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Flashcards in Anemia Deck (43):
1

microcytic anemias

  • MCV < 80fl 
  • iron deficiency//chronic disease, thalassemia

2

normocytic anemias

  • 80 < MCV < 100fl
  • chronic disease, bone marrow, hemolytic anemia

3

macrocytic anemia

  • MCV > 100fl
  • B12 deficiency, folate deficiency, megaloblastic, liver disease

4

MCHC

mean corpuscular hemoglobin concentration = hemoglobin concentration/hematocrit --> normal = 32-36 g/dL

5

MCV

mean corpuscular volume

6

Iron deficiency anemia epidemiology

most common anemia; f>m

7

Iron deficiency anemia causes

lack of available iron limits hemoglobin synthesis: 

  • insufficient intake
  • GI bleed
  • menstrual loss

8

Iron deficiency anemia ID

microcytic anemia, decreased serum iron/ferritin/transferrin, increased total iron-binding capacity (TIBC)

9

Anemia of chronic disease ID

IL6 -> hepcidin excess -> iron retained in macrophages -> EPO restricted by iron

10

Pernicious Anemia

  • autoimmune gastric atrophy -> reduced intrinsic factor production -> reduced B12 production -> defective nuclear maturation/DNA synthesis -> anemia/low reticulocytes • ID: macrocytic anemia, reduced reticulocyte index, abnormal Schilling test, low serum B12 or folate

11

Schillings test

staged radiolabeled B12 to track renal excretion -> increased urinary output diagnosis pernicious --> distinguishes between various causes of low if

12

Aplastic Anemia/Bone marrow failure

• severe normocytic anemia • idiopathic or secondary to medications, toxins, or infections

13

Hemolytic anemia

results from RBC destruction --> initial reticulocytosis but ultimately results in anemia

14

Hemolytic anemia - intravascular hemolysis ID

  • low haptoglobin
  • high hemoglobin
  • hemoglobinuria

in addition to normal hemolytic anemia

  •     increased LDH
  •     increased bilirubin
  •     increased reticulocytes

15

Hemolytic anemia - extravascular hemolysis ID

  • increased LDH
  • increased bilirubin
  • increased reticulocytes

16

Hemolytic anemia - Hereditary spherocytosis

  • autosomal dominant defect of spectrin/ankyrin --> reduces RBC deformability --> splenic mediated hemolysis
  • Epi: Northern europe
  • ID: range of splenomegaly spherocytes, reticulocytosis, elevated MCHC, increased osmotic fragility, negative DAT
  • Tx: splenectomy

17

Hemolytic anemia - Hereditary elliptocytosis

  • autosomal dominant defect of structural proteins --> reduces resistance to shear --> mostly asymptomatic
  • ID: African/Med elliptocytes, normal osmotic fragility

18

Hemolytic anemia - G6PD deficiency

  • X linked defect of oxphos
  • low G6PD -> low NADPH -> low glutathione -> predispose to oxidative damage
  • Epi: most common red cell enzymopathy
    • A-  10% of Afr.Am. men --> only reduced G6PD in old cells
    • B-  5% of Med/Asian --> reduced G6PD in all cells
  • ID: fava beans, sulfa ab's, male, neonatal jaundice, bite cells, heinz bodies, increased LDH, decreased haptoglobin, - coombs test

19

Hemolytic anemia - Autoimmune

Ig mediated destruction of host RBCs

20

Hemolytic anemia - Warm autoimmune

  • mediated by IgG vs. Rh antigens -> Fc phagocytosis in spleen -> transfusion dependent chronic anemia
  • ID: spherocytes, + DAT/Coombs
  • Causes: idiopathic, lupus etc, methyldopa, lymphoproliferative disorders
  • Tx: corticosteroids, splenectomy, immunosuppressive

21

Hemolytic anemia - Cold autoimmune

  • mediated by IgM that react at cold temp --> complement mediated lysis or phagocytosis by C3b Kuppfer cells in liver
  • cause cold agglutinin syndrome or paroxysmal cold hemoglobinuria
  • ID: spherocytes, agglutination at room temp with + DAT/Coombs
  • triggers: cold exposure
  • causes: idiopathic, EBV, mycoplasma, lymphoproliferative disorders
  • Tx: avoid cold, rituximab, plasma exchange

22

Hemolytic anemia - Microangiopathic

  • intravascular hemolysis as RBCs are shredded by fibrin strands attached to injured endothelial beds
  • associated with aortic stenosis, HUS, TTP, DIC, HELLP, eclampsia, heparin-induced thrombocytopenia, sepsis
  • ID: schistocytes

23

Hemolytic anemia - Paroxysmal nocturnal hemoglobinuria

  • rare X-linked PIGA gene mutation -> decreased anchoring protein -> limited expression of DAF/CD55 and MIRL/CD59 (membrane inhibitor of lysis) -> less regulation of complement-mediated lysis -> lysis
  • ID: hematuria, flow cytometry for CD55/CD59
  • Risks: increased risks of DVT, aplastic anemia
  • Tx: iron/folate supplement, blood transfusion, Eculizumab (c5 inhibitor)

24

Hemolytic anemia - Drug-induced

  • Immune mediated:
    • Hapten mediated: penicillin/cephalosporins coats rbc's and acts as AB hapten
    • Neoantigen: drug induces change in membrane exposing a neoantigen
    • Alteration of antigen: drug induces alteration in membrane component, rendering antigenicity
  • Non-immune mediated: drug is toxic to RBCs with underlying mutationsl ike G6PD deficiency
  • Tx: withdrawl of drug

Offending drugs:

  • ßlactams
  • NSAIDs
  • Quinine
  • Ribavirin

25

hemoglobin

  • tetramer composed of four globin chains + heme
  • chromosome 11 and 16
  • relative expression changes with age

26

embryonic hemoglobin

two zeta + two epsilon

27

HbF

  • 2α/2ϒ
  • Fetal Hemoglobin (higher affinity for O₂)
  • 1% in adults
  • Large ⇑ in β-thal major (90%) & small ⇑ in Sickle cell anemia (8%)

28

HbA

  • 2α/2β
  • Major form of Hgb (97% in adults)

29

HbA2

  • 2α/2δ
  • Minor form of Hgb (2% in adults)
  • ⇑ in β-Thal minor/major
  • nl in Sickle cell trait/dz & α-thal trait

30

HbS

  • Point mutation in beta-globin --> HbS aggregates under low oxygen tension --> fiber formation --> sickle cell erythrocyte --> vascular occlusive crises, severe anemia, infection from encapsulated organisms due to asplenia
  • AA: reduced A
  • AS: 60/40 A/S --> deviation = coinherited thal. or transfusion
  • SS: 0 A, mostly S

31

HbC

  • Point mutation in beta globin
  • If person has HbC and HbS, it acts similar to homozygous for HbS

32

HbE

  • Common structural mutation found in Southeast Asians
  • Results from mutation in exon 1 which activates cryptic splice site --> benign clinical course unless inherited with beta-thalassemia gene = major in severity

33

Alpha thalassemia

  • normally 4 alpha alleles are present on chromosome 16
    • 1 gene: normal RBC, normal clinical
    • 2 genes: microcytic//increased RBC, normal clinical
      • if on same on chromosome = cis deletion* --> worse • a/w inc risk of severe thalassemia in offspring
    • 3 genes: microcytic//increased RBC//inclusions, mid anemia, splenomegaly
      • excess B/G chains form tetramers (HbH/Bart's)
    • 4 genes: hydrops fetalis
  • ID: anisocytosis, poikilocytosis, microcytic, hypochromic, Hb Barts/HbH seen on electrophoresis

34

Beta thalassemia

  • usually point mutations (vs. alpha gene deletion) 
    • B0/B+ -Trait
    • B/B0; B/B+: (reduced A) normal clinical or mild anemia 
      • ID: microcytic, increased RBC, target cells, increased HbA2, increased HbF
    • Intermedia B+/B+: non-transfusion dependent anemia 
      • ID: same as trait
    • Cooley B+/B+; B0/B+; B0/B0: (only A2 and F) transfusion-dependent anemia, hepatosplenomegaly, bone deformities, jaundice, frontal bossing
      • ID: microcytosis, schistocytes, elevated bilirubin, reticulocytosis

35

Bohr Effect

The tendency of certain factors to stabilize the hemoglobin in the tense conformation, thus reducing its affinity for oxygen and enhancing the release of oxygen to the tissues. The factors include increased PCO2, increase temperature, increased bisphosphoglycerate (BPG), and decreased pH. Note that the Bohr effect shifts the oxy-hemolobin saturation curve to the right.

36

Thalassemia severity depends on

degree of alpha/beta chain imbalance

37

Iron absorption

diet --> enterocytes --> Fe2 transported by DMT to apical membrane --> stored as ferritin or transported as FE2 by FPN1 on basolateral membrane --> oxidized to Fe3 and attached to transferrin for circulation --> recycled in macrophages

38

Hepcidin

iron regulatory protein that downregulates ferroportin --> reduced intestinal absoprtion and macrophage release

39


Hemolytic Anemia-Infection

  • bacterial toxin destroys RBC membrane --> intravascular hemolysis
  • parasitic infection of RBCs --> removal of RBCs in spleen

Pathogen                 Target Antigen               Immune Response

M.pneumoniae              I                                       IgM cold

EBV                                  i                                      IgM cold

HSV                                Rh                                   IgG warm

A image thumb
40


Megaloblastic Anemia

  • macrocytic anemia caused by impaired synchrony of nuclear and cytoplasmic maturation
  • ID: large, undefined, many lobed nuclei in granulocytes, epithelial lesons (need good DNA synth in these regions), CHF, jaundice, infections/bleeding, neurologic demise-proprioception, ataxia, somnolence (irreversible), B12 level, increased MMA level, increased Homocysteine level, intrinsic factor test
  • Causes: folate deficiency, cobalami n/b12 deficiency, acute mb anemia, drugs (NO -> disrupts b12 cycling, trimethoprim, DNA agents), inborn errors
  • Tx: b12 (intramuscular)   NOT transfusion

41

Megaloblastic anemia- b12/cobalamin deficiency mechanisms

  • Epi: 4% of elderly, mostly whites (autoimmune related)
  • Sources of b12: vegetables (bacteria from ground), meat, dairy
  • B12 pathway: binds to R factors or intrinsic factor in gut after separating from protein conjugate(alkaline mileu) --> required for uptake --> binds TcII in blood (transporter)
  • Gastic causes
    • Pernicious anemia- heritable/acquired autoimmune
    • Gastrectomy
    • Zollinger-Ellison Syndrome - tumor that leads to secretion of gastric acid --> ulcer -->pH too low for pancreatic enzymes to make alkaline mileu for B12 availability
  • Intestinal Causes
    • Ileal resection - no absorption
    • Blind loop syndrome - part of small bowel has bacterial overgrowth which consumes all the b12
    • Fish tapeworm - compete with host for b12
  • Pancreatic insufficiency
  • Vegetarianism/Veganism
  • Increased predisposition to pernicious anemia

42


Megaloblastic Anemia and CHF

  • pts have very low hb --> kneejerk reaction to transfuse
  • however, pts usually have compensatory expanded plasma volume
  • after transfusion, pts have too much volume and go into CHF --> die
  • most individuals with b12 deficiency even with anemia don't need acute transfusion

43


Megaloblastic Anemia-folate deficiency

  • folate involved in many steps (vs. b12 which is needed for one step)
  • cause: poor nutrition, impaired absorption (sprue), pregnancy, hemolytic anemia/cell turnover
  • tx: folic acid pill
  •