Lecture 17 - Red Blood Cell Disorders Flashcards
what is the definition of anemia?
reduction in red cell mass, with consequent decrease in oxygen transport capacity of the blood
what are the clinical parameters used in testing for anemia?
- Red cell count
- Hemoglobin concentration
- hematocrit
- All of these reflect but do not directly measure the red cell mass
Accepted “normal” levels for anemia vary with ____, ___, and _____ ______
age, sex, and geographic location
Anemia results in impaired tissue oxygenation and is manifested clinically by what three features?
- Exertional shortness of breath
- Weakness
- Fatigue
- Pallor
what does polycythemia denote?
increase in red call mass
Anemias can be classified into three broad categories based on the mechanism in which red cell mass is decreased, what are the categories?
- Blood loss
- Decreased red cell production
- Decreased red cell survival
hemorrhage (acute), trauma (acute), GI or GYN disease (acute or chronic, occult blood loss) are examples of what category of anemia?
RBC (blood) loss
iron deficiency anemia, vitamin B12 deficiency, folate deficiency, aplastic anemia, and myelophthisic anemias is in what category of anemia?
decreased RBC production
mechanical trauma, transfusion reactions, hereditary spherocytosis, hemoglobinopathies, thalassemias, G6PD deficiency, erythroblastosis fetalis, malaria are in what category of anemia?
decreased RBC survival
young healthy subjects can tolerate rapid loss of how many mL with few symptoms, but some will have a vasovagal response - sweating, weakness, nausea, slow heart rate, hypotension
500-1000 mL (up to 15-20% of total blood volume)
If blood loss is controlled, interstitial fluid will redistribute within how many hours into the vascular space in an attempt to re-expand the vascular volume
within 24 hours
Red cell loss of 1000-1500 mL produces what side effects?
lightheadedness, orthostatic hypotension
when there is Red cell loss of 1500-2000 mL all patients are symptomatic and experience what side effects?
- thirst
- shortness of breath
- loss of consciousness
- sweating
- rapid pulse
- decreased blood pressure
- clammy skin
rapid loss of how may mL of RBC produces shock?
2000-2500 mL
The loss of RBC stimulates increased production, mediated by ______, resulting in an increase in the reticulocyte count in the peripheral blood
erythropoietin
chronic blood loss causes anemia when the rate of loss exceeds the capacity for RBC regeneration or when ___ reserves are depleted
iron
Chronic GI hemorrhage due to ulcer or neoplasm, or GYN hemorrhage (menorrhagia) are important causes of ____ deficiency
iron
hemolytic anemias are characterized by what
shortened red cell survival and retention of products of red cell destruction (iron)
increased erythropoietin production results in increased red cell production with a _____ to compensate for the anemia
reticulocytosis
In hemolytic anemias, red cell destruction can occur in what two areas?
within the circulation (intravascular hemolysis) or in the reticuloendothelial system including the spleen (extravascular hemolysis)
In intravascular hemolysis the destruction of RBC happens where?
within the circulation
Mechanical trauma (e.g. from a defective heart valve) and hemolytic transfusion reaction are examples of what type of hemolysis?
intravascular
Hemoglobin released from RBC into circulation (hemoglobinemia) is bound to ________, a binding protein and cleared from the circulation by the liver.
haptoglobin
When plasma hemoglobin levels exceed amount of available haptoglobin, free hemoglobin is excreted from where?
urine (hemoglobinuria)
Hemoglobin is toxic to the kidney, and iron that accumulates in what cells of the kidney as a breakdown product of hemoglobin is lost in the urine when these cells are shed (hemosiderinuria)
in the proximal tubular cells in the kidney
Conversion of heme (derived from hemoglobin) to bilirubin leads to what two clinical side effects
hyperbilirubinemia and jaundice
The degree of jaundice is dependent on what?
the functional capacity of the liver and rate of hemolysis
*Levels of haptoglobin are characteristically low
what is Extravascular hemolysis?
destruction of RBC in reticuloendothelial system (spleen, liver)
hereditary spherocytosis, sickle cell anemia, erythroblastosis fetalis (antibody-mediated hemolytic disease of the newborn) are examples of what?
Extravascular hemolysis
Damaged or abnormal RBC are removed where?
spleen - where hemoglobin is broken down intracellularly
in extravascular hemolysis, free hemoglobin is not released directly into the blood and urine, but are hemoglobin breakdown products increased or decreased and what side effect can result?
products are increased (hyperbilirubinemia) and jaundice may result
In extravascular hemolysis, spleen and liver may become enlarged for what reasons?
these are sites of removal of RBC from the circulation
in extravascular hemolysis chronically elevated levels of bilirubin can promote formation of what?
gallstones
Hemolytic anemias are classified by the mechanism of red cell destruction into intrinsic defects (hemoglobin production, membrane abnormality) which are usually ________, and extrinsic defects (antibody, mechanical trauma) which are usually _____ _____
intrinsic defects which are usually INHERITED and extrinsic defects which are usually ACQUIRED abnormalities
hereditary spherocytosis is extravascular hemolysis and an example of what type of intrinsic defect
membrane defect
is hereditary spherocytosis autosomal dominant or recessive in most cases?
autosomal dominant
*Manifest in adult life, severity is variable
in hereditary spherocytosis, removal of spleen results in normal red cell ____ but not normal red cell ____
normal red cell SURVIVAL but not normal red cell MORPHOLOGY
*Production of spherocytes continues, but following splenectomy their destruction is decreased
sickle cell anemia is extravascular hemolysis and an example of what type of intrinsic defect?
abnormal hemoglobin
In sickle cell anemia, under low oxygen conditions the abnormal hemoglobin ________, causing the RBC to assume a sickle shape
polymerizes
Sickle cell disease is characterized by what?
- severe anemia
- vaso-occlusive crises - including acute chest syndrome and stroke
what are some complications of sickle cell anemia?
- autosplenectomy
- painful crises
- leg ulcers
- retinal
- renal thromboses
What percent of blacks in the USA have sickle cell trait (heterozygotes) and are essentially asymptomatic because less than half of the hemoglobin is abnormal and the concentration of HbS within the RBC is insufficient to cause significance?
8%
What is a small advantage of sickle cell anemia?
small but significant resistance to malaria
what is thalassemia
lack of globin chains
- An inherited defect (autosomal codominant) that results in diminished or absent synthesis of either the alpha or beta globin chains of hemoglobin
Decreased globin production results in decreased hemoglobin production and what is the principal clinical manifestation?
anemia is the principal clinical manifestation
What are some clinical manifestations of thalassemia?
they vary from severe transfusion-dependent anemia and iron overload (thalassemia major) to mild anemia (thalassmia minor)
- In almost all cases there is a moderate to marked microcytosis (low MCV) with target cells and basophilic stippling of the red cells present on the blood smear
- as the severity of anemia increases there is increasing abnormalities of red cell shapes and sizes
Thalassemia is relatively common in persons of what descent?
Mediterranean, African, and Southeast Asian descent
*Reduces impact of malaria
What deficiency is described: inherited defect (X-linked) encountered primarily in blacks in which red cells are susceptible to oxidant injury by drugs or toxins (antimalarials, sulfonamides, etc), RBC membranes flexibilty is reduced, leading to extravascular hemolysis, condition is asymptomatic in the absence of the oxidant
glucose-6-phosphate dehydrogenase (G6PD) deficiency
what deficiency is described: also called hemolytic disease of the newborn (HDN), is caused by blood group incompatibility between mother and fetus, disease occurs in utero only when the fetal RBC express antigens inherited from the father that are not present in the mother
erythroblastosis fetalis
what reaction is described: 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 of antibody-coated RBC) and immediate intravascular hemolysis. Activation of coagulation cascade with bleeding, renal failure, shock and death can occur. ABO antigens are most important, but other RBC antigens can produce a similar picture
hemolytic transfusion reaction
what is described: patient makes antibodies to his/her own RBCs. Antibody-coated cells can be lysed (complement activation) or removed by the reticuloendothelial system
autoimmune hemolysis
loss of large portion of membrane produces what?
schistocytes
what happens to RBC in malaria?
- parasites infect RBC and cause lysis of RBC during maturation,
- varying degrees of intravascular hemolysis are experienced by individual patients
what deficiency is the most common cause of anemia worldwide?
iron deficiency
what is iron needed for?
- hemoglobin
- myoglobin
- variety of enzymes
what happens to the RBC in iron deficiency anemia?
RBC become smaller (microcytic) and contain less hemoglobin (hypochromic) than usual
*Anemia develops insidiously and remarkably low levels of hemoglobin can be tolerated with minimal symptoms
iron deficiency anemia occurs most commonly what populations
- infants (inadequate intake)
- adolescents (increased requirement)
- pregnancy
- elderly
- alcoholics
iron deficiency may be a sign of a more serious disorder associated with what?
chronic blood loss (cancer)
how is iron deficiency anemia diagnosed?
-laboratory tests (decreased serum iron, decreased serum ferritin, and increased serum iron binding capacity)
in megaloblastic anemia what is deficient?
vitamin B12 and folate
both B12 and folate are involved either directly or as cofactors in the synthesis of ______, one of the purine bases in DNA
thymidine
In megaloblastic anemia, the impaired DNA synethesis causes a delay in mitotic division: nuclear size increases, but ____ synthesis and _____ maturation proceed normally
RNA synthesis and CYTOPLASMIC maturation proceed normally
what is the end result of RBC in megaloblastic anemia?
- Abnormally large red cell precursor (megaloblast)
- Decreased production of mature RBCs
- Abnormally large red cells (macrocytes- high MCV)
in megaloblastic anemia, the megaloblasts accumulate where releasing too few RBCs into the peripheral blood and causing anemia
accumulate in the bone marrow
the megaloblasts in megaloblastic anemia may undergo what two things in the marrow?
- Autohemolysis in the marrow
2. Be destroyed by phagocytic cells in the marrow (ineffective erythropoiesis)
In megaloblastic anemia, the impairment of DNA synthesis is systemic and affects what?
other rapidly dividing cells in the body (granulocytes, megakaryocytes, epithelial cells)
where can vitamin B12 be found
in animal foods
what are some reasons for a deficiency of vitamin B12?
- decreased intake (strict vegans without vitamin supplementation)
- malabsorption (lack of intrinsic factor, intestinal disease)
patients with pernicious anemia have autoantibodies directed against what?
intrinsic factor
*B12 deficiency also cases a demyelinating disorder
Absorption of vitamin B12 requires intrinsic factor, a protein produced by what?
parietal cells of the gastric mucosa
The absorbed B12 is bound to _____ in plasma which deliver it to the liver and other cells via the bloodstream
transcobalamins
Where can folate be found
in fresh vegetables
what are some reasons for a deficiency of folate?
- increased requirements (pregnancy, hemolytic anemia)
- decreased dietary intake (alcoholics)
- malabsorption (intestinal disease, drugs)
- body stores are relatively small
folate is absorbed where?
proximal small intestine
Since the megaloblastic features are indistinguishable morphologically in folate and B12 deficiencies, diagnosis is established by what?
laboratory tests (serum B12 level, serum and RBC folate levels, presence of antibodies directed against intrinsic factor)
what is the treatment for megaloblastic anemia?
replenishing body stores and defining how the anemia developed
what is aplastic anemia?
production of all cellular elements of the blood (red cells, white cells, and platelets) is markedly decreased (pancytopenia)
in aplastic anemia over half of the cases have no known predisposing cause (idiopathic), but that other factors have been implicated to play a role?
viruses (hepatitis), drugs (chloramphenicol) and toxins (benzene, radiation)
What are the two major pathogenetic theories that exist with aplastic anemia?
- Acquired defect in stem cell production
2. Suppression of stem cells by T lymphocytes
What are the clinical problems that result from aplastic anemia?
- weakness, fatigue
- leukopenia (infections)
- decreased platelets (bleeding)
in aplastic anemia what treatment has been successful, especially in patients less than 40 years old
bone marrow transplantation
What is myelophthisic anemia?
decreased red cell production
-The normal hematopoietic cells in the marrow are crowded out by tumor (usually multiple myeloma or metastatic cancer) or fibrosis
what is polycythemia?
the opposite of anemia
an increased in red cell mass
relative polycythemia occurs with hemoconcentration from what side effects:
- dehydration
- vomiting
- diarrhea
- excessive use of diuretics
absolute polycythemia can be a _____ or _____ phenomenon
primary or secondary
stimuli which increase erythropoietin (a growth and differentiation factor for red cell precursors) can produce what wype of polycythemia?
secondary absolute polycythemia
what are some examples of secondary absolute polycythemia?
- cyanotic heart disease
- pulmonary disease
- living at high altitude
- abnormal hemoglobin
- abnormal hemoglobin
- erythropoietin-producing tumor
what is polycythemia vera?
primary absolute polycythemia occurs when a non-regulated (neoplastic) proliferation of red cells and myeloid cells
- This condition is a stem cell disorder and is associated with normal or low levels of erythropoietin
- Can cause neurologic and visual abnormalities due to sludging of red cells in capillaries
- Treatment is removal of excess RBC by phlebotomy
levels of what are helpful in distinguishing primary from secondary cases of absolute polycythemia
erythropoietin levels
*Secondary absolute polycythemia have increased levels of erythropoietin where as primary absolute polycythemia has normal or suppressed levels of erythropoietin
