Lecture 1 - Introduction to blood Flashcards
What are the components of the blood and what components form when blood is centrifuged?
If anticoagulant is added to the blood sample and it is centrifuged three layers form
* Plasma (55%) - pH 7.0; electrolytes. plasma proteins, various solutes
* Buffy coat - white blood cells and platelets
* Red blood cells (45%)
If anticoagulant isn’t added then serum will be present instead of plasma and there is no buffy coat.
What are the origin of blood cells?
All blood cells originate from one pluripotent stem cell. This cell differentiates into myeloid stem cells and lymphoid stem cells.
Myeloid stem cells go on to from erythrocytes (RBCs) and platelet cells from broken down megakaryoblast cells. It also forms granular leukocytes (Eosinophil, Basophil and Neutrophil) and monocytes (agranular) which are derived from the progenitor cell (colony forming unit - granulocyte macrophage (CFU-GM)).
Lymphoid stem cells form T-cells and B-cells including T-lymphocytes, B-lymphocytes and natural killer cells (agranular).
Why is it iportant to know about haematopoitic pre-cursors?
It is important to have a knowledge and understanding of haematopoietic precursors as they can be used in diagnosis of disease. Precursors are not often seen in blood smears except in leukaemia, severe infection or systemic disease. Erythrocyte pre-cursor cells (have nucleus) can indicate severe anaemia associated with sickle cell anaemia.
Knowledge of precursors allow us to identify what is normal and what is abnormal.
What are the feature of RBCs
Red Blood Cells (erythrocytes)
* 120 day lifespan - as they have no nucleus it is difficult to repair damage
* Biconcave - enhance O2 delivery
* Large SA
* Oxygen transport
* Haemoglobin
* Aerobic metabolism for energy generation - so it doesn’t use the O2 it carries
Describe the structure of Haemoglobin.
A haemoglobin molecule is composed of four protein globin chains (2x alpha and 2x beta), each surrounding a central haem group.
Each haem group consists of a porphyrin ring with an iron atom in the centre. Each iron atom can combine with one molecule of oxygen.
Describe the RBC life cycle.
As the RBCs move around the body they become deformed and start expressing markers that signal to phagocytic macrophages (Spleen, liver and red bone marrow). The product of the breakdown of RBC is Heme and Globin.
1. The globin is broken down into amino acids which are reused for protein synthesis
2. The haem further breaks down into Fe3+ and Biliverdin
a. The biliverdin is broken down into bilirubin which is transported in the blood to the liver where it is subsequently released into the small intestine in the bile. In the large intestine bacteria breaks down the bilirubin into urobilinogen which is either transported to the kidney in the blood where it is excreted in the urine or broken down into stercobilin which is excreted in the faeces.
b. The Fe3+ transported by transferrin to the liver where it is stored in ferritin. It can then be when necessary be transported in the blood to the red bone marrow where it can be used in erythropoiesis to create new red blood cells
The rate of formation by red bone marrow is equal to the rate of RBC destruction by macrophages
If there is an imbalance and there are too many RBCs this can lead to iron deposition in tissues which can lead to toxicity. Conversely if there is too much destruction it can lead to anaemia.
Describe how the structure of RBC help them cope with stress preventing damage.
RBCs experience physical and shear stresses as they move through the blood vessels which can lead to damage.
The structure of the RBC membrane allows the cells to physically transform.
* There are more than 50 transmembrane proteins of various abundance expressed in RBC membranes.
* About half of these transmembrane proteins define the various blood group antigens
* Other proteins are involved in membrane cohesion and stability
○ Ankyrin complex - normal membrane cohesion
4.1R complex - mechanical stability
Describe the structure of the Spectrin-actin-protein 4.1R junctional complex.
Spectrin-actin-protein 4.1R junctional complex
The complex makes the membrane more flexible so that it can maintain its shape and reduce damage.
* The α and β-spectrin form an antiparallel heterodimer
* The head end of the β-spectrin dimer binds to ankyrin as part of the ankyrin complex - normal membrane cohesion
* At the tail end, the spectrin dimer binds to actin filaments which are capped at opposite ends by adducin and tropomodulin
* Actin binds to protein 4.1R and the complex is anchored to transmembrane proteins
The spectrin dimer-dimer interaction and the spectrin-actin 4.1R complex are critical in allowing the red blood cells to undergo deformation and reformation as they move through the circulation.
Define these terms:
Isocytosis
Anisocytosis
Microcytic
Macrocytic
Poikilocytosis
Hypochromic
Isocytosis = cells have the same size
Anisocytosis = cells have unequal size
Microcytic = cells are smaller than usual
Macrocytic = cells are larger than usual
Poikilocytosis = cells have an atypical shape
Hypochromic = cells don’t stain well
What are the quantative and qualatitve values obtained from a CBC?
A complete blood count (CBC) is used to monitor general health, diagnose conditions and monitor condition and treatment.
Quantitative values:
* WBC count - Number of white blood cells/blood volume
* RBC count - Number of red blood cells/blood volume
* Haemoglobin - Amount of Hb/blood volume
* Haematocrit (packed cell vol) - Ratio of volume of RBCs to total blood volume
* Platelet count - Number of platelets/blood volume
Indices/Qualitative values
* Mean Corpuscular volume (MCV) - Size of RBC
* Mean Corpuscular haemoglobin (MCH) - Amount of Hb/cell
Mean Corpuscular Haemoglobin concentration - Amount of Hb/volume of RBCs (% of RBCs that contain Hb)
What are the 8 major blood group antigens?
There are 8 major blood group antigens that are either sugars (ABO, Hh) or proteins (Rh, Diego, MNS, Kell, Kidd, Duffy)
Describe the features of the ABO system of blood grouping.
ABO system of blood grouping
* Of the blood group antigens, ABO antigens produce the strongest immune response and therefore are very important to consider in regards to blood transfusions
* The ABO antigens are encoded by the ABO gene, which has three alleles: A, B, and O.
* A child receives on of each allele from the mother and father = 6 possible genotypes
* The O allele is recessive = 4 possible phenotypes (i.e. 4 blood types)
Describe the formation of ABO antigens.
The H antigen is the precursor for ABO antigens; h (recessive) does not code for H antigen.
The H gene (Chr19) codes for the fucosyltransferase enzyme that adds a fucose (fuc) onto the terminal galactose of an oligosaccharide chain = produces the H antigen
* The A allele (chr9) encodes a glycosyltransferase that adds an N-acetylgalactosamine (galnac) to the terminal galactose - produces the A antigen
* The B allele (Chr) encodes a glycosyltransferase that adds a D-galactose (gal) to the terminal galactose = produces the B antigen
* The O allele (chr9) encodes a non-functional glycosyltransferase so no additions are made to the terminal galactose = produces on AB antigens (i.e. unmodified H antigen)
Describe the Rh blood group.
Of the blood group antigens, Rh antigens produce the second strongest immune response.
* There are 49 different Rh antigens of which D, C, E, c, and, e are the most important
* Two genes -RHD and RHCE (chr1) encode the Rh antigens
* If RHD gene is present = Rh D+; if Rh D gene deleted = Rh D-
Alternative splicing of RHCE gives rise to C, c, E or e proteins
