Download Physiology and histology of white blood cells and platelets - Wk 1-2

Physiology and histology of white blood cells and platelets
1. Outline the physiological role of white blood cells
White blood cells (leukocytes) divided into:


Granulocytes (contain lobed nucleus)
o Neutrophils
o Eosinophils
o Basophils
Agranulocytes (contain unlobed, rounded nucleus)
o Monocytes
o Lymphocytes
Lymphocytes and monocytes circulate in the blood and are also contained in lymph nodes, thumus,
spleen, tonsils, adenoids and Peyer patches.
Lymphoid cells are also contained in the bone marrow, lungs, GIT and other tissue (not as much as in
the lymphoid organs)
WBC respond to foreign bodies presented to the cell and work to discard them
Reactive proliferations of WBC occur during inflammatory responses. This is termed leukocytosis.
During acute inflammation there is a release of cytokines (IL-1 and TNF) and this stimulates bone
marrow stem cells and T cells to produce increased amounts of colony-stimulating factors that
enhance differentiation and proliferation of granulocyte progenitor cells therefore increases
production of neutrophils.
Other growth factors stimulate other WBC. IL-5 enhances differentiation and proliferation of
eosinophils. IL-7 enhances differentiation and proliferation of lymphocytes.
Causes of leukocytosis
Mechanism
Endotoxemia
Increased release from bone marrow
Acute infection
hypoxia
Exercise
Epinephrine
Decreased margination
Glucocorticoids
Decreased extravasation into tissues
Chronic infection or inflammation
Increased numbers of marrow precursors.
Tumours
Myeloproliferative disorders
Reference: Kumar et al, 2005 p. 664
2. Describe the role of platelets, endothelium and coagulation factors in
the maintenance of the integrity of the vascular compartment
Platelets circulate in blood plasma and are membrane bound smooth discs expressing a number of
glycoprotein receptors of the inegrin family on their surfaces. They contain 2 types of granules:


Alpha granules
o
Express P-selectin on their membranes
o
Contain fibrinogen, fibronectin, factors V and VIII, platelet factor 4, platelet derived
growth factor and transforming growth factor β
Dense bodies (δ granules)
o
Contain ADP and ATP, ionised calcium, histamine, serotonin and epinephrine
After a vascular injury, platelets encounter collagen, proteoglycans, fibronectin and other adhesive
glycoproteins all found in the extracellular matrix (ECM), beneath the endothelium.
Once they encounter the ECM, platelets undergo 3 reactions:

Adhesion and shape change
o


Mediated largely via interactions with von Willebrand factor (vWF). This acts as a
bridge between platelet surface receptors (glycoprotein Ib and factors V and IX) and
exposed collagen
Secretion (release reaction)
o
Secretion of the contents of both granule types occurs soon after adhesion.
o
This process is initiated by binding of agonists to platelet surface receptors
Aggregation
o
ADP mediates platelet aggregation, causes further ADP release from other platelets
which leads to surface expression of phospholipid complexes which provide binding
sites for Ca and coagulation factors in the intrinsic clotting pathway.
o
As well as ADP release, there is release of thromboxane (TxA₂) which promotes
platelet aggregation.
o
The actions of both ADP and thromboxane causes platelet aggregation and forms
the first haemostatic plug. This process is reversible however in the coagulation
cascade, thrombin is activated which further causes platelet aggregation by binding
to platelet surface receptor (PAR’s).
o
This is followed by platelet contraction that creates an irreversible fusion of a mass
of platelets. This is the secondary haemostatic plug.
o
While this is happening, thrombin converts fibrinogen to fibrin within and around
the platelet plug essentially cementing it in place.
In summary platelets are freely circulating in the blood, however when they receive chemical
signals from ADP and thromboxane, it causes platelets to bind to the epithelial cells with the help
of vWF that is present in the subepithelial layer of the blood vessel. As the platelets adhere, they
change shape, release more ADP which recruits more platelets to the area and thereby forming
the first haemostatic plug. Once this plug forms, it triggers off the coagulation pathway which
ultimately results in thrombin converting fibrinogen to fibrin. This fibrin forms within and around
the platelet plug, cementing it in place and this is how platelets help to maintain the integrity of
the vascular compartment.
Endothelium

Smooth surface lining blood vessels

Antithrombotic effect:
o

Releases PGI2 (prostacyclin), NO and ADPase that inhibits platelet aggregation in
normal healthy tissue.
Prothrombotic effect:
o
Injury or activation of endothelial cells results in prothrombotic activities
o
Endothelial cells’ production of vWF is an essential co-factor for platelet binding to
collagen
o
Synthesises tissue factor and activates extrinsic clotting cascade. Also binds
activated FIXa and Xa which assists in the catalytic activities of the coagulation
factors
o
Secretes inhibitors of plasminogen activator (PAI’s) which depress fibrinolysis
Coagulation Factors p.128 Kumar

enqymatic conversions turning inactive proenzymes into activated enzymes and eventually
results in the formation of thrombin. Different factors play roles in moving the cascade
forward (see diagram)

Thrombin converts fibrinogen (soluble) to fibrin (insoluble) to form a plug.
3. Discuss the underlying physiology of bruising
A bruise is an injury that does not disrupt the integrity of the skin, caused by a blow to the body,
characterised by swelling, discolouration and pain. It is blood escaping from the blood vessels and
clotting beneath the skin.
Bruising can be caused by:

Trauma which damages blood vessels

Decrease platelet numbers due to increase destruction, decrease production (toxins, viruses,
thrombocytopaenia, leukaemia)

Decreased platelet functioning – acquired or genetic (decrease in vWF)

Abnormalities of coagulation pathway – Vit K deficiency; haemophilia
Changing colours of bruises:
Red/Blue – local haemorrhage
Blue/Green – local formation of biliverdin
Red Bile – bilirubin
Golden Yellow – haemosiderin

Haemoglobin transformed to haemosiderin by macrophages phagocytosing red cell debris
then lysosomal enzymes eventually convert haemoglobin to haemosiderin.
4. Identify the major cell types in a histological blood smear.
Major cell types in a normal blood smear:
 erythrocytes (RBC) most abundant



5.
neutrophils (lobed nucleus)
lymphocytes (unlobed, rounded nucleus)
monocytes (unlobed, rounded nucleus)
Identify major cell types in a bone marrow expirate
erythroblast
Megakaryocyte
Should see an equal ratio of fat cells and haematopoietic cells
Fat cells
Megakaryocytes (bone marrow cell, large lobed nucleus, normally not present in circulating blood)
Erythroblasts
Myeloblasts
Lymphoblasts
It is usually difficult to differentiate the different blast cells.