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Pathology

Systems pathology

QuestionAnswer
Obligate intracellular bacteria. Ricketsia sp., chlamydia sp., anaplasma sp, ehrlichia sp., coxiella burnetti, mycobacterium leprae.
Facultative Intracellular organisms. Fracisella tularenis, listeria monocytogenes, mycobacterium sp., brucella sp., salmonella sp., legionella pneumophila, yersinia sp., nocardia sp., borrelia sp.
Which families of intracellular bacteria do not produce their own ATP? Rikettsia and chlamydia
Describe the zipper mechanism. adhesins of the organism bind integrins and cadherins to induce endocytosis via actin enclosure.
Describe the trigger mechanism. A Type III or IV secretion system injects effectors (such as rho-family GTPase) to stimulate actin and other cytoskeleton components to form endocytic vesicle.
Give examples of organisms that use the zipper mechanism. Listeria, yersinia, campylobacter, helicobacter.
Give examples of organisms that use the trigger mechanism. salmonella, shigella, chlamydia.
List some of the factors inside phagolysosomes that help in destroying pathogens. iNOS, NADPH oxidase, MPO, SOD, V-ATPase, metal transporters, lactoferrin, defensins, proteases.
Familial adenamatous polyposis Adenomatous polyposis coli (APC) tumor suppressor gene mutation that causes colon cancer by age 30yrs
Multiple endocrine neoplasia MEN IIa and RET proto-oncogene mutation leading to medullary thyroid carcinoma, hyperparathyroidism, bilateral pheochromocytoma due to hyperplasia and/or tumor.
Hereditary non-polyposis colorectal cancer. DNA mismatch repair genes MSH-1 and MLH-1 mutation leading to right colon cancer at a young age and potential along with brain, skin, small intestine, endometrium, ovary, and hepatobiliary tract tumors.
xeroderma pigmentosa nucleotide excision repair mutation that leads to basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.
ataxia telangiectsia ATM protein kinase (responds to DNA damage from ionizing radiation) mutation leading to increased risk of lymphoma, leukemia, and breast cancer.
Blooms syndrome BLM gene (chromosome 15 DNA helicase) mutation leading to increased risk of lymphoma and leukemia.
Fanconis syndrome FAC mutation leading to DNA instability with ionizing radiation and alkylating agents; increased risk of lymphom and leukemia.
PDGF-beta growth factor SIS mutation leading to increased risk of astrocytoma and osteosarcoma
FGF grow factor HST1 mutation leading to increased stomach cancer risk
TGF-alpha growth factor mutation leads to increased risk of astrocytoma and hepatocellular carcinoma.
HGF growth factor mutation that leads to increased risk of thyroid cancer.
EGF receptor ERBB1 growth factor receptor mutation leading to over-expression leads to increased risk of squamous cell carcinoma and lung glioma. Tx with cetuximab.
HER-2/NEU ERBB2 Growth factor receptor mutation leading to amplification causes an increased risk of breast cancer. Tx with trastumzab
Neurotropic factor receptor RET growth factor receptor point mutation at MEN-IIa and MEN-IIb leads to increased risk of medullary thyroid carcinoma
PDGF receptor Growth factor receptor over-expression leads to incresed risk of glioma and leukemia
Stem-cell factor receptor KIT growth factor receptor point-mutation leads to increased risk of gastrointestinal stromal tumor. Tx with imatinib.
KRAS GTP-binding protein involved in signal transduction with point mutation leading to increased risk of pancreas/colon/lung carcinomas.
ABL non-receptor tyrosine kinase involved with signal transduction. (9,22) translocation leads to chronic myeloid leukemia and/or acute lymphoblastic leukemia. Tx with imatinib/gleevac to inhibit tyrosine kinase.
BRAF RAS signaling pathway point mutation leads to increased risk of melanoma.
Beta-Catenin WNT signal transduction point mutation or over-expression leads to increased risk of hepatocellular blastoma and hepatocellular carcinoma.
C-MYC Nuclear regulator transcriptional activator protein (8,14) translocation leads to increased risk of Burkitts lymphoma.
N-MYC Nuclear regulator transcriptional activator protein over-expresssion or amplification leads to increased risk of neuroblastoma and/or small cell carcinoma of the lung.
Cyclin D Cell cycle regulator (11,14) translocation leads to increased risk of mantle cell carcinoma.
Cyclin E Cell cycle regulator over-expression leads to incresed risk of breast cancer.
CDK4 Cell cycle regulator amplification/point-mutation leads to increased risk of glioblastoma, melanoma, sarcoma.
INK4/ARF gene encodes Rb and P53 with hypermethylation inhibiting regulation of Cyclin D/CDK4 leading to pancreatic adenocarcinoma > melanoma.
BCL-2 Over-expression by translocation (8,14) leads to inability to undergo apoptosis in B-cells leading to B-cell follicular lymphoma.
MSH2/MLH1 Microsatillite instability leads to DNA mismatch repair malfunction which may cause heriditary non-polyposis colon cancer syndrome.
BRCA1 Binds RAD51 and is involved in DNA repair while regulating estrogen activity and acting as a co-receptor for androgen receptors. Mutation leads to breast and/or ovarian cancer.
BRCA2 Also called Fanconi anemia gene (FANcD1) binds RAD51 and involved with DNA repair with mutation leading to increased risk in male breast cancer, female breast/ovarian cancer
Telomerase functioning in >90% of cancer cells for without, after 6-70 doublings leads to P53 activation causing cell cycle arrest and apoptosis.
Polycyclic aromatic hydrocarbons present in cigarettes and smoked meats causing increased risk of squamous cell carcinoma and urothelial carcinoma.
Acetyl-amino flourene and Azo dyes CYP450 metabolized leading to hepatocellular toxicity and eventually hepatocellular carcinoma.
Beta-Naphthylamine present in aniline dyes and common among rubber workers and chronic smokers with glucourinase metabolism leading to increased risk of urothelial carcinoma.
Aflatoxin Beta Aspergillus Flavus produces this on improperly stored peanuts/corn/rice leading to increased risk of hepatocellular carcinoma risk due to P53 mutation.
Nitrosamines and Amines Nitrites used to preserve meat causes nitrosylation of amines in stomach and leads to nitrosamine formation leading to increased risk of gastric carcinoma.
Diethyl-stilbesterol Causes clear cell carcinoma of vagina and can be passed down to progeny.
Classic Galactosemia Presents with severe liver disease, gram-negative sepsis, and cataracts. could be caused by enzyme deficiency in Galactose-1-phosphate uridyl transferase or UDP-gal-4-epimerase.
Glycogen Storage disease Presents with hypoglycemia, lactic acidosis. Could be due to G6Pase, Pyruvate carboxylase, or pyruvate dehydrogenase deficiency.
Phenylketonuria Presents with musty body odor, growth retardation, seizures, hypopigmentation, phenylketonuria, and mental retardation due to phenylacetic acid. Due to enzyme deficiency of phenylalanine hydroxylase (decreased BH4). tyrosine essential. aspartame bad.
Maple Syrup urine disease Presents with sweet odor from urine and CNS problems. Enzyme deficiency of branched chain ketoacid decarboxylase.
Tyrosinemia Presents with severe liver disease, renal tubular dysfunction and is caused by an enzyme deficiency of fumaryacetoacetate hydroxylase.
G6PD deficiency X-linked recessive condition characterized by hemolytic anemia. oxidative stress can be caused by inflammatory response, fava beans, sulfanimides, primaquine, and anti-TB drugs. Heinz bodies and bite cells. marlarial advantage.
Gauchers Disease B-glucocerebrosidase deficiency leads to a defiency of glucocerebrosides that presents with aseptic necorsis if the femur, erlenmeyer flask deformity in femur, hepatosplenomegaly, bone crisis, and macrophages that look like crumpled paper.
Homocystinuria AR inherited deficiency of either, methionine synthase, cystathionine synthase deficiency, or decreased affinity of cystothione synthase for Vit B6. Presents with marfinoid body habitus, kyphosis, lens subluxation, MR, atherosclerosis
Hunters syndrome Iduronate sulfatase X-linked defect leading to accumulations of dermatan sulfate and heparan sulfate. no corneal clouding, but gargoylism, airway obstruction, developmental delay, and hepatosplenomegaly.
Hurlers syndrome Alpha-L-iduronidase deficiency results in dermatan sulfate and heparan sulfate (monopolysaccharidoses) accumulation. Presents with gargoylism, developmental delay, hepatosplenomegaly, airway obstruction, and corneal clouding.
Krabbes disease galactocerebrosidase deficiency leading to developmental delay, peripheral neuropathy, optopic neuropathy, and globoid cells (multi-nucleated macrophages in parenchyma and around blood vessels)
Lesch-Nyan Syndrome X-linked deficiency of HGPRT preventing hypoxanthine/guanine conversion to IMP/GMP inhibiting purine salvage pathway. Urecemia, gout, mental retardation, self-mutalation, accumulation of PRPP, and choreoathetosis.
Maple Syrup Urine disease. alpha-ketoacid dehydrogenase defect leading to inhibition of branched chain amino acid degredation. Leucine, isoleucine, and valine accumulate to cause sweet smelling urine, seizures and mental retardation.
McArdles disease muscle glycogen phosphorylase deficiency leading to painful muscle cramps after exercise, myoglobinuria (kidney damage), but normal lactic acid in serum. Type V glycogen storage disease
Metachromic Leukodystrophy Arylsulfatase A defect leading to cerebroside sulfate accumulation which causes demyelination, ataxia, and dementia.
Niemann-Pick Disease more common in jewish populations. caused by sphingomyelinase defect leading to sphingomyelin accumulation. presents with hepatosplenomegaly, cherry red macula, neurodegeneration, and high numbers of foam cells.
Ornithine Transcarbamylase Deficiency Most common urea cycle disorder that is x-linked and presents within first few days of life with hyperammonemia, decreased BUN, and buildup of orotic acid (pyrimidine synthesis) in blood/urine.
Orotic aciduria AR defect of orotic acid phosphoribosyl-transferase or orotidine 5-phosphate decarboxylase (denovo pyrimidine synthesis) which convert orotic acid to UMP. presents with orotic aciduria, megablastic anemia, failure to thrive, no hyperammonemia.tx w/uridine
Pompe Disease. lysosomal alpha-1,4-glucosidase (acid maltase) deficiency. Presents with hepatosplenomegaly, cardiomegaly, hypotonicity, and normal serum glucose.
Pyruvate dehydrogenase deficiency. May be caused by thiamine deficiency. 3 enzyme complex converts pyruvate to acetyl CoA with accumulation of pyruvate and alanine occuring with deficiency. Presents with neural defects and lactic acidosis. Tx with ketogenic diet (lysine/leucine)
Tay Sachs Disease More common among ashkenazi jewish populations. hexosaminidase A defeciency leads to accumulation of GM2 ganglioside. presents with cherry red macula, neurodegeneration, developmental delay, and onion skin lysosomes.
Von Gierke's Disease Glucose-6-phosphatase deficiency (glycogenolysis enzyme). Presents with severe fasting hypoglycemia, hypatomegaly (glycogen excess in liver), lactic acidosis, and enlarged kidneys.
Von Willebrand Disease AD condition resulting in increased bleeding time, PTT (mild), normal platelet count and decreased factor VIII. Tx with desmopressin (Wieble Palade body)
Waterhouse-Friderichsen syndrome adrenocortical deficiency resulting in hypotension, hypoglycemia, hyponatremia, and hyperkalemia. Typically caused by neisseria meningitidis/DIC tubercular infection of adrenal gland leading to hemorrhage.
Adenosine Deaminase Deficency prevents the conversion of adenosine to inosine leading to accumulations of ATP and dATP which inhibits ribonucleotide reductase and thus DNA synthesis. Also decreases B and T cells and is a major cause of SCID.
Zellweger syndrome peroxisomal disorder leading to progressive brain, kidney, liver degeneration with death 6 months after onset. presents as cerebro-hepato-renal syndrome with dysmorphic facies. screening is done using serum VLCFA.
Acute Intermittent Porphyria AD condition with late onset and variable expression. Results from porphobilinogen deaminase deficiency leading to ALA and porphobilinogen accumulation. Presents with port-red urine, psychosis, pain in abdomen, but no photosensitivity.CYP450inducres bad.
Porphyria cutanea Tarda AD condition with late onset due to uroporphyrinogen decarboxylase defect. Presents with photosensitivity, inflammation/blistering/skin shearing from UV exposure, hyperpigmentation, and brown to red urine. exacerbated by alcohol.
Acquired porphyria. pyrodoxine and iron deficiency may cause
Letterer-Siwe Disease malignant histiocytes that lead to rash, cystic skeletal defects in infants (<2y/o), and multiple organ involvement. Rapidly fatal.
Eosinophilic granuloma Benign histiocytosis in bone presenting with pathologic fractures in adolescents without prescence of rash. Biopsy shows histiocyte langerhan cells and eosinophils.
Hand-Schuller-Chrisan disease malignant histiocytes that presents with skin rash on scalp, lytic skull defects, diabetes insipidus, exopthalamus, and seen in children >3y/o
Langerhans cell histiocytosis Birbeck or tennis racket granules seen with EM and CD1a+ and S100+ with staining.
Waldens Macroglobinemia B-cell lymphoma with IgM monoclonality, generalized LAD, increased serum protein with M spike, retinal hemorrhage/stroke, bleeding (hyperviscosity). Tx is plasmophoresis.
Monoclonal gammopathy of undetermined significance (MGUS) increased serum protein with M spike without significant symptoms. presents in 5% of 70 y/o while only 1% develop multiple myeloma.
Multiple Myeloma malignant proliferation of plasma cells in bone marrow that secrete IL-6, osteoclast activating factor, and M spike (IgG>IgA). hypercalcemia/punched bone lesions/rouleaux formation/bence-jones proteins/primary AL amyloidoses/myeloma kidney
Hodgkin lymphoma Reed-Sternberg cells with CD15 and CD30 (no CD20) that secrete cytokines causing hyperthermia/myalgia/malaise/arthralgia, attract lymphocytes/plasma cells/macrophages/eosinophils. may lead to fibrosis.
Nodular sclerosis Most common HL that presents with enlarging cervical or mediastinal LN in young female adult. broad bands of fibrosis, lacunar RS cells. relatively favorable clincal course.
Non-Hodgkin lymphoma B cell lymphomas (CD20+) that tend to grow in mantle, follicle, or margin.
Follicular lymphoma NHL B cell lymphoma (CD20+) caused by t(14:18) H-chain and BCL2 translocation. presents in older adults with generalized LAD, BCL2 expression in LN follicle, and monoclonality (3:1 kappa/lambda). Altered LN shows angulated groove cells in nodular pattern
Mantle cell lymphoma NHL B cell lymphoma (CD20+) caused by t(11:14) Cyclin D1 and H-chain. Presents in late adulthood with generalized LAD with neoplasia in mantle zone of LN.
Marginal cell lymphoma NHL B cell lymphoma (CD20+) caused by chronic inflammatory state such as hashimotos thyroiditis, sjogrens syndrome, H. Pylori. expanded marginal zone of LN seen.
Lysosomal storage diseases Niemann-Pick disease, Fabry disease, Hunter syndrome, hurlers syndrome, Tay-Sachs disease, Gaucher disease, Pompe disease, Danon disease, fucosidosis, galactosialidosis, GM1 gangliosidosis, GM2 gangliosidosis, Krabbe disease, metachromatic leukodystrophy
Glycogen storage disease Von Gierks disease, Pompe disease, McArdle disease, Hers' disease, Fanconi-bickel syndrome (GLUT2), RBC aldolase deficiency, Cori's/Forbes' disease, Andersen disease
Hereditary orotic aciduria Presents with poor growth, megablastic anemia, and orate chrystals in urine. Orotate phosphoribosyl transferase or orotidine 5-monophosphate decarboxylase pyrimidine synthesis enzyme deficiency. Tx with cystidine and uridine to bypass enzyme steps.
I cell disease Presents with skeletal abnormalities, coarse facial features, restricted joint movement, and severe psychomotor impairment. Death <10 y/o. GlcNAc phosphoribosyltransferase deficiency impairs mannose6P addition to lysosomal vesicles in golgi apparatus.
medium-chain acyl-CoA dehydrogenase deficiency (MCAD) presents shortly after birth with hepatomegaly, poor feeding, vomiting, hypoglycemia, hypoketonia due to decreased ability to oxidize fatty acids of 6-10 carbons long. highest incidence among caucasions of nothern european descent.
cryptosporidium acute diarrhea in healthy, but severe in immunocompromised. Ingestion of oocytes from water/food allows full life cycle in SI with excyst causing GI epithelial damage and excretion of oocysts. acid fast protozoan. tx-nitrozoxanide/paromycin
Babesiosis Presents with fever and hemolytic anemia with exposure to ixodes tick in northeastern US; risk borrdia burglorferi=lyme disease coinfection; PBS=maltese cross, ring forms; PCR; Tx-atovaquone+azithromycin
Plasmodium falciparum irregular fever, headache, anemia, splenomegaly, hypoglycemai, hyperlactatemia, jaundice; may cause cerebral malaria, kidneys (black water), lungs (ARD), heart (CHF/MI); female anopheles mosquito; PBS-merozoites/gametocytes; Tx-artemisinin ACT/quinine
Plasmodium vivax 48 hr (tertian) fever, headache anemia, splenomegaly; female anopholes mosquito; PBS
Hairy cell leukemia Presents w/ middle-aged man having anemia, leukopenia, massive splenomegaly, and thrombocytopenia. CD19/CD20/CD22/TRAP (+) B cell disease w/ unique cell morphology. Tx- INF-a, 2-chlorodeoxyadenosine, and deoxycoformycin.
Mycosis Fungoides T-cell lymphoma characterized by a rash. Biopsy shows cerebriform CD4+ T cells. Eventually disseminate to LNs and other organs=Sezary syndrome=combination of skin lesions and circulating CD4+ cells.
Hereditary Hemochromatosis extensive accumulation of hemosiderin often w/in liver, pancreas, myocardium, and multiple endocrine glands=damage. Hfe gene on chromosome 6 mutation. micronodular cirrhosis, diabetes mellitus, and skin hyperpigmentation. High [Fe], decreased TIBC.
Criglar-Najjar syndrome severe unconjugated hyperbilirubenemia due to deficiency of glucuronyl transferasse. T1-AR kernicterus results in death. T2-AD response to phenobarbital.
Gilbert syndrome Common hereditary condition w/ modest unconjugated hyperbilirubinemia= asymptomatic. reduced activity of glucuronyl transferase.
Dubin-Johnson syndrome AR form of conjugated hyperbilirubinemia caused by defective bilirubin transport. Presents with discoloration of the liver=nutmeg liver.
Rotor syndrome Asymptomatic conjugated hyperbilirubinemia caused by defective bilirubin transport, but w/o liver discoloration.
Lesch-Nyhan syndrome Presents w/ Hyperuricemia at birth. spastic cerebral palsy, self-mutilation, and developmental delay. X-linked HGPRT deficiency.
Petechia small, punctate hemorrhages occuring in the skin, mucous membranes, or serosal surfaces. Caused by quantitative (thrombocytopenia) rather than qualititative conditions.
Ecchymosis diffuse hemorrhage usually in skin and subcutaneous tissue.
Idiopathic thrombocytopenic purpura (ITP) Dx given w/ thrombocytopenia or increased megakaryocytes w/o exposure to causative agents or splenomegaly. Children have self-limiting post viral infection or immunizations. Adults have chronic. Due to autuimmune antiplatelet antibodies (IgG-GpIIb/IIIa)
Thrombotic thrombocytopenic purpura (TTP) mechanism AdamTS13=VWF metalloprotease deficiency=very-high-molecular-weight multimer of VWF accumulation-> platelet derived hyaline microaggregates, thrombocytopenia, & microangiopathic hemolytic anemia. helmet cells & schistocytes in lab.
TTP clinical findings Presents with neurological abnormalities, renal insufficiency, and fever. Labs show helmet cells and schistocytes w/ hemolytic anemia.
Hemolytic uremic syndrome (HUS) Seen in children preceding E.coli 0157H7 acute diarrhea. Verotoxin damages endothelium causing microangiopathic hemolytic anemia, thrombocytopenia, renal insufficiency. Lab-helmet schistocytes w/ elevated LDH. Tx-dialysis
Bernard Soulier syndrome Genetic Gp1b deficiency resulting in impaired platelet adhesion, thrombocytopenia, and enlarged platelets.
Glanzman thrombasthenia Genetic GpIIb/IIIa deficiency resulting in decreased platelet aggregation due to decreased fibrinogen bridges b/w adjacent platelets.
Hemophilia A Classic Factor VIII X-linked deficiency (also spontaneous) resulting in high deep tissue, joint, post surgical bleeding. Lab-high PTT, low FVIII; normal PT, BT, PC. Tx- recombinant FVIII
Hemophilia B christmas disease w/ X-linked factor IX deficiency resulting in increased deep tissue, joint, post-surgery bleeding. Labs-High PTT, low FIX; normal PT, BT, PC. Tx-recombinant FIX.
Autoimmune coagulation inhibiton Autoimmune Ab against coagulation factor (FVIII most common) that can be differentiated from Hemophilia by a mixing study.
VWF disease most common coagulation disorder caused by AD VWF deficiency that can be qualitative or quantitative. presents w/ mild skin/mucosal bleeding, impaired platelet adhesion, high BT/PTT and normal PT. abnormal restocetin (binds VWF and Gp1b) test.
Vitamin K deficiency Leads to decreased gamma carboxylation of factors II/VII/IX/X by epoxide reductase. caused by newborn, long-term antibiotic Tx, and fat malabsorption.
Heparin Induced thrombocytopenia (HIC) high molecular weight heparin forms complex w/ platelet factor VI which can indcue IgG Ab response and cause platelet destruction leading to platelet activation and potential thrombus formation. Tx-change anticoagulant, but not coumadin b/c skin Rx.
Disseminated intravascular coagulation (DIC) pathologic widespread activation of coagulation cascade leading to microthrombi, thrombocytopenia. caused by obstetric complications, sepsis, adenocarcinoma, AML, and rattlesnake venom. Labs- low PC, high PT/PTT, low fibrinogen, high D-dimer, schistocytes
Lines of zahn indicative of formation of intravascular clot in artery or vein demonstrating layered levels that differentiate from post mortum clots
hypercoagulative conditions protein C/S deficeincy, Factor V leiden (most common), prothrombin 2010A, antithrombin III deficiency.
Iron deficiency anemia microcytic hypochromic anemia w/ high RDW, TIBC, and FEP. low ferritin, [Fe]serum, and % Fe saturation. Tx- ferrous sulfate.
Plummer-Vinson syndrome iron deficiency anemia, esophageal webs, and atrophic glossitis presenting with anemia, dysphagia, and beefy-red tongue.
Anemia of chronic disease Elevated ferritin, FEP; decreased TIBC, [Fe]serum, and % Fe saturation. caused by chronic inflammation decreasing Fe transfer from macrophages to erythrocytes due to elevated hepciden which also suppresses EPO production.
Sideroblastic anemia microcytic anemia caused by ALA synthase deficiency (genetic), alcohol poisponing (mitochondrial toxicity), lead poisoning (ALA deaminase and ferrochetolase), and Vitamin B6 deficiency (cofactor for ALA synthase)
Alpha-thalassemia 1 gene KO is asymptomatic, 2 gene KO on cis genes worse than 2 gene KO on trans genes, but mild anemia; 3 gene KO causes severe anemia with B chain tetramer HbH; 4 gene KO has delta chain tetramers HbBarts and is fatal.
B-thalassemia minor due to B/B+ and is usually asymptomatic with microcytic hypochromic anemia, elevated HbA2 and elevated HbF.
B-thalassemia Major Bo/Bo causes severe anemia a few months after birth w/ elevated HbF, alpha tetramers, hepatosplenomegaly, crew cut skull. increases risk of aplastic anemia due to parvovirus B19 and requires chronic transfusion-> hemochromatosis
Intravascular hemolysis increase Hb release in serum=decrease free haptoglobin and hemoglobinemia leading to hemoblinuria, hemosiderinuria, and decreased [haptoglobin]
Extravascular hemolysis elevated unconjugated bilirubin, jaundice, anemia, splenomegaly, bilirubin gallstones, marrow hyperplasia w/ corrected RC>3%.
Hereditary spherocytosis spectrin, ankryin, protein 4.1 defect. Labs-elevated RDW, MCHC, splenomegaly, jaundice, unconjugated bilirubin, bilirubin gallstones, and aplastic anemia risk to parvovirus B19 infection. Dx-osmotic fragility test. Tx-splenectomy=howel jolly bodies
Sickle Cell Anemia AR mutaiton w/ glutamic acid being replaced by valine on B-chain=HbS. EV hemolysis w/ unconjugated hyperbilirubenemia, bilirubin gallstones; IV hemolysis=low haptoglobin, hepatiomegaly, crew cut skull; aplastic anemia risk to PVB19; sickle crisis, ACS
Hemoglobin C AR mutation w/ glutamic acid replaced w/ lysine on B-chain. presents w/ mild anemia, extravascular hemolysis and HbC crystals.
Paroxysmal Nocturnal hemoglobinemia Absent GPI in myeloid stem cells=high complement lysis due to no Daf or MIRL. IV hemolysis at nigh b/c mild respiratory acidosis->RBC, WBC, and platlet lysis-> hemoglobinemia, hemoglobinuria, hemosiderinuria. Dx-sucrose test,CD55 (Daf) flow cytometry
IgG mediated hemolytic anemia EV hemolysis w/ warm temperature leading to spherocyte production. SLE, CLL, drugs (methyldopa)may cause. Tx-IV Ig, splenectomy, cessation of drug.
IgM mediated hemlytic anemia IV hemolysis in cold temperatures of extremeties=cold agglutination. mycoplasma pneumonia and infectious mononucleosis may cause. Combs test direct and indirect positive.
Microangiopathic hemolytic anemia IV hemolysis, schistocytes or helmet cells due to TTP (ADAMTS13) or HUS (E. Coli 0157:H7), pregnant women, DIC, HELLP, prosthetic heart valves, aortic stenosis, malaria.
Myelophthisic process process that replaces the bone marrow causing hematopoiesis to be impaired leading to pancytopenia. metastatic cancer can be cause.
Achondroplasia AD FGF3R hyperactivity causing impaired cartilage proliferation and growth plate growth of long bones=dwarfism. G1138A (98%) and C1138C (1%) on chromosome 4.
Osteogenisis Imperfecta AD defect in collagen type I. presenting w/ multiple pathological fractures, blue sclera(choroidal veins), hearing loss. Type I is most common and mildest form. Type II causes fetal death.
Osteopetrosis Bone resorption defect most commonly associated with carbonic anhydrase II mutation. CP-bone fractures, anemia/thrombocytopenia/leukopenia and EMH, vision/hearing impairment, hydrocephalus, renal tubular acidosis. Tx- BM transplant
Rickets defective mineralization of bone in kids due to Vit D deficiency caused by low sun exposure, poor diet, fat malabsorption, liver/kidney failure. CP-pigeon breast deformity, frontal bossing, rachitic rosary, bowing of legs.
Osteomalacia defective bone mineralization in adults due to Vit D deficiency. CP-fractures & decreased [Ca]serum, [phosphate], increased PTH/ALP.
Osteoporosis loss of trabecular bone resulting in fragile bone. Risk increases w/ age, diet, exercise, VD3R variant, estrogen. senile; post-menapausal. Dx-DEXA w/ normal [Ca], [phosphate], PTH, ALP. Tx-exercise, VitD, Ca, bisphosphonates. CI-glucocorticoids
Paget Disease Osteoclast hyperactivity w/o osteoblast control. Osteoclastic->osteoblastic stages. CP->60 y/o; localized bone pain, increased hat size, hearing loss, lion-like fascies, high ALP. Tx-calcitonin, bisphosphonates. C-HOCHF, osteosarcoma
Osteomyelitis most often in children due to bacterial infection. metaphysis in kids; epiphysis in adults. CP-bone pain, fever, keukocytosis, lytic focus. Dx-blood culture. S. Aureus>S. pyogenes>H. influenza>N. gonorrhea>Salmonella>pseudomonas>pasteurella> TB (potts)
Avascular necosis of bone causes and complications. caused by trauma/fracture, steroids, sickle-cell disease (dactylitis), caisson disease (gas emboli). C- osteoarthritis & fractures.
Marquis syndrome AR mucopolysaccharide disorder. CP-Dwarfism, short trunk, genu valgum, odontoid hypoplasia leading to atlanto-axial subluxation w/ spinal cord compression injury.
Ostitis Fibrosa Cystica hyperPTH due to 80% tumors and 20% prolonged hypocalcemia leads to excess osteoclast activity=bone resorption & peritrabecular fibrosis. CP- loosened teeth, radiolucent phalanges/clavical. C-brown tumor=giant cell granulomas that develop cysts in bone.
Renal osteodystrophy skeletal changes due to renal failure=hyperphosphatemia, hypocacemia, low VitD3, hyperPTH, increased osteoclast activity= ostitis fibrosa cystica
Ehlers-Danlos syndrome Type I/II most common Col5A1 & Col5A2 mutations= skin hyperextensibility, ciggarrette paper scars/hyperpigmentation, hyperflexibility. Type IV=AD Col3A1 vascular type w/ C-arterial rupture, spontaneous rupture of colon, and rupture of gravid uterus.
Marfan syndrome AD Fibrillin mutation FBN1 on chromosome 15. CP-arachnodactyly, eptoptic lentis, and aortic aneurysm. C-myopia, mitral valve prolapse, mild pectus excavatum, hypermobility.
Osteoma Benign tumor of bone that most commonly arises on the surface of facial bones and is associated with gardner syndrome=familial adenomatous polyposis, fibromatosis of peritoneum & osteomas of facial bones.
Osteoid osteoma occurs in young adults <25 y/o and is an osteoblast proliferation arising on the cortex of long bones=diaphysis of femur. CP-bone pain resolves w/ aspirin, radiolucent core, <2cm, sclerotic rim w/osteoblasts=NIDUS.
Osteoblastoma osteoblast proliferation appearing in young adult males<25 y/o. CP-bone pain does not resolve w/ aspirin, >2cm, arises in cancellous bone such as vertebrae.
Diffuse Large B-cell Lymphoma (DLBCL) most common subtype of NHL and the most aggressive. CP-single large mass containing many large cells that resemble lymphocytes. extranodal (40%) fever, weight loss, drenching nigh sweats, and chronic fatigue. RF-immunosuppression (HIV & HHV-8)& age
Stevens-Johnson syndrome most commonly associated w/ drug exposure (penicillins, sulfonamides, ethosuximide, lamotrigine). CP-fever/fatigue followed by skin/mucocutaneous lesions begining as erythmatous macules, progressing to form bullae and subsequently slough.
Common causes of DIC. Gram-negative sepsis, malignancy, acute pancreatitis, trauma, transfusion Rx, obstetric complication (amnioemia)
Factor V leidon most common cause of genetic hypercoagulability caused by AD mutation in Protein C preventing degredation of factor V. DVT and Pulmonary embolism are common complications.
Patau's Syndrome Trisomy 13 with CP-microcephaly, microphthalmia, polydactyly, hyotonia suggestive of CNS defects, and congenital heart disease suggested by holosystolic murmur. advanced maternal age is risk factor for nondisjunction chromosomal aneuploides.
Fibromyalgia adult females are highest prevelence w/ generalized widespread pain > 3 months (chronic pain), non-inflammatory, tender points, unknown etiology. Tx-exercise, sleep medication, psychotherapy, antidepressants/duloxetine, pregabalin, CAM therapies
Electromyography Records motor unit AP amplitude & duration via direct invasion. Normal- no spontaneous activity A.Neuropathic-AP 2X n. duration B.Myopathic-low AP duration & number of motor units firing C.Neuromuscular JD-low response to rep stim D.myotonia-divebomber
Myotonic dystrophy AD DMPK mutation. myotonia that presents w/ progressive muscle weakness and stiffness, difficulty in releasing their grip. begins in childhood w/ gait difficulty. CP-cataracts, frontal baldness, DBMI, intellectual changes. dx-EMG-Waxing/waning divebomber
Myotonia congenita AD/AR CLCN1 mutation (Cl-channel in muscle). generalized myotonia w/o weakness present at birth. stiffness relieved by exercise and enhanced by cold.
Limb Girdle Muscular Dystrophy AD/AR variable severity, progression. affecting muscles around shoulder girdle and hips. onset 20-30 y/o w/ muscle weakness of upper arms and legs.
Dermatomyositis CP-bilateral proximal muscle weakness, helioptrope rash/malar rash, groton lesions. Labs-elevated creatinine kinase, ANA (+), anti-Jo1 (+), perimysal CD4 inflammation goes to perifascicular atrophy. High visceral cancer risk. Tx-glucocorticoids
Polymyositis Endomysial inflammation w/ necrosis of skeletal muscel in proximal muscles w/o cutaneous involvment and w/ CD8 inflammation.
Inclusion body myositis presents >50 y/o w/ distal muscle weakness & asymmetry. sporadic onset w/ CD8 inflammation, vacuoles in myocytes w/ aggregates of Abeta peptide/hyperphosphorylated Tau. immunosuppressive Tx not beneficial.
Duchenne muscular dystrophy X-linked dystrophin deletion. CP-proximal muscle weakness, 1y/o in thigh/hip common, calf-pseudohypertrophy, elevated creatinine kinase. Death due to cardiac/respiratory failure.
Becker muscular dystrophy Mutated dystrphin presenting w/ milder symptoms than deleted version w/focal skeletal muscle replacement w/ fat and muscle weakness.
Myasthenia gravis Autoimmune autoantibody at postsynaptic AchR of NMJ. more common in women. CP-muscle weakness that improves w/ rest, ptosis, diplopia. Associated w/ thymic hyperplasia, thymoma. Tx-anticholinesterase agents (pyrodostigmine)+immunotherapy (prednisone)
Lambert-Eaton syndrome Autoimmune Ab against presynaptic Ca2+channels of NMF. CP-muscle weakness of proximal muscles w/ eye sparring. ACHase inhibitors do not Tx. weakness improves w/ use. perineoplastic syndrome of small cell carcinoma. Tx-remove tumor.
Lipoma Most common benign soft tissue tumor in adults. composed of adipocytes.
Liposarcoma Most common soft-tissue malignancy in adults. Malignant tumor of adipose tissue w/ lipoblasts.
Rhabdomyoma Benign skeletal muscle tumor w/ cardiac version being associated w/ tuberous sclerosis.
Rhabdomyosarcoma most common soft tissue malignancy in children. malignant cancer of skeletal muscle w/ rhabdomyoblasts desmin (+). most common sites are head and neck. sarcoma botryoides-vaginal tumor at 5y/o girls w/ grap-like nodules. Tx-vc/cc/actinomycin D/radation
Malignant fibrous histiocytoma most common soft tissue malignancy caused by radiation therapy.
Desmoid tumor deep fibromatosis in abdomen or extremities that can be locally aggressive and recur after excision. Not a true neoplasm and not malignant
Nodular fascitis reactive fibroblastic proliferation seen in upper extremeties of young adults after exercise.
Superficial fibromatosis deforming lesion of facial planes developing over a long period of time.
Syphilitic Gumma joint deformity in tertiary phase of syphilis infection preceding syphillic ulcers by yrs.
Osteochondroma Tumor of bone w/ overlying cartilage cap. most common tumor of bone arising from growth plate. Overlying cartilagency my become malignant to chondrosarcoma.
Aplastic anemia causes Fanconi anemia, chloramphenicol, anticonvulsant drugs (phenytoin, carbamazapine), phenylbutazone, gold, benzene, insectasides, CMV/PVB19, hepatitis.
Acute lymphoblastic leukemia Most common in children, association w/ tri21 >5y/o, most common B-cell type w/ CD10, CD19, CD20, TdT (+). t(12:21) most common at 4 y/o; t(9:22) worst prognosis <2y/o or >12y/o.
T-cell Acute Lymphoblastic leukemia Presents most commonly in teenagers w/ thymic mass=mediastinal mass. CD2-CD8 (+), but CD10 (-).
Acute myeloblastic leukemia presents in older adults 50-60 y/o w/ myeloblasts MPO (+) and auer rods. M3=t(15:17) Tx- all-trans retinoic acid allowing promyeloblasts to mature. M5= monoblastic w/ gum infiltration. M7=megakaryoblast MPO (-) associated tri21 <5y/o
Myelodysplastic syndrome cytopenia w/ hypercellularity in BM, increased blasts <20%. Most die from bleeding or infection, but some may develop AML/ALL.
Chronic lymphoblastic leukemia (CLL/SLL) >60 y/o. Naive B-cell proliferation w/ CD5 & CD20 (+). smudge cells seen in PBS. CP-LAD, hypogammaglobinemia (most common cause of death=infection), autoimmune hemolytic anemia. May develop diffuse B-cell lymphoma.
Hairy cell Leukemia Mature B-cell proliferation w/ hairy cytoplasmic projections, TRAP (+), splenomegaly (red pulp), LAD (-), BM dry tap w/ fibrosis. Tx- 2CDA causes adenosine accumulation to toxic levels in B cells.
Adult T-cell lymphoma CD4 (+) T-cell neoplasm associated w/ HTLV-1, Japan, carribean. CP- Rash, hepatosplenomegaly, generalized LAD, lytic bone lesions, and hypercalcemia.
Mycosis Fungoides Mature CD4 (+) T cell neoplasia. CP- Rash, plaques, nodules w/ biopsy showing T cells and called patrier microabscesses. May develop to Sezary syndrome-spread to blood w/ cerebroform nuclei
Chronic myeloid leukemia (CML) Mature myeloid neoplasia w/ granulocytes-basophils. t(9:22)- BCR-ABL is common cauuse. Tx-Imatinib. CP-chronic phase=splenomegaly, accelerated phase=enlarging spleen, ALL or AML. Labs- LAP (-), basophilia, t(9:22)
Polycythemia Vera Mature myeloid neoplasia w/ RBC > granulocytes & platelets. Jak2 kinase mutation common. CP- hyperviscosity, blurred vision, headache, venous thrombosis (bud kiari syndrome), flushed face, itching after bath. Tx- phlebotomy, hydroxyurea.
Essential thrombocytothemia Mature myeloid neoplasia w/ platelets > RBC & granulocytes. Jak2 mutation common. CP- bleeding, thrombis formation. may develop ALL/AML or BM fibrosis; no gout formation.
Myelofibrosis Megakaryocyte neoplasia w/ Jak2 mutation. MK cells produce excess PDGF causing BM fibrosis. CP- splenomegaly, extramedullary hematopoesis, leukoerythroblastic smear, thrombis, bleeding, infection, teardrop cells.
Burkitts lymphoma Intermediate B-cell lymphom CD20 (+) associated w/ EBV. CP- extranodal mass in child or young adult, african=jaw, sporadic=abdomen. t(8:14)= Cmyc on 8; IgHc on 14. starry-sky appearance w/ tingible macrophages in biopsy
Giant cell tumor tumor composed of multinucleated giant cells (osteoclastoma), stromal cells, & neoplastic spindle cells. CP- young adult w/ epiphysis in long bone (knee) showing soap bubbles on X-ray. locally aggressive, may recur. metastasis to lungs.
Ewing Sarcoma Poorly differentiated cells from neuroectoderm (PNET) arises in young male children at diaphysis of long bone w/ onion skin sppearance on X-ray by periosteum. usually fever, w/ lymphocyte looking cells t(11:22)
Chondroma Benign cartilage tumor arising from metaphysis in hands and feet. Oilers disease=multiple. Maffuccis=enchondromatiosis + hemangiomas.
Chondrosarcoma >40 y/o presenting w/ malignant cartilage tumor arising from medulla of small bones of hands and feet.
Chondroblastoma children most at risk w/ epiphysis hyaline cartilage neoplasia w/ chondroblasts and giant osteoclasts.
Chondromyxoid fibroma most common in adolescents w/ cartilage, fibrous, & mixomatous tissue arising from metaphysis and having high risk of recurrence
Fibrous cortical defect can be found at birth as a painless non-ossifying fribroma that is radiolucent on X-ray and is common. may disappear spontaneously
Fibrous dysplasia replacement of bone by fibrous osseous proliferation. biopsy shows woven bone w/o osteoblasts, chinese letters. CP- cafe-au-lait macules & precocious puberty, hip deformity. May lead to hematoma.
Fibrosarcoma=malignant fibrous histiocytoma (MFH) associated w/ old age showing grey-white infiltrate w/ tumors have a herring bone formation, storiform spindle cells, giant fibroblasts, and phagocytic cells.
Degenerative joint disease=osteoarthritis Progressive degradation of articular cartilage due to aging, wear/tear, obesity, and trauma. commonly in hips, lower-lumbar spine, DIP/PIP, knees. CP- stiffness in morning worsens during day. eburnation, osteophytes, herbeden (DIP), bouchards (PIP) nodes
Rheumatoid Arthritis clinical features Chronic systemic autoimmune disease 30-40 y/o women. HLA-DR4 or DR1. synovitis -> pannus in synovium. myeofibroblasts contract -> joint fusion, displacement, ankylosis. CP- stiffness in morning improves w/ activity. symmetric w/ DIP sparing.
Rheumatoid arthritis labs and complications RF (+), synovial fluid showing neutrophils and exudate. Complications- anemia of chronic disease, secondary amyloidosis due to SAA --> AA deposits in tissues
Seronegative spondyloarthropathies CP- pain, stiffness in neck, spine, hips. RF (-) w/ axial skeletal involvement and HLA-B27 association
Ankylosising spondyloarthritis Arrising in young males presenting w/ lower back pain involving sacroiliac joint and spine. may lead to fusion of vertebrae=bamboo spine, uveitis, aortitis. risk of aortic aneurysm.
Reiter syndrome Young adult males after weeks of GI or chlamydia infection show arthritis, urethritis, conjunctavitis = can't see, can't pee, can't bend my knee.
Infectious arthritis bacteria S. Auerus is most common overall; N. Gonorrhea in sexually active young adults; Salmonella in sicklers; H. influenza S. pyogenes (strep B) in children; P. aeuruginosa in IV drug users
Infectious arthritis presentation presents w/ 1 joint, knee most common, being warm, erythematous, limited ROM, fever, high WBC/ESR
Juvenile Rheumatoid arthritis <16 y/o 2:1 F:M ratio w/ RF (+), ANA (+). 80% recover.
Gout Negative birefringence; hyperuricemia w/ deposition of MSU crystals in tissues, especially joints. Acute- Podagra w/ MSU crystals and neutrophil infiltrate. Chronic- trophi w/ MSU crystals in ST and giant cell Rx; renal failure- MSU crystals in tubule
Pseudogout Positive birefringence; calcium pyrophosphate rhomboid shaped crystal deposition often in meniscus rather than other parts of joint. hemochromotosis, family hx, and trauma=risk factors.
Villonodal synovitis synovial lesion composed of fibroblasts, histiocytes, multinucelated giant cells, lipid laden macrophages w/ brown hemosiderin deposits.
Ganglion myxomatous degeneration of connective tissue & tendon sheaths= cystic pea sized swelling on wrists
Polymyalgia rheumatica >50 y/o femal w/ subacute or chronic morning stiffness >30 min. widespread, diffuse, & symmetrical pain. fever, malaise, weight loss, fatigue, anorexia. temporal arteritis associated. Labs-high ESR/CRP. MRI-periarticular inflammation; Tx-corticosteroids
Osteosarcoma most common primary malignant tumor of bone. CP- adolescents, pain, swelling, pathologic fracture about the knee. X-ray- codman triangle and spiculated sunburst pattern of growth.
Henoch-Schonlein purpura Leukocytoplastic angiitis=IgA mediated hypersensitivity vasculitis. CP-hemorrhagic urticaria, fever, arthralgia, and GI/renal involvement. often preceded by upper respiratory infections.
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