L14- RBC Pathology I Flashcards
define the following:
(1) reticulocytosis
(2) erythroid hyperplasia
(3) pancytopenia
1- elevated serum reticulocytes
2- excess precursor cells in bone marrow
3- low RBCs, low WBCs, low platelets
Hb makes up __% of the dry weight of RBCs (include why that is important to lab testing)
95%- means there cannot be hyperchromatic RBCs since there really can’t be that much more Hb in RBCs
describe the breakdown of Hb
HbA, α2β2, 95%
HbA2, α2δ2, ~2%
HbF, α2γ2, ~2 (may slightly inc during pregnancy)
what are the advantages of the RBC shape
Biconcave Disc
=> large SA for Hb-O2 interactions –> reach maximal saturation of Hb
-allows for deformability and passage through small capillaries and splenic sinusoids
Define Anemia, then give the practical evaluation of anemia in a clinical setting
Defn: reduction (below normal limits) of total circulating RBC mass
- in practice it is determined throught [Hb] OR packed cell volume / Hematocrit
- normal [Hb] = 12-15 g/dL
- normal Hc = ~45%
Note- [Hb]:Hc is about 1:3
define MCV
mean cell volume
-average volume of RBC in femtoliters (10^-15L)
define MCH
mean cell hemoglobin
-average Hb content per RBC in picograms
define MCHC
mean cell hemoglobin concentration
-average [Hb] in given volume of packed RBCs in g/dL
define RDW
red cell distribution width
-coefficient of variation of RBC volume (since older RBCs have dec volume)
-normal ~12.5, it will inc with hemolysis
Give the symptoms of Anemia at different severities
Mild: asymptomatic
Moderate (poor O2 supply to tissues): easy fatigability, loss of energy, HAs, fainting/dizziness, SOB, palpitations
(more prominent during exercise)
Severe: angina, CHF, confusion
Note- Sxs are more prominent in rapid onsets; in slow onsets, even severe anemia can be asymptomatic
list the clinical signs of anemia
- pallor
- nail changes
- hemic murmurs
- Inc pulse rate and RR –> inc SV –> high output cardiac failure (if severe enough)
how are anemias classified
- morphological changes of RBCs
- pathophysiological mechanisms causing anemia
what are the morphological classifications of anemia
1) Normo-, Hypo-chromic: degree of hemoglobinization (or pinkness of) of RBCs
2) Macro-, Normo-, Micro-cytic: based on RBC size
list the 3 morphological classifications of anemia seen in practice (include blood work results)
Microcytic Hypochromic anemias: low intracellular [Hb], low MCV
Normochromic Normocytic anemia: normal intracellular [Hb], normal MCV
Normochromic, Macrocytic anemia: normal intracellular [Hb], high MCV
list the microcytic hypochromic anemias
- Fe deficiency
- anemia of chronic disease (also in normochromic, normocytic)
- Pb poisoning
- thalassemia
list the normochromic normocytic anemias
- acute blood loss
- hemolytic anemia
- anemia of chronic disease (also in hypochromic, microcytic)
list the normochromic macrocytic anemias
- cobalamin/B12 deficiency
- folate/B9 deficiency
what are the mechanism classifications of anemia
1) Accelerated RBC loss/destruction: blood loss, inc destruction / hemolytic anemia
2) Impaired RBC production: defective stem cell, abnormal RBC proliferation / maturation, bone marrow replacement, others
response of body to blood loss depends on….
- rate of blood loss
- internal v external loss
Anemia due to blood loss is divided into….
- acute bleeding (hemorrhage)
- chronic blood loss (in stool, menses, etc)
Anemia due to acute hemorrhage:
- (1) is the immediate concern
- (2) type of anemia
- (3) compensation
1- hypovolemia
2- normocytic, normochromatic anemia
3- rise in EPO –> reticulocytosis
describe the mechanism of anemia in chronic blood loss (include type of anemia)
(note- hypovolemia is not a concern)
- Fe stores are gradually depleted –> underproduction of RBCs
- microcytic hypochromatic anemia
(1) list the common features of hemolytic anemias
(2) how are hemolytic anemias classified
1- shortened RBC life span –> inc EPO / erythropoiesis + accumulation of Hb breakdown products
2:
i) by site, intravascular or extravascular
ii) by cause, intrinsic or extrinsic to RBCs
list and provide some examples of the 3 causes Intravascular Hemolysis
- Mechanical Injury: defective cardiac valves, microvascular thrombi, heat
- Complement Fixation: Ab coated RBCs
- Infections: intracellular parasites (malaria), microbial toxins (clostridia)
Extravascular Hemolysis:
- caused by defects that will cause (1) by (2) cells in the (3), therefore it is associated with (4) in relation to (3)
- (5) and (6) are the common mechanisms by which (1) occurs
1- RBC destruction
2- phagocytes
3- spleen
4- splenomegaly
5- RBCs rendered less deformable (spherocytosis, sickle cell)
6- RBCs rendered foreign (immune mechanism- Ab coating)
Peripheral Blood test results that show evidence of hemolytic anemia
normochromic normocytic anemia with polychromasia (bluish tinge) +/- nucleated RBCs
Bone Marrow test results that show evidence of hemolytic anemia
(not usually done)
erythroid hyperplasia
Plasma/Serum test results that show evidence of hemolytic anemia
- elevated unconjugated bilirubin
- elevated LDH
- elevated free Hb levels (ntravascular hemolysis
-dec or absent Haptoglobin levels
Urine test results that show evidence of hemolytic anemia
- hemosiderinuria
- hemoglobinuria (intravascular hemolysis)
Intravascular Hemolysis:
(1) bilirubin levels
(2) haptoglobin levels
(3) hemoglobinuria
(4) hemosiderinura
(5) reticulocyte levels
(6) LDH levels
(7) free Hb levels
(8) splenomegaly
(9) Fe recycling
1- inc 2- absent 3- positive 4- positive 5- inc 6- inc 7- large inc 8- absent 9- minimal
Extravascular Hemolysis:
(1) bilirubin levels
(2) haptoglobin levels
(3) hemoglobinuria
(4) hemosiderinura
(5) reticulocyte levels
(6) LDH levels
(7) free Hb levels
(8) splenomegaly
(9) Fe recycling
1- large inc 2- dec 3- negative 4- negative 5- inc 6- inc 7- inc 8- present 9- maximal
list the common Intrinsic RBC defects causing hemolytic anemia
(usually hereditary)
-Membrane Defect: hereditary spherocytosis
- Enzyme Defect: G6PD deficiency
- Hb Defect: sickle cell, thalassemia
- PNH (paroxysmal nocturnal hemoglobinuria)- ONLY ACQUIRED ONE
list the common Extrinsic RBC defects causing hemolytic anemia
(usually acquired)
Immune mediated damage: autoimmune, drug-associated, transfusion reaction
Non-immune damage: mechanical trauma, infections, chemicals, hypersplenism
Hereditary spherocytosis stems from a defect in (1) in the RBC leading them to have (2) shape and a (3) life span.
- highest incidences in (4) part of the world
- usually inherited in (5) pattern
1- membrane skeleton
2- spheroid shape –> less deformable
3- 10-20 days
4- northern Europe
5- AD (75% of cases)
Hereditary spherocytosis:
- (1) list affected proteins
- (2) pathogenesis (hint- 5 steps)
1- ankyrin, band 3, spectrin, band 4.2
2- reduced membrane stability –> loss of fragments (normal shearing forces in circulation) –> more spherical RBCs –> cannot transverse splenic sinusoids –> phagocytosis / destruction by splenic macrophages (=> splenomegaly)
list the clinical features of Hereditary Spherocytosis (Sxs)
Anemia: mild to moderate, 25% asymptomatic, minority are severely anemic from birth
Splenomegaly
Jaundice: unconjugated hyperbilirubinemia (continous hemolysis)
_____ along with hereditary spherocytosis can induce aplastic / hemolytic crises
parvovirus B19 infection
hereditary spherocytosis Tx
- supportive
- splenectomy –> corrects anemia, spherocytosis persists
Hereditary Spherocytosis diagnosis and lab findings
- FHx
- CBC for anemia
- evidence of hemolysis
- elevated MCHC
- positive Osmotic fragility test
- negative Coombs test
Peripheral blood: normochromic normacytic anemia, spherocytes, polychromatic cells (w/ or w/o nucleated RBCs), Howell-Jolly bodies (post-splenectomy)
explain osmotic fragility test
- confirms presence of spherocytes
- spherocytic RBCs lyse prematurely when exposed to inc hypotonic salt solutions
explain the coombs test for hereditary spherocytosis
- spherocytes are seen in hereditary spherocytosis and in autoimmune
- Neg. coombs test confirms hereditary spherocytosis
Test is specifically for autoimmune hemolysis
G6PD deficiency is inherited in (1) fashion. List the specific alleles / variants for G6PD, (2).
1- X-linked (affects mainly males)
2:
- G6PD A+, high enzyme levels, no hemolysis
- G6PD A-, lower enzyme levels, acute intermittent hemolysis
- G6PD Mediterranean, more severe than other A- variants
- G6PD B, normal variant
G6PD A- variant:
- normally seen in (1) people
- characterized by (2)
1- 10% of american blacks
2- normal enzyme activity, but dec half-life
G6PD Mediterranean variant:
- normally seen in (1) people
- (2) is the reason why it may have high persistance
1- Middle Eastern populations
2- protects against malaria
describe the parameters that allow for the pathogenesis of G6PD deficiency event to occur
Parameters:
- abnormal enzyme are misfolded –> prone to proteolytic degradation
- enzyme is not made, no nucleus in RBC
- Note: G6PD A- half-life is moderately reduced, Mediterranean is severely reduced
describe the pathogenesis of a G6PD deficiency event
1) RBC exposed to oxidants / oxidative stress
2) SH-groups on globin chains of Hb are oxidized
3) precipitation of denatured globins on RBC membrane
4) Heinz body formation
5a) for severe membrane damage –> intravascular hemolysis occurs
5b) less affected RBCs go to spleen –> macrophages ‘bite out’ inclusions => bite cells —> extravascular hemolysis
describe the clinical presentation of G6PD deficiency
- Acute Hemolysis: intravascular hemolysis 2-3 days after exposure to infection, drugs (antimalarials, Sulfas), foods (fava beans)
- Neonatal jaundice, uncommon
- Chronic low grade anemia, uncommon: lacks known environmental triggers
Triggers for G6PD deficiency:
(1) common drugs
(2) common foods
1- antimalarials (primaquine), sulfonamides
2- fava beans
Diagnosis of lab findings for G6PD deficiency
- clinical Hx
- CBC w/ anemia + evidence of hemolysis
- Peripheral blood: normochromic, normocytic anemia, heinze bodies, polychromatic cells (+/- nucleated RBCs), bite cells
- G6PD enzyme assay (complete during hemolytic episodes, repeat 3 mos. after)
