Heart

Lecture 21, 22, 23

The Heart and the blood circulation system

http://www.turbosquid.com/3d-models/human-heart-obj/273886

The heart is part of a complex circulatory system responsible for maintaining the body's continuous and varying requirements of oxygen.
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Heart matters
Every day, your heart beats about 100,000 times, sending 7500 Liters of blood surging through your body. No bigger than your fist, your heart has the mighty job of keeping blood flowing through the 100,000 km of blood vessels that feed your organs and tissues. A mans heart weighs about 10 ounces, while a womans heart weighs approximately 8 ounces. When women have a heart attack -- and more than a half million do each year -- theyre more likely to have nausea, indigestion, and shoulder aches rather than the hallmark chest pain.
Source: WebMd

Heart Anatomy
(For information only, you will not be asked to draw a detailed diagram)
Actual

Simplified

Top View

http://www.physioweb.org/circulation/heart_structure.html http://healthinformation1.4arabs.com/heart/2.html

http://www.urgo.co.uk/260-the-venous-system-withinthe-cardiovascular-system

Heart
Figure 1 The cardiovascular system.
Deoxygenated blood travels from body tissues to the heart along the vena cava (9), the largest vein in the body. Blood drains into the right atrium (1) , which contracts and pumps blood into the right ventricle (2). Once filled, the right ventricle contracts and pumps blood into the pulmonary arteries (3). The pulmonary arteries carry blood to the lungs, where the flowing blood absorbs oxygen and releases carbon dioxide in the capillary beds (4). Oxygenated blood returns from the lungs through the pulmonary veins to the left atrium of the heart (5). As the left atrium of the heart contracts, blood flows into the left ventricle (6). When the left ventricle contracts, blood is pumped into the aorta, the largest artery which carries oxygenated blood to systemic capillary beds (8) throughout the body. Principles of Biology

Heart
Figure 1 The cardiovascular system.

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1.During a relaxation phase (diastole), blood returning from the large veins flows into the atria and ventricles. 2.A brief period of atrial systole forces blood out of the atria into the ventricles when atrioventricular (AV) valves open 3.Then ventricular systole pumps blood into the large arteries when semilunar valves open.

http://bio1152.nicerweb.com/Locked/media/ch42/cardiac_cycle.html

Heart
Figure 2 The cardiac cycle. The heart pumps bloods by alternately contracting and relaxing the atria (upper chamber) and ventricles (lower chambers), aided by the opening and closing of the valves. The ECGs display the electrical signals that trigger systole (pump on or CONTRACTION) and diastole (pump off or RELAXATION state).

Principles of Biology

Heart

Tracing the cardiac cycle means following blood through contracting and relaxing chambers.
The heart fills with blood each time it relaxes and pumps blood when it contracts. One complete cycle of contracting and relaxing is called the cardiac cycle. Systole refers to the contraction phase of the heart, which lasts approximately 0.4 seconds. Diastole refers to the phase in the cardiac cycle when the heart is relaxed and will occur for an additional 0.4 seconds in a person with the average heart rate of 72 beats per minute. The cardiac output is the volume of blood pumped by the heart per minute and is measured by multiplying heart rate by stroke volume. Heart rate is the number of heart beats per minute, whereas stroke volume is the amount of blood pumped by a ventricle per contraction. In humans, the average stroke volume is approximately 70 mL. Heart valves are pieces of connective tissue that can stop blood flow into or out of the chambers of the heart to prevent backflow. A defective valve may allow blood leakage or backflow and causes a distinctive sound, a heart murmur.

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Blood Vessels

Arteries and veins differ in relative structure because they differ in function.

Arteries carry blood from the heart to the cells.

Arteries are vessels that have thick, elastic, tough walls with relatively narrow openings called lumina through which blood flows.

Veins carry blood from the cells back to the heart.

By comparison with arteries, venous vessels have thinner and more elastic walls and wider lumina.

The difference in structure of arteries and veins reflects inverse function.

The heart pushes blood through arteries under high pressure, so artery walls must be strong enough to withstand that pressure and must also be flexible enough to expand and contract under changing pressures from the heart.

vascularconcepts.com
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Blood Vessels

Capillaries have a simpler structure with a critical function.

As blood leaves the heart, it flows through progressively smaller vessels, first through arteries and then through their smaller versions, arterioles. Eventually, blood flows out of the smallest arterioles into capillaries, the only place in the vascular system where the transfer of materials into and out of the bloodstream takes place. Only slightly larger than a red blood cell, capillary walls only have a single layer of cells, facilitating easy passage of small molecules between capillary and interstitial fluid. The flow of nutrients and gases into and out of capillaries involves two factors: hydrostatic pressure and osmotic pressure. Hydrostatic pressure is the pressure of blood on the walls of vessels through which it flows, a pressure produced by the beating of the heart. Osmotic pressure is the pressure caused by differences in the concentration of solutes inside a capillary and in the interstitial fluid surrounding the capillaries.

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Blood Vessels

Capillaries have a simpler structure with a critical function.

The exchange of fluids inside and outside of capillaries takes place through tiny holes or poles in the walls of the capillary endothelium, the tissue that lines the blood vessels, carrying along small molecules of glucose, urea, electrolytes, and other nutrients. Oxygen and carbon dioxide diffuse directly through endothelial cells between the capillary and interstitial fluid.

Approximately 90% of the fluid that leaves a capillary near the arteriole end eventually returns to the capillary at the venule end.
Ten percent of the fluid that leaves a capillary near the arteriole end enters a different capillary network, called the lymphatic system, which carries lymph back to the upper body, where it drains back into the blood system.

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Blood Vessels
Figure 1 Flow of fluids through a capillary.

Differences in hydrostatic (or blood pressure) and osmotic pressures drive the flow of fluids out of and into blood capillaries and into lymph capillaries.

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Lymph system

Ten percent of the fluid that leaves a capillary near the arteriole end enters a different capillary network, called the lymphatic system, which carries lymph back to the upper body, where it drains back into the blood system.
http://www.edu.pe.ca/threeoaks/teacherpages/higginbotham/Biology%20521%20Webpage/resourc es/chapter9images/lymphatic%20system001.jpg

or blood pressure

www.mayomedicallaboratories.com

Fluid movement across the wall of a capillary.

At the arterial end of the capillary, hydrostatic (blood) pressure exceeds osmotic pressure contributed by plasma proteins, and a plasma filtrate is forced outside the capillary. At the venous end, osmotic pressure exceeds the hydrostatic pressure, and fluid is drawn inside the capillary. In this way plasma nutrients are carried into the interstitial space where they can enter cells, and metabolic end products from the cells are drawn into the plasma and carried away.

Blood Vessels
Flow of fluids through a capillary.

miracleofthebloodandheart.com
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Blood Vessels

Blood pressure has two main features.

Heartbeat functions as a two-part cycle in which contraction of the ventricle forces blood out of the heart under a certain pressure (the systolic pressure). The second part of the heartbeat cycle occurs when the ventricle relaxes and refills with blood from the atrium. Blood in the vascular system still exerts pressure on the interior walls of an artery during this time; however, it is a minimal pressure known as the diastolic pressure. When a person's blood pressure is measured, the report includes a pair of numbers, the systolic pressure over the diastolic pressure.

B.P. = 120/80 Systolic Pressure 120, Diastolic Pressure 80

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Blood components

Blood

Blood Composition
Plasma is a pale yellow watery solution that transports a variety of organic and inorganic substances throughout the body. Six inorganic ions, known as electrolytes, are among these solutes: sodium, potassium, calcium, magnesium, chloride, and bicarbonate. All have important functions. Three types of proteins are also transported in blood. Albumin helps maintain osmotic balance and proper pH level in the blood, whereas fibrinogen plays an essential role in blood clotting. The compounds known as immunoglobins are critical elements in the body's immune system. The blood also serves as a transport system for raw materials needed by cells for their proper function as well as the waste products of cell functioning. A small fraction of blood consists of leukocytes (white blood cells) which are part of the immune system. Platelets, also known as thrombocytes, are cell fragments that lack a nucleus and play a critical role in blood clotting. Blood also consists of erythrocytes, or red blood cells (RBCs), which are responsible for transmitting oxygen to other cells and, to some extent, the return of carbon dioxide from cells to the lungs. Each RBC contains approximately 250 million molecules of hemoglobin, a protein molecule with an iron atom at its center. Each iron atom is able to bind to four oxygen atoms, so every RBC has the capacity to transport approximately a billion oxygen atoms from the lungs to other cells. Principles of Biology

Blood composition

http://sydney.edu.au/science/biology/learning/blood_composition/

Blood
Figure 1 The composition of whole blood.

Blood consists of three main portions: plasma, buffy coat (which contains leukocytes and platelets) and erythrocytes.
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Plasma composition

http://sydney.edu.au/science/biology/learning/blood_composition/

Blood cells composition

http://sydney.edu.au/science/biology/learning/blood_composition/

Leukocytes, or white blood cells, are components of the immune system that seek out and destroy viruses, bacteria, and other pathogens, as well as cleaning up mineral particles, dead cells, and other debris throughout the body.

Red blood cells (Erythrocytes) size ~ 7-8um, Lifetime: ~120 days

Platelets
Platelets are colorless cell fragments, about 23 m in diameter and lacking a nucleus. Their most important function is in the clotting of blood. The clotting process involves a complex series of reactions that begins when a blood vessel is cut and some blood is lost. At the same time, the blood vessel constricts to reduce the loss of blood. Platelets in the blood adhere to the damaged area of the blood vessel and become activated. They then release chemicals that attract other platelets and trigger further constriction of the blood vessel. The accumulation of platelets and their release of additional clotting agents is a positive feedback loop that increases the size and density of the plug forming in the wall of the blood vessel. Eventually, a second series of reactions begins that involves more than a dozen substances called clotting or coagulation factors. These factors are present in the blood plasma, and are released by damaged cells in the area of the wound or by platelets. The end result of this sequence of reactions is the activation of an enzyme called thrombin, which converts fibrinogen, found in the blood, to fibrin. The thread-like fibers of fibrin adhere to the wound, making a mesh that prevents red blood cells and other formed elements from escaping through the wound. Platelets securing the wound then release another chemical called Factor XIII. This factor strengthens the fibrin mesh, allowing platelets to pull on the fibers, which tightens the mesh and pulls the wound closed. At this point, the plug has become secure and will remain in place until the wound is completely healed, after which it will dissolve and be carried away in the bloodstream. Principles of Biology

Red blood cells (Erythrocytes)

miracleofthebloodandheart.com

Despite being the smallest cells in the circulatory system, red blood cells still encounter some very narrow passages. The 5micrometer-wide narrow tunnels represent very difficult tunnels for these red blood cells, approximately 7 to 8 micrometers in size, to pass through.
Why dont red blood cells have a nucleus, and how do they function without one? As with most cells, 'form follows function.' A red blood cell has mostly become a rounded gas tank that can carry large amounts of oxygen and carbon dioxide through the bloodstream. A nucleus would take up vital space needed for oxygen storage. Furthermore, RBCs lack any cell organelles and cannot even use any of the oxygen they store for their own aerobic respiration, as they have no mitochondria. RBCs are only capable of anaerobic respiration. This stripping down of RBCs is not without consequence, as red blood cells have lost many of their homeostatic functions. For example, most other cells have the ability, within limits, to counteract changes in the concentration of the extracellular fluid. However, red blood cells lost this ability upon becoming completely specialized for gas transport.

Oxygen Transport proteins

Hemoglobin is an oxygen transport protein, but functions in erythrocytes, enhancing the solubility of oxygen in the blood.
Myoglobin functions as an oxygen transport protein in tissues. It also provides a local oxygen storage site by enhancing the solubility of oxygen.

Myoglobin/hemoglobin slides Adapted from: faculty.weber.edu/ewalker/.../Oxygen%20Transport%20Proteins.ppt

Myoglobin is composed of a single polypeptide chain with 153 amino acid residues. It measures 45x35x25 angstroms with about 70% alphahelix content. Each myoglobin molecule contains a prosthetic (helper) group: a Protoporphyrin IX and a central iron atom collectively called heme.:

 The heme group is held in place by hydrophobic interactions to the non-polar interior region of the protein. It is not attached by any covalent linkages. (In fact, it may be removed, leaving the apoprotein behind.) An iron ion fits perfectly into the center of the protoporphyrin, chelated by four nitrogen atoms of a tetrapyrole ring sytem.

Myoglobin Structure

Since iron ions are hexadentate, each has six coordination sites. One of these two other sites forms a coordinate covalent bond to a nitrogen atom in histidine F8 (proximal). Another histidine (E7, distal) is close to the sixth coordination position.

The iron ion is the binding site for oxygen molecules. The iron ion often converts between the free Fe2+ (ferrous ion) state and the bound Fe3+ (ferric ion) state. In the unbound state, the iron atom is slightly proximal (above) the plane of the protoporphyrin. As oxygen binds to the distal side of the ring, it pulls the iron atom about 0.2 angstrom closer to the plane of the ring. Although this distance is small, the movement is amplified, causing significant shifts throughout the teritary structure of the protein.

The position of the distal histidine (E7) prevents O2 from binding too strongly to the iron atom. Maximal binding strength is achieved when the three atoms [Fe-O=O] form a linear sequence. However, the distal histidine prevents this from occurring, and the diatomic oxygen binds in a bent configuration.

Carbon monoxide also binds to the iron atom in myoglobin. In fact, it will displace oxygen and form a much tighter bond than oxygen, due to its more polar bond.
Even low concentrations of CO can displace O2. This explains how even low concentrations of CO can cause asphyxiation in the presence of O2!

Fortunately, CO also binds in a bent configuration. This weakens the attraction, such that eventually the CO will dissociate over time, allowing recovery.

 Hemoglobin is a much more complex molecule than myoglobin. The protein is nearly spherical with a 55 angstrom diameter and molecular mass of 64.45 kD. It is a tetrahedron containing: 4 protein subunits, 4 protoporphyrins, and 4 iron atoms. Each hemoglobin molecule can transport four oxygen molecules (one per Fe atom).
35

The two alpha subunits have 141 amino acids, while the two beta subunits contain 146 residues.

Hemoglobin is located in erythrocytes, where it greatly increases oxygen solubility, facilitating as much as 68 times higher oxygen concentrations than in water alone.

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 Oxygen binds to hemoglobin each of the four iron atoms. This occurs sequentially, with the affinity of each the four sites changing as the sites become occupied with oxygen. L = ligand of molecular oxygen (O2).

The hemoblogin molecule exhibits lower affinity for the first molecule of oxygen to bind. Its affinity increases as subsequent oxygen molecules bind.

 Plotting oxygen binding to hemoglobin at various oxygen concentrations shows this change in affinity:
Hemoglobin Binding to Oxygen
1.0 Hb 0.5

Fraction of Sites Bound

p50 = 20 Torr 0.0 0 20 40 60 80 100 pO2 (mm Hg)

 When the binding curve for myoglobin is compared to hemoglobin, a distinctly different binding profile is observed:
Mb & Hb Binding to Oxygen
Fraction of Sites Bound

1.0 Mb 0.5 p50= 2 Torr p50=20Torr 0 20 40 60 80 100 Hb

0.0

pO2 (mm Hg)

At lower concentrations of oxygen (as in the capillary), myoglobin has higher affinity for oxygen than does hemoglobin:

Mb & Hb Binding to Oxygen

1.0
Fraction of Sites Bound

Mb

Hb

0.5

0.0 0

Capillary

Lungs

20

40 60 pO2 (mm Hg)

41

80

100

 What causes cooperativity in Hb? The key to understanding this is understanding the changes in Hbs tetrameric structure when O2 binds.

 When the first O2 molecule binds to one of the four heme groups a number of structural changes occur:
The movement of the Fe atom into the heme plane also draws in the F8 [promixal] histidine, leveraging a big change in its subunit. The alpha and beta groups rotate ~ 15 with respect to one another, disrupting non-covalent linkages between its neighboring subunits. The open channel in the center of the subunits becomes much smaller, bringing the beta chains much closer than before

These structural changes increase affinity for oxygen in the remaining three subunits.

Hemoglobin Oxygen Binding Cooperativity

pH of the blood also affects oxygen affinity for Hb. Lower pH decreases oxygen affinity. This automatically releases oxygen in peripheral tissues where active respiration has produced increased levels of carbon dioxide, resulting in lower pH caused by carbonic acid: CO2 + H2O H2CO3 This phenomenon is often call the Bohr Effect.

Gas Exchange Adaptations

Figure 1 Relationship between pH and partial pressure of oxygen on the oxygen saturation of hemoglobin.

As blood pH decreases from 7.6 to 7.2, the ability of hemoglobin to hold oxygen diminishes, called the Bohr shift. Because carbon dioxide is nearly 20 times as soluble in water as is oxygen, it is far less essential for it to bond to hemoglobin to return to the lungs. Solubility of Oxygen: 0.003 ml/(dl.mmHg), Solubility of Carbon Dioxide 0.067 ml/(dl.mmHg) A gas exchange system works most efficiently if it transports oxygen to the cells while simultaneously removing carbon dioxide from the cells to return to the surrounding atmosphere. Blood plays a critical role in gas exchange processes. During gas exchange, most of the carbon dioxide dissolves in the blood, producing hydrogen and bicarbonate ions.
Principles of Biology

Liquid blood

Alveolar gas

O2 content of blood = Dissolved + Hb bound O2

O2 is unloaded in tissues
O2
Hb O 2

tissue metabolism
DAlecy

H Temperature CO2
47

Carbon dioxide is carried in the blood in three forms

1. Dissolved 2. As bicarbonate
CO2 + H2O
H2CO3

C.A.

H2CO3
H
+

+ HCO3

3. As carbamino compounds (bound to Hb)

Hb.NH2 + CO2 Hb.NH.COOH

Gas Exchange Adaptations

Transport of carbon dioxide and oxygen by hemoglobin.
Carbon dioxide can travel between the cells to the lungs as part of carbaminohemoglobin complexes or by reacting with water to form bicarbonate. O2 travels primarily as part of oxyhemoglobin. Both molecules bind to the Heme groups on the hemoglobin, which contains the ferrous ion (Fe2+).

At capillary

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Gas Exchange Adaptations

Transport of carbon dioxide and oxygen by hemoglobin.

At lungs

Carbon dioxide can travel between the cells to the lungs as part of carbaminohemoglobin complexes or by reacting with water to form bicarbonate. O2 travels primarily as part of oxyhemoglobin. Both molecules bind to the Heme groups on the hemoglobin, which contains the ferrous ion (Fe2+). Principles of Biology

Blood

Cholesterol and inflammatory molecules in the blood contribute to disease risk.

Cholesterol is a steroid manufactured by all animals and, in smaller amounts, by plants and fungi. It is an essential component of all animal bodies. The two best known cholesterols are high-density lipoprotein (HDL) and low-density lipoprotein (LDL). HDL and LDL are popularly known, respectively, as "good" cholesterol and "bad" cholesterol because of their roles in the circulatory system.

HDL appears to scour out deposits of cholesterol on the walls of blood vessels and transport them to the liver, where the cholesterol is removed and recycled.

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Blood

Cholesterol and inflammatory molecules in the blood contribute to disease risk.

By contrast, LDL has a tendency to collect on the walls of blood vessels, where it is attacked by macrophages and results in the formation of sticky plaques. As these plaques grow, they restrict or even stop the flow of blood. Atherosclerosis is a condition characterized by the deposition of plaques of fatty material on the inner walls of arteries.

Blockage of a blood vessel as the result of atherosclerosis is only one of the ways in which heart attack or stroke may occur.

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Blood
Stages of atherosclerosis.

Illustration from Libby P: Inflammation in Atherosclerosis. Nature 202;420:868

Blood
Stages of atherosclerosis.

Read more and watch animations on

http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=athero

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Blood

Some blood diseases are genetic.

Some blood disorders have a genetic basis. One example is a group of disorders known as thalassemia, in which a person's body makes an abnormal form of hemoglobin. The disordered hemoglobin is unable to transport oxygen from the lungs to the cells normally, and a person develops anemia. Another is sickle-cell anemia (SCA), characterized by the presence of abnormally shaped red blood cells that are incapable of carrying adequate amounts of oxygen Sickle-shaped red blood cells are stiff and sticky with sharp edges. They have a tendency to coalesce into clumps that can impede blood flow, causing pain, tissue damage, and infections.

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Blood
Figure 8 Normal and sickle-shaped red blood cells.

http://circuitsurfers.com/2013/02/27/sickle-cell-anemia-cpb/ http://learn.genetics.utah.edu/content/disorders/whataregd/sicklecell/