s Dz
 Pituitary Infarction: invariably produces panhypopituitarism  ↓123I Uptake: thyroiditis, pt taking excess thyroid hormone
 Hypopituitarism in Adults: nonfuxning adenoma—most common cause  Cold Nodule: ↓123I Uptake
 MEN I: pituitary adenoma, hyperparathyroidism, pancreatic tumor  Hot Nodule: ↑123I Uptake
 Hypopituitarism in Children: craniopharyngioma—most common cause
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 Mass at Base of Tongue: lingual thyroid  Toxic Multinodular Goiter: 1 or more nodules in a multinodular goiter
 Thyroglossal Duct Cyst: cystic midline mass becomes TSH-independent
 Branchial Cleft Cyst: located in anterolateral neck  Thyrotoxicosis
 Acute Thyroiditis: thyrotoxicosis, ↓123I Uptake o Weight loss w/ a good appetite
 Subacute Granulomatous Thyroiditis: most common cause of painful o Heat intolerance, diarrhea
thyroid, virus induced, no adenapthy o Oligomenorrhea
 Hashimoto’s Thyroiditis o Lid stare, sinus tachycardia, systolic HTN, brisk reflexes
o autoimmune thyroiditis o ↑glucose, Ca, lymphocytes
o type IV (mainly) & type II hypersensitivity o ↓cholesterol
o most common cause of hypothyroidism  A Fib: always order a TSH test to r/o hyperthyroidism
o muscle weakness—common complaint  Grave’s Hyperthyroidism: ↑serum T4/FT4, ↑123I Uptake, ↓serum TSH
o weight gain, dry brittle hair  Grave’s Dz Tx: β-blockers, thionamides
o periorbital puffiness, hoarse voice, signs of myxedema  Thyroid Storm: tachyarrhythmias, hyperpyrexia, coma, shock
o cold intolerance, constipation  Euthyroid Sick Syndrome
o HTN from Na retention, delayed reflexes o serum T3 & T4 abnormalities, normal gland fxn
 Reidel’s Thyroiditis: fibrous tissue replacement of gland & surrounding o block in outer ring deiodinase conversion of T4 to T3, T4
tissue converted to inactive reverse T3
 Subacute Painless Lymphocytic Thyroiditis: develops post partum, o ↓serum T3 & ↑reverse T3
progression to hypothyroidism  Goiter: thyroid enlargement
 Hypothyroidism: hypometabolic  Nontoxic Goiter
 Brain: requires thyroxine for maturation o Absolute or relative deficiency of thyroid hormone
 Cretinism o Hyperplasia/hypertrophy followed by involution initially diffuse
o most often caused by maternal hypothyroidism before fetal then nodular
thyroid is developed  Toxic Nodular Goiter: 1 or more nodules become TSH-independent
o severe mental retardation  Solitary Nodule in Women: majority are benign, 15% malignant
 1° Hypothyroidism: ↓serum T4/FT4, ↑serum TSH, cholesterol  Solitary Nodule in Men/Kids: more likely to be malignant
 Myxedema Coma: stupor, hypothermia, hypoventilation, IV  Solitary Nodule w/ Hx of Radiation Exposure: more likely to be
levothyroxine, corticosteroids malignant—40%
 Thyrotoxicosis: hormone excess from any cause  Follicular Adenoma: most common benign thyroid tumor
 Hyperthyroidism: thyrotoxicosis dt excess synthesis of thyroid hormone  Papillary Carcinoma
 Grave’s Dz o most common endocrine & thyroid cancer—lymphatic invasion
o most common cause of hyperthyroidism & thyrotoxicosis o psammoma bodies
o anti-TSH receptor antibody, type II hypersensitivy  Follicular Carcinoma
o Unique to Graves: exophthalmos, pretibial myxedema, thyroid o most common thyroid cancer presenting as solitary cold nodule
acropachy o hematogenous rather than lymphatic spread
o In Elderly: cardiac & muscle findings predominate, apathetic  MEN IIa: medullary carcinoma, HPTH, pheochromocytoma
appearing  Medullary Carcinoma
 Transient Hyperthyroidism in fetus o derives from C cells
 Thyroid Acropathy: digital swelling & clubbing o calcitonin—tumor marker
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 o Calcitonin converted into amyloid o Diastolic HTN
 1° B-Cell Lymphoma: most often derives from Hashimoto’s thyroiditis o “stones, bones, abdom groans, & psychic moans”
 Anaplastic Thyroid Cancer: rapidly aggressive, uniformally fatal o Intact serum PTH (iPTH)—best initial screen
o ↑serum Ca/PTH
Parathyroid Gland Disorders o ↓serum P/Bicarb
 Superior & Inferior Parathyroids: derive from 4th & 3rd pharyngeal pouch o Cl/P ratio >33
 PTH o ↓serum calcitriol
o ↑renal Ca reabsorption, ↓renal phosphorus & bicarb reabsorp.  1° Hyperplasia: all 4 glands involved
o hypoCa/hyperP ↑PTH  1° HPTH vs Malignancy: ↑PTH—1° HPTH & ↓PTH—malignancy
o hyperCa/hypoP ↓PTH  Malignancy: most common cause of hyperCa in hospital
 Sunlight = major source of vitamin D  2° HPTH: compensation for hypoCa
 Liver: 25-hydroxylase converts cholecalciferol to 25-(OH)2D = calcitriol  Insulin Therapy: danger of developing hypoP
 Kidney: 1α-hydroxylase converts 25-(OH)D to 1,25-(OH)2D = calcitriol  HypoPhosphatemia: alkalosis—most common cause
 Calcitriol: ↑Ca/P reabsorption in bowel, ↑osteoclast production  HyperPhosphatemia: renal failure—most common cause
 Calcitriol Feedback: hypoCa ↑ synthesis, hyperCa ↓synthesis
 Total Serum Ca: Ca bound + Ca free (ionized) Adrenal Gland Disorders
 Hypoalbuminemia: ↓total serum Ca, normal ionized Ca & PTH  Adrenal Cortex
 Alkalosis: normal total serum Ca, ↓ionized Ca, ↑PTH, tetany o glomerulosa  mineralcorticoids
 Tetany o fasciculata  glucocorticoids
o Et comes close to Em, initiates action potential o reticularis  sex hormones
o Thumb adduct into palm, facial twitching after tapping facial  Peripheral Tissue Sites to Produce DHT: skin, testis, prostate, seminal
nerve vesicles, epididymis, liver
 Hypoparathyroidism  Adrenal Medulla: produce catecholamines
o autoimmune hypoparathyroidism most common cause  Metabolic End-Products of Epi/Norepi: metanephrines, VMA
o ↓serum Ca & PTH  Abrupt Withdrawal of Corticosteroids: most common cause of acute
o ↑serum phosphorus adrenocortical insufficiency
 DiGeorge Syndrome: failure of descent of 3rd/4th pharyngeal pouches,  Waterhouse-Friderichsen Syndrome: N. meningitides sepsis  DIC 
absent parathyoids & thymus bilateral adrenal hemorrhage
 Hypomagnesemia  Autoimmune Dz: most common cause of Addisons dz in US
o most common pathologic cause of hypoCa in hospital  Miliary TB: most common cause of Addison’s Dz in developing countries
o diarrhea, aminoglycosides, diuretics, alcohol  Adrenogenital Syndrome: most common cause of Addison’s Dz in kids
 Chronic Renal Failure: most common cause of hypoCa, cause  Addison’s Dz
hypoVitaminosis D o diffuse hyperpigmentation, hypotension, weakness
 1° HPTH o ↓serum Na, cortisol, bicarb
o MENI, IIa association o ↑serum K & ACTH
o Benign Adenoma: most common cause o Hypoglycemia, eosinophilia, lymphocytosis, neutropenia
o Peptic Ulcer Dz, acute pancreatitis  Metyrapone Test: ↓cortisol  ↑ACTH  ↓11-deoxycortisol
o Osteitis fibrosa cystica, subperiosteal bone resortpion,  ↑ 17-KS, Testosterone, DHT: ambiguous genitalia females, precocious
osteoporosis, pseudogout puberty males & females
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 Newborn w/ Ambiguous Genitalia: 1st step is to determine genetic sex o majority benign, unilateral, arise in adrenal medulla
w/ chromosome analysis o orthostatic hypotension, chest pain, ileus
 ↓ 17-KS, Testosterone, DHT: delayed menarche & 2° sex characteristics, o hyperglycemia, neutrophilic leukocytosis
males develop pseudohermaphroditism  Association: neurofibromatosis, MEN IIa/IIb, von-Hippel-Lindau dz
 ↑ Mineralocorticoids: Na retention w/ HTN  Unique Findings: palpitations, paroxysmal HTN, anxiety, drenching
 ↓ Mineralocorticoids: Na losers w/ hypotension sweats, headache
 Classic 21-OHase Deficiency  Dx: plasma free metanephrines—best screen
o most common cause of adrenogenital syndrome  Urine Tests: 24hr collection for metanephrine (best test), VMA
o impaired cortisol & mineralcorticoid production (salt loser),  Neuroblastoma
↑androgens o Malignant tumor postganglionic sympathetic neurons
 Non-Classic 21-OHase Deficiency: impaired cortisol synthesis only, o Childhood tumor & cause of HTN
virilzation o “small cell” tumor, neurosecretory granules
 11-OHase Deficiency: impaired cortisol + mineralocorticoid excess (salt o Child w/ abdom mass + HTN
retainer), ↑androgens  Opsoclonus-myoclonus Syndrome: paraneoplastic syndrome, myoclonic
 17-OHase Deficiency: impaired cortisol & androgens, ↑ jerk, chaotic eye movements
mineralocorticoid production  Insulinoma: ↑serum insulin, ↑C-peptide
 17-OH Progesterone: excellent screening test, ↑21-&11-OHase  Pt Injection Excess Insulin: ↑serum insulin, ↓C-peptide
deficiency, ↓17-OHase deficiency
 Cushing Syndrome Diabetes Mellitus
o Corticosteroid therapy (iatrogenic) most common cause  DM most common cause of blindness, peripheral neuropathy, chronic
o Pituitary Cushing most common pathologic cause renal failure, below-knee amputation
o Truncal obesity, thin extremities, purple stria  Maturity Onset Diabetes of the Young (MODY): Auto dom, not obese,
o Hyperglycemia, hypoK, metabolic alkalosis impaired glucose-induced secretion of insulin
 Pituitary Cushing  Metabolic Syndrome: insulin resistance exacerbated by obesity
o ↑ACTH, ↑Cortisol  Associations: acanthosis nigricans, Alzheimers Dz
o Suppression of cortisol by high-dose dexamethasone  Hyperinsulinemia: ↑VLDL, HTN, CAD, ↓HDL-CH
 Adrenal Cushing: ↓ACTH, ↑Cortisol  Good glycemic control prevents complications of diabetes
 Ectopic Cushing: ↑↑ACTH, ↑Cortisol  Nonenzymatic Glycosylation (NEG): HbA1C hyaline arteriolosclerosis,
 Hypercortisolism: thin extremities, purple stria glomerulopathy
 Hyperinsulinemia: truncal obesity  Aldose Reductase: converts glucose to sorbitol, osmotic damage
 Cushing: HTN, hirsutism  Osmotic Damage: cataracts, peripheral neuropathy, retinopathy
 Screening Tests for Cushing: ↑urine free cortisol, no suppression of  Microangiopathy: diabetic nephropathy, ↑ deposition type IV collagen
cortisol w/ low dose of dexamethasone  Insulin-Induced Hypoglycemia: most common complication of diabetes
 Nelson’s Syndrome: bilateral adrenalectomy causes enlargement of  DKA: complication of type I DM
preexisting pituitary adenoma  Gluconeogenesis: most important mechanism of hyperglycemia in DKA
 1° Hyperalodsteronism: HTN, hyperNa, HypoK, metabolic alkalosis  Ketoacids: synthesized from acetyl-CoA derived from β-oxidation of fatty
 2° Aldosteronism: compensation for ↓ cardiac output, activation of RAA acids
system  Hypertriglyceridemia: ↓ capillary lipoprotein lipase activity, ↓ hydrolysis
 Pheochromocytoma of chylomicrons & VLDL
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  DKA Electrolytes: ↓serum Na (dilutional), ↓Bicarb (metabolic acidosis), o Auto dom, mutation in fibroblast growth factor receptor gene
↑serum K, ↑anion gap metabolic acidosis o Normal head/axial skeleton, short arms/legs
 Hyperomolar Nonketotic Coma: complications of type 2 DM  Osteopetrosis
 HbA1C: marker of long term glycemic control o Deficiency of osteoCLASTS—too much bone
 Impaired Glucose Tolerance (IGT): prediabetic state, insulin resistance o Pathologic frx, visual/hearing loss
 Gestational Diabetes: anti-insulin effect of HPL, cortisol, progesterone  Osteomyelitis
 Macrosomia: ↑insulin causes ↑in adipose & muscle o usually hematogenous spread to bone, metaphysis—most
 Respiratory Distress Syndrome: ↑insulin inhibits fetal surfactant common site
production o S. aureus—most common pathogen
 Neonatal Hypoglycemia: ↑insulin drives glucose into hypoglycemic o Salmonella—sickle cell pts
range, given newborn glucose at birth o TB—Pott’s dz = vertebral column involvement
o Pseudomonas—puncture through rubber soled shoe
Polyglandular Deficiency Syndromes  Sequestra: devitalized bone
 Type I: Addison’s Dz, 1° Hypoparathyroidism, mucocutaneous candidiasis  Involucrum: reactive bone formation in periosteum
 Type II: Addison’s Dz, Hashimotos’s Thyroiditis, Type I DM  Draining Sinuses: danger of squamous cancer
 Osteoporosis
Hypoglycemia o Most common metabolic abnormality of bone
 Hypoglycemia: subdivided into fed & fasting state o Loss of mineralized bone + organic bone matrix (osteoid)
 Reactive Hypoglycemia: excess insulin—most common cause, adrenergic o Women > men
symptoms o 2° Causes: ↑cortisol, heparin, hypogonadism, malnutrition,
 Fasting Hypoglycemia space travel
o alcohol excess, insulinoma, cirrhosis o Dx: dual photon absorptiometry
o Kids: look for inborn errors of metabolism o Prevention: weight-bearing exercises, Ca, Vit D, stop smoking
 Alcohol Excess: ↓glycogen stores, ↓gluconeogenesis, pyruvate o Rx: bisphosphonates 1st line drug
converted to lactate  Estrogen: inhibits production of osteoclasts, enhance osteoblast
 Neuroglycopenia: dizziness, mental status Δs, motor disturbances  ↓Estrogen: ↑ osteoclastic activity, ↓osteoblastic activity
 Dx: prolonged fast, satisfy Whipple’s Triad  Postmenopausal Osteoporosis: compression vertebral frx—most
common
 Aseptic Necrosis
o disruption of microcirculation causes bone infarctions
o femoral head most common site
o subcapsular frx disrupts blood supply
MSK & Soft Tissue Disorders o Scaphoid Bone: most common wrist bone frx, susceptible to
aseptic necrosis
Bone Disorders o Localized pain
 Osteogenesis Imperfecta: Auto dom, defect in synthesis type I collagen o MRI most sensitive early tests
 Blue Sclera: reflection of underlying choroidal veins—ie in osteogenesis  Osteochondrosis: aseptic necrosis of ossification centers
imperfect  Legg-Calve-Perthes Dz: aseptic necrosis of femoral head ossification
 Achondroplasia center
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  Osteochondritis Dissecans  Osteoarthritis: most common disabling joint dz
o variant of osteochondrosis limited to articular epiphysis  Alkaptonuria: homogentisic acid deposits in intervertebral disks, black
o trauma 1° insult, ischemia 2° injury color
o distal femur—most common site  Osteoarthritis
o osteoarthritis late complication o femoral head, knee, cervical/lumbar vertebrae, hands
 Osgood-Schlatter Dz o wearing down of articular cartilage, bone rubs on bone
o Painful swelling tibial tuberosity in boys o osteophytes at joint margins
o Permanent knobby-appearing knees o clefts, subchondral cysts
 Paget’s Dz o no fusion of joint
o Primarily in men >50yo, ? viral etiology o pain—most common complaint
o Osteoclastic phase followed by an osteoblastic phase o joint stiffens after inactivity
o ↑alkaline phosphatase in osteoblastic phase  Ochronosis: auto rec, deficiency homogentisic acid, osteoarthritis
o Weak, thick, vascular bone  Articular Cartilage: proteoglycans, type II collagen
o Complications: frx, osteogenic sarcoma, high-output heart  OA Fingers
failure o Heberdens’ Nodes—DIP joint enlargement/pain
 Fibrous Dysplasia o Bouchard’s Nodes—PIP joint enlargement/pain
o Defect in osteoblastic differentiation & maturation  OA Vertebral Column: cervical/lumbar, degen disk dz, compression
o Medullary bone replaced by fibrous tissue w/ cyst formation neuropathies
o Ribs—most common site  Neuropathic Joint
o Complications: pathologic frx, osteogenic sarcoma, fibrosarcoma o loss of proprioception, deep sensation leading ot recurrent
 Albrights Syndrome: polyostotic bone involvement, café au lait spots, trauma
precocious puberty o Causes: diabetes, syringomyelia, tabes dorsalis
 Metastasis: most common bone malignancy  RA
 Osteochondroma: most common benign tumor o B cells produce rheumatoid factor (RF), an IgM antibody w/
 Giant Cell Tumor: epiphysis distal femur, proximal tibia specificity against Fc portion of IgG
o FR combines w/ IgG to produce immunocomplexes that activate
Joint Disorders complement
 Monosodium Urate Crystals (MSU): negative birefringence—yellow o Hand: involves MCP & PIP joints, bilateral ulnar deviation
when parallel to slow ray o Lung: interstitial fibrosis, effusions
 Calcium Pyrophosphate: positive birefringence—blue when parallel to o Blood: ACD, AIHA, Felty’s Syndrome—autoimmune neutropenia,
slow ray splenomegaly
 Group 1: noninflammatory osteoarthritis, neuropathic joint o Cervical Spine: subluxation atlantoaxial joint, cord/vertebral
 Group II: inflammatory, RA, gout artery compression
 Group III: septic, Lyme Dz, Disseminated gonococcemi o Caplan Syndrome: rheumatoid nodules in lung +
 Group IV: hemorrhage, trauma, hemophilia pneumoconiosis
 Morning Stiffness: RA, SLE, polymyalgia rheumatic o Cardiovascular: pericarditis, aortitis, vasculitis
 Joint Effusion: blood, exudate o Labs: +serum RF, ANA
 Hot Joint: acute inflammation, septic arthritis  Pannus: granulation tissue, releases cytokines that destroy articular
 Joint Crepitus: crackling feeling, osteoarthritis cartilage
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 Repair by fibrosis causes fusion of joint—ankylosis  Reiter’s Syndrome
 Baker’s Cyst: outpouching of posterior joint space in knee o C. trachomatis urethritis, arthritis, conjunctivitis
 Sjorgren’s Syndrome o Achilles tendon periostitis is diagnostic sign
o destruction minor salivary glands & lacrimal glands  Psoriatic Arthritis: sausage-shaped DIP joints, “pencil-in-cup” deformity
o dry eyes, dry mouth  N. gonorrhoeae: most common cause of septic arthritis in urban
o Lab: + serum ANA, RF, anti-SS-A/anti-SS-B, lip biopsy confirms populations
 Juvenile Rheumatoid Arthritis  Disseminated Gonococcemia: septic arthritis, tenosynovitis, dermatitis
o RF is usually negative  B. burgdorferi: gram – spirochete, cause of Lyme Dz
o Still’s Dz: fever, rash, polyarthritis  Lyme Dz
o Polyarticular: limited arthritis, uveitis & potential for blindness o vector Ixodes tick, reservoir white-tailed deer
o Pauciarticular: limited arthritis, uveitis, & potential for blindness o Erythema Chronicum Migrans: pathognomonic of Lyme Dz
 Gout o Disabling arthritis, Bell’s Palsy, Myocarditis
o Male dominant dz  Babesiosis: tick-transmitted hemolytic anemia
o Most cases dt underexcretion of uric acid  Pasteurella multocida: septic arthritis/tendinitis dt cat/dog bite
o Associations: urate nephropathy, renal stones, HTN, artery dz,
Pb poisoning Muscle Disorders
 Acute Gout  Type I: slow-twitch (red), rich in mitochondria, oxidative enzymes, poor
o 1st metatarsophalangeal joint—most often involved in ATPase enzymes
o Free uric acid crystals responsible for initiating the attack  Type II: fast-twitch (white), poor in mitochondria, oxidative enzymes, rich
o Must confirm w/ joint aspiration in ATPas enzymes
o Non-Pharm Rx: eliminate high purine diet, moderation in alcohol  Muscle Weakness: motor neuron, neuromuscular synapse, muscle
intake dysfxn
o Pharm Rx: NSAIDs or colchicine  Neurogenic Atrophy: motor neuron of axon degenerates
o Pharm Prevention: uricosuric agents for underexcretros,  Trichinosis
allopurinol for overproducers o Trichnella spiralis (nematode), from eating encysted larvae in pig
 Tophus: MSU deposits in soft tissue around the joint muscle
 Calcium Pyrophostate Dihydrate Depositition (CPPD) o Calcified larvae visible on Xray
o deposition of Ca pyrophosphate in tissues o Muscle pain, periorbital edema, splinter hemorrhages
o ↑w/ hemochromatosis, hemosiderosis, 1° HPTH o Pronounced eosinophilia
o OA Variant: knee—most common joint, chondrocalcinosis  Invasive Group A Strep
present o Necrotizing fasciitis, myositis, Strep Toxic Shock Syndrome
 Chondrocalcinosis: linear deposits of Ca pyrophosphate in articular o Exotoxin A (superantigen), exotoxin B (protease)
cartilage  Duchenne’s Muscular Dystrophy (DMD)
 Seronegative Spondyloarthropathies o X-linked rec, absence of dystrophin
o RF negative arthritis o Pseudohypertrophy of calf muscles
o Key Points: - RF, +HLA-B27, male, sacroiliitis, spondylitis o Waddling gait dt weakness of pelvic muscles
 Ankylosing Spondylitis o ↑ serum CK at birth, ↓as muscles degenerate
o Over time develop fusion of vertebrae—bamboo spine  Myotonic Dystrophy
o Aortitis, uveitis w/ potential for blindness o Most common adult muscular dystrophy
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 o CTG trinucleotide repeat  Tennis Elbow: extensor tendon pain, lateral epicondyle
o Sagging face, frontal balding, cataracts, testicular atrophy, cardiac  Golfers Elbow: flexor tendon pain, medial epicondyle
involvement  DeQuervain’s Tenosynovitis: chronic stenosing tenosynovitis of 1st dorsal
o Autoantibodies against Ach receptors, synthesized in thymus wrist compartment—ABductor pollicis longus & extensor pollicis brevis,
o Ptosis, diplopia common finding excessive friction thickens tendon sheath, Finkelstein’s Test—ulnar deviat.
o Oropharyngeal dysphagia for solids/liquids  Ganglion (Synovial) Cyst: bulge on wrist dorsum when flexed, F>M
 Myotonia: inability to relax muscles  Compartment Syndrome: ↑pressure in fascial compart., ischemia, 5Ps—
 Tensilon: inhibits AChase pain, paresthesias, pallor, paralysis, pulselessness, Volkmann’s Ischemic
Contracture—displaced supracondylar fx of distal humerous causing
Soft Tissue Disorders compression of brachial artery & median nerve
 Dupuytren’s Contracture: fibromatosis palmar fascia  Carpal Tunnel Syndrome: median nerve entrapment, causes—RA,
 Liposarcoma: most common adult sarcoma pregnancy, obesity, excessive use, acromegaly, ape hand, Dx—Phalens &
 Unhappy Triad: damage to medial meniscus, MCL & ACL Tinels
 Soft Tissue Tumors  Intervertebral Disk Dz: degen of fibrocartilage/nucleus pulposus,
o Lipoma: trunk, neck, prox extremities, most common BENIGN ruptured disk may herniated posteriorly & compress nerve root/cord
soft tissue tumor, from subQ tissue o Radicular Pain: leg pain aggravated by straight leg raising
o Liposarcoma: thigh, retroperitoneum, most common adult o L3-L4 Hern: loss of knee jerk—femoral n. L2-L4
sarcoma, lipoblasts IDed w/ fat stains o L4-L5 Hern: NO loss of reflexes
o Fibrosarcoma: thigh, upper limb, after irradiation o L5-S1 Hern: loss of ankle reflex—tibial n. L4-S3
o Dermotafibroma: LE, benign, spindle cells prolif in dermins,  Knee Joint Injuries
umbilicated red nodule o Valgus: away from midline via lateral force
o Malignant Fibrous Histiocytoma: retroperitoneal, thigh, o Varus: toward midline via medial force
radiation therapy & scarring o McMurray Test: meniscus injuries
o Rhabdomyoma: heart, tongue, vagina, benign, associated w/ o Anterior/Posterior Drawer Tests: ACL & PCL injuries
tuberous sclerosis o Unhappy Triad: medial meniscus, ACL, MCL
o Embryonal Rhabdomyosarcoma: penis & vagina, most common  Scoliosis: idiopathic—teen girls , usually right thoracic curve
sarcoma in kids, grape-like necrotic mass
o Leiomyoma: uterus—most often, stomach
o Leiomyosarcoma: GI tract & uterus
o Neurofibrosarcoma: major nerve trunks, associated w/
neurofibromatosis Skin Disorders
o Synovial Sarcoma: around joints, does NOT arise from synovial
cells—mesenchymal cells, biphasic patterns—epithelial cells Skin Histology & Terminology
forming glands + intervening spindle cells  Stratum Basalis: stem cells for division
 Stratum Corneum: site for superficial dermatophyte infections
Orthopedic Disorders  Melanocyte: neural crest origin
 Colle’s Fx: FOOSH, distal radius fx w/ or w/out ulnar styloid fx  Melanin: synthesized from tyrosine, synthesized in melanosomes
 Rotator Cuff Tear: supraspinatus, infraspinatous, teres minor,  Melanosomes: transferred by dendritic processes to keratinocytes
subscapularis, pain/weakness w/ ABduction

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  Blacks: melanosomes in all layers, melanocytes larger/more dendritic  TSST: produces desquamating sunburn-like rash
processes  S. pyogenes: erythrogenic toxin, erythematous sandpapery rash that
desquamates
Selected Viral Disorders  Scarlet Fever
 Common Wart: HPV o Erythrogenic toxin, erythrematous sandpapery rash that
 Molluscum Contagiosum desquamates
o poxvirus, umbilicated lesions w/ viral particles o ↑risk post-strep glomerulonephritis, rheumatic fever
o common in AIDS  Erysipelas: cellulitis w/ raised borders
 Rubeola  Tuberculoid
o Regular measles o Granuloma, intact cellular immunity, +lepromin skin test
o Prodrome 3 Cs: cough, coryza, conjunctivitis o Digital autoamputation, hypopigmented skin
o Rash after Koplik spots disappear  Lepromatous
o Giant cell pneumonia, acute appendicitis (kids), otitis media o organisms present, impaired cellular immunity, - lepromin skin
 Rubella test
o Maculopapular rash w/ discrete lesion, not confluent, fades in 3 o leonine facies
days  Acne Vulgaris
o Painful postauricular lymphadenopathy o Chronic inflammation of pilosebaceous unit
o Teratogenic o Comedones: open—blackhead, closed—whitehead
 Erythema Infectiosum Parvovirus: slapped face appearance o Androgen receptors located on sebaceous glands
 Polyarthritis in Adults: rubella & parvovirus o Propionbacterium acnes produces lipase
 Roseola
o HHV-6 Selected Fungal Disorders
o Most common viral exanthema children <2yo  Superficial Dermatophytes: live in stratum corneum
o Common cause of febrile convulsions  Wood’s Lamp: detects fluorescent fungal metabolites
 Varicella  T. tonsurans: most common cause in blacks, Wood’s Lamp
o Predominantly a childhood dz  M. canis/audouinii: most common cause in whites, + Woods Lamp
o Infectious—week before rash, week after rash until vesicles  Tinea capitis: oral terbinafine, topical imidazoles do NOT work
become crusted  T. rubrum: most common cause of all other tineas—except versicolor
o Macules, vesicles, pustules  Tinea corposris: annular, outer border raised/scaly, central clearing
o Complications: Kids—Reye syndrome, cerebellitis & Adults—  Tinea pedis: most common tinea infection, sweating important cause
penumonia, encephalitis, hepatitis  Tinea cruris: sweat most important in pathogenesis
 Herpes Zoster  Onychomycosis: raised, discolored nail, nail plate white, thick, crumbly
o Incidence ↑s w/ age, cancer, immunocompromised  Tinea versicolor: alteration in skin prigmentation, hypopigmentation or
o Painful vesicles/pustules follow sensory dermatomes hyperpigmentation
 M. furfur: tinea versicolor, “spaghetti” & “meatballs” KOH appearance
Selected Bacterial Disorders
 Candida skin infections: intertrigo, diaper rash, onychomycosis
 S. aureus
 Seborrheic dermatitis
o gram + coccus in clumps
o dandruff, M. furfur
o abscess, postsurgical wound infections, hidradenitis impetigo
o called cradle cap in newborns
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  Sporotrichosis  Malignant Melanoma: exposure to excessive sunlight at early age most
o SubQ mycosis, Sporothrix schenckii significant risk factor
o Traumatic implantation  Radial Growth Phase: initial phase of invasion spread laterally in papillary
o Chain of suppurating lymphocutaneous nodules dermis, no metastatic potential
 Cutaneous Larva Migrans  Vertical Growth Phase: final phase of invasion, penetrate reticular
o Dog/cat hookworm—Ancyclostoma dermis, metastatic potential
o Larvae penetrate skin, serpiginous tunnels  ABCD Signs of Melanoma: asymmetry, borders irregular, color Δs,
 Chigger diameter ↑
o Small, red mite  Superficial Spreading Melanoma: most common type of malignant
o Intensely pruritic, red popular/urticarial/vesicular rash melanoma
 Human Itch Mite  Lentigo Maligna Melanoma: elderly, occurs on face, least likely to have
o Sarcoptes scabiei vertical phase
o Females bury between fingers  Nodular Melanoma: no radial phase only vertical phase
o Eggs cause pruritus  Acral Lentiginous Melanoma: not UV related, palms/soles, Asians & AA
o Infants—no burrows, rash on palms, soles, face  Prognosis in Malignant Melanoma: depth of invasion most important
 Head Louse  Melanoma Prevention: sunscreen >15 SPF, protect skin w/ clothing
o Pediculus humanis capitis
o Lay eggs—nits—on hair shafts Benign Epithelial Tumors
 Body Louse  Seborrheic Keratosis: most common benign tumor in older people
o Pediculus hominis corporis  Leser-Trelat Sign: phenotypic marker for stomach adenocarcinoma
o Adutls live on skin & breed in clothing  Ancanthosis Nigricans
o Treat clothing NOT pt o Velvety pigmented lesion, common in axilla
 Phthirus pubis: louse, pubic hairs o Associations: metabolic syndrome, insulin receptor deficiency,
 Bedbug: Cimex lectularius, common infest dwellings, feed on blood Polycystic Ovary Syndrome, Stomach cancer
 Keratoacanthoma
Melanocytic Disorders o Benign tumor that histologically mimics squamous cancer
 Solar Lentigo: common in elderly, liver spots, ↑melanocytes o Appears w/in 4-6wks, disappears w/in 6mo
 Freckles: normal # of melanocytes w/ ↑ in melanosomes  Epidermal Inclusion Cyst
 Vitiligo: autoimmune destruction of melanocytes o derives from epidermis of hair follicle
 Albinism: deficiency of tyrosinase, absent melanin in melanocytes o Locations: face, base of ears, trunk
 Melasma: malar hyperpigmentation pregnancy/oral contraceptives  Pilar Cyst
 Nevus Cells: modified melanocytes o Derives form hair root sheaths
 Junctional Nevus: most common nevus in kids o Located on scalp & face
 Intradermal Nevus: most common nevus in adults  Fibroepithelial Tag: flesh colored tag of skin w/ stalk, common in elderly
 Dysplastic Nevus Syndrome: majority develop malignant melanoma
 Melanoma Premalignant & Malignant Epithelial Tumors
o Leading cause of death dt skin cancer  Actinic (solar) Keratosis
o Most rapidly ↑ cancer worldwide o Squamous dysplasia, precursor for squamous cancer
o Lesions recur after being scraped off
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  Basal Cell Carcinoma o associated w/ hepatitis C
o Most common malignant skin tumor  Psoriasis
o Invade but do NOT metastasize o Strong HLA relationship
o Arise from basal cell layer o Unregulated proliferation of keratinocytes
 Squamous Cell Carcinoma o Commonly preceded by strep pharyngitis
o Excessive exposure to UV light, actinic keratosis, scar tissue o Erythematous plaques w/ silver scales
o Most common cancer complicating immunosuppressive therapy o Rash in areas of trauma (ie elbows), pitting of nails
 BCC—favors upper lip o Munro microabscesses in stratum corneum, Auspitz Sign
 SCC—favors lower lip  Piyriasis Rosea: herald patch (plaque) followed by rash in “Christmas
Tree” distribution
Selected Skin Disorders  Erythema multiforms (EM)
 Ichthyosis vulgaris: most common inherited skin disorder, ↑stratum o triggered by infection (mycoplasma, HSV) or drugs
corneum o rash has targetoid appearance, palmar involvement
 Xerosis: most common cause of dried skin & pruritis in elderly o Stevens-Johnson Syndrome involves skin & mucous membranes
 Skin Δs Elderly o Panniculitis involving anterior portion of shins
o ↓hair follicles, sweat glands, skin thickness o Systemic fungal infectios, TB, leprosy, sarcoid, pregnancy, Oral
o ↓dermal collagen/elastic tissue but ↑cross-linking Contraceptives
 Polymorphous Light Eruption  Granuloma annulare: association w/ diabetes mellitus
o Most common photodermatitis  Porphyria cutanea tarda
o Common in Native Americans o deficiency uroporphyringoen decarboxylase, association w/ HCV,
o Rash occurs abruptly after sun exposure alcohol abuse
 Eczema o Precipitating Factors: HCV, alcohol abuse, Oral Contraceptives,
o Group of inflammatory dermatoses Fe
o Acute weep, chronic dry  Urticaria
 Atopic Dermatitis: Type I IgE-mediated hypersensitivity o Mast cell release of histamine
 Contact Dermatitis: type IV hypersensitivity, poison ivy, nickel in earrings o May exhibit dermatographism
 Tetracycline: drug w/ photosensitizing effects  Cherry Angiomas: bright red papules, invariably present in elderly
 Lupus Skin Involvement: immunocomplexes along basement membrane  Acne rosacea
 Pemphigus Vulgaris o causal relationship w/ mite—Demodex folliculorum
o IgG antibodies against desmosomes between keratinocytes o pustules & flushing of cheeks, rhinophyma
o Intraepithelial vesicles, +Nikolsky sign, basal cells resemble  Pyoderma gangrenosum
tombstones o Ulcerative cutaneous dz associated w/ systemic dz
 Bullous pemphigoid: subepidermal vesicles, - Nikolsky sign o Ulcerative colitis/Crohn’s Dz, MPD, RA
 PV & Bullous pemphigoid: type II hypersensitivity rxns o Dysregulation of immune system
 Dermatitis herpetiformis (DH): associated w/ celiac dz, subepidermal
vesicles w/ neutrophils Selected Skin Disorders in Newborns
 Lichen planus (LP)  Erythema toxicum: 30-70% newborns, self-limited
o pruritic, violaceous, flat-topped papules  Sebaceous hyperplasia: yellow-white papules on face, self-limited
o oral mucosa commonly involved, Wickham’s Striae  Milia
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 o superficial epidermal inclusion cysts, pearly white papules  Papilledema: sign of cerebral edema
o called Epsteins pearls when in mouth  Intracranial HTN: papilledema, bradycardia, projectile vomiting, HTN
 Miliaria crystalline: pinpoint clear vesicles, sweat in occluded sweat  Pseudotumor Cerebri
glands o ↑ICP w/out evidence of tumor or obstruction
 Miliaria rubra: prickly heat, erythematous papulovesicles o Most common in young obese women
 Both types of miliaria respond to cooling o ↓CSF resorption in arachnoid granulations
 Mongolian Spot o Headache, blurry vision, diplopia
o Bluish black to gray spot, dark-skinned babies  Cerebral Hernation: complication of intracranial HTN
o Disappears in preschool years  Subfalcine Herniation: compression of anterior cerebral artery
 Uncal Herniation
Selected Hair & Nail Disorders o compression of CN III, Posterior Cerebral Artery, parasympathetic
 Anagen Phase: new hair shaft, hair length determined fibers
 Telogen Phase: resting phase, loss of hair o eye deviated down & out, mydriasis
 Estrogen: causes synchronous hair growth, risk for massive hair loss  Tonsillar Herniation: coning of cerebellar tonsils, cardiorespiratory arrest
 Massive Hair Loss: postpartum, Oral Contraceptives, stress,  Hydrocephalus: enlargement of ventricles
radiation/chemo  CSF: produced by choroid plexus, reabsorbed by arachnoid granulations
 Alopecia areata: hairs in areas of hair loss have appearance of  Communicating Hydrocephalus: ↑production CSF, ↓reabsorption CSF
exclamation marks  Noncommunicating Hydrocephalus: obstruction CSF outflow into
 Nail Anatomy: lunula, nail plate, nail matrix ventricles
 Psoriasis: nail pitting  Sylvius Aqueduct Blockage: most common cause of hydrocephalus in
 Fe Deficiency: koilonychias—spoon nails newborns
 Splinter Hemorrhages: subacute infective endocarditis, trichinosis  Hydrocephalus
 Mees Lines: transverse white lines, arsenic poisoning, systemic illness o Children: ventricles dilate & enlarge head circumference
 Beau’s Lines: transverse grooves parallel to lunula, infections o Adults: no ↑ in head size, dementia, gait disturbance, urinary
 Subungual Hematoma: blood clot under nail plate, confused w/ acral incontinence
lentiginous melanoma  Hydrocephalus ex vacuo: dilated ventricles 2° to brain atrophy
 Normal Pressure Hydrocephalus
o dilated ventricles + triad—dementia, urinary incontinence, wide-
based gait
o potentially reversible cause of dementia w/ shunting
Nervous System & Special Sensory Disorders o Wide-Based Gait/Urinary Incontinence: stretching of sacral
motor fibers
Cerebral Edema, Pseudotumor Cerebri, Herniations, Hydrocephalus o Dementia: stretching of limbic fibers
 Cerebral Edema: intracellular & extracellular types
 Intracellular Edema: ↓serum Na (SIADH), dysfxnal Na/K ATPase pump Developmental Disorders
(global hypoxia)  Neural Tube Defects: failure of fusion of lateral folds of neural plate,
 Extracellular Edema: ↑vessel permeability, meningitis, metastasis ↑AFP
 Respiratory Acidosis, Hypoxemia: ↑cerebral vessel permeability,  Maternal Folate level must be adequate BEFORE pregnancy
enhance cerebral edema  Anencephaly: absence of brain, maternal polyhdraminos
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  Spina Bifida Occulta: dimple/tuft of hair overlying L5-S1
 Meningocele: cystic mass w/ meninges CNS Vascular Disorders
 Meningomyelocele: cystic mass w/ meninges & spinal cord  Global Hypoxic Injury
 Arnold-Chiari: caudal extension medulla/cerebellar vermis through o Hypotensive episodes, chronic CO poisoning
foramen, hydrocephalus, meningomyelocele, syringomyelia o Complications: cerebral atrophy, watershed infarcts, stroke
 Dandy-Walker: partial/complete absence of cerebellar vermis, cystic  Red Neurons: apoptotic neuron
dilation of 4th ventricle, hydrocephalus  Hypoglycemia: ≈effect on brain as global hypoxia
 Syringomyelia  Strokes: ↑ incidence w/ age
o degenerative dz of spinal cord, usually cervical cord  Atherosclerotic Stroke
o cervical cord enlargement, fluid-filled cavity o Most common overall stroke, ischemic type
o ↓pain/temp sensation in hands, loss intrinsic hand muscles o Pale infarction extending to periphery of cerebral cortex
o MRI shows cervical enlargement & cavity o Most occur in MCA distribution
 Phakomatosis: neurocutaneous syndromes o Infarction w/ liquefactive (NOT coagulative) necrosis
 Neurofibromatosis  TIA: transient neurologic deficit lasting <24hr, microembolization of
o Auto dom, incomplete penetrance plaque material
o Both Type 1 & 2—café au lait macules, neurofibromas  Amaurosis Fugax: temporary loss of vision, embolic material trapped at
 NF1 bifurcation of retinal vessels
o optic gliomas, Lisch Nodules, axillary/inguinal freckling  MCA Stroke: contralateral paresis/sensory loss in face/upper extremity,
o associations: pheochromocytoma, Wilm’s Tumor, CML (juvenile) head/eyes deviate to side of lesion
 NF2: bilateral acoustic neuromas, juvenile cataracts, meningiomas  ACA Stroke: contralateral paresis/sensory loss in lower extremity
 Tuberous Sclerosis  Embolic Stroke
o Auto dom
o Ischemic type of stroke dt embolism
o Mental retardation, hamartomas in brain, kidneys
o Hemorrhagic infarction extending to periphery of cerebral
o Key Findings: seizures, mental retardation, angiofibromas, ash
cortex
leaf lesions
 Intracerebral Hemorrhage
o Rhabdomyoma of Heart: highly predictive of tuberous sclerosis
o complication of HTN, rupture of aneurysm
 Sturge-Weber Syndrome: vascular malformations of face, ipsilateral
arteriovenous malformation in meninges in some pts o basal ganglia most common location
 Rx HTN ↓ the incidence of stroke by more than 40%
Head Trauma  Subarachnoid Hemorrhage
 Coup Injuries: site of impact o Rupture of congenital Berry Aneurysm
 Contrecoup Injuries: opposite site of impact o Severe occipital headache, described as “worst headache
 Epidural Hematoma: temporoparietal skull fx, Middle Meningeal A. tear ever”
 CT Scan: imaging test of choice  Berry Aneurysms: jxn of communicating branch w/ main cerebral
 Subdural Hematoma artery
o Venous bleed between dura & arachnoid membranes  Lacunar Strokes
o Most often caused by trauma, ↑ risk w/ cerebral atrophy o microinfarction <1cm
o Tear of bridging veins producing venous blood clot o hyaline arteriolosclerosis dt HTN/diabetes
o CT Scan: imaging test of choice  Stroke Dx: CT w/out contrast—best test
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  Krabbe’s Dz: LSD, deficiency β-galactocerebrosidase w/ ↑ in β-
CNS Infections galactocerebroside in lysosomes
 CNS Infection: most dt sepsis
 Meningitis Degenerative Disorders
o inflammation of pia mater  Alzheimers
o ↑CSF protein—bacterial, fungal & some viruses o Most common overall cause of dementia
o ↓CSF glucose—bacterial, fungal o Sporadic late onset type—most common type
 Bacterial Meningitis: majority of organisms originate in nasopharynx o Prevalence ↑s w/ age
 Viral Meningitis: most often transmitted by fecal-oral route o ↑phosphorylated Aβ  neurotoxic
 Encephalitis: inflammation of brain, headache, drowsiness, coma o ↑ density of NF tangles & senile *neuritic) plaques in brain,
 Cerebral Abscess: hematogenous, contiguous spread occipital lobe usually spared
o Prominent early sign—decline in short-term memory
Demyelination Disorders o Presumptive dx w/ mental status testing, r/o all other causes of
 Demyelination: destruction normal myelin/oligodendrocyte, abnormal dementia
myelin  Activated GSK-3β: phosphorylates Aβ
 Multiple Sclerosis  Aβ
o Most common demyelinating disease o can be converted into amyloid, deposits in cerebral vessels
o CD4 T cells react against self antigens in myeline sheath, o metabolic product of APP, coded for on chromosome 21
cytokines activate macrophages that destroy myelin  Secretases: β-secretases followed by γ-secretases cleave APP  Aβ
o Genetic factors & environmental triggers  Insulin Degrading Enzyme: involved in clearance of Aβ
o Blurry vision dt optic neuritis—MS most common cause  Apo Gene E, Allele ε4: sporadic early onset AD
 Demyelinating Plaques: white matter looks like gray mater  Activated GSK-3β: hyperphosphorylates tau protein
 Sensory Dysfxn: paresthesis, loss pain/temperature/vibratory sensation  Neurofibrillary Tangle: hyperphosphorylated tau protein in neuron
 Upper Motor Neuron Dysfxn: spasticity, ↑deep tendon reflexes, muscle  PIN1 Enzyme: dephosphorylates hyperphosphorylated tau protein,
spasm, Babinski, weakness deficient in some cases of AD
 Autonomic Dysfxn: urge incontinence, sexual dysfxn, bowel motility  Senile (Neuritic) Plaques: core of Aβ surrounded by neuronal cell
dysfxn processes w/ tau protein
 SIN: scanning, speech, intention tremor, nystagmus  Amyloid Angiopathy: risk for cerebral hemorrhage
 Bilateral Internuclear Ophthalmoplegia: pathognomonic for MS,  Confirmation of AD: must be made at autopsy
demyelination of medial longitudinal fasciculus  Parkinsonism
 Lab: ↑CSF lymphs, CSF protein, CSF MBP, normal CSF glucose o Alteration in dopaminergic pathways involved in voluntary
 Oligoclonal Bands in High-Resolution Electrophoresis: sign of muscle movement
demyelination  Dopamine: principle NT in nigrostriatal tract
 Central Pontine Myelinolysis: dt rapid IV correction of hypNa00usually in  Idiopathic Parkinsons Dz
an alcoholic o most common cause of Parkinsonism
 Adrenoleukodystrophy: XR, peroxisomal enzyme deficiency in β- o depigmentation substantia nigra neurons, ↓dopamine
oxidation of fatty acids o Clinical: rigidity, resting tremor, bradykinesia
 Metachromatic Leukodystrophy: LSD, deficiency arylsulfatase A o Expressionless face, blepharospasm, seborrheic dermatitis
 Huntingtons Dz
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 o Auto dom, trinucleotide repeat disorder o Female predominance
o Atrophy of caudate nucleus, putamen, globus pallidus o Psammona bodies
o Chorea, oculomotor abnormalities  Ependymoma: 4th ventricle in kids & cauda equina in adults
 Friedreich’s Ataxia  Medulloblastoma: small cell tumor in cerebellum
o Auto rec, trinucleotide repeat disorder, deficiency frataxin  Oligodendroglioma: frontal lobe calcifications in an adult
o Degeneration Sites: dorsal root ganglia,  1° CNS Lymphoma: occurs in AIDS, EBV-mediated cancer
posterior/spinocerebellar/corticospinal tracts  Metastasis: most common brain malignancy
o Hypertrophic cardiomyopathy, type I diabetes mellitus
 Amyotrophic Lateral Sclerosis Peripheral Nervous System Disorders
o Degeneration of Lower & Upper Motor Neuron  Sensory Δs: demyelination—parethesias, “glove & stocking” distribution
o Atrophy of intrinsic muscles of hand—1st LMN sign  Motor Δs: axon degeneration—muscle fasciculations, atrophy
o No sensory Δs, bowel & bladder fxn intact  Charcot-Marie-Tooth Dz
 Werdnig-Hoffmann Dz: Lower Motor Neuron dz in children o Most common hereditary neuropathy
o Lower legs have “inverted bottle” appearance
Toxic & Metabolic Disorders  Guillain-Barre Syndrome
 Wilson’s Dz: cystic degeneration of basal ganglia o Most common acute peripheral neuropathy
 Lenticular Nucleus—putamen & globus pallidus in the basal ganglia o Preceding Infections: M. pneumonia, C. jejuni, viruses
 Acute Intermittent Porphyria o Causes ascending paralysis
o Urine colorless when 1st voided, exposure ot light produces color o Rx: IV immunoglobulin or plasma exchange
o Deficiency uroporphyringoen synthase, “bellyful of scars”,  Diabetes Mellitus: most common cause of peripheral neuropathy
peripheral neuropathy, dementia  Idiopathic Bell’s Palsy
o Rx: carbohydrate loading inhibits ALA synthase o Facial muscle paralysis dt inflammation of CN VII
 Vitamin B12 Deficiency: subacute combined degeneration, dementia o HSV most common association
 Wernicke-Korsakoff Syndrome  Upper Motor Neuron Bell’s Palsy: contralateral weakness lower face,
o hemorrhage in mammillary bodies sparing of upper face
o confusion, ataxia, nystagmus, ophthalmoplegia  Drugs: vincristine, hydralazine, phenytoin
 Alcoholics receiving IV infusion w/ glucose: supplement IV w/ thiamine  Vitamin Deficiencies: thiamine, pyridoxine, vitamin B12
to prevent acute Wernicke’s Encephalopathy  Schwannoma: benign Schwann cell tumor
 Acoustic Neuroma: schwannoma of CN VIII
CNS Tumors
 Glioblastoma Multiforme: most common 1° CNS tumor in adults
 Childhood Tumors: cystic astrocytoma & medulloblastoma—both in
cerebellum
 Clinical: headache, seizures, intracranial HTN
 Astrocytoma: most common neuroglial tumor
 Glioblastoma Multiforme: grade IV astrocytoma, often crosses corpus
callosum, hemorrhagic/cystic
 Meningioma
o Most common benign brain tumor in adults
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