Week 3: Hematologic Pathophysiology Anemias Flashcards
Definition of Erythrocyte
a red blood cell
Definition of a Reticulocyte
immature erythrocyte (day 1 or 2 in the blood steam)
Definition of Anemia
deficient number of RBCs
Definition of Mean Corpuscle Volume
size
Definition of Normocytic
normal sized cell
Definition of Microcytic
smaller than normal size cell
Definition of Macrocytic
larger than normal size
Definition of Hemoglobin
four folded globin chains (2alpha 2 beta)
Definition of Hemolytic anemia
abnormal hemolysis (breakdown) of RBCs
Symptoms of Anemia
fatigue pallor hypoxia exercise intolerance syncopy hypovolemia/hypotension irregular heart rate SOB chest pain
Primary Function of an RBC
to transport hemoglobin
transport oxygen to tissue
1 gram of Hgb can combine with
1.34ml of oxygen= 100% saturdation
What is the enzyme in RBCs and what is its function?
carbonic anhydrase
catalyzes reaction between CO2 and H2O to form carbonic acid, H2CO3
How is CO2 transported to lungs?
in the form of HCO3- to be removed
How is erythropoietin stimulated?
any condition that decreases oxygen transport to tissues
a glycoprotein formed in the kidneys
Why do you have elevated reticulocytes in pathological states?
Reticulocytes are immature blood cells, in pathological cases RBCs are needed. Therefore a positive feedback loop occurs releasing reticulocytes from bone marrow
What is the main adverse effect of anemia?
decreased oxygen-carrying capacity
WHO definition of anemia
Hb concentration less than 12 g/dl for women and less then 13g/dl for men
What causes pregnancy “physiologic anemia”?
due to decreased Hct in relation to increased plasma volume
What is polycythemia?
increase in circulating RBCs
What is the main adverse effect of polycythemia?
increase in blood viscosity
What are the main causes of anemia?
blood loss
decreased production
increased destruction
What are the two types of blood loss anemia?
acute blood loss and chronic blood loss
What is acute blood loss?
the body replaces fluid portion of plasma in 1-3 days
leaving low concentration of RBCs
What is chronic blood loss?
cannot absorb enough iron from the gut to make Hgb as rapidly as it is lost
RBCs are produced much smaller and have little Hgb inside- microcytic anemia
What is the 10/30 rule?
transfuse if the Hb level is less then 10g/dl or Hct is <30%
no evidence that Hb levels below this level mandate transfusion
What is the transfusion trigger?
Hb levels below 6g/dl will benefit from transfusion
Risks associated with Transfusion
infections and immunomodulatory effects Hep B, Hep C, HIV cancer re-occurance bacterial infections transfusion related acute lung injury (TRALI) hemolytic transfusion reactions
EBL <15%
rarely requires transfusion
EBL 30%
replacement with crystalloids/ albumins
EBL 30-40%
RBC transfusion
EBL>50%
massive transfusion
may need accompanied with FFP and platelets (1:1:1)
What are the four types of anemia based on mechanism?
decreased production
increased destruction (life span <120 days)
Blood loss
infectious
What are examples of anemia from decreased production? (2)
iron deficiency
autoimmune
What are examples of anemia from increased destruction? (3)
thalassemia
hemolytic anemia
sickle cell
What are examples of anemia from blood loss? (2)
acute
chronic
What are examples of anemia from infectious processes? (3)
malaria parasite destroys RBCs
babesia (parasite usually spread by ticks) causes RBC hemolysis
Parvovirus (fifth disease) virus inhibits erythropoiesis
What are three types of anemias based on morphology?
microcytic
normocytic
macrocytic/megaloblastic
What is microcytic anemia? Causes?
mean corpuscular volume <80fL
iron deficiency
thalassemia
What is normocytic anemia? Causes?
mean corpuscular volume 80-100fL
sickle cell anemia
chronic kidney disease, acute blood loss, aplastic anemia
G6PD deficiency
What is macrocytic/ megaloblastic anemia? Causes?
defects in nuclear maturation
folic acid and vitamin B12 deficiency
liver disease, alcoholism
How do you treat iron deficiency anemia?
oral iron: if elective surgery can be postponed for 2-4 months to allow for correction
IV iron- urgent surgery within a few weeks
RBC transfusion
How long do you need to continue oral iron supplements?
1 year after the source of blood has been corrected
What is hemolytic anemia?
accelerated destruction of RBCs
removed to quickly or lysed to early
RBC life <120 days
What will you find in blood test for hemolytic anemia?
increased immature reticulocytes
unconjugated hyperbilirubinemia/jaundice
increased lactate dehydrogenase (an enzyme released from lysed RBCs)
decreased haptoglobin (a plasma protein that binds free hemoglobin)
What is sickle cell anemia?
autosomal recessive disorder caused by a single amino acid substitution in beta globin that creates sickle hemoglobin
What is the most common familial hemolytic anemia?
sickle cell anemia
What is sickle cell anemia protective against?
malaria
Pathogenesis of Sickle Cell anemia
mutation in beta globin that leads to the polymerization of sickle hemoglobin (HbS) into long, stiff chains when it is deoxygenated
What is the most important variable that determines whether HbS-containing red cells undergo sickling is
the intracellular concentration of other hemoglobins
HbA
normal hemoglobin
HbF
fetal hemoglobin
What are consequences of Sickling RBCs?
chronic hemolytic anemia
ischemic tissue damage with episodic pain
spleen auto infarction
What microvascular is affected in sickling RBCs?
acute chest syndrome
joints
strokes
retinal damage
Treatments for Sickle Cell
hydroxyurea
stem cell transplants
How does hydroxyurea help?
raises HbF levels
anti-inflammatory
What is autoimmune anemia or autoimmune hemolytic anemia?
antibodies IgG and IgM are directed against a person’s own RBCs
RBCs lifespan is severely decreased
What are causes of autoimmune anemia?
idiopathic
leukemias
infectious (mononucleosis)
drug-induced (pencillins, quinidine)
What is the treatment to autoimmune anemia?
immunosuppressants and steroids
Describe hemolytic disease of the newborn
incompatibility between mother and the fetus
erythroblastosis fetalis
fetus inherits red cell antigenic determinants from the father that are foreign to the mother
fetal red cells can enter maternal circulation during 3rd trimester and childbirth this sensitizes mother to paternal red cell antigens and leads to productoin of IgG anti-D red cell antibodies that cross the placenta and cause hemolysis of fetal red cells
Fetus has what antigen and mother is?
fetus is RhD antigen positive and mother is RhD antigen negative
Rh Factor
a protein found on the surface of red blood cells
Glucose 6 phosphate dehydrogenase deficiency
X linked genetic disease from the lacking of enzyme, G6PD which is involved in the pentose phosphate pathway
What is the 1/2 life of RBCs with G6PD?
60 days
Why does hemolysis occur with G6PD?
the inability of G6PD RBCs to protect itself from oxidative damage
What can precipitate G6PD?
infection
DKA
medications
fava bean
Peripheral smears of G6PD
bite cells
Oxidative stress is
transient hemolysis with persistent infection or drug exposure, because lysis of older cells leaves younger cells with higher levels of G6PD that are resistant to oxidant stress
What are drugs can induce oxidative stress?
metoclopramide penicillin and sulfa methylene blue hypothermia acidosis hyperglycemia infection
Treatment of G6PD is
no cure
avoid triggers
treat hemolytic episodes with hydration and blood transfusions
How do you develop polycythemia?
sustained hypoxia results in compensatory increase in RBC mass and Hct
What is significant polycythemia? why?
Hct >55-60%
threatens vital organ perfusion
at risk for DVT/ arterial thrombosis
What is relative polycythemia?
concentrated Hct
what can cause relative polycythemia?
dehydration, diuretics and vomitting
Where does Physiologic Polycythemia occur?
natives who live at altitudes of 14,000-17,000 ft
atmospheric o2 is low
What is the RBC count in physiologic polycythemia compared to normals?
rises approximately 30% compared to non-extreme altitude
What causes secondary polycythemia?
due to hypoxia (cardiac disease including congenital heart with R to L shunts and low CO) and pulmonary disease (extreme obesity/ pickwickian syndrome)
due to renal disease
surreptitious use of erythropoietin by high performance athletes
What is polycythemia vera?
stem cell (or myeloproliferative) disorder in which Hct may be as high as 60-70% instead of normal 40-45%
mutation in JAk2 gene (lacks ability to halt production of RBCs when enough present)
produces excess erythrocytes and number of platelets and leukocytes may also be increased
when do most symptoms of polycythemia vera present?
6-7th decade of life
what are the symptoms of PCV?
cyanosis, headache, dizziness, gastrointestinal symptoms, hematemesis, and melena
What are the effects of PCV?
total blood volume increases
viscous and engorged vessels
blood passes sluggishly through skin capillaries and a greater amount becomes deoxygenated resulting in bluish/ruddy appearance
What is seen in 10% of PCV patients?
marrow fibrosis
Treatment of PCV
death from vascular complications occurs within months minimize thrombosis risk avoid dehydration phlebotomy myelosuppressive drug ruxolitinib
Anesthesia and PCV
at risk for thrombosis (reduce Hct prior to surgery)
hydration NPO status vs IV fluids
continue hydroxyurea
