Red Blood Cells and White Blood cells Flashcards
Hemopoesis
the production of blood cells and platelets, which occurs in the bone marrow
Where does haemopoiesis take place?
- In adults haemopoiesis is confined to the bone marrow
- In embryonic life and early infancy it can occur in other sites
Haematocrit
the volume of red blood cells i.e haemoglobin in the blood, normal haematocrit is 0.45
Problems with RBC
Anaemia-Hypoxia
hypo-regenerative vs. hyper-regenerative
reduced production vs. increased destruction
corpuscular (membrane proteins, haemoglobin, enzymes) vs. extra-corpuscular (increased destruction, reduced production, redistribution)
Blood has two phases
Cellular component (45%)
Red cells (form 99% of blood cells), white cells & platelets
Fluid component (55%); Plasma
Plasma without clotting factors is called serum
How much blood do we contain?
5 Litres
Primitive cells
The most primitive cells are stem cells; can be pluripotent (haematocytoblast are primitive o blood cells) - can differentiate into red blood cells, white blood cels and platelets
In the bone marrow the primitive cells (stem cells) proliferate and differentiate into mature cells
Red blood cell lifetime
120 days (make 2 million a second)
RBCs stimulating hormone, produced by the kidney, is called erythropoietin
This hormone influences formation of red blood cells
Platelets lifetime
7-10 days
red blood cells & platelets are anucleate (have no nucleus)
White blood cells lifetime
6 hours
Location of precursor cells of red blood cells
The precursor cells of red blood cells are located in the bone marrow:
- In adults this is in the axial skeleton - skull, ribs, spine, pelvis and long bones - In children this is in all bones
- In utero this is in the yolk sac, then liver and spleen
Precursor cells are not found in blood (if they are this is a sign of leukaemia)
Hormonal growth factors stimulate precursor stem cells to proliferate and differentiate:
- Epo/ Erythropoietin (hormone made in kidney) = red blood cells
- G-CSF (granulocyte colony stimulating factor) = white cells
- Thrombopoietin = platelets
What happens to the O2 dissociation curve when pH is decreased or when temperature is increased?
Shifts to the right
What happens to the O2 dissociation curve when pH is increased or when temperature is decreased?
Shifts to the left
Why do cells with no nucleus or mitochindria have a short lifespan?
They can not repair themselves
What is a Reticulocyte?
Young red blood cell
What do red blood cells consist of?
membrane to enclose Haemoglobin, otherwise the haemoglobin would clog up the kidneys if allowed into the blood on its own
enzymes of glycolysis
Haemoglobin - to carry oxygen
Function of Haemoglobin
Carries oxygen from the lungs to tissues, where it transfers oxygen to myoglobin in muscles
What does Haemoglobin consist of?
the protein haemoglobin, oxygen binds to the Fe 2+ in haem reversibly
Structure of Haemoglobin
is formed of 2 alpha and 2 beta chains and 4 haem groups
In fetus: 2 alpha and 2 gamma (gamma have a higher affinity for oxygen as fetus is codependent so needs higher affinity)
Has an overall quaternary structures - due to the combination of more than two tertiary structures
BLOOD TYPE & TRANSFUSIONS
Some people have the gene that results in the synthesis of the A antigen on the surface of red blood cells, some have the gene that results in the synthesis of the B antigen, some have both genes and some have neither.
Those who have neither are said to have O-type erythrocytes.
Thus the possible blood types are A (more common than B), B, AB (most rare) & O (most common)
Type A
individuals always have anti-B antibodies in their plasma.
A ANTIGEN IS CO-DOMINANT
Type B
individuals always have anti-A antibodies in their plasma.
B ANTIGEN IS CO-DOMINANT
Type AB
have neither anti-A or anti-B antibodies in their plasma, has A + B antigens on surface of red blood cells - UNIVERSAL RECIPIENT
Type O
have both anti-A & anti-B antibodies ( has no A or B antigens) in their plasma [type O is a UNIVERSAL DONOR since don’t have A or B antigens on surface of red blood cell]
O antigen is RECESSIVE
Natural antibodies
These types of antibodies are anti-erythrocyte antibodies
These are anti-A and anti-B antibodies
If a Type A person was transfused with Type B blood…
1) the anti-B antibodies in the recipients blood would attack the transfused blood
AND 2) the anti-A antibodies in the donor blood would attack the recipients blood HOWEVER this is usually of little consequence since the the transfused antibodies become so diluted in the recipients plasma that they are ineffective at inducing a response
- it is the destruction of the TRANSFUSED cells by the recipients antibodies that produces problems
Rhesus antigens
There are many different Rh antigens but only 5 are clinically significant: D, C, c, E, and e
2 genes
-RHD (coding for Rh D)
-RHCE (coding for Rh C and Rh E)
Rh D is the most immunogenic (i.e. likely to produce an immune response) and therefore the most likely to precipitate a transfusion reaction.
The presence or absence of Rh D antigen on the erythrocyte cell surface determines whether the person has Rh positive (Rh+) or Rh negative (Rh-) blood groups
Rhesus positive
Means the D antigen is present
and can receive both Rh+ and Rh- blood
Rhesus negative
Means the D antigen is not present
and should only receive Rh- blood
Anti-D antibody is usually absent in Rh- patients (until they have been exposed to Rh+ erythrocytes). Rh- patients should not be transfused with Rh+ blood as this can cause them to develop anti-D antibodies.This may cause transfusion reactions in the future.
Anaemia
Reduction in haemoglobin in the blood
Normal haemoglobin= 12.5 - 15.5 g/dl
- If lower = anaemia
- If higher = polycthaemia
Polycthaemia cause
smoking, lung diseases, inefficient lungs meaning less O2 is exchanged so more haemoglobin is required etc
Symptoms of anaemia
Tiredness
lethargy
malaise
reduced exercise tolerance
shortness of breath on exertion and angina
Signs of anaemia
Palor, pale mucus membranes
Palmar creases (pink hands)
Glossitis (sore tongue)
Angular stomatitis ( cracking at corners of mouth)
Kylonychia (caused by the iron deficiency - spoon shaped nails)
Classifications of anaemia
Iron deficiency
B12/folate deficiency
Anaemia of chronic disorder
Haemolysis
Bone marrow failure/infiltration
Iron Deficiency anaemia
Iron is needed for haemoglobin production, lack of iron results in the reduced production of small red cells
Red cell size is measure as MCV (mean cell volume)
Normal = 82 - 96 fl 3 KP
In iron deficiency anaemia there is a low haemoglobin and MCV < 80 fl
Causes of Iron deficiency anaemia
- Bleeding:
• Occult gastrointestinal: can affect anyone, most common cause of iron deficiency anaemia
• Menorrhagia (heavy periods): Occurs in premenopausal women only or those who’ve have repeated child birth
- Dietary:
• Not getting enough iron in diet, in the UK the cause is never diet
• Worldwide the most common cause of iron deficiency anaemia is diet
RBCs in Macrocytic Anaemia
normal red blood cell size = 82-96 fl, in macrocytosis anaemia = > 100 fl (large red blood cells)
Macrocytosis can occur without anaemia because…
there will be a raised MCV but normal haemoglobin levels this can be cause by liver disease, alcohol and hypothyroidism
Why does macrocytic anaemia occur?
Macrocytosis is a sign of it.
It occurs due to a vitamin B12 or folate deficiency
How does deficiency of vitamin B12 and folate lead to anaemia?
Vitamin B12 and folate are needed for DNA synthesis, therefore with a B12 and folate deficiency RBCs cannot be made in the bone marrow and thus less are relased
Which cells does this defiency effect?
Will affect all dividing cells, but bone marrow is most active so it id affected first.
Causes of B12 deficiency (1)
In the terminal ileum B12 absorption occurs, however intrinsic factor PRODUCED BY THE GASTRIC PARIETAL CELLS IN THE STOMACH is required for absorption to occur since B12 binds to intrinsic factor and is THEN absorbed.
Thus if the stomach is damaged can result in less parietal cells thus less intrinsic factor thus less B12 absorbed thus anaemia
Causes of B12 deficiency (2)
An autoimmune disease called PERNICIOUS ANAEMIA, causes the antibodies to be made against gastric parietal cells meaning less intrinsic factor can be produced so there is B12 malabsorption and thus ANAEMIA.
However the liver have a vast store of B12 which can last 4 years, thus pernicious anaemia has a slow onset
Causes of folate deficiency:
• Folate is found in vegetables and fruit
• Malabsorption e.g. due to celiac disease
• Dietary e.g. don’t eat enough fruit and vegetables
• Increased need e.g. due to haemolysis or anything that results in increased cell division can cause a folate deficiency
Haemolysis
Normal or increased cell production but DECREASED LIFE SPAN < 30 DAYS, red blood cells are destroyed before their 120 day lifespan
Congenital (present from birth)
- Membrane issues e.g SPHEROCYTOSIS - whereby blood cells are spherical, they get stuck in vessels easily, DOMINANT CONDITION BUT VARIABLE PENETRANCE
- Enzyme issues e.g PYRUVATE KINASE DEFICIENCY - enzyme required to convert phosphoenolpyruvate to pyruvate is deficient, resulting is less ATP production and also a build up of phosphoenolpyruvate, or G6PD DEFICIENCY
- Haemoglobin issues e.g. SICKLE CELL ANAEMIA (defect in beta globin chain in haemoglobin) - whereby red blood cells are sickle shaped thus get trapped in vessels easily, and THALASSAEMIA - mutation in haemoglobin chains, beta is more common in india + Pakistan whereas alpha is more common in east e.g. Thailand
Acquired
- Autoimmune: immune system attacks own red blood cells, can be triggered by a blood transfusion due to the presence of foreign antibodies
- Mechanical: fragmentation of red blood cells by mechanical heart valve, or intravascular thrombosis in DIC (disseminate intravascular coagulation) ]
-Pregnancy
Pregnancy: HAEMOLYTIC DISEASE OF THE FOETUS & NEWBORN [HDFN]:
Mother has Rhesus NEGATIVE blood (RhD negative) and baby has Rhesus POSITIVE blood (RhD positive).
When mothers blood is exposed to babies blood in pregnancy for example, mothers immune system recognises foreign Rhesus positive blood and begins making antibodies against babies blood
- FIRST baby is unaffected since it takes time for antibodies to be produced, the mother is said to be SENSITISED to Rhesus positive blood
However, if mothers second baby also has RhD positive blood, then when mothers blood is exposed to babies, antibodies are produced IMMEDIATELY and begin DESTROYING BABIES RED BLOOD CELLS - resulting in HAEMOLYSIS OF FOETUS/NEWBORN = ANAEMIA AND JAUNDICE.
Whilst mother is carrying the baby, her antibodies can cross to baby via the placenta and begin attacking - THIS IS KNOWN AS RHESUS DISEASE
White Blood Cells
Normal white blood cells are mature cells that circulate in the blood, they are produced from immature precursor cells in the bone marrow which are derived from stem cells.
Rate of production is under hormonal control of G-CSF (Granulocyte Macrophage Colary Stimulating factor)
Types of White Blood cells
Granulocytes:
-Neutrophils
-Eosinophil
-Basophil
Agranulocytes
-Monocytes
-Lymphocytes: B cells & T cells
Phagocytose
Neutrophils:
- Most numerous white cell - lifespan is 10 hours- multi lobed and faint granules
Function: acute inflammatory response
Transfusions of Granulocytes- For severely neutropenic patients with life threatening bacterial infections
Must be irradiated
Phagocytose & kill bacteria
- Release chemotaxins (signal more white blood cells to come to site) and cytokines - important in inflammatory response
- Lack of number or function results in recurrent bacterial infections
Lymphocytes: B cells & T cells
- Vital to immunity
- Some generate antibodies against specific foreign antigens e.g bacteria & viruses
- Others are immunological memory - which generates immunity and allows vaccination
B lymphocytes
named after Bone marrow, made in bone marrow -
stored in secondary lymphoid organs,
differentiate into plasma cells and produced immunoglobulins when stimulated by exposure to foreign antigen
White cell conditions-
- Acute leukaemia:
Proliferation of primitive precursor cells usually found in bone marrow, proliferation WITHOUT differentiation, replaces NORMAL BONE MARROW CELLS - resulting in anaemia (palor and lethargy),
Neutropenia: infections (since white cells are not being differentiated)
Thrombocytopenia: excessive bleeding.
THE PRESENCE OF PRIMITIVE WHITE PRECURSOR CELLS IN THE BLOOD IS A SIGN OF acute leukaemia
White cell conditions-
- Acute myeloblastic leukaemia (AML):
Malignant proliferation of the precursor myeloblasts (unipotent stem cells) in the bone marrow, disease primarily affects adults - 50% survive 5 years
White cell conditions-
- Acute lymphocytic leukaemia (ALL):
Malignant proliferation of the lymphoblast precursor cells in the bone marrow, disease primarily affects children - 80% cured
High grade lymphoma
(lymphocytes in lymph nodes becoming malignant, very similar to leukaemia):
Classified as Hodgkins disease and Non-Hodgkins lymphoma (NHL), disease usually of the lymph nodes that spreads to the liver,spleen, bone marrow and blood
T lymphocytes
made in bone marrow - MATURE in thymus, some are helper cells (CD4, help B cells in antibody generation, responsible for cellular or cell mediated immunity), some are cytotoxic cells (CD8)
Monocytes
Immature cells that can become macrophages and antigen presenting cells
Reinform nucleus
Eosinophil
First cells that are visible in parasitic infection
Release antihistamines to reduce allergic response- bind to IgE receptors
Pink granules
Basophil (Called this in circulation)
Called Mast cells in tissues
Increase the allergic response
Bind to IgE receptors
Have dark blue granules
