Chapter 13 Blood

• Blood serves many functions including the transport of respiratory gases, nutritive molecules such as glucose, metabolic wastes, and hormones. Blood travels through the body in a system of vessels leading from and returning to the heart.

Integrative Functions

• Blood can also transport disease-causing viruses, bacteria and their toxins. To guard against this the circulatory system has protective mechanisms-the white blood cells and the immune system.

• Blood is a connective tissue which involves the function of several different body systems

1. Digestive: blood delivers nutrient

2. Respiratory: blood delivers oxygen and carbon dioxide

3. Urinary: blood delivers urea and other waste products

4. Endocrine: blood delivers hormones

Major Components of the Circulatory System

• The circulatory system consists of two subdivisions: 1) The cardiovascular system and 2) The lymphatic system

Composition of the Blood

• Blood consists of formed elements that are suspended and carried in a fluid called plasma. The formed elements, erythrocytes and leukocytes function to transport oxygen and provide immune defense. Spinning whole blood separates the plasma on top  from the red blood cells on the bottom. The “buffy coat” indicated the zone in which the white blood cells and platelets settle in.

Hematocrit

• The percentage of blood cell volume to whole blood volume in a centrifuged blood sample is called the hematocrit. Normal hematocrit values range from 36% and 46% in women and a little higher 41% to 53% in men. These values may be different in other mammalian species such as sheep’s blood that we look at in the lab.

Composition of Blood: Blood Plasma

• Blood is a connective tissue. Plasma is the extracellular component of this tissue and consists of mostly H2O(90%)

• Plasma proteins make up another 7  to 9% and the rest is composed of gasses, nutrients, wastes, hormones and dissolved salts and minerals.

Plasma Proteins

• Plasma proteins constitute 7% to 9% of the plasma. The three types are albumins, globulins and fibrinogen.

1. Albumines account for most of the plasma proteins they are produced in the liver and provide the osmotic pressure to draw fluids into capillaries

2. Globulins are antibodies produced by lymphocyte cells

3. Fibrinogen is an important blood clotting protein produced by the liver.

Blood Cells: Erythrocytes

• Red Blood cells are filled with hemoglobin and transport oxygen. Each erythrocyte contains about 250 million hemoglobin molecules. Red blood cells do not contain a nucleus. They are essentially sacks of hemoglobin and only last about 120 days before being destroyed in the spleen  and the liver

• Platelets are not actually cells at all. They are vesicular in nature and function to form  blood clots.

Blood Cells: Leukocytes

• White Blood cells come in a variety of types.

• Neutrophils

• Lymphocytes

• Monocytes

• Eosinophils

• Basophils

Hematopoiesis

• Hematopoiesis describes the formation of new blood cells. Erythropoiesis is specific for red blood cell production. Erythropoiesis takes place in the red bone marrow and the human body produces about 200 billion red blood cells each day. Red blood cells are produced by stem cells divided by mitosis. Daughter cells then differentiate, lose their nucleus and are eventually released into the blood. 11

Regulation of Erythropoiesis

• Specialized cells in the kidneys can sense a decline in the O2  availability in blood.

• These cells then secret a hormone called erythropoietin.

• Erythropoietin is transported in the bloodstream to stem cells in the bone marrow and stimulates them to increase RBC production

Self-Recognition: Antibodies and Antigens

• Self-recognition refers to certain proteins in the plasma membrane of all our cells that act as an identifier keeping our immune system from attacking its own body.

• Foreign cells, like bacteria, carry different surface proteins that excite the immune system, these foreign proteins are called antigens. To defend the body lymphocytes (WBCs) produce antibodies which bind to the antigens and target the foreign invader for destruction.

ABO Blood Typing

• Blood cells also have “self recognition” proteins classified as either A or B. Therefore everyone is one of 4 different blood types

1. A - Type A

2. B - Type B

3. AB - Type AB

4. O - Type O

• Type O persons are universal donors: can give blood to anyone

• Type AB persons are universal recipients: they can receive blood from anybody

ABO Blood Typing

• People with type A blood have type A antigens on their red blood cells and antibodies in their plasma against the type B antigen. People with type B blood have type B antigens on their red blood cells and antibodies in their plasma against the type A antigen. 

• Therefore, if red blood cells from one blood type are mixed with antibodies from the plasma of another blood type an agglutination reaction occurs.

Agglutination and Blood Typing

• Antibodies have two antigen binding sites so each antigen can connect  to two red blood cells at the same time.

• Agglutination of red blood cells occurs when cells with A-type antigens are mixed with anti-A antibodies and when cells with B- type antigens are mixed with anti-B antibodies. No agglutination would occur with type O blood. We see some agglutination reactions in lab when we do our blood typing exercise.

The Rh Factor

• Rh factor is another blood cell recognition protein. If it is present you are Rh+ if absent you are Rh-

•  Problem: The immune system of pregnant women can attack the RH factor of their unborn children.

• Rh- women who wish to have children need to be aware of incompatibility issues based on the Father’s genetics.

Hemostasis (Blood Clotting)

• Is the ability to limit blood loss after injury.

• 4 Step Process:

1. Damage is perceived by exposing collagen in blood vessel to platelets

2. Vasoconstriction

3. Platelet Plug Formation

4. A web of fibrin proteins that forms the blood clot.

• In the absence of an injury, prostaglandins and nitric oxide(NO) from endothelial cells prevent platelet aggregation and maintain vasodilation. The endothelium separates the underlying collagen and associated molecules in the wall of the blood vessel from the bloodstream itself.

• When the endothelium is disrupted during an injury platelets adhere to the exposed collagen and are anchored there by von Willebrand’s factor (VWF).

• Also as a result of reacting with the collagen molecules the platelets become sort of “sticky” gluing them to the collagen and to each other.

• As we mentioned before fibrinogen is a soluble protein component of the plasma. When the platelets bind to collagen they become activated, shown as a change in shape in the figure. 

• Activated platelets convert soluble fibrinogen to its insoluble form fibrin. Fibrin fibers tick to the platelets and even to red blood cells forming a platelet sticky.

• A blood clot as shown above is a temporary mass of fibrin, red blood cells and platelets. When the blood vessel wall is repaired plasmin is activated which digests fibrin and breaks down the blood clot.

Clotting Disorders and Anticoagulants

• Though we are not going to study the many blood clotting factors know that the genes for them are found on the X chromosome. Hemophilia, which is the inability to form blood clots is more common in men because of the X-linked genes.

The Circulatory System

• The heart sits in the center of the chest and points slightly to the left. The heart is surrounded by a fluid filled sac known as the pericardium

• The anatomy of the heart is composed of 4 chambers and 4 valves

• Major arteries and veins conduct blood away from the heart and back to it.

Blood Flow through the heart

• Deoxygenated blood enters into the right atrium via the inferior and superior vena cava. Blood passes through the right atrioventricular valve into the right ventricle. Blood leaving the right ventricle passes through the pulmonary semilunar valve to enter the pulmonary trunk which splits into the L/R pulmonary arteries leading to the lungs. 

• Oxygenated blood returning from the lungs enters into the left atrium via the 4 pulmonary veins. Blood passes through left atrioventricular valve into the left ventricle. Blood leaving the left ventricle passes through the aortic semilunar valve to enter the aorta. 

The Circulatory Circuits

• There are two circuits or paths that blood flows in, the pulmonary circuit and the systemic circuit.

• The pulmonary circuit carries blood from the heart to the lungs and back

• The systemic circuit conducts blood from the heart to the body and back.

Cardiac Cycle

• The two atria fill with blood and then contract simultaneously. This is followed by simultaneous contraction of both ventricles which sends blood through the pulmonary and systemic circulations. The phase of contraction is called systole and the phase of relaxation is called diastole usually in reference to the ventricles. 

• The cardiac cycle take a total of about 0.8 of a second therefore about 75 heartbeats can “fit” into a minute. 

Heart Sounds

• The snapping shut of two atrioventricular valves during ventricular systole represents the first heart sounds (lub). The snapping shut of the two semilunar valves during ventricular diastole produces the second heart sound (dub).

Circulatory System

• Blood pressure is the force that blood exerts on the wall of a blood vessel as a result of the pumping action of the heart. You can feel this as the pulse which repeats about 70 times a minute.

• Systole – The highest pressure reached when the ventricles contract and expel blood into the systemic arteries 

• Diastole – The lowest pressure reached when the ventricles relax

Pacemaker Potentials

• The sinoatrial node (SA node) functions as the pacemaker. The cells of the SA node do not maintain a resting membrane potential. Instead during the period of diastole (when the ventricles are filling with blood between heartbeats) cells in the SA node are spontaneously slowly depolarizing. 33 The cells of the sinoatrial node never take a rest  they are in a constant cycle of depolarization and repolarization but do not maintain a resting  potential like regular neurons. What if they did? 

• As the cells in the sinoatrial node repolarize, specific Na+ ion channels (HCN channels) found only in these cells become “leaky” to Na+ and they immediately begin to depolarize once more. This is called a pacemaker potential and is shown in red in the figure.

• Remember that potassium (K+) channels open to repolarize the cell. The process of repolarization (becoming more negative) actually serves as a stimulus causing the HCN channels to open and sodium rushes in to depolarize the pacemaker cell.

• When the cell depolarizes to about -40mV voltage gated Ca2+ channels in the plasma membrane open up and Ca2+ rushes in. The combination of Na+ & Ca2+ entering the cell drives the depolarization of the pacemaker back to about + 20mV. 

Conducting System

• Once nearby myocardial cells have been stimulated by action potentials originating in the SA node they produce their own action potentials. Since all the cells in the heart are interconnected physically, chemically and electrically by intercalated discs this wave of depolarization followed by contraction sweeps first through both atria then eventually into the two ventricles.

• The conducting system of the heart refers to the flow of action potentials that lead to heart contraction. First, the sinoatrial (SA) node emits an action potential that flows through both atria and they contract (Green Arrows).

• Then the atrioventricular (AV) node captures and delays that action potential relays it through the bundle branches in the septum to the ventricles and delivers it to the Purkinge fibers that spread throughout the ventricles (Yellow Arrows). 

Excitation-Contraction Coupling in Cardiac Muscle Tissue

• Voltage gated Na+ channels open 

• Ca2+ channels open in transverse tubules 

• Ca2+ rushes into the cell 

• Ca2+ sensitive release channels in the sarcoplasmic reticulum open

• Ca2+ floods throughout the cytoplasm

• Ca2+ binds to troponin and stimulates muscle contraction • Atria or Ventricles contract

• A Ca2+(ATPase) pump actively transports Ca2+ back into the sarcoplasmic reticulum

• Finally A Ca2+(ATPase) pump actively transports Ca2+ back into the sarcoplasmic reticulum 

Maximum Heart Rates Normal is

• Voltage gated Na+ channels open

•  Ca2+ channels open in transverse tubules

• Ca2+ rushes into the cell

•  Ca2+ sensitive release channels in the sarcoplasmic reticulum open

• Ca2+ floods throughout the cytoplasm

• Ca2+ binds to troponin and stimulates muscle contraction

• Atria or Ventricles contract

• A Ca2+(ATPase) pump actively transports Ca2+ back into the sarcoplasmic reticulum

The Electrocardiogram (ECG or EKG)

• An ECG reflects the electrical pattern of the cardiac cycle conducted through the skin. The pattern is displayed as voltage changes and these changes are called waves.

• P - electrical current spreads throughout atria.

• T- End of electrical activity in the ventricles heart is relaxed for a split second.

• P - Cells in atria depolarized and they contract

• QRS - Wave of depolarization spreads throughout the ventricles and they contract

• T - End of electrical activity in the ventricles heart is relaxed for a split second ventricles repolarize SA node gets ready to fire off another action potential.

• P - cells in atria depolarize and they contract

• QRS - Wave of depolarization spreads throughout the ventricles and they contract

• T - End of electrical activity in the ventricles heart is relaxed for a split second ventricles repolarize.

The Blood Vessels

• The blood vessel can be classified as 3 main types

1. Arteries carry blood away  from the heart

2. Capillaries: Connect arteries and veins and exchange oxygen and nutrients with body tissues.

3. Veins: Carry Blood back to the heart

Similarities Between Arteries and Veins

• Both arteries and veins conduct blood.

• Both arteries and veins consist of an inner lining of epithelial tissue, a middle layer of smooth muscles and an outer layer of connective tissue.

• Arteries and veins, like boines and muscles, are given anatomical names.

• Arteries contain more smooth muscle and are therefore “Thicker” to handle the increased blood pressure in the arterial circulation. Arteries also contain large amounts of elastin fibers which allows them to stretch with pressure which you feel as the pulse each time the heart beats.

Capillaries

• The millions of capillaries in your body connect the arteries to the veins in what is called a closed circulatory system. Capillaries are only about 1 blood cell in diameter. The wall of the capillary is very thin and is leaky due to tiny slits and holes in the capillary wall.

• Capillaries are the functional unit of the circulatory system. No cell in the body is more than 1mm away from a capillary. It is in the capillaries that gases and nutrients such as O2 and glucose are exchanged as well as where waste molecules such as urea are picked up. All of this is due to simple diffusion across the thin, perforated wall of the capillary.

Venous Valves

• Because the blood pressure in veins is so low, the veinous return to the heart is maintained primarily through skeletal muscle activity and one-way veinous valves.

• Varicose vein  are associated with dysfunctional veinous valves which allow blood to pool in the veins, usually of the legs.

Atherosclerosis

• Atherosclerosis is a disease in which fatty deposits form within the wall of an artery reducing blood flow. These deposits (plagues) contribute to heart disease and stroke and are responsible for about 50% of the naturally occurring deaths in the United States. Europe and Japan.

• Factors leading to atherosclerosis include smoking , hypertension, high blood cholesterol and diabetes. The top figure to the right is of a human coronary artery that is partially blocked by an atherosclerotic plaque and a thrombus (blood clot). Below is a cartoon diagram if what you see in the photograph above.

• Heart attack - lack of blood flow to heart muscle tissue

• Stroke - is a blood clot logged in the brain equaling no oxygen to the brain

Lymphatic System

• Lymphatic vessels absorb excess tissue fluid and transport this fluid called lymph  to ducts that drain into veins. Lymph nodes and lymphatic tissue in the thymus, spleen and tonsils produce lymphocytes, which are white blood cells involved in immunity. 

• Three basic functions

1. It transports interstitial fluid back to the blood

2. It transports absorbed fat from the gut into the blood

3. The immune cells it produces called lymphocytes provide defense against disease.

• Lymphatic capillaries are blind- ended and highly permeable so that excess fluid and protein within the interstitial space can drain into the lymphatic system.

• Lymph is eventually returned to the vascular system (blood) by draining into the subclavian veins

• Lymph nodes are small bean shaped bodies enclosed within a dense connective tissue capsule. The Thymus gland, the spleen, lymph nodes and the lymph vessels comprise the lymphatic system. Note the drainage of the lymph into the venous circulation near the heart. 54 This system will be further discussed in the chapter on the immune system which is coming up.