BMS Hem/Onc ID Study Guide PDF

Per big Cardiovascular system: - arteries= carry blood away from the heart (oxygenated) - veins= carry blood towards the heart (deoxygenated) - Artery → arterioles → capillaries → venules → veins - Epithelial cells tend to be the only true avascular system in the body...

Per big Cardiovascular system: - arteries= carry blood away from the heart (oxygenated) - veins= carry blood towards the heart (deoxygenated) - Artery → arterioles → capillaries → venules → veins - Epithelial cells tend to be the only true avascular system in the body - Capillaries only have endothelial cells - Structure of a artery: - Tunica adventitia: connective tissue - Tunica Media - smooth tissue - Tunica Intima: all vessels have these - Vascular endothelium - Lumen- hole the blood travels through - Arteries have thicker walls because they are high intensity - Structure of a vein: - Tunica adventitia: more in vein than artery - Tunica media - Tunica intima - Vascular endothelium - Valve cusp - Lumen- veins have a bigger hole cause they are carrying more blood - Tunica intima: internal layer is a layer of simple squamous epithelium (endothelium) - Tunica media: is primarily smooth muscle (bigger in arteries than viens) - Tunica adventitia: connective tissue layer anchoring the vessel in place - Pulmonary circulation: - RV to pulmonary trunk to R/L pulmonary arteries to lungs to R/L pulmonary veins to LA - Systemic circulation - LV to aorta to systemic arteries to arterioles to capillaries to systemic venules to veins to either superior or inferior vena cava to RA - What are your great vessels - R. Brachiocephalic - L. Common Carotid - L. Subclavian - Your descending aorta sits where - On the left - Off your superior vena cava - Left brachiocephalic vein - Right brachiocephalic vien Lymphatic system: - Roles - Return of interstitial fluid to circulation - Immune protection - Transport of dietary fats - What are the primary structures of the lymph system - Thymus - Red bone marrow - What are the secondary structures of the lymph system - Tonsils - Lymph nodes (cervical, axillary, inguinal) - Spleen- filters blood but has lymphocytes - MALT In small intestine - Lymph is essential plasma without the plasma proteins - Flow of lymph - Interstitial fluid flows into lymphatic capillaries - Lymphatic vessels (called lymph here) Per big - Lymph travels through lymph nodes and exits via efferent vessel - Lymph then moves into lymphatic trunks - Then goes to lymphatic ducts - Thoracic duct - Right lymphatic duct - Then to subclavian veins - Lymphatic trunks - Jugular trunks (paired) - Drains head and neck - Subclavian trunks (paired) - Drains upper limb - Bronchomediastinal trunks (paired) - Lungs - Lumbar trunks (paired) - Legs - Intestinal trunk (unpaired) - Lymph from here flows into cisterna chyli (abdominal origin of the thoracic duct and receives the bilateral lumbar trunks) Skeletal system: - Protection - Composed of collagen for strength and calcium phosphate salts resit bend - Support - Lever for movement - Storage of minerals - Hematopoiesis - Bone marrow is stored inside of bone - Red bone marrow: responsible for the production of formed elements - Yellow bone marrow: inactive red bone marrow, can be converted back to red bone marrow if needed - Medullary cavity of long bones - Spongy bone of epiphyseal ends of long bones - Spongy bone of flat bones - All bones produce red blood cells until age 5 - Long bones produce bone marrow until age 20 - adults : spongy bone found in - Vertebrae, sternum, ribs, and iliac bone Blood: - Is specialized fluid of connective tissue (has its own blood supply) - Can make fibers - Five functions - Transport of dissolved substances - nutrients , vitamins, minerals, oxygen and hormones towards interstitial fluid - Waste material, CO2, and hormones from the interstitial fluid - Regulation of pH and ions - Restriction of fluid losses at injury - Defense against toxins and pathogens - Stabilization of body temperature - What temperature is blood? - 38.4 C or 100.4 F - How many liters of blood do we have - Adult male: 5 to 6 - Adult female: 4 to 5 - What is the physiological pH of blood - 7.40 Per big - What percent does formed elements make up? - 45% - What percent does plasma make up - 55% - What is plasma composed of? - Water - Plasma proteins - Other solutes - What are the formed elements - Erythrocytes - Leukocytes - Thrombocytes - What is the difference between plasma and serum? - Plasma has clotting factors - Serum does not have clotting factors - Plasma proteins - Albumin: helps to hand onto water like a sponge - Made in the liver - Transports substances - Water soluble substances typically dissolve in the aqueous component - Lipid soluble substances are typically bound to a transport in the aqueous component: functions as a transporter for - Fatty acids - Thyroid hormones - Steroid hormones - Globulins - Alpha and beta globulins are produced by the liver and help transport​ - Hormone binding proteins - Metalloproteins - Lipoproteins - Steroid binding protein - Gamma globulin: also known as immunoglobulins (Ig) or antibodies - Produced by activated B cells (plasma cells) - Fibrinogen - Upon activation converts to fibrin (water insoluble fiber) for hemostatsis - Three types of formed elements - Red blood cells or erythrocytes - Transport oxygen - Live 120 days - White blood cells or leukocytes - Part of immune system - Live a long time - Platelets or thrombocytes - Cell fragments involved in clotting - Erythrocytes - Production of RBC - Amino acids- globin - iron - heme - Vitamins, B6, B12 and folic acid - Structure - Small and highly specialized - Thin in middle and thicker at edge - Lacks nucleus - 120 days in adults Per big - 80 in newborn - RBC shape - High surface to volume ration - Quickly absorbs and releases oxygen and CO2 - Disc shape helps RBC to form stacks - Rouleaux formation - Disc bend and flex entering small capillaries - Hemoglobin - Protein molecule - Transports oxygen - Normal hemoglobin - 14-18 g/dl in whole blood in adult male - Four hemolgobin chains - Alpha - Beta - Gamma - Delta - Hemoglobin A - 2 alpha - 2 beta - One oxygen binds per heme= 4 oxygen per hemoglobin - Carbaminohemoglobin - site where CO2 binds - Fetal hemoglobin - 2 alpha - 2 gamma - Has a very high affinity for oxygen - Measuring RBC - Red blood cell count - Hemoglobin - Measures the hemoglobin content of the blood - Hematocrit - Percentage of RBC in centrifuged whole blood - Mean corpuscular volume - Also known as mean cell volume - Provides a measure of hte average RBC volume - Macrocytic vs microcytic Hematopoiesis - Cyte= close to mature - Blast= immature - Starts with pluriptoent hemopoeitc stem cell - Goes to myeloid or lymphoid line - Myeloid stem cell line uses colony stimulating factors - Lymphoid line does not use colony stimulating factors - Erythropoietin ​ - EPO hormone is released from kidneys in response to low renal oxygenation - Dysfunctional RBC - Low blood volume - Poor oxygenation - Poor blood flow - With low renal oxygenation detected - Renal hypoxia triggers release of hypoxia inducible factor (HIF-1) - HIF-1 binds to a hypoxia response element on DNA - This binding triggers EPO transcription Per big - Overall how it works: - Stimulates stem cells to form proerythroblasts - Promotes release of reticulocytes from bone marrow - Timing - Maximized within 24 hours - Increases RBC in 5 days - Regulation of RBC production - When ↓ rbcs present in the blood - ↓ O2 in blood detected at the kidneys - ↑ secretion of the hormone erythropoietin by kidneys - EPO enters the blood and binds to receptors in the red bone marrow - ↑ stimulation of red bone marrow to produce RBC - ↑ RBC - When ↑ rbc at kidney - ↑ O2 at kidney - ↓ secretion of erythropoietin - ↓ stimulation of bone marrow to produce RBC - ↓ rbs Red blood cell destruction - Done by macrophages in the spleen - Iron from red blood is released to blood and carried by transferrin to red bone marrow to be reused - Macrophages phagocytosis break hemoglobin into components - Globular proteins to amino acids - Iron - Heme to biliverdin - Converted to bilirubin in the liver - Bilirubin is excreted by liver mostly via bile - Jaundice is caused by bilirubin buildup RBC Disorders: - Polycythemia – excess - Normal stem cells but there’s just wayyyy too many getting pumped out - Anemia – deficit - Dec RBC production - Inc RBC destruction or blood loss - Physio cause: - Hypo-proliferative of RBCs or amt of hemoglobin inside RBCs - Deficiency of iron/B12/folate - Low EPO prod - Inflammation - Caner - Bleeding - GI, GU, Track - Hemolytic - Sickle cell, thalassemia, Hb variation - Hemolysis - Drugs - Autoimmune Reticulocytes - Immature RBC, still have some RNA material Iron Deficiency Anemia (microcytic) - Poor diet Per big - Poor absorption - Chronic blood/iron loss: GI bleed, menorrhagia, blood donation, renal failure - Inc iron req: pregnancy/lactation, infancy Thalassemias (microcytic) - Low synthesis of alpha or beta hemolgobin chains leads to dec hemoglobin, MCV, and inc retic count - Alpha Thalassemia - Hydrops Fetalis- no alpha at all (stillborn) - Hemoglobin H disease- 3 abnormal genes - Alpha thalssemia minor- 2 abnormal genes usually asx - 1 loss - silent carrier - Beta thalassemia - Point mutation typically - Low beta chains, nml amount of alphas → alphas are unpaired → aggregate to form insoluble tetramers → rbc damage - Heteroygous state= beta thalassemia minor= clinically insignificant - Homozygous state= beta thalassemia major = severe transfusion dependent anmia Vitamin B12 deficiency (macrocytic) - Dec intake - Dec absorption - Pernicious anemia- lack of intrinsic factor needed to absorb B12 - Gastric parietal cells make intrinsic factor - B12- absorbed in the ileum - B12 foods; fish, meat, poultry, eggs, milk products, some legumes, nutritional yeast Folate deficiency (macrocytic) - Affects purine biosynthesis - Ability to repair and replicate DNA is decreased - Vitamin b12 is a cofactor for the activation of folic acid Evidence for hemolysis - Increased retic - Increased indirect bilirubinemia - If RBC lifespan is shortened significantly ( platelet clots > blood flow disruption - Causes: disturbed blood flow, endothelial damage, increased platelet activation - Primary thrombophilia - Factor V leiden - Protein dificinces - Increased levels of Factors I, VIII, IX, and X - Factor v leiden - Autosomal dominant - Reduced anticoagulant function of factor V - Increased procoagulant role of factor Va - Protein S deficiency - Cofactor for protein c - Deficiency homozygous dominant mostly incompatible with life - Vitamin k dependent glycoprotein - Functions as cofactor - Made in liver, endothelial cells, and megakaryocytes - Levels increase with age - Lower in females - Protein C deficiency - Autosomal dominant inheritance - May be acquired as well - Protein c is a vitamin k dependent protein made in the liver - It is activated by thrombomodulin and protein s - Active protein c inactivates coagulation factors V and VIII - What are the bodies natural anticoagulants - Protein c - Protein S - Antithrombin III - Antithrombin deficiency - Potent inhibitor of the coagulation cascade - It is a non vitamin K dependent protease that inhibits coagulation by lysing thrombin and factor X - Pulmonary embolism - Part of the process called venous thromboembolic disease - Formation of extremity deep vein thrombosis and embolic disease to the lungs - Inheritable causes: - Mutated natural anticoagulants - Mutated antithrombin III will not inactivate thrombin - Mutated protein C/S will not inactivate factors V and VIII - Mutated factor V leiden is not inactivated by protein C Per big - Heparin induced thrombocytopenia - Heparin paradox: thrombocytopenia and thrombosis - Pathophysiology: HIT results from antibody formation to platelet factor IV and heparin complex - Disseminated intravascular coagulation - DIC can be translated as the spread of clots within the vessels - Can lead to both thrombosis and bleeding - Caused by: - Sepsis, trauma, OB complications, drugs, liver disease, snake bites - Pathophysiology: ​ - When condition can activate the clotting cascade directly - Releasing pro-coagulants - Inhibiting anti-coagulants - Injury - Leads to diffuse thrombosis using significant number of platelets and coagulation factors - Leading platelets in low numbers - Leading to bleeding Malignancies - ALL - Overproduction of lymphoblasts in the bone marrow - B and T cell lineage affected by hypermethylation - Thought to lead to impaired maturation and accumulation of the malignant cells - AML - Development of heterogeneous precursor myeloblast cells in the bone marrow - Lethal rare - Genetic: inherited abnormality - Promyelocytic leukemia gene on chromosome 15 - Translocation of the retinoic acid receptor alpha on chromosome 17 - Acute promyelocytic leukemia - Preexisting blood disorder - Myeloproliferative neoplasms - Environment - Chemical exposures - Morphology of AML cells - Immature myeloblast - Leukemic myeloblast with auer rod - Promyelocytic leukemia with prominent granules - Stained for peroxidase granules - CLL - Monoclonal proliferation of abnormally functioning B lymphocytes - 80% of cases of CLL are B-Cell (CD19+, CD23+) - CML - Clonal proliferation disorder with abnormal granulocytes - Mostly neutrophils - Translocation between chromosome 9 and 22 leading to philadelphia chromosome - Hodgkin lymphoma - Transcription process are disrupted: cell surface marker and RNA process de regulated - Loss of apoptosis/favor proliferation - Increase cytokine production - Inflammatory response - Non hodgkin lymphoma - Aggressive vs indolent Hemostasis - The cessation of bleeding Per big - Vascular phase - Platelet phase - Coagulation phase - Vascular phase - A cut triggers vascular spasm - Short term - Three steps - Endothelial cells contract - Expose basal lamina to blood stream - Endothelial cells release - Chemcial factors - ADP, tissue factor, and psotacyclin - Local hormones - Enothelins - Fucntion: stimulate smooth muscle contraction and cell division - Enothelial cell membranes become sticky - Platelet phase - Platelet adhesion (attachement) - To stickly endothelial surfaces - To basal lamnina - To exposed collagen fibers - Platelet aggregation (stick together) - Forms platelet plug - Prostacyclin - Released by endothelial cells - Inhibits platelet aggregation - Closes small breaks - What you need; - ADP - Thromboxane and serotonin - Clotting factors - Platelet derived growth factor - Calcium - VwF - GP 11b/111A - Coagulation - Fibrin network - Covers platelet plug - Traps blood cells - Seals off area - Intrinsic vs extrinsic - Common pathway - 12 factors - Most produced by liver except III, IV, VIII - Platelets produce fibrinogen, fibronectin, factor V and VIII - Calcium ions and vitamin k are both essential Immunity - Innate defenses= nonspecific defenses - Ability to resist damaging organisms and toxins - Barriers (skin/gastric) - Cells (neutrophils and macrophages) - Chemicals (lysozyme and complement) - Processes (fever, phagocytosis, inflammation) Per big - Acquired or adaptive defenses= specific immunity - b-cell : humoral or antibody-mediated immunity → comes from activated b cells - T cell: cellular or cell mediated immunity → comes from activated T cells - When you get vaccinated it is doing something to help you fight that disorder specifically - Higher virulence= more likely you will get sick —-------------- Platelets produce: fibrinogen, factor V, factor VIII Protein factors by liver except 3, 4, 8 Spongy bone: vertebrae, sternum, ribs, iliac Plasma has plasma proteins – diff from lymph and interstitial fluid 120 day life – RBC lifespan, 80 d for newborns Binding site on globulin = carbaminohemoglobin Normo: sickle, G6PD, aplastic anemia Micro: TICS Hemolysis: increased retic, increased bilirubin G6PD – NADPH → hemolytic anemia Neutrophils: three to five lobes linked w/ cytoplasmic extensions, pale in cytoplasm Eosinophils: bilobed nucleus w/ red granules in cytoplasm Basophils: bilobed, purple granules in cytoplasm, release histamine and heparin Monocytes: C-shaped nucleus (kidney bean) w/ pale blue agranular cytoplasm - Become macrophages, MHC Megakaryocytes → platelets Prostacyclins – inhibit platelet aggregation NSAIDs inhibit platelets ALL: Overproduction of lymphoblasts in bone marrow - > 80 B cell abnormality AML: Affects myeloblasts CLL: Monoclonal proliferation of abnormally functioning B cells CML: Philadelphia chromosome 9 & 22 Proliferation of abnormal neutrophils Per big Hodgkins lymphoma -reed sternbeg Contiguous spread More B sxs Most B cells NHL: Burkitt, p53 B cells – CD19 & CD20 Many Girls Act Edgy Dancing IgM – produced first time B cell activated, primary response, binds complement (acute) IgG – best killer, secondary immune, does bind complement (chronic) IgA – breastfeeding, no bind complement (can be passed down to baby) IgE – allergies IgD – IDK, help B cells MHC class 1 – CD8, present on all nucleated MHC class 2 – CD4, APCs CD4 – MC, destroyed by AIDS, IL-2 helps CD4 CD25 suppressor T cells help keep u from destroying own cells (autoimmune response) RES – breaks down RBCs into heme to bilirubin Acute – MC, neutrophils Chronic – bad, lymphocytes Granulomatous – scar like Non-specific: heat, erythema, pain, swelling Proinflammatory cytokines: TNF, IL-1, IL-6, IL-8 Infection characteristics: enter, multiply, damage, resist host Pathogenicity – species Virulence – strains Bacteria Cocci, bacilli, spirochetes Anaerobic – GI tract Gram positive cell wall: purple, thick peptidoglycan, retains crystal violet stain, have teichoic and lipoteichoic acid Gram negative cell wall: red, LPS (outer membrane) makes it less permeable, porin proteins, thin peptidoglycan, loses crystal violet stain - RESISTANCE TO BETA LACTAMS BC enzyme for beta lactamases Staph catalase positive Strep catalase negative Clostridium botulinum Clostridium tetani – CNS toxicity Atypicals: cell wall w/ mycolic acid Fungus-like Naked viruses: can survive in more hostile environments Attachment Penetration Per big IN cell Primary replication: where virus replicates , after initial entry Systemic spread: may spread via blood to CNS Secondary replication: susceptible organs following systemic spread DNA viruses are HHAPPPPy Hepadnaviridae Herpesviridae - HSV-1: cold sores, enveloped dsDNA, icosahedral - HSV-2: genital warts, enveloped dsDNA, icosahedral - HHV-3 or VZV: varicella = chickenpox, zoster = shingles - HHV-4 or EBV: infectious mononucleosis - HHV-5 or CMV: salivary glands and kidneys Adenoviridae Parvoviridae Poxviridae Papillomaviridae - HPV: non-enveloped dsDNA, HPV16 – cervical cancer (high risk), genital warts (low risk) Polyomaviridae All dna viruses are ds minus parvoviridae Naked RNA = most virulent and mutate, hard to kill, more variation All RNA viruses are ss except Reoviridae All non-enveloped viruses have icosahedral capsid Filoviridae – Ebola: enveloped ssRNA, hemorrhage disease - Fruit bats to people to monocytes/macrophages/dendritic cells to lymph nodes tosystemic Rhabdoviridae – Rabies: - Enveloped ssRNA, infected saliva, - Replicated for months in cells then goes to CNS Orthomyxoviridae family – Influenza: - Enveloped negative ssRNA - w/ HA and NA - resp secretions - A & B epidemics, A pandemics Coronaviridae – COVID19: - Binds to ACE2 - SARS-CoV o Severe acute respiratory syndrome o Enveloped positive ssRNA o E2 spike protein o Resp secretions - MERS-CoV Flaviviridae – Zika: - Enveloped ssRNA - Vector borne – mosquito Aedes, female - Guillain-Barre Retroviruses Retroviridae – HIV: - Enveloped retrovirus ssRNA - CD4 target cell - Sexual - Enters via viral attachment protein (VAP) Fungi: molds, yeasts, mushrooms Per big Fungi = more opportunistic pathogens Candidiasis: - Candida albicans - Strict anaerobe - Cell surface hydrophobicity & adherens, secretory IgA, phenotype switching & binding to complement, hydrolytic enzyme production Cryptococcus -