Cardiovascular System

RED BLOOD CELL

Red blood cells are the most common type of blood cell and are the vertebrate body's principal means of delivering
oxygen from the lungs or gills to body tissues via the blood.
Red blood cells are also known as RBCs or erythrocytes (from Greek erythros for "red" and kytos for "hollow,"
nowadays translated as "cell"). A schistocyte is a red blood cell undergoing fragmentation, or a fragmented part of
a red blood cell.
Blood diseases involving the red blood cells include:

Anemias (or anemias) are diseases characterized by low oxygen transport capacity of the blood, because
of low red cell count or some abnormality of the red blood cells or the hemoglobin.
Iron deficiency anemia is the most common anemia; it occurs when the dietary intake or absorption of
iron is insufficient, and hemoglobin, which contains iron, cannot be formed.

Sickle-cell disease is a genetic disease, which leads to mis-shaped red blood cells.

Thalassemia is a genetic disease that results in the production of abnormal hemoglobin molecules.

Spherocytosis is a genetic disease that causes a defect in the red blood cell's cytoskeleton, causing the
RBCs to be small, sphere-shaped, and fragile instead of donut-shaped and flexible.

Pernicious anemia is an autoimmune disease wherein the body lacks intrinsic factor, required to absorb
vitamin B12 from food. Vitamin B12 is needed for the production of hemoglobin.

Aplastic anemia is caused by the inability of the bone marrow to produce blood cells.

Hemolysis is the general term for excessive breakdown of red blood cells. It can have several causes.

The malaria parasite spends part of its life-cycle in red blood cells, feeds on their hemoglobin and then
breaks them apart, causing fever. Both sickle-cell disease and thalassemia are more common in malaria
areas, because these mutations convey some protection against the parasite.

Polycythemias (or erythrocytoses) are diseases characterized by a surplus of red blood cells. The increased
viscosity of the blood can cause a number of symptoms.

In polycythemia vera the increased number of red blood cells results from an abnormality in the bone
marrow.

Several blood tests involve red blood cells, including the RBC count (the number of red blood cells per
volume of blood) and the hematocrit (percentage of blood volume occupied by red blood cells). The blood
type needs to be determined to prepare for a blood transfusion or an organ transplantation.

WHITE BLOOD CELLS

White blood cells (also called leukocytes or immune cells) are a component of blood. They help to defend the body
against infectious disease and foreign materials as part of the immune system. There are normally between 4x109
and 11x109 white blood cells in a litre of healthy adult blood - about 7 000 to 25 000 white blood cells per drop. In
conditions such as leukemia this may rise to as many as 50 000 white blood cells in a single drop of blood. As well
as in the blood, white cells are also found in large numbers in the lymphatic system, the spleen, and in other body

tissues.

There are three major types of white blood cells.

Granulocytes
Granulocytes are a category of white blood cells, characterized by the fact that all types have differently staining
granules in their cytoplasm on light microscopy. There are three types of granulocytes: neutrophils, basophils, and
eosinophils (named according to their staining properties).

Lymphocytes
Lymphocytes are much more common in the lymphatic system, and include the so-called "killer T-cells". The blood
has three types of lymphocytes: B cells, T cells and natural killer cells. B cells make antibodies that bind to
pathogens to enable their destruction. CD4+ (helper) T cells co-ordinate the immune response (they are what
becomes defective in an HIV infection). CD8+ (cytotoxic) T cells and natural killer cells are able to kill cells of the
body that are infected by a virus.

Monocytes
Monocytes share the 'vacuum cleaner' function of neutrophils, but are much longer lived as they have an additional
role. They present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so
that an antibody response may be mounted. Monocytes are also known as macrophages after they leave the
bloodstream and enter tissue.

Diseases
Leukopenia is a disease symptom defined as a lower than normal number of white blood cells in the blood.
Leukocytosis refers to an increase in the number of white blood cells in the blood.
Leukemia and lymphoma are two types of cancer in which white blood cells multiply out of control.

Other tissue cells

Histiocytes, found in the lymphatic system and other body tissues, but not normally in blood:
Macrophages
Dendritic cells
Mast cells

PLATELETS

Platelets or thrombocytes are the blood cell fragments that are involved in the cellular mechanisms that lead to the
formation of blood clots. Low levels or dysfunction predisposes for bleeding, while high levels - although usually
asymptomatic - may increase the risk of thrombosis.

Production
Platelets are produced in the bone marrow; the progenitor cell for platelets is the megakaryocyte. This large,
multinucleated cell sheds platelets into the circulation. Thrombopoietin (c-mpl ligand) is a hormone, mainly
produced by the liver, that stimulates platelet production. It is bound to circulating platelets; if platelet levels are
adequate, serum levels remain low. If the platelet count is decreased, more thrombopoietin circulates freely and
increases marrow production.

Circulation
The circulating life of a platelet is 9-10 days. After this it is sequestered in the spleen. Decreased function (or
absence) of the spleen may increase platelet counts, while hypersplenism (overactivity of the spleen, e.g. in
Gaucher's disease or leukemia) may lead to increased elimination and hence low platelet counts.

Function
Platelets are activated when brought into contact with collagen (which is exposed when the endothelial blood vessel
lining is damaged), thrombin (primarily through PAR-1), ADP, with receptors expressed on white blood cells or the
endothelial cells of the blood vessels, among other activators. Once activated, they release a number of different
coagulation factors and platelet activating factors, they also provide a catalytic phospholipid surface (with the
charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase and prothrombinase
complexes. The platelets adhere to each other via adhesion receptors or integrins, and to the endothelial cells in
the wall of the blood vessel forming a haemostatic plug in conjunction with fibrin. The high concentration of myosin
and actin filaments in platelets are stimulated to contract during aggregation, further reinforcing the plug. The
most common platelet adhesion receptor is glycoprotein (GP) IIb/IIIa this is a calcium dependent receptor for
fibrinogen, fibronectin, vitronectin, thrombospondin and von Willebrand factor (vWF). Other receptors include GPIbV-IX complex (vWF) and GPVI (collagen)

Activators
There are many known platelet activators. They include

1. Collagen, especially with von Willebrand factor which is exposed when endothelial blood vessel lining is damaged
and binds to GPVI on the platelet,
2. thrombin primarily through cleavage of the extracellular domain of PAR1 and PAR4,
3. Thromboxane A2 (TxA2) which binds to TP,
4. ADP through creation of TxA2, and it can be blocked by conversion of ADP to cAMP,
5. Human neutrophil elastase (HNE) cleaves the IIb3 integrin on the platelet surface,
6. P-selectin which binds to PSGL-1 on endothelial cells and white blood cells, and
7. Convulxin (a purified protein from snake venom) which binds to GPVI.

Inhibitors
Prostacyclin opposes the actions of Thromboxane A2
Nitric oxide
Clotting factors II, IX, X, XI, XII
Nucleotidases by breaking down ADP

Role in disease
High and low counts
A normal platelet count in a healthy person is between 150 and 400 (x 109/L of blood).

Both thrombocytopenia (or thrombopenia) and thrombocytosis may present with coagulation problems. Generally,
low platelet counts increase bleeding risks (although there are exceptions, e.g. Immune heparin-induced
thrombocytopenia) and thrombocytosis (high counts) may lead to thrombosis (although this is mainly when the
elevated count is due to myeloproliferative disorder).

Low platelet counts are generally not corrected by transfusion unless the patient is bleeding or the count has fallen
below 5 (x 109/L); it is contraindicated in thrombotic thrombocytopenic purpura (TTP) as it fuels the coagulopathy.
In patients having surgery, a level below 50 (x 109/L) is associated with abnormal surgical bleeding, and regional
anesthetic procedures such as epidurals are avoided for levels below 80-100.

Note however that the actual platelet count is only part of the story, since they may not all be functioning normally.
For example, aspirin irreversibly prevents platelets from working correctly and so normal hemostasis may not
return until the aspirin is ceased and the affected platelets have been replaced by new ones, which may take over a

week.

Diseases
Disorders leading to a reduced platelet count:
Thrombocytopenia
Idiopathic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Drug-induced thrombocytopenia, e.g. heparin-induced thrombocytopenia (HIT)
Gaucher's disease
Aplastic anemia

Disorders leading to platelet dysfunction or reduced count:

HELLP syndrome
Hemolytic-uremic syndrome
Chemotherapy
Disorders featuring an elevated count:

Thrombocytosis, including benign essential thrombocytosis (elevated counts, either reactive or as an expression of
myeloproliferative disease); may feature dysfunctional platelets

Disorders of platelet adhesion or aggregation:

Bernard-Soulier syndrome
Glanzmann's thrombasthenia
Scott's syndrome
von Willebrand disease

Disorders of platelet metabolism

Decreased cyclooxygenase activity, induced or congenital
Storage pool defects, acquired or congenital

Transfusion
Platelets are separated from donated blood using an apheresis blood separator. This is necessary because platelets
will not survive at the low temperatures used to store red blood cells, so they must be stored separately using

porous storage bags that allow oxygen to flow in and carbon dioxide to flow out. Typical storage is between 20 and
24 C and continuously agitated to promote gas exchange. Because of the higher risks of bacterial growth at this
temperature, platelets are generally only stored for up to 5 days.

A bag of platelets can be separated from multiple bags of whole blood or from a single donor connected to the
separator for less than two hours. By drawing and returning blood repeatedly, a bag of high quality platelets can be
prepared in about 90 minutes. Platelets collected from a single donor can reduce the infection rates of bloodtransmitted diseases.

People with few platelets or platelets that are dysfunctional may benefit from a platelet transfusion, however
patients with autoimmune disorders that affect platelets may not.

Neutrophil granulocytes
Neutrophil granulocytes, generally referred to as neutrophils, are a class of white blood cells and are part of the
immune system.

Neutrophils are active phagocytes, capable of only one phagocytic event, expending all of their glucose reserves in
an extremely vigorous respiratory burst. Low neutrophil granulocyte counts are termed "neutropenia". This can be
congenital (genetic disorder) or due to acquired factors. It can also be a side-effect of medication, including
chemotherapy.

Eosinophil granulocyte
Eosinophil granulocytes, commonly referred to as eosinophils (or less commonly as acidophils), are white blood
cells that are responsible for combating infection by parasites in the body.

Eosinophils make up about 2.3% of the all white blood cells, and are about 10-12 micrometers in size.

Eosinophils play a role in fighting viral infections, which is evident from the abundance of RNAses they contain
within their granules.

Eosinophils also play a role in the allergic response, and in fibrin removal in inflammation. Eosinophils are
considered the main effector cells in asthma pathogenesis and are associated with disease severity.

Basophil granulocyte
Basophils are the least common of the granulocytes, representing about 1% of circulating leukocytes. Basophils
tend to appear in specific kinds of inflammatory reactions, particularly those that cause allergic symptoms.