Cardiovascular Physiology Notes

General Features of the Circulatory System

• Chapter 12 focuses on cardiovascular physiology, covering the circulatory system's components, pressure, flow, resistance, the heart, vascular system, lymphatic system, regulation of arterial pressure, cardiovascular reflexes/responses, patterns in health/disease, hemostasis, and anticlotting mechanisms.

12.1 Components of the Circulatory System

• Circulatory System:

  • Consists of the heart (pump), blood vessels (tubes), and blood (fluid connective tissue).

  • Transports molecules over long distances between cells, tissues, and organs.

• Blood:

  • Composed of formed elements (cells and fragments) in plasma (liquid).

  • Plasma contains proteins, nutrients, metabolic wastes, and transported molecules.

  • Cells include erythrocytes (red blood cells), leukocytes (white blood cells), and platelets (cell fragments).

    • Erythrocytes: carry oxygen to tissues and carbon dioxide from tissues.

    • Leukocytes: protect against infection and cancer.

    • Platelets: function in blood clotting.

• Hematocrit:

  • Percentage of blood volume that is erythrocytes, measured by centrifugation.

  • Typical values: 45% in men, 42% in women.

  • After centrifugation: erythrocytes at the bottom, plasma at the top, leukocytes/platelets form a buffy coat in between.

• Blood Volume:

  • Approximately 5.5 L in a 70 kg person.

• Plasma Composition:

  • Over 90% water, containing organic/inorganic substances.

  • Plasma proteins: albumins, globulins, fibrinogen.

    • Albumins: most abundant, synthesized by the liver.

    • Fibrinogen: functions in clotting.

• Serum:

  • Plasma with fibrinogen and other clotting proteins removed.

• Blood Cell Production:

  • All blood cells originate from multipotent hematopoietic stem cells.

  • Stem cells differentiate into bone marrow lymphocyte precursors (lymphocytes) or "committed" stem cells (other blood cells).

12.2 Erythrocytes

• Main function is gas transport (oxygen and carbon dioxide).

• Contain hemoglobin, which binds oxygen and carbon dioxide through iron atoms (Fe2+).

• Hemoglobin concentration: 14 g/100 mL in women, 15.5 g/100 mL in men.

• Structure:

  • Biconcave disk shape, 7 μm in diameter.

  • High surface-area-to-volume ratio for rapid diffusion of oxygen and carbon dioxide.

• Production:

  • Occurs in red bone marrow.

  • Erythrocyte precursors produce hemoglobin and lose nuclei/organelles (protein synthesis machinery).

  • Young erythrocytes (reticulocytes) contain ribosomes, comprising about 1% of circulating erythrocytes.

• Lifespan and Destruction:

  • Average life span: 120 days, with almost 1% replaced daily (250 billion cells).

  • Destruction occurs in the spleen and liver.

  • Iron is conserved; bilirubin (hemoglobin breakdown product) gives plasma a yellowish color.

Substances Necessary for Erythrocyte Production

• Iron:

  • Oxygen binds to iron on hemoglobin.

  • Lost via urine, feces, sweat, sloughed skin cells; women lose more via menstrual blood.

  • Sources: meat, liver, shellfish, egg yolk, beans, nuts, cereals.

  • Disruption of iron balance can lead to iron deficiency or hemochromatosis (excess iron deposits).

  • Homeostatic control resides primarily in intestinal epithelium, which actively absorbs iron in a negative feedback manner.

  • Iron is stored in the liver (ferritin).

    • 50% in hemoglobin, 25% in other heme-containing proteins, 25% in liver ferritin.

• Folic Acid and Vitamin B12:

  • Folic acid (leafy plants, yeast, liver) needed for thymine synthesis (DNA, cell division).

    • Deficiency impairs cell division, especially in rapidly proliferating cells (erythrocyte precursors).

  • Vitamin B12 (cobalamin) required for folic acid action, found only in animal products.

    • Absorption requires intrinsic factor (secreted by the stomach); deficiency causes pernicious anemia.

• Hormones:

  • Erythropoietin (secreted mainly by kidneys) stimulates erythrocyte progenitor cell proliferation/differentiation.

    • Secretion increases with decreased oxygen delivery to the kidneys (e.g., heart/lung disease, anemia, prolonged exercise, high altitude).

  • Testosterone stimulates erythropoietin release, contributing to higher hematocrit in men.

Anemia

• A decrease in the blood's ability to carry oxygen caused by:

  • Decreased number of erythrocytes.

  • Diminished hemoglobin concentration.

• Causes:

  • Dietary deficiencies (iron, B12, folic acid).

  • Bone marrow failure (toxic drugs/cancer).

  • Blood loss (hemorrhage).

  • Inadequate erythropoietin secretion (kidney disease).

  • Excessive erythrocyte destruction (sickle-cell disease).

Sickle-Cell Disease

• Genetic mutation alters hemoglobin.

  • At low oxygen levels, abnormal hemoglobin forms fiberlike polymers, distorting the erythrocyte membrane (sickle shapes).

  • Causes blockage of capillaries (tissue damage/pain) and erythrocyte destruction (anemia).

  • Homozygotes manifest full disease; heterozygotes (sickle-cell trait) are more resistant to malaria.

Polycythemia

• More erythrocytes than normal.
  * Adaptive response to high altitude, increases blood's oxygen-carrying capacity.
  * Increases blood viscosity, straining the heart; abuse of synthetic erythropoietin can be lethal.

12.3 Leukocytes

• Involved in immune defenses.

  • Include neutrophils, eosinophils, monocytes, macrophages, basophils, and lymphocytes.

  • Detailed functions described in Chapter 18.

12.4 Platelets

• Nonnucleated cell fragments containing numerous granules.

  • Produced from megakaryocytes in bone marrow (pinching off of cytoplasmic portions).

  • Roles in blood clotting are described in Section 12.26.

Regulation of Blood Cell Production

• In children, marrow of most bones produces blood cells; in adults, activity is limited to bones of the chest, skull base, vertebrae, pelvis, and limb ends.

• Hematopoietic Growth Factors (HGFs):

  • Protein hormones and paracrine agents stimulate progenitor cell proliferation and differentiation.

  • Erythropoietin is one example.

  • Also include colony-stimulating factors (CSFs), interleukins, thrombopoietin, and stem cell factor.

• HGF Physiology:

  • Complex due to multiple types, diverse producing cells, and varied effects.

  • Also inhibit programmed cell death (apoptosis).

  • Specific HGFs have clinical importance (e.g., erythropoietin for kidney disease, granulocyte CSF for bone marrow damage by anticancer drugs).

12.5 Blood Flow

• Rapid flow throughout the body is produced by heart's pumping action.

  • Bulk flow: all blood constituents move together.

  • Extensive vessel branching ensures cells are close to capillaries.

• Capillary Function:

  • Nutrient/metabolic end product exchange between capillary blood and interstitial fluid (diffusion).

    • Interstitial fluid/cell interior exchange via diffusion and mediated transport.

  • About 5% of circulating blood is in capillaries at any moment.

  • Other components (arteries, veins) ensure adequate capillary blood flow.

12.6 Circulation

• Closed loop with two circuits:

  • Pulmonary circulation: right ventricle → lungs → left atrium.

  • Systemic circulation: left ventricle → organs/tissues → right atrium.

• Heart Chambers:

  • Each half contains an atrium (upper) and a ventricle (lower).

• Blood Vessels:

  • Arteries: carry blood away from the heart.

  • Veins: carry blood back to the heart.

• Systemic Circulation:

  • Blood leaves left ventricle via aorta and branches through smaller arteries, then arterioles, to capillaries.

    • Capillaries unite into venules, which form veins (inferior/superior vena cava), returning to right atrium.

    • Arterioles, capillaries, and venules form the microcirculation.

• Pulmonary Circulation:

  • Blood leaves right ventricle via pulmonary trunk to pulmonary arteries (right/left lung).

    • Arteries branch/connect to arterioles, which unite into venules and then veins leading to the four pulmonary veins, which empty into left atrium. High oxygen content.

• Oxygenation:

  • Blood picks up oxygen in lung capillaries.

  • Systemic veins and pulmonary arterial blood have lower oxygen content.

  • Systemic veins connect to systemic arteries only via passage throughout the lungs.

  • Lungs receive all blood pumped via the right side of the heart.
    Parallel: each receiving a fraction supplied by left ventricle.

Distribution of Blood Flow

• Ensures systemic tissues receive freshly oxygenated blood, allows independent regulation of blood flow through different tissues by metabolic activities.

Portal Systems

• Exceptions to typical patterns (e.g., liver, anterior pituitary gland).

  • Blood passes from one capillary bed, to veins, to a second bed, to the veins.

12.2 Pressure, Flow, and Resistance

• Relationship among blood pressure, blood flow, and resistance to blood flow is hemodynamics and follows the general principle of physiology: dictated by laws of chemistry and physics.

• Blood Flow (F):

  • Always flows from higher pressure (P) to lower pressure.

• Pressure (Hydrostatic Pressure): Force exerted by the blood.

• Units for flow rate: Volume per unit time (L/min).

• Units for the pressure difference (ΔP): millimeters of mercury (mmHg).

• Resistance (R): Impeeds flow. Friction force.

• Equation for Pressure, Flow, and Resistance

  F = ΔP/R

• Equation for Calcuating Resistance

  R = (8ηL) / (πr^4)

  • η = fluid viscosity

  • L = length of the tube

  • r = inside radius of the tube

  • 8/π = mathematical constant
    Blood viscosity is a function of hematocrit and changes do occur but vascular length stays constant.

• Factors Relating Valvular Flow

  Flow is analogous to electrical current where Ohm's law applies, blood viscosity is a determinant of resistance and valvular opening determines flow (pressure gradients).

12.3 The Heart

• Location:

  • Muscular organ in protective fibrous sac called the pericardium.

• Epicardium:

  • Thin fibrous layer affixed to the heart.

• Myocardium:

  *Walls of the heart, cardiac muscle.

• Endothelium:
  *Lining to the chambers of the heart,

• Chambers:
  *The human heart is divided into right and left halves, each consisting of an atrium and a ventricle. The two ventricles are separated by a muscular wall, the interventricular septum.

• Valves - Atrioventricular (AV):

  *Permit blood to flow from atrium to ventricle but not backward from ventricle to atrium.

  *Tricuspid Valve: Right AV valve, because it has three fibrous flaps, or cusps.

  *Bicuspid (Mitral) Valve: Left AV valve; two flaps. Bishop head piece.

*Chordae Tendineae fastened to muscular projections (papillary muscles).

*Pulmonary and Aortic (Semilunar) Valves

*Also located in the heart. and allow blood to flow into the arteries during ventricular contraction but prevent blood from moving direction during ventricular relaxation. act in a passive manner.

• Summary of Flow

Cardiac Muscle

• Specialized muscle cells arranged in tightly bound layers that encircle blood-filled chambers; contract to exert pressure on blood.
  Cardiac muscle contracts with beat and has limited ability to replace its muscle cells (1% per year replaced).
  Resiliency and stamina, Excitable tissue converting bond energy into force generation, cross bridge.
  1% cardiac cells do not function in contraction but are essential for Heart Excitation (conducting system) initiates heartbeat and helps spread excitation.

• Innervation

The heart receives a rich supply of sympathetic and parasympathetic nerve fibers.

• The sympathetic postganglionic fibers innervate the entire heart and release norepinephrine, whereas the parasympathetic fibers terminate mainly on special cells found in the atria and release primarily acetylcholine.

• The hormone epinephrine, from the adrenal medulla, binds to the same receptors as norepinephrine and exerts the same actions of the heart.

• The receptors for acetylcholine are of the muscarinic type.

• Blood Supply

The arteries supplying the myocardium are the coronary arteries, and the blood flowing through them is the coronary blood flow. Most of the cardiac veins drain into a single large vein, the coronary sinus, which empties into the right atrium.

12.4 Heartbeat Coordination

Depolarization of plasma membranes triggers contraction. Gap Junctions Interconnects myocardial cells and allow action potentials to spread, allows heart to cells to become excited.
Pumping of blood needs coordination, atrial and ventricular contraction requires
sinoatrial (SA) node that generates action potential and spreads, coupling electrical excitation from contraction of cardiac muscle.
The discharge rate of the SA node, dictates the heart rate (beats contracts per min)
atrial depolarization and ventricular depolarization
link between atrial depolarization and ventricular depolarization. delay allows atrial contraction to be completed before ventricular excitation occurs
propagation of action potentials through the AV node is relatively slow
After the AV node has become excited, the action potential propagates down the interventricular septum (bundle of His)

Purkinje fibers conduct Purkinje network conducts the action potential rapidly to myocytes throughout the ventricles.
simultaneous coordinated contraction for both.
Different action potential shapes from ionic exchanges and controlled membrane materials
Membrane is much more permeable to K therefore cell sits toward equilibrium toward K 90 mv.
Depolarizations Sodium Ion entry, positive feedback. (Na Channels)
Transient permeability, Na channels close.

12.5 Mechanical Events of the Cardiac Cycle

The orderly process of depolarization leads to a cardiac cycle of contraction and relaxation; phases and keyevents
systole period of ventricular contraction and blood ejection
diastole ventricular relaxation and blood filling
phases of the cycle are identical in both halves of the heart.
The ventricle receives blood not just throughout diastole and that contraction adds addition volume
lub soft sounds closing Av valve beginning mark systole. dup aortic valve closing at onset of distole.
laminar flow and normal valves allow smooth closing and opening but turbulent with defects causes murmurs
Heart Defects causing turbulent blood flow and murmurs stenotic damage insufficiency
Volume of blood ventricle pumps time is cardiac output
Systemic and pulmonary are same
Cardiac output = heart rate the number of beats per minute and stroke volume how much blook is ejected with beat
72 beat per min and 70 l equal 5 minutes
Heart rates varies and can be modified by nervous and hormonal activities
Parasympathetic activity decreases while sympathetic neuronal activity increases
Epinephrine binds to the same receptors and has some actions on the heart.
cannot undergo tetanic contractions because of long refractory period

12.5 The Cardiac output

The average pressure during the cycle, referred to as the mean arterial pressure (MAP), is not merely the value halfway between systolic pressure and diastolic pressure, because diastole lasts about twice as long as systole.
The mean arterial pressure can be precisely calculated by complex computational methods, but at a typical resting heart rate it is approximately equal to the diastolic pressure plus one-third of the pulse pressure:

Heart rate increases the time available for diastolic filling decreases, but the quicker contraction and relaxation induced simultaneously by the sympathetic neurons partially compensate for this problem by permitting a larger fraction of the cardiac cycle to be available for filling.
Adrenergic receptors activate a G-protein-coupled cascade that includes the production of cAMP and activation of a protein kinase which enhance contractility
Cellular mechanisms involved in sympathetic regulation of myocardial contractility

• Ca Plasma membrane channel

• Ryan receptor for release

A term used to describe how hard the heart must work to eject blood is afterload. The greater the load, the less contracting muscle fibers can shorten
Autonomic regulation of heart rate is one of the best examples of the general principle of physiology that most physiological functions are controlled by multiple regulatory systems, often working in opposition.
Cardiac cycle:
Aortic pressure and vessel resistance and systolic minus diastole.

Study and Review 12.6: The Cardiac Output Recap

• Echocardiography: assesses wall and valve function

• Cardiac angiography: assesses coronary artery patency and blood flow

• Human cardiac output and heart function can be measured by a variety of methods. For example, echocardiography can be used to obtain two- and three-dimensional images of the heart throughout the entire cardiac cycle

• Cardiac Output, CO = heart rate, HR Stroke volume, SV

12.7 The Vascular System

vascular system has a major function in regulating blood pressure and distributing blood flow to the various tissues.Elaborate branching and regional specializations of blood vessels enable efficient matching of blood flow to metabolic demand in individual tissues.
The structural characteristics of the blood vessels vary by region. Capillaries consist only of endothelium and associated extracellular basement membrane, whereas all other vessels have one or more layers of connective tissue and smooth muscle.
Endothelial cells have a large number of functions, which serve as a physical lining, a permeability barrier, secrete paracrine agents that act on adjacent vascular smooth muscle cells, and can mediate angiogenesis
Have a central function in vascular remodeling by detecting signals and releasing paracrine agents. Contribute to the formation and maintenance of extracellular matrix. Secrete substances that regulate platelet clumping, clotting, and anticlotting. Synthesize active hormones from inactive precursors. Extract or degrade hormones and other mediators.
Pressures decrease as blood flows because of resistance to flow (dissipation of pressure generated by ventricles) and endothelial which helps regulate through smooth muscle interaction

Systemic arterial pressure higher than pulmonary arterial pressure; latter has lower vascular resistance

12.9 Arteries

Arteries have thick walls containing large quantities of elastic tissue suits primary function.
Major functions act low resistance conduits, server as pressure reserves that maintain blood flow to relaxation.
Contraction ejecting blood into arteries systole. Then distend them and increasing arterial pressure when ventriclar contraction ends the arteries then. the elasticity they recoil and drive blood diastolic.
Systolic SP max, Diastolic minimium.
Factor determining pulse Stroke volume speed of ejection of arterial compliance stroke volume vessel volume and compliance. Vessel volume and aorta pulse and measure via Sphygmomanometry to sounds.
Mean Arterial Pressure, MAP is the average pressure driving blood into the tissues
1/3 pressure of pulse.
There are large diameters and therefore similar pressure when body are down. Blood pressure SP and DP through the use of sounds