Erythrocytes/Anemias Flashcards
Erythrocyte Function/structure
- About 4-6 million with 120 day lifespan
- Bi-concave form increases O2 access (main fund to transport O2)
- Mature RBC - no nucleus or mitochondria
- Hgb molecules fill RBC cytoplasm
Hgb Molecule
Made of alpha & beta chains
Contain 4 heme/globin groups
Each heme carries one O2 molecule via Fe binding site
Erythropoiesis
-Stimulated by Renal erythropoeitin in bone marrow
-After age 20, RBC produced in vertebrae, sternum, ribs, and pelvis marrow.
-Expand to more bones in case of anemia.
-Most rbc mature in marrow
-Nucleated RBC in blood indicate disease (infection)
>2% retic count means rapid formation of RBC=infection
-Old RBC lose reversible deformability and removed from circulation.
Reversible Deformability (RD)
- Cells must change shape as they pass capillaries/microcirculation.
- Ability to change back to biconcave shape
- Spleen is testing ground for RBC RD
Erythrocyte Destruction
- Hgb phagocytized by macrophages et broken down to heme, iron, and glob in.
- Heme - degraded to bilirubin. Unconj in blood, conj in liver.
- Iron - in blood as transferrin, TIBC, stored in liver or sk. muscle. Overload in liver/spleen called hemosiderin.
Body Responses to Anemia - true for all anemias
- Increased erythropoeitin & hematopoeitin
- Extramedullary hematopoeisis
- Blood shift to brain/heart
- Tachycardia (increased heart workload)
- Fatigue, weakness, dyspnea
- Tissue hypoxia
Morphological Classification of Anemia - know
- Normocytic, normochromic- decreased cell #
- Microcytic, hypochromic - abnormal hgb production, missing components
- Macrocytic, normochromic- large cells (juvenile,nucleated)
Definitions - know
Poikilocytosis - alteration in cell shape
Anisocytosis- “ “ size
Hemoglobinemia - hgb in plasma
Hemoglobinurea - urine exertion of hgb
Hemosideriuria - iron excretion via urine (brown)
Hemosiderosis - increased iron storage in kidneys, spleen, liver.
Normocytic Anemia - etiology
- Loss of RBCs - hemorrhage
- Increased destruction of RBCs (intra or extravascular hemolysis - premature lysis of erythrocytes in circulation) called hemolytic anemia
- Decreased production of RBCs (aplastic or chronic disease anemia)
Normocytic -Intravascular hemolysis
Intravascular hemolysis- breakdown in circulating blood (mechanical injury, transfusion reaction, exogenous factors)
Normocytic -Intravascular hemolysis- clinical manifestation
marked erythropoeisis hemoglobinemia hemoglobinuria hemisiderinuria hemisiderosis hyperbilirubinemia
Normocytic -Extravascular hemolysis
Defective rbcs trapped in spleen.
Anemias associated Hereditary spherecytosis, G6DP, sickle cell.
Normocytic - Extravas hemolysis -Hereditary Spherocytosis
- Etiology -autosomal genetic disorder
- Patho - gene mutation causing deficiency in Spectrin (alpha or beta) which is protein on cell surface.
- RBC membrane instability through tight spaces is compromised and becomes spherical. Unable to fit through spleen circulation therefore; destroyed.
Normocytic - Extravas hemolysis - Hereditary Spherocytosis- clinical manifestation
-Aplastic crisis
-Splenomegaly and jaundice
-Blood smear - anisocytosis, spherocytes, Howell-Jolly bodies
-Increased hematopoiesis
-Increased reticulocytes
Treatment - splenectomy
Normocytic - Extravas Hemolyisi - Glucose-6-Phosphate Dehydrogenase Deficiency G6DP
- Common in African Americans/Mediterranean/Males
- Etiology- mutation to G6DP gene
- Patho - G6DP deficiency - enzyme required for glutathione production (antioxidant)
- Lack of glutathione (deal with free radicals) results in oxidative stress damage to RBCs.
- -Older cells vulnerable, infections and drugs increase oxidative stress.
Normocytic, Extravas Hemolysis - G6DP clinical manifestation
- Hemolytic anemia - more severe in mediterraneon form
- Hemoglobinemia
- Hemoglobinuria
- Blood smear - spherical cells (poikilo and anisocytosis) and Heinz and bite cells.
Normocytic - Extravascular Hemolysis -Sickle Cell
- Epi - 1 in 500 Afr. Americans with 8% carrying the cell trait. Also occurs in Mid. Eastern and S. Asian countries.
- Etiology - mutation in beta globulin gene of hgb molecule
Normocytic - Ex. Hemolysis - Sickle cell path
- transforms hgbA (HbA) into hgb S.(HbS) Sickle cell disease = all hgbS (HbS)
- Decreased PaO2, pH, volume, dehydration and cold cause Hbs to sickle.
- Sickling - beta chaings in Hbs turn into viscous gel stretching into sickle shape.
- Initially reversible but eventually irreversible.
Normocytic - Ex. Hemolysis - sickle cell clinical manifestation
- Vaso-occlusive cirisis causing tissue hypoxia and pain (bones, liver, lung, brain, spleen, rhabdomyolysis).
- Sequestration crisis (RBCs pool in spleen, chronic hemolysis, decreased blood volume)
- Aplastic crisis - very few RBCs in circulation - erythrocyte survival rate to 10-20 days, infection prone)
- Blood smear - elevated retic count due to increase RBC production)
- Bone marrow hyperplasia and extramedulary hematopoiesis.
Normocytic - Extravas Hemolysis - Sickle cell treatment
- Hydroyxurea forces RBCx to make fetal hgbjj which does not sickle
- NO decreases platelet aggregation
- Symptom support (O2, IV fluids, pain mgmt)
Normocytic anemias -Decreased RBC Production -
Aplastic Anemia
Failure or suppression of myeloid stem cells (pancytopenia)
Etiology - idiopathic (immune mediated suppression), acquired (drugs/chemicals/radiation)
Normocytic anemias -Decreased RBC Production - Aplastic Anemia clinical manifestation
pancytopenia (anemia, neutropenia, thrombocytopenia)
No splenic enlargement
Bone marrow hypo cellular
Treatment - immunosuppressants if idiopathic. If acquired, remove offending source.
Normocytic Anemias - Decreased RBC Production - Anemia of Chronic Disease
-Epi - common in hospitalized pts.
-Patho - production of TNFa, IL-1, IL-6, IL10
Inflammation alters normal iron metabolism, decreased iron for erythropoiesis leads to decreased RBC production.
Normocytic Anemias - Decreased RBC Production - Anemia of Chronic Disease - clinical manifestation
- mild anemia
- low serum iron
- reduced tibc
- high serum ferritin
- low erythropoietin levels
Microcytic Anemias
- RBC cytoplasm primarly composed of Hgb.
- Insufficient hgb (microcytic, hypochromic)
- A and B Thalassemias (common in Mediterranean, Africa, SE Asia)
- Iron deficiency anemia
Microcytic Anemias -Decreased RBC Production - B Thalassemia
Etiology = mutation of Bhemoglobin genes Patho- Reduced synthesis of Bglobulin Absence of Bglobulin, Few B chains lead to fewer hgb molecules Free globulin chains for upstage aggregates Apoptosis of defective RBC precursor Lysis of RBCs containing aglobin chains
Microcytic Anemia - Decreased RBC Production - B Thalassemia - clinical manifestation
- Anemia
- Blood smear - aniso/poikilocytosis, increased retic, normoblasts
- Spleno and hepatomegaly (due to extra medullary hematopoiesis)
- Osteoporosis (bone marrow expansion)
- Hemosiderosis
Microcytic Anemia -Decreased RBC Production - A Thalassemia
-Etiology - Aglobin gene loci deletion
-Patho - Deletion leads from reduction to total absence of aglobin chains
-Clinical manifestations - silent carrier (single gene deletion) to mild/severe anemia (2-3 gene deletion) to fetal death (absence of all 4 genes)
B aggregates may cause less membrane damage leading to less lysis.
Microcytic Anemia - Iron Deficiency Anemia
Insufficient iron to form Hgb molecule (formed by A & B chains). Has iron molecule to bind O2 in each chain.
Epi - most common anemia worldwide
Etiology - low iron intake, impaired absorption, increased requirements (pregnancy or chronic blood loss).
Microcytic Anemia - Iron Deficiency Anemia - when all iron stores are depleted
Patho - deficiency interrupts heme synthesis leads to globin synthesis inhibition
Clinical manifestation - Anemia (hypochromic, microcytic, aniso/poikilocytosis) Pale due to low O2.
Decreased retic
Pica & poor physical development in children
Low ferretin
High TIBC
Macrocytic Anemia
RBCs very large due to impaired erythropoiesis synthesis.
RBC never able to mature past megaloblast.
Macrocytic, normochromic
Types of anemia:
-Vit B12 deficiency
-Pernicious Anemia
-Decreased folic acid
Macrocytic Anemia - Vit B12 Deficiency
Vit B12-Cobalamin (folic acid)
Vit B12 required for DNA synthesis during erythropoiesis
Etiology - decreased intake, malabsorption (gastrectomies, ileum resections) , increased requirements.
Macrocytic Anemia -Pernicious Anemia
Etiology - autoimmune in origin
Epi - Scandinavian, ages 50 and over
Macrocytic Anemia - Pernicious Anemia
Pathology - Antibodies to parietal cells.
Antibodies to intrinsic factor.
Parietal cells release gastric acid and intrinsic factor et both needed for B12 absorption.
Macrocytic Anemia - Pernicious Anemia - clinical manifestations
- Anemia
- Low serum B12 levels (Schilling test)
- Bone marrow biopsy (lg ovoid megaloblasts)
- Blood smear - few retic, Howell-Jolly bodies
- GI cytology - parietal cell atrophy, glossitis
- B12 required for neuronal function/myelination (numbness, tingling, loss of balance, dementia)
Immunological (antibodies to intrinsic factor and parietal cells.
Macrocytic Anemia - Folic Acid
- Require for DNA synthesis for normal erythropoeisis
- Etiology - decreased intake increased demand, impaired absorption, folate antagonist like methotrexate.
Macrocytic Anemia - Decreased Folic Acid - clinical manifestation
- Blood smear - few retic, nucleated RBCs, anisocytosis
- Large, ovoid megaloblasts in marrow biopsy
- Low serum folate
- NO neurologic changes or gastric atrophy here.
Polycythemia/Erythrocytosis
- Men >18.5
- Women > 16.5
- Decreased plasma volume
- Increased RBC mass (primary-gene mutation causes abnormal proliferation of myeloid stem cells, secondary - increased erythropoietin levels from hypoxia).
