Constituents Of Blood Flashcards
What are the 2 phases of blood?
Cellular component (45%):
Red cells form 99% of blood cells
White cells and platelets
Fluid component (55%):
Plasma
What is the volume of red blood cells called?
Haematocrit
Normal haematocrit is 0.45
What is haemopoiesis?
The process of the production of blood cells and platelets which continues throughout life
Where does haemopoiesis occur in adults?
Confined to the blood marrow
What are the most primitive cells?
Stem cells
What is the lifetime of different blood cells?
Red blood cells: 120 days
Platelets: 7-10 days
White blood cells: 6 hours
Where are the precursor cells in adults found?
Axial skeleton- skull, ribs, spine, pelvis and long bones
Where are the precursor cells in children found?
In all bones
What are hormonal growth factors?
Stimulate precursor stem cells to proliferate and differentiate
What are the types of hormonal growth factors?
Epo/Erythropoietin: (hormone made in kidney) red blood cells
G-CSF: (granulocyte colony stimulating factor) white cells
Tpo: platelets
What is haemoglobin?
Carries oxygen from the lungs to the tissues, where it transfers oxygen to myoglobin in muscles
What is haemoglobin formed of?
2 alpha and 2 beta chains
4 haem groups
Overall quaternary structure, due to the combination of more than two tertiary structures
What is anaemia?
Reduction in haemoglobin in blood
What is normal haemoglobin level?
12.5-15.5 g/dl
If lower: anaemic
If higher: polycthaemic ( caused by smoking, lung disease, inefficient lungs meaning less O2 is exchanged so more haemoglobin is required )
What are platelets?
Small cytoplasmic anucleate cells that block up holes in blood vessels
Where are platelets made?
Bone marrow from cells called megakaryocytes
What do platelets determine?
Determine bleeding time: PT (prothrombin time)
What is the lifespan of platelets?
5-10 days
What is reduced number in platelets called?
Thrombocytopenia (main risk is cerebral bleeding)
> 80 = increased bleeding
> 20 = spontaneous bleeding
What is high numbers in platelets called?
Thrombocytosis can lead to arterial and venous thrombosis leading to an increased risk of heart attack and stroke
What are coagulation proteins?
Enzymes produced in liver
They circulate in inactive form to make blood clot, converts soluble fibrinogen into soluble fibrin polymer
What is thrombin?
Makes platelet plug
Why is Vitamin K essential for coagulation proteins?
Essential for correct synthesis of coagulation factors (2,7,9 and 10)
What are plasma proteins?
Soluble and in plasma component
What is albumin?
Most numerous protein in plasma, produced in liver, maintain oncotic pressure
Lack of albumin results in oedema
Carries fatty acids, steroids & thyroid hormones
What are immunoglobulins?
Antibodies produced by plasma cells
IgB (most important)
IgM (all start as this)
IgA/IgE (produced in response to non-self protein antigens
When will an oxygen dissociation curve shift to the right?
When pH is decreased
When temperature is increased
When will an oxygen dissociation curve shift to the left?
When pH is increased
When temperature is decreased
Can red blood cells repair themselves?
No as they have no nucleus or mitochondria
What is a young red blood cell called?
Reticulocyte
What is Type A blood type?
Individuals always have anti-B antibodies in their plasma.
A antigen is co-dominant
What is Type B blood type?
Individual always have anti-A antibodies in their plasma.
B antigen is co-dominant
What is Type AB blood type?
Have neither anti-A or anti-B antibodies in their plasma, has A+B antigens on surface of red blood cells
UNIVERSAL RECIPIENT
What is Type O blood type?
Both anti-A and 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 cells
O antigen is RECESSIVE
What are anti-A/anti-B etc antibodies known as?
Anti-erythrocyte antibodies / Natural antibodies
What would happen if a Type A person was transfused Type B blood?
1) The anti-B antibodies in the recipients blood would attack the transfused blood
2) The anti-A antibodies in the donor blood would attack the recipients blood however this is usually of little consequence since 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 recipients antibodies that produces problems
What is Rhesus?
C,D,E antigens
D antigen is most important
What does Rhesus positive mean?
D antigen is present
What does Rhesus negative mean?
D antigen is not present
What are symptoms of anaemia?
Tiredness
Lethargy
Malaise
Reduced exercise tolerance
Shortness of breath on exertion
Angina
What are signs of anaemia?
Palor
Pale mucus membranes
Palmar creases (pink hands)
Glossitis (sore tongue)
Angular stomatitis (cracking at corners of mouth)
Kylonychia (caused by iron deficiency) - spoon shaped nails
What are classifications of anaemia?
Iron deficiency
B12 folate deficiency
Anaemia of chronic disorder
Haemolysis
Bone marrow failure/infiltration
What is iron deficiency anaemia?
Iron is needed for haemoglobin production, lack of iron results in the reduced production of small red cells
What is red cell size measured as?
MCV (mean cell volume)
Normal = 82-96 fl
Iron deficiency anaemia/low haemoglobin = < 80 fl
What are causes of 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 had repeated child birth
Diet: 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
What is macrocytic anaemia?
Can occur without anaemia, there will be a raised MCV (> 100 fl) but normal haemoglobin levels this can be caused by liver diseases, alcohol and hypothyroidism
What is the cause of macrocytic anaemia?
Occurs due to a vitamin B12 or folate deficiency
Why is Vitamin B12 and folate important?
Needed for DNA synthesis
With a B12 and folate deficiency red blood cells cannot be made in the bone marrow and so less is released leading to anaemia
This deficiency will affect all dividing cells, but bone marrow is most active so is affected first
What are causes of B12 deficiency?
- In the terminal ileum B12 absorption occurs, however intrinsic factors 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
- An auto immune disease called pernicious anaemia causes the antibodies to be made against gastric parietal cells meaning less intrinsic factors can be produced so there is a B12 malabsorption and thus anaemia.
However the liver has a vast store of B12 which can last 4 years, thus pernicious anaemia has a slow onset
What are the causes of folate deficiency?
Folate is found in vegetables and fruit
Malabsorption, due to celiac disease
Dietary, don’t eat enough fruit and vegetables
Increased need, due to haemolysis or anything that results in increased cell division can cause a folate deficiency
What is haemolysis?
Normal or increased cell production but decreased life span < 30 days, red blood cells are destroyed before their 120 days lifespan
Congenital (present from birth)
What is spherocytosis?
Blood cells are spherical, they get stuck in vessels easily
Dominant condition but variable penetrance
What is pyruvate kinase deficiency?
Enzyme required to convert phosphoenolpyruvate to pyruvate is deficient, resulting in less ATP production and also a build up of phosphoenolpyruvate or G6PD deficiency
What is sickle cell anaemia?
Defect in beta globin chain in haemoglobin
Red blood cells are sickle shaped thus get trapped in vessels easily
What is Thalassaemia?
Mutation in haemoglobin chains
Beta is more common in India + Pakistan
Alpha is more common in East e.g. Thailand
What is autoimmune?
Immune system that attacks own red blood cells, can be triggered by a blood transfusion due to the presence of foreign antibodies
What is mechanical?
Fragmentation of red blood cells be mechanical heart valve, or intravascular thrombosis in DIC
(disseminate intravascular coagulation)
What is HDFN?
Haemolytic disease of the foetus and newborn
Mother has Rhesus negative blood (RhD negative) and baby has RhD positive.
When mothers blood is exposed to babies blood in pregnancy, 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.
What happens if the mothers second baby is also RhD positive?
When the mothers blood is exposed to babies, antibodies are produced immediately and begin destroying babies red blood cells, resulting haemolysis of foetus/newborn = anaemia/jaundice.
Whilst mother is carrying the baby, her antibodies can cross to baby via placenta and begin attacking
What are 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
What are neutrophils?
Release chemotaxins (signal more white blood cells to come to site) and cytokines, important in inflammatory response
Phagocytose and kill bacteria
Lack of number or function results in recurrent bacterial infections
Most numerous white cell - 10 hours
What are lymphocytes?
B cells & T cells
Vital to immunity
Some generate antibodies against specific foreign antigens e.g. bacteria & viruses
Others are immunological memory - generates immunity and allows vaccination
What are 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)
What is acute leukaemia?
Proliferation of primitive precursor cells usually found in bone marrow, proliferation without differentiation, replaces normal bone marrow cells
What is 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
What is acute lymphocytic leukaemia (ALL)?
Malignant proliferation of the lymphoblast precursor cells in the bone marrow, disease primarily affects children - 80% cured
What is high grade lymphoma?
Lymphocytes in lymph nodes become 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
What is homeostasis?
The arrest of bleeding, involving the physiological processes of blood coagulation and the contraction of damaged blood vessels
Blood is usually fluid inside blood vessels:
- Proteins of the coagulation cascade and the platelets circulate in an inactive state
- Proteins and platelets are only activated by tissue factor, which is present on every single cell apart from endothelial cells, so when endothelium is punctured blood comes into contact with tissue factor and thus starts clotting
What happens it blood clots inside vessel?
Thrombosis
What happens if blood fails to clot outside vessels?
Bleeding disorder
What does bleeding result in?
Results in the beginning of the coagulation cascade:
- series of proteolytic enzymes that circulate in an inactive state being activated (usually by exposure to tissue factor) in a cascade or waterfall sequence
- In order to generate the key enzyme Thrombin which cleaves fibrinogen creating fibrin polymerisation e.g. a blood clot
What is coagulation cascade?
Very complex, multiple steps allow for biological amplification & allows for regulation
Can be graduated in response to severity of challenge
What is haemophilia?
Recessive X-linked
Severe bleeding disorder; bleeding into muscles and joints, not enough clotting factors in blood = slow clotting time or long PTT (prothrombin time)
Only affects males since it’s X-linked inheritance
Females are carriers
What is Haemophilia A?
Bleeding into muscles and joints
Rare: 1 in 10,000 males
Deficiency in clotting factor VIII (8)
Treat with factor VIII
What is Haemophilia B?
Bleeding into muscles and joints
More rare: 1 in 50,000 males
Deficiency in clotting factor XI (9)
Treat with factor XI
Less common since gene is smaller
What is Von Willebrands Factor (VWF)?
VWF is required for platelets to bind to damaged blood vessels, so lack of VWF = platelet dysfunction, hence muco-cutaneous bleeding
Usually a mild bleeding disorder
What is muco-cutaneous bleeding?
Bleeding in skin and mucous membranes e.g. easy bruising, prolonged bleeding from cuts, nose bleeds (epistaxis), spontaneous gum bleeding/GI loss etc
Incidence up to 1% = common
Often unrecognised and undiagnosed
What are acquired bleeding disorders?
Recent onset, not lifelong and no family history
May be generalised or localised bleeding
Most common cause: anti-platelet or anti-coagulation medication
Other causes: Liver disease
What is Vitamin K deficiency caused by?
Caused by malabsorption - especially in obstructive jaundice
Treat with IV Vitamin K
What does aspirin affect?
Platelet function
What is heparin and warfarin and what do they do?
Most widely used oral anticoagulant
Works by inhibiting Vitamin K, affects coagulation cascade
What do steroids do to tissue?
Makes tissues thin and causes bruising and bleeding
What is disseminated intravascular coagulation (DIC)?
Breakdown oh haemostatic balance
Simultaneous bleeding and microvascular thrombosis
Life threatening condition
What are causes of DIC?
Sepsis
Obstetric (anything that goes wrong with pregnancies)
Malignancy
How is a platelet plug formed?
When a vessel is injured/ruptured, this disrupts the endothelium, resulting in the exposure of collagen
Platelets adhere to the collagen fibres via an
intermediary called (VWF)
The platelet adheres to the factor, which itself is adhered to the collagen via a receptor on the platelet membrane called the glycoprotein 1B receptor
What does the binding of platelets to the collagen fibre wall cause?
Triggers the platelet to release the contents of their secretory vesicles via exocytosis
This includes platelet dense granules, which are also released upon cell activation, from these granules ADP is released which acts on the P2Y1 and P2Y12 causing platelet amplification
What is platelet activation?
Thrombin binds to PAR1 and PAR4 receptors, inducing platelet activation and further thrombin release
This results in the platelet changing shape from a smooth discoid shape to a more spiculated (spiky) with pseudopodia, this increases the surface area of the platelet
What does platelet activation cause?
Causes an increase in the expression of glycoprotein IIb/IIIa (GPIIIb/IIIa) receptors on the platelets which binds to fibrinogen (from alpha granules) enabling new platelets to adhere to old ones, a positive feedback mechanism called platelet aggregation
What do platelet plugs do?
Completely seal small breaks in vessels
Its effectiveness is enhanced by its other property which is contraction
Platelets contain a very high concentration of actin and myosin, resulting in compression and strengthening of the platelet plug
What is the primary mechanism used to seal breaks in vessel walls?
Platelet plug
What is coagulation cascade?
Blood coagulation or clotting is the transformation of blood into a solid gel called a clot or thrombus which consists mainly of a protein polymer called fibrin
Clotting occurs locally around the platelet plug and is the dominant haemostatic defence - its function is to support and reinforce the platelet plug and to solidify blood that remains in the wound channel
The cascade can be divided into two parallel pathways, extrinsic and intrinsic
Under physiological conditions, the pathways are in fact not parallel but instead are activated sequentially with thrombin serving as the link between them
What happens in the intrinsic pathway?
What happens in the extrinsic pathway?
