Hematologic Pathophysiology Anemias Flashcards
Macrocytic refers to
larger than normal size cells
Microcytic refers to
smaller than normal size cells
Reticulocytes are
immature erythrocyte (day 1 or 2 in the blood stream)
Hemoglobin is
four folded globin chains (2 alpha & 2 beta)
Hemolytic anemia is
abnormal hemolysis (breakdown) of RBCs
Primary function of RBC is to
transport hemoglobin
-transport O2 to tissue
1 gm of hemoglobin can combine with
1.34 mLs of oxygen= 100% saturation
Red blood cells are produced in
bone marrow
Any condition that decreases oxygen transport to tissues will
stimulate erythropoietin- a glycoprotein formed in the kidneys
Red blood cells contain
carbonic anhydrase- enzyme that catalyzes the reaction between CO2 & H2O to form carbonic acid H2CO3 transport CO2 (in the form of HCO3-) to lungs for removal
RBC production and maturation occurs with
pluripotent stem cell–> proerythoblast–> erythroblast–> reticulocyte–> erythrocyte
Causes of anemia include
blood loss, decreased production, & increased destruction
Describe polycythemia
increase in circulating RBCs- main adverse effect is increased blood viscosity
Anemia is the
reduced number of circulating RBCs
The main adverse effect of anemia is
decreased oxygen-carrying capcaity
WHO defines anemia as hemoglobin concentration less than
12 g/dL for women & less than 13 g/dL for men
Anemia in pregnancy is due to
decreased Hct in relation to increase plasma volume
With acute blood loss, the body replaces fluid portion of
plasma in 1-3 days- leaving a low concentration of RBCs
the RBC concentration usually returns to normal within 3-6 weeks
Chronic blood loss anemia is when
cannot absorb enough iron from the gut to make hemoglobin as rapidly as it is lost
RBCs are then produced much smaller with little Hgb inside- microcytic hypochromic anemia
Transfusion preoperatively in asymptomatic patients for elective surgery
are rare
Describe the 10/30 rule.
transfuse if the hemoglobin level is <10 g/dL or the Hct is <30%
- no evidence that hemoglobin levels below this level mandate transfusion
There is clear evidence that hemoglobin levels below
6 g/dL benefit from transfusion
When deciding whether to transfuse for a procedure, we must take into account
patient’s medical history, ongoing bleeding, and risk of end-organ dysfunction
e.g. active coronary artery disease may require lower transfusion thresholds
RBC transfusions can transmit
Hep B, Hep C, HIV
Immunomodulatory effects of transfusion include
cancer reoccurrence, bacterial infections, transfusion related acute lung injury, & hemolytic transfusion reactions
Describe estimated blood loss & transfusion thresholds.
EBL <15%- rarely requires transfusion
EBL 30% replacement w/ crystalloids/albumins
EBL 30-40%- RBC transfusion
EBL >50% massive transfusion protocol- may need accompanied FFP & platelets (1:1:1 ratio)
Describe types of anemia that are decreased production problems.
iron deficiency
autoimmune
Describe types of anemia that are increased destruction (life span <120 days).
thalassemia, hemolytic anemia, sickle cell
Describe types of anemia that include blood loss.
acute & chronic
Describe types of anemia that fall under the infectious category.
malaria parasite destroys RBCs
Babesia (parasite usually spread by ticks) causes RBC hemolysis
parovirus (“fifth disease”) virus inhibits erythropoiesis
Types of anemia based on morphology include:
microcytic, normocytic, & macrocytic/megaloblastic
Iron deficiency anemia is the result of
nutritional deficiency of iron- common in infants, small children, & developing countries
- depletion of iron stores (e.g. chronic GI bleeds or mensturation)
- pregnancy
Iron deficiency anemia results in pregnancy because
of the increased RBC mass required during gestation
Mild anemia may require
preop iron
Hb 9-12 g/dL
Pica is
the drive to consume non foodstuff
because they’re not getting enough iron
Depletion of iron stores are due to
unable to absorb sufficient iron from the diet at the same rate as chronic loss
_______ is required for hemoglobin synthesis
Iron
Iron deficiency impairs
red cell maturation & diminishes red cell production
-produces a microcytic hypochromic anemia
The most important adverse effect of anemia is
decreased O2 delivery
Treatment of iron deficiency includes:
oral iron–> if elective surgery can be postponed for 2-4 weeks to allow correction of the iron deficiency
should be continued for at least 1 year after the
source of blood loss has been corrected
IV iron–> urgent surgery within a few weeks
RBC transfusion
Hemolytic anemia is due to
accelerated destruction (hemolysis) of RBC’s
- removed too quickly or lysed too early
often seen in immune disorders
RBC lifespan is
<120 days
Blood tests for hemolytic anemia include
increased immature erythrocytes (reticulocytes)
unconjugated hyperbilirubinemia/jaundice
increased lactate dehydrogenase (an enzyme release from lysed RBCs)
decreased haptoglobin (a plasma protein that binds free hemoglobin)
Sickle cell anemia is an
autosomal recessive disorder caused by a single amino acid substitution in B-globin that creates sickle hemoglobin
The most common sickle cell anemia is
familial hemolytic anemia
Sickle cell anemia is protective against
malaria in heterozygotes
“aka carrier”
In sickle cell anemia, the mutation in B-globin leads to
polymerization of sickle hemoglobin into long, stiff chains when it is deoxygenated
- cell assumes an elongated sickle shape but it returns to its normal shape when oxygenated
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
Newborns with sickle cell anemia are asymptomatic until
HbF falls at 5-6 months of age
Consequences of sickling of RBCs include:
chronic hemolytic anemia
Ischemic tissue damage with episodic pain
spleen auto infarction
Describe chronic hemolytic anemia as a result of sickling of RBCs
repeat sickling damages the red cell membrane, eventually producing irreversible sickled cells that are removed from circulation
Describe ischemic tissue damage with episodic pain as a result of sickling of RBCs.
Localized obstruction in the microvasculature
- acute chest syndrome
- joints
- strokes
- retinal damage
Describe the implications of spleen auto infarction.
increases the risk of sepsis with encapsulated bacteria
Treatment for sickle cell includes:
hydroxyurea
stem cell transplants
Describe what hydroxyurea does to treat sickle cell.
raises HbF levels
anti-inflammatory
decreases the rate of acute chest syndrome & blood transfusions by 50%
Autoimmune anemia is also known as
autoimmune hemolytic anemia
Autoimmune anemia is due to
antibodies (IgG & IgM) directed against a person’s own RBCs
RBCs lifespan is severely decreased
Causes of autoimmune anemia include
idiopathic
leukemias
infections (i.e. mononucleosis)
drug-induced (i.e. penicillin, quinidine)
Treatment for autoimmune anemia is
immunosuppression & steroids
Hemolytic disease of the newborn is due to
incompatibility between the mother & the fetus- erythroblastosis fetalis
fetus inherits red cell antigenic determinants from the father that are foreign to the mother
Hemolytic disease of the newborn results when the fetus is
RhD-antigen positive and mother is RhD antigen negative
Fetal red cells can enter maternal circulation during 3rd semester and childbirth (fetomaternal bleed) which
sensitizes the mother to paternal red cell antigens and leads to production of IgG anti-D red cell antibodies that cross the placenta & cause hemolysis of fetal red cells
Rhesus (Rh) factors is a
protein found on the surface of RBCs
-its genetically inherited
________ antigen is the most immunogenic of all the non-ABO antigens
Rh(D)
Rh(D) status of an individual is normally described with
a positive or negative suffix after the ABO type (e.g. someone who is A positive has the A antigen and the Rh(D) antigen, whereas someone who is A negative lacks the Rh(D) antigen
Generally, the first-antigen incompatible pregnancy
does not produce disease because the mother does not produce anti-red cell IgG antibodies (the type that cross the placenta) before delivery
When an Rho(D) incompatibility is detected, the mother receives an
injection at 28 weeks gestation and at birth to avoid the development of antibodies towards the fetus
The vast majority of Rh disease is preventable in modern antenatal care by injections of
IgG anti-D antibodies (Rho(D) immune globulin) aka RhoGAM
G6PD deficiency is an _______
X linked genetic disease
G6PD is a
metabolic enzyme involve in the pentose phosphate pathway which is important in RBC metabolism
The half life of erythrocytes in G6PD is approximately
60 days
G6PD can be precipitated by
infection, DKA, medications, fava beans
In G6PD, ________ occurs due to inability of G6PD deficient RBCs to protect itself from
hemolysis; oxidative damage
G6PD deficiency peripheral smears appear to have
“bite” cells, red cells with severely damaged membranes that have portions “bitten off” by macrophages removing patches of membrane with associated hemoglobin precipitates known as Heinze bodies leading to intravascular hemolysis
In G6PD, the hemolysis is often transient, even 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
For patients with G6PD, avoiding risk of hemolysis includes
not exposing the patient to oxidative drugs such as: metoclopramide penicillin & sulfa methylene blue hypothermia acidosis hyperglycemia infection
Treatment of G6PD deficiency includes
no cure
avoid triggers
treat hemolytic episodes with: hydration & blood transfusions
Polycythemia is the result of
sustained hypoxia which results in compensatory increase in RBC mass & Hct
increases blood viscosity which slows blood flow & decreases oxygen delivery
Polycythemia is significant when
Hct >55-60%
- threatens vital organ perfusion
- at risk for venous/arterial thromboses
Relative polycythemia is also known as ____ and can be a result of
concentrated
-dehydration, diuretics, & vomiting
Physiologic polycythemia occurs in
natives who live at altitudes of 14,000 to 17,000 feet
some evidence of heritable genetic adaptation- Tibet in Asia, Andes of the Americas, Ethiopia in Africa
Polycythemia vera is a
stem cell (or myeloproliferative) disorder in which Hct may be as high as 60-70% instead of the normal 40-55%
Polycythemia vera is due to the mutation of the
Jak2 gene which doesn’t stop the production of RBC when there are already too many present
-tyrosine kinase JAK2 is a signaling molecule in pathways downstream of the erythropoietin receptor & other growth factor receptors
Most symptoms of polycythemia vera appear in the
6th & 7th decade of life & include cyanosis, HA, dizziness, GI symptoms, hematemesis, & melena
With polycythemia vera, there are excess erythrocytes and possibly
platelets & leukocytes
Without treatment for polycythemia vera,
death from vascular complications occurs within months
- minimize risk of thrombus
- phlebotomy- helps extend survival by 10 years
- myelosuppressive drugs (e.g. hydroxyurea)
Anesthetic considerations for patients with polycythemia vera include
at risk for thrombosis- reduce Hct prior to surgery- phlebotomy & hydration
Hydration- NPO status vs. IV fluids
continue hydroxyurea (cytoreductive agent)
Effects of polycythemia vera include
total blood volume increases–> hepatic, coronary or cerebral thrombosis is common presenting sign
viscous & engorged vessels–> increases viscosity
blood passes sluggishly through skin capillaries & a greater amount becomes deoxygenated resulting in a bluish/ruddy skin appearance
Marrow fibrosis (the marrow is replaced by fibroblasts & collagen)
30% of patients with polycythemia vera will die from
cancer-leukemia (30%) thrombotic complications (30%)
