The Cardiovascular System: From Blood Flow to Cardiac Output

Blood

Centrifugation separates blood into three distinct layers:

  • Top: Plasma (55%)
  • Middle: Buffy coat of leukocytes & platelets (1%)
  • Bottom: RBCs (44%)

The percentage of blood composed of RBCs is known as the hematocrit.

Functions of Blood

Blood serves several vital functions in the body:

  1. Gas Exchange: RBCs transport oxygen from the lungs to tissues and carry carbon dioxide from tissues to the lungs for exhalation.
  2. Solute Distribution: Plasma carries nutrients, hormones, and waste products. Blood also transports ions and regulates their concentration in tissues.
  3. Immune Functions: Leukocytes and immune system proteins use blood as a transport system to reach sites of infection or injury.
  4. Body Temperature Maintenance: Blood carries away heat generated by metabolizing tissues, helping to maintain a stable body temperature.
  5. Blood Clotting: Platelets and clotting proteins work together to form clots that seal damaged vessels, preventing excessive bleeding.
  6. Acid-Base Homeostasis: Blood components, particularly plasma proteins acting as buffers, help maintain a stable pH between 7.35 and 7.45.
  7. Blood Pressure Stabilization: Blood volume is crucial for maintaining constant blood pressure.

Plasma Proteins

Plasma proteins constitute about 9% of plasma volume and play various roles:

  • Albumin: A large protein synthesized in the liver, responsible for maintaining blood’s colloid osmotic pressure.
  • Immune Proteins: Gamma globulins, also known as antibodies, are produced by white blood cells and are essential components of the immune system.
  • Transport Proteins: These proteins bind to lipid-based molecules, using blood as a transport system.
  • Clotting Proteins: These proteins, along with platelets, are crucial for stopping bleeding by forming blood clots.

Erythrocytes (Red Blood Cells)

Erythrocytes, or red blood cells (RBCs), have a unique structure that enables them to efficiently transport oxygen and carbon dioxide:

  • Biconcave Disc Shape: This donut-like shape increases the cell’s surface area, which is vital for gas exchange.
  • Anucleate: Mature RBCs lack a nucleus and most other organelles, creating space in the cytosol for enzymes and oxygen-binding hemoglobin (Hb).

Hemoglobin (Hb)

Hemoglobin is a complex protein consisting of four polypeptide subunits (two alpha and two beta chains). Each subunit binds to an iron-containing heme group.

  • Oxygen Binding: When iron is oxidized, it forms oxyhemoglobin (HbO2), giving blood its characteristic red color.
  • Carbon Dioxide Binding: In areas with low oxygen levels, Hb binds to carbon dioxide, forming carbaminohemoglobin, which accounts for about 23% of CO2 transport in the blood. Hb can also bind to carbon monoxide, forming carboxyhemoglobin.

Erythrocyte Lifespan and Hematopoiesis

RBCs have a lifespan of 100-120 days due to the harsh environment they endure. Hematopoiesis, the process of blood cell formation, takes place in red bone marrow. Erythropoiesis, the specific process of RBC formation from hematopoietic stem cells (HSCs), takes about 5-7 days.

Erythropoietin and RBC Regulation

Erythropoietin, a hormone secreted by the kidneys, regulates RBC production through a negative feedback loop:

  1. Stimulus: Blood oxygen levels fall below the normal range.
  2. Receptor: Kidney cells detect low oxygen levels.
  3. Control Center: Kidneys produce and release erythropoietin into the blood.
  4. Effector/Response: Erythropoietin stimulates red bone marrow to increase RBC production.
  5. Homeostasis: Blood oxygen levels rise to the normal range.

RBC Death and Recycling

When RBCs reach the end of their lifespan:

  1. They become trapped in the sinusoids of the spleen.
  2. Spleen macrophages engulf and digest the old RBCs.
  3. Hemoglobin is broken down into amino acids, iron ions, and bilirubin.
  4. Iron ions and amino acids are recycled for new hemoglobin synthesis in red bone marrow.
  5. Bilirubin (yellow pigment) is sent to the liver for excretion.
  6. Excess heme is converted to biliverdin (green pigment).

Leukocytes (White Blood Cells)

Leukocytes, or white blood cells (WBCs), are larger than RBCs and have a nucleus. They are divided into two categories: granulocytes (contain visible granules) and agranulocytes (lack visible granules).

Granulocytes

  • Neutrophils: The most common type of WBC, neutrophils have a light lilac color and a nucleus with 3-5 lobes. They are phagocytes that engulf and destroy bacteria. Chemotaxis is the process by which injured cells release chemicals that attract neutrophils to the site of injury.
  • Eosinophils: These WBCs have a bilobed nucleus and appear red. They are involved in allergic reactions and parasitic infections.
  • Basophils: The least common type of granulocyte, basophils have an S-shaped nucleus and appear purple-blue. They release histamine and other inflammatory mediators.

Agranulocytes

  • Lymphocytes: The second most common type of WBC, lymphocytes are involved in adaptive immunity. There are two main types:
    • B cells: Produce antibodies.
    • T cells: Directly attack infected or cancerous cells.
  • Monocytes: The largest WBCs, monocytes have a U-shaped nucleus and differentiate into macrophages.
  • Macrophages: Phagocytic cells that engulf and digest dead cells, bacteria, and cellular debris.

Leukopoiesis

Leukopoiesis, the formation of WBCs, occurs in the bone marrow from HSCs. There are two main cell lines:

  • Myeloid cell line: Produces most formed elements, including RBCs, platelets, granulocytes, and monocytes.
  • Lymphoid cell line: Produces lymphocytes.

Platelets and Hemostasis

Platelets, also known as thrombocytes, are small, anucleate cell fragments that play a crucial role in hemostasis (blood clotting).

Steps of Hemostasis

  1. Vascular Spasm: Blood vessel constriction reduces blood flow to the injured area.
  2. Platelet Plug Formation: Platelets adhere to the exposed collagen fibers of the damaged blood vessel, forming a temporary plug.
  3. Coagulation: A complex cascade of enzymatic reactions leads to the conversion of fibrinogen to fibrin, forming a stable blood clot.

Clotting Disorders

  • Bleeding Disorders: Examples include hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency).
  • Hypercoagulable Conditions: These conditions increase the risk of blood clot formation. Examples include deep vein thrombosis (DVT) and pulmonary embolism.

Blood Groups

Antigens on the surface of RBCs determine blood groups. The two most important blood group systems are ABO and Rh.

ABO Blood Group

The ABO blood group is based on the presence or absence of A and B antigens:

  • Type A: Only A antigen present.
  • Type B: Only B antigen present.
  • Type AB: Both A and B antigens present.
  • Type O: Neither A nor B antigen present (there is no O antigen).

Rh Blood Group

The Rh blood group is based on the presence or absence of the Rh factor, also known as the D antigen:

  • Rh positive (Rh+): Rh factor present.
  • Rh negative (Rh-): Rh factor absent.

Combining the ABO and Rh blood groups results in eight common blood types. Type O+ is the most common, while AB- is the least common.

Agglutination

Antibodies called agglutinins can bind to specific blood group antigens, causing RBCs to clump together (agglutination). Agglutination can lead to hemolysis (destruction of RBCs).

The Heart

Heart Structure and Function

The heart is a muscular organ that pumps blood throughout the body. It consists of four chambers: two atria (receiving chambers) and two ventricles (pumping chambers).

  • Right Atrium: Receives deoxygenated blood from the body through the superior and inferior vena cava.
  • Left Atrium: Receives oxygenated blood from the lungs through the pulmonary veins.
  • Right Ventricle: Pumps deoxygenated blood to the lungs through the pulmonary artery.
  • Left Ventricle: Pumps oxygenated blood to the body through the aorta.

Pulmonary and Systemic Circuits

The heart pumps blood through two circuits:

  • Pulmonary Circuit: Carries deoxygenated blood from the heart to the lungs for gas exchange and returns oxygenated blood to the heart.
  • Systemic Circuit: Carries oxygenated blood from the heart to the rest of the body and returns deoxygenated blood to the heart.

Heart Valves

Heart valves ensure one-way blood flow through the heart:

  • Tricuspid Valve: Between the right atrium and right ventricle.
  • Pulmonary Valve: Between the right ventricle and pulmonary artery.
  • Mitral (Bicuspid) Valve: Between the left atrium and left ventricle.
  • Aortic Valve: Between the left ventricle and aorta.

Coronary Circulation

The heart muscle itself receives oxygenated blood through the coronary arteries, which branch off the aorta.

Cardiac Conduction System

The heart’s electrical activity is regulated by the cardiac conduction system, which consists of specialized cells that generate and conduct electrical impulses:

  • Sinoatrial (SA) Node: The heart’s natural pacemaker, located in the right atrium. It initiates the heartbeat.
  • Atrioventricular (AV) Node: Located between the atria and ventricles. It delays the electrical impulse, allowing the atria to contract before the ventricles.
  • Purkinje Fibers: Conduct the electrical impulse throughout the ventricles, causing them to contract.

Electrocardiogram (ECG)

An electrocardiogram (ECG) records the electrical activity of the heart. The main components of an ECG are:

  • P Wave: Atrial depolarization.
  • QRS Complex: Ventricular depolarization.
  • T Wave: Ventricular repolarization.

Cardiac Cycle

The cardiac cycle refers to the sequence of events that occur during one complete heartbeat. It consists of two main phases:

  • Diastole: The period of relaxation when the heart chambers fill with blood.
  • Systole: The period of contraction when the heart pumps blood.

Phases of the Cardiac Cycle

  1. Ventricular Filling: Blood passively flows from the atria into the ventricles.
  2. Atrial Systole: The atria contract, pushing the remaining blood into the ventricles.
  3. Isovolumetric Contraction: The ventricles contract, increasing pressure and closing the AV valves.
  4. Ventricular Ejection: Ventricular pressure exceeds aortic pressure, opening the semilunar valves and ejecting blood into the aorta and pulmonary artery.
  5. Isovolumetric Relaxation: The ventricles relax, pressure decreases, and the semilunar valves close.

Cardiac Output

Cardiac output (CO) is the amount of blood pumped by each ventricle in one minute. It is calculated as follows:

CO = Heart Rate (HR) x Stroke Volume (SV)

  • Heart Rate (HR): The number of heartbeats per minute.
  • Stroke Volume (SV): The amount of blood ejected by each ventricle with each heartbeat.

Factors Affecting Stroke Volume

  • Preload: The degree of stretch on the heart muscle before it contracts.
  • Contractility: The force of contraction.
  • Afterload: The resistance the heart must overcome to eject blood.

Regulation of Cardiac Output

Cardiac output is regulated by both intrinsic (within the heart) and extrinsic (outside the heart) factors:

  • Intrinsic Regulation: Includes the Frank-Starling law of the heart, which states that the heart pumps more blood when it is stretched more.
  • Extrinsic Regulation: Includes neural and hormonal control. The sympathetic nervous system increases heart rate and contractility, while the parasympathetic nervous system decreases heart rate. Hormones such as epinephrine and norepinephrine also increase heart rate and contractility.

Blood Vessels

Blood vessels form a closed system of tubes that carry blood throughout the body. There are three main types of blood vessels:

Arteries

Arteries carry blood away from the heart. They have thick, elastic walls that can withstand high pressure.

Capillaries

Capillaries are the smallest blood vessels. They have thin walls that allow for the exchange of gases, nutrients, and waste products between blood and tissues.

Veins

Veins carry blood back to the heart. They have thinner walls than arteries and contain valves that prevent backflow of blood.

Circulation

– heart is supplied by these vessels 

L ventricle pumps into ascending aorta; R & L coronary arteries branch from ascending aorta

L coronary arteries branch into anterior interventricular artery (LAD) & circumflex artery

Coronary sinus drains into posterior R atrium, receives blood from great cardiac vein, small cardiac vein & middle cardiac vein


Symptoms of MI – shortness of breath, sweating, anxiety & nausea &/or vomiting – women may have shortness of breath or back, jaw, or arm pain

Pacemaker cells – electrical activity is coordinated by these cardiac muscle cells 

Contractile cells – generated by action potentials from pacemaker cells; display autorhythmicity (set their own rhythm)

Slow initial depolarization – Na ions to leak into cell & K ions leak out which results in this phase

Full depolarization – voltage-gated Na ion channels open, allowing Ca ions to enter the cell

Repolarization – Ca ions are time-gated for closing, voltage-gated K ion channels open allowing K ions to exit the cell

Minimum potential – K ion channels remain open until membrane reaches its minimum potential

SA node –  upper R atrium, has fastest rate of depolarization normally, about 60-70 times/min subject to influence by symp & parasymp nervous systems

AV node – slower than AV node, 40 action potentials/min; posterior & medial to tricuspid valve

Purkinje fiber system – slowest, 20 times/min, three components: AV bundle in interatrial septum & superior interventricular septum, R & L bundle branches in interventricular septum, & terminal branches penetrate  ventricles & contact contractile cardiac muscle cells

Rapid depolarization – sodium ions

Initial repolarization – potassium ions

Plateau – calcium ions

Repolarization – sodium & calcium ion; potassium open

P wave – atrial depolarization of all except SA node; upward deflection

QRS complex – ventricular depolarization & 3 separate waves, down up down

T wave – after S wave of QRS & represents ventricular repolarization, upward deflection


Ventricle contract – AV open, semilunar close

Ventricle relax – AV valves close, semilunar open

Lub – S1, AV close; Dub – S2, semilunar close

Cardiac cycle – diastole: relaxation,  systole: contraction

4 main phases – filling, contraction, ejection, relaxation

End-diastolic volume (EDV) – 120 ml of blood found in each ventricle after atrial systole 

Isovolumetric contraction phase – shortest phase of the cardiac cycle; closes AV & causes S1 sound

Isovolumetric relaxation phase – semilunar closes, S2 sound, AV stays closed until volume of blood is constant

Cardiac Cycle:

Ventricular filling, Isometric contraction, Ventricular ejection, Isometric relaxation

Heart undergoes average of 60-80 cardiac cycles/min aka heart rate (HR); determines cardiac output (CO)

CO – amount of blood pumped into pulmonary & systemic circuits in 1 min

Stroke volume – CO determined by amount of blood pumped in one heartbeat

Calculate SV – subtracting ESV from EDV

Calculate CO – multiplying HR by SV; resting CO averages about 5 liters/min

Ejection fraction – used in place of SV, percentage of blood  ejected w/ each ventricular systole, equal to SV divided by EDV; Normal ejection fraction is about 50-65%

3 factors influence SV – preload, contractility, afterload 

2 factors influence EDV – length of time ventricle spends in diastole, amount of blood returning to R atrium from systemic circuit (venous return)

Increasing contractility increases SV & decrease ESV

Afterload – determined by BP

CO – regulated by nervous & endocrine which influence both HR & SV


Norepinephrine – released by symp division, increases CO

Acetylcholine – released by parasymp, affects SA node, decreasing rate of action potential generation

Cardiac regulation – hormonal: thyroid, glucagon, aldosterone, antidiuretic, atrial natriuretic 

Factors influencing CO – electrolyte concentration in extracellular fluid, body temp, age, physical fitness, & exercise

Pulmonary circuit – transport btw heart & lungs

Systemic circuit – transport btw heart & body

Arteries – distribution system, travel away from heart; P – deoxygenated, S – oxygenated 

Capillaries – exchange system; gases, nutrients, wastes & substances exchange btw cells & blood through capillary walls 

Veins – collection system; drain blood and return it to heart; P – oxygenated, S – deoxygenated