Components of Blood -

1 - Formed elements:

Red blood cells (or erythrocytes)

White blood cells (or leucocytes)

Platelets (or thrombocytes)

2 - Plasma = water + dissolved solutes

Red blood cell, platelet, and white blood cell

Red Blood Cells (or erythrocytes):

1 - biconcave discs
2 - lack a nucleus & cannot reproduce (average lifespan = about 120 days)

3 - transport hemoglobin (each RBC has about 280 million hemoglobin molecules)

4 - Typical concentration is 4-6 million per cubic mm (or hematocrit [packed cell
volume] of about 42% for females & 45% for males)

5 - contain carbonic anhydrase (critical for transport of carbon dioxide)

Determining the hematocrit

Erythropoiesis = formation of erythrocytes

the body must produce about 2.5 million new RBCs every second

in adults, erythropoiesis occurs mainly in the marrow of the sternum, ribs, vertebral
processes, and skull bones

begins with a cell called a hemocytoblast or stem cell (below)

rate is regulated by oxygen levels:

hypoxia (lower than normal oxygen levels) is detected by cells in the kidneys

kidney cells release the hormone erythropoietin into the blood

erythropoietin stimulates erythropoiesis by the bone marrow

training.seer.cancer.gov
Three main classifications of blood cells derive from haematopoietic stem cells
(HSCs) (Katsura 2002).

Myeloid cells. This includes macrophages (monocytes) and granular white blood cells
(or granulocytes; neutrophils, basophils and eosinophils). Macrophages have a role in
adaptive immunity, cooperating with T and B cells through antigen presentation and
the production of cytokines.

Erythroid-megakaryocytes. Erythrocytes (red blood cells) carry oxygen through

blood vessels, whereas platelets derived from megakaryocytes work to prevent blood
loss.

Lymphoid cells. This includes T-cells and B-cells. Natural killer (NK) cells are
thought to be the prototype of T cells. Thymic, as well as pre-thymic, T-cell
progenitors are able to generate dendritic cells. B cells secrete antibodies.

Hemoglobin

composed of globin (made up of 4 highly folded polypeptide chains) + 4 heme groups

(with iron)

each molecule can carry 4 molecules of oxygen

called oxyhemoglobin when carrying oxygen & called reduced hemoglobin when not
carrying oxygen

can also combine with carbon dioxide & helps transport carbon dioxide from the
tissues to the lungs
 The binding and release of oxygen illustrates the
structural differences between oxyhemoglobin and
reduced (or deoxy-) hemoglobin. Only one of the four
heme groups is shown
(Source: wikipedia).

Hemoglobin and oxygen transport

White blood cells (or leucocytes or leukocytes):

have nuclei & do not contain hemoglobin

typical concentration is 5,000 - 9,000 per cubic millimeter

types of WBCs:

granular white blood cells include:

neutrophils (50 - 70% of WBCs)

eosinophils (1 - 4%)

basophils (less than 1%)

agranular (or non-granular) white blood cells include:

lymphocytes (25 - 40%)

monocytes (2 - 8%)
Granular white blood cells contains numerous granules in the cytoplasm, & their
nuclei are lobed. Agranular white blood cells have few or no granules in the
cytoplasm & have a large spherical nucleus. Granular white blood cells are produced
in the bone marrow, while agranular white blood cells are produced in lymph tissue,
e.g., Lymph nodes (specialized dilations of lymphatic tissue which are supported
within by a meshwork of connective tissue called reticulin fibers and are populated by
dense aggregates of lymphocytes and macrophages).

How white blood cells are formed

The primary functions of the various white blood cells are:

Neutrophils - phagocytosis (bacteria & cellular debris); very important in

inflammation

Neutrophils

Eosinophils - help initiate and sustain inflammation and can activate T-cells (directly
by serving as antigen-presenting cells and indirectly by secreting a variety of
cytokines). Eosinophils can also kill bacteria by quickly releasing mitochondrial DNA
and proteins (described below).
Eosinophils respond to diverse stimuli, including tissue injury, infections, allografts,
allergens, and tumors. Eosinophils can also release a variety of cytokines,
chemokines, lipid mediators, and neuromodulators. Eosinophils directly communicate
with T cells and mast cells. Eosinophils activate T cells by serving as antigen-
presenting cells.

Basophils - along with mast cells, play a role in inflammation and allergic responses
Release of histamine (that contributes to the 'symptoms' of allergies) by mast cells
requires the production of antibodies (IgE) by B-cells and
that process is regulated, in part, by cytokines produced by basophils (Bischoff 2007).

Monocytes - phagocytosis (typically as macrophages in tissues of the liver, spleen,

lungs, & lymph nodes) & also important antigen-presenting cells
Once distributed through the blood stream, monocytes enter other tissues of the body
such as the liver (Kupffer cells),
lungs (alveolar macrophages), skin (Langerhans cells), and central nervous system
(microglia) (Gordon 2003).

Lymphocytes - immune response (including production of antibodies)

Lymph system
Eosinophils (in green with red nucleus) catapult their mitochondrial DNA out of the
cell, forming tangled traps (red) that ensnare foreign bacteria.
(Photo credit: Hans-Uwe Simon, Institute of Pharmacology, University of Bern,
Switzerland)

Catapult-like release of mitochondrial DNA by eosinophils -- Although

eosinophils are considered useful in defense mechanisms against parasites, their exact
function in innate immunity remains unclear. Yousefi et al. (2008) found that
eosinophils in the gastrointestinal tract release mitochondrial DNA in a rapid,
catapult-like manner—in less than one second. The mitochondrial DNA and proteins
released by the eosinophils bind to and kill bacteria. This is a previously undescribed
mechanism of eosinophil-mediated innate immune responses that might be crucial for
maintaining the intestinal barrier function after inflammation-associated epithelial cell
damage, preventing the host from uncontrolled invasion of bacteria.

Some important characteristics of White Blood Cells (particularly neutrophils):

1 - phagocytic

2 - capable of diapedesis (also called extravasation)

3 - capable of ameboid movement

4 - exhibit chemotaxis (attracted to certain chemicals, such as those released by

damaged cells)
Phagocytosis

Lymph system

Chemotaxis & ameboid movement

Platelets (or thrombocytes)

1 - formed in the bone marrow from cells called megakaryocytes

Megakaryocytes. (A) & (B) immature cells. (C) mature cell producing platelets.
(Source: Battinelli et al. 2001).

2 - have no nucleus, but can secrete a variety of substances & can also contract
(because they contain actin & myosin)
3 - normal concentration in the blood is about 250,000 per cubic millimeter

4 - remain functional for about 7 - 10 days (after which they are removed from the
blood by macrophages in the spleen & liver)

5- play an important role in hemostasis (preventing blood loss)

Platelet adhesion and aggregation

Plasma:

1 - Water - serves as transport medium; carries heat

2 - Proteins

Albumins

60-80% of plasma proteins

most important in maintenance of osmotic balance

produced by liver

Globulins

alpha & beta

some are important for transport of materials through the blood (e.g., thyroid hormone
& iron)

some are clotting factors

produced by liver

gamma globulins are immunoglobulins (antibodies) produced by lymphocytes

Fibrinogen

important in clotting

produced by liver

Twenty-two proteins constitute 99% of the protein content of plasma (Tirumalai et al.
2003).

3 - Inorganic constituents (1% of plasma) - e.g., sodium, chloride, potassium, &

calcium

4 - Nutrients - glucose, amino acids, lipids & vitamins

5 - Waste products - e.g., nitrogenous wastes like urea

6 - Dissolved gases - oxygen & carbon dioxide

7 - Hormones
Hemostasis - prevention of blood loss from broken vessel (check this Hemostasis
animation and this one and this one):

Blood coagulation

1 - Vascular spasm - vasoconstriction of injured vessel due to contraction of smooth

muscle in the wall of the vessel. This 'spasm' may reduce blood flow & blood loss but
will not stop blood loss.

2 - Formation of a platelet plug - platelets aggregate at the point where a vessel

ruptures. This occurs because platelets are exposed to collagen (a protein found in the
connective tissure located just outside the blood vessel). Upon exposure to collagen,
platelets release ADP (adenosine diphosphate) & thromboxane. These substances
cause the surfaces of nearby platelets to become sticky and, as 'sticky' platelets
accumulate, a 'plug' forms.

3 - Blood coagulation (clotting):

Used with permission of Michael W. King, Ph.D / IU School of Medicine

The result of all of this is a clot - formed primarily of fibrin threads (or polymers), but
also including blood cells & platelets.
Blood clots in the right places prevent the loss of blood from ruptured vessels, but in
the wrong place can cause problems such as a stroke (see below under inappropriate
clotting).

Clot retraction:

"tightening" of clot

contraction of platelets trapped within clot shrinks fibrin meshwork, pulling edges of
damaged vessel closer together

Over time (with the amount of time depending on the amount of damage), the clot is
dissolved and replaced with normal tissue.
Fibrinolysis:

dissolution of clot

mechanism = plasminogen (a plasma protein) is activated by many factors & becomes

PLASMIN. Plasmin then breaks down fibrin meshwork & phagocytic WBCs remove
products of clot dissolution

(Modified from en.wikipedia.org/wiki/Fibrinolysis)

Inappropriate clotting:

thrombus - clot formed in an intact vessel, possibly due to:

roughened vessel walls (atherosclerosis; see normal & occluded coronary arteries
below)

slow-moving blood (e.g., in varicose veins) = small quantities of fibrin form &
accumulate

check this animation about deep vein thrombosis

embolus - 'moving' clot

Source: http://www.ors.od.nih.gov/medart/portfolio/Donny/embolus.html

Thrombus and embolus