Flashcards in Red Blood Cell Disorders Deck (108):
A reduction in red cell mass with consequent decrease in oxygen transport capacity of blood
What are the three clinical parameters used in testing for anemia?
1. Red cell count
2. hemoglobin concentration
*all reflect but do not directly measure red cell mass
What is the result of impaired tissue oxygenation that is associated with anemia?
-shortness of breath
What are the three common mechanisms for establishing anemia?
1. RBC loss (hemorrhage, trauma, GI disease)
2. Decreased survival of RBC (malaria, transfusions, etc)
3. Decreased production of RBC (nutrition deficiency, aplastic anemia, myelophthistic processes)
What is "aplastic anemia?"
a condition that occurs when the body stops producing enough new RBCs
What is polycythemia?
an increase in red cell mass (opposite of anemia)
What are the laboratory tests for anemia?
1. Complete Blood Count (CBC)
2. Blood smear review
3. Reticulocyte Count (new/immature RBC)
4. Iron Indices (transferrin, ferritin, B12, folate)
5. Hemolysis Work-up (bilirubin, haptoglobin, LDH, Coomb's test, Plasma hemoglobin, electrophoresis)
What is the Coomb's Test?
It detects antibodies against RBCs that are present unbound in the patient's serum. In this case, serum is extracted from the blood sample taken from the patient.
("Coomb" rhymes with "womb" = common in prenatal testing)
Hemorrhage can be either _____ or ______.
How much blood loss can a young, healthy individual handle with few symptoms?
(15-20% total blood volume)
Some healthy individuals could experience a ______ response (sweating, weakness, nausea, slowed HR, and hypotension) with a loss of 1000mL. What level of rapid blood loss will produce shock?
With controlled blood loss, how long does it take for interstitial fluid to redistribute into the vascular space? Why does it do this?
-its an attempt to re-expand the vascular volume
RBC production is mediated by _______. RBC production will cause an increase in the ______ count in the peripheral blood.
What is chronic hemorrhage?
the rate of RBC loss exceeds the capacity for RBC regeneration (could be due to decreased iron that is available)
What are two common causes of iron deficiency?
1. Chronic bleeding of GI tract due to ulcer or neoplasm
2. Menorrhagia (heavy menstrual bleeding)
______ anemias are due to decreased red blood cell survival.
Hemolytic Anemia can be either _____ or ______.
extravascular (more common)
What is the difference between intravascular and extravascular hemolytic anemia?
intravascular: destruction of red cells within the circulation
extravascular: destruction of red cells within the reticuloendothelial system (tissue macrophages of the spleen and liver)
Intravascular hemolysis can be immune, such as in _________, or it can be non-immune, such as in _______.
Immune = transfusion reactions
Non-immune = mechanical trauma such as shearing by defective heart valve
What is the key feature of intravascular hemolysis?
decrease in serum haptoglobin
(this causes a problem because hemoglobin >>haptoglobin....so now hemoglobin is excreted in the urine = hemoglobinuria)
True or False: Jaundice is associated with intravascular hemolysis.
hemoglobin>>haptoglobin = hemoglobinuria
hemoglobin = toxic to kidney
iron accumulates in proximal tubules = hemosiderinuria
heme conversion to bilirubin = jaundice
degree of jaundice depends on fxnl capacity of the liver
True or False: Both intra- and extra-vascular hemolysis have immune and non-immune causes.
Immune-related extravascular hemolysis is caused by ____ defects.
Non-immune related extravascular hemolysis is caused by _____ defects.
Give three examples of extrinsic (immune) defects.
2. erythroblastosis fetalis
3. transfusion reaction
Give three examples of intrinsic (non-immune) defects.
1. RBC membrane defects
3. metabolic defects
_______ is also associated with extravascular hemolysis (destruction in the spleen or liver) because free hemoglobin is not released directly into the blood/urine and breakdown products are therefore increased.
True or False: Hepatosplenomegaly is associated with intravascular hemolysis.
false, EXTRAvascular...spleen and liver breakdown the RBC
With extravascular hemolysis, which defect type is inherited?
intrinsic are inherited (non-immune defects)
-lack of globin chains
Classify "hereditary spherocytosis" based on type of hemolytic anemia and defect.
EXTRAvascular hemolysis (spleen or liver)
What is hereditary spherocytosis?
an inherited defect in the red cell membrane that results in less deformability of the cell = can't squeeze through splenic sinusoids = sequestered and destroyed
What do spherocytes look like?
Round balls, not biconcave disks
Hereditary spherocytosis is either a qualitative or quantitative deficiency of which structural protein of the cytoskeleton?
(Spectrin + Spheres = MINE)
M embrane defect
IN trinsic defect
E xtravascular hemolysis
How serious is Hereditary spherocytosis? Is it curable?
its an autosomal dominance inheritance pattern that manifests in adult life with VARIABLE severity
-removal of the spleen results in normal RBC survival but not normal red cell morphology
-following splenectomy, spherocytes ARE still produced but destruction of cells is decreased
Sickle Cell anemia is a type of ________ hemolysis associated with ________ defects of the _______.
Sickle cell anemia is autosomal _____ condition that causes a _______ substitution in DNA between valine and glutamic acid at position 6 in the beta chain.
codominant (occurs in homozygotes for HbS)
single base pair
What happens to the hemoglobin in sickle cell anemia?
the globin chain is defective and causes the hemoglobin to gel upon deoxygenation and assume its sickle shape
Why are the sickled cells a problem?
-they are rigid and vulnerable to splenic sequestration
-they can block the microcirculation causing ischemia and/or infarction
What are the two leading causes of ischemia-related death for patients affected by Sickle Cell Anemia?
1. Acute chest syndrome
True or False: Heterozygotes of sickle cell are clinically asymptomatic because less than half of the hemoglobin is abnormal and HbS concentration is too low to cause sickle shaped cells.
___% of blacks in the USA are heterozygous carriers of sickle cell trait.
True or False: Autosplenectomy is a complication of hereditary spherocytosis.
False, autosplenectomy = sickle cell anemia
What is Thalassemia?
INTRINSIC defect of EXTRAVASCULAR hemolysis
-results in diminished or absent synthesis of either the alpha or beta globin chains of hemoglobin
The type of thalassemia is named for the ____.
globin chain that is produced in a reduced amount
What is the principal clinical manifestation of thalassemia?
anemia (due to decreased hemoglobin production)
thalassemia leads to anemia...thalassemia leads to anemia...thalassemia leads to anemia....thalassemia leads to anemia....thalas.....you get it
True or False: Thalassemia is common in persons of Mediterranean, African, and Southeast Asian descent.
True or False: Thalassemia reduces the impact of malaria.
(both sickle cell and thalassemia change the hemoglobin chains...and they both provide protection against malaria. coincidence?)
In almost all cases of Thalassemia there is a moderate to marked ________ with target cells and ________ of the RBCs on the blood smear.
microcytosis (low MCV= small cells)
basophilic stippling (small dots in the periphery from ribosomes)
What type of deficiency causes a metabolic defect (intrinsic) that results in extravascular hemolytic anemia?
Glucose-6 Phosphate Dehydrogenase (G6PD) deficiency
-sex linked defect (primarily black men)
-red cells are susceptible to oxidant injury usually precipitated by drugs/toxins or infections
-RBC membrane is less flexible and subjected to extravascular hemolysis in the spleen
What is the cytomorphologic hallmark of G6PD deficiency?
-not very flexible
True or False: In the absence of the oxidant trigger (antimalarials, sulfonamides, etc), G6PC deficiency is asymptomatic.
True or False: Bite Cells are more flexible than normal RBCs.
Extrinsic defects associated with extravascular hemolysis. include _______ disease of the newborn and _____ hemolysis.
Hemolytic disease of the newborn occurs _______.
What is another name for hemolytic disease of the newborn (HDN)? What causes it?
-blood group incompatibility between mother and fetus
-fetal RBC expresses antigens inherited from the father that are not present in the mother
-during the third trimester or during delivery, the mother is exposed to the antigens = antibody response
-during future pregnancy, the mother's immune system makes antibodies that cross the placenta and attach to fetal RBC = extravascular hemolysis of RBC in new fetus (liver and spleen)
Which antigens are most important in the Hemolytic Disease of the Newborn?
Rh-negative mothers are given _____ within 72 hours of delivery of an Rh-positive fetus. Why?
-anti-D binds to the Rh-positive fetal cells and removes them from maternal circulation before the mother can generate an antibody response and become sensitized
When does ABO hemolytic disease occur?
Group A or Group B infants born to group O mothers
-certain group O mothers produce IgG anti-A or anti-B in addition to the usually IgM antibodies (lysis of fetal RBC is minimal because fetal cells express A or B antigens weakly)
True or False: IgM does not cross the placenta.
True or False: IgG can cross the placenta.
IgM = M om only
IgG = G oes across
What is a hemolytic transfusion reaction?
a type of intravascular hemolysis
-transfusion of incompatible red cells into a sensitized patient results in binding of antibody (in patient) to antigen (transfused RBC) with activation of complement (lyses antibody-coated RBC) and immediate intravascular hemolysis
Which antigen type is most important in hemolytic transfusion reactions?
Hemolytic transfusion reactions will activate the coagulation cascade with bleeding, _____ failure, ______ and ______.
True or False: Hemolytic Transfusion Reactions are always intravascular.
following transfusion = intravascular
delayed reaction = extravascular
What is autoimmune hemolysis?
-extravascular or intravascular hemolysis reaction
-patient makes antibodies to his/her own RBCs
-antibody coated cells can be removed by the reticuloendothelial system = extravascular
-antibody coated cells can be lysed via complement activation = intravascular
What is the hallmark of autoimmune hemolytic anemia?
What are spherocytes?
--partial loss of red cell membrane (cytoskeleton) makes the RBC ball-like and less deformable
-they are sequestered by the spleen and therefore further enhance the anemia
What test is done to determine presence of autoimmune hemolytic anemia?
The Coomb's Test
-agglutinaton test/RBC aggregation
Name two examples of extrinsic defects contributing to hemolytic anemia that are the result of mechanical trauma. Are these intra- or extra-vascular hemolysis?
1. Cardiac Valve Prosthesis
**INTRAVASCULAR** occuring within the circulation (not the reticuloendothelial/spleen/liver)
How do cardiac valve prostheses contribute to intravascular hemolytic anemia?
-RBCs are disrupted by physical trauma as they pass through areas of turbulence and abnormal pressure related to abnormal valve function
How does DIC contribute to intravascular hemolytic anemia?
-RBCs are lysed as they pass through fibrin clots/strands in the microcirculation
What is a good indication of hemolysis due to mechanical trauma?
-RBC fragments that lost a large portion of their membranes and look mishapen and squashed
True or False: Infections can cause intravascular hemolytic anemia.
-parasites can infect RBCs and cause lysis of RBC during maturation (ex. Malaria)
-different degrees experienced by different patients
How do nutrition deficiencies lead to anemia?
deficiency of a substance needed for erythropoiesis will decrease the red cell PRODUCTION
What are the common nutrition deficiencies associated with anemia?
_____ deficiency is the most common cause of anemia worldwide. It is needed for _______, _______, and a variety of enzymes.
What are the common settings for iron deficiency anemia?
1. inadequate intake (infants, alcoholics, elderly)
2. increased demands (pregnancy, adolescents)
3. increased loss (bleeding, cancer)
What happens to red cells when there is inadequate iron intake?
they become smaller (MICROCYTIC) and contain less hemoglobin (HYPOCHROMIC) than usual
Anemia develops _____ and low levels of Hb can be tolerated with _____ symptoms.
Describe the laboratory results used to study iron deficiency anemia.
- low serum iron
-low serum ferritin
-increased serum iron-binding capacity
-microcytic red cells
-hypochromic red cells
True or False: Iron deficiency anemia may be linked to a more serious condition.
True, chronic blood loss associated with cancer is a possibility
Both B12 and folate are involved (either directly or as cofactors) in the synthesis of _______, one of the _____ bases in DNA.
________ anemia results from folate and B12 deficiency.
Why is it called "megaloblastic" anemia?
B12 + folate = thymidine = DNA base
-impaired DNA synthesis = delayed mitotic division
- nucleus does not mature appropriately but RNA synthesis and cytoplasmic maturation proceed normally
-results = abnormally large red cell precursors (megalobasts), decreased production of mature RBC, and abnormally large red cells (macrocytes)
What is the histological evidence of megaloblastic anemia?
-abnormally large red and white cell precursors
-hypersegmented neutrophils (lobulated)
Megaloblasts accumulate in the _____ and release too few RBCs into the peripheral blood, causing anemia.
Megaloblasts may undergo ______ in the marrow or may be destroyed by ______ cells in the marrow.
True or False: The impairment of DNA synthesis associated with megaloblastic anemia is systemic and affects other rapidly dividing cells in the body.
In what food source is folate found? Is it stored in the body?
in fresh vegetables (absorbed through proximal small intestine)
*body stores are SMALL*
In what food source is B12 found? Is it stored in the body?
in animal foods (absorbed in distal ileum; IF-b12 complex attaches to epithelial cells)
*body stores are LARGE
Absorption of B12 requires _____, a protein produced by parietal cells of the gastric mucosa.
Patients with _____ anemia have autoantibodies directed at intrinsic factor.
(B12 deficient and association with atrophic gastritis)
Which transport protein is responsible for delivering the absorbed B12 to the liver and other cells?
--glycoprotein produced by the salivary glands, protects b12 from acid degradation--
True or False: Folate deficiency can be associated with neurologic symptoms.
False, B12 can!!
Name two examples of anemia associated with decreased red cell production.
1. aplastic anemia
2. myelophthisic anemia
What is aplastic anemia?
a stem cell abnormality results in marked diminution of hematopoiesis
-production of all cellular elements of the blood are decreased
True or False: Over half of the cases of aplastic anemia have no known predisposing cause.
True, but viruses, drugs, and toxins have been implicated
What type of treatment for aplastic anemia has been successful, especially in patients under 40 years old?
bone marrow transplantation
What is myelophthisic anemia?
decreased production of red cells due to replacement (by tumor or fibrosis) of marrow elements
What is often seen on a blood smear in a patient with myelophthistic anemia?
mishapen RBCs resembling teardrops
What type of cancer is usually involved with myelophthistic anemia?
What is polycythemia?
an increase in red cell mass (opposite of anemia)
"polyCYthemia"..."CYke! its not anemia"
______ polycythemia occurs with hemoconcentration of red cells due to dehydration, vomiting, diarrhear, or excessive use of diuretics.
______ polycythemia can be a primary or secondary phenomenon.
When does primary absolute polycythemia occur?
(polycythemia vera) non-regulated proliferation of red cells and myeloid cells
-this is a stem cell disorder and is associated with normal or low levels of EPO
-causes sludging of red cells in capillaries = neurologic and visual abnormalities
How doe you treat polycythemia vera?
removal of excess RBC by phlebotomy
How does secondary absolute polycythemia occur?
through stimuli that increase EPO
ex.: cyanotic heart disease, pulmonary disease, high altitude living, abnormal Hb, tumor producing EPO