hematopoietic pathology part 1 ! fragmentation of precursor megakaryocytes.

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