Anemia Flashcards
What is the shape of RBCs?
Small Biconcave discs
What is in RBCs?
Cytoplasm- proteins, hemoglobin, electrolytes
No oraganelles
What are platelets?
Thrombocytes (fragments of megakaryoctyes)
Filled with chemicals for clotting rxn
Where do RBCs originate in fetus?
Yolk sac, then move to liver/ spleen
Where do RBCs originate in the adult?
Bone marrow - reticular tissue
What is hematopoiesis?
Blood cell formation
What is erythropoiesis?
Hemocytoblast to RBC
What is leukopoiesis?
Hemocytoblast to WBC
List the stages of hemocytoblast –> Erythrocyte
Hemocytoblast –> Proerythroblast –> Erythroblast –> Normoblast –> Recitulocyte –> Erythroctye
What are the two stages of hematopoiesis?
Mitotic division (proliferation) Maturation (Differentiation)
In erythropoiesis, where does the production of hemoglobin come from?
Ribosomes
What does erythropoiesis involve?
Loss of organelles, production of hemoglobin, loss of nucleus (forms reitulocyte)
When does the reticulocyte lose mitochondria and ribosomes?
When it leaves the bone marrow and enters blood
What do the mitochondria form the reticulocyte from?
Porphyrin ring
What makes up 90% of the dry weight of RBC?
Hemoglobin
What is the shape of hemoglobin?
Tetramer- 2 pairs of globin chains
What is attached to each globin?
Heme
How many O2s can be bound per hemoglobin?
4 O2
Where does the oxygen bind in the RBC?
Directly to the heme group
Where does CO2 bind on the RBC?
Directly to proteins
Each time O2 binds to the Heme group- what happens?
Conformational change so it is easier for O2s to hop on
What O2 is the easiest to take off the Heme group?
The first O2
If resting, what is the lowest normal O2 saturation your Heme will be at?
75% (loss of one O2)
What vitamins are needed for erythropoiesis?
Fe, B12, folate B6, riboflavin, pantothenic acid, niacin, ascorbic acid, Vitamin E (these are coenzymes for cellular metabolism)
What is required for vitamin B 12 absorption?
Intrinsic factor (why you need stomach- produces this factor so small intestine can absorb Vitamin B 12)
In the absence of vitamins there is no….
Erythropoiesis
What other nutrition is needed for erythropoiesis?
Proteins, vitamins, minerals
Are O2 and CO2 binding in erythrocytes energy dependent?
No
What energy source do RBCs use?
Glucose
What does the Rapoport-Leubering pathway form?
DPG (or BPG)
What does DPG (or BPG) facilitate in tissues?
Oxygen release
What produces 90% of glucose metabolism?
Embden-Meyerhof pathway
What produces 10% of glucose metabolism?
Hexose-monophasphate shunt
NADPH and GSH to reduce cellular oxidants
What is ATP needed for in erythrocytes
High intracellular K, low intracellular Na, low intracellular Ca, reduced hemoglobin, reduced GSH, membrane integrity and deformability
What is erythron?
Blood cells and precursors in marrow (describes blood as a single system)
What does EPO do?
Drives more cells through erythropoiesis
Where is EPO produced?
In the kidneys
Hypoxia can trigger…
Erythropoiesis
When is methemoglobin formed?
As RBC ages (when iron oxidizes)
What removed aging RBCs?
MPS (mononuclear phagocytic system) in liver and spleen
What is globin broken down into?
Amino Acid and Fe is recycled
What happens to porphyrin as cell ages?
Reduced to bilirubin (to liver) –> pigments that are part of feces
What is jaundice due to?
Increased bilirubin in blood (increased RBC destruction)
What is saturation?
The amount of Hb bound to O2 relative to total Hb
What is the percentage of saturation of venous blood?
60-80%
What is the arterial saturation?
95%-100%
What is this equation? Co X (CaO2 - Cv)2) X10
and what does it show?
Fick equation- shows gas transport acid-base balance
The bulk of CO2 is in what form?
Bicarbonate
Bicarbonate acts as what type of buffer?
pH
What factors stimulate EPO release?
Hb mass (anemia) and decreased SaO2 (hypoxia)
What disorder is an actual decrease in RBC number?
Absolute anemia
What type of anemia has normal total RBC mass but disturbances in regulation of plasma volume?
Relative anemia
Clinically, what is anemia?
Reduced O2 carrying capacity
What are compensatory mechanisms of anemia?
Increased HR, CO, circulatory rate, preferential organ related blood flow
Why is there an increase in DPG as a compensatory mechanisms for anemia?
DPG allows O2 to dissociate easier
What are 4 types of anemia due to decreased RBC production?
Aplastic anemia
Anemia of chronic renal failure
Anemia related to Vitamin B12 or folate deficit
Iron deficit anemia
What type of anemia is a stem cell disorder?
Aplastic anemia- reduction of hematopoietic tissue
What is pancytopenia?
Decrease in RBCs, WBcs, and platelets
Besides familial causes, what can cause aplastic anemia?
Radiation, immunologic injury, mycobacteria, viral infection, pregnancy
What type of onset does aplastic anemia have?
Insidious
The magnitude of what is important for aplastic anemia?
Granulocytopenia
What type of penia has fever, chills, bacterial infections?
Neutropenia
What type of penia involves petecia, brusing, nose bleeds?
Thrombocytopenia
Why is there anemia with chronic renal failure (primarily)
Impaired EPO production due to renal endocrine failure
What are secondary causes of anemia from chronic renal failure?
Hemolysis, bone marrow cell depression, blood loss (all from failure of excretory function)
Will WBC and platelet values be abnormal in anemia of chronic renal failure?
No- they will be normal
What will the RBCs look like in anemia of chronic renal failure?
Normal but with spikes on the outside surface
How do RBCs look in aplastic anemia?
Normal
What causes anemia in Vitamin B 12 or Folate deficiency?
Disruption of DNA synthesis in blast cells of bone marrow
What do Vitamin B12 and Folate contain that is needed for RBC synthesis?
Coenzymes for DNA synthesis
What is the difference b/w symptoms of pernicious anemia and folate deficiency anemia?
Pernicious anemia shows neurologic defects due to lack of Vitamin B12
What can cause a folate deficiency?
Dietary deficiency, alcoholism, cirrhosis, pregnancy, infancy
What type of anemia has RBCs that are smaller and paler than normal (hypochromic, microcytic)?
Iron deficiency anemia , thalassemia
What are the 4 types of anemia related to inherited disorders of the RBC?
Thalassemia
Sickle-cell anemia
hereditary spherocytosis
Glucose-6-phosphate dehydrogenase deficiency
What is a result of Thalassemia?
Decreased RBC survival
What classifies Thalassemia?
Chain of aberrant synthesis (alpha or beta)
What is the alpha chain deficiency Thalassemia associated with?
Asian populations
What is the beta chain deficiency of Thalassemia associated with?
Mediterranean, Middle east, India, Pakistan populations
What type of thalassemia does not allow the child to survive?
Thalassemia major
What is sickle cell anemia due to?
A genetic defect in HB synthesis (val replaces glu in 6th position of B-chain –> sickle cells
When do cells sickle in sickle cell anemia?
When the person is oxygen stressed
What is wrong with RBCs in hereditary spherocytosis?
They have defective membrane skeletons, altered membrane properties, and they are spherical which leads to their destruction
What type of genetic disorder is hereditary spherocytosis?
Autosomal dominant
There is an increase amount of what in RBC for individuals with hereditary spherocytosis.
Hemoglobin
What population is hereditary spherocytosis found in?
Northern Europeans
What is glucose-6-phosphate dehydrogenase deficiency caused by?
Enzyme deficiency –> altered glycolysis (can’t keep Na/K at normal levels)
Membrane damage in glucose-6-phosphate dehydrogenase anemia causes what?
Early phagocytosis- anemia
When does a person discover they have glucose-6-phosphate dehydrogenase anemia?
Drug challenge- example- primaquine (anti-malarial)
What type of genetic condition is glucose-6-phosphate dehydrogenase anemia?
X-linked recessive
What populations is glucose-6-phosphate dehydrogenase common in?
African Americans and Sephardic Jews
What are the three types of anemia related to extrinsic RBC Destruction or Loss?
Hemolytic disease of the newborn
Antibody-mediated drug rxns
Acute blood lost
What happens in hemolytic disease of the newborn to baby’s RBCs?
Destroyed by maternal anitibodies
What will baby’s RBCs in hemolytic disease of the newborn have?
Nucleated RBCs in peripheral blood (reticulocytosis)
What happens with antibody-mediated drug rxns?
Drug induced immune hemolytic anemia
What are the 4 mechanisms of antibody mediated drug rxn
Hapten, neoantigen, membrane modification, autoantibody induction
What occurs in hapten mechanisms of antibody-mediated drug rxns?
Drug attached to outside of RBC and immune system creates antibodies against that drug (only recognizes drug)
What happens in neoantigen formation (antibody-mediated drug rxn)?
Drug binds to outside of RBC membrane- combination of drug and RBC produces a new antigen (antibodies attack RBC and drug at the same time)
What happens in membrane modification (antibody-mediated drug rxn)?
drug alter proteins on RBC and immune system comes in and destroys cell
What occurs in autoantibody induction (antibody-mediated drug rxn)?
Drug produces autoantibodies directed to RH antigen- triggers destruction of RBCs
What drug is involved in autoantibody induction (antibody mediated drug rxn)?
Methyldopa
Where is there anemia with acute blood loss?
Plasma is replaced before hemoglobin
What percentage of blood loss leads to death?
50%
What is polycythemia?
Excess of RBCs- increased whole blood viscosity and BV
What is a clinical symptom of polycythemia?
Hypertension
What is polycythemia vera due to?
Neoplastic transformation of stem cells in bone marrow; chronic panmyelosis (genetic)
What happens with secondary polycythemia?
Chronic hypoxia with increased EPO production- due to a primary disease
No WBC or platelet increase
What is relative polycythemia due to?
Dehydration, endocrine disorder
