Pathology Flashcards
Microcytic anemias
Iron deficiency, anemia of chronic disease, thalassemias, lead poisoning, sideroblastic anemia
Normocytic anemias
Hemolytic or non-hemolytic (chronic disease, aplastic anemia)
Macrocytic anemias
Megaloblastic (folate/B12 defciciency), non-megaloblastic (liver disease, alcoholism)
Iron deficiency anemia
MICROCYTIC - chronic bleeding, malnutrition, or increased demand – decreased iron and ferritin, increased TIBC (transferrin) – fatigue, conjunctival pallor, spoon nails, difficulty swallowing
Plummer Vinson syndrome
Plumbers DIE – Dysphagia, Iron defciency anemia, Esophageal webs
a-thalassemia
MICROCYTIC - a-globin gene deletions (chromosome 16) – cis (Asians) or trans (African) – 4 deletions (Hb barts - y4 - hydrops fetalis), 3 deletions (HbH disease)
B-thalassemia
MICROCYTIC - point mutations in Kozak sequence (chromosome 11) - Mediterranean – defective mRNA processing – minor (heterozygote) - Less B chain, asymptomatic, increased HbA2 – major (homozygote) - no B chain (have HbF), requires blood transfusions – crew cut on x-ray, skeletal deformities, chipmunk facies, extramedullary hematopoiesis (increased risk of parvovirus B12 aplastic crisis)
Lead poisoning
MICROCYTIC – Inhibits ferrochelatase and ALA dehydratase – increase RBC protoporhyrin IX and d-ALA and decrease heme – basophilic stippling (retained aggregates of rRNA) – LEAD (Lead Lines on gingiva and bones, Encephalopathy, Abdominal colic and sideroblastic Anemia, Drops (wrist and foot) – Tx: Dimercaprol and EDTA (Succimer for kids)
Sideroblastic anemia
Defect in heme synthesis — X-linked defect in d-ALA synthase – can be acquired, alcohol, lead, vitamin B6 deficiency, copper deficiency, isoniazid) – ringed sideroblasts (iron-laden PRUSSIAN BLUE STAIN mitochondria) – increased iron/ferritin, normal/decreased TIBC – Tx: Pyridoxine (B6)
Hepcidin
Made in liver (decreases intestinal iron absorption and iron release from macrophages) – increased when iron is low
Pure RBC Aplasia
Microcytic, hypochromic – CD8/IgG attack RBC precursors — d/t parvovirus B19, thymoma, leukemia
Folate deficiency
MEGALOBLASTIC (hypersegmented PMNs) – impairs purine/pyrimidine synthesis – d/t malnutrition, malabsorption (jejunum), drugs (methotrexate, TMP, phenytoin), pregnancy – INCREASE HOMOCYSTEINE, NORMAL METHYLMALONIC ACID – No neurologic symptoms
B12 (cobalamin) deficiency
MEGALOBLASTIC – Insufficient intake, malabsorption (ileum), pernicious anemia (no intrinsic factor), gastrectomy – INCREASED HOMOCYSTEINE AND METHYLMALONIC ACID – Neurologic symptoms (degeneration of spinocerebellar tract, lateral corticospinal tract, and dorsal column
Orotic aciduria
Can’t convert orotic acid to UMP (defective UMP syntahse) – Failure to thrive, developmental delay, megaloblastic anemia refractory to folate/B12 – Orotic acid in urine – Tx: Uridine monophosphate
Schilling Test
Give oral B12 – if normal urinary excretion then dietary deficiency — if decreased excretion then impaired absorption (can further test with intrinsic factor)
Intravascular hemolysis
Decreased haptoglobin, increased LDH, schistocytes, increased reticulocytes — hemoglobin, hemosiderin, and urobilinogen in urine
Extravascular hemolysis
Macrophages in spleen destroy RBCs – spherocytes, increased LDH, increased unconjugated bilirubin
Anemia of chronic disease
Increased hepcidin, decreased iron, decreased TIBC, increased ferritin (storage) – Tx: EPO for chronic kidney disease
Aplastic anemia
Myeloid cell issue due to radiation and drugs (chloramphenicol), viral agents (B19, EBV, HIV, HCV), Fanconi anemia, or idiopathic – pancytopenia (increased EPO due to compensation), hypocellular bone marrow with fat infiltrate – fatigue, pallor, mucosal bleeding, petechiae, infection – Tx: immunosuppression, bone marrow allograft, RBC/platelet transfusion, bone marrow stimulants
Hereditary spherocytosis (E)
Defect in ankyrin, band 3, protein 4.2, spectrin (membrane proteins) — increased MHC, decreased haptoglobin, increased LDH, increased reticulocytes — splenomegaly, aplastic crisis, risk for gallstones – positive osmotic fragility test – Tx: splenectomy
G6PD deficiency (I/E)
X-linked recessive — abnormal hexose monophosphate shunt (decreased glutathione so increased oxidative damage) — anemia following oxidative stress (sulfa drugs, dapsone, antimalarials, infections, fava beans) — Heinz bodies, bite cells
Pyruvate kinase deficiency (E)
Hemolytic anemia in a newborn - autosomal recessive – decreased ATP
HbC defect (E)
Glutamic acid to lysine mutation in B-globin
Paroxysmal nocturnal hemoglobinuria (I)
Increased complement mediated RBC lysis – increased acute leukemias — pancytopenia, aplastic anemia, Coombs negative, venous thrombosis — CD55/59 negative — Tx: Eculizumab
Sickle cell anemia (E)
Glutamic acid to valine substitution allows hydrophobic interaction between Hb in anoxic conditions — low O2, high altitude, or acidosis leads to anemia and vaso-occlusive disease — newborns are asymptomatic because HbF is protective – heterozygotes have malaria resistance — Crew cut on skull x-ray (marrow expansion) – decreased haptoglobin — Tx: hydroxyurea (increases HbF)
Sickle cell complications
Aplastic crisis (parvovirus B19) – autosplenectomy (Howell-Jolly bodies, increased risk of encapsulated organisms) – splenic infarct (microvascular infarcts) – Salmonella osteomyelitis – painful crises (vaso-occlusive - acute chest syndrome, avascular necrosis, stroke) – renal papillary necrosis
Autoimmune hemolytic anemia
Warm agglutinin (IgG - chronic in SLE an dCLL or with drugs) – Cold agglutinin (IgM - acute in CLL, Mycoplasma pneumonia, Mono) – Coombs positive
Coombs tests
Direct is checking for antibody on RBC – indirect is checking for antibody in patient’s serum
Microangiopathic anemia
RBCs damaged when passing through obstructed vessel – DIC, TTP/HUS, SLE, malignant hypertension — schistocytes
Macroangiopathic anemia
Prosthetic heart valves and aortic stenosis – schistocytes
Corticosteroid cell effects
Increase neutrophils, decrease lymphocytes and eosinophils
Acute intermittent porphyria
Deficient porphobilinogen deaminase – accumulation of porphobilinogen, d-ALA – 5Ps (Painful abdomen, Port wine colored urine, Polyneuropathy, Psychological issues, Precipitated by drugs (cyp450 inducers, alcohol) – Tx: Glucose and heme
Porphyria cutanea tarda
Uroporphyrinogen decarboxylase deficiency – accumulate uroporphyrin (tea colored urine) – blistering cutaneous photosensitivity, red teeth, super hairy
Heme pathway diseases
GAP UP (substrates - Glycine, Aminolevulinic acid, Porphobilinogen, Uroporphyrinogen, Protoporphyrin) = Some Doctors Prescribe Unlimited Ferrochelatase (enzymes - Synthase, Dehydratase, Porphobilinogen deaminase, Uroporphyrinogen decarboxyalse, Ferrochetalase) = SLAP Lead (diseases - Sideroblastic anemia, Lead poisoning, Acute intermittent porphyria, Porphyria cutanea tarda, Lead poisoning)
Iron poisoning
Cell death due to peroxidation of membrane lipids – Tx: chelation (deferoxamine, deferasirox)
Hemophilias
Increased PTT, normal PT – A (VIII - XR), B (IX - XR), C (XI - AR) — macrohemorrhage, hemarthroses, easy bruising, bleeding after trauma — Tx: desmopressin (releases factor 8 and vWF from endothelium) plus missing factor concentrate
Vitamin K deficiency
Increased PT and PTT but normal bleedign time — decreased factors 2, 7, 9, 10, protein C/S
Platelet disorders
Increased bleeding time and microhemorrhage (mucosal bleeding, epistaxis, petechia)
Bernard Soulier syndrome
Increased BT, large platelets – decrased GpIb (defect in platelet to vWF adhesion)
Glanzmann thrombasthenia
Increased BT – decreased GpIIb/IIIa (defect in platelet to platelet aggregation) – agglutination with ristocetin cofactor assay
Immune thrombocytopenia
Decreased platelet count, increased BT – anti-GpIIb/IIIa antibodies (viral illness) – increased megakaryocytes – Tx: steroids, IV Immunoglobulin
Thrombotic thrombocytopenic purpura
Decreased platelet count, increased BT – deficient ADAMST13 (decreased degradation of vWF multimers) – increased large vWF multimers and increased platelet aggregation/thrombosis – schistocytes, increased LDH — neurologic and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia – Tx: plasmapheresis, steorids
von Willebrand disease
Increased BT and PTT – lifelong history of mucosal bleeding – autosomal dominant – Ristocetin cofactor assay (decreased agglutination) – Tx: desmopressin
DIC
Decreased platelet count, increased BT/PT/PTT, increased D-dimers (fibrin split products), schistocytes, decreased fibrinogen, decreased factors V and VIII — deficiency in clotting factors — STOP Making New Thrombi (Sepsis, Trauma, Ob complections, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion, and snake bite)
Antithrombin deficiency
Diminishes increase in PTT following heparin
Factor V leiden
Resistant to degradation by activated protein C – DVT, pregnancy loss, cerebral vein thrombosis
Protein C or S deficiency
Increased risk of thrombotic skin necrosis with hemorrhage following warfarin administration – Protein C Cancels Coagulation
Prothrombin gene mutation
Increased plasma levels or prothrombin and venous clots
Packed RBCs
Increase 1Hb/unit – acute blood loss, severe anemia
Platelets
Stop significant bleeding
Fresh frozen plasma
Immediate warfarin reversal, cirrhosis, DIC
Cryoprecipitate
Fibrinogen, factors 8, 13, vWF, fibronectin — coagulation deficiencies involving fibrinogen and factor 8
Leukemoid reaction
Increased LAP – HUGE WBC count, left shift, lots of neutrophils
Hodgkin lymphoma
Single group of nodes, contiguous spread, young adults and > 55, associated with EBV – B signs (fever, night sweats, weight loss) — Reed Sternberg cells (CD15/30 positive - owl eyes) – nodular sclerosing form is most common
Burkitt lymphoma
B cells – young people – t(8;14) c-myc and heavy chain Ig — starry sky (macrophages) – associated with EBV – jaw lesion in Africa, pelvic/adomen in US
Diffuse large B cell lymphoma
Older adults — MC type in adults – large lymph node or extranodal mass, Waldeyer ring, very agressive
Follicular lymphoma
MC indolent form, can progress to DLBCL — t(14;18) - BCL-2 (inhibits apoptosis) and Ig heavy chain – painless, waxing and waning lymphadenopathy — Tx: Rituximab
Mantle cell lymphoma
B cells - Older males – t(11;14) - cyclin D1 (G1 -> S) and heavy chain Ig — CD5+
Adult T cell lymphoma
Caused by HTLV – cutaneous lesions, lytic bone lesions, hypercalcemia
Mycosis fungoides/Sezary syndrome
Skin patches/plaques (cutaneous T cell lymphoma), atypical CD4+ T cells — Sezary syndrome when it gets into circulation (T cell leukemia)
Multiple myeloma
Plasma cell cancer that makes a lot of IgG or IgA — people > 40-50 — increased infections, punched out lytic bone lesions, M spike, Ig light chains in urine (Bence Jones protein), Rouleaux formation — CRAB (hyperCalcemia, Renal involvement, Anemia, Back pain/Bone lytic lesions)
Monoclonal gammopathy of undetermined significant
Monoclonal expansion of plasma cells, asymptomatic, no CRAB findings
Waldenstrom macroglobulinemia
M spike = IgM –> hyperviscosity (blurred vision and Raynauds)
Acute lymphoblastic leukemia
KIDS – T cell can present as mediastinal mass (SVC like) — DOWN SYNDROME! — INCREASED LYMPHOBLASTS — TdT+, CD 10+, Responds well to methotrexate – t(12;21) has best prognosis
Small lymphocytic lymphoma/chronic lymphoblastic leukemia
Adults > 60 (most common) – CD20+, CD5+ – SMUDGE CELLS – Tx: Prednisone, Rituximab
Hairy cell leukemia
Adults, hair like projections on cells — dry tap on aspiration – TRAP POSITIVE (tartrate resistant acid phosphatase) - old men with pancytopenia and splenomegaly — Tx: Cladribine, pentostatin
Acute myelogenous leukemia
Age 15-59 — AUER RODS!!!!!!! – Myeloperoxidase +, LOTS of circulating myeloblasts — t (15;17) - M3 AML subtpye (Tx: ATRA causes differentiation of myelobalsts, DIC complication of treatment) — Tx: Cytarabine
Chronic myelogenous leukemia
Age 30-59 — PHILADELPHIA CHROMOSOME t(9;22) BCR-ABL – increased neutrophils, metamyeloblasts, BASOPHILIA – very low LAP – Tx: Imatinib
Langerhans cell histiocytes
Lytic bone lesions and skin rash in child or recurrent otitis media with mass — S-100 stain and Cd1a – Birbeck granules (tennis rackets)
Chronic myeloproliferative disorders
JAK2 (cytoplasmic tyrosine kinase) mutation — activates JAK-STAT pathway
Polycythemia vera
Increased hematocrit (increased RBCs/WBCs/platelets) – decreased EPO due to negative feedback – Intense itching after hot shower – erythromelalgia (burning pain with red/blue color) due to blood clots in vessels of extremities — Tx: phlebotomy/hydroxyurea
Essential thrombocytosis
Overproduction of abnormal platelets – enlarged megakaryocytes
Myelofibrosis
Increased fibrosis in bone marrow – TEARDROP RBCs – dry tap – massive splenomegaly — Tx: Ruxolitinib
Polycythemias
Relative (decreased plasma volume d/t deyhdration/burns) — appropriate absolute (increasd RBC mass, decreased O2 saturation, increased EPO - lung/heart disease) — inappropriate absolute (increased RBC mass, increased EPO - kidney/liver cancer due to ectopic EPO) — vera (increased plasma volume, huge increased RBC mass, decreased EPO)
