5.1 - RBC's Flashcards
What is hematopoiesis?
- process by which blood cells are made
- occurs in bone marrow
- starts with hematopoietic stem cells that can differentiate into any type of cell
What 2 progenitor cells are made by hematopoietic stem cells?
1) myeloid progenitor
- cells involved in oxygen transport, immune responses, and blood clotting
2) Lymphoid progenitors
- produce lymphocytes (needed for adaptive immune response)
Blood Cell Lineages
1) Erythrocytes - RBC’s
- erythropoesis - production of RBC’s
2) Lymphocytes
- T cells, B cells, NK cells
- lymphopoiesis: lymphocyte production
3) Myeloid cells
1. granulocytes
- neutrophils, basophils,
eosiniphils
2. monocyte & macrophages
- do phagocytosis
4. megakaryocytes
- plateletes
How an HSC differentiates?
1) HSC develop into mulitipotent progenitor cell (MPP)
2) MPP becomes myeloid progenitor cells
3) Myeloid progenitor becomes granulocyte-monocyte progenitors
4) These become eosinophiloblasts (immature eosinophil)
5) Immature eosinphils produce granules to become mature
What controls the growth and differentiation of HSC’s?
- Cytokines and growth factors
- Colony stimulating factor: stimulates proliferation of progenitor cells
Hematopoiesis occurs in 2 pools:
1) Stem Cell Pool
- pluripotent stem cells; differentiate into any type of cell
2) Bone Marrow
- stores cells that are actively proliferating or maturing
Once mature blood cells enter circulation, they divide into 2 pools:
1) Circulating
- cells actively moving through bloodstream
2) Migrating
- neutrophils adhering to blood vessel walls
2 Types of Bone Marrow
Red
- produces blood cells
-active
-found in pelvis, vertebrae, cranium, ribs
Yellow
- contains fat
- inactive
2 Types of Bone Marrow Niches
1) Osteoblastic
- where HSC’s are inactive
2) Vascular
- where HSC’s proliferate and differentiate
Extra medullary
Medullary Hematopoiesis
- blood cell production occurs within BONE MARROW
- in fetus, hematopoiesis occurs within liver and spleen
Medullary HematoPAResis
- failure/suppression of this process
- can be caused by chemo radiation, and aplastic anemias: bone marrow stops producing new cells
Extra medullary Hematopoesis
- production of blood cells OUTSIDE of bone marrow
- occurs in liver, spleen and lymph nodes
- occurs when the body/bone marrow is unable to keep up with bodys demands for RBC production
What is involved in the lymphatic system?
Primary Organs
- bone marrow and thymus
Secondary Organs
- spleen, lymph nodes
Role of Spleen
- reservoir for blood
ex. in case of low BP, spleen can release stored blood to increase BP - where fetal RBC production occurs
- filters blood and removes damaged/old blood cells
White pulp: T and B cells
Red pulp: filters RBC’s
Role in Lymph Nodes in the Immune Response
1) antigens encounter lymphocytes
2) lymphocytes (B and T cells) enter lymph nodes and interact with antigens
3) lymphocytes get processed by macrophages and dendritic cells
4) B cells proliferate into plasma
5) Macrophages filter lymph and debris
Erythropoiesis
- kidneys stimulate erythropoiesis when they detect low oxygen in circulation
- final immature stage of an RBC is a reticulocyte
- RBC production is regulated by the hormone erythropoietin
- tissue hypoxia increases production of EPO which triggers increases RBC production
- in chronic kidney disease, kidneys fail ton produce EPO which then causes decreased RBC production = anemia
- conditions that lower O2 (COPD triggers kidneys to produce EPO and stimulate RBC production
Process of Hemoglobin Synthesis
- protophorphyrin + iron = heme
- heme + globin chains = hemoglobin
- each heme has 2 alpha and 2 beta globin chains - heme is made in the mitochondria and cytoplasm of RBC precursor cells
Role of Vit B12 in Erythroporeosis
- b12 forms thymidine (needed for DNA replication)
- low B12 = impaired DNA synthesis = abnormal RBC production
- produces larger than normal erythrocytes: megaloblasts
- B12 is absorbed with the help of intrinsic factor
- low intrinsic factor = poor B12 absorption = pernicious anemia
Role of Iron in Erythroporeosis
- iron is required to make heme
- low iron = impaired hemoglobin synthesis (RBC can not properly transport oxygen) = abnormal RBC production = iron deficient anemia
Iron Cycle
- iron is stored as ferritin
- apoferritin - iron free version
Hemosiderin
- iron-storage complex that is deposited in tissues (esp when there is excess of iron)
- less accessible for immediate use
Transferrin
- transports iron in the blood (iron binds to transferrin receptors)
- once iron is absorbed, transferrin - now apotransferrin get released back into bloodstream
Role of Hepcidin
Hepcidin - regulates iron levels
- hepcidin binds to ferroportin - iron exporter
- when hepcidin binds to ferroportin, ferroportin breaks dow and stops iron from being released into blood
- hepcidin levels increase when iron levels are high
- low iron or ↑ erythropoesis = less hepcicin (body needs more iron when making RBC’s)
Iron Absorption
- if iron is low, iron is absorbed rapidly in intestine and transported to plasma
- if iron is sufficient, excess iron gets stored as ferritin
RBC Destruction
- when hemoglobin from RBC’s breaks down, heme is converted to bilirubin
- bilirubin gets sent to liver where it gets processed and then excreted in bile
- in intestines, bilirubin gets converted into urobilin
- if too much RBC’s are destroyed, there are increases levels of unconugated bilirubin which can increase gallstones
Role of Blood
- removes waste products
- delivers nutrients and oxygen to tissues
- defends against injury
Layers of blood
1) Erythrocyte - bottom
- carries oxygen
2) Buffy coat layer - middle
- contains leukocytes and thrombocytes
3) Plasma - top
- contains nutrients, waste products, hormones, gases, proteins, electrolytes
Plasma
1) Albumin
- maintains oncotic pressure
- decreased albumin = fluid imbalance and swelling
2) Globulin
- provides immune defence in the form of antibodies
3) Fibrinogen (clotting)
4) Transferrin (for transporting iron)
RBC Count
Erythrocytosis - elevated RBC count
- ex. in chronic hypoxia where the body compensates for low O2 by increasing RBC production
Decreased RBC
- occurs due to blood loss, bone marrow suppression (chemo)
What is Hematocrit
- % of RBC’s in proportion to plasma volume
-
Interpretations of Hematocrit Value
Elevated
- can be elevated in cases of chronic hypoxia where body is producing RBC’s to compensate
- can be FALSELY elevated
ex. in dehydration, there is less plasma volume, which increase Hct (but there is not an increased amount of RBC’s)
Decreased
- can have true decreased (in anemia) where there is less RBC production
- can have false decrease
ex. when overhydrated, plasma volume increases which makes Hct appear low (but there are not actually fewer RBC’s)
Always interpret hemoglobin levels in relation to ___________?
hematocrit; hydration status can affect hgb levels and make them appear falsely high or low
Polycythemia Vera (elevated RBC)
Cause
- mutations in JAK 2 gene which causes uncontrollable RBC proliferation
- results in high # of RBC’s, WBC’s, and plts
Structural Changes
- increased blood viscosity
- hyperactive bone marrow
S&S
- fatigue, headache dizziness; slowere circulation due to thicker blood
- red/flushed skin - due to a lot of RBC’s
Complications
- thrombosis: thick blood can clot
- Splenomegaly: spleen has to filter out increased # of RBC’s; it is overworked and enlarged
Anemias
- decreased total # of RBC’s
Caused by:
- increased RBC destruction
- blood loss
- impaired RBC production
cytic - cell size
chromic - hbg/colour
Pernicious Anemia (macrocytic; noromochromic)
Cause
- deficient B12 and intrinsic factor
Patho
- DNA synthesis impaired = impaired RBC production = magaloblasts
Changes
- large and abnormal RBC
S&S
- weakness, fatigue, paraesthesia, loss of appetitie, abdominal pain, sore tongue
- ↓ RBC, ↓ Hbg, ↓ Hct, ↑ MCV (large size)
Iron Deficiency Anemia (microcytic; hypochromic) ; marissa
Cause
- insufficient iron
Patho
- inadequate iron to bone marrow = iron deficient RBC’s
Changes
- microcytic - small
- hypochromic: pale
S&S
- fatigue, weakness, SOB, irritability, headache
↓ Hbg, ↓ Hct, ↓ MCV (small), ↓ MCHC, ↓ MCH
Beta Thalassemia (microcytic; hypochromic)
Cause
- mutation in the HBB gene = reduced or absent globin chain production
Patho
- accumulation of unpaired glob chains = ineffective RBC production
Changes
- microytic
- hypochromic - pale
- bone marrow produced fewer RBC’s
- RBC’s are deformed/dysfunctional
S&S
- minor: asymtompatic
- major - trasnfusion-depednent
Sickle-Cell Anemia (normocytic; normochromic)
Cause
- mutation in HBB gene = abnormal hemoglobin (hemoglobin S)
Patho
- low oxygen = hemoglobin S polymerizes = causes sickle shape = sticks to vessel walls = vasoocclusion
Changes
- sickle cell shaped
- bone marrow hyperplasia; there is increased demand for RBC production to compensate
S&S
- Chronic: pallor, fatigue, SOB
- Vaso-occlusion: tissue/organ ischemia
- Infetcion risk bc of spleen damage
Aplastic Anemia (normocytic, normochromic)
Cause
- bone marrow fails to produce enough RBC’s
- due to bone marrow suppression: chemo, radiation
Patho
- damage to bone marrow = stem cell destruction
Changes
- bone marrow is replaced with fat = decrease in HSC cells
- pancytopenia: decreased RBC’s, WBC’s, and platelets
S&S
- Low RBC’s: fatigue, dizziness, SOB
- Low WBC’s: infection risk
- Low plts: bleeding risk
