RBC path Flashcards
\_\_\_\_ system Blood cell forming system Lymph tissue Bone Marrow Red bone marrow Yellow bone marrow Circulating blood
Hematopoietic System
Process in which red and white blood cells are
produced
Red bone marrow
Hematopoiesis
Erythropoiesis Regulated by kidneys Erythropoietin 1% of RBCs replaced daily Life span 120 days (4 months)
Erythrocytes
Immature red blood cells
Reticular network of RNA in cytoplasm
Normal range: 0.5% to 1.5%
Indicator of bone marrow activity
Reticulocytosis – elevated number of reticulocytes in blood
Reticulocyte count should be appropriate to the clinical situation
Reticulocytes
Heme – non-protein portion
Iron porphyrin - 4 pyrrole rings + iron
Globin – protein portion
HbA (Adult Hb) – 2 alpha, 2 beta
HbF (Fetal Hb) – 2 alpha, 2 gamma
Normal adult red cells contain mainly HbA
Hemoglobin
A reduction in the erythron – a reduction in the total red cell mass
below normal limits
Reduction in the oxygen carrying capacity of the blood leading to
tissue hypoxia
Usually diagnosed based on:
Inadequate numbers of erythrocytes (low hematocrit - the ratio
of packed red cells to total blood volume)
Inadequate level of hemoglobin – the hemoglobin concentration
of the blood
Anemia
The lifespan of a red blood cell is about ____ days
120 days
Increased RBC destruction
Decreased RBC production
Blood loss
Anemia
Clinical Features of \_\_\_\_\_: Pallor – pale skin and mucosa Lethargy – lack of energy, fatigue, weakness Dyspnea – labored breathing, SOB Tachycardia, arrhythmia, chest pain Koilonychia - spoon-shaped nails Atrophic glossitis Cognitive problems, dizziness Cold extremities Headache
Anemia
A hemoglobinopathy
Inherited, mis-sense mutation of beta chain
A single AA substitution of valine for glutamic acid
Forms a new, abnormal hemoglobin, Hemoglobin S - HbS
Sickle cell disease – homozygous HbS
Sickle cell trait - heterozygous, a less serious condition
Sickle cell anemia
Individuals with sickle cell trait (heterozygous for HbS) have a survival
advantage in malaria-endemic areas
Homozygous normal – increased mortality due to malaria
Heterozygous – survival advantage
Homozygous – increased mortality due to sickle cell disease
About 8% of African Americans are heterozygous (sickle cell trait)
1 in 600 African Americans are homozygous (sickle cell disease)
HbS
Clinical Consequences of \_\_\_\_\_\_\_ Increased susceptibility to infection with encapsulated organisms Pneumococcus pneumoniae Hemophilus influenzae
Splenectomy
“Mediterranean” anemia Group of inherited diseases Quantitative problem - too few globins synthesized Underproduction of normal globin proteins due to mutations in regulatory genes Ineffective production of globin chains Alpha globin chains (α Thalassemia) Beta globin chains (β Thalassemia) Regular transfusions – iron overload – organ damage Bone deformities – expansion of marrow space Splenomegaly - splenectomy Impaired growth Bone marrow transplantation
Thalassemia
Two genes involved in making beta chain (one from
each parent)
Severity depends on number of affected beta chain
genes
One gene – beta-thalassemia minor - beta-thalassemia
trait
Mild disease
Two genes – beta-thalassemia major (Cooley’s anemia)
Severe disease
Beta Thalassemia
Four genes involved in making alpha chain (two from each parent)
Severity depends on number of affected alpha chain genes
One gene – asymptomatic carrier
Two genes – alpha-thalassemia minor - alpha-thalassemia trait
Mild disease
Three genes – hemoglobin H disease
Moderate to severe disease
Four genes – alpha-thalassemia major – (lethal)
Alpha Thalassemia
ABO mismatch leads to _______
intravascular hemolysis
Rh- mom Rh+ fetus Fetal RBCs cross the placenta and enter the maternal circulation during birth trauma Prophylactic anti-Rh (D) immune globulin (Rhogam) within 72 hours of delivery Rhogam lyses fetal RBCs in the maternal circulation – effectively removing any available antigen, so the mom doesn’t develop anti- Rh antibodies
Erythroblastosis Fetalis:
1st Pregnancy at Delivery
2nd Pregnancy at Delivery Rh- mom, with anti-Rh from prior pregnancy Rh+ fetus Anamnestic response rapidly produces anti-Rh (IgG) Anti-Rh IgG crosses placenta and lyses fetal RBCs Rh-mediated hemolytic disease
Erythroblastosis Fetalis:
Immunoglobulin
Administered to Rh-negative women after pregnancies
in which they carried Rh-positive fetuses
Anti-D antibodies
Rhogam:
Rhesus Immune Globulin - RhIg
Rh incompatibility
Hemolytic anemia in utero
Rh-negative mother develops antibodies against Rh-positive erythrocytes of
fetus
Antibodies cross placenta and hemolyze fetal erythrocytes
High levels of bilirubin and biliverdin
Deposition in developing teeth
Only primary teeth affected
Erythroblastosis Fetalis
Clinical Features of __________
Anemia caused by immune destruction of erythrocytes
Erythroblasts in peripheral blood
Hyperbilirubinemia
Kernicterus (bilirubin encephalopathy) if bilirubin reaches a high
levels
Developmental dental defects reported
Erythroblastosis Fetalis
X-linked disease; most common human enzyme defect (African-American male population)
Most are asymptomatic; at risk for non-immune hemolytic anemia upon exposure to oxidative stress
Oxidative stress: infections, drugs (aspirin)
G6PD / NADPH / Glutathione pathway - maintains supply of reduced glutathione to scavenge free
radicals (anti-oxidant)
Red cells sustain damage from oxidizing free radicals (phagocytosed in spleen)
All individuals with Favism (hemolysis due to Broad Beans(fava)) are G6PD deficient
Survival advantage in Malaria endemic environments
Glucose-6-Phosphate
Dehydrogenase Deficiency
Protozoal disease – primarily Plasmodium falciparum
Female Anopheles mosquito vector, human reservoir
Reproduction in red cells – showers of organisms
produce shaking, chills and fever
Hemolytic anemia
High morbidity, mortality
Malaria
Most common anemia in US Lack of Fe most common nutritional deficiency in the world Microcytic, hypochromic Seen most often in females – more iron lost in menses than replaced by nutrition Treated with iron supplements When in males, suspect internal bleeding
Iron Deficiency Anemia
Dietary lack
Impaired absorption
Increased requirement
Chronic blood loss
Iron deficiency
Iron Deficiency is Usually Caused by
______ or ______
Dietary Lack or Blood Loss
Scandinavian, Northern European women Severe Fe-deficiency anemia Mucosal atrophy - atrophic glossitis Esophageal webs - dysphagia Increased risk for squamous cell carcinoma Esophagus Oropharynx Posterior Oral Cavity
Plummer-Vinson Syndrome
Absorption of \_\_\_\_\_\_\_ requires intrinsic factor, which is secreted by the parietal cells of the stomach
vitamin
B12
Autoimmune disease
Not due to dietary deficiency of B12
A form of megaloblastic anemia caused by
autoimmune gastritis and failure of intrinsic factor
production leading to vitamin B12 deficiency
Loss of ability to absorb Vitamin B12
Vitamin B12 (cobalamin) required for normal folate
metabolism and DNA synthesis
Pernicious anemia
Megaloblastic anemia
Dietary deficiency of folic acid
Folate required for DNA synthesis
Folic acid deficiency
Marrow aplasia secondary to supression of multipotent myeloid
stem cells (erythrocyte, leukocyte and thrombocyte series),
resulting in pancytopenia
May be caused by known myelotoxic agents (eg. whole body
radiation)
Antineoplastic drugs (alkylating agents, antimetabolites)
Benzene
Chloramphenicol
Pathogenesis may involve T cell attack on myeloid stem cells
Prognosis unpredictable
Transfusion, bone marrow transplant
Aplastic Anemia
An increase in the RBC mass
Relative polycythemia – dehydration – decreased plasma volume with normal red
cell mass
Absolute polycythemia – a true increase in red cell mass
Primary polycythemia (polycythemia vera)
Erythropoietin-independent
Acquired, clonal stem cell disorder (a chronic myeloproliferative disorder)
Secondary polycythemia
Erythropoietin-dependent
Compensatory response to tissue hypoxia
Chronic lung disease
Cigarette smoking
Residence at high altitude
Paraneoplastic syndromes
Polycythemia (Erythrocytosis)
