BMS2021 Lecture Notes - Lecture 18: Chemokine, Yolk Sac, Hydroxycarbamide
30 May 2018
School
Department
Course
Professor
Week 7. Thrombosis and haemostasis
COMPONENTS OF BLOOD AND THEIR FUNCTIONS
• Blood is classified as a connective tissue and consists of two main components:
1. Plasma
2. Formed elements: enclosed in plasma membrane and have definite shape (are cells
except platelets which are tiny fragments of bone marrow cells)
• All cells in blood are derived from stem cells in bone marrow
• What is the function of blood?
o Carry essential oxygen to tissues
o Carry away waste (CO2/from liver and kidneys), nutrients from digestive tract, hormones
o Protection: roles in inflammation (leukocytes, WBS, antibodies, platelets)
o Regulation: pH, water balance
• What is blood made out of:
-normal circulating blood is 4-6 L
-22% solid, 78% water
-buffy coat is leukocytes and platelets
Hematocrit
o Volume of red cells
(percentage of blood volume made up by cells)
Plasma
o Fluid in fresh blood
(fluid matrix, without clotting)
o 91% water
o Has plasma proteins eg. albumin
-HDL = good, cholesterol from body to liver ->
excrete
-LDL = bad, cholesterol from liver to other sites
o 2% nutrients (amino acids, sugars, lipids),
hormones and electrolytes
Serum
o Fluid after blood has clotted
(blood centrifuged with clotting)
Plasma
o Serum + fibrinogen (and other clotting factors)
• 4 main components of blood:
Erythrocytes
o RBC
Platelets
o Thrombocytes
Leukocytes
o WBC
-granulocytes = leukocytes, neutrophils, eosinophils and basophils
-agranulocytes = lymphocytes and neutrophils
1. Monocytes: after they leave blood become mature -> macrophages
2. Lymphocytes: B cells (produce antibodies) and T cells (CD8 kill virus infected
and damaged cells, CD4 help cytotoxic T cells and B cells in their function)
3. Granulocytes: neutrophils (phagocyte bacteria), basophils (secrete
find more resources at oneclass.com
find more resources at oneclass.com
histamine), eosinophils (regulate inflammation, phagocytose parasites)
-only T cells are from thymus
Plasma or serum
o
• Migration of WBC out of bloodstream/veins (extravasation – leaving circulation)
1. Tethering and rolling
-selectins on EC (endothelial cell) tether to WBC
2. Activation:
-chemokines on EC attrat ad atiate WBC’s
3. Arrest and flattening
-Integrin engagement stops WBC rolling (integrin is on WBC)
4. Locomotion to interendothelial junctions
-locomotion
5. Extend protrusions through interendothelial junction
-chemokines from damaged tissue/inflammation promote protrusion and basal lamina is
digested
• Blood donations:
o RBC: for acute blood loss or severe anemia
-has long shelf life
o Fresh frozen plasma: blood loss, low platelet count, preoperative
o Concentrate of blood platelets: low platelet count, chemotherapy
o Cryoprecipitate: blood proteins, coagulation deficiency, fibrinogen deficiency
o Rarely white cells
• Haemopoietic cells (stem cells) are generated in bone marrow and occur in embryo (yolk sac),
fetus (liver), infant (almost entire skeleton) and long bones in adults.
• Stem cells divide slowly but are self-renewing:
Once daughter stem cell is fated to become differentiated
-> becomes TAC (transit amplifying cells)
-> generate many differentiated cells -> myeloid or lymphoid cells
(stem cell needs to be in contact with stromal cell eg. osteoblast to keep its self-renewing
property)
-high osteoblasts = high HSC
-Ligand: Kit (on osteoblast)
-Receptor: c-kit (on HSC)
-without interaction -> HSC becomes committed to death/differentiation
find more resources at oneclass.com
find more resources at oneclass.com
• Lymphoid precursors -> lymphocytes
• Myeloid precursors -> all other blood cells
• Platelets are fragments that bud off megakaryocytes (which are large cells that persist in the
bone marrow after maturation)
• Colony stimulating factors (CSF) are glycoproteins that promote proliferation and differentiation
of progenitor cells
o Signal can be auto, para or endocrine
o Can stimulate specialised cell function of terminally differentiated cells
Eg. G-CSF inhibits osteoblasts/stimulates osteoclasts for HSC mobilisation
o Stimulates erythrocyte production
EPO binds to CFC-E progenitors in response to hypoxia (deprived of adequate
oxygen supply) due to bleeding, anaemia, high altitude etc.
Maturation occurs in bone marrow and includes loss of nucleus/mitochondria
Energy via glycolysis
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Hematocrit: volume of red cells (percentage of blood volume made up by cells) Plasma: fluid in fresh blood (fluid matrix, without clotting, 91% water, has plasma proteins eg. albumin. Hdl = good, cholesterol from body to liver -> excrete. Ldl = bad, cholesterol from liver to other sites: 2% nutrients (amino acids, sugars, lipids), hormones and electrolytes. Plasma (blood centrifuged with clotting: serum + fibrinogen (and other clotting factors, 4 main components of blood: Plasma or serum o: migration of wbc out of bloodstream/veins (extravasation leaving circulation, tethering and rolling. Selectins on ec (endothelial cell) tether to wbc: activation: Chemokines on ec attra(cid:272)t a(cid:374)d a(cid:272)ti(cid:448)ate wbc"s: arrest and flattening. Integrin engagement stops wbc rolling (integrin is on wbc: locomotion to interendothelial junctions. Chemokines from damaged tissue/inflammation promote protrusion and basal lamina is digested: blood donations, rbc: for acute blood loss or severe anemia. Once daughter stem cell is fated to become differentiated.
