Blood Cells and Haemopoesis Flashcards
Where are blood cells first produced in the foetus?
By the mesoderm and the yolk sac
Where are the blood cells produced after the mesoderm of the yolk sac?
By the liver and spleen, and then finally by the bone marrow
Where do all the cellular components of the blood arise from?
Stem cells
What are stem cells capable of?
Division and differentiation
What two main lines develop from stem cells?
NAME?
What is meant by ‘blasts’?
Cells capable of division
What are myeloid blasts the precursors of?
- Erythrocytes
- Granulocytes
- Monocytes
- Platelets
What are erythrocytes?
Red cells
What are granulocytes?
White cells with granules in the cytoplasm
What are monocytes?
Macrophage precursors
What are lymphoblasts the precursors of?
Lymphocytes
What happens to lymphocytes once they have been produced?
They leave the bone marrow, and some pass through the thymus
What happens to lymphocytes that pass through the thymus?
They transform into T cells
What can T cells do?
Some can kill virus infected cells in cellular immunity
What do B cells do?
Produce antibody molecules responsible for humoral immunity
Where can further division of differentiation of lymphocytes occur?
In lymph nodes and lymphoid aggregates throughout the body
Where are early blood cells held?
In the bone marrow
What holds early blood cells in the bone marrow?
Adhesion molecules
Give 2 examples of adhesion molecules
- Collagen
- Fibronectin
What happens as blood cells mature?
The adhesion molecule receptors on their surface downregulate, leading to the release of mature cells into circulation
What regulates the rate of division and differentiation of blood cells?
Various growth factors known as cytokines
What is the function of red blood cells?
- To carry oxygen from the lungs to all the tissues of the body
- To transport CO 2 back to the lungs
What is RBC production regulated?
By a feedback system which increases the production of erythropoietin form peritubular endothelial cells in the kidney in response to hypoxia
What does erythropoietin do?
Increases the rate of RBC production and release from teh bone marrow, thereby increasing oxygen carrying capacity of the blood
How is oxygen carried in RBC?
Bound to haemoglobin
What does haemoglobin consist of?
4 globin chains (2 α and 2 ß)
What does each globin chain carry?
A haem molecule
What does each haem molecule do?
Binds to oxygen
Are globin chains tightly or loosely bound?
Loosely
What does globin chain interaction depend on?
Oxygen tension
What is the end effect of haem binding?
A very efficient oxygen dissociation curve
What is the oxygen dissociation curve of haemoglobin so effective?
Because oxygen is more tightly bought in areas of high oxygen tension, and more readily released in areas of low oxygen tension
How long does the average RBC survive for?
120 days
What happens when a RBC has reached the end of its lifespan?
It is broken down, with other abnormal RBCs, in the lvier and spleen
What happens to the components of RBC on breaking down?
- The iron is recycled
- The protoporphyrin of haem is metabolised to bilirubin
What are leucocytes?
Nucleated cells which circulate in the blood
What do leucocytes include?
- Neutrophils
- Eosinophils
- Basophils
- Monocytes
- Lymphocytes
What do mature neutrophils have?
Multi-lobed nucleus and small granules in the cytoplasm
What is the function of neutrophils?
To migrate out of the circulation to a site of infection and destroy foreign material by phagocytosis
What is the process of migration to site of infection known as?
Chemotaxis
What does chemotaxis occur in response to?
Chemotactic substances released by bacteria or other white cells already presented in the infected or damaged tissue
What do some cytokines do regarding neutrophils?
- Increase neutrophil production
- Increase chemotaxis and phagocytosis
Give an example of a cytokine that has an influence on neutrophils?
G-CSF
How long does the average neutrophil survive?
About 10 hours
What do eosinophils have?
Bilobed nucleus and orange granules
What do eosinophils do?
- Phagocytosis
- Release cytotoxic enzymes
What is the purpose of the cytotoxic enzymes released by eosinophils?
To damage larger particles
What are numbers of eosinophils increased in association with?
Allergic reaction and atopy
What do basophils have?
Many large, dark purple granules
What do basophils do?
Mediate acute inflammatory reactions
What do mediatory basophils include?
Heparin and histamine
Describe a monocyte
Large, with folded nucleus, grey/blue cytoplasm and occasional vacuoles
When can monocytes move out of circulation?
After 20-40 hours
What happens once monocytes have moved out of the circulation?
They migrate to become macrophages in many other oragans in the body
What are macrophages known as in the liver?
Kupffer cells
What are macrophages known as in the brain?
Glial cells
What do monocytes do?
Chemotaxis, moving towards areas of infection, inflammation or neoplasm. Can phagocytose and interact with T cells
Describe lymphocytes
Small cells, with round nucleus and rim of pale blue cytoplasm
What % of lymphocytes are T?
75%
What are T lymphocytes responsible for?
Cellular immunity
What are T lymphocytes processed by?
Thymus
What cells are released from lymphocytes?
Only those which can recognise self-histocompatibilty molecules (HLA- human leucocyte antigens), but not react against them
What are helper cells?
T cells expressing CD4 on their surface
What do helper cells do?
Recognise antigens attached to HLA class II molecules, and stimulate cytotoxic cells
How to helper cells stimulate cytotoxic cells?
By expressing CD8
What does CD8 expression do?
Recognises and kills virally infected host cels
What does CD4-expressing helper T cells permit?
The transformation of B cells to plasma cells
What are B lymphocytes responsible for?
Humoral immunity
What can B cells be stimulated by?
Antigens
What happens to B cells on stimulation with antigens?
They transform into immunoblasts, and then plasma cells
What do plasma cells do?
Secrete immunoglobulins
What are immunoglobulins?
Antibody molecules
What are platelets?
Small round blue particles
What produces platelets?
The cytoplasm of megakaryocytes in the bone marrow
What do platelets have?
- Cytoplasm containing alpha granules and dense granules
- Complex surface membrane
What do alpha granules contain?
Fibrinogen, von Willebrand’s Factor and other large molecules
What do dense granules contain?
Small molecules such as ADP and calcium
What does platelet activation result in?
Adhesion to damaged cell wall and aggregation with other platelets
What to platelets present?
A phospholipid surface
What is the purpose of the presentation of the phospholipid surface by platelets?
Provides binding sites for clotting factors during the activation of the clotting cascade
What is blood classified as?
A loose connective tissue
What are the two main parts of blood?
NAME?
Give two examples of the formed elements of blood
- Blood cells
- Platelets
What is the liquid phase of blood called?
Plasma
How does plasma appear histologically?
Structureless, homogenous
What % of blood volume does plasma constitute?
55%
What are the cells of the blood called?
Blood corpuscles
What are the two types of blood corpuscles?
NAME?
What are leucocytes further classified into?
- Polymorphonucleur granulocytes
- Agranulocytes
What are polymorphonucleur granulocytes?
Cells whose nuclei are lobed, and whose cytoplasm is filled with granules
What are agranulocytes?
Cells having normal looking nucleus and cytoplasm, free of granules
What does the blood contain in addition to these corpuscles?
Platelets
Does a mature erythrocyte possess a nucelus?
No
What shape in a mature erythrocyte?
A biconcave disc, about 7.5µm in diameter
Why do erythrocytes often appear circular in blood smears?
They are often orientated ‘face on’
What must be true for an erythrocytes true form to be seen in micrographs?
The film must be sufficiently thick for them to be seen in lateral profile
What is an important characteristic of erythrocytes?
They are extremely flexible
What is the advantage of erythrocytes being extremely flexible?
They can pass through the smallest of blood vessels, the capillaries, whose diameter may be less than theirs
What are a small proportion of red blood cells known as?
Reticulocytes
How much of the circulating RBCs are known as reticulocytes?
1%
What are reticulocytes?
Newly formed RBC which have only just been discharged into the blood from the bone marrow
What stain is used for blood smears?
Leishmanns
What should be looked for when inspecting a blood smear?
- Scan the slide for even cell distribution
- Avoid periphery of slide as spread is too thick where the drop of blood was placed, and too thin where the cells are widely dispersed where smear ended
What shape are polymorphonuclear granulocytes?
Round
How big are polymorphonuclear granulocytes?
10-12µm
What do polymorphonuclear granulocytes have?
A nucleus which has 2-5 lobes
Cytoplasmic granules
What are the polymorphonuclear granulocytes classified as?
- Neutrophils
- Eosinophils
- Basophils
What are the most numerous of the granulocytes?
Neutrophils
How do neutrophils appear?
Pale cytoplasm containing very indistinct granules
What kind of cells are neutrophils?
Phagocytic
What do histological methods show regarding neutrophils?
The granules are actually lysosomes containing digestive enzymes
How long do neutrophils cells last?
Short lived
What happens to neutrophils?
They become pus cells
Where are gross accumulations of pus cells visible?
In abscesses as pus
What are neutrophils able to do?
Migrate through the walls of the blood vessels to reach sites where their phagocytic action is required
How do eosinophils appear?
They have a cytoplasm which is completely filled with large granules which stain red
Describe the properties of eosinophils
- Highly mobile
- Weakly phagocytic
What do eosinophils ingest?
Antigen-antiobdy complexes
What is the result of eosinophils ingesting antigen-antibody complexes?
The blood level of eosinophils is abnormally high in allergic conditions such as asthma or hay fever
What are the least common cells in blood?
Basophils
What is the most distinctive feature of basophils?
Their granules stain intensely blue
What do basophil granules contain?
Heparin, serotonin and histamine
What do basophils resemble?
Mast cells
What are basophils concerned with?
The inflammatory response
When are basophils released into the tissue?
After local tissue damage, released into site of injury
What does histamine cause?
Vasodilation and leakage of fluid into the tissues (oedema)
What does heparin do?
Prevents clotting of the blood
What are the two types of agranulocytes found in the circulating blood?
Monocytes and lymphocytes
What system to monocytes belong to?
Macrophage
What kind of cells are monocytes?
Actively phagocytic
How big are monocytes?
Largest cell in peripheral blood, being almost twice the size of neutrophils
Describe the nucleus of monocytes
Classified as mononuclear cells, but the nucleus irregular in shape, often kidney-shaped and so indented that it may appear to be lbed
What differentiates monocytes from lymphocytes?
Monocytes have abundant cytoplasm
Does monocytes have lysosomes?
Yes, they are present in the cytoplasm, but are barely visible under the light microscope
What are the main characteristics on monocytes?
Their mobility and phagocytic power
What is meant by the motility of monocytes?
They readily pass through the walls of the smallest blood vessels into the surrounding tissues
What are monocytes known as once they are in the tissue?
Histiocytes (tissue macrophages)
What happens to monocytes when the immune reaction subsides?
They may return to the circulation
Describe the appearance of lymphocytes
They have a very high nucleo-cytoplasmic ratio, with a thin rim of cytoplasm evident around the nucleus
Under the electron microscope, small cytoplasmic projections are visible on the surface
What is different about larger lymphocytes?
The cytoplasm is more abundant
How does the nuclear chromatin of lymphocytes stain?
Darkly, usually clumped appearance
What does the identification of different lymphocyte subsets require?
The use of monoclonal antibodies
What do small lymphocytes do?
They are actively mobile cells, which can pass between endothelial cells lining the blood vessels and thus enter adjacent tissues
How is the presence of accumulation of lymphocytes in various tissues explained?
By their migration out of the circulation
Where by aggregations of lymphocytes be found?
In certain chronic inflammatory states and around skin grafts
What happens to lymphocytes that have left the circulation?
They return to the main blood stream by way of the lymphatic system
What is the importance of the lymphocytes?
They are a fundamental part of the adaptive immune response to foreign materials
What are the smallest cells in the blood?
Blood platelets (thrombocytes)
Do platelets have nuclei?
No
How do platelets tend to occur?
In groups
How do platelets appear in blood smears?
Centre appears dark purple, while periphery may be lighter in colour
What is the function of platelets?
To assist in clotting (coagulation or thrombosis) or blood
What are platelets rich in?
- Compounds which cause constriction of blood vessel walls
- Phospholipid factor III
What compound causes constriction of blood vessel walls?
Serotonin
Where do platelets accumulate?
At sites of injury
What do platelets do at sites of injury?
Release serotonin to cause constriction
What are platelets responsible for?
Forming the clot or thrombus
What does phospholipid factor III do?
Activates prothrombin into thrombin
What does thrombin does?
Converts soluble fibrinogen to insoluble fibrin in blood
What does blood plasma contain?
Large number of substances such as proteins (albumins, globulins and fibrinogen), and traces of mineral ions, all of which are dissolved in water. Also contains minute fat globules (chylomicrons) and small particles of broken down blood corpuscles
What % of plasma does water constitute?
90%
What are the stages of haemopoiesis?
Proliferation
Differentiation
What happens in proliferation?
Starting with a stem cell, the cell divides into two
Why does the stem cell divide into two in proliferation?
One to replace the original stem cell (self-renewal), and one that differentiates
What happens in the differentiation stage of haemopoiesis?
The haemopoietic progenitor will first differentiate to form either a myeloid blast or a lymphoid blast
What do myeloid blasts go on to be?
RBC, WBC or platelet
What do lymphoid blasts go on to be?
Immuneresponse cells
What does the progenitor cell differentiate into under the influence of?
A particular cytokine
What is eryhtropoiesis controlled by?
Partial pressure of oxygen
What does a low partial pressure of oxygen stimulate?
Increase in erythrypoietin
What is the life span of a red blood cell?
120 days
What shape is a RBC?
Biconcave, flexible disc
What is the purpose of the shape of RBCs?
It facilitates the passage through microcirculation
Describe the process of haem catabolism?
- Red blood cells are broken down into haemoglobin
- Haemoglobin is broken down into haem
- Haem is broken down in bilirubin
- Bilirubin passes into the liver
- Once in liver, bilirubin either passes to kidney, or to gall bladder through bile duct to small intestine.
- If in small intestine, bilirubin passes down to large intestine, and is either converted to stercobilin or urobilinogen
- Stercobilin continues down large intestine
- Urobilirubin is passed to kidney and excreted
