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Step Notes 1) Wegner’s Granulomatosis a. TRIAD: i. Necrotizing Granulomas of Upper Airways (Nose), Kidney Dease, and Vasculitis b.

C-ANCA c. Correlations: i. Goodpastures also has c-ANCA 2) Rheumatic Fever: Strep Pyogenes (Beta Hemolytic, Bacitracin Sensitive G.A.S) a. Type 2 hypersenstivity i. Autoantibodies bind to antigens on cells and tissues ii. Strep antibodies cross react w/ antigens of heart, skin, and nerovus tissue b. 2 Major or 1 Major and 2 Minor i. Major 1. Migratory Polyarthritis 2. PanCarditis a. Endocarditis, Myocarditis, Pericarditis 3. Subcutaneous Nodules on the back of wrist, outside elbow, and front of knees 4. Erythema Marginatum 5. Sydenham Chorea a. Difficulty writing, involuntary grimacing, purposeless (choreiform) Movements of arm and legs, Speech impairment, Generalized weakness, Emotional Lability b. Hyperextended Joints, Hypotonia, Diminshed Deep Tendon Reflexes, Tongue Fasciculations (Bag of worms), Milk sign (relapsing grip demonstrated by alternate increase and decreases in tension w/ handshaking) c. If No Huntingtons  Dx is almost always Rheumatic Fever ii. Minor 1. Fever 2. Arthralgia: Joint pain w/o swelling 3. Increased ESR/C-Reactive Protein/Leukocytosis 4. Prolonged PR interval on EKG 5. GAS evidence: Antistreptoysi O titer, or DNAase

GENETICS
3) Genetics: a. Chromosomes: i. 1 1. Neuroblastoma in kids (1p) 2. Presenilin 2 ii. 2p (N-myc) 1. Neuroblastoma in kids: Worse prognosis iii. 3 1. Von Hippel Lindau: Hemangioblastoma of Retina, Cerebellum, and Medullua w/ Renal Cel Carcinomas 2. FGF3: Achondroplasia iv. 5 1. APC: FAP  5q2 (Adenomatous polyps after puberty) 2. Werding-Hoffmann Disease: Spinal Muscular Atrophy (child ALS) a. SMN1 surviavl motor neuron gene v. 6 1. HLA system vi. 7 1. Procollagen Type 1: Osteogenesis Imperfecta vii. 9 1. Tuber Sclerosis viii. 10: 1. MEN 2a,2b syndromes a. Pheocromocytoma, Medullary Carcinoma (amyloid), Primary HyperPTH b. Men 2B: i. Medullary Carcinoma of thyroid, Pheochromocytoma, Oral and intestinal ganglioneuromatosis (mucosal neuromas), and MARFANOID HABIUTS w/out HyperPTH ix. 11p13 1. WT1, Wilms tumor (Solid palpable renal mass) 2. MEN1 Gene: Werner’s Syndrome a. Parathyroid Adenoma (Muscle weakness and Muscle twitching w/ hyperca and decreased PTH) b. Pancreatic Tumor (Zollinger Ellison/Gastrinoma  increased Gastrin)\ i. Tumor producing Insulin, Glucagon, or VIP: 1. 1st Line Tx: Surgical Resection ii. Tumor Producing Gastrin: 1. Omeprazole: Proton Pump INhibitor c. Pituitary Adenoma (Prolactinoma  Hypogonadism/Lack Libido) i. Tx: Bromocriptine x. 12p 1. K-ras, colorectal cancer (Intermediate adenoma) xi. 13q14

1. RB gene: a. Germline mutations = Retinoblastoma and Osteosarcoma b. Somatic Mutation + Breast, lung, prostate, bladder cancer 2. Marfan’s: FBN-1 Fibrillin-1 3. BRCA 2 a. Tumor Suppressor Gene xii. 14 1. Presenilin 1 xiii. 15: 1. Prader-Willi/AngelMan xiv. 16 1. Tuber Sclerosis xv. 17 1. NF1: Gene product is Neurofibromin a. Neurofibroma, Café au lait, Lisch Nodules (pigmented nodules on iris) 2. P53 3. Procollagen Type 1: Osteogenesis Imperfecta 4. BRCA1 a. Tumor Suppressor Gene xvi. 18q 1. DCC/DPC/SMAD-2/SMAD-4, Colorectal Cancer (Late Adenoma) and Pancreatic Cancer (DPC) xvii. 19 1. Myotonic Dystrophy: Autosomal Dominant Trinucleotide repeat a. Sustained Involuntary Contractions  Can’t release grip 2. ApoE gene for Alzheimers xviii. 21 1. Down’s 2. APP - Amyloid Precursor Protein: ABeta 3. Superoxide Dismutase a. ALS subsets xix. 22 1. NF2: Gene product is Merlin (cytoskeletal protein similar) a. Schwannomas 2. 22q11: Truncus arteriosus, Tetralogy of Fallot 3. DiGeorge b. Trinucleotide Repeats i. Huntington’s (Chr4): CAG, Huntington Gene ii. Fragile X (ChrX): CGG, Fragile X Mental Retardation Protein: FMRP iii. Myotonic Dystrophy (Chr19): CTG, DMPK Gene -Myotonic Dystrophy Protein Kinase iv. Freidrich Ataxia (Chr9): GAA, FXN Gene: Frataxin v. Spinocerebellar Ataxia: CTG c. X-Linked Recessive: (Males only) i. G6PDH, Lesch-Nyhan, Hemophilia A, DMD, Wiskott-Aldrich, Bruton Agammaglobulinemia, SCID (sometimes), Hyper-IgM Sydnrom (HIGM) ii. Females rarely get X-linked recessive: Protected by second X chromosome

1. Get it if she inherits 2 diseased X chromosomes, or she has Turners w/ only one X chromosome (the diseased one) a. Turners = Short stature, Cystic Hygroma (Webbed neck), swelling of hands and feet (lymphedema) iii. Males have only one copy of X chromosome: Gene located on X  Genotypic frequencies equation is diffent for male and females: 1. In Males: P+q =1  Allele frequencies AND Genotypic Frequencies a. Incidence in males for X recessive = frequency = q b. Males have only a single X chromosome, each affected male has one copy of recessive mutation i. Incidence of X disease in male prtion of population is a DIRECT estimate of the gene frequency of population 2. In Females: a. Allele Frequency: P+Q =1 b. Gene Frequency: p^2 + 2pq + q^2 =1 iv. G6PDH, Lesch-Nyhan, Hemophilia A, DMD, Wiskott-Aldrich 1. DMD vs Becker Muscular Dystrophy a. DMD: Frameshift Deletions or Insertions i. Dystrophin Gene: See BMD in MS sction b. Becker Muscular Dystrophy: In-Frame Deletions or Insertions v. Wiskott-Aldrich: X-Recessive 1. WASP gene: Wiskott-Aldrich Serum Protein a. Participates in reorganization of hematopoeitic cell cytoskeleton in response to external stimui b. Hematopoietic cells cannot migrate in response to normal stimuli  Disease 2. TRIAD: THROMBOCYTOPENIA, ECZEMA, and Recurrent Sinopulmonry Infections a. Defective response to PLYSACCHARIDE Ags  Cytoskeletal defect in T cells that INHIBIT BINDING TO B CELLS 3. Skin Rash, Epistaxis, Sinopulmonary Infections, Bleeding deaths a. Persistent Itchy rash, refractory to topical cream i. Dry and lightly scaly skin w/ many excoriations ii. Chronic Eczematous dermatitis resembin atopic dermatitis b. Recurrent infections i. Suppurative Otitis Media, Pneumonia, Or Puruent skin infections c. Thrombocytopenic Purpura i. Petechiae and easy bruising ii. Bleeding outside of skin also occurs d. Hepatosplenomegaly and Cervical Adenopathy i. Splenectamy can help bleeding diathesis and increase platelet counts ii. Requires continuous antibiotic prophylaxis thereafter e. Often il w/ colds and ear infections, f. Bruises easily i. Bruises in various stages ii. Petechiae 4. Labs a. Low IgM and Low Platelts

b. High IgA and IgE in absence of IgM (vs. Ataxia Telangiectasia w/ Low IgA and IgE vs. Hyper IgM w/ High IgM and Low IgG and IgA) i. IgE, IgA and IgM synthesis are accelerated, but accelerated catablism results in decreased IgM while IgA and IgE remain elevated c. Normal/Low IgG 5. Most Dieh before age 6 due to infection, bleeding, or malignancy. 6. High association w/ Lymphoid Malignancies 7. Tx: Bone Marrow Transplant: Permanent Cure w/ same HLA type d. X-Linked Dominant i. Fragile X: Trinucleotide Repeat: CGG 1. Most Common heritable Cuase of MENTAL RETARDATION 2. ANTICIPATION 3. Poor eye contact, Chewing on Hands, Flapping Hands, MachroOrchidism 4. Delayed Social Motor and Language Skills 5. Long Narrow Face, Large Ears, and Flat Feet ii. Hypophosphatemic Rickets e. Autosomal Recessive: (Unaffected parents have children of both sexes w/ dx) i. Sickle Cell, Tay Sachs, Cystic Fibrosis (Chr 7q, CFTR chloride channel gene – deltaF508 – membrane channel mutation), PKU, Werdning-Hoffman Dx, Kartagener Syndrome, ChedikHigashi Syndrome (microtubules) 1. Kartagener: Dynein Mutation, cytoskeletal mutation  No side arms of microtubule doublets that allow motility of cilia a. Situs Inversus! b. Axonal transport problems, spermatozoa and respiratory epithelium issues. i. Retrograde transport of intracellulr materials in axons c. Chronic Upper and Lower respiratory tract disease i. Chronic Sinusitis, Bronchitis, Recurrent Otitis Media ii. Nasal Mucosas Pale and swollen w/ ucopurulent secretions iii. Retracted Tympnaic membrane w/ absent motility iv. Middle Ear Effusion d. Infertility, Defective bacterial clearence and recurrent pulmonary infctions (Bronchiectasis) i. Lung infections cause destruction o and subsequent dilation of bronchial walls ii. Abnormal and permanent dilation of bronchi that can be focal or diffuse 2. Cystic Fibrosis: a. Pancreatic Digestion  Prancreatitis i. Pancreas secretes digestive enzymes into mall intesting  essential in digestion of fats, proteins, and carbs ii. Reduced secretion of fluid into pancreatic ducts  Accumulation of enzymes in ducts  Activated in pancreatic ducts -> Autodigest pancreas  Inflammation, gallstones, cysts, internal bleeding, HYPOCALCEMIA f. Autosomal Dominant: i. Neurofibromatosis (Chr17/22), Ehlers-Danlos, Huntington, OI, Retinoblastoma, Idiopathic Hypertrophic Subaortic Stenosis, Familial Hypercholesterolemia, Marfan, von Hippel Lindau

(Chr3), Myotonic Dystrophy (chr19), Hereditary Angioedema (Deficiency of C1 esterase Inhibitor  Edema of mucosal surfaces), Acute INtermitten Porphyria (women), Achondroplasia 1. Achondroplasia: a. FGF-Receptor 3 (cell signaling): DE NOVO MUTATIONS i. Old father b. Inhibits chondrocyte proliferation c. Reduced size, disorganization, and premature sealing of growth plate d. Abnormally shortened limbs, while Chest is NORMAL e. Enlarged head w/ a bulging forehead 2. Osteogenesis Imperfecta a. Connective Tissue Dx: Collagen 1 b. Pleiotropy i. Multiple, seemingly unrelated, physical effects by a single Gentoype c. Excess or atypical fractures, scoliosis, basilar skull deformities, Blue Sclerae, Opalescent teeth, Laxity of Ligaments and skin g. Imprinting: i. Differential transcriptional activity of genes inherited from father vs. mother ii. Chromosome 15: Prader-Willi/Angelman 1. Deletion transmitted by father = Prader-Willi a. Hyperphagia, obesity, mental retardation 2. Deletion transmitted by mother = Angelman a. Severe mental retardation, Happy dispositin, Puppet like posture of limbs h. Trisomy i. 16: Most common Trisomy of Spontaneous Abortions (along w/ triploidy and 45 XO) 1. Only Turner Syndrome is viable ii. 21 (Down’s): Most common of Live birth trisomies 1. Increased risk of Acute Lymphoblastic Leukemia (older) and ALL in newborns. 2. Epilepsy, malformed head and neck (atlantoaxial dislocation  quadriparesis), Cardiac malformations (atrial and ventricular septal defects, tetralogy of fallot, PDA), Hypopharynx maldevelopment (aspiration pneumonia nd obstruction), duodenal atresia and imperforate anus. Acquired Autoimmune Hypothyroidism. 3. Infertile boys, but subfertile girls. 4. Alzheimer by mid-adulthood, strabismus, nystagumus, myopia. a. Associated w/ presence of an extra copy of gene for Amyloid Precursor Protienn (APP) on chromosome 21 i. Transmembrane protein expressed on cell surface ii. Alzehiemer Associated Amyloid ABeta Amyloid 1. Derives from Proteiolytic cleavage of APP 2. Accumulates w/in core fo senile plawues iii. b. Senile Plaques and neurofibriallyr tangles in Cerebral cortex and hippocampus 5. Cardiac Malformations due to inadequate migration of Neural Crest Cells to form endocardial cushion defects 6. Nondisjunction during Meiosis 1: 7. Moscaicism:

a. Nondisjunction occursd during MITOSIS (normally during meiosis) b. 47, +21/46) c. Pt presents different degree of characteristics of syndrome d. Higher IQ (~90, instead of 25-80) 8. Balanced Translocation a. Does not produce features in patient b. May affect progeny when translocated chromosome is added to a complement of otherwise normal chromosomes. 9. Robertsonian Translocation (4%): a. Full-Blown iii. 8 1. Live Birth Trisomy that is vary rare: Mosaic Karyotype necessary iv. 13: Patau Syndrome 1. Early developmental defect of prechordal mesoderm a. Origin of midface, eye, and forebrain b. Midline Disorders 2. Holoprosencephaly, Absence of olfactory nerve/bulb, Sloping Forehead, Severe Eye Defects, Deafness, and Cleft Lip and/or palate 3. Coloboma of Iris, scalp defects, dermal sinuses. 4. Polydactly 5. Cardiac Dextroposition and Septal Defects v. 18: Edwards 1. Second Most Common Trisomy of Live Births 2. Involves any organ system: 3. Hypertonia, Prominent Occiput, Small Mouth, Micrognathia, Short Sternum, HORSESHOE KIDNEY, ectopic pnacreatic tissue, Small pelvis, 4. Flexed Finges w/ overriding index fingers or third fingers 5. CLENCHED FISTS, ROCKERBOTTOM FEET, 6. Congenital Heart Disease i. Turner Syndrome: XO i. Short Stature, Webbed Neck, Shield Chest ii. Primary Amenorrhea, Infertility iii. COARCTATION OF AORTA iv. Knuckle-Knuckle-Dimple-Knuckle j. Klinefelter: XXY – Nondisjunction of sex chromosomes i. Sparse, Completely Hyalinized Seminiferous Tuubels ii. Hypergonadotrohic hypogonadism WITH GYNECOMASTIA and Small Testes iii. Complete Absence of Germ Cells iv. Males w/ tall stature, eunuchoid body, lack of male secondary characteristics 1. Hypogonadism testicular atrophy, high pitched voice, breast buds, 2. Elevated FSH and LH, Low Testosterone v. Rare Sertoli Cells and Leydig Cells present in LARGE CLUMPS b/w Hyalinnized tubules vi. Infertile, Barr Bodys, Gynecomastia, No Sperm, vii. Hypogonadism, Eunochoid Body w/ Lack of 2ndary male sex characteristics k. Sex Problems

i. Testicular Feminization Syndrome: 46 XY w/ Phenotypic Female 1. Genetically Determine Unresponsiveness to Testosterone l. DNA-Repair Deficiency i. Ataxia-Telangiectasia: ATM gene 1. Cerebral Ataxia, Telangiecctasia, and IgA and IgE deficiencies 2. Kinase involved in cell cycle mutation 3. 2-5 years 4. Combined Partial T and B cell deficiency m. Frameshift Mutation: i. Tay-Sachs: Insertion of 4 nucleotides into coding region for alpha subunit of Hexosamnidase A gene.  Premature stop codon 1. Ashkenazi Jews, 1/25 carrier rate, Death by 4 years, 2. Cherry red spot, can’t sit up, motor retardation, unresponsive to visual or auditory stimuli. Peripheral macular pallor w/ accentuation of reddishc color of choroid in macula of both eyes. n. Mitochondrial i. Leber Optic Neuropathy, MERRF (myoclonic epilepsy w/ myopathy) o. Congenital Malformations: i. DiGeorge: 3rd and 4th pharyngeal pouches fail 1. Thymic Hypoplasia or aplasia (No thymic shadow on Xray) a. Alpha-beta T cells not educated and selected for maturation b. Gamma-Delta T cells do NOT undergo thymic selection, NOT AFFECTED 2. Parathyroid Hypoplasia a. Hypocalcemia  Tetany 3. Facial and Cardiac Malfomrations a. Low set ears, Vertically elongated mouth and profile. p. Risks for genetics: i. MZ and DZ each have own risks: 1. If concordance rate in DZ is <1/2 of MZ  CANNOT BE Autosomal Dominant 2. If concordance rate in DZ is <1/4 of MZ  CANNOT BE Autosomal Recessive ii. Could be multifactorial and more complex iii. Risk for an affected sibling is higher than general poualtion, but lower than risk if strictly determined by genetics 1. Square root of risk in general population (Cleft Lip/Palate) q. Tests: i. PCR probes to Amplify Microsatellite Repeats = Paternity Testing 1. Microsatellites: Repetas of 2-4 bp – 150 bp 2. Called Simple Tandem Repeats (STRs) 3. Cannot detect Single-Base Pair Mutations ii. PCR to detect Mutations 1. Cystic Fibrosis/Sickle Cell iii. Chromosomal Karytoyping 1. Detect Chromosomal Abnormalities: Trisomy/Monosomy r. Locus Stuff i. Pleiotropy: Multiple seemingl unrelated phsycal effects caused by a single genotype

1. Osteogenesis Imperfecta ii. Allelic Heterogeneits: 1. Variable Expression in patients 2. Also in Osteogenesis Imperfecta iii. Locu Heterogeneity 1. Mutation in different Gene causes same disease 2. Also Osteognesis imperfecta: a. Chromosome 7 (Type 1 procollagen gene) b. Chromosome 17 (Type 1 procollagen gene) s. Reading DNA Sequencing Gels i. Bottom is +, smallest fragment goes to bottom ii. SO READ FROM BOTTOM UP! 1. Reads from 5’ to 3’ because that is how DNA is polymerized 2. This is the Template sequence iii. Then Original Sequence of the coding gene is the Complement of what is on the Gel 1. Draw in comlementary Anti-parellel sequence, which will be from 3’ to 5’ 2. So Then write that backwards to get original sequence code in 5’ to 3’

Micro
4) Micro: a. Bacterial Genetics i. Hfr donor transfer Chromosomal genes to F1. OriT first, Tra last operon (least transferred) 2. Likelihood of recombination is function of placement of genes and time 3. Mechanism of genetic exchange that involves transfer of chromosomal DNA from one cell to another during conjugation a. Since linear piece of DNA is transferred, it must be followed by HOMOLOGOUS RECOMBINATION, requiring RECOMBINASE A (recA) ii. Conjugation with Plasmids exist in F+, not in Hfr 1. No time dependency, all gnees transferred 2. Bacterial Resistence: Plasmids mostly (chromosomal mutations with Fluoroquinolones) 3. Donation of plasmids from F+ to F4. Only means of DNA transfer that DOES NOT Require Homologous Recombinatin to occur as a final step 5. Homologous recombination is process by which linear pieces of DNA w/ sequence homology for recipient cell’s chromosme may be stably integrated by recombinase A enzyme (product of recA gene) iii. iv. Bacteriophage Transfers: 1. Cholera Toxin, Salmonella O Ag, Botulinum Exotoxin, Strep Pyogenes exotoxins, Diptheria Toxin, Shiga Toxin. 2. Temperate Phage: Specialized Transduction = Error of Phage Life Cycle a. Genes transferred are closest to insertion site of phage. b. Toxins: i. Anthrax Toxin: cAMP inducer

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1. Three component toxin: B component for both a. A single binding component (protective antigen) i. PA  Protective antigen b. Two Active Componenets i. Edema Factor: EF  Adenylate Cyclase  Fluid loss from cells ii. Lethal Factor: LF  Endoprotease  Apoptosis 2. Decreses phagocytosis, causes edema, kills cells 3. Black necrotic lesion Botulinum Toxin: 1. Neurotoxin that prevents neurosecretory vesicles from fusing w/ synaptic membranes 2. Prevents RELEASE of Ach Cholera Toxin: cAMP inducer 1. Acts to Increase Adenylate Cyclase Activity by Ribosylation of GTP-binding Protein C. Perfringens: Alpha Toxin - Cytoysin 1. Lecithinase damages cell membranes and causes myonecrosis 2. Gas Gangrene Diphtheria Toxin – Protein Synthesis Inhibitor 1. ADP Ribosyl Transferase Inactivates Elongation Factor 2 (eEF-2) 2. Targets Heart nerves, epithelum 3. Inhibits Protein Synthesis E. Coli 1. Labile Toxin: cAMP inducer a. ADP ribosylation of GTP-binding protein stimulates adenylate cyclase and induces cAMP b. SIMILAR TO CHOLERA 2. Stabile Toxin: 3. Verotoxin (Shiga-Like) – Protein Synthesis inhibitor a. Interferes w/ 60S robsomal subunit to inhibit protein synthesis Pertussis Toxin: - cAMP inducer 1. Fluid Loss by ADP Ribosylating Gi  leads to increase in cAMP 2. Histamine Sensitizing, Lymphocytosis promotion (inhibits chemokine receptors) 3. Islet activation Pseudomonas: Exotoxin A 1. ADP Ribosylase inhibits eEF2, blocks protein Synthesis a. Primarily in LIver 2. Creates lesion with BLACK, Necrotic Center and Raised Erythematous edges (Ecythyma Gangrenosum) 3. SIMILAR TO DIPHTHERIA TOXIN (primarily in heart and nerves) Salmonella Typhi: 1. IgG for Enteric Fever Shiga Toxin: 1. Decreses protein synthesis by Inhibitng the 60S ribosomal Unit 2. Enterotoxic, Cytotoxic, Neurotoxic Staph Aureus: 1. TSST-1: Superantigen a. Fever,

b. Super antigen crosslink T cell receptors and MHC2 of unrelated T lymphocytes and macrohpages i. Causes polyclonal stimulation and production of dangerous amounts of cytokines ii. Macrophages make: IL-1, Il-6, and TNF-Alpha iii. TH1 Cells Make: IL-2 and IFN-Gamma c. Induces IL-1, IL-6, TNF-a, IFN-gamma d. Decreases Liver clearance of LPS e. Causes fever, increased susceptibility to LPS, Rash, Shock, Capillary leakage f. Fever, Nausea, Diarrhea, Hypotension, and a DIFFUSE ERYTHEMATOUS RASH WITH DESQUAMATING ERYTHEMATOUS RASH OVER PALMS of HANDS i. Mediated by IFN – Gamma g. ASSOCIATED W/ TAMPONS IN YOUNG WOMEN (i.e. LNMP 2. Alpha Toxin: Cytolysin a. Pore former that causes membranes to leak xii. Streptococcal Erythrogenic Toxins: 1. Exotoxin A (pyrogenic) a. Superantigens to Increase Cytokine Production b. Phage encoded c. Causes Scarlett Fever: i. Complication of strep throat or strep wound ii. Fever, sore throat, rash, swollen, bright red tonsils, enlarged Anterior Cervical Lymph nodes, Diffuse, erythematous, symmetrical rash w/ rough, sandpaper-like texture iii. Palms and soles are SPARED iv. Circumoral pallor, STRAWBERRY TONGUE, Nausea and vomiting 2. Hyaluronic Acid Capsule (23 serotypes) a. Non-immunogenic, b. Makes it difficult for immune system to recognize infection c. Spreading factor d. Vaccine to capsular polysaccharide i. No protein  ONLY IgM response 3. M Protein a. Anti-phagocytic surface prtoein xiii. Tetanus Toxin 1. Neurotoxin that inhibits release of inhibitory Neurotransmitters: a. Glycine and GABA 2. IgG antibody against toxin xiv. c. Tests: i. 42 C or 107.6 F = Campy ii. 4 deg C or 39.2 F = Listeria or Yersinia Enterocolitica iii. MacConkey and Eosin Methylene Blue 1. Lactose fermenters (E. Coli) vs. non-Lactose (Salmonella and Shigella) iv. Sorbitol MacConkey 1. EHEC (no growth) vs. E.Coli (growth)

d. Treatment/Medications: i. Staph Aureus + Bacterial Pneumonia w/ Cavitary Lesions 1. Nafcillin or Oxacillin ii. Community acquired MRSA: 1. Clindamycin, TMZ-SMZ, Vancomycin a. CLINDAMYCIN CAUSES AAC  C. DIFFICLIE SUPERINFECTION i. Foul, Watery diarrhea iii. Topical Wound treatmint 1. Bacitracin: a. Bacteriocidal: Gram Postive and Gram b. Prevents transfer of mucopeptides into the growing cell wall and inhibits peptidoglycan synthesis c. Serious nephrotoxicity so only topical iv. Group B Strep in Neonatal Period 1. Prevent Mother  Child transmission: Ampicillin v. Strep Pneumonia: Gram + Diplococci 1. Azithromycin for Community Acquried Pneumonia 2. If Allergic to macrolide: 2nd Gen Cephalosporin: Cefuroxime 3. Pneumococcuss: a hemolytic and susceptible to optochin a. Blood/rust colored sputum, also fever, chills, ha, malaise, and pleuritic chest pain b. FIRST LINE TX: PENICILLIN OR AMOXICILLIN (B lactam) c. Resistant to Penicillin  Vancomycin for pneumococcus vi. Surgical Prophylaxis and Cellulitis 1. Cefazolin vii. Traveller’s Diarrhea: E. Coli, Shigella, Campy Jejuni 1. Abdominal Cramps, Vomiting, Low grade fever, Non Bloody Diarrhea (10-12 x/day) a. Fecal Leukocytes present 2. Adults: Fluoroquinolones: Ciprofloxacin, Ofloxacin, Norfloxacin 3. Children: Triepthorprim/Sulfamethoxazole viii. Pseudomonas: 1. First line For Bacteremia, Wound Infection, Pneumonia, Or Endocarditis: a. Antipseudomonal Penicillin + Aminoglycoside i. Piperacillin/Tazobactaam + Gentamicin b. For Penicllin Allergies: i. Aztreonam 2. First Line for CNS infections or Malignant Otitis Externa a. 3rd Gen Cephalosporin: Ceftazidime, Cefoperazone + Cefepime (4th gen) i. Ceftadizime Crosses the BBB and has Enterobacteriacea activity 3. Kid w/ CF and Pseudomonas Pneumonia a. If Only Option: Gentamicin (Severe gram – rod infections) 4. Other Options: a. Cefepime is 4th gen Cephalosporin but is VERY EXPENSIVE so not first line 5. DOC: Penicillin + Aminoglycoside a. Perperacillin-tazobactam – extended specturem penicillins (Ticar, carbeni, piper) ix. Anaerobic Infection

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1. Above Diaphragm: Lung Abscesses/ Aspiration Pneumonia a. Clindamycin 2. Below Diaphragm: a. Metronidazole, UTI: Shigella, Salmonella, Serratia, PCP 1. TMP-SMZ: Trimethoprim-sulfamethoxazole UTI: E. Coli and Staph Saprophyticus (MOST COMMON) 1. Acute, Uncomplicated UTI: 3 day Trimethoprim-Sulfamethoxazole OR Ciprofloxacin a. Ciprofloxacin if patient has Sulfa Allergy 2. Multi-Drug Resistant Urinary Pathogens (OR Fluoroquinolone allergy: a. 2nd line CEftraixone or Gentamicin i. 2nd line b/c many adverse effects (ototoxic for gentamicin) UTI + Enterococci 1. TMP-SMZ + Ampicillin UTI + Pregnancy 1. Use 1st Gen Cephalosporin: Cephalexin  Cystitis during pregnancy since it is not contraindicated and has sufficient coverage 2. DO NOT USE: a. TMP-SMX = Kernicterus b. Tetracyclines = Decreased Bone Growth and Dental Stains c. Fluoroquinolones = Cartilage damage d. Aminoglycosides = Ototoxic Lyme Dx, and Rickettsial Infections: Rocky Mountain, Typhus, 1. DOC: Doxycycline (tetracycline) 2. For Lyme Dx w/o Neurologic complications or heart block: a. Doxycycline and Amoxicillin with or w/o clavulanate 3. For Lyme Dx w/ Neurologic ocmplications or heart block: a. IV therapy Ceftriaxone (3rd gen Cephalosporin) Sickle Cell Pts: 1. Give Pneumoccocal Vaccine to aplenic pts bc capsulated organisms are dangerous. 2. Also: Salmonella and HiB Pyelonephritis: 1. Acute Pyelonephritis: E. Coli, Proteus, Klebsiella, and Enterobacter a. IV Ampicillin and Gentamicin 2. Mild Pyelonephritis and Cystitis: a. Nitrofurantoin Cholecystitis 1. Acute: Anaerobic, Gram negative OR Select Gram + 2. Cefotaxime/Cetriaxone a. Tx w/ Third Gen Cephalosporin: b. Broad Gram negative and Gram positive coerage Meningitis: H. Influenza/N. Meningitidis/Strep pneumonia/ L. Monocytogenes(Maybe Bacteroides/Salmonella as well) 1. Ceftriaxone (1st before you know) a. Also possibly Vanc 2. Chloramphenicol (Gray Baby Syndrome + Aplastic Anemia)

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3. Ampicilin a. Listeria Species in the Very Young and the Very Old Acne Vulgaris 1. Tetracycline/Doxycycline, 2. Spironolactone Neisseria: 1. Ceftriaxone, Ciprofloxacin, Tetracycline (gonorrhea) Chlamydia 1. Azithromycin 2. Tetracylcines (Doxycycline) Atypical Pneumonia: (Mycoplasma/Chlamydia/Legionella) 1. Azithromycin/ Erythromycin Ureaplasma/Chlamydia/Mycoplasma/Legionella/Campy 1. Macrolides: Erythromycin, Axithromycin, Clarithromycin Mycobacterium TB: 1. First Line: a. Isoniazid, Rifamin, Pyrazinamide, Ethambutol i. Give B6/pyridoxine w/ INH 2. Prophylaxis, 6 mo a. Isoniazid 3. Short Course Terhapy a. Pyrazinamide Listeria: 1. Ampicillin Enterobactericaee 1. Carbapenems: Imipenem Yersinia Enterocolitis: 1. Quinine, 3rd gen Cephalosporin, or TMZ-Sulfamethoxazole Fungal Infection: 1. <12: Azoles – Tinea Corporis 2. >12 Azoles or “-Fines” (terbinafine) – Tinea corporis, cruris, pedis Protozoa: Pneumocystosis -PCP 1. Trimethoprim-Sulfamethoxazole 2. IV Atovaquone or Pentamidine as backup Prtozoa: Toxoplasmosis: 1. Pyrimethamin and Sulfadiazine: Folate inhibition Protozoa: Leishmaniasis 1. Stibogluconate: Antimony Containig for Cutaneous Localized 2. Amphotocerin B for Cutaneous Diffuse or Visceral Protozoa: Amebiasis, Giardiasis, Trichomoniasis 1. Metronidazole 2. Furazolidone for Giardia as backup 3. Diloxanide for NONINVAISVE INTESTINAL AMEBIASIS Protozoa: Trypanosomiasis (Chagas Dx/African Sleeping sickness) 1. Nifurtimox: Chagas Dx 2. Arsenicals, Pentamidine, Suramin: African Sleeping Sickenss

xxxiv. Helminthic Worms: Enterobius Vermicularis, Trichuris Trichiura, Ascaris Lumbricoides 1. Mebendazole xxxv. Severe Leg Cramps: 1. Quinine xxxvi. CMV Retinitis: AIDs 1. Retinitis on fudnoscopy w/ white fluffy spots 2. 1st line: Ganciclovir: a. Activated by phosphorylation by viral protein thymidine kinases and acts as an ANALOG TO dGTP (same as Acyclover for Herpes Zoster). Forms guanine analog i. Guanine analog results in chain temriantion when read by viral DNA polymerase ii. Competitively inhibits th eincorporation of dGTP into replicating viral DNA b. Must monitor pts for Myelosuppresion and Nephrotoxicity nd 3. 2 Line (Ganciclover Resistant CNV): Foscarnet a. Does NOT require thymidine kinase b. Inhibits DNA polymerase at pyrophosphate binding site c. Toxic i. Renal e. Gram Positives i. Staph: Catalase Positive 1. Coagulase Positive: Aureus – Beta Hemolytic 2. Novobiocin: Saprophyticus (Resistant) vs. Epidermidis (Sensitive) 3. Cause of Bacterial Pneumonia w/ Pulmonary Abscess/Cavitary Lesion Complication a. Most destructive to lung tissu and cause cavitary lesion 4. ii. Strep: Catalase Negative 1. Optochin: Strep Pneumonaie (Sensitive) vs. Viridans (Resistant) 2. S. Pyogenes a. Associated w/ Pharyngitis, Poststreptococcal Glomerulonephritis, Rheumatic Fever, and Scarlete Fever, Erysipelas, Impetigo b. Group A Strep  Acute Rheumatic Fever: Strep Pharyngitis sequela c. Lead to Thickened, blunted, cardiac valve leaflets w/ fibrous bridging b/w leaflets and calcification 3. Strep Pneumonia: Diplococci a. Cuases Lobar Pneumonia, Rusty Sputum b. Fever, shaking chills, productive cough, rust spuutm c. Most Common cause fo Typical pneumonia in US d. NO GROUP b/c no C cell wall carbohydrate e. Encapsulated organism i. Resist phagocytosis ii. Opsonization (enhancement of Phagocytosis w/ IgG and/or C3b is most important mechanism for removing pathogens f. IgG mediated opsonization in spleen is immunologic mechanism i. Spleen slows down blood flow to allow for potential cell-cell interactions

f.

ii. Opsonization makes engulfment of slippery encapsulate dorganism occur up to 4,000 times faster than in absence g. Adult vaccine contains only capsular polysaccharides i. Stimulates ONLY IgM synthesis ii. Opsonizton would require IgM activation of complement and C3B fragments h. Infected patient  Isotype switching occurs and get IgG medated Opsoniazation 4. Strep Bovis: a. Group D strep i. Cell wall Carbohydrate composed of GLYCEROL TEICHOIC ACID b. Significant association b/w S. Bovis Bacteremia and Endocarditis w/ Carcinoma of Colon and other colonic diseases c. Every pt w/ S. Bovis bacteremia should undergo GI and Cardiac Evaluation i. Have underlying colonic malignancies 5. Eneterococcus Faecalis (group D) a. Endocarditis and Urinary and Biliary Tract infections 6. Strep Agalactiae a. GBS b. Number one cause of Neonatal Meningitis and Septicemia in US 7. Strep Mutans and Sanguis a. Viridans Strep  Normal Oral Mucosa flora b. Associted w/ Bacterial Endocaditis after invasive dental work and a preexisting heart valve defect Gram Negatives: i. E. Coli: 1. Lactose Fermenter 2. Salads, Unwashed fruits, Hamburger. 3. Human Colon as reservoir, ii. Yersenia: 1. Enterocolitica: a. Gram -, Oxidase -, Enterobacteriaceae b. Grow in Cool temp (70 deg) i. Can grow in 4 dec C, 40 deg F c. Pediatric Diarrhea!!! i. Seere Diarrhea, Dysentary, Appendicitis, Chronic Relapsing Ileocolitis ii. Ages 3-5 years, Leukocytes, Blood, and Mucus, Fever, and LRQ pain iii. Mini epidemics iv. Common in colder cimates v. Adults less infected than children vi. Tx: 1. Quinolone, 3rd Gen Cephalosporin, or TMZ-Sulfamethoxazole d. Pseudoappendicitis: Yersinia Enterocolitica: i. Fever and Severe RLQ pain – DDx of Appendicitis ii. Mesenteric Lymph Nodes are VERY enlarged + have Focal areas of MICROABSESSES iii. Transmitted via Contaminated Milk

iii. iv.

v.

vi.

vii. viii.

ix.

e. Intestinal Abscesses: Anaerobic Normal Flor (endogenous) Pseudomonas: 1. Gram -, Nonfermenting Rods: From Contaminated water/plastic 2. Burns, Hot Tubes, Plastic, Diabetics (skin lesion  ecthyma gangrenosum), Otitis Externat, Pneumonia in Cystic Fibrosis, 3. Necrotic Skin lesions in Burn patients and Diabetics a. Blue-green pus w/ Fruity odor 4. Osteomyelitis in Diabetecs 5. Capsule/Slime layer allows formation of pulmonary microcolonies a. Difficult to remove by Phagocytosis H. Influenza: 1. Gram – COCCOBACILLUS 2. Enacpsulated 3. Bronchitis in smokers a. So are Legionella and Moraxella catarrhalis Neisseria Gonorrhea 1. Over 1 million variants of pili: Absence of immunity to reinfection a. Pili protect against phagocytosis and mediate attachemtn to mucosal surfaces 2. Complement mediated destruction 3. TX: Ceftriaxone 4. Grow on Thayer Martin (VPN) OR ON CHOCOCLATE AGAR, but not Blood agar Bordatella Pertussis 1. Lymphocytic Response, NOT Leukocytic: I.e. T cells not neutrophils Campy Bacteria: 1. Gram Negative Curved Rods that grow at 42 deg C (107.6) a. Comma shpae 2. Acquired from Poultry 3. Bloody Diarrhea, Abd. Pain, and Feer 4. Fecal Leukocytes = Invasive Infection 5. Oxidase Positive a. Oxidase test to distinguish b/w Campy, Neisseria, H. Pylori, and Vibrio vs. Enterobacteriaceae (all Oxidase Negative) i. Flood Colonies w/ Phenylenediamine ii. If black deposit forms  Cytochrome C oxidase is being produces Vibrio Vulnificus and V. Parahaemolyticus 1. Gram-Negative, Comma-Shaped Rods Isolated on Alkaline Media 2. Raw Oysters a. Fever, Chills, Hypotension, Fluid-filled blisters that progress to muscle necrosis, ESP in lower limbs b. Also Hep A is acquired from raw oysters 3. Septicemia in patients after they eat raw shellfish 4. ONLY V. VULNIFICUS CAUSES GASTROENTERITIS PLUS CELLULITIS a. Wound infections, cellulitis, fasciitis, and myositis after exposure in seawater or cleaning shelffish 5. High risk

a. Liver dx, CHF, Diabetes, Renal Failure, Hemochromatosis, Immunosuprres 6. Tx: a. Tetracycline or 3rd Gen Cephalopshorin (Ceftriaxone/Cefoxtamine) x. Salmonella 1. Non-Lactose Fermenters, H2S Positive (Like Proteus) 2. From Poulty 3. Typhi  Typhoid Fever a. Not common in US b. Fever, Abdominal Rash, Splenomegaly c. DIARRHEA NOT CONSISTENT FEATURE 4. Enteritidis: a. SECOND MOST COMON Bacterial cause of Diarrhea in US (CAMPY IS FIRST) b. 6-8 hr incubation c. Nausea, Vomiting, Bloody, loose stools d. Associated w/ fever, abd pain, myalgia, HA e. NO SEPTICEMIA xi. H. Pylori 1. 95% of duadenal ulcers and 100% of gastric ulcers (if not due to NSAIDs/Aspirin) 2. High urease activity: a. Urease  Urea INTO AMMONIUM b. Ammonium allows bacteria to withistand acid environment of stomach + Damages Gastric mucosa i. Cytotoxic and directly damages epithelial cells in stomach ii. Increses permeability of gastric mucosa  ULcer g. Anaerobes i. Lung abscesses 1. Most common from aspirated oral flora in patients w/ compromised neurolgical status (anesthesia, coma, intoxication) or in depressed cough reflex a. Alcoholic, Elderly, Demented 2. Most common and typical Oral flora: a. Bacteroides, Fusobacterium and, Peptococcus h. Meningitis: HA, Fever, Vomiting, Malaise, Nuchal Rigidity i. Classification by CSF: 1. Increased Neutrophils = Acute Pyogenic Meningitis a. Gram + = Listeria in the young and old 2. Increased Lymphocytes Alone= Acute Lymphocytic Meningitis 3. Lymphocytes, Plasma Cells, Macrophages, and Fibroblass = Chronic Meningitis a. Glucose decreased, Protein Elevated ii. Treatment: 1. Ceftriaxone and Vancomycin Empirically 2. ADD AMPICILLIN IF LISTERIA IS SUSPECTED (Gram + Bacilli) iii. Neonates: GBS, S, Agalactia  CAMP Test Positivie, Bacitracin Resistant 1. Gram + cocci in chains in CSF 2. Fever, Lethargy, Seizures, Nuchal Rigidity, and Bulging Fontanelles 3. CSF: High neutrophil and Gram+’s

iv.

v. vi. vii. viii.

ix.

x.

i.

xi. xii. Pneumonia i. Classifications: 1. Lobar: Single Pulmonary Lobe a. Most common = Strep Pneumonia b. Small cases of: i. Klebisella, Staph, H. Influenza, Pseudomonas, and Proteus 2. BronchoPneumonia: Multilobar and Bilateral a. H. Influenza b. Klebsiella ii. Bacterial Pneumonia in context of Influenza: 1. Staph Aureaus, H. Influenzae, Strep Pneumonia a. Staph Aureus most likely to cause Cavitary Lesion/Pulmonary Abscess b. Pt w/ Flulike symptoms  Then gets High fever, Dyspnea, Severe caugh, and Mental Status Changes, c. X ray shows cavitary lesion in lung d. Tx: Nafcillin or Oxacillin iii. Chlamydia Pneumonia in Infants/neonates (4th day):

4. TX: 4th gen Penicillin/Ampicillin + 4th Gen Gentamicin a. Or Ceftriaxone and Vancomycin (w/ Ampicillin added if Listeria) 5. Then E. Coli/Listeria Children: Strep. Pneumonia / H.influenza B if unvaccinated 1. Alpha Hemolysis 2. Then HiB if child is unvaccinated Teenagers: Neisseria Meningitis Adults: Strep Pneumonia Old: 1. S. pneumonia, Gram -, Listeria (Gram + Bacili) Chronic Meningitis 1. Mycobaterium Tuberculosis (Classic Cause) 2. Syhpilis 3. Brucellosis 4. Chronic Fungal INfections HIV/Immunocompromised: 1. Cryptococcus Neoformans a. Monomorphic, Encapsulated Yeast b. CSF: Normal Glucose, Increased Protein, Increased Cells (WBC) 2. Aspergillus (less likely) Viral: 1. Enteroviruses (Coxsackie 2. HSV-2 (HSV-1 = Encephalitis) 3. HIV a. Cryptococcus, CMV, Toxo (Brain abscess), JC Virus (PML) 4. West Nile Virus 5. VZV Tuberculosis meningitis:

iv.

v. vi.

vii.

viii. ix. x. xi.

1. Conjunctivitis before Pneumonitis (Tachypnea, Hypoxemia, Crackles, Wheezing, and Eosinophlia). Staccato Cough (inspiration b/w each cough). 2. X-Ray: Scattered Infiltrates and Hyperinflation of lung. Bilateral Consolidation in lower lobes H. Influenza: 1. Pharyngitis, Pneumonia, Meningiits, and Epiglottitis: Unvaccinated Children b/w 3 months and 2 years Mycoplasma Pneumonia: 1. MOST COMMON Atypical Pneumonia in the young Pneumocystis Jiroveci (PCP) 1. MOST COMMON AIDS and immunocompromised Pnuemonia 2. Fever, Nonproductive cough, shortness of breath 3. Fungus w/ CD4<200 4. Attaches to and kills type 2 pneumocytes and damages alaveolar epithelium a. Serum leaks into alveoli  Exudate w/ honeycomb appearance on H&E 5. Silver Stain: a. Holes (from honeycomb) = Cysts and Trophozoites 6. Chest X-Ray: a. Patchy/Ground Glass appearance, SPARES LOWER LOBES b. Bilateral Diffuse Interstitial Infiltrates 7. ELEVATED LDH 8. Prophylaxis encouraged 9. Commonly Confined to lungs 10. Acquired Early, but remains dormant in healthy peeps 11. TX: a. FIRST Line: Trimethoprim-Sulfamethoxazole b. SECOND: Trimethoprim Plus Dapsone: Clindamycin Plus Primaquine OR Pentamidine c. THIRD: Atovaquone Strep Pneumoniae: (alpha hemolytic diplococcus) 1. MOST COMMON typical pneumonia in Adults 2. Capsular Polysacchardies are highly antigenic and type-specific a. Type scpecifc anticapsular antibodies result in effective Opsonization and host recovery b. Recoery is due to opsonizing antibody if left untreated c. Ascaris Lumbricoides: From eggs 1. Pneumonia and Eosinophilia w/ Ascariasis Varicella 1. Pneumonia w/ Pruritic Skin lesions Nosocomial Infection: Occurs 48 Hours AFTER admission Treatments 1. Klebsiella: 3rd Gen Cephalosporin a. Cefotaxime, ceftriaxone, ceftazidime 2. Legionella: Erythromycin (Macrolide)

j.

3. Pseudomonas: Penicillan + Aminoglycoside to improve efficacy of broad spectrum antibiotics Splenectomy: Danger of Encapsulated Organisms i. Low levels of IgG2 and IgM b/c splenic Lymphocytes are Major producers of these antibodies 1. Provide protection against encapsulated organisms ii. S. Pneumonaie, iii. H. Influenzae iv. Neisseria Meningitidis

k. Self limited and Malignant Otitis Externa – Pseudomonas: Gram -, Oxidase +, produce blue-green pigments i. Hearing loss, pain and discharge from ear, tender pinna, swelling and erythema of EXTERNAL auditory canal, and purulent discharge. Tympanic membrane not visualized ii. CT Scan: Temporal bone erosion, new bone formation, soft tissue swelling iii. OSTEOMYELITIS and CN PALSIES iv. Malignant external most common in OLD DIABETIC PTs 1. Pseudomonas also ASSOCIATED with: a. Septicemia, wound/burn infections, UTI in catheterized patients, pneumonia in Cystic Fibrosis l. Otitis Media: Ear pain, fever, and BULGING ERYTHEMATOUS TYMPANIC MEMRANE i. Most commonly caused by: 1. Step Pneumonia, H. Influenza, and Moraxella Catarrhalis ii. Strep Pneumoniae: Most common cause: Gram +, Catalase -, Alpha hemolysis 1. Polysaccharide Capusle protects agains phagocytosis 2. Pneumolysin: Destorys ciliated epithelial cells iii. H. Influenza: Gram – bacteria requiring factors X and V (from Staph Aureus) iv. S. Pyogenes and S. Agalactiae (GBS): Gram +, Catalase -, Beta Hemolysis 1. S. Agalactiae MOST COMMON cause of NEONATAL septicemia and Meninjitis m. Rash On Palms and Soles: CARS-H i. Cox A, Ricketssia, Syphillis, Herpes (Erythema Multiforme) n. Erythema Multiforme (Also SJS) i. Immune complex deposition in dermal blood vessels ii. Herpes, Enteroviruses, Mycoplasma Pneumoniae, Chlamydia, Histoplasmosis 1. With Herpes -> Antigens expressed by infected keratinocytes  triggers CD8+ Cytotoxic cells  Apoptosis of keratinocytes o. Echtyma Gangrenosum: i. Pseudomonas Lesion on Diabetic Patients: 1. Several weeks then becomes painful 2. Black necrotic center, Raised erythematous edges 3. eEF-2 Toxin  SIMILAR TO DIPTHERIA! a. Block Protein Synthesis p. TB: i. Primary TB: Asymptomatic 1. Lung lesions found in lower part of Upper lobes, oror upper part of lower lobes 2. Lung subajacent to pleura and mediastinal nodes inovled. ii. Active (Re-Infection) TB: Symptomatic

1. Fever, Night sweats, weight loss, cough 2. Lesions in APEX OF LUNG q. Fungi i. Cryptococcus Neoformans: Encapsulated Budding Yeasts 1. Meningitis in AIDs 2. Monomorphic  Same yeast form in both Environment and in Clinical Speciman 3. CSF: Increased Cells, WBC (Lymphocytes), Increased Protein, Decreased Glcose 4. Latex Particle Agglutination Best Test: Most Sensitive a. Detecs Capsular Antigens Shed into CSF 5. India Ink also used, but only 50% caught ii. Histoplasmosis: Intracellular yeasts w/in Macrophages 1. Birds or Bat Droppings 2. Mississipi/Ohio River Valley (Southeast US, even up to Pennsyl) 3. Not Easily communicable b/c intracellular a. Particularly w/in reticuloendothelial system and in lungs b. 2-4 micrometer yeast forms 4. At body temperature: yeast 5. At loer temp: Hyphal form w/ macroconidia and microconidia reproductive structures 6.Infection by spore inhalations iii. Blastomyces: Broad-Based Budding EYasts 1. Presents with Skin and Bone Lesions iv. Coccidioides: Spherules with Endospores 1. Fungal Meningitis in Immunocompromised 2. Southwest US: Sonoran Desert Zone, San Jaquin Valley, Arizone 3. Environmental Form: Arthroconidia 4. Diagnostic Form: Spherules v. Paracoccidioides: Budding Yeast with Pilot’s Wheel 1. Primary Pulmonary Disease 2. Central and South America vi. Aspergillus: 45 Degree Septate Hyphae 1. Opportunistic Infection, Meningitis. 2. Sinus infections and Meningitis vii. Zygomycosis: Rhizopus, Absidia, Mucor 1. Rhinocerebral Infections in Ketoacidotic Diabetics a. Following inhalatin of sporangiospores (normally harmless bread molds) b. Diabetes w/ severe prefrontal headache c. Sweling of orbit of eye and black nasal discharge d. Silver stain of discharge shows 90 branching hypae 2. Nonseptate (ribbon like) Hypahe w/ 90 deg branching a. Silver stain viii. Sporothrix Schenckii 1. Environmental = Hyphae w/ Rosettes of Microconidia 2. Rose gardner’s disease  Cutaneous Mycetoma w/ traumatic implantation ix. Candida: 1. Pseudohyphae, Germ tube test (inoculation into animal serum) growth

r.

2. Women a. Vaginal itch w/ white LUMPY vaginal discharge 3. x. Ringworm/Tinea Corporis = Tinea Circinata 1. Trichophyton Rubrum 2. Ring shaped lesions w/ an advancing scaly border + centra clearing a. Occasionally w/ Hyperpigmentation 3. KOH preparation of peripheral scales to reveal Hyphae 4. Get from infected CAT 5. Tx: a. Under 12: Topical conazole cream i. Clotrimazole, Miconazole, econazole b. Adults: i. Conazle, or topical agents: Naftifine, Terbinafine, Butenafine Vector Bacteria i. Lyme Dx: Borrelia Burdorferi (Ixodes Scapularis) - Spirochete 1. AV nodal heart block!! 2. Woods, Rash, Nuerologic, Cardiac, and/or Musculoskeletal 3. Erythema Migrans (bull’s eye lesion at bite) 4. Fever, Chills, myalgia, stiff enck, meningeal irritation (aseptic meningitis) 5. Bilateral Bel Palsy (Facial nerve) 6. Arthritis from an immune complex hypersensitivity (several months after) a. Exacerbation and remmision b. Knees and HIps ii. Ehrlichiosis: Ehrlichia Phagocytophilia 1. Ixodes Tick  ALSO BORRELIA BURGDORFERI (lyme) AND BABESIA MICROTI 2. Present similar to Rocky Mountain Spotted Fever (Rickettsia) but NO RASH 3. Intracellular Berry-Like Cluster of Organisms in Granulocytes = Diagnosis 4. Fever, Joint and Muscle pain, Photophobia and Malaise. 5. Absolute Leukopenia, Thrombocytopenia, and Increased Serum Transaminases 6. NO rash, ulceration, or petechiae. iii. Tularemia: Francisella Tularensis – Gram - Coccobacillus 1. Ulceroglandular Disease: Fever, chills, myalgias and arthralgias 2. Ulcer at Bite Site with black base, and LAD 3. Dermacentor Tick  ALSO RICKETTSIA 4. Tx: Streptomycin iv. Rocky Moutnain Spotted Fever: Fickettsia Rickettsii 1. Rash that starts on ankles and wrists and moves toward trunk a. Rash Generalized with Palms and Soles 2. Petechaie, Fever, Headache, Myalgias, Respiratory Symptomes 3. Positive Weil-Felix Test (Ab that agglutinate Proteus) 4. Dermacentor Tick  ALSO FRANCISELLA TULAREMIA v. Typhus, SCRUB type: Rickettsia Tsutsugamushi 1. Mites of Leptotrobium  Also Rickettsialpox (Rickettsia Akari) 2. Rash + Weil Felix + vi. Typhus, EPIDEMIC: Rickettsia Prowazekii

vii. viii. ix.

x.

xi.

1. Rash from Trunk to Extremities: NO PALMS SOLES OR FACE 2. Petechia  Purpura 3. Fever, Headache, Myalgias, and Respiratory Symptomes 4. Weil-Felix Positive Typhoid Fever: Salmonella 1. Bacteremia, Abdominal Rash, Malaise, NOT REALLY DIARRHEA Brucella: 1. Brucellosis after ingestion of contaminated milk or contact w/ infected livestock Leptospira 1. Leptospirosis and Weil Disease 2. Ingest or aerosol of water contaminated with animal urine 3. Fresh water, High Fever, renal impairment, Mild hepatitis, Petechiae, Lower leg, Flank pain, proteinuria, myalgia Bartonella: 1. Cat Scratch Fever 2. LAD (chronic), and Basillary Angiomatosis (immunosuppressed) a. Characteristic Mullbery lesion on skin and subcutaneous tissue (AIDs pts) Tropheryma Whippelii 1. Whipple Dx = Small Intestinal Malabsorption syndrome due to infection

s. Viruses i. Replication: 1. ALL RNA Viruses Replicate in the Cytoplasm except Orthomyxo (influenza)  can replicate in Enucleated cells a. Orthomyxo do transcription and RNA replicationin nucleus b/c they canniblzie capped 5’ termini of cellular RNSs for use as primers for viral mRNA transcription 2. ALL DNA viruses replicate in Nucleus except for Poxvirus (cytoplasm) ii. Viruses That Need Polymerases: 1. –RNA, dsRNA, Poxviruses, Retroviruses iii. Herpes: 1. HSV  Retrograde into Sacral Ganglia or Trigeminal Ganglia a. Lytic infectins in mucoepithelial cells b. Herpes Encephalitis = Hemorrhagic Necrosis of Temporal Lobes = HSV 1 c. Neonatal Encephalitis = HSV 2 i. Also get vesicular skin lesions, Hepatitis, Pneumonitis, DIC, Temprature instability, Lehtargy, Hypotonia, Respiratory Distress, and Apnea d. Infect Ganglion cells: i. Particularly satellite cells around ganglion cells in Dorsal Root ganglia or Trigeminal Ganglion e. 2. VZV/Chicken Pox  Dorsal Root Ganglion 3. CMV  Mononuclear Cells a. Heterohpile NEGATIVE Mono b. Transmitted by Leukocytes in Blood or Perinatal in utero, intrapartum, or postpartum c. Infants:

iv.

v.

vi. vii. viii.

i. Blueberry Muffin Babies, Multiple petechae, ecchymoses, pmacules, papules, plaques ii. BlueBerry Muffin Baby = Cutaneous Hemorrhages iii. Intrauterine Fetal Infection TRIAD: 1. Cutaneous Hemorrhages (Blueberry Muffin), Deafness, Periventricular CNS Intracerebral Calcifications 2. Petechial Rash, Cutaneous Hemorrhagic Lesions, THromboyctic Purpura, Jaundice, Microcephaly and Hepatosplenomegaly d. Adult: i. Influenza-Like syndrome w/ Mild Fever and LAD e. Immunosuppressed i. Severe Dx: RETINITIS, Pneumonia, Encephalitis, Adrenalitis, GI Ulcers f. Cytomegalic ells: Abnormally large cells w/ large PURPLE intranuclear INlcuison and Granular Basophilic INlcusion in cytoplasm 4. EBV  B Cells a. Transeint erythematous, maculopapular rash Rubella: 1. Teratogenesis in Utero: 2. Congential Rubella Sydnrome: a. PDA, Pulmonary Stenosis, Microcephaly, Cataracts, and Deafness Neonatal Syphillis 1. Transplacentally 2. Perforated Palate, Notched Teeth, Maculopapular Bronzing Rash, Bone Deformations, and CNS damage Neonatal Toxo: 1. Retinochoroiditis of Late Onset, Hdyrocephalus, Intracerebral Calcifications Reverse Transcriptase: RNA-Dependent DNA Polymerase and ALSO 1. TELOMERASE HIV 1. Reservoirs of HIV a. Follicular Dendritic Cells in Germinal Centers of Lymph Nodes b. Dendritic Cells have Receptros to the Fc portion of Igs that serve to trap HIV virions coated w/ Anti-HIV antibodies c. HIV coated particle retain ability to infect CD4 T cells as they traverse dendritic cells 2. HIV Encephalitis: a. Encephalitis seen in AIDS patient b. Direct involvement of CNS by HIV i. Dementia, Incontinence, Seizures ii. Microglial nodules = Collections of lymphocytes, histiocyte,s and microglial cells w/ variable numbers of MULTinucleated giant cells 3. Testing: a. Reverse Trancriptase PCR: Detection of Viral Load b. DNA-PCR: Detection of pro-viral DNA early in infection or in newborns of mothers who are HIV positive c. ELISA: Screening Test for HIV infetion (Detects antibodies to proteins)

ix.

x.

xi.

xii.

d. Western Blot: Confirmatory test for HIV (Specific Antibody to proteins) 4. Mother-Child a. All children born to HIV positive mothers are born with POSITIVE ELISA AND WESTERN BLOT i. Mother IgG antibodies against virus transfer to her bloodstream across placenta b. Cannot diagnose in utero infection using these test i. Only use PCR or viral cultures of infant tissue c. Only 20% of children actually inected: Placenta is an effective barrier HPV 1. Koilocytosis, Nuclear enlragement, Perinuclear Vacuoles, Condyloma a. Koilocytosis = Mild Atypia = Low grade squamous intraepithelial lesion 2. 16, 18  Cervical Carcinoma a. E6 and E7 proteins inactivate p53 and Rb tumor suppressor genes 3. 6, 11  Low risk growth Pox Virus: 1. Ds DNA; REPLICATES IN CYTOPLASM 2. CARREIS DNA-DEPENDENT RNA POLYMERASE into cell 3. Eosinophilic Cytoplasmic Inclusion bodies 4. Molluscum Contagiosum a. Benign, Umbilicated Warts in School-aged children b. UMBILICATED, FLESH COLORED PAPULES on trunk c. Wrestiling teams 5. Parvo Virus: 5th disease = Erythema Infectiosum 1. Human to Human spread (no animals for this one) 2. Disease contagious prior to onset of facial rash 3. Initial symptoms (during contagion) = Nonspecific constitutional a. Fever, Myalgia, Lethargy, Coryza, Pharyngitis, and Abd Pain 4. Typical Slapped Cheek Rash begin = NOT COntagioius a. Erythematous Cheeks  Upper part of body becomes red and reticulated (lacy appearance of rash) b. Can come and go for 3 weeks 5. Causes: a. Aplastic Anemia (Crisi in sickle cell) b. IN pregnant women in 1st trimester: i. Fetus w/ aplatic anemia = Non immune Hydrops Fetalis ii. Infects Immature Erythrocytes  Sever anemia  Death by cardiac failure ArboViruses: 1. Hanta Virus = Bunyaviridae = Sin Nombre Virus a. Deer Mouse  Inhalation of aerolized secretions b. Fever, Myalgia, RAPID DEVELOPMENT OF RESPIRATORY FAILURE  DEATH i. Prodrome = Fever, Myalgia, GI disturbances ii. 4-5 days later: Respiratory Sypmtoms = Cough, Dyspnea, Tachypnea iii. Rapid progression to ARDS and Death

c. Four Corners states: i. New Mexico, Arizona, Colorado, Utah 2. California Encephalitis a. Mosquitos b. Children Younger than 10 years c. Myalgias and arthralgias, Fever, HA, PHOTOPHOBIA, Nausea, and Vomiting d. SEIZUREs in infants and Young e. Midwest US xiii. Hepatitis 1. Hep A = Picorna a. Fecal-Oral transmission b. Not chronic 2. Hep B = Hepadna DNA virus a. Chronic Infections and Hepatocellular Carcinoma b. Vaccine can eliminate Hepatocellular Carcinoma c. ONLY TUMOR VACCINE AVAILABLE? d. Test for HBsAg In Pregnant woman w/ previous infection i. Negative if completely recovered ii. Positive if Carrier 3. Hep C = Flaviviridae a. Transmitted sexually or parenterally b. Chronic and Carcinogenesis 4. Hep E Virus: a. Hepeviridae family b. High mortality in pregnant women c. Enterically transmitted acute hepatitis i. India, Asia, Africa, Central America xiv. Coxsackie Virus: 1. Hand, Foot, and Mouth disease a. Coxsackie A: Disseminated disease: Heart, Liver, Brain i. Disease RESOLVES few weeks later (vs. CMV) ii. Always dilated cardiomyopathy xv. Measles 1. Subactue Sclerosing Panencephalitis (SSPE) a. Brought b/c of behavioral changes, mild intellectual deterioration, and “laziness” i. Develops progressive clumsiness, frequent involuntary jerky movmemtns ii. Myoclonus, Ataxia, Ocular abnormalities, spasticity, coma iii. EEG shows periodic activity iv. Alterations of white mater of both hemispheres and brain stem b. Lab: CSF shows Oligoclonal bands of IgG on electrophoresis c. Cause: i. Persistent, possibly abnormal measles virus and to Autoimmune damage caused by antibodies directed against virus d. Normally 2 years of age or younger get measles, and then 6 years later get SSPE

xvi.

xvii.

xviii. xix.

xx.

xxi.

xxii.

e. Death in two years 2. Infect Oligodendrocytes (like JC virus) 3. Causes Syncytia Polio 1. Fecal to oral 2. Acute Symptoms a. Malaise, HA, fever, Nausea, Abd pain, Sore throat 3. Chronic: Lower Motor Neuron Dx a. Degeneration of Ventral Horn Motor Neurons b. Fasciculations, Muscle weakness, Muscle atrophy, Hyporeflexia Viral Signs: 1. Nuclear Enlargment w/ Perinuclear Vacuolization: HPV Condyloma a. Koilocytosis b. Condensed nuclei w/ irregular contours: Raisin like appearns c. Cyoplasm vacuolization  Perinuclear Halo 2. Vesicles/Ground Glass Nuclei/Cowdry A inclusions: HSV ½ a. Sacral Ganglion b. Painless Blisters which cause Painful Ulcers/erosions 3. Intracytoplasmic Cytopatholyg: Chlamydia a. Silent in Women, Symptomatic in Men: Chlamydia b. Urethritis/ Lymphogranuloma Venerum, Trachoma (Eye infection) 4. Elongated Intracytoplasmic Neuronal Inclusions = Negri Bodies = Rabies a. Filled w/ Virus particles b. Most often in Hippocampus and Purkinje Neurons of Cerebellar Cortex c. Vampire Bats  Exposure w/out bat: Central America d. Extraordinary excitability, EHadache, Difficulty swallowing, convulsions, coma 5. Large Purple INTRANUCLEAR Inclusion and Granular Basophilic INTRACYTOPLASMIC inclusion = CMV Cytomegalic Cells a. CMV encephalitis= in utero infection of fetuses and immunocompromised 6. Microglial Nodules = HIV Encephalitis a. Collections of lymphocytes, histiocytes, and microglial cells w/ variable number of multinucleated giant cells 7. Frothy White Discharge + Itching a. Trichomonas PicoRNA viruses: PEECoRnA 1. Polio, Entero, Echo, Coxsackie, Rhino, hep A Positive sense RNA: 1. Call Henry, Pico, and Flo to Come Right away a. Calici, HEpevirus, Picornavirus, Flavivirus, Togavirus, Coronavirus, Retrovirus Pox Virus: 1. Molluscum Contagiousm a. Umbilicated warts Herpes 6: 1. Roseola Infantum a. Mild febrile disease followed by a rash Adenovirus:

1. Conjunctivitis, pharyngoconjunctivitis, Upper Respiratory dx, and gastroenteritis 2. Kids at camp w/ swimming pool xxiii. Viral Encephalitis: 1. Fever, HA, Metnal Status Change  Coma 2. Focal Neurolgic Defects and Seizures may also be present a. Disoriented to Time and Place b. Gait ataxia and Double vission 3. CSF: a. Elevated Lymphocytes, Normal Glucose, and Normal or Slightly Elevated Proteins 4. Most Common Cause of Viral Meningoencephalitis in US a. Hepres Simplex: Transmitted by direct contact i. Lumbar Puncture = High opening pressure + Multiple RBCs in CSF ii. Causes Focal Temporal Lesions and Hemorrhage into CSF 5. Most common Causative AGENT  Summer Months: Mosquitoes (Arthropod) a. Flaviviridae: i. St. Luis Virus, West Nile Encephalitis b. Toga: i. Eastern, Western, And enezuelan Equine Encephalitis Viruses 6. t. Amoeba: Free living – Infect brain and meninges i. Acanthamoeba 1. Immnosuppressed bc of diabetes, alcholims, cancer, or HIV ii. Naegleria Fowleri 1. Healthy adolescents or divers iii. Prominent perivascular infection which causes Multifocal Hemorrhagic Necrotizing Meningoencephalitis iv. Skin ulcers, Nasal Infection, Pneumonia v. Toxin Causes host tissue necrosis u. Protozoa/Parasites i. Toxoplasmosis: HIV 1. Most common cause of RING ENHANCING BRAIN LESION in HIV pts 2. Cyst reactive when patient’s CD <200 3. Seizures, Altered Mental Status, Focal Neurologic Defects 4. Centrally Necrotic, Focally Hemorrhagic Lesions Contain a. Large, Round Encysted Bradyzoites b. Free, Crescent-Shaped Tachyzoites toward edge of lesion 5. Tx: Pyrimethamine and Sulfadiazine ii. Leischmaniasis 1. Female Phlebotomine SANDFLY 2. Cutaneous: a. Erythematous Macules/Papules b. Skin Ulcers  at Bite site, and heal over LONG TIME c. Ulcers of mouth, tongue, gums, lips, Nose, and Nasal Septum d. Dysphagia w/ Esophageal involvement and dyspnea e. Can progress to Mucosal or Visceral Leishmaniasis

3. Visceral: a. Persistent Fever: Weeks or Irregular Cycles b. Night sweats, fatigue, weakness, anorexia, weight loss c. Thinning of hair, SCALY, OR GRAY, DARK, ASHEN SKIN d. Skin i. Erythematous macules/papules and slow healing ULCERS e. Ulcers of Skin, Mouth, Tongue, Gums, Lips, Nose, and Nasal Septum f. Dysphagia w/ esophageal involvement and dyspnea g. Death in 2 years if not treated i. From complications (infections) 4. All continents except Australia 5. Americas: a. Mexico and South America 6. Tx: a. Cutaneous Localized Leishmaniasis i. Antimony Contaiing Compounds for Cutaneous, Localized Leishmaniasis 1. Sodium stibogluconate and Meglumine Antimonate 2. Also Pentamidine and Ampho B (but DOC for visceral) b. Cutaneous Diffuse or Visceral Leishmaniasis i. Amphotericin B iii. Trypanosoma Cruzi: Chagas Dx 1. South America 2. Person to Person by Reduviid bug: Kissing Bug ( a triatomid) 3. Intracelular protozoan localizes in HEART and NERVE cells of MYENTERIC PLEXUS a. Visualize in tissue sections 4. Myocarditis and dysmotility of Hollow organs (Esophagus, Colon, ureter) 5. Cardiac a. Vetnricular dilatation and CHF secondary to myocyte encrosis and fibrosis 6. Acquired Achalasia a. Distal third of esophagus dilates b/c of loss of innervation 7. Acquried Megacolon and Megaureter a. Loss of innervation v. Nematodes i. Ascaris Lumbricoides 1. Large nematode: Migrates through lung during its maturation to adulthood 2. Shortness of breath, wheezing, exertional dyspnea, occasional urticaria 3. Stool shows Rough Shelled Brown ova 4. Sputum show nematode larvae and eosinophilia 5. Acquired by ingestion of ova of parasite from soil contaminated w/ Human Feces a. Larvae hatch out of eggs  Intestine  Migrate into bloodstream to be carried to lung  Break out of alveoli  Coughed up and swallowed  Mature to adulthood in small intestine  Mate + Proudce eggs into feces 6. One of most potent allergens in nature 7. Migration  Mass IgE and Eosinophilia  Loeffler Syndrome a. Type 1 hypersensitiv

Immuno
5) Immuno: a. Tests: i. Flow Cytometry 1. CD18: Leukocyte Adhesion Deficiency (LAD-1) 2. Dihyrdo-Rhodamin 123 (DHR) fluorescence: Chronic Granulomatous Dx a. Replaced Nitroblue Tetrazolium Test ii. Examination of Nucleated Blood Cells for Large inclusion 1. Chediak-Higashi Syndrome a. Defect in Microtobule Polymerazation defect i. LYST Gene: Lysosomal Trafficking Regulator Protein b. No phagolysosomes c. Large lysosomal vessels: Phagocytes, Neutrophils d. Partial Albinism, Peripheral Neuropothy, Light skin, silvery hair, photophobia, RECURRENT PYOGENIC INFECTIONS iii. Neutrophil Myeloperoxidase Deficiency Histochemical Analysis 1. Clinically Silent, But may present w/ Disseminated Candidiasis, esp in diabetics 2. Myeloperoxidase, enzyme found in lysosomal granules, acts on H2O2 to produce toxic Halide radicals: Hypochlorite iv. Total Hemolytic Complement Assessment 1. Screen for a Complement Disorder: Check Cascade 2. zDeficiency can present with: a. Life threatening infections, lupus like disorders, hereditary Angioedema, Paroxysmal Nocturnal Hemoglobinuria b. Vaccine i. MMR: CD3CD8 1. Live attenuated, requires cell mediated immune response c. MHC 1: HLA A, B, & C  CD8 T cytotoxic i. On all cells except RBCs ii. Present peptides from intracellular killing of INTRACELLULAR organism (tumors,) iii. Present to CD8+ T cells (Cytotoxic T Lymphocyte) iv. 2-Chain structure w/ two subunits: 1. Beta-2 Microgloblin HOLDS Alpha Chain in place v. Loss of MHC 1 DEACTIVATES CD8 T cels, but ACTIVATES NK Cells to kill d. MHC 2: HLA DP, DQ, DR  CD4 T Helper i. On APCs (macrophages) ii. Present antigens of peptide fragments from intracellular killing of EXTRACELLULAR organisms iii. Present to CD4+ T helper cells. iv. Dx = Bare Lymphocyte Syndrome 1. Depressed numbers of CD4+ cells, but normal maturation of B cells e. HLA i. A3 - Hemochromatosis ii. B8 – Graves Dx, Celiac iii. B27 – Psoriasis, Ankylosing Spondylitis, Inflmmatory Bowel Disease, Reiter’s Sydnrome 1. (PAIR) iv. Cw6

f.

1. Psoriatic Arthritis v. DQ2 or DQ8 1. Celiac Dx vi. DR21. Multiple Sclerosis, SLE, Goodpastures, Hay fever 2. Homozygous = REDUCED RISK of Diabetes type 1 vii. DR2/DR3: 1. SLE, Psoriasis, IBD, Reiter Syndrome viii. DR3 – Diabetes Mellitus Type I 1. Antibodies to Islet cells include: Anti-Glutamic Acid Decarboxylase (anti-GAD) 2. Tx: Insulin or Pramlintide ix. DR4 – Rheumatoid ARthirtis, Diabetes Mellitus Type I 1. HLA DR3 AND DR4 = 33x Greater risk of Diabetes 1 x. DR5 – Pernicious Anemia, Hashimoto’s, HIV DILS: Diffuse Infiltrative Lymphocytic Syndrome (CD8+ T Cell cause Sicca/Sjogren’s INflamation of Parotid Gland xi. DR7 – Steroid Responsive Nephrotic Syndrome (MCD??) CD types i. CD3: Count Total T cell 1. ALL T cells, needed to be activated 2. Cisgnal Transduction molecule ii. CD4: T helper Cells 1. Ab mediated and Cell-mediated immune a. Exogenous peptides presented on MHC 2 by macrophages 2. Cell-Mediated Delayed Hypersensitivity 3. Production of cytokines for stimulation of Ab from B cells 4. Stimulation of macrophages iii. CD8: Cytotoxic T cells 1. Identify Alterations in MHC 1 molecules of virus infected cells 2. CANNOT KLYSE RBCs bc RBCs DO NOT HAVE MHC 1 iv. CD14: Endotoxin Receptor on Macrophages 1. Ingest and destroy Infect RBCs in spleen, but not extracellular lysis v. CD16: Receptor for IgG Fc component. On NK, Macrophages, and Neutrophils. vi. CD18: Mutation  Leukocyte Adhesion Deficiency (OMPHILITIS 1st sign) 1. CD18 = Common beta chain for beta-2 leukocyte integrins: a. Integrins are responsible for tight adhesion of neutrophils to injured endothelia b. No integrins = no migration to inflammation 2. LAD-1 recurrent bacterial and fungal infections and depressed inflammation despite extreme neutrophilia a. Long lasting infections of Skin, Respiratory Tract, Lower intestinal tract, Mouth, and Genital tract b. Lead to chronic ulcerations c. Pathogens (similar to severe neutropenia): i. S. Aureus, Enteric Gram -, Fungi 3. Delayed separation of umbilical cord and omphalitis (infection of cord) 4. Diagnose w/ Flow Cytometry of CD18 integrin subunit. vii. CD19+: B cell count

1. Dx: Bruton’s X linked Agammaglobunemia viii. CD 20 1. B Cell Marker ix. CD 21 1. B Cell Marker 2. Receptor for EBV x. CD40-CD40L 1. B cell switching signal from TH cells a. Required w/ IL-4 2. Dx = Hyper IgM Syndrome a. IgG and IgA deficient b. Pyogenic infections c. Autoantibodies to neutrophils, platelts, or tissue antigens d. X Linked recessive xi. CD56: NK Cells: 1. Innate host defense 2. Cytotoxic Cells that kill Extracellularly using Two singal recognition System 3. Inhibitory signal is Presence of MHC Class 1 molecules 4. NK cells do extracellulary Lysis of infected RBCs a. Babesia 5. NK cells kill Virus infected cells and tumor cells a. Secrete Granzymes and PErforins g. Complement Deficiency i. C1q: Combined Immunodeficiency w/ SLE-like Symptoms ii. C1 Esterase Inhibitor: Deficiency = Hereditary Angioedema iii. C1rs, C1s, C2, C4: SLE-like syndrome and Glomerulonephritis iv. C3 or C5: Pyogenic Infections v. C6, C7, C8: Recurrent Neisseria h. Complement i. C1q 1. Classical pathway 2. Binds to constant heavy domain of two IgG molecules or one IgM that has reacted w/ a pathogen surface epitope 3. Functions as an enzyme in early cascade 4. NOT involved in opsonization or removal of immune complexes ii. C3b 1. Most critical molecule in both classical and alternative complement path a. From C3 = Most abundant protein of all comlements proteins i. Cleaved into C3a and C3b 2. Opsonin of microorganisms by phagocytosis a. Attaches to bacterial surfaces b. Organism gets coated, and is more easily phagocytized. 3. Binds to Mast cells and basophils a. Activate them and produce Histamine release 4. Removal of Immune complexes from Serum a.

5. Not chemoattractive iii. C5 1. Splits into C5a and C5b iv. C5b 1. Inititates assembly of Membrane Attack Complex a. C5b, C6, C7, C8, C9 v. C5a 1. Neutrophil Chemotaxis 2. Stimulates Inflammatory Response vi. Factor B 1. Activator Protein of Alternative Path 2. Combines w/ C3b to form C3bBb = C3 Convertase of Alt pathway 3. Turned on by surfaces of bacteria Cytokines: i. IL-1, IL-6, TNF-a 1. Fever, 2. Stimulation of acute-phase ractions 3. Stimulation of fibroblasts 4. Stimulation of endothelial exresion of adhesion molecules ii. IL-2 1. From CD4 T lymphocytes 2. Causes Cells to undergo Mitosis a. Cloning of T Cells and NK cells n cell-meidated immunity against intracellular pathogens 3. Gamma Chain 4. Stimulates TH1 subste, CD8 T cytotoxic cells, activates NK cells 5. Causes cloning of cells of cell-mediated immunity 6. Dx: SCID  Fialure of proliferative responses of BOTH B and T lymphocytes iii. IL-3 1. Growth factor for Hematopoietic Stem Cells and Mast Cells iv. IL-4 1. TH2 lymphocytes: Required for B cell Isotype switching 2. Development of IgE Ab by B lymphocytes and Plasma cells 3. Extracellular Pathogens 4. Inhibits TH1 v. IL-5 1. From Th2 Cells 2. Stimulate Isotype Switching in B lymphocytes to IgA in submucosa 3. Mucosal protection and eosinophil production in bone marrow vi. C5a, IL-8 1. Neutrophil Chemotactic Factors vii. IL-10 1. TH2 Cells a. Inhibits TH1 cells b. Mainting humoral response against Extracellular Pathogens 2. TH0 Cells

i.

a. Activates T-Reg cells viii. IL-12, INF-gamma 1. Intracellular Pathogens 2. Activates TH1 ix. IL-17 1. Activates TH17 cells x. TNF-Alpha 1. Macrophages and NK cels 2. Cytotoxic for Tumor Cells 3. Induces Cytokine Produciotn 4. Causes Cachexia of Chronic INflammation xi. INF-alpha 1. Leukocytes 2. Inhibits Viral Replication xii. INF-Beta 1. Fibroblasts 2. Inhibits Viral Replication 3. Treat Multiple Sclerosis xiii. INF-Gamma 1. TH1 Cells 2. Activates NK cels 3. Acts on macrophages to enhance intracellular pathogen killing in phagocytic cells. a. Macrophages from Epithelioid Cells and Multinucleated Giant Cells in Granulomas 4. Intracellular Bacterial Infections a. Mycobacterium TB!! 5. Inhibits TH2 j. Shock w/ LDS Endotoxin from Gram -: i. Macrophages respond to LPS by producing TNF-alpha 1. Triggers a cytokine cascade (IL-1,6,8,NO, and PAF) 2. Leads to Generalized vasodilation  Acute hypoteniosn (Shock)  Decreased inotropism 3. Widesrpead activation of coagulation cascade  DIC k. Leukotrienes i. LTC4, LTD4 1. Vascular Permeability l. Prostaglandin i. PGI2, PGD2 1. Vasodilation ii. PGD2 1. Pain iii. PGE 1. Important mediator of TEMPERATURE CONTROL MECHANISMS in BRAIN 2. Acute Phase Reesponse of Inflammation  Increase PGE in brain  FEVER 3. Sensitizes Cell endings to pain by bradykinin m. Gamma-Delta T cells and T Cells in DiGeorge Syndrome:

n. o.

p. q.

i. Congenital absence of Thymus b/c Third and Fourth paharyngela Pouches fail ii. Only Gamma-Delta T Cells do not require education and selection in thymus iii. Possesss a T cell receptor that has gamma and delta chains instead of normal alpha-beta T cell receptors. iv. Majority of cells in submucosa and intraepithelial spaces T Cell Deficiency: i. SCID, Fungal infections, opportunistic infections (Candida, Pneumocystis, or CMV) Common Variable Immunodeficiency i. Heterogeneous complex of diseases of differing etiology (acquired normally) ii. Clinical Profile 1. Onset of Recurrent bacterial infections secondary to markedly decreased antibody levels 2. Reacant 3. Becomes clinically evident in Second or Third Decade of Life 4. Some have Intact Cellular Immunity; Other have variably severe T cell defects 5. B cells normal, T cells may be lower 6. Autoimmune conditions common (Addison Dx, Thyroiditis, and Rheumatoid arthritis) in pt and relatives 7. GI symptoms related to nodular Lymphoid Hyperplasia in Gi tract 8. Bronchiectasis, Carcinoma, and Lymphoma iii. Different than X-Linked Hypogammagloblunemia 1. X-Linked has LOWER than normal levels of B cells and patient presents w/ symptoms in EARLY childhood a. Defect in tyrosine kinase so B cells cannot mature iv. Different from Hyper IgM : 1. Hyper IgM due to absence of CD40L on T cells  NO isotype Switching 2. IN absence of singal, IgM producing B cells cannot swithch so High Igm and low others v. Different than DiGeorge Syndrome 1. DiGeorge Presents in Infancy w/ Hypocalcemia, Cardiofacial Abnormalities, and AbSENCE of T lymphocyte sin blood vi. Different than SCID: 1. SCID from Adenosine Deaminase def presents in INFANCY as SCID b/c Absence of enzyme causes build up of Toxic Products in Lymphocytes of ALL Categories in bone marrow Neutrophil Deficiency: i. Extracellular Microorganisms Immunoglobulins i. IgA: Dimeric 1. Mucosal Ig, Dimer held together by single J chain. 2. Secretory component added by mucosal cell and is transported int lumen of organ 3. Protects against Giardia Lamblia (Extracellular Parasitic Protozoan) that adheres to surface of mucosa via ventral sucking disc) 4. Selective IgA deficiency is MOST COMMON of PRIMARY IMMUNODEFICIENIES a. RECURRENT BACTERIAL AND VIRAL INFECTIONS OF RESPRIATRY TRACT due to no Secretory IgA in Mucosal Immune System b. Seen in Second Year of Life bc mom’s IgG (placenta) and IgA (in milk) protect child

c. Get Increased Atopy as IgA loss  Increased IgE switching  Increased anaphlyaxis and rashes and responses ii. IgM: Pentameric 1. Most Important Primary Immune Response 2. Naïve B Cell Antigen Receptor (w/ IgD) 3. Activates Complement, Classical Path to C9 for destruction iii. IgG 1. Mediates Antibody Dependend Cell-mediated Cytotoxicity: a. Binding of Fc region to NK cells, Neutrophils, and Macrophages causes desctruciton of cells 2. Activates Complemetn Classical Path to C3B 3. Opsonization 4. Acts as Memory B cell antigen Receptor iv. IgE 1. Allergic Reactions, Allergens, Hypersensitivty, Parasites and Worms 2. Loeffler Syndorme = Eosinophilia + Urticaria + wheezing a. Allergic Hypersensitivity manifested in Lung b. Maybe called Verminous Pneumonia 3. Occurs w/ Nematodes!!! 4. Use IgG blocking antibodies to desensitive and protect against overactive IgE a. Against allergen, IgG reacts w/ allergen first v. IgD r. Oxygen Dependent Killing: (CGD) i. NADPH Oxidase activation is critical first step  Produce toxic oxygen radicals w/in phagolysosome. ii. Hydorgen Peroxide, product of this reaction, serves as substrate for Myeloperoxidase (2nd most important killing mechanism)  Produces Toxic Halid Radicals iii. Catalase + Bactereia destroy H2O2 they produces so neither of oxygen dependent mechaisms can fucniton in intracellular killing. iv. NAPDH Defeciency = CGD = Susceptible to CATALASE + Infections 1. S. Aureus, Aspergillus, Nocardia, Salmonella, and Candida s. Oxygen Independent Killing: Phagocytic Killing i. Lysozyme, Lactoferring, Hydrolytic Enzymes, Defensins (least powerful) t. Adhesion and Diapedesis in Inflammation i. LFA-1: Bind to endothelium 1. Strong binding b/w Injured epithelium and: monocytes, T lymphocytes, macrophages, neutrophils, dendritic cells 2. Member of Beta-2 Integrin family – 3. Interacts w/ Intercellular adhesion molecule ICAM-1 ii. ICAM-1: Diapedesis 1. Member of Immunoglobulin Ig Superfamily w/ 5 Ig-like domains 2. Causes strong adhesion to promote Diapedesis into area of acute inflmmation iii. LAD-1: Beta chain for beta-2 Leukocyte integrins: Tight Neutrophil Adhesion 1. Dx = LAD w/ Recurrent Bacterial and Fungal infections and depressed inflammation despite extreme neutrophilia u. Neutrophil Chemotaxis

i. C5a and IL-8, Fibrinopeptides, Leukotrien B4, and Formyl Methionyl Peptides (from bacteria) v. Dx i. Bruton X-Linked Agammaglobulinemia 1. Only Humoral Immune Deficiency w/ No Peripheral B cells = NO CD19+ 2. Mutation in Bruton Tyrosine Gene (BTK) a. Required fro pre-B cells to develop to immature B cells in bone marrow 3. Reccurent bacterial infections after 6 months (mothers IgG goes down) a. Sore throat, Rhinorrhea, Fever, productive caugh, infections of skin, ear, and respiratory tract b. Extracellular Organisms: S. Pneumonia and HiB 4. Low IgG and Ig’s of ALL Classes 5. Normal Cell-mediated immunity 6. Tx: Monthly Gammaglobulin replacement and Antibiotics for infection w. Chediak-Higashi i. Large Inclusions in ALL NUCLEATED BLOOD CELLS 1. Giant granules interfere w/ ability to traverse endothelial cell passages into tissues ii. Defective Neutrophil Granules  Increased susceptibility to infection iii. x. SCID: i. IL-2 Receptor Absence, 1. Failure of proliferative responses in both B and T lymphocytes ii. Adenosine Deaminase 1. Build up ot toxic Products in lymphocytes  Decreases levels in peripheral blood and elsewhere

Anatomy
6) Anatomy: a. Reflexes: i. Ankle: S1 1. S1 innervates: a. Peroneus Longus and Brevis (via Superficial Peroneal Nerve) i. Test by Flex and Ever foot against opposition b. Biceps Femoris (via Tibial portion of sciatic nerve) i. Hamstring weakness c. Gastrocnemius muscle: i. Achilles Tendon Reflex d. Dermatome: i. Lateral Foot ii. Knee: L2-L4, ESPECIALLY L4 1. L4 a. Patellar Reflex b. Muscle Test: Tibialis Anterior (via Deep Peroneal Nerve) i. Resistance to Dorsiflexion and INversion c. Dermatome i. Medial Aspect of Foot

2. L2, L3, and L4 = Femoral Nerve a. Quadriceps Muscle i. Hip Flexion b. Hip Adductors 3. L2, L3 Dermatome a. Anterior Thigh 4. L5 a. No reflex test or muscle test for Tibialis Posterior b. Muscle Test for Peroneus Longus and Brevis (via Sup. Peroneal Nerve) i. Plantar flex and Evert foot against opposition c. Dermatome i. Central Dorsum of Foot iii. Biceps: C5-C6 iv. Triceps: C6-C7 b. Tongue: i. Anatomy 1. Ant 2/3 a. Follate Papilla on Side b. Fungiform Papillae and Filliform Papillae on top 2. Post 1/3 a. Circumvallate Papillae b. Foramen Cecum ii. Taste: 1. Ant 2/3 – 7 a. Chorda Tympani branch 2. Post 1/3 – 9 3. Epiglottis – 10 iii. Motor 1. Intrinsinc and Extrinsic Skeletal muscles: 12 2. Palatoglossus Muscle iv. Sensation 1. Genaral Somatic Ant 2/3 – V3 a. Lingual branch 2. Post 1/3 – 9 3. General Somatic Palate, Upper gums, and Upper Lip – V2 4. Lower Pharynx - X c. Abdominal i. Microvilli: Actin and Myosin (non muscle) 1. Extensions of bundles of actin filaments (microfilaments) 2. Dx: Congenital Microvillus Atrophy a. Reduction of myosin bands  Abnormal binding of myosin to the actin cable b. Secretary diarrhea due to lack of absorption of nutreintss 3. Facilitate absorption and secretion 4. ii. Gastrosplenic (greater stomach curve) and Gastrohepatic (lesser stomach curve) ligaments OK to excise to access left and right lesser peritoneal sac (respectively)

iii. Hepatoduodenal Ligament (hepatic artery, portal vein, bile duct) and splenorenal ligament (tail of pancreas and splenic vessels) are not ok to cut iv. Splenic Artery  Short gastric and Left gastroepiploic artery 1. Left Gastroepiploic artery Anastomose w/ Right gastroepiploic artery 2. If blocked proximal to branch point, short gastic vessels can be supplied by backflow from the left gastroepiploics v. Gastrin is ONLY HORMONE IN ANTRUM and also is present in Duodenal and Jejunal Mucosa vi. Transversalis fascia weakened in INDIRECT inguinal hernia (posterior lateral wall.) vii. Vomiting: 1. Preceded by Antiperistalsis a. May begin as far down as Ileum 2. Exciting factor to initiate vomiting: a. Distensions of upper portions of GI: Duodenum 3. Onset of vomiting a. Strong contractions of duodenum, b. Partial relaxation of LES 4. During Vomiting a. Relaxation of stomach, principallty, w/ some contractions (angular notch) b. Propulsive action: i. Smal intestine, Abdominal Muscle, and Diaphragm Contraction c. Specific Actions: i. Deep Breath  Relaxation of UES  Closure of glottis  Strong abdominal muscle and diaphragm contractions viii. Direct Inguinal Hernia: 1. Pass ABOVE Inguinal Ligament and THROUGH SUPERFICIAL INGUINAL RING, MEDIAL TO INFERIOR EPIGASTRIC VESSELS a. Through Superficial Inguinal ring, emerging THROUGH posterior wall of inguinal canal = Fascia Transversalis b. Protrude Medial to inferior epigastric sand pass through Inguinal triangle (TRIANGLE OFHESSELBACH) i. Lateral Border: Inferior Epigastric Vessels ii. Medial Border: Rectus Abdominis iii. Inferior Border: Inguinal Ligament. ix. Indirect Hernia (Inguinal Hernia): 1. Pass Through BOTH Deep inguinal Ring AND Superficial INguianl Ring, LATERAL TO INFERIOR EPIGASTRIC ARTERIES 2. Reducible Mass in Scrotum a. Dnager for Incarceration/Strangulation i. Abdominal Pain, Vomiting, Hypotension b. Peritoneal effusion  Increase ammonia w/o increase in creatinine (Bacterial proliferation in damaged intestine) c. Gram Stain = Enteric Flora 3. Pass Through Inguinal Canal, ABOVE inguinal Ligament Into Testes a. Canal Contains Round Ligament and Ilioinguinal Nerve (Females) b. Canal Contains Spermatic Cord and Ilioinguinal Nerve (Males) c. Roof of Canal:

i. Internal Abdominal Oblique and Transverse Abdominus Muscles d. Anterior Wall: i. Aponeurosis of External Abdominal Oblique and Internal Abdominal Oblique e. Floor of Canal: Inguinal Ligament f. Posterior Wall: i. Transversalis Fascia Laterally and Conjoined Tendon Medially ii. Conjoined Tendon = Aponeurosis of Internal Oblique and Transversus Abdominus Muscle x. Femoral Hernias 1. Pass Below Inguinal Ligament, Medial to Femoral Artery xi. Intussusception: 1. MOST COMMON CAUSE of GI Obstruciton in children 3 mo to 6 years (peak 5-10 months) 2. Telescoping of bowel segments into another more distal segment 3. Due to poor support offered by thin mesentery 4. Produces intestinal obstruction, sichemia, infarction a. Sudden onset of vomiting w/ bouts of crying and distress b. No prior problems c. Abdominal x ray shows air-fluid levels xii. Spleen: 1. Follows long axes of ribs 9-11 and lies in posterior axiallary line 2. Posterior to stomach, above colon, and partly anterior to kidney. a. Pleural cavity and possibly lower part of inferior lung lobes pierced before spleen. xiii. Colon Layers: 1. Mucosa  Submucosa (Meissner’s Plexus)  Muscularis externa (Auerbach’s Plexus) Serosa a. Meissner’s plexus: i. Web of enteric nerves embedded w/in submucosal layer of bowel: ii. Coordinates secretion and absorption throughout bowel b. Auerbach’s Plexus i. Between inner circular and outer longitudinal muscle layers of muscularis externa layer ii. Enteric Nerve layer that coordinates peristalsis along length of bowel c. Diverticulum: i. False: Mucosa, Submucosa, Serosa ii. True (Meckel’s): Mucosa, Submucosa, Muscularis externa, Serosa xiv. Hemorrhoids 1. External: Inferiro Rectal Vein Varicosities 2. Internal: Superior Rectal Vein Varicosities d. Brachial Plexus i. C5: 1. Flexion, Abduction, and Lateral Rotation of the shoulder 2. Flexion of the Elbow ii. C5 & C6

iii. iv. v. vi. vii.

viii.

ix. x.

1. Suprascapular Nerve 2. MusculoCutaneous Nerve 3. Axillary Nerve C7 & C8 1. Extensions of Fingers, Shoulders, and Pronation of Elbow C8 & T1 1. Ulnar Nerve SUBLCAVIUS MUSCLE PROTECTS BRACHIAL PLEXUS Crutches 1. Injure Posterior Cord of Plexus  Injure Radial Nerve Anterior Displaced Humerus Injury 1. Axillary Nerve Injury 2. Head of Humerus Dislocates from glenohumeral joint, exits inferiorly where joint capsule is weakest, and stretches axiallary nerve where it exits from axilla in QUADRANGULAR SPACE 3. Deltoid Muslce Weakness Axillary Sheath 1. First portion of Axillary artery and Three cords of Plexus and Axillary vein enclosed 2. Within Axilla Axillary Artery Aneurism 1. Cords of Brachial Plexus Susceptible to COmpression Klumpke Paralysis: Excessive stretching of arm injures LOWER TRUNK (C8 and T1) of Brachial Plexus 1. Occurs w/ Breech delivery of baby with hyperextended arm over head 2. Ulnar and Median nerves  Loss of function of all intrinsic muscles of hand by these nerves: a. Interosseous muscles: i. Adbduction and adduction of digits b. Opponens Muscle: i. Opposition of Thumb c. Loss of motor function of intrinsic hand muscles d. Numbness along inner aspect of hand (ulnar sdie) e. w/ T1: Horner Sydnorme (miosis, ptosis, and anhidrosis) may be present

xi. xii. Thoracic Outlet Syndrome: Cervical Rib 1. Compression of Neurovascular Bundles a. Paresthesia on medial aspect of one hand and forearm and diminished radial pulse on affected side b. Numbness and tingling and/or circulatory changes in upper extremity c. Pain and Paresthesia in distribution of ulnar nerve, the lower two nerve roots of brachial plexus i. Pain and tingling and numbness in fourth and fifth digist and in medial forearm. ii. More pain w/ arms overhead iii. Mild swelling of hand

2. Lower Turnk of Brachial Plexus and Subclavian Artery pass Laterally over the Upper surface of First rib, and lie Posterior to Scalenus Anterior 3. Structures may be compressed between the scalenus anterior and a cervical rib 4. Tx: Incision of Anterior Scalene Muscle Relieves Symptoms 5. DANGER: PHRENIC MUSCLE LIES ALONG ANTERIOR SCALENE  DAMAGE xiii. Long Thoracic Nerve (C5,6,7): Serratus Anterior 1. Draws scapula forward and rotates it upward 2. Major muscle used in all reaching and pushing movements 3. Lesion = WINGED SCAPULA a. Medial border of scapula is prominent. b. Injured during resection of axilla as well as axiallary tail of breast w/ mastectomy xiv. Lower Subscapular Nerve: 1. Subscapularis a. Rotator cuff muscle for Supraspinatus, infraspinatus, and teres minor to maintain approximation of head of humerus in glenoid cavity b. Assists in medial rotation of arm while in a dependent positions 2. Teres Major xv. Upper Subscapular Nerve 1. Innervates subscapularis w/ Lower Subscapular nerve xvi. Suprascapular Nerve 1. Supraspinatus and infraspinatus of rotator cuff xvii. Musculocutaneous Nerve 1. Coracobrachialis a. When arm is in an extended position, coraco brings it forward and medially 2. Biceps Brachii a. Shoulder flexion, elbow flexion, supination of forearm 3. Brachialis a. Flexes elbow joint xviii. Rotator Cuff: 1. Supraspinatus 2. Infraspinatus 3. Subscapularis 4. Teres Minor e. Cubital Fossa: i. TAN = Tendon of Biceps Brachii, Brachial Artery, Median Nerve 1. Lateral to Medial at elbow f. Dupuytren Contracture: i. Palmar Fascia ii. Caused by interation of Myofribroblasts w/ Collagen fibrils of fascia 1. Myofibroblasts = spindle shaped cells (fibroblastic) w/ bundles of microfilaments g. Lower Body: i. Arteries: 1. Femoral Artery (exits Adductor hiatus)  Poplitial Artery (behind knee joint)  anterior and posterior tibial arteries (at lower border of popliteus muscle) 2. Posterior tibial  Peroneal Artery

ii. Trendelenburg Sign: Gluteus Medius + Minimus iii. Gluteus Maximus: Rise from a seated position iv. Popliteal Fossa 1. Diamon shaped region bounded by a. Biceps Femoris: Superolaterally b. Semimembranosus and Semitendinosus: Superomedially c. Two EHads of Gastrocnemius: Infero-Laterally and Medially d. Floor of Fossa: Superior to Inferior i. Popliteal surface of femur ii. Knee Joint capsule iii. Popliteus Muscle e. Within Fossa: Posterior to anterior: i. Tibial Nerve ii. Popliteal Vein iii. Popliteal Artery f. Lateral Fossa: Common Peroneal (fibular) Nerve i. Lies against tendon of biceps femoris ii. Danger of damage w/ Baker Cyst v. Baker Cyst: 1. Cystic Enlargement of Popliteal Bursa: Filled w/ Synovial fluid a. Become inflamed and Painful b. Limitation of movement at knee, esp in flexion c. Swelling behind knee that progressively grows w/ pain d. Erythematous, fluid filled mass overlying tendon of biceps 2. DANGER IN LATERAL PART OF FOSSA FOR DAMAGE TO COMMON PERONEAL (FIBULAR) NERVE  Immediately adjacent to tendon of biceps a. Popliteal Artery lieds deep in fossa vi. Sciatica: 1. Weak Extension of Thigh, Flexion of Knee, Loss of Function below Knee, Pain and/or Sensory loss on Posterior Thigh, Lateral Leg, and Foot 2. Sciatic Nerve: a. Tibial Nerve and Common Peroneal Nerve i. Tibial: Anterior L4-S3 ii. Common Peroneal: Posterior L4-S2 vii. Femoral Ring Boundaries: Femoral Hernias 1. Medial: Lacunar Ligament 2. Anterior: Inguinal Ligament 3. Posterior: Pubis 4. Lateral: Femoral Vein viii. Lower Limb Innervation: 1. L2-S3: Sciatic Nerve 2. Common Peroneal Nerve: Posterior L4-S2 a. Located superficially at neck of fibula i. Compressable when lying on right side for periods of time ii. See in bed bound patiens b. Short Head of Biceps Femoris: Flex Knee

3.

4.

5.

6.

7.

8.

9.

c. Divides into Superficial Peroneal and Deep Peroneal Nerve d. Dx: Atrophy of Lateral and Anterior Lower Leg Compartments Motor and Sensory of Dorsum of foot Deep Peroneal Nerve: Anterior Leg a. Tibialis Anterior (dorsiflex), Extensor Hallucis, Extensor Digitorum, Peroneus Tertius i. Dorsiflex Foot and Extend Digits ii. Sensory of Dorsum of foot b. Dx: Charcot-Marie-Tooth Dx: Hereditary Sensory Neuropathy Type 1 i. Foot Drop + HighArched Feet (Pes Cavus) Superficial Peroneal Nerve: a. Lateral Compartment of Leg: i. Peroneus Longus and Peroneus Brevis ii. Evert Foot 1. Peroneus Longus: Plantar Flex and Evert 2. Peroneus Brevis: Evert and limit inversion b. Sensory Innervation of Dorsum of Foot for Femoral Nerve: a. Anterior Compartment of Thigh: Extension at knee i. Dmage is Weakend hip flexion, extension at knee, sensatin on Anterior Thigh, Medial Leg and foot Inferior Gluteal Nerve: L5-S2 a. Gluteus Maxiums: b. Weak Hip Extension and Difficulty rising from seated postion/Climbing stairs Superior Gluteal Nerve: L4-S1 a. Exits Greater Sciatic Foramen ABOVE the Piriformis Muscle w/ Superior gluteal artery and vein b. Gluteus Medius, Minims, and Tnesor Fasciae Latae c. Loss od ABDUCTIn of Limb, and Trendelenburg Gait Obturator Nerve: Anterior L2-L4 a. Exits through Obturator Canal (Opening in the Obturator Membrane) b. Medial Compartment of Thigh i. Gracilis, Adductor Longus, Adductor Brevis, Anterior Adductor Magnus ii. Adduct and Medially Rotate Thigh c. Anterior Thigh with Weakened Sensory and Motor of Medial Thigh: d. Weakened thigh ADDUCTIOn and MEDIAL rotation of thigh PUdenedal Nerve: From S2,3, and 4 a. Exits Greater Sciatic Foramen BELOW piriformis i. Lies against lower border b. Enters gluteal region briefly, wraps around ischial spine and sacrospinous ligament, and then passes BACK THROUGH LESSER SCIATIC FORAMEN to enter perineum i. Palpate Ischial Spine to locate nerve block through transvaginal approach. ii. Ischial Tuberosity is Important Landmark c. Sensory and Motor innervation to perineum structures

d. Anesthesized in labor i. Feel for Ischial Spien 10. Inferior Rectal Nerve a. Arises from Pudendal Nerve after it exits greater sciatic foramen b. Crosses ischioanal fossa to reach anal canal c. Innervates External Anal Sphincter 11. Tibial Nerve: Anterior L4-S3 a. Posterior Compartment of Thigh i. Semimembranosus, Semitendinosus, Long head of Biceps Femoris, Posterior Adductor Magnus b. Posterior Compartment of Leg i. Gastrocnemius, Soleus, Flexor Digitorum Longus, Flexor Hallucis Longus, Tibialis Posterior c. Plantar Muscles of Foot d. Flex Knee, Extend Thigh, Plantar Flex Foot, Flex Digits, Invert Foot. i. Flexor Hallucis Longus: Plantar Flexion of foot ii. Tibialis Posterior: Plantar Flex and Invert Foot h. Ear: i. Loud Sounds damage Organ of Corti hair cells w/ hairs in tectorial membrane Lymph Drainage i. Testes  Para-Aortic Nodes ii. Butt, Lower limbs, Anterior Abdominal Wall, Perineum Superficial Inguinal Nodes  Deep Inguinal Nodes  External Iliac Nodes iii. Bladder, Male Internal Genital Glands, and Parts of Uterus and Cervix  Internal Iliac Nodes j. Bone: i. Periosteum supplies cells that develop into osteoblasts  Major produces of new bone that reunites two ends in Fracture k. Brain: i. Hypothalamus: 1. Supraoptic and Paraventricular: ADH and Oxytocin ii. Cranial Nerves: 1. CN 9: Afferent arc of Gag reflex + Innervation of parotid glands  Salivation!ß i.

Physiology
7) Physiology: a. Sodium i. Hypernatremia: Dehydration/Volume Depletion 1. Nausea, Vomiting, Confusion, delirium, Irritability, Muscle Twitching ii. b. Chloride i. Hyperchloremia: 1. Seen in Metabolic Acidosis c. Calcium i. HyperCalcemia 1. EKG: Short QT with Absent ST

2. Increase Systolic and Diastolic BP 3. Vomiting ii. HypoCalcemia 1. Tetany, Weakness, Tremors, Msucle Fasciculations, and Seizures 2. Positive Trousseau Sign a. Inlfate blood pressure cuff above systolic BP for 2 minutes  Carpal tunnel spasms 3. Positive Chetstak Sign d. Potassium i. Hyperkalemia 1. Increase extracellular K  Depolarization 2. Damaged Cells release into blood (Severe Burns or Trauma or Tumor cell therapy 3. EKG: a. Tall, Tented T wave from excessive Repolarization b. Prologned PR intervals c. Absent ST Segment 4. Numbness and Tingling, vomiting, nausea, areflexia, weakness, paresthesia, flaccid paralysis 5. See w/ Sprionolactone alone 6. Stimulates Adrenal Cortex to make Aldosterone ii. Hypokalemia: 1. ECG: Decreaed Amplitude, Braodening of T waves, Prominent U Waves, and Premature Ventricular Contractions: Everything pulled down 2. Weakness 3. 4. Diuretics cause Hypokalemia from induction of volume depletion, stimulation f angiotensin 2 and consequent increase in plasma aldosterone  excretes potassium. iii. Renal Phys: 1. Proximal Tubule reabsorbs 55% of filtered, 2. Thick Ascending Limb reabsorbs 30% (dependent on Na) 3. Cortical Collecting Duct: a. Principal Cells: Secrete Potassium i. Greater Secretion when Potassium is normal or Positive potassium balance ii. b. Intercalated Cells: Reabsorb Potassium 4. Hyperkalemia stimulates very sensitive Adrenal cortex to make Aldosterone: 5. Aldosterone a. Increases number and/or activity of Na/K-ATP ase pumps i. Increases Potassium Inside Principle Cells b. Increase Potassium channels in Luminal Membrane  Drive potassium to tubular Lumen e. Magnesium: i. Hypermagnesemia: 1. EKG: Prolonged PR and QT intervals 2. Hypotension

3. Respiratory Depression 4. Impaired Ach release  Decreased movement. ii. Hypomagnesemia: Functional Hypoparathyroidism 1. Alocoholism  Malnutrition  Severe Magnesium Deficiency 2. Tetany (w/ alcoholic cirrhosis) Due to Induced Hypocalcemia a. Weakness, Tremors, Msucle Fasciculations, Seizures b. Positive Trousseau sign (Blood pressure cuff) = Latent Tetany i. Carpal spasm w/ relaxation occurring w/in seconds after deflating cuff 3. Acute Hypomagnesium  Increase in PTH 4. Chronic Hypomagnesium  Decreased PTH secretion (and action) a. Administration of magnesium  Prompt increase in plasma PTH  Restore Ca to normal f. Cardiac: i. Baroreceptors and Chemoreceptors: 1. Aortic arch transmits via VAGUS NERVER TO MEDULLA: RESPONDS ONLY TO INCREASE BP 2. Carotid Sinus transmits CN 9 TO SOLITARY NUCLEUS OF MEDULLA: RESPONDS TO BOTH INCREASE AND DECREASE BP ii. Baroreceptors: Carotid Sinus 1. Hypotension  Decrease arterial pressure  Decrease stretch  Decrease afferent firing  INCREASE EFFERENT SYMPATHETHIC FIRING AND DECREASE PRASYMPATHETIC STIMULATION  VASOCONSTRICTION, INCREASE HR, CONTRACTILITY, AND BP a. Responses to Severe Hemorrhage 2. CAROTID MASSAGE: Increase pressure on Carotid artery  Increase stretch  Increase afferent firing  DECREASE HEART RATE iii. Chemoreceptors: 1. Peripheral: a. Carotid and Aortic Bodies: RESPOND TO DECREASE PO2 (,60), INCREASE PCO2, and DECREASE pH OF BLOOD b. First response! 2. Central a. Responds to Changes in pH and PCO2 of BRAIN INTERSTIITAL FLUID, which in turn are influenced by arterial CO2 b. DO NOT DIRECTLY RESPOND TO PO2 c. RESPONSIBLE FOR CUSHING REACTION i. Increase Intracranial pressure constricts areterioles  Cerebral ischemia  Sympathetic response and Hyeprtension  Reflex Bradycardia d. Cushings Triad: i. Hypertension, Bradycardia, Respiratory Depression iv. g. Renal Phys: i. Proximal Tubule: Reabsorbs 55% of Filtered Potassium h. Hyperosmolar NonKetotic Coma i. Hyeprglycemia, Increased Serum osmolarity, osmotic diuresis 1. Due to fluid loss b/c of filtered glucose

ii. Same as Diabetic Ketoacidosis, but no ketone bodies. i. Insulin i. C-peptide: Cleaved from proinsulin ii. Blocked by Alpha-2 Receptor Agonist: Clonidine 1. Directly inhibit pancreatic insulin secretion iii. Glucagon Enhances Insulin secretion: Tx as Hypoglycemia j. Gastrin Needed to prevent GI atrophy and Gastrin, CCK, and Secretin for Exocrine Pancrease Atrophy i. During long term IV feeding ii. Gastrin stimulate mucosal growth thorugh GI (except Esophagus and antrum) as well as exocrine k. GIP is only GI hormone released by all three major foods: Fats, protein,and carbs i. GIP REsoponsible for Higher Oral Glucose load response releasing more insulin and being metabolized more reapidly than IV glucose ii. GIP strong stimulator of insulin (Glucose Dependent Insulinotropic peptide) l. Gastrin is ONLY GI hormone released Antrum of Stomach ?? m. Secretin is used to Diagnose for ZES n. Blood Gases: i. PO2 = Partial Pressure of Oxygen 1. Only free (Dissolved) molecules of O2 a. Hb-Bound O2 Exerts NO PRESSURE 2. Normally P)2 = 100 mm Hg 3. Amount dissolved depends ONLY on PO2 and solubility coefficient: HENRY’s Law a. Does NOT depend on Hb concentration or binding characteristic of Hb ii. sO2 = Hb saturation with O2 1. Percentage of Hb present as Oxyhemoglobin (saturated w/ Oxygen) a. Each gram Hb binds 1.34 mL of O2 b. Depends on PO2 2. Arterial Blood: a. Normally 97-99% in arterial blood w/ PO2 = 100 m Hg 3. Venous Blood: a. 75% at rest iii. cO2 = Oxygen Content = Oxygen Concentration 1. Sum of O2 bound to Hb AND Dissovled O2 2. Anemia – Lower arterial O2 concentration b/c they have less Hb

Biochem
8) Biochem: a. Vitamins: i. Niacin B3: Lower Cholesterol 1. Decreases Hepatic LDL and VLDL production (5-7 days – 3-5 weeks) 2. Inhibits Adipose Tissue Lipolysis 3. Increases Lipoprotien Lipase Activity 4. Prevents Hepatic Triglyceride Esterfication 5. Side Effects: a. Flushing w/ Sensation of warmth, esp in face

b. Hepatotoxicity, Tachycardia, Hypoalbuminemia, Hyperglycemia, Nausea, Vomiting, Hyperuricemia, Glucose Intolerance, Pruritus, Peptic Ulcer Dx, Dry Skin b. Heme: i. Acute INtermitten Porphyria: AD (Young Women mostly) 1. Diffuse Abdominal pain, fever, nausea, vomiting, constipation, peripheral neuropathy, paralysis, a. Symmetric Bilateral weakness of lower extremeites b. Loss of deep tendon reflexes 2. Agitation, Depression, paranoia, visual Hallucinations, Emotional Lability 3. Restlessness, diaphoresis, weakness, paleness 4. Labs: a. Leukocytosis, elevated Porphoblinogen, elevated d-ALA 5. Preciptated by Drugs: a. Sulfonamides, Phenobarbital c. Carbohydrate Alterations i. N-Linked Carb Chains in RER attached to Dolichol Phosphate are Transferred to: 1. Nitrogen of Asparagine: Secreted Glycoproteins (Albumin) 2. Retained in Plasma Membrane: Insulin Receptor 3. Attached to Hexosaminidase A: To Lysosomes (Lysosomal Storage disease) d. Terminal Mannose-6-Phosphte Residue: Target Lysosomal Enzymes for Lysosomes i. Newly translated lysosomal enzymes sorted through the Golgi  Specific mannose residues must be phosphorylated before they are correctly targeted to lysosomes ii. Deficiency of Enzyme leads to mistargeting into exocytotic pathway, and release of lysosomal enzymes into extracellular space. iii. I-Cel Dx e. I-CELL Dx: Defect in Addition of Mannose-6-Phosphate Moiety to Lysosomal Enzyme to direct them to lysosomes: i. Mucolipidosis = General Lysosomal disorder, Very Rare 1. Abnormal N-acetyl-glucosaminotransferase (N-acetylglucosamine-1phosphotransferase) 2. Enzymes released into Extracellular Space: SO CULTURE MEDIUM CONTAINS LYSOSOMAL ENZYME ACTIVITY 3. Defect in Protein-Associated Mannose Phosphorylation ii. Type 1: Early Death, iii. Type 2: Partial Deficiency = Milder = Pseudo-Hurler = Adults iv. Labs: 1. Elevated Proteases, Glycosylases, and Lipases v. Physical: Coarse Facial Features, Thick Gums, Large Tongue, 1. Gargoyle Facies vi. Hepatomegaly, Cardiac, and CNS Abnormalities vii. Skeletal Abonormalities 1. Congential Dislocatin of Hip 2. Clubbing of Feet 3. Immobility of Extremeties 4. Pscyho Motor Retardations

5. Hypotonia and poor head control viii. Developmental Delay and Growth failure 1. Linear growth decelartes and ceases by age 2 2. Social Smile acquired and objects grasped, 3. NO ROLL OVER and cannot support heir wight f. Membrane Protein Expression on cell: Begins in cytosol on free rbosomes  RER i. Protein folding causes loss of protein bc no delivery to Golgi ii. Polyubiquitinated and dgradated by prteasomes iii. Chaperones that help: CARETICULIN and CALNEXIN g. SRP: Allows protein to enter RER by binding to N-Terminal Amino Acid of proteins made for Plasma Membrane or organelles of Endocytic/exocytic pathway h. VEGF: i. NOT excreted by Endothelial Cells, but important for growth and survival of Endothelial cells ii. Heparin-Binding Glycoprotein  Secreted as homodimer iii. Secreted under Hypoxic Conditions  1 hr after excercising. iv. Cause endothelial proliferation and growth of new capillarires in muscle. v. Decreased levels  Regression and disappearance of muscle capillaries i. Niacin Defiiciency: Pellegra and Hartnup Disease i. Dermatitis (red, scaly rash), Diarrhea, Dementia (or Cerebellar Ataxia) ii. Can be due to: 1. Low Niacin Intake: Pellegra 2. HARTNUP disease a. Defective Transporter for Large, Neurtal Amino Acids (ESPECIALLY TRYPTOPHAN) in Intestine and kidneys i. Tryptophan is precursor for biosynthesis of Niacin ii. Transporter that would reabsorb them in kidneys Is not effective iii. So no large quantities in blood, but yes in urine. b. Large Urine output of Neutral Amino Acids j. Alkaptonuria/Ochronosis: (Aut Recess) Tyrosine Build-up due to i. Arthritic Dx casued by deficiency of Homogentisic acid oxidase (homogentisate 1,2 dioxygenase) 1. Lack of Oxidase blocks metabolism of Phenylalanine-Tyrosien at level of Homogentisic acid  Accumulation of Homogentisic acid in body  Excreted (turns urine black when oxidized) OR Selectively binds to collagen in connective tissues, tendons, cartilage  Blue Black pigmentation most evident in Ears, Nose, and Cheeks = OCHRONOSIS ii. Most serious problem: Osteoarthritis w/ NEGATIVE RHEUMATOID FACTOR 1. Deposits of pigment in articular cartilages of joints  loss of normal resiliency  Cartilage becomes britlle and fibrillated  Wear nd tear erosion of abnormal cartilage  Denudation of subchondral bone  Cartilage fibrillates and driven into underlying bone = worse damage a. Intervertebral disc (# 1 site of attack), knees, shoulder, and hips later b. Degenerative arthropathy develops slowly iii. Urine Turns black on standing and get Debilitating Arthritis from Tyrosine Buildup iv. Ochronosis when Cartilage turns dark brown/black k. Cystinuria: i. Defect in epithelial transport of cystine and basic amino acids: Lysine, Arginine, Ornithine ii. Cystine Nephrolithiasis (Cystine Stones)

l.

Homocystinuria: i. Sulfur-Containing Amino Acid Disorder 1. Methionine Accumulates in blood  Decrease in Cystine ii. Mental Retardation iii. MARFAN-LIKE HABITUS, 1. Unlike Marfan: Mental Retardation, Limted Joint mobility, Seizures iv. DVT, Limited Joint Mobility, Increase Cardiovascular Dx m. Phenylketonuria: i. Deficiency of Phenylalanine Hydroxylase ii. Mental Retardation n. Metachromatic Leukodystrophy: i. Varied Neurologic and Psychiatric Symptoms: ii. Arylsulfatase A deficiency

Embryo
9) Embryo: a. Hydatidifrom Mole i. Partial = Fetus = triploid (69 XXX) = NO Choriocarcinoma = Normal/Enlarged villi ii. Complete = No fetus = 46 XX = Choriocarcinoma = Grapelike rd b. 3 and 4th Pouches  DiGeorge: No Thymus or PTH Gland, Chr 22q11 i. Tetany and severe hypocalcemia

Pharm
10) Pharm a. BPH: Due to DHT i. Finasteride 1. Inhibit conversion of testosterone to DHT by inhibiting 5a-reductase 2. Prevent DHT binding to nuclear androgen receptos to stimulate mitogenic growth factors that cause stromal and epithelial pherplasia + promote secondary sex characteristics in mean and women 3. DHT, not testosterone, is responsible for hyeprpalsia b/c DHT has slow dissociation from prostatic nuclear androgen receptor b. Cardiac: i. CHF 1. Reduce Mortality w/: a. ACEi, B-Blockers, Angiotensin Receptor Agonists, Spironolactone 2. Treat Symptoms w/ a. Thiazide or Loop Diuretics b. Nitrates ii. Supraventricular Tachycardias: 1. Atrial Fibrillation, flutter, and AV node reentrant tachycardia 2. TX: Slow down conduction through AV Node: a. DOC: IV Adenosine i. Endogenous nucleoside w/ VERY SHORT half life

ii. Rapid termination of SVT and converts to normal rhtyhm iii. Slows conduction velocity and increases refractoriness at AV node b. Use short acting B1-selective antagonist – Esmolol iii. Digoxin: Cardiac Glycoside 1. In CHF and Atrial Fibrillation a. Increase Contracitlity in CHF b. Decrease Conduction at AV node and depress SA node w/ A Fib 2. Effect: a. Inhibit NA-K-AtPase  Increase Intracellular calcium by indirect inhibition of Na/Ca2 exchanger i. During Depolarization, Na and Ca enter into myocardial cells. During Repolarization, NA is extruded OUT of cell via membrane bound Na-KATPase. Ca is extruded out via a Na-Ca2+ Transporter that exchanges Na for Ca2 and is driven by the transmembrane Na gradient. ii. Digitalis Inhibits Na/K-ATPase, which pumps out 3 Na ion and pulls IN 2 K+ ions. Because digitalis increases the Intracellular Na concentration by inhibiting the ATPase, Ca2+ increases in the cell  Increased force of cardiac myocyte contraction during systole iii. Digitalis ALSO DECREASES CONDUCTION THROUGH THE SA AND AV Nodes and INCREASES THE AUTOMATICITY of cardiac tissue iv. With Higher does of Digitalis, Inhibition of Na-K-ATPase ELSEWHERE IN BODY results in CLINICALLY SIGNIFICANT HYPERKALEMIA v. HYPERKALEMIA can cause FATAL CARDIAC ARRHYTHMIAS b. Also Stimulates Vagus Nerve c. Positive inotorpy  increase cardiac contractility and decreased AV node 3. Toxicity: a. Cholinergic: Increased parasympathetic tone i. Nause, Vomiting, Diarrhea, Blurry Yellow Vision (Van Gogh) b. Blurry Yellow Vision, Arrhyhtmias, c. ECG: T wave inversion, Increased PR interval, Shortened QT interval i. Arrhythmia and HyperKalemia d. WORSENED BY i. RENAL FAILURE (Decrease Excretion) ii. HYPOkalemia (Permissive for digoxin bindng at K+ Binding site on Na/K ATPase) 1. Hypokalemia potentiates digitalis toxicity b/c it decreases the Na-K-ATPase activity and potentiates the drug’s major effect. iii. Quinidine (Decrease Digoxin clearance b/c displaces from tissue binding site) 4. Treatmetn for Toxicity: a. 1st step = Normalize Potassium Levels, SLOWLY i. Hypokalemia potentiates digoxin and worsens toxicity b. Lidocaine, Cardiac Pacing, Anti-Dig FAB fragments, Magnesium iv. Pacemaker Action potential 1. SA node determines heart rate w/ slope of phase 4 slwo diastolic depolarization by spontaneous Na funny gates

2. ACH/Adenosine DECREASE rate of diastolic Depolarization and DCREASE Heart reate 3. Catechlamines INCREASE depolarization and INCREASE EHart rate 4. Sympathetic Stimulation Increases the CHANCE that the NA-f Channels are open v. Torsades de Point: TREAT W/ MG 1. Anything that prologns QT  Ventricular Tach. Can progress to V-fib. 2. Caused by low potassium: A potentially fatal rapid ventricular rhythm (250-350/min) 3. Quinine (Malaria) and Quinidine (Antiarrythmia), a. Occurs at therapeutic or even subtherapeutic levels 4. Potassium Channel Blockers (Sotalol) 5. Congential Abnormalities: Long QT syndrome a. Defects in Cardiac Sodium or Potassium Channels vi. AFib: Irregularly irregular w/ no P wave b/w irregular QRS 1. Treat w/ B blocker, Ca channel Blocker, or Digoxin 2. Warfarin for thombosis prophylaxis vii. A flutter 1. Antiarrhythmics Class IA, IC, or III viii. AV Block 1. 2nd Degree: Mobitz type 1 (Wenckebach) - PR interval longer till drop beat a. B-Blockes, Digoxin, Ca Blockers (NOT FELODIPIN), Increased Vagal tone rd 2. 3 degree: From Lyme dx. P waves no relationto QRS a. Pacemakers 3. Due to Increased Vagal tone a. Atropine: i. Anticholinergic to Increase AV Conduction ix. Acute Coronary Syndrome 1. Unstable Angina/ Myocardial INfarc (acute) 2. Tx: Nitroglycerine x. Hypertrophic Cardiomyopathy 1. B blocker or NON-DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKER (VERAPAMIL) xi. Vascular Dx 1. Temporal Giant Cell Arteritis a. High Dose Steroids 2. Polyarteritis Nodosa a. Corticosteroids, Cyclophosphamide 3. Kawasaki a. IV Immunoglobulin and Aspirin b. Coronary Aneurysms! 4. Buerger’s Dx: THromobonagiitis obliterans a. Stop smoking 5. Wegner Granulomatosis: a. Corticosteroids, Cyclophosphamide xii. ANP: 1. From atria in response to Increase BV and Atrial Pressure 2. Cause generalized vascular relaxation 3. DILATES RENAL AFFERENT ARTERIOLES (cGMP)

xiii.

xiv. xv.

xvi. xvii.

xviii.

xix.

4. CONSTRICTS EFFERENT RENAL ARTERIOLES (cGMP) a. Diuresis and Escape from Aldosterone BNP: Nesiritide 1. Recombinant B-Type Natriuretic Peptide  Increase in cGMP and Vasodilation 2. USE FOR ACUTE DECOMPENSATED HEART FAILURE 3. Toxic: HYPOTENSION Acute Coronary Syndrome and Angioplasty 1. Abciximab to bind Gp IIb/IIIa on activated platelets and prevent fibrinogen binding PDA 1. Indomethacin a. ENDomethacin ENDS the PDA b. NSAIDs Close PDA 2. PGE a. PGEE keeps it open b. Misoprostol Keeps bitch open (PGE) Cardiogenic Shock 1. NO B-BLOCKERS!!! Potassium Channel Agonists: Minoxidil (w/ Diazoxide) 1. Blood Vessels and B-Cell of Pancrease 2. Use in SEVERE/MALIGNANT HTN 3. Open KATP channes a. Vascular Smooth Muscle  Hyperpolarized and Vasodilate b. Pancreas B cell  Hyperpolize  Decrease Ca entry  Decrease Insulin release 4. Toxic: a. Hypertrichosis, Pericardial Effusion, Reflex Tachycardia, Angina, Salt Retention, Hyperglycemia Calcium Channel Blockers: 1. HTN, Angina, Arrhythmias (Not Nifedipine), Prinzmetals angina, Raynauds 2. Nifedipine, Verapamil, Diltiazem, Amlodipine a. Nifedipine SIMILAR TO NITRATES b. Verapamil SIMILAR TO B BLCOKERS 3. Block Voltage Dependent L=type Ca Channels of CARDIAC AND SMOOTH MUSCLE 4. REDUCE MSUCLE CONTRACTILITY 5. VASCULAR: a. Nifedipine > Diltiazem > Verapamil 6. HEART: a. Verapamil > Diltiazem > Nifedipine i. V for Ventricle 7. Toxic: a. Cardaic Dperesson, AV block, Peripheral Edema, Flushing, Dizziness, Constipation B-Blockers: 1. B1: Heart a. Do NOT GIVE Beta-1 To Diabetics b/c it blocks appearance of hypoglycemia! b. Can Use as ANTIDOTE TO THEOPHYLINE POISONING

i. Theophylline is a phosphodiesterase inhibiter that leads to decreased hydrolysis of cAMP to Adenosine monophosphate. OD of Theophyliine results in elevated intracellular levels fo cAMP ii. B Blocekrs (metoprolol) may be given to REDUCE cAMP lvels through INACTIVATION OF ADENYLATE CYCLASE iii. BE cardioselective to avoid asthma and bronchial hyperreacitivty 2. B2: Lung 3. B-Blockers a. Leters A-M are Beta1 i. Except Carvedilol and Labetalol 1. Labetalol is A1, B1 and B2: Pheochromocytoma and HTn Emergencies 2. b. Letters N-Z are Beta2 4. TWO B BLOCKERS NOT RECOMMENDED FOR ANGINA DUE TO CARDIOSTIMULATORY EFFETS (INTRINSIC SYMPATHOMIMETIC ACTIVITY) a. ACEBUTOLOL And PINDOLOL (Glaucoma) xx. Prophylaxis: 1. Post Stroke or w/ A fib: Chronic Anticoagulation a. Warfarin i. Inhibits gamma-carboxylation of Vitamin K dependent clotting factors and is used for chronic anticoag 1. 2, 7, 9, 10, Protein C, S ii. Reverse w/ Free Plasma Protien and coagulation factors iii. 2. Immediate Anticoagulation: IV a. Heparin i. Reverse w/ Protamine Sulfate b. Direct thrombin inhibitors for HIT i. Lirudins? 3. Prevention of Myocardial Infarction a. Aspiring 4. Clot busters: a. tPA b. Streptokinase xxi. Arrhythmia: 1. Action Potentials are affected: a. Action Potential for Atrial Cells i. Very Short  Adenosine is a good choice to treat atrial arrhtyhmia/SVT b. Action Potential for Ventricular Cells: i. Longer potential and treat by acting on Inactivated Sodium Channels (Lidocaine) c. Action 2. All Act as local anesthetics to slow or block/decrease conduction (esp depolarized cells) a. Decrease the slope of Phase 0 deopolarization b. Increase Threshold for Firing in Abnormal Pacemaker cells

c. All are state dependent  Selectively depress overactive tissue 3. Class 1: Na Channel Blockers: HYPERKALMIA CAUSES INCREASE TOXICITY a. Class 1A: Quinidine, Procainamide, DisoPyramide i. Use 1. Atrial and Ventricular Arrhythmias a. Especialy Reentrant and Ectopic Supraventricular and ventricular Tachycardia 2. Porcainamide: Ventr Arrythmia, and Increased AV node conduct 3. Quinidine: Atrial Fib/Flutter + Anticholinergic a. Decrease Vagal Tone and Increase AV node conduct (indirectly) ii. Effect 1. Increase Action Potential Duration, Increase Effective Refractory Period a. Procainamide DECAREASE SODIUM CONDUCTION  INCREASES Duration of Action Potential + Makes Action Potential LESS ENGATIVE  Increases QT Interval 2. Increase QT interval iii. Toxic 1. Quinidine: Cinchoonism  HA, Tinnitus 2. Procainamide: SLE-Like Sypmotms 3. Thrombocytopenia 4. Torsades de pointes  b/c of Increased QT interval b. Class 1B: Lidocaine, Mexiletine, Tocainide, Phenytoin i. Use: 1. Acute Ventricular Arrhythmias (Especially Post-MI) a. Greater effect on INACTIVATED SODIUM CHANNELS 2. Digitalis Induced Arrythmias 3. 1B is Best Post MI ii. Effect: 1. Decrease Action Potential Duration 2. Primarily Ischemic or Deopolarized Purkinje and Ventricular Tissue iii. Toxic 1. Local Anesthetic, CNS stimulation/depression, CV Depression c. Class 1C: Felcainide, Popafenone i. Use: 1. V-Tach that progress to V Fib 2. Intractable SVT 3. Last Resort in Refracoty Tachyarrhythmias 4. NOTE: USE IN PATIENTS W/O STRUCTURALLY ABNORMALITIES AND CONTRAINDICATED IN POST-MI patients ii. Effect: 1. Signficianly prolongs refracotyr period in AV Node 2. No Effect on AP iii. Toxic:

1. Pro-Arrhythmic, especially Post-MI 4. Class 2: B-Blocker: Propranolol, Metoprolol, Atenolol, Timolol, Esmolol a. Use i. V-Tach, SVT, A-Fib, and A-Flutter (Slowing Ventricular Rate) 1. ESMOLOL VERY SHORT ACTING b. Effect i. Decrease cAMP  Decrease Ca Currents ii. Decrease Slope of Phase 4  Suppress abnormal pacemakers iii. Increase PR interval, w/ AV NODE PARTICULARLY SENSITIVE c. Toxic i. Impotence, Exacerbation of Astham, ii. CV: 1. Bradycardia, AV block, CHF iii. CNS 1. Sedation, Sleep alterations iv. MASK SIGNS OF HYPOGLYCEMIA v. Metoprolol  Dyslipidemia d. Treat Toxic: GLUCAGON 5. Class 3: Potassium (K) Channel Blockers: Sotolol, Amiodarone, Ibutilide, Dofetilide, a. Use: i. When Other Anti-Arrythmics Fail (Bad situation) b. Effect i. Increase Ap duration, Increase Effective Refracotry period (ERP) ii. Increase QT interval c. Toxic i. Sotolal: 1. Torsades de pointes 2. Excessive B Block ii. Amiodarone: Class 1, 2, 3, and 4 effects b/c it alters lipid membrane 1. Pulmonary Fibrosis, Hepatotoxicity, HYPO/HYPERTHyroidism a. 40% iodine by weight b. Weight loss, Hyperreflexia, Palpitations (Hyperthyroidism) c. Increased FEV1FVC ratio (restircitve lung dx) 2. Corneal Deposits, Skin deposits (blue/gray)  Photodermatitis 3. Nuerologic effects 4. Constipation 5. CV effects a. Bradycardia, Heart Block, CHF 6. CHECK: PFTs, LFTs, and TFTs w/ Amiodarone iii. Ibutilide 1. Torsade de Points iv. Bretylium 1. New Arrhythmias, Hypotension 6. Class 4: Ca-Channel Blockers: Verapamil and Diltiazem a. Use

i. b. Effect i. ii. iii. c. Toxic i. ii.

Prevention of Nodal Arrhythmias: SVT Decrease Conduction Velocity Increase ERP Increased PR interval Constipation, Flushing, Edema CV 1. CHF, AV Block, Sinus Node Depression 2. 1st Gen Ca worst for CHF

7. Others: a. Adenosine i. Use: 1. DRUG OF CHOICE in Diagnosing/Abolishing Supraventicular Tachycardia a. Very short ating (15 sec) ii. Effect 1. Increase Efflux of K out of cell  Hyperpolarization of cell and Decrease of Ca channel. 2. Slowls conduction velocity and increases refractoriness at AV Node 3. Convert ACUTE SVT into normal rhtyhm iii. Toxic: 1. Flusihng, Hypotension, Chest Pain iv. Treat Toxic 1. THEOPHYLLINE b. Mg i. Use: TREAT TORSADES DE POINTS AND DIGOXIN xxii. Angina: 1. Reduce Myocardial O2 Consumption (MVO2) by decreasing 1 or more of determinants of MVO2 a. EDV, Blood Pressure, Heart Rate, Contractility, Ejection Time 2. Nitrates (Preload): NTG, Amyl Nitrate, Isosorbide Dinitrate  Increase O2 a. 1st Line: Stable Angina + Unstable Angina (ACS) – Nitroglycerine – Diagnosis and Treatment of angina pectoris b. Decrease EDV, BP, Ejection Time, and MVO2 i. Stable Angina: Transient Chest pain brought on by situations that increse Oxygen demans (exercise, cold, stress) and is relieved by stress 1. Due to Atheromatous plaque that allows enough blood at rest, but is insufficient to meet demands of heart in exertion  Ischemia and chest pain ii. NTG: Release NO on vascular smoth muscle  Vasodilate via a cGMP dependent mechanism iii. At low doses: More veins than arterioles  Decrease venous return  Decrease PRELOAD + O2 demands

iv. Also dilates Coronary Arterioles Directly  Increased blood flow  Important in cases of angina due to coronary vasopsams c. High doses: Dialte both venous AND ARTERIOLE widespread  Decrease Afterload  Hypotension and Relex tachycardia  REFLEX RESPONSE!  Increase Contractility and Heart Rate d. Side effects: i. Dilation of facial and meningeal arterioles: Flushing and HA 3. B-Blockers (Afterload): Propanolol, Metoprolol, Atenolol  Adrenergic Antagonist a. Decrease BP, Contratility, HR, and MVO2 b. Increase EDV and Ejection Time c. 2 CONTRAINDICATED i. PINDOLOL AND ACEBUTOLOL ii. Partial B agonists 4. Nitrates + B-Blocers a. Decrease BP and HR: VERY STRONG DECREASE IN MVO2 b. Cancelled Out Effects: EDV, Contracitlity, Ejection Time 5. Ca Channel Blockers:  Muscle Relaxation a. Verapamil/Diltiazem  Similar to B-Blcoker b. Nifedipine  Similar to Nitrates i. Use in Vascular Spasm: Prinzmetal Angina xxiii. Nitroglycerin + Isosorbide Dinitrate 1. Angina and Pulmonary Edema, Also as aphrodisiac and erection enhancer 2. Release NO in smooth muscle  Cause Increase in cGMP and smooth muscle relaxation 3. Toxic: a. Relfex Tachycardia, HYPOTension, Flusihng, HA, b. MONDAY Dx in Industrial Exposure: Tachycardia, Dizziness, and HA on exposure i. Developemtn of tolerance for vasodilation during work week, and loss of tolerance over weekend  Tachycardia, HA, Dizziness ii. SEVERE Consequence  Compensatory vasoconstriction is unopposed in critical areas such as coronaries, leading to nonatherosclerotic related ischemia and Cardiac Arrest c. Hypertension: i. Malignant HTN: 1. Nitroprusside a. Short: Increases cGMP via direct release of NO b. TOXICITY: RELEASES CN  Cyanide toxicity 2. Fenoldopam a. Dopamine D1 receptor agonist that relaxes RENAL VASCULAR SMOOTH MUSCLE 3. Diazoxide + Minoxidil a. K Channel Opener  Hyperpolarize and relax VASCULAR SMOOTH MSUCLE b. Toxic: Reduces Insulin rlease and can cause Hyperglycemia c. ii. Severe HTN 1. Hydralazine: Vasodilate Arterioles iii. Essential Hypertension: 1. Diuretics, ACEi, ARBs, Ca-Blockers

iv. AntiHTN + CHF: 1. Diuretcis, ACEi/ARBs, B-Blockers (compensated CHF), K-Sparing, (Spironolactone) Hydralazine a. B-Blcokers used cautiously in decompensated CHF v. AntiHTN + Diabetes Mellitus 1. ACEi/ARBs, Ca-Blcokers, Diuretics, B-blockers, Alpha-Blockers a. ACEi = Protective against Diabetic Nephropathy and 1st line vi. AntiHTN + Pregnancy 1. Hydralazine: a. Increase cGMP Smooth Muscle Relaxation b. Vasodilates Arterioles > Veins  AFTERLOAD REDUCTION (TPR) c. Co-Adminster w/ B-Blocker to Prevent REFLEX TACHYCARDIA d. CONTRAINDICATED IN ANGINA/CAD e. Toxic: i. Compensatory Tachycardia, Fluid Retention, Nausea, HA, Angina, LUPULIKE SYNDROME 2. MethylDopa vii. ACE Inhibitors (Captopril, -pril): 1. Use: a. HTN, CHF, Diabetic renal Dx b. Diabetics w/ HTN c. Protective against diabetic nephropathy d. Protective against Heart remodeling due to Chronic HTn 2. Contraindicated in pts w/ history of ACEi-Induced ANGIOEDEMA, Herediatry Angioedema, or Idiopathic Angioedema 3. Contraindicated w/ Bilateral Renal Artery Stenosis a. ACEi significantly DECREARES GFR by preventing constriction of EFFERENT ARTERIOLES  Increases Serum Creatinine 4. Side Effects: a. Hypersensitivity: i. Direct results of alterations in bradykinin generation in sensitive individuals b. Hacking Cough: i. Kinin Production alterations -> Excess Bradykinin  Chronic Cough ii. NOT A RESULT DUE TO ARBs c. HyperKalemia i. From decreased potassium d. Cough, Angioedema, Proteinuria, Tate Changes, hypotension, Pregnancy Problems w/ fetal renal damage, Rash, Increased Renin, Lower Angiotensin 2 viii. Captopril  ARF (From Prerenal Azotemia) 1. More relaxed efferent arteriole compared to afferent  Decrease GFR  increased Serum Creatinine 2. HTN w/ Diabetic Nephropathy and Hyperuricemia 3. Slow Renal Dx progression 4. Side Effects: a. Decrease of GFR with Renal Artery Stenosis

i. Blocks AT-2 which acts as a vasoconstictor of EFFERENT ARTERIOLES to increase GFR and decrease RBF. d. Diuretics: All Increase NaCL excretion and K excretion (except K sparing). All Increase Ca excretion (except Thiazides). Loop and Thiazides cause Alkalemia. Carbonic Anhydrase and K sparing  Acidemia i. Thiazides: Hydrochlorothiazide and Indapamide 1. Use: a. First Line HTN for Elderly and African Americans b. HTN/Edema w/ CHF but NOT FOR PULMONARY EDEMA c. Idiopathic Hypercalciuria (too much ca excretion) d. Nephrogenic Diabetes Insipidus i. Normally urine is diluted to below physiologic osmolarity by transport of solutes w/o water in Thick Ascending Limb and Distal Convoluted Tubule. This allows dilute urine to be excreted in absence of vasopressin. ii. In presence of vasopressin, there is an increase in permeability of the LATE distal convoluted tubule and collecting duct to water, allowing Osmosis of water into the HYPERTONIC interstitium. iii. The thick ascending limb contributes strongly to this hypertonic environment via Solute Transport and Deposition of ions in the Medullary Interstitial Flui. iv. In Nephrogenic Diabetes Insipidus, patients excrete large volumes of dilute urine. Hydrochlorthiazide intereferes w/ urine dilution by inhibiting the reabsorption of sodium from the Water Impermeable Early Distal OCnvoluted Tubule. Because Thiazide Diruetics affect ONLY the OSMOLARITY of the renal cortex (by blockin na transport from DCT), their use does NOT greatly Change medullary hypertonicity or urine concentrating ability 2. Effects: a. Binds to CHLORIDE receptor on Early distal tubule to inhibit Na/CL b. Decreases Ca Excretion 3. Side Effects: a. Hypokalemia, Metabolic Alkalosis, Aldosterone Excess, Hyperglycemia and Hyperlipidemia, and Hyperuricemia b. Can Precipitate an Acute gout attack 4. Only good for CrCl of 40 mL/min, NOT LOWER. a. i.e. Not for renal failure ii. Loop Diuretic: Furosemdie 1. Use: a. DOC for Flash/Emergency Pulmonary Edema and Edematous states (CHF, Cirrhosis, Nephrotic Sydnorme, Pulmonary Edema) and Hypercalcemia and Renal Disease 2. Rapid acting and have SIGNIFICANT DIRECT SMOOTH MUSCLE RELAXING EFFECTS IN THE PULMONARY VESSELS 3. Use for Edema in CHF, Hepatic Cirrhosis, and Renal Disease 4. Can use if CrCl is as low as 10 mL/min 5. Toxic:

a. Ototoxic, HYPOKalmeia, Dehydration, SULFA Rxn, Nephritis Interstitial, Gout i. Muscle weakness and hard of hearing 6. USE ETHACRYNIC ACID if Sulfa Allergy to Furosemide iii. Acetazolamide: Block Bicarb resorption 1. ACIDazolamide causes Acidosis 2. DOC for Glaucoma, ALTITUDE SICKNESS, URINARY alkalinization, and metabolic Alkalosis 3. NOT for CHF iv. K Sparing: Spironolactone, Triamterene, Amiloride, Eplerenone 1. Use a. Hyperaldosteronism, K depletion, Prevent Cardica Remodeling, CHF 2. Effect: a. Spironolactone: Competatitve Block of Aldosterone receptor (antagonist) in Cortical Collecting Tubule b. Traimterene and Amiloride: Block Na channels in CCT 3. Side Effect a. Hyperkalemia  Arrhythmia b. Endocrien effects w/ Aldosterone Atagonists c. Spironolactone: i. Gynecomastia and Anti-Androgen effects v. Mannitol: 1. Use: a. INTRACRANIAL/INTRAOCULAR PRESSURE INCREASE, Shock, Drug OD, 2. Effect: a. Osmotic Diuretic  Increase fluid tubule osmolarity  Increase urine flow 3. Toxic a. CHF, Pulmonary Edema, Dehdyration, CONTRAINDICATED IN ANURIA e. Lipid Drugs: i. All decrease LDL, All increase HDL [except Ezetimibe), All decrease TG (Except bile acids resins and Ezetimibe) ii. Statins: HMG-CoA Reductase Inhibitors 1. Effects a. GREATLY DECREASE LDL b. Increase HDL and Decrease TG 2. Mechanism: a. Inhibit Cholesterol Precursor, Mevalonate by inhibitng HMG-CoA reductase (rate limiting enzyme in hepatic cholesterol synthesis)  Compensatory upregulation of LDL receptors on hepatocyte cell surface membrane and clear more plasma LDL to decreae blood levels 3. Toxic: a. Hepatotoxicity  increase LFTs b. RHABDOMYOLYSIS!!! ESP WHEN COMBINED W/ FIBRATE (-fibrate/gemfibrozil) iii. Niacin 1. Effects a. GREATLY INCREASE HDL b. Decrease LDL and TG 2. Mechanism

a. Inhibit Lipolysis in Adipose Tissue  Reduces hepatic VLDL secretion and triglyceride secretion b. Prevents Hepatic VLDL cholesterol secretion  decrease in blood LDL levels and increase HDL levels 3. Toxic a. Red, Flushed face: i. TX w/ ASTHMA b. Hyperglycemia and Hyperuricemia i. Acanthosis Nigricans and GOUT EXACERBATION iv. Bile Acid Resins/ Sequestration: Cholestyramine/Colestipol/Colesevelam 1. Effects a. Decrease LDL b. Slight Increase HDL and TG 2. Mechanism a. Preevent Intestinal Reabsorption of Bile acids  Liver use cholesterol to make new b. Positively charged  Binds to negative charges of bile acids Resin bnds bile from GI tract and makes insoluble complexes in intestine  Excreted in stool c. Lack of bile acid resorption  choleterol converted to bile acids  reduction hepatic cholesterol level  LDL cholesterol receptor gene upregulated  Increased numbers of LDL cholesterol Receptors  Bind more LDL cholesterol and lower blood levels 3. Toxic a. PATEINTS HATE IT: Bad Tase and GI discomfort b. FAT Soluble Vitamins Decreased c. Cholesterol Gallstones v. Cholesterol Absorption Blocker: Ezetimibe 1. Effects a. Decrease LDL, no other effects 2. Mechanism a. Prevent Cholesterol Reabsorption at Small Intestine Brush border 3. Toxic a. Rare LFTs vi. Fibrates: Clofibrate/Gemfibrozil/Fenofibrate/Bezafibrate 1. Effect a. GREATLY DECREASE TRIGLYCERIDES b. Increase HDl and decrease LDL 2. Mechanism: a. Induce syntheis of major HDL cholesterol apolipoportiens: ApoA-1 and apoA-2 b. Upregulate LPL  Increase Triglyceride cleance and VLDL turnover c. Increases activity of Peroxisome Proliferation activated receptor alpha receptors: i. Increases Lipoprotein Lipase activity  Incrasesd VLDL clearance and increased HDL levels  Large Decrease in tirglyceride levels and some lowering of LDL and VLDL levels 3. Toxic

a. Myositis, Hepatotoxicity (increase LFTs), Cholesterol Gallstones b. WHEN COMBINED W/ A STATIN  INCREASE RISK OF RHABDOMYALSIS vii. Olestra 1. Effect: a. Food additive that mimics taste and texture of triglycerides but has no nutritive (caloric) value. 2. Mechanism: a. Made from Sucrose molecules attached to five or more FA chains b. Very bulky molecule resistant to digestion by lipases and absorption by gut wall c. Not absorbed and is excreted in feces f. Liver Toxicities i. Peri-Portal / Zone 1 1. Phosphorus poisoning 2. Eclampsia ii. Centrilobar / Zone 3 (Terminal Hepatic Vein) 1. Acetaminophen 2. CCL4, Bromobenzene, Halothane, Rifampin iii. Hepatic Fibrosis 1. Chronic Hepatitis and/or Hepatocellular Injury 2. Ethanol, Methotrexate, Amiodarone iv. Granuloma Formation 1. Sulfonamides, Methyldopa, Quinidine, Hydralazine, Allopurinol v. Microvesicular Fatty Change 1. Tetracycline, Salicylates (ASA), ethanol vi. g. Pseudomembranous Colitis: i. Due to: 1. Clindamycin (used to tx anaerobic C. perfringens) 2. Ampicllin 3. Cephalosporin h. Sulfa Allergies: i. Celecoxib, Sulfonylureas, Sulfamethoxazole, Sulfasalzine, Thiazide Diuretics i. Steven Johnson Syndrome i. Immune complex mediated hypersensitivity reaction that involves mucocutaneous membranes 1. Lies on Urticaria-Erythema Multiforme-Toxic Epidermal Necrolysis spectrum 2. Extensive Shedding of epidermis, Blistering of nasal, oral, and gential mucosa as well as conjunctiva a. Severe pain on swallowing and dehydradtion 3. Erythema, Palpable Purpura, Epidermal Necrolysis ii. Clinical Picture: 1. Prodrome of Fever and Fatigue 2. Skin and Mucocutaneous lesions a. Lesions begin as erythematous macules, progress to form bullae, and subsequently slough off

j. k.

l.

m. n. o.

b. Diffuse, Generaized erythematous macules and patches are tender totouch and accompanied by BURNING SENSATINO of Skin iii. Potentially fatal iv. Drugs: (Penicillins, Sulfonamides, Ethosuximide, Lamotrigine) 1. Anti Convulsants a. Lamotrigine (partial and tonic clonic – blocks Na channels) i. GI Upset, Dizziness, Diplopia, Amnesia b. Phenytoin (1st line for tonic clonic and partial – Increased Na Inactivation) i. Nystagmus, Diplopia, Ataxia, Gingival Hyperplasia, Hirsutism, Megaloblastic anemia (blockage of folate absorption and increased folate utilization  Hypersegmented Neutrophils) c. Ethosuximide (absence) i. Alsoc causes: GI distrubacnes, fatigue, dizziness, Blood Dyscrasias d. Carbamazepine (Partial and tonic clonic): Inactivate Sodium Channels and inhibits NMDA receptors i. Diplopia, INdcution of Cytochrome P450, Blood Dsycrasias, Liver tox 1. Agranulocytosis (Get Pneumonia b/c no Neutrophils), Aplastic anemia, Ataxia, Diplopia, Liver Toxiciity, Teratogenic 2. Must monitor CVC and LFT Cutaneous Flushing: i. Niacin, Adenosine, and Vancomycin Red Man Syndrome i. Rapid Aministration of Vancomycin 1. Tx of C. Difficile, S. Aureaus ii. Anaphylactoid reaction mediated by IgE that leads to histamine: 1. Confluent erythematous patches 2. Redness of face, neck, upper body, back and arms 3. Tachycardia, hypotension, nausia iii. LACK OF EXOFLIATION OF SKIN!! 1. Different than other erythroderma from drugs iv. Prevent/tx w/ Diphenhydramine 1. First gen H1 receptor antagonist 2. Ethanolamine family: Marked sedation Disulfiram like rxn i. Metronidazole, Cephalosporins (Cefamandole and cefoperazone), chloramphenicol, griseofulvin, quinidine, procarbazine, 1st gen sulfonylureas: Tolbutamide Lupus Like Syndrome i. Hydralazine, Procainamide, Acetylation drugs Septic Shock i. Tx: 1st lien Norepinehprine (a1, a2, B1 agonist) Tuberculosis i. Prophylaxis in asymptomatic patients w/ postive PPD 1. Isoniazid for 6 months  prevents 90% activation of latent tb for 20 yeras ii. Children: 1. 6 months w/ Isoniazid and Rifampin w/ additional coverage of Pyrazinamide for first 2 months

iii. Rifampin: MOST POTENT (Not used b/c Significant lvier toxicity risk) 1. Use to treat TB: a. Blocks RNA synthesis by binding to beta subutin of Dna dpendent RNA polymerase (encoded by rpo gene) and blocking RNA trasncritpoin 2. Side Effects: a. Significant liver toxicitiy b. Reddish/Brown discoloration of urin c. Induces P450 iv. Isoniazid: 1. Inhibits Mycolic Acid Synthesis, Intefereing w/ Cell wall maintenance 2. Effectively penetrates human Cells and interacts w/ intracellular pathogens 3. Used as monopharm prpohlyaxis w/ a positive PPD and in combo tx 4. Side effects a. Most serious: Hepatitis b. Everything in the world, c. Hepatotoxic d. SLE, i. Joint pain, photosensitivity, and facial rash e. G6PDH Hemolysis f. Inhibition of P450 and Elevated Liver Function tests g. Seizures v. Ethambutol 1. Use a. TB 1st line of 4 (INH, Pyrazinimdine, Rifampin, Ethambutol) b. Used w/ Rifampin for patients who either cannot tolerate isoniaize or are infected w/ INH resistant M. TB 2. Mechanism a. Inhibits Arabinosyl Transferase mediated synthesis of Arabinogalactin for mycobacterial cell walls: Cell wall synthesis inhibition b. Inhibiton of polymerization of cell wall precursors 3. Toxic a. Red-Green Color Blindness b. Retinotoxicity: Dose dependent visual disturbances c. Decreased visual acuity d. Optic neuritis e. Retinal Damage vi. Pyrazinamide: 1. Use a. M. TB 2. Mechanism a. Fatty acid synthase gene 3. Toxic a. Hepatotoxicity, rare at normal doce b. Hyperuricemia and gout 4. vii. Dapsone:

1. Use a. Leprosy 2. Mechanism a. Inhibit Folic acid synthesis 3. Toxic 4. p. Antifungals i. Ketaconazole 1. Used to treat tinea corporis 2. Effects: a. Blocks formation of fungal membrane sterols and blocks enyme Desmolase/P450 b. Inhibits Ergosterol Synthesis 3. Side effects a. Block of desmolase/CYP450scc  Block adrenal production of testosterone and cortisol from cholesterol  Block feedback inhibition of POMC gene  Cuases increase in ACTH, Lipotropin, MSH, Endorphis  Hyperpigmentation in skin (like addisons) b. Hyperpigmentation, Decreased libido, Impotence, Gynecomastia, INHIBITS Cytochrome P450 ii. Fluconazole: 1. Same As Ketoconozale BUT NO ENDOCRINE SIDE EFFECTS 2. Use for Cryptococcus Neoformans and has GOOD CSF Penetration 3. Side Effects a. Nausea and vomiitn iii. Itraconazole 1. Lacks Endocrine Effects of Ketoconazole 2. Use for Blastomycosis and AIDS-Histoplamsosis a. Use with Flucytosine for Chromoblastomycosis 3. Side Effects a. Nausea, Vomiting, Rash on Immunocompromised iv. Amphotericin B 1. Use a. Systemic Mycoses 2. Effect a. Binds to Ergosterol: Disrupt Fungal Wall Synthesis 3. Side Effects: a. Fever/Chills, Decreased Creatinine clearance, Hypotension, Anemica, Arrythmias, Nephrotoxicity, Hypokalemia, decreased erythropoeiten, hypomagnesemia, renal tubular acidosis, decreased GFR, nausea and vomiting, Hyopotension v. Flucytosine 1. Use: a. Solely in Combo w/ Ampho B to tx Cryptococcus and Systemic Cnadida 2. Side Effects:

a. Pancytopneia, Elevated Liver enzyme Levels, Nausea and vomiting, Anemia, Leukopenia, Thrombocytopenia, Parkinsonian effects (restlessness, drowsiness, fatigue, depression, constipation) vi. Griseofulvin 1. Use: a. Superficial Infections: Tinea or Ringworm (Dermatophytes) b. Oral treatment of superficial infections 2. Effects a. Interfreres w/ Microtubule function and disrupts mitosis b. Deposits in keratin containing tissue (nails) 3. Side Effects: a. Teratogenesis, Carcinogenesis, Confusion, HA, INDUCTION OF CYTOCHROME P450 vii. Terbinafine 1. Use: a. Dermatophytoses, specifically Onychomycosis (nail fungal infections) 2. Effects: a. INterefres with Ergosterol Biosynthesis b. Inhbits fungal enzyme Squalene Epoxidase 3. Side Effects a. NO P450 effects b. Causes accumulation of a toxic metabolite viii. Caspofungin 1. Use: a. Invasive Aspergillosis 2. Effect a. Inhibit cell wall synthesis 3. Side Effects: a. GI upset and Flushing b. DO NOT TAKAE WITH CYCLOSPORINE  Elevated Liver enzyme levels q. Antibiotics i. Clindamycin: 1. Use: Anaerobic Abscesses 2. Side Effects: a. Pseudomembranous colitis ii. B lactams: 1. B-Lactamases: Hydrolyze B lactam 2. Cephalosporin a. 3rd gen: Gram – (Meningitis) 3. Toxic a. Hypersensitivity Rxn, Rash, GI upset iii. Vancomycin 1. Ototoxic iv. Aztreonam: 1. Use: Strong activity agains gram negative and highly resitsnat to B lactamse degradation v. Aminoglycosides

vi.

vii.

viii.

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1. Inactivation by Phosphorylation, Acetylation, Adenylation a. Group Transferases that covalently modify antibiotic b. Plasmid mdiated 2. Acute Rxn: a. Ototoxic, Nephrotoxic, Teratogen i. Acute Tubular Necorsis  Reduce GFR and rise in Serum Creatinine ii. Nephrotoxic effects greatly increased when combined w/ cephalosporin (cefoxitin) Macrolides: (Clindamycin, Chloramphenicol, Erythromycin) 1. Bind to 50S and inhibit translocation  inhibit protein synthesis 2. Treat a. Upper Repsiratory Infections b. Gram + (Azithromycin), Legionnaire’s dx, syphilis, Community acquired Pneumonia, Corynebacterium Diphteira 3. Toxic a. GI Discomfort, Eosinophilia, Skin Rashes b. Azithromycin i. Allergic Hepatitis and Thrombophlebitis c. Erythromycin and Clarithromycin i. CHOLESTATIC HEPATITIS!!!! ii. Thrombophlebits  IV Erythromycin 4. Tetracycline, 1. Bind 30S of ribosome and prevent attachment of aminoacyl-tRNA a. Treat V. Cholera, Chlamydia, and Ureaplasma 2. Efflux 3. Modification of ribosomal Binding sites 4. Acute Rxn: a. Tooth Discoloration, PHotosensitivity Doxycycline 1. Community Acuired pneumonia, Chlamydia, Lyme, etc 2. Toxic a. GI distress, Tooth discoloration in children, Photosensitivity Chloramphenicol 1. Modification of ribosomal bidnign sites 2. Life threatening dx such as Bacterial meningitis, Rickettsial Dx, or Life threatening dx where patients are allergic to other antibiotics 3. Borad spectrum and low cost, so used elsewehre 4. Toxic a. APLASTIC ANEMIA and GRAY BABY i. Suppression of all blood cell lines: Erythroid, myeloid, thrombocityes ii. Anemia, ENutropenia, Thrombocytopenia: 1. Fatigue, Infection, Excessive bleeding, easy bruising, malaise, PALE CONJUNCTIVAE b. Use in Foreign Countries for Meningitis Empiric Therapy Macrolide (Erythormycin, Azithormycin)

1. Reduced Permeability 2. Modification of ribosomal binding sites 3. Acute rxn: a. GI discomfort, Acute Cholestatic Hepatitis, Eosinophilia, Skin Rash xi. Polymixin: Severe Gram – only 1. Bind to cell membrane phospholipids and destroy membrane by acting like a detergent 2. Toxic: a. Nephro and Neurotoxic b. Numbness of extremetieis, dizziness, drowsiness, confusion, nystagmus, blurred vission xii. Fluoroquionolones: -Floxacins 1. Mechanism a. Inhibit Toperisomerase 2 and 4, DNA gyrase 2. Use: a. Gram negative rods of URINARY AND GI TRACTS i. Pseudomonas, Neisseria, and Some Gram positive organisms b. Community acquired pneumonia (Gatifloxicin) c. 3. Side Effects: a. Tendinitis, esp Achilles’ Tendinitis: i. Affected tendon can rupture  Soft muscular mass on nproximal poritono f right calf and exquisite tenderness around ankles when reflexes are tested ii. Unable to plantar flex iii. People at Risk: 1. <50 yrs old, history or renal dx, hemodialysis, renal transplant, or long term glucocorticoid use b. GI Upset, Superinfectins, skin rashes, HA, dizziness c. Contraindicated in Pregnant women and children due to DAMAGE TO CARTILAGE d. Leg cramps and myalgias in kids 4. Resistance a. Chromosome encoded Mutation in DNA Gyrase xiii. Antivirals 1. Acyclovir a. Use i. HSV, EBV, VZV, CMV b. Mechanism i. Purine analog that inhibits viral DNA polymerase c. Toxic i. Neurotoxic ii. Nephrotoxic 2. Amantadine a. Use i. Orthomyxovirus (Influenza A) w/in first 48 hours ii. Prophylaxis

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b. Mechanism i. Inhibits endosome mediated uncoating of single stranded RNA viruses before transcription and replication c. Toxic i. Insomnia, ATAXIA, Dizziness, SLURRED SPEECH 1st line CMV: Ganciclovir: a. Activated by phosphorylation by viral protein thymidine kinases and acts as an ANALOG TO dGTP (same as Acyclover for Herpes Zoster). Forms guanine analog i. Guanine analog results in chain temriantion when read by viral DNA polymerase ii. Competitively inhibits th eincorporation of dGTP into replicating viral DNA b. Must monitor pts for Myelosuppresion and Nephrotoxicity 2nd Line CMV (Ganciclover Resistant CNV): Foscarnet a. Does NOT require thymidine kinase b. Inhibits DNA polymerase at pyrophosphate binding site c. Toxic i. Renal Hep B: a. Acute Hep B: i. Abdominal Pain, Positive HBsAg, and presence of IgM anti-HBcAb ii. Up to 15 weeks after exposure, pt is positive for HBV DNA, HBsAg, and Anti-HBcAB, and HBeAg, but NEGATIVE for ANTI-HBeAba dn Anti-HBsAB iii. Tx: 1. Lamivudine and Interferon-a a. Lamivudine = Cytidine analog that inhibits Reverse trasncritpon and blocks haptitis replication 2. INterferone a blocks viral replication b. Vaccinated: i. ONLY Anti-HBsAb Hep C: a. Ribarvirin w/ pegylated Interferon a Interferon a. Use i. Hep C (use w/ Ribavarin) b. Mechanism i. Block c. Toxic i. Bone Marrow Suppression (leads to anemia, but not w/ hemolysis) ii. Liver toxicity, weight loss, FLUI LIKE SYMPTOMS, DEPRESSION Ribavarin a. Use i. Treat Hep C b. Mechanism i. Inhibits Inosine Monophopshate Dehydrogenase  Inhibit nucleotide formation

r.

c. Toxicity i. Hemolytic Anemia w/ Decreased Hematocrit, Haptoglobin, and Increase LDH and unconjugated bilirubin 9. Protease Inhibitors: -vir a. Use b. Mechanism c. Toxic i. Fat redistriubtion ii. Gi Intolerance iii. Indinavir 1. Kidney stone formation: Crystal induced nephrpathy 2. Precipattes in urine and obstucs flow  Flank pain and hematuria, w/ needle shaped crystals in sediment 3. hyperlipidemia 10. NRTI: Vudines a. Use b. Mechanism c. Toxic i. Peripheral Neuropathy, GI intolerance, Pancreatitis ii. Bone Marrow Supression: REVERSE w/ G-CSF iii. Lactic Acidosis, Rash, MeGALOBLASTIC ANEMIA 11. Integrase Inhibitors: Raltegravir a. Use b. Mechanism c. Toxic i. Hypercholesterolemia Immunosuppression i. Sulfasalzaine 1. Use a. Ulcerative Colitis  Pyoderma Gangrenosum on Legs: i. Ulcerated lesions w/ violaceous borders on legs 2. Mechanism a. Combo of Sulfapyridine (Antibacterial) and Mesalamine (Anti Inflammatory) 3. Toxic a. Malaise, Nasuea, Sulfonamide Toxic, Reversible Oligospermia ii. 6-MP 1. Use a. Cancer, Ulcerative Colitis, Chron’s Dx 2. Mechanism 3. Toxic iii. Methotrexate 1. Use a. Cancer, Ulcerative Colitis, Chron’s Dx 2. Mechanism

a. Folate Analog that Inhibits Dihydrofolate Reductase  Decreased elvels of Tetrahydrofolate (TH4) and Deoxythymidine Monophosphate (nucleic acid precursor) b. Arrest cell division in HIGH GRADE CANCERS: CNS Lymphoma c. Interferes w/ normal cellular utilization of folic acid 3. Toxic a. Megaloblastic Pancytopenia: Supplement w/ Leucovorin (Folinic Acid / 5formyltetrahydrofolate) which overcomes methotrexate inhibition by providing product of DHFR enzyme iv. Infliximab 1. Use a. Chron’s Dx: Esp w/ anal fistulas b. 2nd for Ulcerative Colities after Aminosalicylate: Sulfasalazine 2. Mechanism a. Antibody to TNF-a 3. Toxic v. Inhaled Corticosteroids: Beclomethasone 1. Use a. Long term asthma/ chronic asthma 2. Mechanism a. Inactivating NF-kB  Block transcrption factor ciritcla in production of inflammatory mediators (TNF-a) that mediate asthma attacks 3. Toxic a. Oral Thrush  immune modulation properties attenuate local immune response of Oropharynx and Upper Airways vi. Long acting B2: Salmeterol 1. Use 2. Mechanism 3. Toxic a. Temor and Arrhythmia s. GGPDH deficiency hemolysis  Severe Anemia i. Durgs w/ High redox potential ii. Primaquine and Sulfonamides, Isoniazid iii. Juanidce, Pallor, and Dark urine w/ Back pain t. Granulocytopenia: Low granulocytes (WBCs) i. Clozapine, Ticlopidine, Sulfasalazine, Antithyroid drugs ii. Trimethorpim and Dapsone from antibiotics u. NSAID Renal failure i. CHF  Diuretic  Decrease body fluids  Angiotensin 2 released by body to compensate with vasoconstrictions -> Kidneys simultaneously release prostaglandin E at both afferent and efferent arterioles arterioles to VASODILATE ii. NSAIDS inhibit COX-1 and 2 and block prostaglandin production  NO Afferent arterial dilation  Kidneys no longer perfused  Prerenal Azotemia v. Warfarin i. Coumarin Anticoagulant ii. Prophylaxis and Tx of Thromboembolic Complications associated w/ Cardiac valve replacement

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iii. Prophylaxis and Treatment of Venous Thrombosis and Pulmonary Embolism iv. Tx for Atrial Fibrillation v. Side Effects: Warfarin Necrosis 1. Necrosis of Skin b/w 3rd -10th days of therapy a. Breast, Thighs, Buttocks) 2. Lesions are initially sharply demarcated, erythematous, and purpuric 3. May resolve OR progress to Large, irregular, hemorrhagic bualle that can become necrotic 4. Due to warfarin’s ability to deplete Protein C  Hypercoagulability and thrombosis in cutaneous microvasculature vi. Side Effect: Cholesterol Embolism, Purple Toes Syndrome, Easy Bruisability, and Dizziness Autonomic Nervous System Fun: i. Saliva: 1. Both Sympathetic and Parasympathetic 2. Block both to decrease saliva: a. Anticholiergic (Tolterodine) and a Anti Adrenergic (Metoprolol block B2 salviary gland)) ii. In Pulseless Electrical Activity or Asystole: 1. Atropine (paraysmp inhibitor) and Epinephrine (sympathicomimetic nonspecific) iii. Pheochromocytoma: 1. Phenoxybenzamine (a block) and Metoprolol (B block) METHemoglobin TX = METHylene Blue or Ascorbic Acid i. Nitric oxide administration for pulmonary hypertensive dx of newborn ii. Nitric Oxide reacts w/ Hg to produce Methemoglobin 1. Methemoglobin reduces O2 carrying capacity of RBC  Cause dizziness, dyspnea, confusion, seizures, coma. iii. Methylene blue or Ascorbic acid resortes hemoglobin to proper state. 1. Mehtyleen blue enhances conversion of Methemoglobin to Hemoglobin by increasing activity of enzyme Methemoglobin Reductase 2. Ascorbic Acid reduces Ferric (Fe3+) into ferrous (Fe2+) ions. Chloramphenicol Gray Baby i. Newborns who get chloramphenicol immediately after birth or before delivery ii. Order of Symptoms 1. Abdominal Distention w/ or w/o emesis 2. Progressive pallid cyanosis 3. Vasomotor collapse, frequently with irregular respiration iii. Also: 1. Loose, greenish stools, a refusal to suck/feed, ashen color, and lactic acidosis iv. Death occurs in a few hours Malignant Hyperthermia: i. Autosomal Dominant Genetic Dx affecting skeletal muscle ii. Presents as Muscular Rigidty and Hyperthermia when patient gets Halothane 1. Also due to Inhalational anesthetics (EXCEPT N20) and Succinylchline iii. Due to increase in Free Calcium contentration from abnormal Ryanodine Receptors iv. Tx: Dantrolene to prevent Calcium release from SR and thereby relax muscles Dantrolene

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i. Malignant Hyperthermia ii. Neuroleptic Malignant sydnorme Bisphosphonate: Etidronate, Alendronate, etc i. Use 1. Paget dx of bone, Metastatic bone dx, Osteoporosis, Malignancy associated HyperCa ii. Effect 1. Inhibit osteoclastic activity, redcue both formation and resorption of hydroxyapatite 2. Decrease pain and factures by reducing number and activity of osteolcasts iii. Toxic 1. Osteonecrosis of Jaw, Corrosive esophagits (not Zoledronate), hypocalcemia Serum Sickness: i. Hypersensitivity to drugs: 1. Drug acts as hapten  Binds to plasma proteins 2. Drug-Protein Complex recognized as being foreign to body  Serum Sickness ii. Fever, Cutaneous Eruptions (Mrobilliform and/or urticarial), LAD, Arthralgias 1. My Bones Hurt iii. Erythema Multiforme may also appear in severe case iv. Rxn delayed or 7-10 days after initial exposure for IgG ab to form v. Cefaclor  Much higher sickness in infants and children vi. Glomerulonephritis, Neurophaty, and Severe Vasculitis may occur vii. Tx: Oral Prednisone and Diphenhydramine 1. Prednisone tx for arthralgias and skin rash 2. Diphenhydramine for Urticaria Drugs that cause SIADH i. Tricyclic, SSRI, MAOIs, antipsychotics, Carbamazepine, and antineoplastics Progesterone and Early Abortion (by day 49): i. Mifepristone: RU-486 1. Use 2. Mechanism a. Progesterone receptor antagonist b. Progesterone = setorid hormone produced in resonse to LH by corpus luteum during second half o fmenstural cycle: it Inhibits secretion of LH and FSH thereby preventing further ovulation c. After conception it stimulates production of thick cervical mucus to prevent further sperm entry into uterus d. It is produced by placenta during 2nd and 3rd trimesters. e. It acts to maintain pregnancy by stimulating endometrial proliferation and relaxing the uterine smooth muscle to prevent contactions f. No conception = end of progesterone = Menstruation begins 3. Toxic 4. Seizures: i. Status Epilepticus 1. DOC: Diazepam a. Short acting to increase GABA effects by increcing opening frequency of chloride channel

b. Immediate effect, Readily available in PREHOSPITAL settings, Does not require refrigeration c. IV or Ass 2. Lorazepam in hospital ii. Generalized Tonic Clonic 1. DOC: Phenytoin and Carbamazepine and Valproic Acid 2. DOC Prophylaxis: Phenytoin (Parenteral) iii. Partial and Generalized Tonic Clonic 1. Carbamazepine, Phenytoin, a. Carbamzaepine blocks repetitive activation of Na channels i. 2. Phenobarbital a. Second line for these iv. Absence: 1. Ethosuximide a. Blocks low threshold T-type calcium Channels v. Simple Partial or Complex Partial 1. DOC: Carbamazepin 2. Gabapentin a. Blocks H-Current modulators, and is an analog of GABA vi. Febrile Seizures in Cihldren 1. Phenobarbital a. Requires longer time, but it is very effetive b. Higher incidence of respiratory depression c. Increases Duration of Chloride channel opening vii. Preeclampsia 1. Hypertension and Proteinuria in a pregnant woman a. HA, Blurred vision, Abdominal pain, Edema of Face and extremities, Altered mentation,a dn Hyperreflexia b. Thrombocytopenia nd Hyperuricemia may also occur nd 2. 2 or 3rd trimester: 3. HELLP sydnrome: a. Hemolysis, Elevated iver Function tests, Low Platelts 4. TX: a. 1st line: Deliver the BABY! b. IV Magnesium to PREVENT ECLAMPSIA/SEIZURES i. Toxic: 1. Depressed Tendon Reflexes, Respiratory paralysis, Cardiac Arrest nd c. 2 Seizure prevention line: Diazepam and Phenytoin gg. Poisons: i. Salicylate Toxicity (Aspirin) 1. Gi Irritation and Prolonged bleeding occur at therapeutic levels 2. Uncouple Oxidative Phosphorylation, Inhibit Krebs Cycle Enzymes, and inhibit Amino Acid Synthesis 3. Tinnitus = Threshold from mild to severe toxicity

Tinnitus, Vomiting, Vertigo = Salicylism Decrease Hearing are First Signs of Toxicity Metabolic acidosis and Hyperventilation occur leater Respiratory Alkalosis  Directly stimulating respiraty center in brain stem: Central Hyperventilation and Hyperpnea 8. Metabolic Acidosis w/ Elevated Anion Gap  Interference w/ Kreb cycle  Reversion to Anaerobic Glycolysis  Lactic Acidosis  Metabolic Acidosis ii. Acetaminophen (Tylenol) 1. Nausea, Vomiting, Abdominal Pain, and Shock 2. Irreversible Hepatic Failure w/in 8 hours 3. Extensively metabolized in liver 4. Forms Nontoxic Sulfate and Glucornide Conjugates 5. Small Portion of drug metablized by Cytochrome P-450 Mixed Oxidase enzyme system to form a toxic, intermediate metabolite, which (under normal circumstances) conjugates w/ Glutathione to form nontoxic Cysteina nd Mercapturic Acid derivatives a. In OD, Glucuronide and Sulfate Conjugation pathways become saturated b. Large protion of drug shunted into P-450 path  Depletion of hepatic stores of Glutathione  Subsequent binding of metabolite to other hepatic proteins  Cellular Necrosis 6. Tx: N-Acetylcysteine to make Glutathione (w/in 10 hours) a. ACetylcystein decreases extent of injury by maintiang or restornign glutathione levels b. Acts as an alternative substrate for conjugation w/ reactive metablie and subsequent excretion into urine iii. Hydrochlorothiazide: 1. Metabolic Alkalosis w/ Compensated Respiratory acidosis (decreased breathing) iv. Lead Poisoning (Chronic) 1. Anemia w/ Basophilic Stippling of RBCs, Neuropathy, and Abdominal Pain v. Mercury poisoning (chronic) 1. CNS atrophy, gingivitis, gastritis, Renal tubular changes 2. Acute can cause Renal tubular nencrosis and GI epithelial Necrosis hh. P450: SER of hepatic cells i. Detox 1. Barbiturates, Carcinogenic Hydrocarbons, Steroids, CCl4, Alcohol, Insecticides ii. Induced By: 1. Phenobarbital, Primidone, Barbiturates, Rifampin, Carbamazepine, Steroids Phenytoin, Pioglitazone, Omeprezole, Smoking, Charcoal Grilled food iii. Inhibited by: 1. Cimetidine, Fluoroquinolones, Fluvoxamine, Amidoarone, Fluconazole, Isoniazid, some SSRIs, Zafirlukast, Bupropion. Fluoxetine, Quiniden, Paroxetine, Amiodarone, Azoles, Diltiazem, Grapefruit Juice, HIV Protease Inhibitors, Macrolides (NOT Azihtromycin) ii. Endometriosis: i. Tx: Danazol for Pelvic Pain 1. Androgen that used to endometriosis by giving excess testosterone to decrease gnoadotropin releasing hormone secretion from hypothalamus  Decreases LH and FSH.

4. 5. 6. 7.

2. SE: a. Menstrual irregularities, thrombotic events, benign hepatic adenomas, benign intracranial hypertension (Pseudotomor Cerebri), weight gain, acne jj. Cholesterol: i. Niacin (VB3) 1. Decrease VLDL, LDL, Triglyceride levels 2. Increase HDL 3. Causes Facial Flushing – Primary reason for noncompliance ii. Statins’ 1. Rhabdomyalasis kk. Amphetamiens i. Toxicity tx w/ Benzo for symptoms and AMMONIUM CHLORIDE to acidify urine and trap in urine ii. Pheochromocytoma 1. DOC: Phenoxybenzamine a. Irreversible, nonselective alpha antagonist w/ a longer duration of action than phentolamine b. Use until patient can be taken to OR to surgically remove mass 2. Part of Men 2A and 2B a. 2A: Pheochromocytoma, Parathyroid, And Medullary Carcinoma of Thyroid b. 2B/3: Pheochromocytoma, Medullary Carcioma of Thyroid, and Mucosal Neuroma ll. Cholinergics mm. Adrenergics i. B-Blockers: 1. B1: Heart a. Do NOT GIVE Beta-1 To Diabetics b/c it blocks appearance of hypoglycemia! 2. B2: Lung 3. B-Blockers a. Leters A-M are Beta1 i. Except Carvedilol and Labetalol 1. Labetalol is A1, B1 and B2: Pheochromocytoma and HTn Emergencies 2. b. Letters N-Z are Beta2 4. TWO B BLOCKERS NOT RECOMMENDED FOR ANGINA DUE TO CARDIOSTIMULATORY EFFETS (INTRINSIC SYMPATHOMIMETIC ACTIVITY) a. ACEBUTOLOL And PINDOLOL (Glaucoma) nn. Antihistamine with BPH: Want No Anticholinergic Side effects (anti-SLUDG) i. Cetirizine, Fexofenadine, Loratadine oo. Antihistamines with AntiCholinergic and Drowsiness i. Brompheniramine, Chlorpheniramine, Diphenydramine, Clemastine 1. Reversible Competitive Antagonism of H1 Receptors a. Inhibits vascular, GI (M3), and Respiratory Smooth Msucle Contraction b. Decreases Capillary Permeability  Decrease Wheal, Flare, and Itching 2. Anticholinergic effects: a. Dry Mucus Secretions

pp. qq. Migraines i. Triptans: Sumatriptan: 5-HT1D and 5-HT1B Agonist 1. 1st line Acute tx: Abort Migraine or Cluster HA a. Migraines w/ or w/o aura b. Not Long term 2. Can Cause SEVERE HYPERTENSIVE CRISIS (>130 mm Hg) a. Esp in poorly controlled BP ii. Ergotamine: 1. Tx and Prevention of Vascular HA 2. Partial Agonist/AAntagonist activity at a. Tryptaminergic, Dopaminergic and Alpha-Adrenergic 3. SE: a. Nausea and Vomiting b. Cyanosis, Absence of Peripheral Pulse, Cold Extremities, Potentially Gangrene c. Contraindicated: Prinzmetal Angina d. Mild Hypotenson or Hypertension, depending on pt iii. Methysergide: Blocks Serotonin 1. Prophylaxis and Prevention of Vascular HA and Migraines 2. Ergot alkaloid derivative 3. Blocks Serotonin action and inhibits vasoconstricot effects 4. SE: a. Nausea and Vomiting b. Retroperitoneal Fibrosis, Pleuropulmonary Fibrosis, c. Fibrotic Thickening of Cardiac Valves iv. Amitryptyline 1. Prophylaxis of Migraine, 2. TCA  Decrease reuptake of NE and 5-HT 3. Treat depression, Neuropathy, Chronic Pain v. Propranolol / Nadolol 1. Migraine Prophylaxis vi. Metoclopramide/Proochlorperazine/Promethazine 1. Antiemetics (DA receptor Antagonist) rr. Depressors: i. Anti-Anesthesia: 1. Naloxone: Opioid Antagonist 2. Flumazenil: Benzodiazepine Antagonist ss. AntiPyschotics: i. Dopamine Antagonists (D2 receptors) 1. Fluphenazine, Haloperidol (High potency) 2. Thioridazine (Low Potency)  Less EPS, more autonomic side effects 3. Metoclopramide, Prochlorperazine (Peripheral) 4. EPS symptoms a. Acute dystonia, Drug-induced Parkinosnims, Akathisia, Tardive Dyskinesia i. Acquired Torticollis is a type of acute dystonia ii. Atypical Antipyschotics: Treat positive AND negative symptoms of Schizo

1. Olanzapine, Risperidone, Clozapien, Quetiapine, Ziprasidone 2. Less EPS tt. Extra Pyramidal Syndromes of Neuropleptic drugs: Antipsychotics or Abrupt withdrawal of Dopamine Agonists i. Dystonia: Acute EPS 1. Repeated, Sustained Involuntary Msucle contractions w/ Abnormal postures of trunk, face, and/or extremities a. Sustained Eye Deviation = Oculogyric Crisis 2. Pain in affected muscles is common and prominent 3. Tx: Antihistamines (Diphenhydramine) and Anticholinergic (Benztropine), Botulinum Toxin, or Diazepam ii. Tardive Dyskinesia: 1. Frequency increase w/ age and length of therapy: NOT ACUTE 2. Irreversible Syndrome a. Involuntary, Choreoathetoid movements in patients w/ antipsychotic meds iii. Akathisia: During First few months 1. Feeling of Restlessness, Frequent repetitive stereotyped movements 2. Inability to sit still for mare than short period of time iv. Neuroleptic Malignant Syndrome: First 10 days 1. Rare, Potentially Fatal 2. Fever, Encephalopathy, Muscle Rigidity, Dystonia, Diaphoresis, Tachycardia, and Labile Blood Pressure v. Parkinsonisms:~3 weeks after 1. Mask-like facies, droling, tremors, pill rolling motion, cogwheel rigidity, shuffling gait uu. AntiDepressant i. TCAs: Block Norepinephrine and Seratonin 1. Amitriptyline/Imipramine a. Increase ADH!  SIADH b. Convulsions, coma, cardiotoxicity 2. Side Effects a. Antimuscarinic/cholinergic Effects, Sedation, Confusion, Orthostatic Hypotension, Decreased Libido, Impotence, cardiac dysrhythmias b. Sedation, Alpha Blocking effects c. Red as Beet (flushing), Dry as bone (anhidrosis), Hot as hare, blind as bat (blurry vision), mad as hatter (hallucinations/delirium), full as flask (Urinary Retention) 3. OD: 3’ C’s a. Coma, Convulsions, Cardiotoxicity 4. Muscle Relaxants similar to Tricyclics 5. Treat Parkinson dx and depression a. By restoring balance to DA/AcH levels. b. Strong antichlinergic side effects 6. Can Cuase Acute Narrow Angle Glaucoma: a. Severe ocular pain w/ halos around lights b. HA, Nausea, vomiting, eye redness, corneal edema, elevated Intraocular pressure

c. Cuased yby anticholinergic actions acting on muscarininc receptors on pupillary constircot muscle of iris which is blocked  Pupillary dilation  Narrows angle in anterior chamber of eye 7. Treatment: a. NaHCO3-to alkalanize urine ii. MAOi: PHenelazine 1. Use for Atypical or Refractory Depression 2. Inhibits Monoamine Oxidase: Which inactivates excess neurotransmitter 3. Gastric and Hepatic MAO inhibited 4. MAOi interact w/ tyramine  Hypertensive crisis 5. Large quantities of tyramine reach systemic circulation  enters synaptic temrinals of Postganglionic sympathetic neurons  Displace massive amounts of NE; 6. Neuronal MAO also inhibited, so NE cant be metabolized. 7. Lead to sympathetic crisis: a. Diaphoreis, Severe HA, Tachycardai. 8. Wine and Cheese. 9. Can Cause SIADH 10. MAO-B breaks down Dopamine: Blocked by Selegiline to tx Parkinson 11. Side effects a. No Anticholinergic Properities, but can cause similar effects i. Dry mouth, Urinary Retention b. Tyramine Crisis: i. Tannin rich foods: Red wine and aged cheese iii. SSRI 1. Paroxetine: Impotence and Ejaculatory disturbances 2. Can Cause SIADH iv. 2nd Gen: 1. Trazodone a. Priapism, Sedation, Postural Hypotensions vv. Seotonin Syndrome i. Excessive Stimulation of 5-HT1a and 5-HT2 CNS receptors by serotonin ii. SSRIs are main cause: 1. Also w/ TCAs, MAOis 2. Don’t mix w/ Meperidine, Lithium, Dextromethorphan, Cocaine, Caffein iii. Severe Tremor, Tachycardia, Herptonia, Fever, Confusion, Agitation, Flushing, Myoclonus, Hyperreflexia, Autonomic Instaiblity, Mydriasis, Hyperthermia, Seizures, Rhabdomyolsys, DIC iv. Treatment: 1. Cyproheptadine: Serotonin Receptor Antagonist a. Discontinue if no effect after first 2 hours ww. Mania: i. Lithium: 1. Side Effets: a. Sedation, Ataxia, Aphasia, Edema, Thyroid Enlargement, Reversible Kidney Damage (Nephrogenic Diabetes Insipidus) b. Benign and Transient HYPOTHYROIDISM  Check TSH every 6 mo i. If Elevated TSH, tx w/ levothyroxine

c. Also Check Serum Creatinine i. Li elimanted by kidneys ii. Valproate: 1. Moniter Liver transaminases  May be elevated 2. Monitor Platelet Count  May have Thrombocytopenia and Platelet Dysfunction xx. Amphetamines: Weak Base i. Hasten excretion by acidifying urine w/ Aluminum Chloride ii. yy. Buproprion: NE and DA reuptake inhibitor antidepressant i. Used for smoking and MDD ii. NO USE IF BULIMIA OR ANOREXIA NERVOSA  Seizures zz. SSRI FOR BULEMIA: FLUOXETINE IS FDA APPROVED (ONLY DRUG) aaa. Ethylene Glycol Poisoning i. Metabolic Acidosis, Coma, and Oxalate Cyrstals in Urine ii. Normal transaminases, sodium, and potassium. iii. Nausea, vomiting, carpopedal spasm, lumbar pain, renail failure, respiratoy distress, and convulsion. bbb. Cholescystis i. Meperidine: ccc. Biliary Colic / Cholelithiasis: Biliary Pain i. Tx: Ursodiol (ursodeoxycholic acid) – Primary Bile acid  Decreases Cholesterol synthesis, Secretion, and absorption. ddd. Gout: i. Start Tx with Colchicine or NSAIDs 1. Colchine stops leukocyte migration and phagocytosis by stopping microtubule assembly  Decreases inflammation of urate cyrstals eee. Acromegaly: Heypersecrtion of GH i. Increased plasma GH, IGF-1, Hyperglycemia, Insulin, ii. Impaired Glucosed Tolerance and Failure of glucose administration to suppress GH secretion fff. Acute Pyelonephritis: i. IV Ampicillin and Gentamycin ggg. Osteoporosis: i. DOC: Bisphosphonates (Risendronate) to inhibit osteoclasts 1. Also use Ca + Vit D hhh. Breast Cancer: i. Long term: Tamoxifen iii. Esophageal Varices and Acute Gastric Hemorrhage: i. Octreotide (Somatostatin)  Decrease Blood flow to portal system ii. Endoscopic Ligation jjj. GI: Stool i. Cause constipation: 1. Opiates (codeine, morphine, etc), Calcium Channel Blockers, Anticholinergics, Tricyclic Antidepressants, and antipsychotics 2. Hypercalcemia, Hypothyroidism, Parkinosn Dx, Diabetes Mellitus, Dx of Colon 3. Tx: a. Stool softener = Docusate

b.

c.

d. e.

i. Detergent to allow water and fatty substances to mix  Increase luminal mass ii. Anionic Surfactant (surface-active agent) to reduce surface tension at oil water interfeace of feces  Allows water and lipids to penetrate stool iii. Helps to hydrate and soften fecal material Bulk Laxatives: Psyllium and Methylcellulose (Tx for Diarrhea) i. Cause Water retention in bowel lumen, and are poorly absorbed  Luminal mass increase  Stimulation of peristalsis ii. Promote Regular Bowel Movements Irritant Laxatives : Castor Oil, Senna, Bisacodyl i. Decrease water reabsorption from bowel lumen + increase intestinal secretion Lubricating Laxatives = Mineral Oil and Glycerin i. Coat fecal contents and decrease water reabsorption from stool Osmotic Laxatives: Magnesium hydroxide/citrate, sorbitol, lactulose, polyethylene glycol i. Soluble but nonabsorbable agents that increasee stool liquidity

kkk.Metoclopramide: i. Use 1. Prokinetic agent for Diabetes Mellitus Gastroparesis ii. Mechanism 1. Dopamine D2 Receptor ANTAGONIST 2. Increases RESTING TONE, Contractility, Lower Esophageal Tone, and Motility 3. DOES NOT CHANGE TRANSIT TIME THROUGH COLON iii. Toxic 1. EPS: Dystonia, Parkinsonism, Akathisia iv. lll. GI: GERD i. Misoprostol 1. Prostaglandin E1 Analog a. Increased production and secretion of gastric mucous barrier b. Useful in concomitant chronic NSAID use to DECREASE NSAID-Indcued peptic ulcers c. CONTRAINDICATED IN WOMEN OF CHILDBEARING POTENTIAL i. Abortifacient properties ii. Can be used to TERMINATE PREGNANCY of <49 days (in conjunction w/ MIFEPRISTONE) iii. Can be used off-label for RIPENING AND LABOR INDUCTION d. Can Cuase Diarrhea mmm. Heparin Induced Thromboytopenia: HIT i. IgG autoantibody that racts w/ Platelet Factor 4 (PF4) on platelet surface ii. Forms irreversible complex with heaprin iii. Two types 1. Type 1 = Nonimmune response to heparin a. Begins 1-2 days after heparin initiation. 30% ofp patients b. Thrombocytopenia is mild to moderate

c. Plateletc count ~>100,000 2. Type 2 = Immune mediated: HITT (Thrombocytopenia and Thrombosis) a. Thrombocytopenia, thromboses, and thromboembolic complications i. Skin Necrosis and Gangrene b. 4-14 days after initation c. Tx: Rudins: Direct Thrombin Inhibitor: i. Lepirudin, Bivalirudin, derivatives of Hirudin ii. Lepirudin: Action independent of Anti-thrombin 3 1. Froms compact stoichiometric complex w/ molecule of thrombin and neutralizes acitons of thrombin nnn. Tetracycline LESS EFFECTIVE w/ ANTACIDS i. Blood levels decrease dramatically ii. Two agents bidn together and precipitate in Intestianl tract. iii. Bacteriostatic w/ mild-moderate gram- and gram+ coverage iv. Tx of rrickettsial, spirochetal, and chlamydial infections v. DOC for Uncoplicated gonococcal and Acne Vulgaris vi. DOXYCYCLINE  NOT EXCRETED RENALLY, SO GOOD FOR RENAL FAILURE! ooo. Diabetes Type 2: i. 1st line: Oral Hypoglycemic Agent 1. Metformin: Biguanide Oral Hypoglycemic agent a. Cheically distinct from Sulfonylureas (Chlorpropamide and Glipizide) b. Monotherapy or in conjunction w/ others 2. Sulfonylureas: If no Sulfa Allergy nd ii. 2 Line: NPH Insulin (intermediate) 1. Use when one or more oral therapies fail to obtain effect ppp. Severe Hypoglycemia i. Glucagon 1. But Worsens hyperglycemia qqq. Appetite Stimulant = Megestrol Acetate i. Progestational hormone w/ anti-neoplastic proerpties ii. Used fro Advanced Carcinoma of Breast (Hormone Receptor POstivie breast cancer) and Endometrium, Ovarian Carcinoma, and Anorexia related HIV iii. Large doses, can increase appetite in most individuals, even w/ advanced cancer iv. Also Dronabinol (Cannabinoid) for Chemotherapy related nausea and comiting and anorexia/weight loss rrr. Hodgkins and Non-Hodgkin’s Lymphoma i. Cyclophosamide: 1. Alkylating agent that alkylates DNA and causes Cross linking 2. Side effects: a. Bone Marrow Suppresion b. Hemorrhagic Cystitis (Tx w/ Mesna) c. Hepatotoxicity sss. Fluoroquinolones i. Affected by Antacids  Decrease in bioavailability ii. Upper and Lower Respiratory infections AND UTIs iii. UTIs for sulfa allergies

Path
11) Path: a. Hand/Feet Red i. Coxakie A 1. Dilated Cardiomyopathy ii. Ricketssia iii. Syphillis 1. Maculopapular Bronzing Rash iv. Staph Aureus: TSST 1. Desquamating Rash v. Kawasakies 1. Vasculitis in Kids 2. Dry lips 3. Conjunctivitis 4. Coronary Artery Dx vi. Beurger’s Dx vii. Endocarditis? 1. Red nodules b. Conjunctivitis i. Adenovirus 1. Swimming bitch ii. Chlamydia iii. c. Things to Measure: i. Lipase and Amylase: Acute Pancreatitis ii. Alkaline Phosphatase: 1. Liver and Biliary Tract Pathology iii. Serum Blirubin 1. Not Specific: Gallstone Impaction? iv. Hematocrit: 1. Secondary to Third-Space Fluid Losses 2. Anemia d. AutoAntibodies: i. Anti-Ribonucleoprotein: Mixed connective Tissue Disorde 1. Joint Pain, Myalgia, Pleurisy, Esophageal Dysmotility, Skin Dx a. Mix of SLE, Systemic Slcerois, and Polymyositis 2. Low titer RF and anti-ssDNA ii. Anti-Centromere: CREST (limited Scleroderma) iii. Anti-DNA Topoisomerase I Ab (Scl-70): Diffuse Scleoderma iv. AntiHistone: Drug Induced Lupus 1. Hydralazine (For HTN in Pregnant), Isoniazid (B6 defic), Procainamide v. Anti-dsDNA: Lupus vi. Anti-SS-A (Ro): Sjogren and Lupus vii. Anti-SS-B (La): Sjogren, against ribonucleoproteins viii. RF: IgM against Fc of IgG – Rheumatoid Arthritis, Crhonic Infections, Sle, Sjogren, Chronic Diseases (Pulmonary, Hepatic, Renal)

ix. Anti-dsDNA and Anti-Smith: SLE x. Antimicrosomal Antibodies: Hashimotos xi. Antimitochondrial: Primary Biliary Sclerosis / Primary Sclerosing Cholangitis e. AMYLOID: i. Alzheimer’s: 1. ABeta from Amyloid Precursor Protein (APP) on chr 21 a. Down’s patients @ 40 years b. Triplicate copy of APP on chr 21 c. Proteolytic cleavage of APP gives ABeta i. Accumulates w/in Core of senile plaques d. APP = Transmembrane protein expressed on cell surface 2. Hereditary Earl Onset AD also by Mutations in APP 3. Homozygotes for Allele 4 of Apoliprotein E gene (chr 9) a. ApoE2 b. ApoE4 c. Maredkly increased risk w/ ApoE2 4. PResenilin 1 (Chr 14) and Presenilin 2 (Chr 1) a. Hereditary Cases ii. Amyloidosis: 1. f. Migrating Thrombophlebitis = Trousseau’s Sign i. Carcinoma ii. Most associated w/ Pancrease, Lung, and Colon g. Pancreatic Carcinoma i. Vague Abdominal, Back, and GI complaints ii. Obstructive Jaundice, Weight Loss, Trousseau’s (Migrating Thrombophlebitis) h. Primary Biliary Cirrhosis i. Conjugated Hyperbilirubinemai ii. Increased Alkaline Phosphatase iii. Chronic Granulomatous inflammation around medium sized intrahepatic bile ducts iv. Antimitochondrial antibodies v. Generalized itching and mild jaundice i. Diabetic Neuropathies i. Atrophy of lumbricals and interosseus muscles in feet secondary to neuropathy 1. Altered sensation in feet: Walking on pebbles 2. Clawing of toes w/ flexion of interphalangeal joints and extension of the metatarsophalangeal joints j. Reye Syndrome: POST VIRAL INFECTION or Aspirin use or Upper Resp Infection i. Fatty Liver with Encephalopathy  Microvascular Steatosis ii. Acute Postviral injury w/ Severe Mitochondrial Damage  Enlarged Mitochondrai iii. Affects: Liver, brain , skeletal muscle,heart, kidneys. iv. Viruses: Varicella and Influenza A and B v. Five days after virus: Vomit and Letharyg  Unresponsive 1. Elevated Liver enzymes and Hyperammonemia and hepatomegaly k. Abdominal X ray signs:

i. Air-Fluid Level: Small Bowel Obstruction 1. Related to Cholelithiasis, due to gallstone ileus 2. Presentation: a. Woman in 40s, Generalized camping abdominal pain, progressive, Nasuesous but no emesis. No last bowel movement b. Distened abdomen and hyperactive bowel sounds c. Diffuse tenderness to palpation w/o rebound pain ii. Thumb Print Sign: Mesentaric Ischemia 1. Presenation: a. Severe abdominal pain disproportionate to exam findings b. Pain due to ischemia nd possible infarction c. Sudden pain iii. Double-Bubble Sign: Duodenal Atresia 1. Presentation a. Bilious vomiting and proximal stomach distention 2. Congenital dx: Associated w/ Down’s iv. Omega Loop Sign: Sigmoid Volvulus 1. Presentation: a. Colicky abdominal pain b. Obstipation (lack of flatus and bowel movements) c. Abdominal distention, Anorexia, Nausea, and vomiting 2. Risk: a. Chornic illness, Old age, Institutionalization, CNS dx b. Chronic Constipation and laxative abuse and abd surgery l. Gastritis: i. Acute: 1. Patches of Erythematous Mucosa, sometimes w/ petechiae and ulceration 2. Complication of variety of other coditions (alcohol Aspirin/NSAIDs, Renal Failure) 3. Non-bloody, Non-bilious vomiting w/ epigastric pain, and nausea. 4. Comting and Hematemesis, and heartburn ii. Chronic Fundal (Type A): 1. Pernicious Anemia, Achlorhydria, Intrinsic Factor Deficiency iii. Chronic Antral (Type B): MOST COMMON in US 1. H. Pylori iv. Hypertrophic (Menetrier) 1. Idiopathic w/ Enlarged Mucosal Folds  Loss of Protein Absorbption v. Lymphocytic: 1. Associated w/ Celiac Sprue m. Crohn Dx: i. Actue Abdominal Pain and Diarrhea w/ Enteric Fistuals 1. Fistulas b/c inflammatory process invoves entire bowel wall 2. Can Fistula into bladder  Mixed flora urinary tract infection w/ pyelonephritis a. WBC in urine w/ gram – b. Brownish-yelow urine (fecal contamination) n. Breast: i. Male Breast Lump:

1. Young Male: Gynecomastia a. Painless lump in single brest b. Firm, mbile mass beneath nipple. No fluid 2. Older Male: Ductal Carcinoma, Invasive ii. Women Breast: 1. Fibroadenoma: a. Most common benign tumor of breast b. Before age 30 c. Mixxture of Fibrous stroma and Glandular Tissue i. Fibroblastic component is true neoplastic population d. Well-Circumscribed, Mobile Nodule w/in Breast e. NO inflmmation 2. Fibrocystic Breast Changes: Only women  Response to cyclical lvels of sex hormones a. Late Reproductive years: b. Fibrosis, Cyst formation, Epithelial changes (hyperplasia and apocrine metaplasia), increases innumber of acini and fibrosis c. No giant cell formation d. Sclerosing Adenosis: i. Proliferative disease of breast w/ proliferation of acini (adenosis) and fibrosis  may lead to cancer ii. Proliferation of small duts and myoepithelial cells near terminal duct lobular unit iii. Fibrosis that distorts gland and lobules into a WHORLED pattern iv. Hyperplastic changes, atypical lobular hyperplasia, or atypical ductal hyperlasia  Risk for invasion e. Risks in increasing order: Florid hyperplasia < Atypical Ductual Hyperplasia < Ductal Carcinoma in Situ, for Developing Invasive Ductal carcinoma 3. Bloody Nipple: Intraductal Papillomas: BENIGN a. Major Lactiferous Ducts beneath nipple b. Papillary Mass arising w/in ducts (Papillary Fronds) c. Consistent presence of Fibrovascular core and both epithelial and myoepithelial cells d. Single Subareolar tumor e. Discharge = Bloody or Serous f. Distinguish from Papillary Ductal Carcinoma of breast by: i. Papilloma = Epithelial and Myoepithelial (small contractile cells around breast ducts) cells in papillary fronds, Fibrovascular core ii. Carcinoma = Cytologic atypia, abnormal mitoses and a cribriform growth patern 4. Paget = Ductal Carcinoma In Situ (97%)  Underlying Ductal Cancer a. Erythematous Ulcerating Lesion of Nipple b. Large, Clear, Mucin-Filled Cells w/ Abundant Cytoplasm (Paget Cels) i. Intraepidermal Spread of Cells into ductal system ii. DO NOT CROSS Basement Membrane c. Lesions: i. Scaly, Vesicular, or Oozing

ii. Start in Nipple and spread to areola d. Sometimes bloody discharge e. Pain, Burning, Pruritis before lesions appear 5. Invasive Ductal Carcinoma (Also Paget?) a. Hard, Stellate, and Fibrous Tumor 6. Invasive Lobular Carcinoma = Moveable around a. Indian Filing of Cells: All in a single line b. Terminal Ductules of breast c. Poorly circumscribed, rubbery breast mass. 7. Breastfeeding/pus/erythematous/infected = Acute Mastitis = Staph a. Painful b. Accute inflammation and Tissue Necrosis c. Infection of lactating breast w/ Staph Aureas d. Acute purulant inflammatory respone w/ abscess formation maybe 8. Focal Fat Necrosis in Breast a. Release Lipids into interstitium  Chronic nflammatory response  Granuloma w/ Multinucleated Giant cells (from histiocytes) i. Lipid0filld macrophages 9. RISK FACTORS: a. Positive Family History is MOST SIGNIFICANT RISK for Breast Cancer b. Hereditary = BRCA1 and BRCA2 (tumor suppressor) c. P53, Lifraumeni, Cowden Sydnrome (Chrom 10 mutation), ATM gene (ataxia telangiectasia) iii. Women Vulva: 1. Condyloma Acuminatum: HPV a. Koilocytes and no cross Basement Membrane 2. Extramammary Paget Dx a. Individual Tumor cells  STAIN FOR MUCIN 3. Vulvar Intraepithelial Neoplasia: a. No Cross Basement Membrane 4. Melanoma: a. Melanocytes (S-100) or HMB-45 5. Squamous Cell Carcinoma: a. Itchy White Patch, Squamous Epithelial Lesions, NO Koilocytes b. Lesion shows Papillary Projections, i. Disordered Squamous epithelium ii. Well-Differentiated Cells (ONLY IF SPONTANEOUS, otherwise poorly differentiated if arising from others) c. BASEMENT MEMBRANE AT DERMAL-EPIDERMAL JUNCTION IS DISRUPTED d. May arise from Vulvar Intraepithelial Neoplasia, Condyloma, or spontaneously. o. Orchitis: i. Nonspecific: Neutrophils ii. Gonorrhea: Neutrophils and Epididymis invovlved iii. Mumps: Parotiditis accompanies iv. TB: Acid fast bacteria in granulomas

p.

q.

r.

s.

t.

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v.

w.

v. Syphilis: Gummas or obliterative endarteritis w/ perivascular cuffing of prominent lymphocytes and plasma cells Apoptosis i. Both Graft vs. Host and Menstruation, intestinal crypt epithelia rapid proliferation, and in developing thymus. ii. Fragmenation of cell with formation of cytoplasmic blebs and apoptotic bodies that are phagocytized by other healthy cells 1. Epithelial cells with fragmented, hyperchromatic nuclei and small discrete blebs with cytoplasm and nuclear fragments Necrosis: i. Liquefactive: Cerebral abscess 1. Focal tissue destructive bacterial infections and in ischemic necrosis of brain ii. Gangrenous: Diabetic feet iii. Coagulative Necrosis: MI 1. Coagulated, anuclear cell ghosts iv. Caseous Necrosis: TB 1. Necrotic, Amorphous Granular debris surrounded by a granulomatous response Steroid Myopathy: i. Asthma pts, long use of steroids, insidious onset of proximal muscle weakness (thighs and arms) preferential for Type 2 Fibers, remember Goljan and Cushing’s lecture about protein break down Hyperplastic Polyps: i. Sawtooth Glandular Epithelium w/ Proliferated Goblet cells, Columnar Epithelium, and No Atypia. Not malignant. Adrenal Hyperfunction, Primary (Conn Syndrome) i. Hypervolemia, Hypernatremia, Hypokalemia (Increased Aldosterone)  LOW RENIN (vs. 2ndary Hyperaldosteronism) ii. Hypercalcemia, Hypercalciuria, Hyperglycemia (Increased Cortisol) iii. Metabolic Alkalosis, Diastolic Hypertension, Weakness, Fatigue, Polyuria, Dipsia. Sjogren: Dry Eyes and Mouth i. Associated with Rheumatoid Arthritis (Proliferative Synovitis w/ many lymphocytes, Macrophages, and Plasma Cells) Diabetic Ketoacidosis i. Tx:Potassium Supplementation + IV Fluids 1. : Isotaonic saline or Lactated Ringer’s Solution ii. pH<7.1 or Hyperkalemia (>5.2)  Bicarbonate supplement iii. If Hypokalemic: Serum glucose < 200-300: 5-10% Dextrose 1. Insulin can rapidly cause Hypoglycemia and HypoKalemia a. Potassium co-transported into cell with glucose in presence of insulin. Sarcoidosis i. Young AA women, progressively worsening shortness of breath, dry cough ii. Hilar Lymphadenopathy on X-Ray, Diffuse abnormalities of lung parenchyma iii. Non caseating granulomas 1. Small, hard, contain giant cells 2. Pulmonary Invovlement: Restrictive Pulmonary Dx a. Fibrosis and Cor pulmonale b. Increased elasticity (decreased compliance)

iv. Negative Acid-Fast, and PAS stains x. Lupus i. Prototype Connective tissue disease ii. 4 of 11 criteria met: 1. Malar Rash: COMPLEMENT MEDIATED LYSIS OF BLOOD VESSELS 2. Discoid Rash 3. Phtosensitivty, 4. Oral ulcers 5. Arthritis 6. Serositis 7. Renal Disorder a. Most common is Diffuse Proliferative Glomerular Nephritis b. Type 3 hypersensitivity reaction ot high levels of circulating immune complexes, can either deposit in glomeruli or develop in situe i. Accumulate in subendothelium and activate complement  Chemoattract neutrophils  Cause glomerular tissue damage  Characteristic wire looping appearance of DPGN seen on EM c. Nephritic syndrome i. Proteinuria <3.5 g/d, Hematuria, HTN, and immune complex in wire loop distribution along subendothelial margin of glomerulus 8. Neurologic Diosrder 9. Hematoligc Disorder 10. Immunoligc Disorder 11. Anti Nuclear Antibody: ANA (95%) a. Anti-dsDNA – (70%) b. Anti-Sm (Smith) – (30%) i. Pathognomonic c. Anti-SSA (Ro) (30-50%) 12. TX: Cyclophosphamide (after NSAIDs and Glucocorticoids have failed) a. SLE w/ significant organ involvment: Severe lupus-induced nephritis b. Give w/ glucocorticoids to reduce titier of autoantibodies iii. Drug Induced: 1. Procainamide (similar to quinidine), Hydralazine, Chlorpromazine, Isoniazid, Methyldop 2. Antihistone ab seen iv. Type 3 Autoimmune Hypersensitivity: Production of Autoantibodies agains own Nuclear constituents v. Detection: Indirect Fluorescent Antibody Test: 1. Serum plus Antigen Plus Fluorescent Antihuman Immunoglobulin 2. Reacting a serum sample from patient w/ known source of antigen (nuclei or dsDNA) then treat w/ a fluorescently labeled antihuman Immunoglobulin in animals y. CREST: Limited Scleroderma i. Calcinosis, Raynaud, Esophageal Dysmotility, Scleroderma, Telangiectasias ii. Anti-Centromere (90%) vs. Antitopoisomerase for Diffuse scleroderma (deadly systemic fibrosis) iii. z. Hemorrhoids: Bright Red Blood in Stool  Alcoholic Liver Disease/Vascular Injury/ Portal HTN aa. Alcoholic Hepatitis:

bb.

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i. AST/ALT > 1.5, Mallory (Hyaline Bodies) Neutrophil infiltration Halothane Hepatitis i. Hepatitis w/ focal to massive hepatic necrosis ii. Due to formation ofhepatotoxic metabolic intermediates and immune hypersensitivity iii. Elevated bilirubin (mildly obstructed biliary tree due to disruption of hepatic architecture secondary to swelling) iv. Elevated AST>ALT  Hepatocellular death has occurred w/ lysis and enzyme release v. Also see hyperthermia (malignant), cardiac arrhythmias, and BP chagnes Biliary Cirrhosis: i. Elevated ALP ii. Primary = Antimitochondrial Antibodies ??? Wound Healing i. No Scar: Epidermal Cells (Labile Cells) 1. Regenerate and fll a wound defect ii. Scar Formation 1. Fibroblast iii. Wound Contraction: 1. Myofibroblasts (contractile proteins: Actin and Myosin) 2. Also Atheroma Formation Kawasaki: Mucocutaneous Lymph Node Syndrome i. Fever >5-10 days, Desquamating rash on fingers/palms and toes/soles and Mouth, oral ulcers, bilateral conjunctivitis, Cervical LAD, polymorphous rash, oral lesions and/or fissured/dry lips, pharyngeal erythema, STRAWBERRY TONGUE ii. Small, Medium , and Large arteries affected: Transmural inflmmation and variable necrosis iii. #1 cause of coronary artery aneurysm in children 1. Vasculitic changes in coronaries w/ subsequent aneurysim and Myocardial infaractions 2. Checek w/ echo’s iv. Children < 5 years v. Self limiting, possibly autoimmune vi. Typical presenation: Findings on mouth, skin, and lymph nodes 1. FEVER< CONJUNCTIVITIS, ERYTHEMA OF ORAL MUCOSA, CERVIACL LAD 2. Fever, Cervical LAD, Hand Edema (dorsal?), Injected Conjunctiva vii. Most common histopathologic sign: Acute Necrotizing vasculitis of small and medium sized vessels viii. Do Echo to check for Coronary artery aneurysm, valvular regurgitation (mitral), pericardial effusion. 1. Also stress test, angiography, CT/MRI: Preventative measures ix. Tx: 1. IVIG, Aspirin for cardiacvascular protection, and steroids 2. Pt may get HIV from IVIG transfusions: Treat w/ TMZ-SMZ for PCP prophylaxis, or if allergic to sulfa: Pentamidine, Dapsone, and Atovaquone (Treas malaria and toxoplasmosis, and acts by inhibiting mitochondrial electron transport) Pancreatic Path i. Pancreatic Pseuodcyst 1. Exocrine pancreas = Bag of enzymes 2. Chronic Pancreatisis  Cause release of enzymes  Liquefactive necrosis

gg. Liver Path: i. Zones: 1. Zone 1: Periportal zone a. Most sensitive to toxic injury b. Shows Infiltration with hepatitis 2. Zone 2: Intermediate Zone a. Ischemic injury (2nd most sensitive) 3. Zone 3: Pericentral Vein Zone (Hepatic Vein) a. P450 Oxidase Enzyme System i. Chemical Modification or degradation of chemicals b. Most susceptible to Ischemia ii. Ito Cells: 1. Fat-Containig Mesenchymal Cells in Space of Disse 2. Site of Vit A storage. iii. Inherited Bilirubin Disease 1. Gilbert: Unconjugated Hyperbilirubinemia: COMMON/BENIGN 2. Crigler Najjar: Unconjugated Hyperbilirubinemia: RARE/severe a. Absent/deficient UDP-glucuronyl Transferase b. Prevents glucuronide conjugation of bilirubin by hepatocytes  prevents canalicular organic anion transporter (cMOAT) from transporting it into bile c. Unconjugated bilirubin builds up in plasma (too tightly bound to albumin to be excreted) d. Phototherapy modifies enough to allow some urinary excretion and prevent Kernicterus in brain, but not enough to resolve jaundice 3. Dubin Johnson: Conjugated Hyperbilirubinemia + Dark Liver a. Deficiency in the Hepatocyte Canalicular Organic Anion Transporter (cMOAT) b. Elevated Direct bilirubin 4. Rotor: Conjugated Hyperbilirubinemia + NORMAL Liver iv. Bile Stones: 1. Cholesterol  80% of Bile Stones a. Cholesterol Monohydrate Crystals b. Yellow Stones, Radiolucent, 50-100% holesteral c. Minimal Calcium Salts i. Calcium Carbonate and Poshphate d. More Females b/c Estrogen plays role in formation i. Estrogen Icnreases the Synthesis and Uptake of Cholesterol in Liver e. Clinically Silent 2. Black a. High Calcium Salt and Unconjugated Bilirubin, Radio-opaque b. Precipitation of Unconjugated Bilirubin c. Chronic Hemolytic Diseases 3. Brown a. Calcium Soaps: i. Calcium with Plamitate and Stearate ii. Mix of Unconjugated Bilirubin, Calcium Soaps, and Cholesterol Crystals 4. Risks:

a. Cholesterol i. Risk: 5 F’s 1. Female, Fat, Forty, Fertile, Flatulent b. Mixed stones and Cholesterol stone risks: i. Obesity, High Estrogen, Multiparity, Crohn Dx, Rapid Weight los,CLOFIBRATE, Native Americans c. Pigment stoen risks: i. Chronic Hemolysis, Alcoholic Cirrhosis, and biliary infection v. Mallory Bodies 1. Intracytoplasmic Hyaline Inclusions derived from cytokeratin intermediate filaments 2. Seen in: a. Chornic Alcoholic Hepatitis b. Primary Bliiary Cirrhosis c. Wilson’s Dx d. Chronic Cholestatic Syndroems e. Hepatocellular TUmors vi. Hepatitis 1. Chronic Alcoholic a. Fatty Change, Neutrophilic Infiltrate, Mallory Bodies i. Mallory Bodies = Intracytoplasmic Hyaline Inclusions derived from cytokeratin intermediate filamnts 2. Cocaine Induced a. Acute Sub-Fulminant Hepatitis b. No Mallory bodies, no neutrophilic infiltrate c. Path exam: Necrosis and Microvesicular Steatosis 3. Acute Viral a. Diffuse swelling of hepatocyte: Ballooning degeneration b. Fatty change ONLY w/ Hepatitis C c. No Mallory bodies 4. Pregnancy a. Fatty liver of pregnancy: Acute hepatic failure during 3rd trimester b. Microvesicular liver cahgne 5. A1-Antitrypsin a. Autosomal Recessive dx  Liver failure, Pancreatic insufficiency, Emphysema b. Cytoplasmic Globular Inclusions in hepatocytes  PAS Positive hh. CGD: NADPH Oxidase deficiency  Recurrent infections w/ Catalase + Organisms and Fungi i. Staph Aureus, Klebsiella, Candida ii. Decrease Neutrophil Oxidative Index ii. Wilson’s Disease: Copper: High Copper, Low Ceruloplasm i. Failure of copper to enter circulation in form of ceruloplasmin (protein bound form) ii. Copper accumulates in Liver, Brain, and Cornea 1. Tremor, Asterixis, Basal Ganglia Degeneration  Parkinsonian symptoms, Chorea, Corneal Deposits (Kayser-Fleischer Rings) 2. Fatty change, hepatitis, Cirrhosis of liver 3. Mutations in 5’ Untranslated Region (UTR) of Wilson Disease Gene (ATP7B)

iii. Tx: Penicillamine: Chelate Copper 1. Or Zinc Acetate to block absorption jj. Dermatomyositis and Polymyositis: Autoimmune Inflammatory Myopathies i. Skeletal Muscles affected ii. Proximal Limb Muscles iii. Inclusion Body Myositis is a slowly developing disease: 1. Asymmetric and in Old fucks kk. Urticaria: Hives i. Pruritic Wheals form after mast cells degranulate 1. Tirgger Localized Dermal Edema w/ Dilated Superficial Lymphatic channels 2. Not always triggered by IgE Ag interactions ii. Caused yb allergic or nonallergic mechanisms ll. Pituitary Apoplexy: (SHEEHAN syndrome or Infarction of gland from blood loss) i. First Tx w/ Glucocorticoids and Thyroid Hormones mm. Obstructive Sleep Apnea  Elongated Uvula nn. Sickle Cell Dx i. Point mutation in Beta Globin Chain that transforms HbA into HbS: 1. Alpha2/Beta2 2. Poor solubility when deoxygenated a. Aggregates and polymerizes 3. Rigid, nodeformable cells  Easily destroyed by spleen  HEMOLYTIC ANEMIA ii. Sickle Cell pain cirisi w/ infection or exposure to cold 1. Adhere to microvasculature and occlude small blood vessels 2. Ischemic necrosis of organs: Bones lungs, liver, brain, spleen iii. Shorted fingers in kids b/c dmage in bone growth iv. Vasa Recta of Medulla has high sickle danger b/c of High osmolarity and hypoxia v. Give Pneumococcal vaccine and HiB vaccine to splenectomized patients because of danger of encapsulated organisms w/o spleen. vi. Also Salmonella Osteomyelitis is danger. vii. oo. Anemia: i. Spherocytosis: 1. Defective erythrocyte structure 2. Defective structural proteins: Spectrin or Ankyrin 3. RBCs lack normal concave shape. Broken membranes, etc ii. Intermittent Hemolytic Anemia 1. G6PDH and Pyruvate Kinase Deficiency iii. Cardiac Compensation: 1. Increased HR, SV, CO, Pulse Pressure (from increase SV) 2. Decreased Systemic Vascular Resistance pp. Hemosiderosis: i. Prolonged Systemic OVerlaod of Iron ii. From Hemolytic Anemias, Repeated blood transfusion, or increased iron absorption (rare). 1. Severe forms of sickle-cell or thalassemia are very prone iii. Macrophages are hemosiderin aladen: 1. In liver, spleen, lymph nodes, and parenchyma of heart, liver, and endocrine organs

2. Pigment is coarse, golden-brown granules w/in cytoplasm qq. Osteopetrosis i. Osteoclasts unable to Resorb bone ii. Increased density of cortex w/ narrowing of erythropoietic medullary cavities 1. Impaired Hematopoiesis secondary to bony overgrowth of marrow cavity 2. Pancytopenia = Anemia (low Htc, low WBC) and Thrombocytopenia: a. Decrease in marrow cavity size 3. Radiologic = Diffuse Symmetric Skeletal Sclerosis iii. Brittle bones, anemia, blindness, deafness, hydrocephalus, cranial nerve palsies 1. Despite density, bones are brittle b/c osteoclast activity is bunk. iv. Autosomal Recessive: Children and early death due to anemia + infections b/c no bone marrow v. Autosomal Dominant: Adutls - Fractures rr. Retinopathies: i. Age Related Macular Degeneration 1. Slow or Sudden loss of Central Visual fields (Peripheral and color preserved) 2. Two Forms: a. Atrophic Macular Degeneration = DRY FORM i. Pigmentary changes seen in maculae ii. NO scarring or hemorrhage in macular area are present b. Exudative Macular Degenartion = Wet form i. Network of new vessel formation below retina 1. Source of Intraretinal Hemorrhage and Subretinal Fluid ii. YES scar formation ii. Central Retinal Artery Occlusion 1. Sudden Unilateral Painless Visual Loss iii. Diabetic Retinopathy 1. Nonproliferative DR: a. Microaneurysms, Hemorrhages, Exudates of Retina 2. Proliferative DR: a. Changes of Nonproliferative (Microaneurysms, Hemorrhages, Exudates of Retina) AND b. Neovascularizatin w/ Extensions of Vessels into vitreous iv. Retinal Detachment 1. Seen as raised area of retina (unless hemorrhage into vitreous blocks it)

Pulmonary
12) Pulmonary: a. Clubbing + New bone formation beneath periosteum of DIP: Intrathoracic Cancer causing Hypoxemia i. New subperiosteal bone is Hypertrophic Osteoarthropathy b. Lung Tests: 3 volumes, 3 capacities, and TLC i. Tidal Volume = Air inspired/expired w/ normal breath 1. ERV and RV are left after expiration = FRC ii. Inspiratory Reserve Volume = Air inspired w/ maximal inspiratory effort over and above tidal volume

1. Brings you up to max TLC iii. Expiratory Reserve Volume= Volume expelled by active expiratory effort after passive expiration 1. Only RV is left iv. Inspiratory Capacity = Max air inspired after passive expiration 1. IRV and Tidal Volume together v. Vital Capacity = Largest amount of air expired after maximal inspiration 1. Only RV is left 2. IRV, TV, and ERV together vi. Functional Residual Capacity = Amount of air left after normal exhalation 1. ERV and RV together vii. Total Lung Capacity: All of your air abilities = FRC + IC 1. IRV, TV, ERV, and RV together 2. VC and RV together 3. IC and FRC together viii. Helium Dilution Technique Measures Residual Volume 1. RV + Expiratory Reserve = FRC ix. Only FRC and RV represent amount of air remaining in lungs (instead of changes of volume measured by spirometer) c. A-a gradient: Large gradient = Underlying Lung Disease i. A-a = PAO2 (Alveolar Partial Pressure)– PaO2 (arterial Partial Pressure) 1. PAO2 = PIO2 – PACO2/R 2. PIO2 = .21(Pbarometric – Pwater vapor) = .21(760-47) = 149 3. R = Respiratory exchange ratio ii. PaO2 and PACO2 given in labs d. Forein Objects: i. Right Bronchus is wider and more vertical: Superior Segmental Bronchus of Lower Lobar bronchus = only segmental bronchus that exits from posterior wall of lobar bronchi 1. Supine  Superior Segmental Bronchus of Lower Lobe e. Cavitary Lesions = Pulmonary Abscess i. Staph Aureus ii. Anaerobic Bacteria

Cardiac
13) Cardiac a. Thrombi: i. Premortum Thrombus: Lines of Zahn 1. Thin white laminations composed mostly of platelets 2. Due to afib prior to death  forms clots 3. Large clump of adherent red material found in dialted left atrium ii. Postmortum 1. No lines of Zahn, But they resemble chicken fat b. Arterioles: Greatest Resistance c. Venules and Veins: Systemic  Greatest Proportion of Total blood volume (supine/basal state) i. 64% of 5L = 3.2 L d. Capillaries: Largest surface area: Facilitate diffuision exchange of nutrients, slowest flow

e. Heart Failure: i. 1st line of defense: ACEi for CHF is only tx that shows decrease in mortality 1. Other drugs: a. Digoxin: Imporves symptoms but not decrease mortality. Also for Afib b. Diuretics: Use for edema and HTN, but no decrease in mortality ii. EKG findings: 1. U wave = Hypokalemia, Bradycardia 2. Prologned PR = AV Block 3. T wave inversion + Pathologic Q waves a. Recent MI (transmural infarct) b. Myocardial Ischemia (Acute Coronary Syndrome) 4. ST Depression: a. Stable Angina (2nd to Athersclerosis) i. w/ retrosternal chest pain on exertion b. Unstable Angina: (2nd to Thrombosis but no necrosis) i. w/ chest pain at rest or minimal exertion + Crescendo c. MI: Subendocardial Infarct 5. ST Elevation: a. Prinzmetal’s Angina (2nd to Spasm) b. MI: Transmural Infarct iii. Cardiomyopathies: 1. Dilated: Most common a. S3, Dilated heart, balloon appearnce, Systolic dysfunction, Eccenctric hypertrophy (sarcomeres addied in series) b. Alcohol, Wet Beriberi, Coxsackie B virus, Cocaine, Chagas dx, Doxorubic, Hemochromatosis, Peripartum Cardiomypotah i. ABCCCD-HP (Heart Problems) f. Heart Sounds: i. S3 = CHF 1. Low pitched sound occurring at termination of rapid filling. 2. Also in AV valve incompetence 3. Also maybe normal in young athelets ii. S4 = Stiff Wwall: 1. Second phase of ventricular filling, when atria contact just before S1 2. Resistance to ventricualr filling: a. Hypertrophy, hypertension, CAD, Aortic Stenosis, and Cardiomyopathy g. EKG: i. Prolongation of QRS = Bundle Branch Block

1. Delay in rate of electrical impulse through heart a. Prevents action potential from passing through branch of conduction system b. Tissue distal to block will not depolarize normally, and timing is off c. Activaiton of ventricle disatl to block delayed = Prolonged QRS 2. Right Bundle Branch, Left Bundle Branch, or Anterior or Posterior Fascicle of Left bundle 3. Ac 4. Due to a. Coronary Artery Dx, ischemia, Damage to conduction system ii. iii. iv. Atrial Fibrillation

1. Small Cell groups (up to thousands) of atrial muscle act independently of others 2. NO DETECTABLE P WAVES b.c no synchronous depolarization 3. Action potentials arrive at AV node at Random intervals a. Erratic Ventricular Rhythm w/ FLUCTUATING R-R Intervals 4. IRREGULLARLY IRREEGULAR a. Altered flow in fibrillating atrium can cause clot formation (esp if odler) b. Anticoag must be intiated i. Heparin first (b/c Warfarin takes time to work) ii. Then Warfarin for long term 5. TX: a. Stabalize pt w/ Diltiazem then Heparin then Warfarin b. Address Rate control, Chronic Arrhythmia and Anticoag i. Antigcoag 1. Old Age and Past history of thromboembolic dx: a. Heparin  Warfarin 2. Younger (<75) and NO past hx of thromboembolic a. Aspirin v. Acute Coronary Syndrome (Unstable Angina or Acute Myocardial Infarction) 1. Vomiting and Signs of Clammy hands and anxiety (women) 2. Pain to back: B/w shoulders. Severe pain for 6 mins 3. T wave inversions 4. Tx: Nitroglycerin vi. Bradycardia 1. Hypothyroidsm, can be caused by Beta blocker, and cause AV block vii. Third degree AV Block

1. 2. No relation b/w P and QRS complexes 3. Complete heart block; 4. Pacemaker develops in ventricles with both atria nd venticle sbeating at their own rates, a. AP from atria does not reach ventricle 5. Caused: a. Coronary artery dx, Degeneration of Conduction system 6. Tx: Atropine, Isoproterenol, Dopamine viii. ST Elevation: 1. Nonspecific finding: a. Myocardial Infarction b. Aortic Dissection (thoracic) Pericarditis h. Phys: i. Cardiac i. Infarction Markers: i. 1st: Troponin = Best Serum Marker w/in first 8 hours (GOLD STANDARD) 1. Stays elevated for 7-10 days 2. Useful for small, CK-negative infarction for several days after event: 3. Cardiac specific forms of Troponin-T and Troponin-I increase 20-fold nd ii. 2 : CK-MB 1. Most useful from 8-24 hours: Peaks at 12-18 hours 2. High Serum Creatinine Kinase MB fractino (CK-MB) = Infarction, NOT Angina 3. Known, Prologned, Severe hypotension = Subendocardial (not transmural) a. ECG = Flat ST-segment Depression b. Subendocardial muscle fartherst from arterial supply rd iii. 3 : LDH-1 1. 2-7 days after, 2. Cardiac Specific form Lactic Dehydrogenase j. Pericarditis: i. Acute Symptoms: 1. Severe Chest Pain + Fever ii. Fibrinous: After Recent MI 1. Takes 2-10 weeks after MI or surgery 2. AutoImmune Condition a. Serofibrinous (Dressler Syndrome) 3. Low grade fever, Pleuritic Chest pian a. CHANGES with respiration and body position 4. Pericardial Frictin rub, Pericardial Effusion

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5. Tx: NSAID iii. Serous 1. Noninfections inflammations a. Rheumatic fever, SLE, Scleroderma, Tumors, Uremia iv. Caseous: 1. TB v. Hemorrhagic 1. TB, Malignant tumors, Bleeding Diatheses, Chest Surgery vi. Purulent 1. Pyogenic infections involve pericardium a. After Cardiothoracic surgery b. Hypertension: i. In Pregnancy: DOCs 1. Methyldopa (to a-methylnorepinephrine) which is alpha-2 agonist 2. Hydralazine: Peripehral Vasodilator byCalcium Trasnport Interference ii. Meds that INCREASE Lipid levels: 1. Beta Blockers (specifically Metoprolol) and Thiazides iii. With BPH: 1. A1 Antagonists: Terazosin Prinzmental Angina: Coronary Artery Spasm at rest i. ST-Segment Elevation (transmural Ischemia) ii. Use Ergonovine or ACH to provoke spasm. HOCM: Hypertrophic Cardiomyopathy, and SAM (systolic anterior motion of mitral valve) i. Disastolic Dysfuntion, Systolic Ejection Murmer, Loud S4 ii. Murmer Accentuated by exercise/standing. Lessend by Lying down or squatting iii. SAM, Asymmetric Left Ventricular Hypertrophy, Early closing followed by reopening of aortic valve. iv. Tx: Beta Blocker to prevent dynamic outflow obstruction by improving diastolic filling. Also, Cachannel blockers Stable Angina: Focal Fibrosis and Subendocardial Myocardial Vacuolization from loss of myoscytes Increased Ejection Fraction and Impaired Diastolic Function i. Idiopathic Hypertrophic Subaortic Stenosis (Hypertrophic cardiomyopathy) ii. Systolic Ejection Murmur and thrill iii. Common cause of SUDDEN DEATH in young athletes iv. Autosomal Dominant LEFT ATRIUM CRUSHES ESOPHAGUS bc it is posterior wall of heart i. Left Ventricle is Left border and diaphragmatic surface ii. Pulmonary trunk is on Anterior Surface of Ehart iii. Right Atrium is Right border of heart iv. Right Ventricle: Anterior Wall of heart and some diaphragmatic Aortic Dissection  Bilateral Renal Infarct i. Sharp Tearing pain that radiates to back, and then Location of Pain MOVES as Dissection progresses 1. Occludes renal arteries  Bilateral renal infarct w/ FLANK PAIN and HEMATURIA Wide Pulse Pressure:

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i. Aortic Regurgitation, Greater than 100 mmHg ii. Due to large inrease in stroke volume due to an increase in the end-diastolic volume. Aortic Coarctation: i. Erosion of Inferior aspect of Ribs (Rib Knotching) 1. Desc thoracic aorta supplied via reverse collateral flow in Intercostal arteries. Cyanosis: (NOT bicuspid aortic valve = non-cyanotic obstruction from aortic stenosis) i. Early 1. Transposition of Great Vessels 2. Truncus Arteriosus 3. Tricuspid Atresia (w/ ASD) ii. Late 1. Uncorrected PDA Valvular Abnormalities: i. Aortic Stenosis = Calcium Phosphates (vs. Oxalates in kidney stones) ii. From Acute Rheumatic Fever  Mitral Stenosis 1. Follows Gropu A Strep Pharyngitis 2. Chronic Rheumatic Heart Disease w/ Valvular Damage as sequelae 3. Most often Mitral and/or Aortic Vlaves a. Thickened, Blunted Cardiac valve leaflets w/ Fibrous bridging b/w Vlave leaflets and Clacification i. Fish-mouth or buttonhole appearance w/ stenotic morphology ii. Mitral stenosis = Loud S1, opening snap, and distolic murmur over apex iii. Ballooning of Vlave Leaflets = Mitral Valve Prolapse iv. Irregular Beadlike calcifications on Annulus = Clacificaiton of Mitral Annulus 1. Elderly patients v. Large Vegetations and Leaflet Perforation = Acute Bacterial Endocarditis 1. Inovles healthy, rather than previously damaged valves vi. Tiny Vegetations along line of closure = Marantic (nonbacterial thrombotic) Endocarditis 1. Seen at Autopsy in patient w/ protracted illness Mitral Valve Prolapse = MVP = Mitral Regurgitation i. Ballooning of Valve Leaflets ii. Holosystolic Apical Murmur 1. Radiates to axilla and Acoompanied y thrill iii. Wide Splitting of S2 b/c of Early Closure of Aortic Valve Mitral Stenosis: i. Pulmonary Wedge Pressure elevated to 30 ii. Pulmonary artery pressure elvated to 45/25 iii. LVED normal, but NOT equal to pulmonary wedge pressure: 125/5 iv. PRESSURE GRADIENT OF 25 across mitral valve = Clear indication of stenosis (30-5) v. Diastolic Murmur Endocardial Defects: (Down’s 21) i. Failure of Migrating Neural Crest Cells: Inadequate migration Pericardial Effusion into Pericardial Space: i. B/w Epicardium (Visceral Pericardium) and Parietal Pericardium ii. Causes Tamponade  Decreased BP and CO due to decrease Diastolic filling Congenital Defects:

i. Most Common Congenital Heart Defect: VSD 1. Acyantoic 2. Left to right shunt 3. Harsh Holosystolic Murmur at left lower sternal border 4. Increased Right Ventricle O2 sat ii. Most common general population cardiac defects: ASD 1. Atrial Septal Defect due to Inadequate formation of Septum Secundum 2. Presentation: Most Common = Exercise Intolerance a. Easy fatigability during exercise, Unable to run more than a few minutes b/c of SOB b. Symptoms get worse c. Loud Systolic Ejection Murmur over Midsternal Border i. Larger volume crossing the right Ventricular outflow tract and into pulmonary artery d. Wide, Fixed Split of S2 i. Significant dealy in closure of pulmonic valve 3. Symptoms absent or minimal until late in hcildhood/3rd decade of life iii. Most common Down’s Syndrome Cardiac defect 1. Endocardial Cushion Defects iv. Most Common Early Cyanosis: Tetralogy of Fallot 1. Ventricular Septal Defect 2. Right Ventricualr Outflow Tract Obstruciton 3. Right Ventricular Hypertrophy 4. Overriding Aorta 5. Caused by Failure of AP septum to align v. Most Common Cyanotic Congenital Heart Disease in Neonates: Transposition of Great Vessels 1. Failure of AP septum to twist 2. More common in kids of DIABETIC MOTHERS vi. VSD 1. Murmur = Harsh and Holosystiolic a. Left Lower Sternal Border b. Thrill is frequently associated.

Vascular
14) Vascular a. Vertebral Arteries Enter at C6 level and travel in the transverse foramina i. External compression can lead t decreased blood flow to brain stem 1. Cranial nerve and/or cerebellar abnormalities a. Motor weakness in arms and legs, mild ataxia, slight ophtalmoplegia 2. Pain when roation of head side to side 3. Compare Vs. Spinal Nerve compression at cervial level a. Pain, burning and tingling sensation, weakness or numbens I nshoulder, arms, or hands ii. Maybe due to osteoarthritic osteophytes 1. Pain in joints too

b. Artery Changes: i. Hyperplastic Arteriolosclerosis (Onion skinning) = Malignant HTN 1. Also see NEcortizing Arteriolitis w/ Wall Necrosis and Fibrin Deposits ii. Hyaline Arteriolosclerosis = Diabetes or Mild HTN iii. Monckeberg Arterio = Medial Calcification of Small Arteries iv. Focal Acute Inflammation = Polyarteritis Nodosa c. Chagnes in Vascular Resistance i. Systemically: 2ndary to Sepsis, Anaphylaxis, Anesthesia, and Afterload Reducing drugs (ACEi/ARBS) d. Fibromuscular Dysplasia (Medial dysplasia) i. Uncontrolled HTN due to Bilateral Renovascular Stenosis in Women, Esp Middle age ii. BEADED PATTERN ON ANGIOGRAPHY e. Beurger Dx i. Narrowing/Sclerosis of Vessels of Extremities of MALE smokers f. Polyarteritis Nodosa i. Small and Medium Sized Arteris w/in kidney g. Takayasu Arteritis i. Arteries arising from aortic arch h. Monckeberg Arteriosclerosis = Medial Calcific Sclerosis i. Ring-Like Calcifications form in media of Medium sized to small muscular arteries 1. Linear calcifications of femoral artery ii. NOT A VASCULITIS  NO INFLAMMATION iii. NO Change in vessel Luminal diamtere  Not clinically significant i. Thrombocytopenia and Purpura: i. Thrombocytopenia = Decreas in platelet count 1. Bleeding from small vessels: Petechiae and Purpura 2. Cuases: a. Decreased Production i. Aplastic Anemia, Drugs, Vit B12 or folate deficiency b. Increased Destructon i. DIC, TTP, ITP, Drugs, Malignancy c. Abnormal Sequestratoin ii. ITP = Decreased platelets and NORMAL RBCS iii. TTP = Decreased platelets and FRAGMENTED RBCs iv. Microangiopathic Hemolytic anemia (MIHA) = NORMAL PLATELETS and FRAGMENTED RBCs v. Thormbasthenia and vWF dx = NORMAL Platelets, Decreased Platelet FUNCTION and NORMAL RBCs 1. Platelet count normal, but FUNCTION impaired vi. Idiopathic Thromboyctopenic Purpura (ITP) 1. Immune Mediated destruction of platelets by the spleen 2. Easy bruising and petechiae 3. Thromobcytopenia with presences of Few large, young platelets, and increase megakaryocytes 4. Normal RBCs, Normal Cell Lines vii. ITP VS. Microagniopathic Hemolytic Anemia and Thrombotic Thrombocytoenic Purpura 1. Contain FRAGMENTED RED CELLS/SCHISTOCYTES

viii.

Neuro
15) Neuro a. Olfactory i. Olfactory nerves are on mucosal side of cribriform plate 1. Send process through plate to synapse in olfactory bulb ii. Olfactory bulb, then sends axons to the PIRIFORM CORTEX = Primary olfactory cortex b. Wernicke’s i. Lesion of superior part of temporal lobe = Fluent, receptive aphasia ii. Cannot comprehend spoken language and have fluent verbalization that lacks meaning = WORD SALD 1. READING AND WRITING ALSO AFFECTED iii. Visual Radiations affected = Right Upper Quadrantanopia = Pie in the sky 1. From Lateral Geniculate Nucleus c. Broca’s i. Posterior part of Left Inferior Frontal Gyrus ii. Impaired Fluency iii. Right Facial Hemiparesis might accompany due to proximity of Broca’s Area to MOTOR strip in precentral gyrus d. Ring Enhancing Lesions i. Glioblastoma 1. Brain tumor w/ necrosis and hemorrhage ii. Toxoplasmosis 1. HIV/Immunocompromised/Infant iii. Staph Aureus  Acute Bacterial Endocardiits 1. Brain Abscess as complication of endocarditis when vegetations fragment and release septic emboli e. Increased Intracranial Pressure: i. Bilateral Papilledema, Nausea/Vomiting, Nuchal Rigidity, Mental Status Change ii. Can be due to Blocking of 4th ventricle  Increase CSF f. Normal Pressure Hydrocephalus = Intermittently Raised Pressure Hydrocephalus i. TRIAD: Dementia, Urinary Incontinence, and Gait Abnormalities ii. Intermittent increases in CSF pressure 1. Lead to progressive damage to cerebral white amtter and dilatation of venticles iii. NO significant cortical atrophy present 1. Lack of Alzheimer related changes in biopsy and Increased CSF pressure iv. TX: Ventricular shunt to Relieve CSF PRessure g. Arnold Chiari: Cerebellum through Foramen Magnum w/ or w/o NTD i. Type 1: Cerebella Tonsils, Aymptomatic, Hydrocephalus of Ventricles  Macrocephaly ii. Type 2: Small Posterior Fossa  Cerebellar Vermis and Medulla, Associated Lumbar Abnormalities: h. Dandy Walker: Abnormally large Posterior Fossa i. No Cerebellar Vermis  replaced by Large ependymal lined midline cyst

ii. Expanded 4th ventricle. iii. Abnormal Brainstem nuclei i. Eye Disorders: i. Parinaud Sydnrome: Pineal Tumor Compressing Superior Colliculi and Pretectal area of dorsal midbrain = Pinealoma 1. Superior Colliculus, Pretectal Area of Dorsal Midbrain = Vertical Gaze 2. Frequently ONLY SIGN = FAILURE OF UPWARD GAZE = PARINAUD 3. Headaches, Paralysis of upward gaze, bilateral papilledema, and pupils that React to Accommodation, but not to direct light 4. Compress Vertical gaze Center of the Tectum 5. Palsy upaward gaze, dissocition of light and accomodation, failure of convergence 6. Can also get hydrocephalus b/c of aqueduct compression 7. Insomnia Pineal Gland  Melatonin from Serotonin a. Inadequate supply of melatonin = INSOMNIA j. Aneurysms i. Berry Aneurysms: Circle of Willis and branches 1. Subarachnoid hemorrhage 2. APCKD, Marfan, Ehlers Danlos, HTN, Smoking ii. Charcot- Bouchard Anneurysms 1. Intraparenchymal Hemorrhage  Subarachnoid space 2. HTN iii. AV Malformation 1. Mixed Parenchymal and Subarachnoid Hemorrhages 2. Headaches, Hemorrhage or Epilepsy 3. Associated with: a. Osler-Weber-Rendu, Sturge Weber, Neurofibromatosis, Hippel-Lindau k. Locked In Syndrome: i. Stroke of Basilar Artery  Ventral Pons Lesion 1. Quadriplegia, Vertical Eye Movement, Ability to Blink 2. Descending Corticospinal and Corticobulbar fibers are interrupted 3. Lose Facial, Pharyngeal, or Limb Musculatre l. Cerebellar Dx i. Normally have planninga dn fine tuning of movements and balance ii. Vermis dx 1. Midline of cerebellum  Gets input from spinal cord 2. Dx shows signs of truncal ataxia but NOT appendicular ataxia 3. Manifests as wide-based, drunken sailor gait a. Walks as if drunk, staggering and losing balance, b. Wide-based, unsteady gait, and a tendancy to fall to one side c. No abnormalities of finger to nose or heel to shin and rapidly alternating movements are normal. m. True Coma: i. Bilateral Lesions that damage reticualr formations in Upper Pns and Midbrain ii. Tegmentum of pons  No awareness of surroundings n. Friedreich Ataxia: Autosomal Recessive GAA trinucleotide repeat disorder i. Chromosome 9, FXN gene mutation for frataxin. Ages 8-15

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ii. Dorsal root ganlgions degenerate leading to atrophic changes of spinal cord: 1. Spinocerebellar tracts, Corticospinal Tracts, and Posterior Columns iii. Stumbling, Falls, Broad-based, slow clumsy gait. Lurch from Side to Side iv. Clumsiness of fine movements and coarse intention tremor of upper limbs, Dsyarthria and Dysphagia, v. Kyphoscoliosis and Foot Deformities vi. Death by early age, pneumonia Olivopontocerebellar Atrophy i. Similar to Friedrich Ataxia Cerebellar Defects: Ataxia is prominent symtopm Hemiballism: i. Wild finging movements of half of body: ii. Hemorrhagic destruction of Contralateral Subthalamic Nuclei iii. HTN patietns Progressive Supranuclear Palsy i. Degenerative disorder, Older Individual ii. Opthalmoplegia, Pseudobulbar Palsy, Axial Dystonia, Bradykinesia 1. Initially present w/ Opthalmoplegia esp Vertical Gaze, 2. 60-70 yr old male 3. Atypical Parkinsonism – Lack or resting tremor iii. Widespread Neuronal Loss and Gliosis in Subcortical Sites w/ Sparing of cerebral and cerebellar cortices 1. Vertical Gaze problems, Difficulty Walking down stairs, Double Vision reading books in lap, Limitation of extraocular eye movements 2. Dysarthric speech 3. Rigidity of Proximal Muscles and Poverty of Movement, Axial Rigidity 4. Looks Around by moving head, rather than eyes iv. Tau Pathology Pick’s Disease = Frontotemporal Dementia i. Loss of outer 3 layers of cortex = lobar atrophy: Frontal and Temporal ii. Frontal lobe damage: 1. Disinhibition, Impaired judgment, Personality changes iii. Temporal Damage: iv. Rapid degeneration v. Mutation in Tau vi. Swollen Neurons (Pick Cells) vii. Pick Bodies: Round to oval inclusions that stain w/ silver stains Parkinson i. Degeneration of Dopaminergic neurons of Substantia Nigra 1. B/w Crus Cerebri and Midbrain tegmentum ii. Pill rolling Tremor, Rigidity, Akinesia, Masklike face, trouble inititating movements, Slow shuffling gait 1. Tremor decreases w/ active movement 2. Soft voice 3. Stooped posture iii. iv. Some get dementia

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1. Difficult to differentiat from dementia w/ Lwy Bodies v. Lewy Bodies are absent in cortical regions of Parkinson patients. Diffuse Lewy Body Dx i. Old man, dies w/in 5 years ii. Memory loss, Progressive Dementia, Parkinsonism, and VISUAL ALLUCINATIONS iii. Dementia w/ Lewy Bodies (Intracytoplasmic eosinophilc Inclusion) containing ubiquitin 1. Ubiquitin Immunoreactive Inclusions iv. Alpha-synuclein or ubiquitin Inclusions in neurons of 1. Substantia nigra, limbic cortex, basal nucleus of Meynert (cholinergic neurons) v. Presence of Extrapyramidal Symptoms and Viusal Hallucinatinos, together with an undulating clincal course. Vascular Dementia: i. Memory loss w/ focal neurologic symptoms depending on location of damage ii. MRI shows old or recent infarcts w/ white matter disease iii. Multi infarct dementia: 1. Multiple, scattered brain infarcts secondary to atherosclerosis of large arteries of Circle of Willis and/or Carotids iv. Binswanger Disease: 1. Rarefaction of cerebral white mater 2. Due to HTN arteriolosclerosis v. Lacunar Infarcts 1. Small (<1 cm) infarcts in Striatumand Thalamus 2. Arteriolosclerosis Alzehimer: i. 60% of all cases of dementia ii. Motor is fine iii. High numbers of senile plaques and neurofibrillary tangles 1. In Hippocampus, Neocortex, Cholinergic Nuclei of the Basal Forebrain 2. NOT IN SUBSTANTIA NIGRA SO NO EXTRAPYRAMIDAL SYMPTOMS (vs. Lewy Body/Parkinosn) Huntington’s: (AD) – Unstable Trinucleotide Repeat: Chromosome 4- Huntington protein i. Chorea (multiple, rapid, random movements ii. Athetosis (slow writhing movements) iii. Personality changes, Dementia iv. 20-40 years v. Degeneration of GABAergic neurons in neostriatum (caudate) 1. Atrophy ofneostriatum and ventricular dilation vi. Anticipation and Genomic Imprinting vii. Tx: Antipsychotic, Benzo, Anticonvulsants Creutzfeldt-Jacob Disease: CJD/Prions i. Prototype prion disease ii. Personality changes, memory loss, seizures, death w/in few months to one year iii. Slow, diffuse EEG changes iv. Spongiform Encephalitis/ Spongiform changes to brain ALS

i. Degeneration of motor neurons in anterior horns of spinal cord and/or large pyramidal neurons in the primary motor cortex (Area 4) ii. Porgressive weakens involving lower and upper extremities: Over course of decade 1. Results in paralysis of ALL VOLUTNARY MUSCLES 2. Die of Respiratory Failure iii. Upper Motor Neurons: 1. Hyperreflexia, Spasticity, Babinski reflex iv. Lower motor Nuerons 1. Weakness, Msuclar Atrophy, Fasciculations v. Skeletal muscles become atrophic (amyotrophic) 1. Denervation pattern on biopsy vi. Rarely dementia is aassociated vii. z. Guillain –Barre: Inflammatory Polyneuropathy: MOST SIMILAR TO MS (AUTOIMMUNE ATTACK ON MYELIN OF BRAIN AND SPINAL CORD, WHILE GB IS ON PERIPHERAL ENRVES) i. Follow Viral Infections, Upper Respiratory, or GI infections ii. Rapidly evolving limb weakness with SYMMETRIC HYPOREFLEXIA but NORMAL SENSATION (mild sensory symptoms may be present: paresthesia, numbness, pain) + Cranial Nerve involvement 1. Severe Lower Back Pain, Muscle Weakness and tingling in extremeties 2. No Appreciable Sensory Loss iii. REFELXES DECREASED/ABSENT iv. Autonomic dysfunction may be prominent (bowel control) v. Ascending path Complete paralysis w/ Respiratory failure vi. DEMYELINATION of PERIPHERAL NERVES 1. Chronic Inflammatory Infiltrate 2. Elevated CSF protein w/ normal cell caoutn: 3. Albuminocytologic dissociation aa. Charcot-Marie-Tooth Dx (Stork Leg, Foot Drop, Pes Cavus- High arched feet) i. Hereditary Sensory Motor Neuropathy Type 1 ii. MOST COMMON INHERITED NEUROPATHY iii. Abnormal proprioception/vibration sensation iv. Slowly Progressive Distal Limb Weakness w/ muscle wasting: Late Childhood or adolescence 1. Lower before upper extremities v. Damage to Deep Peroneal Nerve  Wasting of muscle f anterior compartment of lower limb  Stork Like appearance of legs 1. Foot Drop and Pes Cavus (high arched Feet) 2. Tibialis Anterior, Extensor Hallucis, Extensor Diigtorum, Peroneus Tertius vi. Clumsy chidren, fall frequently (injuries to knees and ankle) bb. PML (JC virus): i. Inflmmation localized to Small portion of spinal cord or cerebral cortex 1. (Lateral corticospinal tract, Precentral gyrus) 2. Parietal and Occipital Lobes ii. JC Virus infects Oligodendrocytes (like Measels) iii. Varied neurologic symptoms, dementia iv. HIV, Parietal-Occipital Lobes, Non-contrast enhancing lesions v. Weakness, Vision problems, can’t walk/talk.

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vi. Demyelination, Astrogliosis, Lymphohistiocytosis vii. Immunosuppressed, especially AIDS Multiple Sclerosis: MOST SIMILLAR TO GUILLAIN BARREE i. Chronic, Progressive Neurologic Disease: Autoimmune! 1. Cell mediated response against white matter antigens 2. Icnreased IgG (oligoclonal bands) in CSF ii. Multiple periods of Exacerbation and Remission: Sensory and Motor deficits separated in Space and Time 1. Internuclear Ophtalmoplegia: MLF DEGENERATION 2. Vision Loss: Optic Neuritis iii. Well-Circumscribed regions of gray discoloration of various brain regions from Demyelination of white matter (Pathognomonic) 1. Inflammation localized to small protion of spinal cord or cerebral cortex iv. Eyes usually FIRST SIGN: Diplpia w/ a demyelinating Central nervous system lesion on MRI 1. Medial Rectus Palsy when attempting lateral conjugate gaze, 2. CONVERGANCE IS NORMAL 3. Binocular Diplopia w/ misalignment of two eyes 4. Inability to ADDUCT Right eye on a LEFT lateral Gaze (or viceversa) 5. Pathognomonic for Internuclear Ophthalmoplegia (INO) 6. Damage to Medial Longitudinal Fasciculus (MLF) which links abducens nucelus of CN 6 w/ oculomotor Cn 3 nucleus during lateral gaze 7. One eye straight (can’t look towards nose), the other eye lateral) v. Hyperreflexia present: Upper Motor Neuron Sign vi. More common in northern regions and 2x more in women: 3rd/4th decade vii. HLA-DR2 viii. Tx: High dose steroids, Interferon Beta, Glatiramer , Natilizumab Central Pontine Myelinolysis i. Overly Aggressive Correction of HYPONatremia ii. Focal demyelination of central area of basis pontis 1. Corticosponal and corticobulbar tracts (crus cerebri) iii. Pseduobulbar Palsy, Spastic quadriparesis, Mental Changes, iv. Produced LOCKED IN syndrome v. Fatal vi. Seen in severely malnourished, alcoholics, liver disease Tourette: i. Motor tics and vocal tics, ii. Associated w/ OCD and ADHD iii. Tx: Antipsychotics Malignant Hyperthermia from Anesthetics i. Rare, but occurs after use of paralytics like succinylcholine (depolarizing agent) and inhalational agents (sevoflurane, desflurane, isoflurane) ii. Due to an inherited gene mutation that causes tetany, increased muscle metabolism, tacycardia, cyanosis, increased end-tidal carbon dioxide, and excessive heat production w/ anesthetic administration 1. Ryanodine Receptor is found w/in muscle cells and allows calcium to be released from SR, causing contraction

a. Mutation in gene coding for ryanodine receptor are predisposed to develop malignant hyperthermia b. In presence of anesthetic agent, mutated receptor allows for uncontrolled calcium release from SR  Sustained muscle contraction  Heat + CO2 2. As malignant hyperthermia progresses, severe life threatening complications can occur a. Hypotension, dysrhythmias, rhabdomyolysis, and DIC b. Rhabdomyolysis  Acute Renal Failure  Increased Creatinine level w/ or w/o oliguria iii. Core temp begins to rise  45 deg C iv. Treat w/ Dantrolene and cooling

Cancer
16) Cancer a. Tumor Markers: i. A-fetoprotein: 1. Hepatocellular Carcinoma 2. Germ-Cell Tumors (Non Seminomas) a. Yolk Sac tumor (testes or ovaries) ii. Alkaline Phosphatase (placental) (PLAP) 1. Seminoma 2. Dysgerminoma iii. APC tumor suppressor gene 1. FAP colorectal cancers 2. Chromosome 5q iv. B-hCG 1. Trophoblastic Tumors, Choriocarcinoma v. Bcl-2 1. Low-Grade Lymphomas vi. Bombesin: 1. Neuroblastom, Small Cell Carcinoma, Gastric Carcinoma, Pancreatic Carcinoma, Carotid Body Tumor vii. CA-19-9 1. Pancreatic Adenocarcinoma viii. CA-125: 1. Ovarian epithelial Tumors (serous papillary cystadenocarcinoma) 2. Also Associated with other female tumors, abdominal inflmaations, pregnancy, endometriosis ix. Calcitonin 1. Medullary Carcinomas of Thyroid x. CEA: 1. Cancers of Colon, Pancreas, Lung, and Stomach xi. GFAP: Intermediate Cytoskeletal filament (Keratin) 1. Astrocytes and Ependymal Cells xii. HMB-45: 1. Vulvar Melanoma

xiii. Ki-67: Neoplastic Replicative Activity  Rate of growth and prognosis 1. Astrocytoma/Glioma 2. Burkitt Lymphoma (100%) xiv. Parathyroid Related Peptide (PTH-rP) 1. Squamous cell carcinoma of Lung xv. Prostatic Acid Phosphatase and Prostate-Specific Antigen (PSA) 1. Porstate Cancer xvi. S-100 1. Melanoma, Neural tumors, Astrocytoma, Schwannoma xvii. Smooth Muscle Actin 1. Leiomyoma: w/ WHORLED PATTERN xviii. TRAP: Tartrate-Resistant Acid Phosphatase 1. Hairy Cell Leukemia xix. Ubiquitin: Low MW heat shock (intraneuronal inclusions from neurodegenerative dx) 1. Lewy Bodies, Pick Bodies, and Neurofibrillary Tangles b. Oncogenes i. Abl 1. CML 2. Tyrosine Kinase ii. BCL-2 1. Follicular and Undifferentiated Lymphomas 2. Anti-Apoptotic Molecule iii. C-Myc: 1. Burkitt’s Lymphoma 2. Transcription Factor iv. ERB-2 1. Carcinoma of Breast, Ovary, and Stomach 2. Tyrosine Kinase v. K-ras 1. Adenocarcinomas of Lung 2. Colorectal Cancer – Intermediate Adenoma vi. L-Myc 1. Small Cell Carcinomas of Lung 2. Transcription Factor vii. N-Myc: 2p 1. Neuroblastoma: a. Most common malignant extracranial solid tumor of kids b. Adrenal Medulla/Sympathetic Chain c. Worse prognosis 2. Transcription Factor viii. Ras: 1. Colon Carcinoma 2. GTPase ix. RET 1. MEN 2a and 2b 2. Tyrosine Kinase

c. Tumor Suppressor Genes: Two Hit hypothesis i. APC: (Chromosome 5q) 1. FAP Colorectal Cancers: 2. ii. BRCA1 (Chr 17) and BRCA 2 (Chrm 13) 1. Breast Cancer, hereditary iii. DCC: (Chromosome 18q) 1. Colon and Gastric Carcinomas iv. DPC: (Chromosome 18q) 1. Pancreatic Cancer v. NF-1: (Chromosome 17q) 1. Neurofibromatosis Type 1 vi. NF-2: (Chromosome 22q) 1. Neurofibromatosis Type 2 vii. P53: 1. Li Fraumeni, increased risk of breast cancer, colon carcinoma 2. HPV E6 viii. RB: (Chromosome 13q) 1. Osteosarcoma, Retinoblastoma, HPV E7, Soft tissue tumors ix. VHL: Chromosome 3 1. Von Hippel Lindau: Hemangioblastoma of retina, cerebellu, and medulla w/ Renal Cell carcinoma x. WT1: Chromosome 11p13 1. Wilms Tumor d. Tumor Cachexia: Tumor Wasting Syndrome i. Reduciton in lean body mass w/ Profound loss of appetitie and weakness ii. TNF-a and IFN-gamma and IL-1 mediate cachexia by increasing catabolism of proteins and fat iii. e. Common Signs: i. Hydrocephalus: (Obstructive of 4th ventricle): Headache and Papilledema 1. Medulloblastoma: Cerebellar Vermis (Midline) 2. Ependymomas: (Ependymal cells of 4th ventricle) 3. Hemangioblastomas: (Cerebellum, Ataxia w/ polycythemia) ii. Pseudopallisading Necrosis = Glioblatoma Multiforme iii. Rosettes: 1. Epnedymoma in small lumen 2. Medulloblastoma: Small blue cells in perivascular rosettes at Cerebellar vermis iv. Pseudorosettes: 1. Ependymoma (Perivascular) 2. Medulloblastoma (perivascular) v. Psamomma Bodies: Round, Extracellular Concretions of Calcium 1. Mengioma 2. Papillary Carcinoma of Thyroid vi. Whorling Pattern 1. Leiomyoma a. Whorls of SPINDLE-SHAPED SMOOTH MUSCLEs

b. Fibroids of Uterus c. Well-Circumscribed, Rubbery, WHITE-TAN mases d. Cause Pain, Infertility, or pregnancy complications 2. Schwannoma: Antoni A cells 3. Meningioma a. WHORLS AND PSAMMOMA BODIES i. Meningioma cells encircle one oantoehr b. Seizures may occur c. From Dura Matter or arachnoid d. Sharply demarcated from brain tissue e. Incite an osteoblastic rxn in overlying cranial bones f. Leg weakness, due to leg motor fibers passing thorugh internal capsule originate in Parasagittal cortical regions vii. Rosenthal Fibers 1. Pilocytic Astrocytoma 2. Corkscrew-shaped, intensely eosinophilic structures deriving from accumulation of alpha-beta crystallin w/in astrocytic processes viii. The Hard Diseases 1. NF2: a. Meningioma, Bilateral Shwannoma 2. NF1 a. Pigmented Iris Hamartoma = Lisch Nodule, Café au lait = Hyperpigmented, sharply bordered, ovoid macules that are >5 mm prepuberyty and >15mm post puberty, Neurofibromas = subcutaneous, Marked skeletal disorders, neural tumors 3. Fragile X a. Macro Orchidism, unusually long face, large jaw, large everted ears, mental retard 4. Von Hippel Lindau a. Hemangioblastoma, Renal Cell Carcinoma, Cerebellar Tumor, Leptomeningioma b. Ataxia + Polycythemia (2ndary) + Primary brain tumor w/ Foamy Stromal Cells within a highly vascular neoplasm (Hemangioblastoma)  Increase Erythropoetiin c. Chromosme 3: VHL gene 5. Tuberosclerosis a. Hypopigmented, ash leaf spots =, Shagreen patches = Orange peel rough raised patch on lumbosacral area, Angiofibroma on face = orange/red raised spots on face, tubers = calcified in ventricle  seizures/epilepsy, astrocytoma, mental retardation, rhabdomyomas, renal cell carcinoma, calcified hamartoma in periventrical region = Tuber 6. Molluscum Contagiosum a. Umbilicated, Skin/Flesh colored, Pearly-white Papule, Benign 7. Bacterial Endocarditis a. Tender, Violascious Subcutaneous nodules of fingers and toes = Osler’s Nodes 8. Acanthosis Nigricans (Diabetes, obesity, GI Adenocarcinoma)

a. Thickened and hyperpigmented skin on back of neck and axillae 9. Wilm’s Tumor a. Primitive glomeruli b. Encapsulated resectable kidney tumor composed of embryonic appearing glomeruli. c. Associated w/ Aniridia and Hemihypertrophy, Genitourinary Malformations, and Mental- Motor Retardation: i. WAGR syndrome d. May have blood in urine. e. Tumor looks like clear jelly stuff too 10. Leydig Cell Tumor a. Reinke’s Crystals ix. Found in Pilocytic astrocytoma, Reactive Gliosis (especially around tumors and vascular malfomration), and Alexander Dx (a rare leukodystrophy x. Cauliflower: Condyloma – 1. HPV w/ Koilocytic Cells, Enlarged Nuclei, Perinuclear Cytoplasmic Vacuolization. f. Lymphoma i. Hodgkin: 1. Night sweats, Fever, and Weight Loss 2. Mediastinal LAD 3. Reed-Sternberg Cells a. Neoplastic ginat cells w/ multiple nuclei (owl eye) 4. Associated w/ EBV!! g. Renal cell Carcinoma i. Von-Hippel Lindau ii. Tuberosclerosis h. Kaposi Sarcoma: Herpes Virus 8 in HIV i. Reddish (Purple-Red), Slightly raised rash on face, chest, and mouth ii. Proliferating cells MOST SIMILAR to ANGIOSARCOMA 1. Proliferating Stromal cells and endothelium creating vascular channels that contain blood i. Tuberosclerosis: Autosomal Dominant i. Genetics: Genes regulate cellular growth and didfferentiation 1. TSC-1 Mutation on Chromosome 9 – Hamartin Protein 2. TSC-2: Chromosome 16 – Tuberin Protein (G-protein homology) a. Related to RAS in regulation of entry into S phase and production of Hamartomous ii. Cortical tubers, Renal angiomyolipomas, astrocytomas, pulmonary lymphangioleiomyomatosis iii. Facial Angiofibroma = Adenoma Sebaceum = Red and Yellow Papules on Face and mouth iv. Large, Firm, White Hamartomatous Nodules =Tubers- Cortex and Subependymal sites 1. Aberrantly Arranged Neurons and/or Glia v. Hypopigmented areas (ovoid, on trunk and) = Ash-leaf spot (vs. Hyper in neurofibroma) = vi. Shagreen Patch = Leathery Thickening and Localized patches vii. Epilepsy and Mental Retardation viii. MRI shows multiple nodules of glial proliferation in the basal ganglia, ventricles, and cortex ix. Associated with

1. Liver/Kidney/Pancreatic Cysts, Renal Angiomyolipomas (Tubers of blood vessel, muscle, and fatty tissue), and Cardiac Rhabdomyomas 2. Maybe Astrocytoma in tuber x. Called Phakomatoses j. Von Heppel-Lindau (AD) i. Chromosome 3: Tumor Suppressor Gene ii. Cavernous HemAngioma, Capillary Hemangioblastoma + Renal Cell Carcinoma + Polycythemia iii. Tumors and/or cysts involving: 1. Retinal angiomas, Capillary Hemangioblastomas of CNS (CEREBELLUM), Renal Cel Carcinoma, 2. AAngiomatous/Cystic Lesions of other organs: Epididymis, kidneys, liver, pancreas, lung, skin iv. Produce Erythorpoeitn  POLYCYTHEMA v. Foamy stromal cells within highly vascular neoplasm of hemangioblastoma k. Sturge-Weber i. Leptomeningeal Angiomatosis ii. Port-Wine Stain = Nevus Flammius (Birthmark) = Vascular Ectasia (opening) 1. Trigeminal Nerve Distribution 2. EncephaloTrigeminal Angiomatosis iii. Associated with 1. Mental Retardation, Seizures, Hemiplegia l. Neurofibroma (AD_: i. Genetics: Tumor suppressor genes 1. NF1: Chromosome 17 – Neurofibronin (NF1) Tumor suppressor gene a. Regions homologous to RAS gene: Signal transduction 2. NF2: Chromosome 22: NF2 tumor suppressor gene 3. Variable Penetrance, Autosomal dominant ii. Neurofibromas and Café Au lait spots 1. Multiple nodules just below skin surface 2. Proliferation of fibroblasts or Schwann cells in peripheral nerves 3. Possibly due to ras hyperactivation iii. Lisch Nodules in Iris (NF1): Pigmented Iris Hamartomas 1. Pigmented iris nodules iv. Hyperpigmented Café-Au-Lait Spots 1. Numerous tan macules on skin v. Associated with: 1. Pheochromocytoma, Glioma, Meningiomas vi. Acoustic Neuromas 1. Bilateral in NF2 vii. Tx: Surgical resection of symptomatic tumors m. Kaposi Sarcoma: Multiple Brownadn Purple Plaques on Face and Oral Muscosa n. Carcinoid i. Site and Size = Malingancy o. Marfan: i. Chromosome 13: Fibrillin Gene

1. Elastic fibers, ECM, connective tissue dx ii. Myxoid degeneration of Mitral valve leflets: Floppy vlave/ regurge iii. Cystic Medial Necrosis  Aortic Dissection (vs. Athersclerosis or Syphilis) iv. Valsalva maneuver increases sound of mitral valve prolapse in systole: Systolic click w/ murmur into late systole p. Meningioma: i. MOST COMMON Benign Intracranial Neoplasm (adults) ii. Dural-based tumor arising from meningothelial cells of arachnoid iii. Grow along dural convexities of Parasagittal region iv. Consists of WHORLS of elongated cells w/ Scattered Psammoma bodies 1. Round, extracellular concretions of calcium v. Spindle shaped cells w/ indistinct borders vi. Expands downard, compresses brain, but no invasion q. Glioblastoma Multiforme: i. Most frequent Primary Malignant intracerebral tumor in Adults 1. Grade 4 astrocytoma ii. Cerebrl white matter in middle age/elderly iii. Spread along white matter tracts, ESP CORPUS CALLOSUM 1. BUTTERYFLY GLIOMA = Large tumor extending from right to left cerebral hemisphere across corpus callosum iv. Most malignant of Primary CNS: 12 months to live v. Cerebral Cortex in Adults vi. Brainstem in Children vii. Neoplastic transformation of astrocytes within white matter 1. Astrocytomas viii. Variegated appearance w/ areas of solid tumor alternating w/ necrosis and hemorrhage ix. Areas of necrosis surrounded by rows of neoplastic cells 1. PSEUDOPALISADING NECROSIS x. Brisk mytotic rate, extreme nuclear pleomorphism, histologic atypia r. Medulloblastoma i. Cerebellar vermis in children (midline) 1. Wide-based, ataxic gait w/ Mass in Cerebellum ii. Nueronal and Glial Differentiation (ONLY TUMOR W/ THIS) iii. Obstructive Hydrocephalus  Headache and papilledema 1. 4th ventricle iv. Grey-White masses in cerebellum of children and in Cerebral Hemispheres of adults v. Histo 1. Primitive neuroectodermal tumor 2. Sheets of densely packed, poorly differentiated small cells. 3. Cells show spindle cell morphology and stain for GFAP 4. May have Rosettes 5. Smal blue cells arranged in perivascular rosettes at cerebellar vermis vi. Primitive Neuroectodermal Tumor s. Oligodendroglioma = Fried Egg Cells i. Tumor cells w/ Round nuclei (yolk) and cleared cytoplasm (white): Perinuclear halo of round, regular nuclei.

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ii. Contain areas of Calcification, Hemorrhage, or cyts iii. Occur in Cerebral Hemisphere of Middle age patients of both sexees Ependymoma: i. Rod shaped blepharoblasts (basal ciliary bodies) ii. Ependymal cell tumors most commonly in 4th ventricle  Hydrocephalus iii. Perivascular Pseudorosettes Neuro: Gray-White Matter Junction Tumors i. Metastatic Cancer 1. Malignant w/ Brown Pigment = Melanoma (sun risk) Pilocytic Astrocytoma i. Elongated astrocytes w/ longBipolar cells, located in Cerebellum of YOUNG CHILDREN appearing as a cyst w/ a mural nodule and containg Rosethanl Fibers 1. Cerebellar and hypothalamic regions most common ii. Tumor of Posterior Fossa consiting of a large cyst w/a nodular mass attached to its wall iii. ROSENTHAL FIBERS! 1. Corkscrew-shaped, intensely eosinophilic structures deriving from accumulation of alpha-beta crystallin w/in astrocytic processes 2. Found in Pilocytic astrocytoma, Reactive Gliosis (especially around tumors and vascular malfomration), and Alexander Dx (a rare leukodystrophy) iv. Acute vomiting and Nuchal rigidity v. Stain w/ GFAP Thyroid Cancer: i. Most common: Papillary Carcinoma: Female predominance 1. Mass in neck, does NOT concentrate radioisotopes (cold nodule) 2. Solid balls of neoplastic follicular cells, 3. Microscopic blood vessels and fibrous troma in centers of balls = Papillary clusters a. Pathognomic for Papillry carcinoma rd th 4. 3 -5 decade of life (20-40) ii. Associated w/ radiation to neck region, and good prognosis, even thoug it spreads to lymps Craniopharyngioma = Adamantinoma = Ameloblastoma (tooth enamal origin) i. Cystic Mass above Pituitary gland 1. Machine Gun Oil/Dark, Oily Fluid w/ granular debris ii. Histology: 1. Ameloblastom b/c resemblane to TOOTH ENAMEL ORGAN a. Which contains ameloblasts 2. Pituitary forms from a. Downward growth of brain  post pituitary b. Upward growth of mouth  Anterior lobe i. RATHKE’s POUCH iii. Occupy sella trcica or be suprellar, in hypothalamus iv. Mass Effects: 1. Headaches, Poor visual tracking v. Or Pituitary Insufficiency 1. Schwannoma: i. Cerebellopontine Angle

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Schwann cell tumor: Third most common primary tumor Localized to CN 8 (acoustic neuroma) Hearing loss, tinnitus, vertigo, hydrocephalus, and increased intracranial pressure Antoni A cells 1. Spinld cells palisading and from whorl appearance, pink cytoplasm vi. Antoni B Cells 1. Loosely arranged tissue after tumor degneration Rhabdomyosarcoma i. Malignant tumor of skeletal muscle ii. Most common in children iii. Composed of undifferentiatedp pleomorphic cells admixed with STRAP VELLS containing myofilaments Liposarcoma i. Very common soft-tissue tumor 1. Middle age and elderly 2. Thigh and Retroperitoneum ii. Pleomorphic Lipcytes that resemble embryonal lipblasts 1. Cytoplasm filled w/ lipid vacuoles (Positive for fat stains) 2. Indentation of nuclear membrane 3. Pleomorphic clear cells w/ vacuolated cytoplasm 4. Nuclei of cells indented by ctoplasmic vacuoles, staining positive for lipids Lipoma i. Idnetical to mature fat tissue ii. Adipocytes w/ a single large cytoplasmic droplet that DISPLACES the nucelus to periphery Chondrosarcoma i. Cartilage tumors, mostly in pelvic region ii. Anaplastich Chondrocytes iii. Produce Chondroid = Basophlic intercellular substance Zollinger-Ellison i. Gastrin Secreting tumor (gastrinoma) 1. Pancras, Duodenal Wall, or Lymph Nodes ii. TEST FOR IT: 1. Secretin injection a. Secretin inhibits antral gastrin Normally b. Stimulates gastrin secretion in patients w/ ZES i. Increase in serum gastrin of more than 200 ng/ml = Diagnosis Gastric Carcinoma: i. Epigastric Discomfor w/ no relation to meals ii. Guaiac Positive Stool iii. Ulcerated mass in natrum of stomach, w/ infiltration of adjacent mucosa iv. Risks: 1. Japanese: Food Preservitives a. Increased concentration of Polycyclic Hydrocarbons in smoked fish b. Nitrites I preserved foods Peptic Ulcers, Gastric Lymphoma, and Adenocarcinoma: i. H. Pylori: in antral mucosa

ii. iii. iv. v.

gg. Squamous Cell Carcinoma of Bladder i. Smoking, ii. Schistosomiasis (Egypt) 1. May injur liver, bladder or intestines hh. Transitional Cell Carcinoma; i. Discovered b/c of hematuria ii. Papillary neoplasm located in TRIGONE iii. NO muscular Hypertrophy ii. Male Testes i. Seminoma 1. Most common Germ Cell tumor testicular tumor in adult males 15-35 yrs 2. Peak in men in their 50s 3. Appears as a large, bulky, gray-tan mass 4. Large cells in lobules, with watery cytoplasm 5. Elevated Alkaline Phosphatase 6. Good prognosis 7. Nuclear atypia present ii. Choriocarcinoma: 1. 15-20 yrs old 2. Smal primary tumor w/ extensive hemorrhage and necrosis 3. Early and Widespread metastasis 4. Beta-hCG is elevated 5. May have gynecomastia and testicular enlargment iii. Embryonal Carcinoma 1. 20-30 years 2. Bulky mass w/ hemorrhage and necrosis 3. Alpha Fetoprotein and Beta hCG elevated 4. Aggressive iv. Yolk sac Tumor 1. Rare, but aggressive 2. Infants and children 3. Elevated alpha fetoprotein v. Teratoma 1. Most common in infants and younger children 2. Cystic mass from multiple germ layers 3. No specific tumor marker a. Mature b. Immature: i. vi. Leydig Cell Interstitial Tumor (non germ cell) 1. 20-60 years 2. Elaboarte adnrogens or estrogens, and rarely, steroids 3. Unilateral! 4. Present w/ testicular mas, but also gynecomastia or precosiuos puberty a. Gyneomastia = Estrogen b. Or Masculinization

5. Golden-brown tumor, 6. Large, uniform cells w/ indistinct cell borders and rod-shaped crystals (of REINKE) vii. Sertoli Cell Tumor (non germ cell) 1. Unilateral 2. Gray-white to Yellow 3. Form cordlike structures resembling seminiferous tubules 4. Small amounts of estrogen or androgens produced  No clinical symptoms 5. Benign

MusculoSkeletal
17) MusculoSkeletal: a. Arthritis i. Rheumatoid 1. Proliferative Synovitis w/ Many lymphocytes, Macrophages, and Plasma Cells. 2. Associations: Sjogrens, SLE 3. Amyloid deposits due to chronic inflammation causes RESTRICTIVE CARDIOMYOPATHY a. AA = Amyloid Associated Protien: Many organ systems b. Rigid and waxy texture. Stains Congo Red to apple green color birefringence ii. Osteoarthritis: 1. Most Common Rheumatologic Disease a. Prevalance increases w/ age 2. Repetitive Low-Level trauma to joints 3. Excessive Cartiage Loss and Reactive Bone Formation (spurs) 4. Most commonly weight bearing joints a. Distribution in Lower Vertebrae, Pelvic Bones, Proximal Femur 5. Sclerotic bone = Reactive bone formation a. Develops as a rexn to injury b. Responsible for Elevated Serum Alkaline Phosphatase levels in Elderly 6. MUST CHECK FOR PROSTATE CANCER w/ OSTEOBLASTIC METASTASES to vertebrla Column and pelvis a. PSA and Digital rectal exam i. Palpation of Prostate can raise serum prostate levels iii. Septic: Gonococcal 1. Non-Proliferative Synovitis w/ many neutrophils and Gram – Diplococci 2. Single joint b. Gout and Pseudogout i. Gout 1. Big Toe 2. Monosodium Urate 3. Needle Shaped, Negatively Birefringent ii. Pseudogout 1. Knee and Large Joints 2. Rhomboid Shaped CALCIUM PYROPHOSPHATE Crystals 3. Positively Birefringent ( blue/basophilic) 4. Tx: Colchicine + Steroids

c. Stones: i. Gallstones: 1. Cholesterol a. Risk: 5 F’s i. Female, Fat, Forty, Fertile, Flatulent 2. Mixed stones and Cholesterol stone risks: a. Obesity, High Estrogen, Multiparity, Crohn Dx, Rapid Weight los,CLOFIBRATE, Native Americans 3. Pigment stoen risks: a. Chronic Hemolysis, Alcoholic Cirrhosis, and biliary infection ii. Kidney 1. Cystine and Struvite 2. Calcium Oxolate d. Osteoporosis i. Decreased or low bone density ii. Thin trabeculae w/ normal calcification and normal amounts of osteoblasts and osteoclasts 1. Normal Serum Calcium iii. Diagnosis based on prior history of fragility fracture or LOW BONE MASS DENSITY: DXA T score < 2.5 iv. Tx DOC: Use Bisphosphonates (alendronate, risedronate, ibandronate etc) 1. Risedronate: (Postmenopausal, Steroid-Induced, Male osteoporosis, as well as Paget Disease) 2. Inhibit osteoclast activity  Reduce bone resorption and turnonver v. Tx Also: Ca and vitamin D e. Erythema Multiforme/S-J-S i. Immunosuppressed w/ abrupt intensely itchy rash ii. Multpile erythematous patches of distal arms, legs, and palms and soles iii. Target Lesions: Patches have pale, vesicular, or eroded centers w/ surroudngin erythematous rings iv. Produced by immune coplex depositin in dermal blood vessels: v. Causes 1. Infections: a. Herpes, Enteroviruses, M. Pneumoniae, Chlamydia, Histoplasmosis 2. Drugs: a. Penicillin, Sulfa, Phenytoin, Aspirin, Steroids, Cimetidine, Allopurinol, OCP 3. Neoplasias: a. Leukemia, Lymphoma, MM, Internal malignancies, 4. Sarcoidosis 5. Foods: Emulsfiers in margarine f. Becker Muscular Dystrophy: X linked Recessive (but females can get) i. Muation of Dystrophin Gene on X –Chromosome 1. Dystrophin links intracellular contractile apparatus in muscle cells w/ ECM 2. Serves to transfer the force of contraction to Extracellular Connective Tissue 3. Absence of functional dystrophin leaves muscle cells forced to absorb entire force load, resulting in premature degeneration that characterizes disease ii. Physical

1. Progressive difficulty walking and arising from chairs 2. Significant proximal muscle atrophy and hypertrophy of calves 3. Elevated Creatine Kinase and Lactate Dehydrogenase iii. Females can get, especially if they have Turner syndrome and have only one X 1. Short stature, webbed neck, swelling of hands, redundant folds of skin at neck. g. Myotonic Dystrophy: Autosomal Dominant i. Trinucleotide Repeat Expansion on Chromosome 19 ii. Myotonia: Sustanied involuntary contraction of a group of muscles iii. Shaking hands  can’t release grip h. Werdin-Hoffman Dx: Autosomal Recessive (Similar to ALS) i. Spinal Muscular Atrophy (infantile Motor neuron dx) ii. Mutation of the survival motor neuron gene (SMN1) on Chromosme 5 iii. Death by 3 years

Renal
18) Renal a. Arteriole Effects: i. Constrict Afferent: 1. Decrease RPF 2. Decrease Delta P: Hydrostatic Pressure Gradient ii. Dilate Afferent: 1. Increase RPF 2. Increase Delta P: Increases Glomerular capillary pressure iii. Constrict Efferent: 1. Decrease RPF 2. Increase delta P iv. Dilate Efferent: 1. Increase RPF 2. Decrease delta P v. Constrict Afferent AND Dilate Efferent 1. RPF Effects Cancel out: a. Decreases RPF and then Increases RPF 2. Both Decrease Delta P: Glomerular capillary pressure b. Increase of RPF: RPF = (Mean arterial pressure – Right atrial pressure)/ Renal Vasc Resistance i. Decreases filtration fraction along length of glomerular capillary, so rising change in plasma protein oncotic pressure occurs SLOWER ii. Greater difference b/w Net Hydrostatic pressure and Plasma oncotic pressure iii. Decrease in renal vascualr resistance iv. Occurs w/ dilation of afferent or efferent c. Renal Cell Carcinoma i. Von-Hippel Lindau and Tuberosclerosis ii. Polycethmia: Secondary d. 95% of Salt intake excreted by Kidneys. 5% in sweat and Feces i. Salt IN = Salt Out e. Least Osmolarity of Kidney:

i. Cortical Thick Ascending Loop of Henle and Early Distal Tubule, ii. Macula Densa is this border b/w TAL and Early portion of Distal convoluted tubule. f. Most Osmolarity of Kidney: i. Vasa Recta of Renal Medulla and Sickle Cell Dx 1. High osmolarity and Hypoxia lead to Sickle Crisis 2. Patchy Papillary Necrosis, Proteinuria, and Renal Scarring g. Glucosuria Threshold: 200 serm glucose, h. Renal Failure Diet i. Low Protein ii. Low Phosphate iii. High Carbohydrates 1. Glucose used by the body is continually being provided exogenous sources 2. This limits gluconeogenesis  limits protein catabolism and nitrogen production iv. Moderate Fat v. Limit Sodium and Water b/c of decreased GFR i. Renal Shutdown (Trauma) i. Edema, Metablic ACIDosis, Increased in Non-Prortein Nitrogens (urea, Creatinine, Uric Acid), ii. Increase in plasma ions (Na, K, H) iii. Death by Hyperkalemia j. APCKD i. Associate with BERRY ANEURYSMS in CIRCLE OF WILLIS and SUBARACHNOID HEMORRHAGES ii. Tx: ACEI or ARBs 1. Cyst impair perfusion of glomeruli  Renin by JGC  RAAS 2. ACEi also increase renal blood flow and protect renals k. Wegner: c-ANCA i. C-ANCA 1. Staining of cytoplasm of neutrophils a. Proteinase 3 (PR-3) ii. Concurrent Pulmonary, Sinus, and Rneal Involvement 1. Entire respiratory tract, including nasal 2. Chest x-ray shows multiple opacities which can be cavitated 3. Renal is a necrotizing glomerulonephritis with crescent formation iii. Focal, necrotizing vasculitis of unclear etiology iv. Prominent granulomas, some centered on vascular lesions. v. Poumonary Sympotms 1. May be clinically silent w/ only infiltrates on x ray 2. May present as cough and hemoptysis vi. Upper Respiratory Tract 1. Sinus pain, and drainage, purulent or bloody nasal discharge w/ or w/o nasal Ulcerations 2. Nasal Septal Perforation may follow vii. Middle age men: Hematuria, hemoptysis, chest pain, and chronic rhinitis viii. Tx Steroids and Cyclophosphamide l. Angiotensin 2: Block w/ ARB (-sartans) i. Most Powerful Na Retaining Homrone of Body 1. Direct Stimulation fo Na Reasortpion in Proximal and Distal Tubules 2. Stimulation of Aldosterone Secretion

m.

n.

o.

p.

3. Constriction of Efferent Arterioles in kidney  Decrease Peritubular Capillary Pressure  Enhance reabsorption of salt and water Renal Hypertension: i. Hyaline Arteriolosclerosis, Patchy Ischemic atrophy, fibroelastic Hyperplasia 1. Fibroelastic: Thickening of Elastic Lamina and Fibrosis of Media Diabetic Nephropathy: i. Mesangial Prliferation, Nodular Sclerosis/Depostis of MEsagnial Matrix, Thick Basement Membranes ii. Early Renal changes: Diffuse mesangial expansion in glomeruli iii. Late/Advanced: Nodular glomerulosclerosis (Kimeelstie Wilson Nodules) 1. Increased cellularity and mesangial matrix deposition 2. Hyaline masses and thickening of the lamina densa 3. Nephrotic or nephritic, but Nephrotic more common Neuroblastoma: 1p Deletion and N-myc translocation i. Childhood tumor of sympathetic nerves ii. Most commonly along paravertebral chain or w/in adrenal medulla 1. Palpable, asymptomatic abdominal mass on physical iii. Malignancies of Neuroblasts (Neural Crest Cells) 1. Pluripotent cells that populate adrenal medulla nd sympathetic chain iv. Histo 1. Small, round, blue cells of varying degrees of differentiation v. Genetics: 1. 1p deletion and N-myc translocation a. N-myc = oncogene that rsdies on chromosome 2p and is amplified up to 300 times in Neurobalstoma b. Amplification of N-myc = WORSE PROGNOSIS vi. Younger = Better outcome vii. If Ganglion cells present = focal differentiation into a GANGLIONEUROMA Paroxysmal Nocturnal Hemoglobinuria (PNH): (ChrX) i. Striking Hemoglobinuria w/ Red-Brown to Black Urine, Mid-Adulthood 1. Seen in morning b/c of Mild Acidosis at Night  Hemolysis 2. Hemosiderinuria ii. Presenation: 38 yr old male w/ Abdominal Pain and HA 1. Urine is darker in color. Hx of Hepatic Vein Thrombosis 2. Mild Jaundice, NO HEPATOSPLENOMEGALY 3. Pancytopenia: Low Hct, Platelet, and WBC 4. Increased Reticulocytes 5. Positve Dipstick Urinalysis for Blood iii. Defective synthesis of Phosphatidylinosoitol Glycan A (PIG-A) 1. Associated w/ Somatic Mutations in PIG-A Gene (X Chromosome) 2. Deficiency  RBCs extraordinarily sensitive to Complement Lysis a. ESPECIALLY IN ACIDIC ENVIRONMENT b. Infection, Menstruation, Surgery, Cold, Vaccines, Stress iv. Prone to Venous Thrombosis and Thromboembolsim  Abdominal Pain and HA 1. Most Frequent Immediate Cuases of Death 2. Esp in Intrahepatic Veins  Budd-Chiari Syndrome)

v. Pigment Gallstones (Chronic Hemolysis), Granulocytopenia, Frequent INfectins vi. Can Develop Aplastic Anemia and Leukemias q. Glomerular Nodules i. Kimmelstiel-Wilson 1. Diabetes Mellitus ii. Amyloid: 1. Congo Red stains: a. Red in normal Light b. Apple-Green Birefringence w/ Polarized light 2. Amorphous Red Nodules within the glomerular Mesangium in H&E stained material 3. Most Common: a. AL type amyloid due to deposition of altered immunoglobulin light chains 4. AA Type seen in Crhonic Antigenic Inflammation  Tuberculosis r. Renal Changes: i. Diffuse Capillary and Basement Membrane Thickening: 1. Membranous Glomerulonephritis: Nephrotic Syndrome ii. Enlarged Hypercellular Glomeruli w/ ENutrophils + SubEpithelial Deposists 1. Acute Poststreptococcal Glomerulonphritis: Coca Cola Urine iii. Segmental Slcerosis w/ Hyalinosis: 1. FSGS iv. Glomeruli Demonstrating a wire loop appearaeance w/ SUBENDOthelial Basement membrane deposits: 1. SLE s. Bladder Hypertrophy of Smooth Muscle i. Compensatory hypertrophy due too chronic flow imediment ii. Most common cause = Prostatic hyperplasia iii. Trabeculation occurs 1. Prominence of smooth muscleunderneath bladder mucosa 2. Creates meshwork of intersecting bundles t. Polycythemia i. Primary Polycythemia 1. Excess RBCs due to an Abnormality of bone marrow a. Polycythemia Ruba Ver b. Myeloproliferative Syndrome ii. Secondary 1. Increased Erythropoietin a. Poduced in kidneys and stimulates erythroid cell line in bone marrow b. Renal Transplantation i. Due to chronic Renal failure c. Renal Cell Carcinoma 2. Impaired Oxygenation a. Pulmonary Dx, CHF, High altitudes iii. Relative: 1. Fluid loss w/ stable RBC mass a. Vomiting, Diarrhea, Burns

Adrenal
19) Adrenal a. Addison: i. Autoimmune destruction of Adrenal Cortex (all three zones) ii. Decreased Cortisol, Aldosterone, and Adrenal Androgens iii. HYPERPIGMENTATION IS CLASSIC FINDING 1. Due to increase serum ACTH b/c of loss of negative cortisol feedback at pituitary and hypothalamus iv. Low cortisol  GI symptoms 1. Nausea, Vomiting, Anorexia, Fatigability, and Weakness 2. Low Blood pressure, and orthostatic hypotension a. Arterioles less responsive to catecholamine induced constriction w/o cortisol v. Low Aldosterone  Bad CV sympotoms 1. Hyperkalemia, Hyponatremia b. Conn Syndrome: i. Hypersecretion of aldosterone ii. Hypertension, Hypernatremia, Hypokalemia c. Cushings: i. Hypersecretion of Cortisol ii. Central obesity, buffalo hump, moon facies, HTN and Hypokalemia d. Nelson Syndrome: i. Patients w/ Adrenaletomy to tx Cushing’s Disease ii. Extreme Hyperpigmentation 1. Excessive ACTH from a pituitary adenoma that is no longer suppressed by cortisol e. Secondary and Tertiary Adrenal Insufficiency i. Low Serum ACTH  Hypocortisolism  GI complaints + Fatigability ii. NO HYPERKALEMIA, NO HYPERPIGMENTATIONS iii. Normal Aldosterone, N

Repro
20) Repro a. Women’s Egg divisions: i. Before Birth  Ovulation (~40 years) 1. Diplotene Stage of Prophase 1 of Meiosis 1 2. Primordial Ova: In ovary as a single large cel surrounded by a layer of epithelium that is one cell thick a. Large numbers of unusually large cells surrounded by one cell alyer thick epithelial cells ii. Ovulation: Oocyte = Graafian follicle is ovulated 1. Metaphase of Meiosis 2 iii. Fertilization 1. Completion of Meiosis 2  Mature OOCyte b. Pregnancy Hormones i. hCG: 1. First makrer of trophoblastic differentiation

2. Concentration DOUBLES EVERY TWO DAYS, REACHES MAX AROUND 10 WEEKS, THEN DECLINES ii. hPL: 1. Concentration RISES THROUGH PREGNANCY AND is PROPORTIONAL TO FETAL MASS iii. Progesterone: 1. Same profile as hPL, Rises through pregnancy 2. First Tirmester: Source Corpus Luteum till 10 weeks, Then Placenta 3. iv. 17-OH Progesterone is made ONLY IN CORPUS LUTEUM 1. Rises in first five weeks, then declines w/ corpus luteum a. Placenta lacks 17-a-hyrodxylase 2. Similar to hCG v. CRH 1. Sharp Increase in placental CRH around week 28 to Gestation: 2. Labor and Lung Maturaiton c. Primary Amenorrhea i. Most common cause: Turner Sydnrome: 46XO 1. Pt NEVER has menstruation 2. Tanner stage 1 breasts and genitalia w/ sparse pubic hair 3. Weak pulses in lower extremities (coarctation) 4. Increased LH and FSH due to lack of feed back by ovarian secretions a. Ovary shows fibrous stroma arranged in whorls: Streak Ovaries b. High during infancy, rise again after 9-10 years of age 5. Decreased serum levels of free T3 and T4: HYPOHTYROIDISM ASSOCIEATED 6. Increase risk to Gonadoblastoma if Mosaic (45,xo and 46 xy) 7. Dysgenesis of Ovaries w/ Atrophic or “STREAK” Ovaries 8. Lack steroids required for breast deelopment and cyclic function of hypothalamus, pituitary, ovaries ,and uterus 9. Short, widely spaced nipples, webbing of neck, cystic Hygroma, micrognathia, fishlike mouth, shield chest, low-set ears, ptosis, webbed neck 10. Coaractation of aorta or bicuspid aortic valve, hypothyroidism, and diabetes a. Preductal type of coarctation, proximal to ducturs arteriosus  Weak pulses, hypotension, and CYANOSIS of lower extremities b. Rib notching (erosion of lower border of ribs from intercostal enlargment w/ collateral flow) c. RV hypertrophy w/ increased pulmonary marking d. Endocrine i. Testosterone Bound to Sex Steroid Binding Globulin in plamsa and a little to albumin. 1. Protects from renal filtration/degredation ii. FSH stimulates spermatogenisis and Sertoli Cell Function 1. Inhibin secreted by Sertoli cells as endogenous glycoprotein a. Feedback inhibition of FSH e. Preeclampsia: Tx – Delivery i. Proteinuria and HTN after 20 weeks in absence of preexisting HTN ii. Also: Weight gain (excessive), generalized edema, ascites, Hyperuricemia, hypocalciuria, increased plasma concentration of vWF and cellular fibronectin, reduced plasma concentration

of anti-thrombin 3, thrombocytopenia, increased hematocrit, increased liver enzymes, intrauterine growth retardation, intrauterine hypoxia f. Spontaneous Abortion: i. Early Trimester: Most due to chromosomal abnormalities: 10 ii. Second and Third: Chorioamnionitis 1. Infections through vaginal canal infect chorioamnionic membranes and lead to rupture iii. Third Trimester: Placentia Abruptio 1. Placenta detaches prematurely from implanation site and reptroplacental hemorrhage develops w/in space b/w placenta and uterine wall  interruption or revere redcuiton in blood supply to fetus g. Polycystic Ovary Syndrome i. Young woman, Amenorrhea, Obesity, Hirsutism ii. Lab: 1. Increase LH, Testosterone 2. Decrease FSH 3. Cystic follicles in ovary iii. PCOS results in amenorrhea secondary to excessive ovarian androgen production caused by increased plasma LH 1. Possibly due to excessive secretion of GnRH by hypothalamus iv. Pituitary responds to abnormal pattern of GnRH by increasing LH secretion and decreasing FSH v. Increased LH causes theca cell hyperplasia and excessive androgen secretion (testosterone) vi. With Low FSh levels, granulosa cells become atrophied and have insufficient aromatase activity to onvert androgens to estrogen vii. Local high androgen concentration may be responsible for formation of numerous small cystic follicles viii. Hirsutism likely due to increased ovarian secretion of androgen. h. Hirsutism i. An excessive growth of thick dark hair in uncommon locations 1. Face, Chest, Areolae see male pattern growth of body hair ii. Due to 1. Overproduction of androgens, 2. Increased periopheral conversion of androgens 3. Increased androgen rceptor binding iii. Testosterone effects: 1. Testosterone must first be converted into DHT, a more potent follicle active metabolite a. 5a-reductase, found in hair follicle, performs conversion iv. Drugs that cause: 1. Testosterone, Danazol, DHEA-S, Anabolic steroids 2. Phenytoin, Cyclosporine, Streptomycin, High dose steroids, phenothiazines, acetazolamide v. TX: (Absolutely contraindicated during pregnancy) 1. Antiandrogens: a. Spironolactone, Flutamide, Cyproterone acetate i. Spironolactone: Mineralocorticoid receptor antagonist ii. Txs for acne vulgaris, PCOS, Female Hirsutism iii. Ptassium sparing diuretic

i.

2. Estroen Progestin OCPs 3. Oral Steroids 4. Finasterid (5aReductase inhibitor) 5. Eflornithing HCL – Inhibits ornithine decarboxylase (enzyme required for hair growth) Ovarian Tumor: By Cell of Origin i. Surface Epithelium (Coelomic Mesothelium): Cystic Structures 1. Tubal Line: Serous Cystadenoma/Cystadenocarcinoma a. 40% of all ovarian tumors b. Serous Cystadenocarcinoma is MOST FREQUENT Serous tumor i. 2/3 Bilateral ii. 40-65 yrs iii. Cystic Tumor with Clear fluid and a cystic wall lined by malignant epithelial cells forming papillary fronds 2. Cervical Line: Mucinous Cystadenoma/Cystadenocarcinoma 3. Endometrial Line: Endometrioid Tumors ii. Germ Cell Origin (20%) 1. Teratoma a. Mature Cystic i. Majority and benign ii. More than one germ layer b. Immature, i. Malignant/Aggressive c. Monodermal 2. Choriocarcinoma: Elevated B-HCG and hyperemesis gravidarum a. Ovary and Placental. Lots of hCG i. Placental responds to chemo, ovarians do not b. Precursors: i. Complete Mole: 1. 46 XX or HY from haploid sperm replicates win empty egg 2. NO FETAL PARTS 3. Snowstorm appearance, honeycombed uterus, cluster of grapes 4. Increse uterine size ii. Partial Mole: 1. 69 XXY or XXX: Two haploid sperm fertilize a haploid egg 2. Less Nausea and Vomiting and less increase of B-HCG 3. Fetal Parts 3. Dysgerminoma a. Ovarian counterpart of Seminoma of testis b. Expresses Placental Alkaline Phosphatase (PLAP_ c. Hormonally Inactive iii. Sex Cord Stromal 1. Granulosa Cell Tumors a. Mix of Granulosa Cells and Theca Cells b. Produce large amounts of estrogens  Precocious Puberty in preadolescents but Endometrial hyperplasia and fibrocytic breast change in mature women c. Call-Exner Bodies

2. Fibro-Thecomas a. Fibroblasts, j. Only three types of ovarion tumors produce large amounts of steroid hormones: Precocious Sexual Development (Preadolescent) or Endometrial Hyperplasia/carcinoma or Fibrocystic change of breast (Adult) i. Steroli-Leydig Tumors 1. Precursors of Sertoli and Leydig Cells: 2. Produce Male Hormones, manifesting with Masculinization or Defeminization ii. Fibro-Thecomas: 1. Stromal cells, Composed of fibroblasts. Rarely with endocrinologic signs iii. Granulosa Cell tumors 1. Actively secrete estrogens from granulosa cells. k. Pseudomyxoma Peritonei i. Produced when a malignant or benign mucus-producing tumor produces gel-like mucus that fills the peritoneal cavity 1. Spread by rupture into the peritoneal cavity rather than true metastsis 2. Mucus producing tumor = mucinous cystadenoma or mucinous cystadenocarcinoma ii. Origin from Ovary or Appendix iii. Hard to treat bc mucus producing cells are spreading all over the peritoneal lining and cannot be effectively removed. 21) Behavioral a. Ach is the Neurotransmitter of Primary importance for Induction of REM Sleep