1 Flashcards
What is the life span of a red blood cell?
100-120 days
A RBC is approximately ……………. micro metres in diameter
6.2-8.2
Where are RBCs produced?
In the bone marrow.
What is polycythaemia?
When you have a high number of erythrocytes/high levels of Hb.
What is the condition called where you have a low number of erythrocytes and therefore a reduction of Haemoglobin?
Anaemia
What is the production of RBCs stimulated by?
Erythropoietin.
What is erythropoietin and where is it secreted from?
It is a glycoprotein cytokine mainly secreted by the kidney.
What is primary polycythaemia?
Where the bone marrow cells recklessly produce RBCs due to a change in their genetic code.
What is secondary polycythaemia?
Where an underlying condition causes increased production of erythropoietin which in turn increases RBC production.
Define corpuscula.
The problem is within the erythrocytes.
Define extra-corpuscular.
The problem is occurring outside the erythrocyte.
What is hypo-regenerative?
The bone marrow isn’t producing enough RBCs.
What is hyper-regenerative?
There is an increased destruction of RBCs.
What is the life span of a white blood cell?
most = hours/days
some eg. memory cells = years
The diameter of a white blood cell is ………… micro metres.
7-30.
Where do WBCs develop?
In the bone marrow/thymus depending on what type of WBC they go on to become.
What is the function of white blood cells?
Immunity.
Name the 2 types of immunity.
Specific (adaptive) and non-specific (innate).
Which WBCs are involved in the specific immune response?
Lymphocytes:
B cells
T cells
Natural Killer cells
Which WBCs are involved in the non-specific immune response?
Neutrophils Basophils Eosinophils Macrophages Mast cells
What is granulocyte/stem cell production stimulated by?
G-CSF (Granulocyte-colony stimulating factor).
What is the condition where you have too many neutrophils?
Neutrophil leucocytosis
What is another name for white blood cells?
Leukocytes
What is the condition where you have too few neutrophils?
Neutropenia
What is Eosinophilia?
An increase in eosinophils in response to allergens, drugs, parasites, and some leukaemia.
What is Eosinopenia?
The number of eosinophil granulocytes is low- predictor of a bacterial infection; induced by stress, burns and acute infections.
Does Basopenia have much clinical significance?
No
Basophilia is usually ………….
malignant.
What is monocytosis?
An increase in the number of monocytes in the blood.
Occurs in association with infectious processes, or when the bone marrow is recovering from a toxic injury.
…………. is where there is a low number of monocytes in the blood.
Monocytopenia
Explain the humoral response.
B lymphocytes produce plasma cells. These produce immunoglobulins, which bind to intruders and destroy them.
Explain the cell mediated response.
An antigen is presented by the phagocyte. T lymphocytes recognise this and become active T cells/memory cells.
Name two treatments for white blood cell abnormalities.
1) Granulocyte transfusion
2) cellular therapy
When is granulocyte transfusion used?
Rarely, when there is an overwhelming sepsis.
Where are platelets produced?
In the bone marrow.
What are platelets produced by?
Megakaryocytes shedding particles (exocytosis).
What is thrombocytopenia?
A low platelet count.
What is thrombopoietin?
It is a glycoprotein hormone produced by the liver and kidney which regulates the production of platelets.
Thrombopoietin has TPO receptors on the short arm of the 3rd chromosome. TPO binds to these, activating pathways which stimulate megakaryocyte growth/platelet production. Using this info, what are used to increase platelet production?
Drugs called TPO receptor agonists are used to increase megakaryocyte production. These include eltrombopag and romiplostim.
Platelets have a diameter of …………
2-5 micrometres
What are the 3 stages of platelet activation?
1) Initiation
2) Propagation
3) Stabilisation
Explain initiation of platelet activation.
There is injury to the endothelium.
Collagen and VWF adhere platelets.
The platelets change shape, tether, spread and adhere to each other.
Explain propagation of platelet activation.
Granular release.
Platelets are activated.
Platelet activation stimulated by fibrinogen, which binds to the receptor GPIIb-IIIa.
Explain stabilisation of platelet activation.
Primary platelet thrombus.
Clot takes place on surface.
This is a thrombin/fibrin network.
What are the 4 features of the structure of a platelet?
1) plasma membrane
2) cytoskeleton
3) dense tubular system
4) secretory granules
Name the four secretory granules of platelets.
1) alpha granules (VWF, PF4, plasminogen)
2) dense granules (serotonine)
3) lysosome
4) peroxisome
lysosome and peroxisome clear debris
How can thrombocytopenia be classified.
1) reduced production of platelets
2) increased destruction of platelets
3) altered redistribution of platelets
4) pseudo thrombocytopenia
What is thrombocytopathy?
Any of several blood disorders characterized by dysfunctional platelets, which result in prolonged bleeding, defective clot formation, and a tendency to haemorrhage.
The platelet count is normal but there is a problem with their function.
How can thrombocytopathy be classified?
It can be congenital or acquired.
Bernard-Soulier syndrome is an example of ……………. and is ……………….
a congenital type of thrombocytopathy,
a rare AR bleeding disorder that is caused by a deficiency of the GpIIb receptor.
What are some examples of causes of acquired thrombocytopathy?
Medication.
Underlying diseases such as renal failure, paraproteinemia, MPN, MDS and liver disease.
Platelet and haemophilia ‘types’ are types of what?
Bleeding
Give 5 reasons for platelet type bleeding.
1) Genetic disorder
2) Low platelet count
3) Medication
4) Liver disease
5) Renal failure
Give 3 displays of platelet bleeding.
1) Skin/mucosal bleeding eg. gum/nose
2) Early post-procedural bleeding (mins)
3) petechial rash; non blanching
Give 3 displays of haemophilia bleeding.
1) Muscle/joint bleeding
2) late post procedural bleeding (hours/days)
3) large suffusions/haematomas
What are the 2 types of thrombocytosis?
1) Primary/clonal/essential
2) Secondary/reactive
…………… thrombocytosis poses a much higher risk of clotting or bleeding than ………… thrombocytosis.
Primary
secondary/reactive
What is a young RBC known as?
Reticulocyte
What does a RBC consist of?
A membrane, enzymes of glycolysis and Haemoglobin
Why do RBCs need a membrane?
To enclose Haemoglobin, otherwise haemoglobin would clog up the kidneys if allowed into the blood on its own.
Where does Hb transfer oxygen to from lung?
Myoglobin in muscles.
What is Hb formed from?
2 alpha and 2 beta chains.
4 haem groups.
What is the normal level of Hb?
12.5 - 15.5 g/dl
What is it called if you have a low Hb level?
Anaemia.
What is it called if you have a high level of Hb?
Polycythaemia.
What are symptoms of anaemia?
Tiredness lethargy malaise (general feeling of discomfort/illness) reduced exercise tolerance shortness of breath angina
If a patient presented with any of the following, along with tiredness, lethargy and malaise, what could you suspect?
Palor, pale mucus membranes, palmar creases, glossitis, angular stomatitis, kylonychia
Anaemia
Iron deficiency anaemia:
Iron is needed for Hb production.
Lack of iron results in reduced proportion of small red cells.
In IDA there’s low Hb and MCV (mean cell volume) of < 80 fl
Causes of anaemia may include:
Bleeding: occult GI (most common cause of IDA); menorrhagia (heavy periods)
Dietary: not getting enough iron in diet (worldwide most common cause of IDA)
B12 and Folate deficiency anaemia:
V B12 and folate both needed for DNA synthesis .
With deficiency RBCs can’t be made in bone marrow -> less are released
Deficiency will affect all dividing cells but bone marrow is most active so is affected first.
What is macrocytic anaemia?
When RBC size is larger than 100 fl.
Occurs due to VB12 or folate deficiency.
Causes of B12 deficiency:
Intrinsic factor (produced by gastric parietal cells in stomach) needed for absorption of B12 in terminal ileum.
It binds to B12 and is then absorbed.
If stomach is damaged -> less parietal cells -> less intrinsic factor -> less B12 absorbed -> anaemia
Autoimmune disease called Pernicious Anaemia causes production of antibodies against gastric P cells -> less intrinsic factor produced -> anaemia
Why does Pernicious anaemia have a slow onset?
The liver has a store of B12 which can last 4 years.
Causes of Folate deficiency:
Lack of fruit and veg in diet.
Malabsorption eg. due to celiac disease
Increased need eg. due to haemolysis/ anything that results in increased cell division.
What is haemolysis?
When blood cells are destroyed before their 120 day lifespan.
Examples of congenital haemolysis:
Membrane issues eg. Spherocytosis (blood cells are spherical and get stuck in vessels easily).
Enzyme issues eg. pyruvate kidney deficiency (less pyruvate produced -> less ATP -> build up of phosphoenolpyruvate -> G6PD deficiency)
Haemoglobin issues eg. sickle cell anaemia
Examples of acquired haemolysis:
Autoimmune (immune system attacks own red blood cells)
Mechanical (fragmentation of RBCs by mechanical heart valve) OR intravascular thrombosis in DIC
Pregnancy- haemolytic disease of foetus and newborn
What does a lack of number/function of Neutrophils lead to?
Recurrent bacterial infections
What are WBCs produced from?
Immature precursor cells in bone marrow which are derived from stem cells.
Which is the most numerous WBC?
Neutrophils
What do neutrophils do?
Phagocytose & kill bacteria Release chemotaxins (signal more WBCs to come to site) and cytokines (important in inflammatory response)
What do lymphocytes do?
Some generate antibodies against specific foreign antigens
Others are immunological memory
…. …………………… are made in the bone marrow, stored in secondary lymphoid organs, differentiate into plasma cells and produce immunoglobulins when stimulated by exposure to foreign antigens.
B lymphocytes
…. …………………….. are made in the bone marrow, mature in the thymus, some are helper cells (CD4- help B cells in antibody generation- responsible for cell mediated immunity), some are cytotoxic cells (CD8)
T lymphocytes
Explain acute leukaemia:
Proliferation (rapid increase in number of) primitive precursor cells in bone marrow.
Proliferation without differentiation- replaces normal bone marrow cells resulting in anaemia, neutropenia (infections) and thrombocytopenia (excessive bleeding).
Presence of primitive white precursor cells in blood is a sign of acute leukaemia.
Explain acute myeloblastic leukaemia:
malignant proliferation of precursor myeloblasts (unipotent stem cells) in bone marrow.
Primarily affects adults.
50% survive 5 years.
Explain acute lymphocytic leukaemia:
malignant proliferation of the lymphoblast precursor cells in bone marrow.
Primary affects children.
80% cured.
Explain high grade lymphoma:
lymphocytes in lymph nodes become malignant, very similar to leukaemia.
Classified as Hodgkin’s disease and Non-Hodgkin’s lymphoma.
Disease usually of lymph nodes that spreads to liver, spleen, bone marrow and blood.
What is the lifespan of a platelet?
5-10 days.
What is the normal number of platelets?
140-400 x10^9/l
What is thrombocytosis?
A high number of platelets.
What is the main risk of thrombocytopenia?
cerebral bleeding.
>80 = increased bleeding >20 = spontaneous bleeding
What can thrombocytosis lead to?
arterial and venous thrombosis -> increased risk of heart attack and stroke
Where are coagulation proteins (enzymes) produced?
The liver
What is the key coagulation protein/enzyme?
Thrombin
What does thrombin do?
It creates a platelet plug.
Which vitamin is essential for the correct synthesis of coagulation factors II, VII, XI & X?
(REMEMBER 1972)
Vitamin K
What is the function of coagulation factors?
They circulate in the blood in their inactive form, and make blood clot. They convert soluble fibrinogen to insoluble fibrin polymer.
Which is the most numerous plasma protein?
Albumin
Where is albumin produced?
The liver
What does albumin carry?
fatty acids, steroids and thyroid hormones.
What are immunoglobulins?
antibodies produced by plasma cells.
eg. IgG, IgM, IgA, IgE
