THE CIRCULATORY SYSTEM

Prof. Atsma 2005, 2009

The following is a narrative summary of the topic. Click here for the Blood "Classroom Notes" that you can print out and bring to class to save yourself a lot of note-taking. Click here for the Heart classroom notes.  Click here for the Blood Vessels Classroom Notes. 

THE BLOOD

Blood is a 'connective tissue' which chemically connects all of the interdependent, specialized tissues in the body. The blood is divided into two components - the plasma and the formed elements (mostly red blood cells, but also white blood cells and platelets).

Plasma

Most important nutrients (glucose, ions, amino acids, etc.) and wastes are simply dissolved in the plasma. But other important items such as the proteins (albumin, antibodies, clotting) are also suspended in the plasma. The proteins and electrolytes dissolved in plasma contribute to its osmotic pressure. By making the plasma hypertonic to most body fluids, water is held in the blood vessels which would otherwise slowly leak away. More on the clotting proteins will be found later in the discussion of blood clotting.

Formed Elements

Formed elements are so-named because they are formed in the red bone marrow. The erythrocytes and leukocytes arise from stem cells called hemocytoblasts, and platelets come from megakaryocytes.

Erythrocytes: Also called red blood cells or "RBC's," erythrocytes are incapable of maintaining themselves for more than about 4 months, since they expel their nucleus in order to fill with more hemoglobin and take on a special "biconcave" shape. This shape makes the cells more flexible, allows them to stack when pushed through narrow vessels, and provides more surface area for gas exchange. The hemoglobin found filling RBC’s is a protein which coils around an iron atom such that the iron easily picks up oxygen at the lungs, but lets go of it when reaching oxygen-poor tissues.

RBC production erythropoiesis is stimulated when certain kidney cells detect low blood oxygen levels and release a hormone ("erythropoietin"). The hormones stimulates hemocytoblasts (stem cells) in the red bone marrow to divide and begin faster RBC production. Thus, only low oxygen levels will cause an increase in our number of RBC's. In summary, hemocytoblasts divide and become erythroblasts, which turn nearly all of their energy to hemoglobin production. When nearly full of hemoglobin and rough ER needed to make hemoglobin, the cell expels its nucleus and becomes a reticulocyte. The ER deteriorates as the cell finishes filling with hemoglobin and takes on the biconcave shape of a mature erythrocyte.

HEMATOCRIT: By measuring the percentage of cells vs. plasma, one can estimate the percentage of RBC's in whole blood. Hematocrit measurements of 40-52% are considered normal for males, and 37-47% for females. (Note: this percentage varies slightly among experts and authors.). The effect of the male's extra muscle mass on oxygen levels accounts for much of the sexual difference in hematocrit. The term "anemia" relates to a wide variety of disorders in which the blood has a reduced oxygen-carrying capacity. Low iron, poor absorption of protein, chronic blood loss, and improper blood cell formation are the main causes of the various anemias. Polycythemia is the term used to describe abnormally high RBC counts, and can be due to many different lung diseases, or can be the natural result of living in high-altitude environments.

Blood Typing: Certain genes control the "shape" of the marker molecules that stick out of the cell membrane. The immune system learns to recognize the "faces" of all body cells and knows a stranger when it sees one. Some leukocytes make antibodies, which are proteins that can lock onto these foreign shapes like chemical handcuffs and clump them together for removal by other WBC's. This clumping of antigens when antibodies attach is called agglutination.

Molecule shapes on the surface of human red blood cells come in a few easily recognizable varieties (A & B). Your blood type simply relates to whether you have molecule shape A, B, both ("AB"), or neither ("O"). Since your immune system only "knows" to ignore the shapes it has seen in your body, it will produce antibodies against these other "foreign" varieties of RBC's if they enter your body. Refer to your textbook and lab manual for diagrams and more information on "cross matching" blood types.

Erythrocytes and Blood Typing

Antibodies added to each drop:  

Anti-A   Anti-B

Anti-A   Anti-B

Anti-A   Anti-B

Anti-A   Anti-B

Agglutination Response

+       -

-       +

+       +

-       -

Blood type

A

B

AB

O

Antibodies present in vivo

B

A

Neither

A & B

Note: "+" = clumping or agglutination; "-" = no clumping or agglutination.

Leukocytes: Also called white blood cells or "WBC’s," leukocytes are divided into "granular" (neutrophils, eosinophils, basophils) and "agranular" (lymphocytes and monocytes) categories. The characteristics and functions of all of these leukocytes are summarized nicely in your lab manual and textbook. A differential white blood cell count tells us which WBC's (if any) are present at unusually high levels. Since each leukocyte seems to have a specialty, elevated levels of a particular WBC may be an indicator of the type of disease the body is trying to counter.

Neutrophils and monocytes are phagocytic cells, while basophils and eosinophils use chemicals stored in their cytoplasm to do their job. Lymphocytes participate in your specific immune response by producing antibodies and directly attacking foreign substances they have been made to attack. See your lab manual for more information on the leukocytes.

Leukocytes compared to Erythrocytes


Normal Value

Clinical significance
of increased value

Clinical significance
of decreased value

Erythrocytes

4.5-5.5 Million/mm3 Polycythemia Anemia

Leukocytes

5000-10,000/ mm3 Possible infection More susceptible to infection

Neutrophils

about 65% Acute infection *

Eosinophils

<5% Parasitic infection *

Basophils

<1% Allergy/inflammation *

Lymphocytes

about 20% Specific immune response *

Monocytes

about 8% Chronic infections *

 * Although this could represent a bone marrow disorder, for each leukocyte type, low levels of a particular leukocyte may just mean there are proportionally more of the others.

Platelets: These small fragments of large stem cells in the bone marrow are specialists in assisting with the clotting process. They become sticky when near damaged tissues (broken blood vessel walls) and can block small openings the same way that damp, sticky salt clogs up the small holes of a salt shaker. They also release chemicals from their "cytoplasm" that further stimulate the clotting process.

CLOTTING

Clotting involves both platelets and plasma proteins. Prothrombin and fibrinogen are soluble proteins made by the liver. Damaged tissues cause the release of chemicals that eventually cause the production of a prothrombin activator (PTA), which converts prothrombin to thrombin. Thrombin then helps to convert fibrinogen to fibrin, and insoluble protein that coagulates blood. Together, the fibrin net and platelet plug block the flow of blood from a damaged vessel. Small amounts of clot-dissolving enzymes are continuously produced by the body to slowly dissipate the clot, and keep them from blocking vessels should they break away from the injured site.

Technically speaking, the clotting response is often includes the vascular spasm, or immediate constriction of the damaged blood vessel in order to help reduce blood loss until the above mentioned pathway can take place. Also, the source of PTA determines whether it is the extrinsic pathway (tissues release the PTA) or intrinsic pathway (platelets release the PTA). This is often described as a rare example of a place where the body uses positive feedback, as more PTA produces more fibrin, which traps more platelets, which causes the release of more PTA, and so on….

THE HEART AND GENERAL CIRCULATION

HEART ANATOMY

Most people have already learned by now that the heart is composed of four chambers - two small (superior) atria, and two larger (inferior) ventricles. The left ventricle pumps blood to the entire body and is therefore the chamber that is thick walled on both sides. The right ventricle has a thinner wall as it only needs to be strong enough to pump blood the short distance to the lungs. The vessels that are attached to the heart are: superior/inferior vena cava (rt. atrium), pulmonary artery (rt. ventricle), pulmonary vein (l. atrium), aorta (l. ventricle).

Valves in the heart prevent back-flow and improve efficiency. A-V valves are "parachute-like" valves between each atrium and ventricle and prevent blood from being pushed back up into the atria. Preventing back-flow from the great arteries into the ventricles, the semilunar valves are at the base of the aorta and pulmonary trunk.

Coronary arteries: These are the relatively small vessels that feed the heart muscle, and the coronary veins drain blood from the heart. However, it is the arteries, not the veins, which are medically significant since they are far more likely to develop a blockage in some people. As you look at a diagram of the heart, you will see the rather obvious vessels on the outside of the heart which branch extensively and disappear into the heart muscle. You may notice that the arteries (particularly the circumflex artery) branch apart and reconnect - an excellent strategy for ensuring that blockage of one vessel will not prevent blood from reaching large areas of the heart. The term describing branching and reconnecting of these and many smaller vessels is anastomosis. When several of these arteries become blocked, by-pass surgery is used to shunt blood flow around these vessels. The anastomosis of these vessels may explain why you don’t hear of "single by-pass" surgery, as blockage usually becomes life threatening only when two or more vessels are blocked.

CONDUCTION SYSTEM

Unlike most other muscles in the human body, the heart does not need the stimulation of neurons in order to contract. The heart is capable of stimulating itself approximately once per second (faster if necessary). The nervous system can influence heart rate, but is not directly responsible for causing contraction.

Located in the right atrium, the sino-atrio node (SA node) is an area of cardiac muscle specialized in rapid repolarization. This area automatically depolarizes and starts an impulse after repolarization. For this reason, the SA node is referred to as the heart's pacemaker. This impulse spreads through the muscle tissue of the atria, causing them to contract. The spread of the action potential through the atria is the P-wave on an ECG.

The atrio-ventricular node (AV node) picks up the impulse, which is located in the inferior part of the right atrium. The AV bundle then carries the impulse into the interventricular septum, where it branches into two lines appropriately named the bundle branches. Each bundle branch carries the impulse to the bottom of each ventricle, where it branches into perkinje fibers. The perkinje fibers carry the impulse to the myocardium of the ventricles. This spread of impulse through the ventricles corresponds to the EKG's QRS-complex. The EKG's T-wave corresponds to repolarization of the ventricles. Note that this system encourages the ventricles to contract from the bottom up, where the aorta and pulmonary trunk are located.

THE CARDIAC CYCLE

Contrary to popular belief, the atria are not responsible for completely filling the ventricles. As the heart relaxes, all chambers, both pairs of atria and ventricles, fill with blood. The atria simply push in another 20-30% into the ventricles, stretching the ventricles as a result. This stretching of the ventricles is directly related to stronger contraction, and exemplifies one of the laws of heart physiology - the Frank-Starling Law, essentially stating that the heart will be able to pump whatever blood it receives. More blood filling the heart ("venous return") is harder to push, but extra stretching of the heart muscle translates into the extra strength needed for contraction. Cardiac output is simply a measure of the blood pumped with each beat (stroke volume) multiplied by heart rate (beats per minute).

The steps of the cardiac cycle may be summarized as follows: 1) Passive filling: The heart relaxes and all four chambers fill passively (blood is sucked in as the heart expands). 2) Atrial contraction: the atria contract and push a little more blood into already full ventricles, stretching the ventricles as they do. 3) Ventricular contraction: The muscle of the ventricles contracts, pressure builds, and blood is ejected into the aorta and pulmonary trunk. The last step is the most intricate and important step as the ventricles must first build enough pressure to overcome the blood pressure in the arteries. Understanding this helps to make clear why high blood pressure is dangerous – the ventricles must work extra hard, and will still probably eject less blood when the pressure they must overcome in the arteries remains over 100 or more at all times.

 

BLOOD VESSELS

Arteries are the vessels which carry blood away from the heart (not always oxygen-rich blood), and veins return blood to the heart. Note that the vessels carrying blood to and from the lungs (the pulmonary circuit) have low-oxygen blood in the arteries and high-oxygen blood in the veins.

Both arteries and veins have the same basic tissue layers: a smooth epithelial lining on the inside, a (smooth) muscle layer in the middle, and a connective tissue casing (technically a membrane with some epithelial cells too) on the outside. Arteries are thicker (especially in the smooth muscle portion) than veins since they must withstand greater pressures, and also because they regulate blood distribution by adjusting their diameter. The blood in veins is under low pressure, which allows blood to easily drain out of the capillaries. Veins also have semilunar valves to allow the push and suction of skeletal muscle contraction and breathing to assist in returning this low-pressure blood to the heart.

Deposits of cholesterol in the arterial walls reduce both the diameter and flexibility of the vessels (referred to as "hardening of the arteries"). As mentioned previously, veins are less likely to narrow with age, and tend to become blocked only when blood clots break away from damaged areas.

Important arteries are the aorta (originating from the left ventricle) and its branches such as the common carotid (feeds the head), subclavian (feeds the shoulder/arm), celiac (pronounced sea-lee-ak, feeds the digestive organs), renal (feeds the kidneys) and the common iliac (feeds the leg). The major veins include the jugular (drains the head), subclavian (drains the shoulder/arm), renal (drains the kidneys), hepatic portal (drains the digestive organs), hepatic (drains the liver), common iliac (drains the leg), and the vena cava (enters the rt. atrium).

The arteries that are closest to the heart are called elastic arteries because of their extensive elastic connective tissue in their walls. Their stretch during ventricular ejection, and recoil while the heart is filling actually helps to maintain a relatively stable blood pressure level and constant flow of blood throughout the body. Muscular arteries have a thick layer of smooth muscle in their wall, and are important for adjusting blood pressure with their constriction (increases BP) and dilation (decreases BP). Constriction and dilation of muscular arteries and particularly smaller arteries, helps to regulate the flow of blood to parts of the body depending upon where it is needed most. Arterioles lead into individual tissues, where they branch into capillary beds. Here, local control (i.e. local hormones) usually determines whether blood fills the capillaries or passes through. Both the small diameter, slower flow, and the thin walls of capillaries facilitate exchange of materials (including gasses) with the tissues. Venules drain capillary bed and merge to form the veins of the body.

BLOOD PRESSURE: Systolic pressure is the pressure exerted on the walls of the arteries at the peak of ventricular contraction/ejection. Diastolic pressure is the naturally lower pressure in the arteries when the heart is filling (at rest) and is not forcing blood out into the arterial system. Since the bigger arteries expand and (and very importantly) recoil with each beat of the heart, a relatively high pressure is maintained in the arteries (as long as the heart beats at least once every 2 seconds).

BLOOD PRESSURE REGULATION: Baroreceptors located near the aorta and carotid arteries detect blood pressure changes and inform the medulla. The cardiac center will speed heart rate (and therefore cardiac output) if blood pressure is too low, and will conversely slow the heart rate when it is too high. The vasomotor center will send impulses to the smooth muscle of the blood vessels when it is necessary to induce vasoconstriction and raise blood pressure. Conversely, it will relax the vessels when vasodilation and lower blood pressure is desired.

Shock occurs when blood pressure drops so low that blood flow slows to a crawl and cells (including those in the heart, blood vessels, and brain) begin to die. This is an example of inappropriate positive feedback, as the heart will beat weaker and weaker as less and less blood returns to it through the venous circulation. Excessive bleeding or extensive uncontrolled vasodilation may be the cause of shock, and treatments must be rapid in order to save the patient. Immediate halting of blood loss, replacing blood, and/or use of vasoconstrictors such as adrenalin may be necessary (depending upon the cause of shock). If enough cells die in the heart and blood vessels, the shock may be irreversible, as the cardiovascular system will be unable to respond to attempts to break this vicious cycle.

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