Haematopoies And Introduction To Blood Cells Flashcards
What is blood
-Blood is a special type of fluid connective tissue derived from mesoderm
-bright red In arteries and dark in veins
-ph=7.35-7.45
-38c
-3x more viscous than water
-5-6L
Blood composition
1)plasma
• Least dense component • Contains:
• Electrolytes e.g. Na+, K+, Ca2+ , Cl-, HCO3
• Proteins, e.g. haemostatic proteins,
immunoglobulins, transport proteins
• Small organic molecules e.g. glucose
2) Buffy coat
Buffy coat composed of
• Leukocytes
• Platelets
3)Red blood cells
• Most dense component
• Haematocrit: the ratio of the volume of red
blood cells to the total volume of blood
Full blood count
The full blood count (FBC) is the most requested in Haematology
• Blood cell counting is used in the differential diagnosis of:
• Anaemia
• Leukaemia
• Thrombocytopenia
• FBCs are performed by automated counting machines e.g. Coulter Analysers
Haematopoiesis
All cells of the blood originate from multipotent stem cells in the bone marrow- HAEMATOPOIETIC STEM CELLS (HSCs)
• Erythropoiesis: the formation of red blood cells • Myelopoiesis: the formation of white blood cells • Thrombopoiesis: the formation of platelets
Stem cells
Stem cells are undifferentiated cells that have two unique features: 1. Capacity of self-renewal
2. Ability to differentiate into a variety of mature cell types
HAEMATOPOIETIC
STEM CELLS
(HSCs)
• HSCs are rare, ≈ 1 in every 20 million nucleated cells in the bone marrow
• Long-term HSCs: able to repopulate the bone marrow for › 16 weeks
• Short-term HSCs: engraft transiently for few weeks
• CD34+ CD38- LIN-
• Appear like a medium size lymphocyte
SITES OF HAEMATOPOIESIS
Foetus
0.2 months yolk/sac
2-7 months liver and spleen
5-9 months bone marrow
Infant:bone marrow
Adults:vertebrae,ribs,sternum,skull,sacrum and pelvis,proximal ends of femur
HAEMATOPOIESIS IN THE ADULT
• Major sites of adult haematopoiesis: the sternum, femur and pelvis
• Minor sites of adult haematopoiesis: ribs, skull and sacrum
• Haematopoiesis occurring in the bone marrow is called intramedullary haematopoiesis
• Haematopoiesis occurring in the liver and the spleen is called extramedullary haematopoiesis
REGULATION OF HAEMATOPOIESIS
STROMAL CELLS:
mesenchimal stem cells, Adipocytes, fibroblasts, osteoblasts, endothelial cells and macrophages
Stromal cells secrete: EXTRACELLULAR MATRIX PROTEINS: collagen, fibronectin, thrombospondin, hyaluronic acid and other glycosaminoglycans
GROWTH FACTORS: allow stem cell survival and haematopoiesis
RED BLOOD CELLS
• Most common cell type in adult blood
• Adult humans produce aprox 2.3 million
erythrocytes/second or 138 million/minute
• That’s 1012 new erythrocytes/day: Adult male: 4.50 – 6.50 x 1012/L Adult female: 3.80 – 5.80 x 1012/L
• Erythrocyte life span is 120 days
• Balance between erythrocytes production and
destruction depends on:
Hormonal control (EPO)
Adequate supplies of iron, B vitamins, aminoacids, etc
Red blood cells carry O2 to the tissues and return CO2 from the tissues to the lungs. They contain haemoglobin, a specialised protein that loads and unloads O2
REGULATION OF ERYTHROPOIESIS BY ERYTHROPOIETIN
-low oxygen levels (hypoxia) due to decreased red blood count act as a stimulus
-decreased amount of haemoglobin so decreased about of o2 available
-kidneys release epo
-epo stimulates red bone marrow
-enhanced erythropoises increased red blood cell count
-02 carrying ability of blood Rises
Production of red blood cells
Lecture capture
RED BLOOD CELL INDICES
• RBC indices help to classify the RBCs • Based on size and Hb content
• Important RBC indices:
• Mean corpuscular volume (MCV)
• Mean corpuscular hemoglobin (MCH)
• Mean corpuscular hemoglobin concentration (MCHC)
• RBC indices correlate with RBC morphology seen on the stained blood film
• Used to help classify anaemias
MEAN CORPUSCULAR VOLUME (MCV) AND THE MEAN CORPUSCULAR HAEMOGLOBIN CONCENTRATION (MCHC)
RBCs classification based on MCV
Red blood cells that have a normal size or volume (normal MCV) are called normocytic
When the MCV is high, they are called macrocytic When the MCV is low, they are called microcytic
RBCs classification based on MCHC
Red blood cells containing normal amount of haemoglobin (normal MCHC) are called normochromic
When the MCHC is abnormally low, they are called
hypochromic
When the MCHC is abnormally high, they are called
hyperchromic
ANISOCYTOSIS
Red blood cells of unequal sizes
POIKILOCYTOSIS
Abnormally shaped red blood cells
PLATELETS
• Anucleate (no nucleus)
• 1-3μm in diameter
• Normal = 150 – 400 x 109/L
• Higher than normal thrombocytosis
• Lower than normal thrombocytopenia
• Platelet circulate for 7-10 days
• Each day, 100 billion/day are produced from megakaryocytes to maintain the normal platelet count
• Platelets are major players of the haemostatic response, they adhere to the injured vasculature and to prevent bleeding
PLATELET BIOGENESIS
• Platelets are released in the blood through the endothelium of the vascular niche of the bone marrow where megakaryocytes reside
• Plateletproductiontakes10days
THROMBOPOIESIS
Phase I - Megakaryocyte maturation
• Endomitosis (DNA replication without cell division)
• Cytoplasm enlargement (cytoskeletal proteins and platelet granules)
Phase II - Platelet generation
• Mature megakaryocytes extend long branching processes (proplatelets)
• Organelles and granules are transported to proplatelets
• Driven by cytoskeletal rearrangements
NEUTROPHILS
• Life span: 6-10 hrs •
• 12-15 μm in diameter •
• Nucleus has 2-5 distinct •
lobes separated by narrow •
filament
• Condensed chromatin
pattern •
• Cytoplasm has fine, evenly
distributed granules
EOSINOPHILS
Life span: days • 12-17 μm in diameter • Bi-lobed nucleus • Large, spherical granules red/orange • in colours
Granules more coarse and larger than those of neutrophils
BASOPHILS
Life span: days
10-14 μm in diameter Nucleus obscured by blue/black granules Rarely found in the peripheral blood circulation
MONOCYTES
Life span: 20/40 hours
• 12-20 μm in diameter
• Largest peripheral
blood cells
• Large amount of grey-
blue cytoplasm; often
vacuolated
• Large indented/folded
nucleus
• Irregular cytoplasmic
outline
LEUKOCYTE ORDER OF PREVALENCE
Neutrophils Lymphocytes Monocytes Eosinophils Basophils
LEUKOCYTE ORDER OF PREVALENCE
Neutrophils Lymphocytes Monocytes Eosinophils Basophils
LYMPHOCYTES
• • • •
LYMPHOCYTES
Life span: weeks/years
10-16 μm in diameter
Scanty cytoplasm/high nuclear to cytoplasmic ratio Usually have a round or slightly indented nucleus
LYMPHOCYTES
• • • •
LYMPHOCYTES
Life span: weeks/years
10-16 μm in diameter
Scanty cytoplasm/high nuclear to cytoplasmic ratio Usually have a round or slightly indented nucleus
low white cell count, usually low neutrophils (neutropenia)
Leukocytosis
increased white cell count, may be a consequence of infection or inflammation
Leukaemias
malignant (neoplastic) proliferation of white cells or their precursors
Lymphomas
lymphoid neoplasm
Multiple myeloma
plasma cell neoplasm
HAEMATOLOGICAL MALIGNANCIES
Non-epithelial cancers that arise from the haematopoietic tissues – i.e.blood forming cells
LEUKAEMIA= Acute lymphocytic leukemia (ALL) Acute myelogenous leukemia (AML) Chronic myelogenous leukemia (CML) Chronic lymphotic leukemia (CLL)
MYELOMA= Multiple myeloma (MM)
LYMPHOMA= Non-Hodgkin’s lymphoma (NHL) Hodgkin’s lymphoma (HL)
HAEMATOLOGICAL MALIGNANCIES
Haematological malignancies are clonal diseases that derive from a single cell in the bone marrow or peripheral lymphoid tissue, that has undergone genetic alteration
Classification of leukaemia
1)Acute
-lymphoid=all acute hymphoid leukaemia
-myeloid=AML (acute myeloid leukaemia)
2)chronic
-lymphoid=CCL(chronic lymphoid leukaemia )
-myeloid=CML(chronic myeloid leukaemia)
ACUTE
-affects all ages
-sudden clinical onset
-course of disease lasts weeks-months
-blasts are the predominant cells
-white blood count is variable
Chronic leukaemia
-affects typically adults
-clinical onset is insidious
-course of disease is months-years
-mature forms are the predominant cells
-white blood count is increased
MULTIPLE MYELOMA
• A neoplastic proliferation characterised by plasma cell accumulation in the bone marrow
• A plasma cell is a mature B lymphocyte
• Secrete a single type of antibody (monoclonal)
LYMPHOMA
• Lymphoma is a cancer that begins in cells of the lymph system
• Lymphoma can occur in both children and adults
The two main types of lymphoma:
• Hodgkin’s lymphoma (Reed- Sternberg cells)
• non-Hodgkin lymphoma (NHL)