Hematologic Pathophysiology Anemias Flashcards
Erythrocyte
Red blood cell (RBC)
1° function to transport hemoglobin
Transport oxygen to tissues
Contains carbonic anhydrase - enzyme that catalyzes reaction b/w CO2 & H2O to form carbonic acid H2CO3
Produced in the bone marrow
Lifespan 120 days
Individual erythrocyte contains ≈ 300 million Hgb molecules
Reticulocyte
Immature erythrocyte
Day 1 or 2 in the bloodstream
Anemia
↓RBCs Reduced number circulating RBCs Adverse effect ↓oxygen-carrying capacity Hgb <12g/dL Pregnancy - physiologic anemia d/t ↑plasma volume
Mean Corpuscle Volume
Size
Normocytic
Normal sized cells
Microcytic
Smaller than normal size cells
Macrocytic
Larger than normal size cells
Hemoglobin
Four folded globin chains
2 alpha α
2 beta β
Hemolytic anemia
Abnormal hemolysis (RBC breakdown)
Erythropoetin
Glycoprotein
Formed in the kidneys
Epo stimulated when any condition ↓oxygen transport to tissues
Erythropoesis
Red blood cell production
Pluripotent hematopoietic stem cell → proerythroblast → erythroblast (Hgb synthesis begins) → reticulocyte → erythrocyte
Erythroblast loses nucleus
Reticulocyte loses remaining organelles
Polycythemia
↑circulating RBCs Adverse effect ↑blood viscosity Slows blood flow ↓oxygen delivery Significant when Hct >55-60% - Threatens organ perfusion - Risk venous/arterial thromboses Relative polycythemia - dehydration, diuretics, vomiting
Anemia Causes
Blood loss - acute or chronic
↑destruction (thalassemia, hemolytic anemia, sickle cell)
↓production (iron deficiency or autoimmune)
Infectious (malaria, babesia, parvovirus)
Polycythemia Causes
Sustained hypoxia results in compensation
↑RBC mass ↑Hct
Cancer
COPD (not enough O2)
High altitude adaption
Acute Blood Loss
Body replaces plasma fluid portion in 1-3 days leaving low RBC concentration
RBC concentration usually returns to normal w/in 3-6wks
Chronic Blood Loss
Unable to absorb enough Fe (via GI) to make Hgb as rapidly as lost
RBCs produced smaller & have little Hgb inside - microcytic hypochromic anemia
Blood Transfusion Thresholds
10/30 rule
Hgb <10g/dL
Hct <30%
*Hgb <6g/dL clear benefit from transfusion
EBL <15% no intervention
30% replace w/ crystalloids/albumin
30-40% RBC transfusion
>50% massive transfusion 1:1:1 RBC / FFP / Plt
Transfusion Risks
Viral illness transmission (Hep B/C or HIV)
Bacterial infections
TRALI or TACO
Hemolytic transfusion reactions
Iron Deficiency Anemia
Causes
Nutritional Fe deficit - Lower income - Pica Fe stores depletion - Chronic GI bleeds of menstruation Pregnancy ↑RBC mass required during gestation
Iron
Iron required for hemoglobin synthesis
Fe deficiency impairs RBC maturation & diminishes RBC production
Produces microcytic hypochromic anemia
Small & pale RBCs ↓O2 delivery
Iron Deficiency Anemia
Treatment
Fe supplements Elective surgery postpone 2-4mos PO supplements to correct deficiency Continue at least 1yr after corrected Urgent surgery IV w/in few weeks RBC transfusion
Hemolytic Anemia
Accelerated RBC destruction/hemolysis Immune disorders Lifespan <120 days ↑immature erythrocytes (reticulocytes) Unconjugated hyperbilirubinemia ↑lactate hydrogenase ↓haptoglobin
Sickle Cell Anemia
Autosomal recessive disorder caused by single amino acid substitution in β globin that creates sickle hemoglobin (HbS)
β globin mutation leads to HbS polymerization into long stiff chains when deoxygenated → elongated sickle shape
Returns to normal shape when oxygenated
Most common familial hemolytic anemia
Protective against malaria in heterozygotes
HbA
Normal hemoglobin
HbF
Fetal hemoglobin
Newborns w/ sickle cell anemia are asymptomatic until ↓HbF at 5-6mos
Sickle Cell Crisis →
Chronic hemolytic anemia
Ischemic tissue damage
Spleen auto infarction
Chronic Hemolytic Anemia
Repeat sickling damages the RBC membrane
Eventually producing irreversible sickled cells that are removed from circulation
Ischemic Tissue Damage
Localized microvasculature obstruction → acute chest syndrome, joints, stroke(s), retinal damage
Spleen Auto Infarction
↑sepsis risk w/ encapsulated bacteria
Sickle Cell Treatment
Hydroxyurea ↑HbF levels
Anti-inflammatory
↓rate acute chest syndrome & blood transfusions 50%
Stem cell transplants
Autoimmune Anemia
Autoimmune hemolytic anemia (AIHA)
IgG & IgM antibodies directed against RBCs
RBC lifespan severely decreased
Autoimmune Anemia
Causes
Idiopathic
Leukemia
Infectious (mononucleosis)
Drug-induced (PCN or Quinidine)
Autoimmune Anemia
Treatment
Immunosuppression & steroids
Newborn Hemolytic Disease
Incompatibility b/w mother & fetus
- Erythroblastosis fetalis
Fetus inherits RBC antigenic determinants from father that are foreign to the mother
Mother Rh¯
Father Rh+
Baby Rh+
Fetal RBC enter maternal circulation during 3rd trimester & childbirth (fetomaternal bleed)
- Sensitizes mother to paternal RBC antigens leading to IgG anti-D antibodies that cross the placenta & cause fetal RBC hemolysis
2nd pregnancy Rh antibodies attack Rh+ fetus RBCs causing Rh disease (RBC lysis)
Rh
Rhesus factor
Protein found on RBC surface
Genetically inherited
Factor refers to Rh (D) antigen only - most immunogenic all non-ABO antigens
Rho(D) Immune Globin
Rh disease preventable w/ modern antenatal care
RhoGAM IgG anti-D antibody injections
1st antigen-incompatible pregnancy does not produce disease bc mother does not produce anti RBC IgG antibodies (cross the placenta) before delivery
When any incompatibility detected mother often receives an injections at 23wks gestation & birth to prevent antibody development towards the fetus
G6PD Deficiency
Glucose-6-Phosphate Dehydrogenase
X-linked genetic disease
G6PD metabolic enzyme involved in the pentose phosphate pathway (important to RBC metabolism)
Erythrocyte half-life ≈ 60 days
Hemolysis occurs d/t inability G6PD deficient RBCs to protect self from oxidative damage
What precipitates G6PD deficiency?
Infection
DKA
Medications
Fava beans
G6PD Deficiency Peripheral Smears
Bite cells - RBCs w/ severely damaged membranes that have portions bitten off by macrophages to remove patches associated w/ Hgb precipitates known as Heinz bodies leading to intravascular hemolysis
Oxidative Stress
Hemolysis often transient even w/ persistent infection or drug exposure
Older cells lysis leaves younger cells w/ ↑G6PD levels that are resistant to oxidant stress
G6PD Deficiency Treatment
No cure Avoid triggers Treat hemolytic episodes - Hydration - Blood transfusions
Physiologic Polycythemia
Natives who live at altitude 14,000-17,000 feet
Low atmospheric oxygen
↑RBC 30%
Heritable genetic adaption
Polycythemia Vera
PCV
Stem cell or myeloproliferative disorder Hct 60-70%
JAK2 gene mutation - does not stop RBC production when too many present
Excess erythrocytes
Platelets & leukocytes potentially also increase
S/S appear 60-70s
PCV S/S
Cyanosis, headache, dizziness, GI symptoms, hematemesis, & melena
↑total blood volume
Common presenting sign hepatic, coronary, & cerebral thrombosis
30% patients fatal thrombolytic complications
30% mortality r/t leukemia
Viscous & engorged vessels
Blood passes sluggishly through capillaries
↑amount deoxygenated resulting in bluish/ruddy skin appearance
Marrow fibrosis in 10% patients (marrow replaced by fibroblasts & collagen)
PCV Treatment
W/o treatment death d/t vascular complications w/in mos
Minimize thrombosis risk
Phlebotomy helps extend survival 10yrs
Myelosuppressive drugs (Hydroxyurea)
Polycythemia
Anesthesia Management
Thrombosis risk
Reduce Hct prior to surgery - phlebotomy & hydration
Hydration NPO status vs. IV fluids
Continue hydroxyurea (cytoreductive agent)
