hematopoietic system Flashcards
anemia
-RBC, Hct, Hmg decrease
-present with pallor, fatigue, weakness, dyspnea, palpitations, heart failure
-ALL anemias
how does anemia occur
-1. acute blood loss (trauma)
-2. chronic blood loss:
-GI- bleeding ulcers, carcinoma etc.
-Gyn- menses, postmenopausal bleeding etc.
-3. increase destruction of RBC- hemolytic anemia
-4. decrease or impaired production:
-problem in proliferation of stem cells (aplastic anemia)
-problem of proliferation and maturation of erythroblasts
-defective DNA synthesis (iron deficiency anemia)
-defective globin synthesis (thalassemia)
hemolysis causes
-Hereditary causes
-RBC membrane problems (e.g. hereditary spherocytosis)
-Enzyme disorders (e.g., G-6-PD deficiency)
-Hgb disorders (hemoglobinopathies such as sickle cell anemia)
-Acquired causes
-RBC membrane problem (e.g. paroxysmal nocturnal hemoglobinuria)
-Antibody mediated
-Mechanical trauma (e.g prosthetic heart valves)
-Others include infections, drugs, toxins, splenic sequestration
-Intravascular hemolysis (in vessels) VS Extravascular hemolysis (spleen)
-Extravascular hemolysis presentation = anemia, splenomegaly, jaundice
hemolytic anemia
-Life span < 120 days
-bone marrow erythroid hyperplasia = compensating response to…
-loss of RBC
-release of EPO produced by kidney
-increases in bilirubin, hemosiderosis, etc.
-Coombs tests = always used in work-up of hemolytic anemias
-Direct – rbc cells tested for surface antibodies
-Indirect – serum tested for antibodies
hereditary spherocytosis
-hemolytic anemia
-GENETIC
-Autosomal dominant
-affecting RBC membrane proteins -> Ankyrin and spectrin
-RBCs will be round without normal central pallor
==> These spherocytes are fragile and break down
G-6-PD deficiency
-hemolytic anemia
-G-6-PD = an enzyme which converts glucose-6-phosphatase
-!!Rate limiting step of pentose phosphate pathway
==> Hemolysis after eating some food (classically Fava beans) or use of oxidant drugs (i.e., chloroquine or infections)
-Usually either recessive or X-linked
-Morphologically RBCs will show Heinz bodies which is precipitated hemoglobin
sickle cell anemia
-hemolytic anemia
-hemoglobinopathy
-beta chain defect (amino acid substitution)
-Heterozygous versions are usually asymptomatic
-Homozygotes – RBCs sickle in peripheral blood and along with anemia
-jaundice, pain, vaso-occlusive disorders (sickle cells get “stuck” in vessels).
-susceptibility to infections such as Strep. pneumonia or Salmonella osteomyelitis
-Sickle cells trapped in sinusoids –> Spleen can basically become non-functional (auto infarct) –> encapsulated microorganisms infection common since spleen usually deals with these types of microorganisms
-Protection against Malaria
thalassemia
-hemolytic anemia
-Hgb Alpha or Beta chain problems, aka deficient synthesis
-Presents w/ “Crew cut” skull X-ray
<– erythroid hyperplasia expanding bone
-many different types
-ex. alpha-thalassemia
-ex. Hydrops fetalis! = all 4 alpha chains are deleted, usually fatal (fetus does not make it to term)
-If born, infant will have severe hemolytic anemia, edema (hydrops), massive hepatosplenomegaly
PNH- paroxysmal nocturnal hemoglobinuria
-hemolytic anemia
-Acquired mutation of PIGA = acquired RBC membrane disorder
-Not always paroxysmal or nocturnal
-Don’t need to know too much about this!!!
immunohemolytic anemias
-hemolytic anemia
-antibodies and/or complement present on RBC surface
-= autoantibodies that react with RBC at temp ≥ 37° C (warm antibody hemolytic anemia) or < 37° C (cold agglutinin disease)
-May not be auto-immune, can be caused by certain drugs
-Antibodies:
-warm IgG (will not hemolyze at room temp)
<~~ may be idiopathic or 2ndary to malignancies (lymphomas and leukemias)
-cold agglutinin IgM (will hemolyze at room temp)
<~~ Mycoplasma pneumoniae, HIV, mononucleosis
-cold hemolysin IgG
e.g. cold paroxysmal hemoglobinuria- very rare, caused by presence of cold-reacting autoantibodies in blood and !characterized by the sudden presence of hemoglobinuria, typically after exposure to cold temp!
hemolytic anemias due to trauma
-hemolytic anemia
-mechanical heart valves
-microangiopathies such as thrombotic thrombocytopenic purpura (pentad of fever, thrombocytopenia, anemia, renal and neurological manifestations, deficiency of enzyme ADAMTS-13 – see later) and HUS (usually follows E. coli GI infections in children– see later)
anemias due to decreased/impaired production include
-megaloblastic anemia
-iron deficiency anemia
-anemia of chronic disease
-aplastic anemia
megaloblastic anmiea
-impaired DNA synthesis
-Vitamin B12 and folate deficiency
-macrocytic –> MCV > 94 (large RBCs) + neutrophils are hypersegmented (4 + lobes)
-Vitamin B12 deficiency
-decreased oral intake (diet)
-B12 combines with Intrinsic Factor in stomach to be absorbed in terminal ileum. -Any problem at those sites will also cause deficiency
-Folate deficiency
-decreased oral intake (diet), alcoholism, intestinal disease causing poor absorption, chemo, drugs (e.g anti-convulsants), hemodialysis (increased loss), pregnancy and infancy (increased requirement) and impaired usage
iron deficiency anemia
-Increase loss of iron or decreased intake (oral)
==> RBCs are microcytic and hypochromic (small and paler)
==> Decreased serum iron levels, transferrin saturation, and ferritin
==> Increased Total iron-binding capacity (TIBC)- measures blood’s capacity to bind iron with transferrin
-Ferritin = protein for iron storage, releases iron as body requires
-Low levels = low iron storage
-Stored in body’s cells until it receives signal to make more RBC -> ferritin then binds to transferrin
-Transferrin- transport ferritin to where new RBC are made
anemia of chronic disease
-chronic infections, chronic immune diseases, neoplasms, liver or kidney failure
-Very similar to iron deficiency anemia
-Iron is present in bone marrow in anemia of chronic disease unlike in iron deficiency anemia.
aplastic anemia
-All 3 cell lines (RBCs, WBCs, platelets) are affected
-idiopathic, caused by drugs, radiation, or viruses
-Fanconi’s anemia!! = a disorder of aplastic anemia -> assoc with short stature, skeletal abnormalities, and increased risk of solid tumors and leukemias
increased platelet destruction (ITP, TTP, HUS, DIC, drugs, infectious diseases (e.g. HIV))
-Immune thrombocytopenic purpura (ITP) -autoimmune:
-Acute- KIDS after viral illness
-develop anti-platelet antibodies
-self-limited
-Chronic- adults -> dx of exclusion
-decrease platelet # but normal PT/PTT (measures clotting factors) -> large platelets in circulation
-anti-platelet antibodies, increase in bone marrow megakaryocytes (compensatory mechanism)
-Tx- steroids and sometimes splenectomy
-Never give a pt with ITP a platelet transfusion -> autoantibodies will destroy platelets entered into circulation by transfusion
-Thrombotic thrombocytopenic purpura (TTP)
-Pentad presentation
-Microangiopathic anemia
-Characteristic schistocytes (helmet cells!!!) <– As RBCs travel through microthrombi they become sheared or fragmented
-Thrombocytopenia
-Fever
-Neurological manifestations
-Renal manifestations (neurological more so than renal)
-Causes:
-Acquired
-Inherited ADAMTS13 enzyme deficiency: vWF (von Willebrand Factor) multimers aggregate –> platelet activation, etc.
-platelets deposit as microthrombi in microcirculation (platelets are consumed by making thrombi – consumptive coagulopathy)
-tx is usually plasma exchange to remove antibodies
-Hemolytic-Uremic Syndrome (HUS) – similar to TTP but renal manifestations (increase in BUN/Cr) > neurological
-follows a GI E. coli infection from eating uncooked meat, etc.
-E. coli produce a toxin
disseminated intravascular coagulation
-pathological activation of coagulation cascade caused by many different things
—> widespread formation of microthrombi –> As platelets are used up to make microthrombi -> platelet count decreases
-!!!!!==> Therefore both coagulation factors and platelets are consumed (consumptive coagulopathy)
-Possible causes - trauma, obstetrics complications, sepsis, some types of adenocarcinoma, acute promyelocytic leukemia
-Acute DIC – usually more associated with bleeding
-more likely caused by OB complications, sepsis, and trauma
-Chronic DIC – usually more associated with thrombosis
-more likely caused by malignancy
-Treat underlying cause
