Cardiovascular System

Heart

The heart (Latin cor) is a hollow, muscular organ that pumps blood through the blood vessels by repeated, rhythmic contractions. The term card= iac means "related to the heart", from the Greek kardia for "heart".

Structure

In the human body, the heart is normally situated slightly to the lef= t of the middle of the thorax, underneath the sternum (breastbone). It is enclos= ed by a sac known as the pericardium and is surrounded by the lungs. In normal adults, its mass is 250-350 g, but extremely diseased hearts can be up to 1000 g in mass. It c= onsists of four chambers, the two upper atria (singular: atrium) and the two lower ventricles A septum divides the right atrium and ventricle from the left at= rium and ventricle, preventing blood from passing between them. Valves between t= he atria and ventricles (atrioventricular valves) maintain coordinated unidirectional flow of blood from the atria to the ventricles

The function of the right side of the heart (see right heart) is to collect deoxygenated blood from the body and pump it into the lungs so that carbon dioxide can be dropped off and oxygen picked up. This happens throug= h a process called diffusion. The left side (see left heart) collects oxygenated blood from the lungs and pumps it out to the body. On both sides, the lower ventricles are thicker than the upper atria Oxygen-depleted or deoxygenated= The right ventricle pumps the deoxygenated blood from the body enters the right atrium through two great veins, the superior vena cava, which drains the up= per part of the body and the inferior vena cava that drains the lower part. The blood then passes through the tricuspid valve to the right ventricle.oxyyge= nated blood to the lungs, through the pulmonary artery. In the lungs gaseous exch= ange takes places and the blood releases carbon dioxide into the lung cavity and picks up oxygen. The oxygenated blood then flows through pulmonary veins to= the left atrium. From the left atrium this newly oxygenated blood passes through the mitral valve to enter the left ventricle. The left ventricle then pumps= the blood through the aorta to the entire body. Even the lungs take some of the blood supply from the aorta via bronchial arteries.

The left ventricle is much more muscular (1.3 - 1.5 cm thick) than t= he right (0.3 - 0.5 cm thick) as it has to pump blood around the entire body, which involves exert= ing a considerable force to overcome the vascular pressure. As the right ventri= cle needs to pump blood only to the lungs, it requires less muscle.<= /span>

Even though the ventricles lie below the atria, the two vessels throu= gh which the blood exits the heart (the pulmonary artery and the aorta) leave = the heart at its top side.

The contractile nature of the heart is due to the presence of cardiac muscle in its wall, which can work continuously without fatigue. The heart = wall is made of three distinct layers. The first is the outer epicardium, which = is composed of a layer of flattened epithelial cells and connective tissue. Beneath this is a much thicker myocardium made up of cardiac muscle. The endocardium is a further layer of flattened epithelial cells and connective tissue which lines the chambers of the heart.

The blood supply to the heart itself is supplied by the left and right coronary arteries, which branch off from the aorta.

3D"Text

The cardiac cycle

3D"Text

The function of the heart is to pump blood around the body. Every sin= gle beat of the heart involves a sequence of events known as the cardiac cycle, which consists of three major stages: atrial systole, ventricular systole a= nd complete cardiac diastole. The atrial systole consists of the contraction of the atria and the corresponding influx of blood into the ventricles. Once t= he blood has fully left the atria, the atrioventricular valves, which are situ= ated between the atria and ventricular chambers, close. This prevents any backfl= ow into the atria. It is the closing of the valves that produces the familiar beating sounds of the heart, commonly referred to as the "lub-dub" sound. The ventricular systole consists of the contraction of the ventricles and flow of blood into the circulatory system. Again, once all the blood empties from the ventricles, the pulmonary and aortic semilunar valves clos= e. Finally complete cardiac diastole involves relaxation of the atria and ventricles in preparation for refilling with circulating blood.<= /span>

Regulation of the cardiac cycle

Cardiac muscle is self-exciting. This is in contrast with skeletal muscle, which requires either conscious or reflex nervous stimuli. The hear= t's rhythmic contractions occur spontaneously, although the frequency or heart = rate can be changed by nervous or hormonal influences such as exercise or the perception of danger.

The rhythmic sequence of contractions is coordinated by the sinoatrial and atrioventricular nodes. The sinoatrial node, often known as the cardiac pacemaker, is located in the upper wall of the right atrium and is responsi= ble for the wave of electrical stimulation (See action potential) that initiates atria contraction. Once the wave reaches the atrioventricular node, situate= d in the lower right atrium, it is conducted through the bundles of His and caus= es contraction of the ventricles. The time taken for the wave to reach this no= de from the sinoatrial nerve creates a delay between contraction of the two chambers and ensures that each contraction is coordinated simultaneously throughout all of the heart. In the event of severe pathology, the Purkinje fibers can also act as a pacemaker; this is usually not the case because th= eir rate of spontaneous firing is considerably lower than that of the other pacemakers and hence is overridden.

Other physiological functions=

The heart also secretes ANF (atrial natriuretic factor), a powerful peptide hormone, that affects the blood vessels, the adrenal glands, the kidneys and the regulatory regions of the brain to regulate blood pressure = and volume.

Diseases and treatments

The study of diseases of the heart is known as cardiology. Important diseases of the heart include:

· = Coronary heart disease is the lack of oxygen su= pply to the heart muscle; it can cause severe pain and discomfort known as Angin= a.

<= span style=3D'mso-list:Ignore'>· A heart attack occurs when heart muscle cells die because blood circulation t= o a part of the heart is interrupted.

<= span style=3D'mso-list:Ignore'>· Co= ngestive heart failure is the gradual loss of pumping power of the heart.

<= span style=3D'mso-list:Ignore'>· En= docarditis and myocarditis are inflammations of the heart.

<= span style=3D'mso-list:Ignore'>· Ca= rdiac arrhythmia is an irregularity in the heartbeat. It is sometimes treated by implanting an artificial pacemaker

<= span style=3D'mso-list:Ignore'>· Co= ngenital heart defects.

<= span style=3D'mso-list:Ignore'>· If= a coronary artery is blocked or narrowed, the problem spot can be bypassed wi= th coronary artery bypass surgery or it can be widened with angioplasty.<= /o:p>

Beta-blockers are drugs that lower the heart rate and blood pressure = and reduce the heart's oxygen requirements. Nitroglycerin and other compounds t= hat give off nitric oxide are used to treat heart disease as they cause the dilation of coronary vessels.

Circulatory system=

&n= bsp;

3D"Text The circulatory system or car= diovascular system is the organ system, which circulates blood around the body of most animals.

It consists of Heart - Aorta - Arteries - Arterioles - Capillaries - Venules - Veins - Venae cavae - Pulmonary arteries - Lungs - Pulmonary vein= s - Blood

AORTA

The largest artery in the human body, the aorta originates from the l= eft ventricle of the heart and brings oxygenated blood to all parts of the body= in the systemic circulation.

The course of the aorta

The aorta is usually divided into several segments. The portion above= the diaphragm (in the thorax) is called the thoracic aorta and is sometimes fur= ther subdivided into the ascending aorta, aortic arch and descending (thoracic) aorta. The portion below the diaphragm (in the abdomen) is known as the abd= ominal aorta.

Thoracic aorta

The initial part of the aorta, the ascending aorta, rises out of the = left ventricle, from which it is separated by the aortic valve. The two coronary arteries of the heart arise from the aortic root, just above the cusps of t= he aortic valve.

The aorta then arches back over the right pulmonary artery. Three ves= sels come out of the aortic arch,

Brachiocephalic artery,

Left common carotid artery<= /span>, and

Left subclavian artery.

These vessels supply blood to the head, neck, thorax and upper limbs.=

The aorta gives off several paired branches as it descends in the tho= rax. These includes the

Bronchial arteries,

Esophageal arteries<= span style=3D'font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:Arial; font-weight:normal;mso-bidi-font-weight:bold'> and

Intercostal arteries= .

ABDOMINAL AORTA

The abdominal aorta travels down the posterior wall of the abdomen, t= he abdominal aorta runs on the left of the inferior vena cava, giving off major blood vessels to the gut organs and kidneys. There are many recognized vari= ants in the vasculature of the gastrointestinal system. The most common arrangem= ent for the abdominal aorta is to give off (in order) a

Celiac artery,

Superior mesenteric artery and

Inferior mesenteric artery.

The renal arteries usually branch from the abdominal aorta in between= the celiac artery and the superior mesenteric artery.

The aorta terminates by dividing into two branches, the left and right common iliac arteries that branch to supply blood to the lower limbs and the pelvis.

Features

The aorta is an elastic artery, and as such is quite distensible. When the left ventricle contracts to force blood into the aorta, the aorta expan= ds. This stretching gives the potential energy that will help maintain blood pressure during diastole, as during this time the aorta contracts passively= .

Diseases

Aneurysm of sinus of Valsalva

Aortic aneurysm

Dissecting aortic aneurysm

Aortic coarctation

Marfan’s syndrome

Inborn cardiovascular defects

ARTERY

Arteries are muscular vessels that carry blood away from the heart to= the tissues and organs of the body (The vessels which return blood to the heart= are veins).

The circulatory system is extremely important in sustaining life. Its proper functioning is responsible for the delivery of oxygen and nutrients = to all cells, as well as the removal of carbon dioxide, waste products, maintenance of optimum pH, and the mobility of the elements, proteins and cells, of the immune system. In First World countries the two leading causes of death, myocardial infarction and stroke, are each direct results of an arterial system that has been slowly and progressively compromised by years of deterioration.

Description

The arterial system is the higher-pressure portion of the circulatory system. Arterial pressure varies between the peak pressure during heart contraction, called the systolic pressure, and the minimum, or diastolic pressure between contractions, when the heart rests between cycles. This pressure variation within the artery produces the pulse which is observable= in any artery, and reflects heart activity.

Anatomy

Arteries are composed of distinct layers of tissue; The innermost lay= er, which is in direct contact with the flow of blood is the tunica intima, commonly called the intima. This layer is made up of mainly endothelial cel= ls. Outside this layer is the tunica media, or media, which is made up of smooth muscle cells and elastic tissue. The outermost layer is known as the tunica adventitia or the adventitia, and is composed of connective tissue.

Types of arteries:

There are several types of arteries in the body:

Pulmonary arteries

The pulmonary arteries carry oxygen deficient blood that has just returned from the body to the lungs, where carbon dioxide is exchanged for oxygen.

Systemic arteries

Systemic arteries deliver blood to the arterioles, and then to the capillaries, where nutrients and gasses are exchanged.

The Aorta

The aorta is the root systemic artery. It receives blood directly from the left ventricle of the heart via the aortic valve. As the aorta branches= and these arteries branch in turn, they become successively smaller in diameter, successively down to the arteriole. The arterioles supply capillaries, whic= h in turn empty into venules.

ARTERIOLES

Arterioles, the smallest of the true arteries, help regulate blood pressure and deliver blood to capillaries.

Arterioles and Blood Pressure

Arterioles have the greatest collective influence on both local blood flow and on overall blood pressure. They are the primary "adjustable nozzles" in the blood system, across which the greatest pressure drop occurs. The combination of heart output (cardiac output) and total peripher= al resistance, which refers to the collective resistance of all of the body's arterioles, are the principal determinants of arterial blood pressure at any given moment.

Capillaries

Though not considered true arteries, the capillaries are where all of= the important action happens in the circulatory system:

Functions of capillaries

These vessels have no smooth muscle surrounding them and have a diame= ter less than that of a red blood cell; a red blood cell is typically 7 microme= ters outside diameter, capillaries typically 5 micrometers inside diameter. The = red blood cells must distort in order to pass through the capillaries.

This small diameter of the capillary provides a relatively large surf= ace area for the exchange of gases and nutrients.

What are the functions of capillaries:

In the lungs, carbon dioxide is exchanged for oxygen

In the tissues, oxygen and carbon dioxide and nutrients and wastes are exchanged

In the kidneys, wastes are released to be eliminated from the body

In the intestine nutrients are picked up, and wastes released

Blood pressure

Systemic arterial pressures, are generated by the forceful contractio= ns of the heart's left ventricle.

Healthy resting arterial pressures, are relatively low, mean systemic pressures typically being under 100 mmHg, about 1.8 lbf/in², above surrounding atmospheric pressure (about 760 mmHg or 14.7 lbf/in² at sea level).

To withstand and adapt to the pressures within, arteries are surround= ed by varying thicknesses of smooth muscle, which have extensive elastic and inelastic connective tissues.

The pulse pressure, i.e. Systolic vs. Diastolic difference, is determ= ined primarily by the amount of blood ejected by each heart beat, stroke volume, versus the volume and elasticity of the major arteries. <= /p>

Over time, elevated arterial blood sugar (see Diabetes Mellitus), lipoprotein cholesterol, and pressure, smoking, and other factors are all involved in damaging both the endothelium and walls of the arteries, result= ing in atherosclerosis. Diabetes Mellitus also leads to capillary damage. =

Arteriole

An arteriole is a blood vessel that extends and branches out from an artery and leads to capillaries.

Arterioles have thick muscular walls and are the primary site of vasc= ular resistance. The mean blood pressure in the arteries supplying the body is a result of the interaction between the cardiac output (the volume of blood t= he heart is pumping per minute) and the vascular resistance, usually termed to= tal peripheral resistance by physicians and researchers.

The up and down fluctuation of the arterial blood pressure is due to = the pulsatile nature of the cardiac output and determined by the interaction of= the stroke volume versus the volume and elasticity of the major arteries.<= /o:p>

The muscular contraction of arterioles is targeted by drugs that lower blood pressure (antihypertensives), for example the dihydropyridines (nifedipine and nicardipine), which block the calcium conductance in the muscular layer of the arterioles, causing relaxation. This decreases the resistance to flow into peripheral vascular beds, lowering overall systemic pressure.

Capillary

The word capillary is used to describe any very narrow tube or channel through which a fluid can pass. See capillary action for details.

Capillaries are the smallest of a body's blood vessels, measuring 5-10 μm. They connect arteries and veins, and most closely interact with tissues. Capillaries have walls composed of a single layer of cells, the endothelium. This layer is so thin that molecules such as oxygen, water and lipids can pass through them by diffusion and enter the tissues. Waste prod= ucts such as carbon dioxide and urea can diffuse back into the blood to be carri= ed away for removal from the body. Capillary permeability can be increased by = the release of certain cytokines.

The endothelium also actively transports nutrients, messengers and ot= her substances. Large molecules may be too big to diffuse across endothelial ce= lls. In some cases, vesicles contained in the capillary membrane use endocytosis= and exocytosis to transport material between blood and the tissues.<= /span>

In an immune response, the endothelial cells of the capillary will upregulate receptor molecules, thus "catching" immune cells as th= ey pass by the site of infection and aiding extravasation of these cells into = the tissue.

The "capillary bed" is the network of capillaries supplying= an organ. The more metabolically active the cells, the more capillaries it will require to supply nutrients. The capillary bed usually carries no more than= 25% of the amount of blood it could contain, although this amount can be increa= sed through autoregulation (e.g. active muscle cells) by constricting smooth muscle.

Venule

A venule is a small blood vessel that allows blood to return from the capillary beds to the larger blood vessels called veins. Venules have three layers: An inner endothelium composed of squamous epithelial cells that act= as a membrane, a middle layer of muscle and elastic tissue and an outer layer = of fibrous connective tissue. The middle layer is poorly developed so that ven= ules have thinner walls than arterioles.

Vein

In biology, a vein is a blood vessel, which returns blood from the microvasculature to the heart. Veins form part of the circulatory system. T= he vessels carrying blood away from the heart are known as arteries.

Veins have one-way valves to prevent backflow caused by gravity.=

In systemic circulation, de-oxygenated blood from the capillary blood vessels is taken by veins to the right part of the heart. Differently, in t= he pulmonary circulation oxygenated blood from the lungs is taken to the left = part of the heart by pulmonary veins. Another special case is portal circulation where the portal vein transports blood rich in products of digestion from t= he intestines to the liver.

NAMES OF IMPORTANT VEINS:

<= span style=3D'mso-list:Ignore'>· Pu= lmonary veins

<= span style=3D'mso-list:Ignore'>· Po= rtal vein

<= span style=3D'mso-list:Ignore'>· Su= perior vena cava

<= span style=3D'mso-list:Ignore'>· In= ferior vena cava

<= span style=3D'mso-list:Ignore'>· Fe= moral vein

<= span style=3D'mso-list:Ignore'>· Gr= eat saphenous vein

Veins are used medically as points of access to the blood stream, permitting the withdrawal of blood specimens (venipuncture) for testing purposes, and enabling the infusion of fluid, electrolytes, nutrition, and medications. The latter is called intravenous delivery. It can be done by an injection with a syringe, or by inserting a catheter (a flexible tube).

If an intravenous catheter has to be inserted, for most purposes this= is done into a peripheral vein (a vein near the surface of the skin in the han= d or arm, or less desirably, the leg.) Some highly concentrated fluids or irrita= ting medications must flow into the large central veins, which are sometimes used when peripheral access cannot be obtained. Catheters can be threaded into t= he superior vena cava for these uses: if long term use is thought to be needed= , a more permanent access point can be inserted surgically.

The precise location of veins is much more variable from person to pe= rson than that of arteries.

VENAE CAVAE

The superior and inferior venae cavae are the veins that return the b= lood from the body into the heart. They both empty into the right atrium.

The inferior vena cava travels up alongside the abdominal aorta with blood from the lower part of the body.

The superior vena cava is above the heart, and forms from a convergen= ce of the left and right brachiocephalic veins that contain blood from the head and the arms. The vena cava carries blood from the body to the right atrium= of the heart.

PULMONARY ARTERIES

The pulmonary arteries carry blood from the heart to the lungs. They = are the only arteries (other than umbilical arteries in the fetus) that carry deoxygenated blood.

In the human heart, the pulmonary trunk begins at the base of the rig= ht ventricle. It is short and wide - approximately 5 cm (2 inches) in lengt= h and 3 cm (1.2 inches) in d= iameter. It then branches into two pulmonary arteries, which connect to the base of = each lung.

Role in disease

Pulmonary hypertension occurs alone and as a consequence of a number = of lung diseases. It can be a consequence of heart disease (Eisenmenger's syndrome) but equally a cause (right-ventricular heart failure); it also oc= curs as a consequence of pulmonary embolism and scleroderma. It is characterized= by reduced exercise tolerance. Severe forms, generally, have a dismal prognosi= s.

PULMONARY VEINS

The pulmonary veins carry oxygen rich blood from the lungs to the left atrium of the heart. They are the only veins in the adult human body that c= arry oxygenated blood.

There are four of them:

Right inferior

Right superior

Left inferior

Left superior

MAJOR BLOOD VESSELS

= <= span style=3D'mso-list:Ignore'>· HE= AD: ARTERIES: carotid - common carotid - internal carotid (ophthalmic, retinal, anterior cerebral, middle cerebral, posterior communicating) - external carotid (fac= ial, maxillary, superficial temporal artery) - posterior cerebral - anterior communicating - basilar - circle of Willis - middle meningeal | VEINS: jugu= lar - vein of Galen

= <= span style=3D'mso-list:Ignore'>· AR= MS: ARTERIES: axillary (superior thoracic, thoracoacromial, lateral thoracic, subscapular, anterior circumflex humeral, posterior circumflex humeral) - brachial - radial - ulnar - dorsal scapular | VEINS: axillary - brachial - radial - ulnar - median cubital - basilic – cephalic

= <= span style=3D'mso-list:Ignore'>· TH= ORAX: ARTERIES: aorta - brachiocephalic - bronchial - thoracic (lateral thoracic, internal thoracic) - subclavian - vertebral - axillary - pulmonary | VEINS: venae cavae (superior - inferior) - brachiocephalic - subclavian - portal - ductus venosus - azygos – pulmonary

= <= span style=3D'mso-list:Ignore'>· AB= DOMEN: ARTERIES: celiac artery - marginal - artery of Adamkiewicz - gastroduodenal= - gastroepiploic - left gastric - umbilical - mesenteric (superior - inferior= ) | iliac (common - external - internal) - Internal pudendal - renal - hepatic - common hepatic - splenic | VEINS: mesenteric (inferior, superior) | iliac (common - external) - renal - hepatic – splenic

= <= span style=3D'mso-list:Ignore'>· LE= GS: ARTERIES: dorsalis pedis - femoral - peroneal - popliteal - profunda femori= s - tibial (anterior, posterior) | VEINS: femoral - saphenous (great, small) - peroneal - popliteal - profunda femoris - tibial (anterior tibial, posterior tibial)

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 gi= lls 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 undergoi= ng fragmentation, or a fragmented part of a red blood cell.<= /p>

Blood diseases involving the red blood cells include:

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ An= emias (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 c= ells or the hemoglobin.

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ Ir= on deficiency anemia is the most common anemia; it occurs when the dietary int= ake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ Th= alassemia is a genetic disease that results in the production of abnormal hemoglobin molecules.

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ Sp= herocytosis is a genetic disease that causes a defect in the red blood cell's cytoskele= ton, causing the RBCs to be small, sphere-shaped, and fragile instead of donut-shaped and flexible.

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ Pe= rnicious 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.

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ He= molysis is the general term for excessive breakdown of red blood cells. It can have several causes.

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ 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.

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ Po= lycythemias (or erythrocytoses) are diseases characterized by a surplus of red blood ce= lls. The increased viscosity of the blood can cause a number of symptoms. <= /o:p>

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ In polycythemia vera the increased number of red blood cells results from an abnormality in the bone marrow.

<= span style=3D'font-size:8.0pt;font-family:Symbol;mso-fareast-font-family:Symbol; mso-bidi-font-family:Symbol;font-weight:normal;mso-bidi-font-weight:bold'><= span style=3D'mso-list:Ignore'>¨ Se= veral 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 vo= lume occupied by red blood cells). The blood type needs to be determined to prep= are for a blood transfusion or an organ transplantation.

WHITE BLOOD CELL=

White blood cells (also cal= led leukocytes or immune cells) are a component of blood. They help to defend t= he 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 whi= te 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 oth= er 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, basop= hils, and eosinophils (named according to their staining properties).<= /span>

Lymphocytes

Lymphocytes are much more common in the lymphatic system, and include= the so-called "killer T-cells". The blood has three types of lymphocy= tes: B cells, T cells and natural killer cells. B cells make antibodies that bin= d 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 kill= ed, 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 ce= lls 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 invol= ved 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 plate= lets 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 fre= ely 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 hen= ce low platelet counts.

Function

Platelets are activated when brought into contact with collagen (whic= h is exposed when the endothelial blood vessel lining is damaged), thrombin (primarily through PAR-1), ADP, with receptors expressed on white blood cel= ls or the endothelial cells of the blood vessels, among other activators. Once activated, they release a number of different coagulation factors and plate= let 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 stimulate= d 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 GPIb-V-IX complex (vWF) and GPVI (collagen)

Activators

There are many known platelet activators. They include

<= span style=3D'font-size:8.0pt;font-family:Verdana;mso-fareast-font-family:Verdan= a; mso-bidi-font-family:Verdana;font-weight:normal;mso-bidi-font-weight:bold'>= 1.&n= bsp; Co= llagen, especially with von Willebrand factor which is exposed when endothelial blo= od vessel lining is damaged and binds to GPVI on the platelet,

<= span style=3D'font-size:8.0pt;font-family:Verdana;mso-fareast-font-family:Verdan= a; mso-bidi-font-family:Verdana;font-weight:normal;mso-bidi-font-weight:bold'>= 2.&n= bsp; th= rombin primarily through cleavage of the extracellular domain of PAR1 and PAR4,

<= span style=3D'font-size:8.0pt;font-family:Verdana;mso-fareast-font-family:Verdan= a; mso-bidi-font-family:Verdana;font-weight:normal;mso-bidi-font-weight:bold'>= 4.&n= bsp; ADP through creation of TxA2, and it can be blocked by conversion of ADP to cAM= P,

<= span style=3D'font-size:8.0pt;font-family:Verdana;mso-fareast-font-family:Verdan= a; mso-bidi-font-family:Verdana;font-weight:normal;mso-bidi-font-weight:bold'>= 5.&n= bsp; Hu= man neutrophil elastase (HNE) cleaves the αIIbβ3 integrin on the plat= elet surface,

<= span style=3D'font-size:8.0pt;font-family:Verdana;mso-fareast-font-family:Verdan= a; mso-bidi-font-family:Verdana;font-weight:normal;mso-bidi-font-weight:bold'>= 6.&n= bsp; P-= selectin which binds to PSGL-1 on endothelial cells and white blood cells, and =

<= span style=3D'font-size:8.0pt;font-family:Verdana;mso-fareast-font-family:Verdan= a; mso-bidi-font-family:Verdana;font-weight:normal;mso-bidi-font-weight:bold'>= 7.&n= bsp; Co= nvulxin (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 thrombocy= topenia) 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 procedu= res 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 hemost= asis 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 platel= et 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 adhes= ion or aggregation:

Bernard-Soulier syndrome

Glanzmann's thrombasthenia

Scott's syndrome

von Willebrand disease

Disorders of platelet metabolism

Decreased cyclooxygenase activity, induced or congenital <= /span>

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 separate= ly 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 ri= sks 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 blood-transmitted diseases.=

People with few platelets or platelets that are dysfunctional may ben= efit 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 eve= nt, 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 abou= t 1% of circulating leukocytes. Basophils tend to appear in specific kinds of inflammatory reactions, particularly those that cause allergic symptoms.