hematopoietic pathology part 1 platelets -- ! aka thrombocytes, are small, clear cell fragments derived from ! ! fragmentation of precursor megakaryocytes. ! --avg. lifespan is ~5-9 days (wiki). ! --fundamental role in hemostasis ! ! primary hemostasis --> platelet plug formation, adhere to damaged ! ! ! endothelium and then degranulate. ! ! secondary hemostasis --> blood coagulation, fibrinogen added to platelet ! ! ! plug, then converted to fibrin (clot). ! --natural source of GFs evaluating clotting: !(coag. panel) ! --bleeding time = ! 2-9 minutes ! --platelet counts = ! 150-450K/mm3 ! ! --this should be confirmed w/ a smear. ! --prothrombin time (thromboplastin aka tissue factor and Ca2+) =! 11-16 sec ! ! PT measures the EXTRINSIC pathway of coagulation. ! ! --factors: ! I, II, V, VII, X, prothrombin, fibrinogen. ! ! --INR (0.8 - 1.2) ! when to use PT?! --coumadin dosage ! ! ! ! --liver disease ! ! ! ! --vitamin K status ! --partial thromboplastin time (kaolin, cephalin, Ca2+) = !25-39 sec ! ! PTT measures the INTRINSIC pathway of coagulation. ! ! --factors: ! V, VIII, IX, X, XI, XII, prothrombin, fibrinogen. ! ! --acquired inhibitor. disorders: ! may be quantitative or qualitative... ! quantitative: !thrombocytopenia ! ! ! --prolonged BT ! ! ! --LOW platelet count ! ! ! --PT, PTT both WNL. ! ! ! ! <100K ! ! ! ! ! --petechiae, ecchymosis, hematoma ! ! ! ! 20-50K = post-traumatic bleeding ! ! ! ! <20K = spontaneous ! ! ! ! ! --epistaxis - nose bleed. ! ! ! ! <10K -- this can be FATAL! ! ! ! ! ! --GI, urinary tract. ! ! ! ! ! --brain, lungs. ! ! why does this happen? ! ! ! decreased production: ! aplastic anemia ! ! ! ! ! ! myelophthisic anemia ! ! ! ! ! ! drugs !! --chemo ! ! ! ! ! ! ! ! --EtOH ! ! ! ! ! ! ! ! --Thiazides ! ! ! ! ! ! infections ! ! --measles ! ! ! ! ! ! ! ! ! --HIV 1 ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! survival/destruction issues: ! ! autoimmune ! ! --ITP (immune thrombocytopenic purpura) ! ! --SLE (systemic lupus erythematosus) ! isoimmune ! drugs (ex. heparin, quinidine, sulfa) ! infection (ex. mono, CMV, HIV) ! consumption ! ! --DIC (disseminated intravascular coagulopathy) ! ! --TTP (thrombotic thrombocytopenic purpura) ! sequestration -- normally 33% in spleen. ! marrow shows compensation... ex. immune/idiopathic thrombocytopenic purpura ! --secondary to SLE, HIV. ! --primary... ! ! acute: kids, viral. ! ! chronic: females, 20-40, insidious, bleeding diathesis. ! --anti-platelet Igs. ! --anti-membrane glycoproteins (IIb/IIIa or Ib/IX) ! --spleenʼs role: ! --Ab production ! ! ! ! --destruction ! ! ! ! --normal size ! --tx. is splenectomy --> remission in 2/3. thrombotic micro-angiopathies ! ex. TTP (pentad, know this) ! ! 1 - fever ! ! 2 - TP ! ! 3 - micro-angiopathic hemolytic anemia (MAHA) ! ! 4 - transient neurologic deficits ! ! 5 - renal failure ! --ADAMTS13 metalloproteinase that is inhibited by ABs. ! ! --normally degrades high MW vWF. ! --tx. by plasma exchange. ! ex. HUS (hemolytic-uremic syndrome) ! ! --similar to TPP, but... ! 1. ADAMTS13 is WNL ! ! ! ! ! 2. NO neuro deficits ! ! ! ! 3. dominance of renal failure ! ! 4. childhood onset -- prodrome - bloody diarrhea. ! ! --E. coli - gastroenteritis. ! ! ! --shiga-like toxin. ! ! ! --endothelial damage. ! ! --renal damage. ! ! --10% other causes: ! --factor H - compliment ! ! ! ! ! --drugs, XRT - endothel. damage thromocytosis ! primary thrombocytosis (essential) 2 ! ! ! ! --increased numbers of megakaryocytes producing ! ! ! ! ! dysfunctional platelets. ! ! ! ! reactive thrombocytosis ! ! ! ! --asplenia (absence of normal spleen fx) ! ! ! ! --inflammatory disorders: ! thrombopoietin ! ! ! ! ! ! ! ! acute phase reaction ! qualitative: ! ASA (acetylsalicylic acid) -- aspirin. ! ! ! --inhibits aggregation for the lifetime of platelets (irreversible). ! ! ! ! --Rokos says 8-10 days. ! ! ! NSAID -- ibuprofen, naproxen. ! ! ! --inhibits aggregation until drug is eliminated (reversible). ! ! ! --most are metabolized in the liver. ! ! ! --affects enzyme -- non-selective COX inhibitors. ! ! ! Von Willebrand ds. (specifically type 2) ! ! ! --multimers of vWF are structurally abnormal/absent. ! ! ! --compound defect involving platelet fx. and coagulation pathway. ! ! ...aka thrombasthenia! --BT is prolonged. ! ! ! ! ! ! --count, PT, and PTT all WNL. What is normal? ! WBC count = 4000-11000 ! ! ! PMNs --> ! ! 45-78% ! ! ! Lymphocytes --> ! 15-47% ! ! ! Monocytes --> ! 0-12% ! ! ! Eosinophils --> ! 0-7% ! ! ! Basophils --> ! 0-2% ! ! ANC = WBC count x % of PMNs ! leukocytosis -- in increase in total circulating WBCs. neutrophilia (granulocytosis) -- typical of bacterial infections. lymphocytosis -- typical of viral infections. eosinophilia -- typical of parasitic infections, allergic reactions. leukemoid reaction -- an elevated WBC count that is a physiologic response to stress or ! ! ! infection. leukopenia -- a decrease in total circulating WBC count. neutropenia -- anti-neoplastic therapy, drugs, idk what else... the slide is blocked. ! --normal adult peripheral WBC count --> ! 4500-11000/mm3 ! --clinically relevant neutropenia --> ! ANC <500/mm3 ! --susceptibility to bacterial and fungal infections. ! decreased production: ! ! ! --congenital vs. acquired. ! ! --drugs. ! ! --hematologic ds. - cyclic neutropenia. ! ! --infection - bacterial, viral. ! ! --nutritional deficiency - B12, folate (B9). ! ! --myelophthisis/systemic. ! increased destruction: ! ! --autoimmune (ANCA - anti-neutrophil cytoplasmic antibody = dx. test) ! --in severe neutropenia, the signs of inflammation may be absent; no pus... 3 ! cyclic neutropenia -- defect in ELA-2 gene (neutrophil elastase) ! ! --regular, periodic reductions in neutrophils. ! ! --symptoms greatest at nadir (lowest point... lowest count). ! ! ! ! --fever, lymphadenopathy, malaise, pharyngitis, ! ! ! ! ! ulcerations, periodontitis. ! ! --dx: CBCs over time. ! ! --tx: supportive care, cytokine therapy (G-CSF) ! ! ! --granulocyte colony stimulating factor. lymphopenia -- steroid therapy. pancytopenia -- reduction in number of RBC, WBC, as well as platelets. ! --affects all cell lines - anemia, thrombocytopenia, neutropenia. **terms agranulocytosis, granulocytopenia, and neutropenia used interchangeably. leukemia and lymphoma ! --neoplasms of hematopoietic cells. ! --terms describe the tissue distribution of disease. ! ! ! leukemia = neoplastic cells in blood. ! ! ! lymphoma = neoplastic cells in lymph nodes. ! leukemia -- arises in bone marrow. ! ! --spills into peripheral blood. ! ! acute -- abrupt, stormy onset. ! ! ! --no maturation - precursor cells (“blasts”) proliferate. ! ! ! --kills rapidly without tx. ! ! ! --cure is possible. ! ! chronic -- insidious course. ! ! ! --maturation -- mature cells proliferate. ! ! ! --often not treated unless symptomatic. ! ! ! --cannot be cured. ! --leukemias are classified by cell of origin and clinical course: ! ! acute lymphoblastic leukemia - “childhood leukemia” ! ! acute myeloid leukemia - adult onset. ! ! chronic lymphocytic leukemia - mature, growing out of control. ! ! chronic myeloid leukemia. symptoms of acute leukemia: ! ! 1 - cytopenias - depression of normal bone marrow fx. ! 2 - bleeding - petechiae, ecchymoses, epistaxis, gingival hemorrhage due to TP. ! ! --spontaneous ging. hemorrhage is a nonspecific clinical symptom. ! ! --palatal petechiae. ! ! --ecchymoses on palate indicate bleeding diathesis. ! 3 - fever - infections due to absence of mature granulocytes. ! 4 - fatigue - anemia. ! 5 - bone pain. ! 6 - LAD (leukocyte adhesion deficiency). ALL (acute lymphoblastic leukemia): --most common childhood malignancy -- 33% of all pediatric cancers. ! --lymphoblasts - immature precursor B/T lymphocytes arrested at early stage of ! ! development. 4 ! --ds. of children. ! --good prognosis w/ aggressive chemotherapy - 90% cure rate. ! genetic predisposition: ! --Down syndrome, Fanconi anemia, XLA, SCID, etc. AML (acute myeloid leukemia): --”anything that is not a lymphocyte”. ! --myeloblasts - immature myeloid precursors (granulocytic, monocytic, erythroid, ! ! megakaryocytic) w/ no terminal myeloid differentiation. ! --ds. w/ adult onset. ! --prognosis - chemotherapy, bone marrow transplantation, more difficult to tx. ! --gingival enlargement in monocytic types of AML. ! --bleeding diathesis (tendency...) ! --M0-M8 (subtypes) ! --M3 --> APL --> responsive to ATRA (all trans retinoic acid) therapy. ! --Auer rods (M1-M4) --> dx. on blood smears. symptoms of chronic leukemia: ! 1 - often clinically silent. ! 2 - incidental leukocytosis on CBC. CML (chronic myelogenous leukemia): ! --adult. ! --insidious onset, slow progression. ! --Philadelphia chromosome - t(9:22) bcr-abl fusion gene... again. ! ! --translocation - proto-oncogene (abl) on long arm of chr. 9(q34) is ! ! ! transposed to bcr region (breakpoint cluster region) on chr. 22(q11). ! ! ! --gene product is abnormal tyrosine kinase - always on. (gain of fx.) ! ! ! --induces cell proliferation. ! ! --tx. = Gleevac, a tyrosine kinase inhibitor. ! --splenomegaly, fever, fatigue. ! --blast crisis - final phase, behaves like acute leukemia. ! --bone marrow transplantation. CLL (chronic lymphocytic leukemia): --most common type of leukemia. ! --adults, often asymptomatic. ! --hypogammaglobulinemia - infections... ! --anti-red cell auto-antibodies - autoimmune hemolytic anemia. ! --anti-platelet auto-antibodies - autoimmune thrombocytopenia. ! --Richter syndrome - may transform to high grade lymphoma. ! smudge cells --> B cells resemble normal lymphocytes under the microscope, ! ! although slightly smaller, and are fragile when smeared onto a glass slide ! ! giving rise to many broken cells. lymphoid neoplasms: ! ! lymphocytic leukemia ! Hodgkin lymphoma ! non-Hodgkin lymphoma ! plasma cell neoplasms 5 --clinical presentation (anatomic distribution): ! --lymphoma - non-tender lymph node enlargement, extra-nodal mass. ! --leukemia - cytopenias due to suppression of hematopoiesis. ! --plasma cell neoplasms - bone pain, pathologic fracture. lymphoma -- arises in peripheral lymphoid tissue, usually in lymph nodes. ! ! --forms a discrete tissue mass. ! ! --may eventually spread to peripheral blood and bone. ! ! --all are malignant. ! ! ! --degree of aggressiveness varies. ! ! ! low grade - indolent, difficult to cure. ! ! ! high grade - aggressive, often curable. ! --”Bʼs are better. Tʼs are terrible”. ! --Rokos NHL (non-Hodgkin lymphoma) -- painless lymphadenopathy w/ firm, enlarged, rubbery, ! ! ! ! ! freely moveable, non-tender lymph nodes. ! --generally involves multiple lymph nodes in a non-contiguous pattern. ! --frequently involves extranodal sites. ! ! --most NHL arise within lymph nodes (70%). ! ! --may also arise extranodally (30%). ! ! --oral mucosal NHL is extranodal. ! Burkitt lymphoma - high grade. ! ! --most aggressive malignancy -- rapidly growing. ! --”African jaw lymphoma” - endemic form has a predilection for jaws of children. ! ! --oral findings: rapidly growing painless swelling, producing paresthesia, ! ! ! ! loose teeth. ! ! ! --”teeth floating in air”. ! ! ! --rapid demise if untreated - short term high dose chemo. ! ! --”starry sky pattern”. ! ! 3 clinical forms: ! 1 - endemic (African) - EBV association. ! ! ! ! ! 2 - sporadic ! ! ! ! ! 3 - HIV-associated ! --B-cell NHL, associated w/ EBV. ! --cytogenetics --> translocation, t(8:14) is common. ! ! --c-myc proto-oncogene on chr. 8 has a role in cell cycle progression. ! ! --Ig gene promoters cause overexpression of c-myc. ! ! ! --promotes inappropriate cellular proliferation. ! ! **diseases associated w/ EBV (HHV-4):! 1 - infectious mononucleosis ! ! ! ! ! ! ! ! 2 - lymphomas (NHL and HL) ! ! ! ! ! ! ! ! 3 - nasopharyngeal carcinoma ! ! ! ! ! ! ! ! 4 - oral hairy leukoplakia ! diffuse large B cell lymphoma - intermediate grade. ! ! --palatal lymphoma. ! ! --associated w/ HIV infection. ! ! --50% of all NHL. ! MALT lymphoma - low grade. ! ! --”MALT-oma” - mature B cells. ! --often indolent. 6 ! --salivary glands, Sjogren syndrome. ! --may transform to high grade lymphoma. ! follicular lymphoma - 40% of NHL, 20% of all lymphomas. ! ! --slight female predominance. ! ! --adults (rare in <20 y.o.) ! ! --lymph nodes, Waldeyerʼs ring, GI. ! ! --DLBC transformation (Gr. III). --staging - characterizes extent of disease. ! I -- single lymph node region; can be treated w/ radiation. ! II -- multiple lymph node regions, same side of diaphragm. ! III -- multiple lymph node regions, both sides of diaphragm. ! IV -- disseminated ds.; more chemo, less radiation tx. ! --”B” symptoms for staging NHL: ! ! --recurrent, unexplained fevers. ! ! --night sweats (also associated w/ TB). ! ! --unintended weight loss. treatment of NHL: ! low grade -- treat only if symptomatic. ! ! ! high grade -- !localized stage: radiation therapy. ! ! ! ! ! advanced stage: chemo or combo of CT/RT. HL (Hodgkin lymphoma) -- the neoplastic cell is the Reed-Sternberg cell. ! --bimodal age distribution - young adults, older adults. ! --painless lymphadenopathy. ! --constitutional symptoms (variable): ! fever (Pel-Ebstein) ! ! ! ! ! ! ! ! --fevers which cyclicly increase ! ! ! ! ! ! ! ! then decrease over an average ! ! ! ! ! ! ! ! period of 1-2 wks. ! ! ! ! ! ! ! night sweats ! ! ! ! ! ! ! weight loss ! ! ! ! ! ! ! generalized pruritis ! ! ! --some are associated w/ EBV. ! --unilateral contiguous lymph chain involved. ! --hurts when they drink alcohol. ! --uniform, predictable pattern of spread from one LN region to the next. ! --Reed-Sternberg cell: ! --a minor fraction of tumor mass. ! ! ! ! --most are of B cell origin. ! ! ! --bilobate nucleus w/ large, cherry-red inclusion-like nucleoli. treatment: ! (stage determines tx. protocol). ! --localized (stage I): local radiation therapy. ! --disseminated (stage IV): chemotherapy. ! --risk of second cancers. prognosis: ! (stage is most important). ! --histologic subtype is least important: ! nodular sclerosis ! ! ! ! ! ! ! lymphocyte rich ! ! ! ! ! ! ! mixed cellularity ! ! ! ! ! ! ! lymphocyte depleted ! ! ! ! ! ! ! nodular lymphocyte predominated 7 ! curable --> stage I (90% cure rate). comparison -- this is good to know.... HL NHL location single axial group of nodes - e.g. cervical. multiple peripheral nodes. spread predictable orderly contiguous spread. unpredictable non-contiguous spread. Waldeyerʼs ring rarely involves WR. commonly involves WR. rare. common. extra-nodal “If you know what is what, it is what it is.” --Vandana blood vessel pathology mech. of vascular ds.: ! narrowing of lumen ! ! ! ! ! --atherosclerosis ! ! ! ! obstruction of lumen ! ! ! ! ! --thrombus ! ! ! ! ! --embolus ! ! ! ! weakening of wall ! ! ! ! ! --dilation ! ! ! ! ! --rupture arteriosclerosis -- generic term for hardening of the arteries. ! 3 patterns: ! 1 - atherosclerosis ! ! ! ! --atheromatous plaques project into and obstruct the lumen ! ! ! ! ! and weaken the t. media. ! ! ! ! --accumulation of lipid material in t. intima of vessel. ! ! ! 2 - medial calcific sclerosis ! ! ! ! --calcification of t. media; does NOT encroach on lumen. ! ! ! ! --makes aa. harder, less elastic. ! ! ! 3 - arteriolosclerosis ! ! ! ! --”morphologic manifestation of HTN”. ! ! ! ! --affects arterioles. ! ! ! --thickened walls reduce lumen diameter (narrowing), causing ! ! ! ! ischemic injury. ! ! ! ! hyaline arteriolosclerosis: ! --benign HTN. ! ! ! ! ! ! ! ! --diabetes mellitus. ! ! ! ! hyperplastic arteriolosclerosis: ! --malignant HTN. ! ! ! ! ! --hyperplasia, occludes lumen, leads to kidney ds. 8 ischemia - reduction in blood supply due to factors in blood vessels. infarct - complete loss of blood supply. hypoxia - general term denoting a shortage of oxygen, (in tissue). atherosclerosis --> ! a chronic inflammatory response of the arterial wall initiated ! ! ! ! by injury to the endothelium. pathogenesis:! 1. chronic endothelial injury. ! ! 2. accumulation of lipoproteins, mainly LDL (the bad cholesterol). ! 3. oxidation and phagocytosis of lipoproteins by histiocytes (foamy macrophages) 4. migration and hyperplasia of sm. m. cells w/ ECM deposition. ! ! --atheromatous plaques located in t. intima obstruct lumen and weaken ! ! vascular wall. ! ! --clinical events eventually occur and symptoms are produced. ! stages: ! a) fatty streak - earliest lesion of atherosclerosis. ! ! ! ! --lipid-filled foam cells (macrophages) within intima, leads to ! ! ! ! turbulent flow. ! ! ! b) atheroma (plaque) - covered by fibrous cap, may ulcerate --> CP. ! ! ! --plaque-like lesion - begins in the intima and impinges on lumen. ! ! ! c) complicated plaque - ulcerated! ---> exposes thrombogenic ! ! ! ! material. ! complications (why is this bad?): !--eventually a vulnerable (asymptomatic) ! ! ! ! ! ! plaque becomes a complicated plaque, and ! ! ! ! ! ! this inevitably leads to clinical events: ! ! ! ! ! ! ! --angina, cardiac ischemia, etc. atheromas? ! 1) Ischemic injury - compromised blood flow to distal organs. ! ! 2) Disruption - exposes thrombogenic substances. ! ! 3) Thrombosis - clotting on surface of ulcerated plaque causing further ! ! ! narrowing. ! ! 4) Embolization - thrombus or plaque material may embolize ! ! ! (thromboembolus). ! ! 5) Hemorrhage - a hematoma may expand or rupture plaque. ! ! 6) Aneurysm - weak wall may dilate and rupture. --clinical phase (middle age to elderly usually): !vulnerable plaque may: ! ! --aneurysm and rupture. ! ! --occlusion by thrombus. ! ! --critical stenosis. major clinical consequences of atherosclerosis: ! myocardial infarct - heart attack; tissue subject to coagulative necrosis, fibrosis. ! cerebral infarct - stroke; neural tissue subject to liquefactive necrosis. ! aortic aneurysm - rupture (bad). ! peripheral vascular ds. - gangrene of legs; non-infected, infarcted tissue. ! ! --”dry gangrene”. risk factors (atherosclerosis): ! constitutional (non-modifiable) : ! --age, gender, ! ! ! ! ! ! ! ! family hx., genetic abnormalities. ! ! major (modifiable): ! --hyperlipidemia, HTN, cigarette smoking, DM. 9 ! additional: ! --obesity, phys. activity, personality type, alcohol, trans FA, ! ! ! lipoprotein (a), hyperhomocysteinemia, systemic infl. state (CRP ! ! ! C-reactive protein). ! --multiple risk factors have a multiplicative effect. serum lipids -- major risk factor... !total cholesterol: ! <200mg/dL ! ! ! LDL: ! <100mg/dL ! ! ! --bad cholesterol. ! ! ! --delivers cholesterol to peripheral tissues. ! HDL: ! >40mg/dL ! --good cholesterol. ! --mobilizes cholesterol from atheromas and transports it to the liver!for excretion. oral-systemic connection ! -- possible mech. for link btw. chronic oral infection & CV ds. ! --release of systemic infl. mediators (CRP) w/ atherogenic effects in response to ! periodontal infection. ! --direct invasion of arterial wall by periodontal pathogens. ! --enter blood stream, not well understood. syphilitic aneurysm -- most commonly in aortic arch. ! --syphilitic aortitis of ascending aorta --> occurs in tertiary syphilis. ! --obliterative endarteritis of vasa vasorum. congenital “berry” (saccular) aneurysm -! --subarachnoid hemorrhage - secondary to rupture. ! --developmental lesion of cerebral vasculature. ! --NOT related to atherosclerosis. arterial dissection -- an intimal tear allows dissection of blood into media; may rupture ! ! leading to massive hemorrhage. ! ! --risk factors: HTN, connective tissue abnormality (Marfan syndrome). ! ! cardiac tamponade -- fluid accumulation in pericardium. venous disorders: ! varix -- distended (dilated) vein. ! esophageal varices ! ! --cirrhosis of liver causes portal HTN. ! ! --rupture producing massive upper GI bleed. pathology of the heart I. hypertensive heart ds. ! optimal bp = <120(s) and <80(d) ! stage I HTN --> 140-159(s) or 90-99(d) ! ! --compensatory myocardial hypertrophy --> ! due to exercise against ! ! ! ! ! ! ! ! ! resistance (high bp). ! end organ damage and complications of HTN: ! ! CV system ! --accelerated coronary atherosclerosis ! ! ! ! --increased myocardial O2 demand ! ! ! ! --ventricular remodeling (hypertrophy?) ! ! ! ! --heart failure ! ! ! ! --increased risk of arrhythmias ! ! peripheral vascular system ! --atherosclerosis 10 ! ! ! ! ! ! ! --aortic dissection ! ! ! ! ! ! ! --abdominal aortic aneurysm ! ! ! ! ! ! ! --peripheral vascular ds. ! ! renal system! --hypertensive nephrosclerosis ! ! ! ! ! --end-stage renal ds. ! ! CNS ! --hemorrhagic CVA ! ! ! --thromboembolic CVA ! ! visual system ! --retinal infarction ! ! ! ! ! --hypertensive retinopathy ! ! ! ! ! --blindness ! ! “HYPERTENSION IS THE SILENT KILLER!” II. heart failure congestive heart failure -- final common pathway of many forms of heart ds. ! --inability of the heart to pump a sufficient amount of blood through the body. ! ! --onset is preceded by compensatory mech. -- cardiac hypertrophy. ! left-sided HF -- seen in lungs - pulmonary edema/congestion. ! right-sided HF -- peripheral edema - congestion in systemic circulation. cause? ! --systolic dysfunction - deterioration of contractile fx. ! ! ! --ischemic heart ds. ! ! --diastolic dysfunction - inability to relax, expand, and fill. ! ! ! --this is how my brain feels most of the time. ! ! ! --left ventricular hypertrophy. ! cardiac hypertrophy -- compensatory mechanism to: ! ! ! 1--pressure overload: ! --concentrically increased wall thickness. ! ! ! ! ! ! --seen in HTN, aortic stenosis (aorta does not ! ! ! ! ! ! ! open all the way, heart must work harder ! ! ! ! ! ! ! against this). ! ! 2--volume overload: ! --dilation of chambers. ! ! ! ! ! ! --valvular incompetence. LHF -- pulmonary edema/congestion. ! findings: ! --edemal fluid in alveolar spaces. ! ! ! --”heart failure cells” -> macrophages containing phagocytosed ! ! ! ! RBC (hemosiderin), seen in lung. ! ! ! --dyspnea, orthopnea, paroxysmal nocturnal dyspnea. RHF -- core pulmonale = pure RHF. ! --right ventricular hypertrophy and dilation. ! --pulmonary HTN. --typically not seen by itself, usually caused by LHF. ! --may have stasis dermatitis -- affects legs due to insufficient venous return. ! 1--congestion in systemic and portal venous circulations. ! 2--congestive hepatomegaly -- chronic passive congestion -- “nutmeg” liver. ! 3--congestive splenomegaly. ! 4--pleural effusion. ! 5--peripheral edema -- “pitting”. ! 6--ascites -- not a beer belly, but sort of... III. ischemic heart ds. 11 ! --result of coronary artery atherosclerosis. ! ! --imbalance between myocardial O2 supply and demand. ! --angina pectoris ! ! --transient myocardial ischemia. ! ! --does NOT produce myocardial necrosis (infarction). ! ! --paroxysmal, recurrent precordial chest discomfort. ! ! ! --constricting, squeezing, choking, knife-like. ! ! --may radiate to arm or mandible (might be interpreted as dental pain). ! ! stable? ! --due to a fixed stenosis - an atherosclerotic plaque reduces ! ! ! ! ! ! coronary perfusion to critical level. ! ! ! ! --increased demand produces ischemia. ! ! ! --relieved by rest or nitroglycerin. ! ! unstable? ! --due to a complicated plaque - a variable stenosis. ! ! ! ! --frequently occurs at rest. ! ! ! ! --medical emergency - may evolve into MI. ! ! variant angina? ! --aka Prinzmetal angina. ! ! ! --coronary arterial spasm secondary to vascular hyper-reactivity. ! ! ! --occurs at rest. ! ! ! --may be unassociated w/ arteriosclerotic coronary artery disease. ! ! ! --cocaine users --> vasospasm. ! --myocardial infarction ! ! pathogenesis of transmural acute myocardial infarction: ! ! ! --coronary atherosclerosis ! ! ! --complicated plaque (most common cause) ! ! ! --platelet adhesion and activation ! ! ! --thrombus formation ! ! ! --vessel occlusion ! ! ! --myocardial infarction (cellular necrosis) --infarcted tissue may appear tan, but youʼll be dead when they see that so who cares? ! 3-4 days --> acute inflammation, at risk for rupture. ! ~7 days --> granulation tissue grows in from periphery. ! ~21 days --> collagenous scar - pale pink appearance. serum cardiac markers : ! 1) cardiac-specific troponin (T or I) ! ! ! ! 2) creatine phosphokinase (MB fraction) - CPK-MB post-MI complications: ! (still at risk several days following MI) ! --wall rupture ! --papillary muscle rupture ! --aneurysm ! --mural thrombus what determines risk of developing detectable IHD? ! ! --number, distribution, and structure of atheromatous plaques. ! ! --degree of narrowing. IV. valvular heart ds. ! stenosis - doesnʼt open completely (impedes forward flow). ! insufficiency/incompetence - doesnʼt close completely (allows reverse flow). ! --abnormalities of flow produce murmurs. 12 ! major lesions: ! aortic stenosis ! ! ! ! aortic insufficiency ! ! ! mitral stenosis -- rheumatic heart ds. ! ! mitral insufficiency -- myxomatous degeneration (mitral valve prolapse). ! --tx.: mechanical valve prosthesis, or porcine bioprosthesis. ! acute rheumatic fever -- complication w/ group A streptococcal pharyngitis. ! ! --ABs cross react w/ cardiac antigens. ! ! --inflammation leads to fibrotic valvular ds. ! ! --Aschoff bodies (microscopic). ! --most frequent cause of mitral stenosis. ! ! --fibrinous pericarditis -- can lead to scarring adhesions w/ healing. ! rheumatic heart disease: ! ! pericardium -- fibrinous pericarditis ! ! myocardium -- myocarditis ! ! valves -- ! mitral vegetations ! ! ! ! thickened leaflets ! ! ! ! fused commissures V. infective endocarditis -- most frequently bacterial. ! --Strep. viridans, Staph. aureus (IV drug abusers) ! ! --virulence of organism determines course. ! ! --thrombus formation on damaged endothelium -- vegetations. ! ! --bacteremia results in microbial colonization of vegetations. ! ! --septic emboli. ! --LEFT side of heart is most commonly affected (aortic valve). ! --right side -- for IV drug abusers. ! --mortality due to heart failure. cardiac conditions requiring premed. for IE: ! 1) prosthetic heart valves ! ! ! ! ! ! 2) previous hx. of IE ! ! ! ! 3) congenital heart disease. ! ! ! ! ! --unrepaired or incompletely repaired cyanotic ! ! ! ! ! ! congenital heart ds. ! ! ! ! --first 6 m. after repair of cong. heart defect. ! ! --repaired cong. heart defect w/ residual defect !inhibiting endotheliazation. ! ! ! 4) cardiac transplant recipient w/ valvulopathy. ! VI. congenital heart ds. -- abnormalities of heart and great vessels. ! --#1 birth defect, leading cause of death during infancy from birth defect. ! --faulty embryogenesis -- 3-8 weeks (i.u.) ! --susceptibility to IE -- antimicrobial prophylaxis. --most have NO identifiable cause - ! multifactorial, environmental, genetic, and ! ! ! ! ! ! maternal factors. ! ! environmental: ! infectious - fetal rubella or CMV infection. ! ! ! ! ! drugs - accutane, lithium, anti-seizure meds, cocaine, ! ! ! ! ! ! alcohol. ! ! genetic: ! ex. trisomy 21, Turner syndrome, etc. 1) malformations causing LEFT-TO-RIGHT shunts: ! --all contain a “D”, like Dan. 13 ! --pulmonary blood flow increased. ! ! --pulmonary HTN. ! ! --shunt reversal --> cyanosis (Eisenmenger syndrome). ! A) ventricular septal Defect ! B) patent Ductus arteriosus: ! ! d.a. is a normal fetal blood vessel that allows blood to bypass the lungs. ! ! --shunt from aorta to pulmonary artery. ! ! --when pulm. HTN develops, shunt reverses and cyanosis develops. ! C) atrial septal Defect ! D) atrial-ventricular septal Defect 2) malformations causing RIGHT-TO-LEFT shunts: ! --cause cyanotic heart ds. ! --all begin w/ “T”. ! --pulmonary blood flow is decreased, allowing poorly-oxygenated blood to enter ! ! the systemic circulation. ! --may be associated w/ paradoxical embolism ! -- a septal defect allows venous ! ! ! ! ! ! ! ! emboli to bypass the lungs and ! ! ! ! ! ! ! ! enter systemic arterial circulation. ! ! --cyanosis and clubbing of fingers. ! A) tetralogy of Fallot -- most common form of cyanotic cong. heart ds. ! ! i) ventricular septal defect -- most common form of cong. heart ds. ! ! ii) sub-pulmonary stenosis ! ! iii) right ventricular hypertrophy ! ! iv) aorta overrides VSD. ! B) transposition of great arteries -- no mixing of pulm. and syst. circulations, this ! ! ! ! ! ! is not compatible w/ life without a shunt. ! ! stable shunt -- VSD ! ! unstable shunt -- ! patent foramen ovale ! ! ! ! ! patent ductus arteriosus ! ! --RV hypertrophy ! ! --LV atrophy 3) malformations causing OBSTRUCTIONS: ! coarctation -- obstruction to flow (narrowing...) ! coarctation of aorta -- obstructive defect located in area of the ductus that may be ! ! asymptomatic until adulthood. ! ! --typically, collateral circulation is increased around this. ! --hypertension proximal (upstream) to coarctation. ! --hypotension distal (downstream) to coarctation. 14