Korean, Edit

Chapter 13. Circulatory system

Higher category: 【Biology】 Biology Index 

1. Circulatory System

2. Blood Composition and Function

3. Circulatory System and Heart

4. Vascular System

5. Blood Flow Control

6. Blood Coagulation

7. Cardiovascular Disease

8. Cardiovascular Diagnosis

1. Circulatory System

⑴ Types of Circulatory Systems

① Open Circulatory System

○ Organisms: Arthropods and mollusks

○ Simplicity: No capillaries; no clear distinction between hemolymph and interstitial fluid

○ Efficiency: Low hydraulic pressure saves energy; no need to form capillary networks, making it easier to build and maintain the circulatory system

② Closed Circulatory System

○ Organisms: Annelids, cephalopods, vertebrates, and other large or highly mobile organisms

○ Complexity: Presence of capillaries creates a distinction between blood and interstitial fluid

○ Efficiency: High hydraulic pressure allows efficient delivery of oxygen and nutrients; osmotic pressure is maintained by large molecules in the blood, helping to regulate blood pressure

⑵ Circulatory System in Vertebrates (Cardiovascular System) – Closed Circulatory System

① Animals with high metabolic rates possess more complex blood vessels and a more powerful heart compared to those with lower metabolic rates

② The complexity and distribution of blood vessels in an organism are proportional to the metabolic activity of each organ

③ Fish (1 atrium, 1 ventricle) – Single Circulation

○ No separation between systemic and pulmonary circulation; blood must pass through two capillary beds before returning to the heart, limiting blood flow speed.

○ Maintains necessary blood flow via skeletal muscle activity.

○ Only deoxygenated blood flows through the heart.

④ Amphibians (2 atria, 1 ventricle) – Double Circulation

○ Systemic and pulmonary circulations are separated, allowing more blood supply to the brain and muscles; however, mixing of oxygenated and deoxygenated blood reduces efficiency

○ To compensate for lower oxygen efficiency, a cutaneous circulation system is developed

⑤ Reptiles (2 atria, partially divided 2 ventricles) – Double Circulation

○ Less mixing of oxygenated and deoxygenated blood improves the efficiency of material exchange

⑥ Birds and Mammals (2 atria, fully divided 2 ventricles) – Double Circulation

○ Complete separation of oxygenated and deoxygenated blood enables efficient material exchange

○ This system supports endothermic animals, which consume approximately 10 times more energy than ectotherms of the same size

⑦ Human Circulatory System

○ Systemic circulation: Left ventricle → Aorta → Whole body (capillaries) → Vena cava → Right atrium

○ Pulmonary circulation: Right ventricle → Pulmonary artery → Lungs (capillaries) → Pulmonary vein → Left atrium

2. Blood composition and function

⑴ Blood centrifugation: Separate blood by component

① Centrifugation with Anticoagulant: Separated red blood cells, soft layers, and plasma from below to top

○ Soft layer (buffy coat): leucocytes + platelets

○ Plasma: Liquid composition of blood

② Centrifugation without anticoagulant: Separated into blood clots and serum from below to top

○ Blood clot: Ingredients of coagulated blood, red blood cells + leucocytes + platelets + blood coagulation factors

○ Serum: Liquid components remaining after blood clotting, removal of fibrinogen and other components from plasma

○ Cellular elements are entangled by fibrinogen in plasma

③ Erythrocyte volume fraction (hematocrit): Ratio of red blood cell volume to total blood volume

○ Normal adult man: 0.41 to 0.51

○ Normal adult woman: 0.36 to 0.45

○ Why men use power more than women

○ Anemic people have small hematocrit

○ Viscosity is proportional to erythrocyte volume fraction

⑵ Composition of blood

Figure 1. Composition of blood

① Blood: 7% of female weight, 8% of male weight

② Blood = plasma (55%) + cellular component (45%)

○ The amount of blood in a person with a body weight of 70 kg is about 5 L.

③ Plasma = Water (92%) + Protein (7%) + Other (1%)

○ Water: Solvents Carrying Other Materials

○ Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl^-, HCO₃^-: Osmotic balance, membrane permeability control

○ HCO₃^-, H₂PO₄^-, Albumin, Hb (Bore effect): pH buffer

○ Fibrinogen: Blood clotting elements

○ Albumin: Osmotic balance. Involved in the transport of lipids. 60% of plasma proteins. Stored energy sources in plasma. 3.5 to 5 g / dl. Half-life of 20 days.

○ Globulin: It has a large molecular weight like albumin, so it can’t escape capillaries, increasing osmotic pressure in blood vessels

○ Immunoglobulins (antibodies), interferon: Defensive function, acting faster than NK cells

○ Lipoprotein: Carrying fat

○ Hormone binding protein: Especially carrying fat-soluble hormones

○ Transferrin: Iron-carrying protein

○ Nutrients, Metabolic Wastes, Respiratory Gases (O₂, CO₂), Hormones

④ Cellular elements

Figure 2. Types of Cellular Elements

⑶ Cellular elements: Red blood cells

① Structure: Concave, flexible disc-shaped cells on both sides filled with hemoglobin

○ A concave disc in the middle: Increased gas exchange efficiency by increasing the contact area between oxygen and red blood cells

○ Structure that can be folded and crumpled, making it easier to pass narrow capillaries

○ Hemoglobin is about 3 million per red blood cell

Figure 3. Type of red blood cells

○ Hemoglobin: The blood is red because it contains iron

Figure 4. Structure of hemoglobin

② Function

○ Hemoglobin has the ability to bind to O2, which can carry oxygen

○ Erythrocytes are also involved in the transport of CO2

③ Production

○ Derived from bone marrow stem cells (or myeloid cells) in the ribs, thorax, pelvis, vertebrae, etc.

○ Erythroblast: A precursor cell of red blood cells.

○ During fetal period, red blood cells are produced from liver, spleen and bone marrow

○ 5 to 6 million pieces per mm3

○ 84% of human cells are red blood cells

○ Erythropoietin (EPO) produced by the kidney regulates red blood cell production

Figure 5. Oxygen deficiency and red blood cell production

④ Maturity: Other organelles are destroyed when the amount of hemoglobin in red blood cells reaches 30%

○ No oxygen consumption due to mitochondria removal during maturation and lactic acid fermentation to produce ATP

○ Only glucose is used as an energy source

○ Mammalia: Lack of nucleus, capable of containing large amounts of hemoglobin

○ Remainder: Nucleated cells

⑤ Place of destruction: Liver, Spleen

○ Erythrocyte lifespan: About 120 days

○ Spleen damage in sickle cell anemia

○ Spleen: Located in the back of the stomach, and it is able to produce leucocytes and destroy waste red blood cells.

○ Bile formation with bilirubin produced as a result of destroying red blood cells

⑥ Evolution Theory: Number of hemoglobin amino acids that differ from humans

○ Gorilla (1), Rhesus Macaque (8), Dog (15), Horse (25), Chicken (45), Frog (67), Hyperoartia (125)

⑷ Cellular elements: leucocytes (white blood cell)

① Originated from bone marrow stem cells, 5,000 to 10,000 per 1 mm³

② life span: 100 to 200 days

③ Characteristic

○ Unlike red blood cells, they also exist in intracellular and lymphatic fluids

○ Nucleus is present and used for karyotyping

○ The shape is not constant and amoeba movement

○ Swarming: Free movement within tissue

④ Production: Produced by colony stimulating factor (CSF) produced by endothelial cells, bone marrow fibroblasts and other leucocytes

⑤ Granulocyte: Phagocytosis, pus formation, allergic reactions, inflammatory reactions

○ Main feature: High density due to many polymorphonucleus and granules

○ Classified into neutrophils, eosinophils, basophils according to dyes for staining granulocytes

○ Neutrophils

○ Function: Antibody-Coated Pathogen Phagocytosis

○ Distribution: Account for 60-65% of total leucocytes. 12-14 μm

○ Granule form: Forming three lumps

○ Eosinophils

○ Function: Antibody-coated parasite death and allergic hypersensitivity involvement

○ Distribution: Account for 1% of total leucocytes

○ Shape: 2 lumps formed. Relatively large granules. 12 to 17 μm

○ Dyed red by Eosin.

○ Basophil neutrophils (basophils)

○ Function: Histamine and heparin release promotes T lymphocyte development

○ Distribution: Account for 0.2% of total leucocytes.

○ Shape: Dispersed granules, large granules, 14 ~ 16 ㎛

○ Dyed in dark purple by methylene blue

⑥ Mast cells: Release of histamine, leukotriene, etc., due to damage or antigen binding

○ Refers to basophilic leucocytes that act on tissue cells

⑦ Monocytes: Phagocytic cells. They make up about 4% of all white blood cells. Size: ~20 µm

○ Monocytes originate from hematopoietic stem cells located in the bone marrow.

○ Type 1: Macrophages

○ Type 2: Foreign body giant cells

○ Monocytes differentiate into macrophages and dendritic cells.

⑧ Macrophages

○ Engulf and digest microorganisms, present antigens, and activate T lymphocytes

○ Microglia in the brain are also a type of macrophage

○ Classification 1: Based on Function

○ 1-1. M1 Macrophages (Classically Activated or Inflammatory Macrophages)

○ Pro-inflammatory cells: Involved in cell death and anti-tumoral activity.

○ Elongation factor: Ratio of long axis to short axis is close to 1.

○ Cytokines that induce M1 type: TLR, TNF-α, IFN-γ, CSF2, LPS, STAT1, IRF5, IL-17A

○ Cytokines secreted by M1 type: IL-6, IL-8, IL-23p40, TNF-α, IL-1β, IL-12p70, IL-12p40, IFN-γ

○ Gene markers of M1 type: HLA-DR, CD11c, CD86, iNOS, pSTAT1, IL-12, MHC-II, CD80, 27E10, CCL2, S100A8, S100A9

○ 1-2. M2 Macrophages (Alternatively Activated or Anti-inflammatory Macrophages)

○ Anti-inflammatory cells: Involved in tissue repair and pro-tumoral activity.

○ Elongation factor: High ratio of long axis to short axis.

○ Cytokines that induce M2 type: IL-4, IL-10, IL-13, TGF-β, PGE2, STAT3, STAT6, IRF4

○ Cytokines secreted by M2 type: IL-10

○ Gene markers of M2 type: CD68, CD163, CD204, CD206, VEGF, cMAF, ARG1, YM1, CCL20, CCL22, IDO1

○ Most tumor-associated macrophages (TAMs) are of the M2 type.

○ Classification 2: Based on Tissue Location

○ Kupffer cells: Macrophages located in liver capillaries.

○ Part of the innate immune system known as the reticuloendothelial system (RES).

○ The only macrophages located within blood vessels.

○ Splenocytes: Located in the spleen.

○ BMDM (Bone-Marrow-Derived Macrophage): Located in bone.

○ Dust cells: Located in the lungs.

○ Microglial cells: Located in the brain.

○ TAM (Tumor-Associated Macrophages): Found within tumor microenvironments.

Table 1. M1-like TAM과 M2-like TAM

⑨ Dendritic cells: Antigen Expression in T Lymphocytes

⑩ Lymphocytes: B lymphocytes, T lymphocytes, natural killer cells, accounting for 20-35% of all leucocytes, 6-9 μm

○ Lymphocytes do not move into the blood vessels and only work within the lymph vessels

○ High percentage of nuclei compared to other leucocytes

⑷ Cellular elements: Platelets

① A fragment of the cytoplasm of bone marrow special cells (bone marrow megakaryocytes)

○ Characteristic: No nucleus, and involved in blood coagulation

○ Uneven in shape and very small compared to erythrocytes and leucocytes

② Produce

○ 250,000 to 400,000 cells per mm³

○ Produced by TPO (thrombopoietin) produced by the liver

③ Life span: 9-12 days

④ Function: Blood Coagulation

⑤ Anti-platelet agent

○ Aspirin

○ P2Y12 inhibitor: clopidogrel, prasugrel, ticagrelor, etc.

○ Tirofiban: glycoprotein Ⅱb / Ⅲa receptor inhibitor

○ HBA(hydroxybenzy alcohol): anti-inflammatory and anti-platelet activity

3. Circulatory system and heart

⑴ Structure of the heart

Figure 6. Structure of the heart

① The heart is located beneath the sternum and is about the size of a fist, mostly composed of cardiac muscle.

② It consists of the atrium, which receives blood, and the ventricle, which delivers blood: two atria and two ventricles for human.

③ The ventricles have a thicker muscle layer than the atria and have a stronger contractile force.

○ In particular, the left ventricle contracts with much stronger force, sending blood to each organ in the body

○ The left ventricle contracts more powerfully than the right ventricle, but the same amount of blood is released in one contraction

④ Valve: Four valves in the heart prevent blood from flowing back

Figure 7. Valve structure

○ Atrioventricular valve: Between the atria and the ventricles, tricuspid and bicuspid

○ Meniscus valve: Between the ventricle and the artery

○ Abnormal sound (heart noise) occurs when blood is ejected through an incomplete valve when the valve is abnormal

⑵ Heart muscle

① Characteristic

○ High density of capillaries and mitochondria: Aerobic respiration

○ Red due to high myoglobin content

○ Nutrition: Fatty acids ≫ Glucose, lactic acid (∴ aerobic respiration only)

○ Coronary artery: Blood supply to heart muscle, lack of blood supply to heart muscle causes cardiac arrest, heart attack, myocardial infarction

② Pacemaker Potential of Autorhythmic Cells

○ Autorhythmic cells: Sinoatrial (SA) node (located in the right atrium), Atrioventricular (AV) node (located in the right atrium), Purkinje fibers

○ SA node: Generates pacemaker potentials without external electrical signals

○ AV node and Purkinje fibers: Amplify potentials when they receive external electrical signals

○ The SA node shortens the diastolic period and increases heart rate under sympathetic stimulation

○ The SA node lengthens the diastolic period and decreases heart rate under parasympathetic stimulation

○ The autonomic nerve that acts on the SA node is a branch of the vagus nerve (vagus n.)

③ Plateau Potential of Ventricular Myocardium

○ Ventricular myocardium is influenced only by the sympathetic nervous system, which regulates stroke volume

④ Contraction Mechanism of Ventricular Myocardium

⑶ Cardiac cycle: How the heart pumps and receives blood

Figure 8. Cardiac cycle

① Pulse: Changes in blood vessels according to the cardiac cycle

② Systolic: Blood flow in the ventricles → arteries

③ Diastolic: Blood flow atrium → ventricles

④ Atrium, Ventricular Relaxation: Intravenous → Atrium → Ventricular. Bicuspids and tricuspids open. Meniscal valve closed (0.4 seconds)

⑤ Atrial contraction, ventricular relaxation: Atrial blood → ventricles, Bicuspids and tricuspids open, meniscus closed (0.1 second)

⑥ The delayed time (0.1 seconds) that prevents the atria and ventricles from contracting simultaneously originates from the atrioventricular (AV) delay.

⑦ Delayed time so that the atria and the ventricles do not contract at the same time (0.1 second) is due to the atrioventricular delay

⑧ Cardiac arrest

○ Cardiac arrest due to synchronization failure, fibrillation, arrhythmia

○ Synchronization by electric shock (re-defibrillation)

⑷ Electrocardiography (ECG)

① Summary

○ It represents the heartbeat as electrical signals and does not involve attaching electrodes directly to the heart; it is typically measured using 12 electrodes.

○ Divided into waves and segments

○ Wave: If it goes up above the baseline and then goes down

○ Segment: Baseline between two waves

Figure 9. Electrocardiogram

○ Understanding ECG signals: Measures whether the electric field direction of the external electrodes aligns with the electric field direction within the heart.

② P wave: Depolarization of the SA node

○ Sinoatrial node (SA node): Tissue that voluntarily generates action potentials

○ A signal from the sinoatrial (SA) node causes atrial depolarization, leading to atrial contraction within 100 ms.

○ Initial state of valve: Atrioventricular valve open, meniscus valve closed

○ All cardiac muscle cells in the atria are connected by gap junctions, allowing the electrical signal from the sinoatrial (SA) node to rapidly spread throughout the entire atria.

③ P-Q interval: Atrioventricular (AV) Delay

○ AV delay: A delay of approximately 0.1 seconds in the action potential at the AV node, allowing time for blood to flow from the atria to the ventricles

○ Atrioventricular (AV) node

○ Gap junction pathway between the atria and ventricles

○ A pacemaker that receives signals from the SA node and generates fibrillation, synchronized with the SA node

④ Q point: The action potential reaches the bundle of His.

⑤ QRS Complex: Depolarization of the bundle of His and Purkinje fibers, i.e., ventricular depolarization

○ The bundle of His and Purkinje fibers are also considered pacemakers.

○ Depolarization of the Purkinje fibers → Ventricular depolarization → Triggers ventricular contraction.

○ As the ventricles contract, atrial repolarization occurs simultaneously → Leads to atrial relaxation.

○ Valve status: Atrioventricular (AV) valves are closed to prevent backflow from ventricles to atria; meniscus valves are also closed.

○ First heart sound (S1) occurs: The AV valves close, producing the “lub” sound

⑥ QRS-T Interval: The phase when the ventricles are actively contracting

○ Valve status: AV valves closed, meniscus valves open

○ After ventricular contraction, the meniscus valves open and blood is ejected into the arteries

○ Ventricular pressure rises and then begins to fall during this stage

⑦ T Wave: Ventricular repolarization, also includes a portion of the ST segment

○ Ventricular repolarization → Leads to ventricular relaxation

○ Valve status: To prevent blood from flowing back from arteries into ventricles, both AV and meniscus valves are closed

○ Second heart sound (S2) occurs: Meniscus valves close, producing the “dub” sound

⑧ U Wave

○ A small wave occurring after the T wave

○ It is presumed to be a relaxation signal caused by the vesicles following depolarization.

⑨ R-R Interval: Also referred to as the interval or heart rate

⑩ Summary of Valve Status

○ Lub Dub (≒ thump-thump): The sound of heart valves closing

○ Lub (at Q point): AV valves closing; meniscus valves closed

○ At S point: AV valves closed; meniscus valves opening

○ Dub (just before T wave): AV valves closed; meniscus valves closing

○ Just after T wave: AV valves opening; meniscus valves closed

⑪ Electrical Axis of the Heart

⑸ Frank-Starling Curve: Ventricular Pressure-Volume Curve

① Isovolumetric Contraction

② Ventricular Ejection

③ Isovolumetric Relaxation

④ Ventricular Filling

⑤ Cardiac Cycle: Isovolumetric contraction → Ejection (0.3 s) → Isovolumetric relaxation → 0.4 s → 0.1 s

○ Reason for isovolumetric contraction: Due to the high pressure in the aorta

○ Reason for isovolumetric relaxation: To receive blood from the atria

⑹ Fetal heart

① Blood with gas and mass exchange in the placenta enters the right atrium through the inferior vena cava (93% circulatory circulation, 7% pulmonary circulation)

② Foramen ovale: An opening between the left and right atria that remains open during the fetal stage.

○ 60% of the blood going to the pulmonary artery goes to the aorta

○ At birth, the left atrium contractions are greater than the right atrium contractions, which push the lid of the foramen ovale and block it.

○ Incomplete closure of the foramen ovale (atrial septal defect): The foramen ovale fails to close properly, causing mixing of pulmonary and systemic circulation, leading to reduced exercise capacity (congenital).

③ Ductus arteriosus (Botallo’s duct): In the fetus, it allows blood from the pulmonary artery in fetus to flow into the aorta.

○ Incomplete closure of the ductus arteriosus (patent ductus arteriosus) (congenital)

4. Vascular system

⑴ blood vessel

Figure 10. The structure of blood vessels

① Artery: Consists of three layers (intima, media, outer membrane), many elastic fibers and muscle fibers (smooth muscle), aorta (with 11% blood)

○ The proportion of elastic tissue is relatively higher than that of veins → elasticity ↑

○ With thick blood vessel walls, can withstand high blood pressure

○ The elasticity of the artery wall allows the artery to return to its original state and maintain high blood pressure when the heart relaxes

○ The aorta regulates its contraction and relaxation by itself

○ The arterioles are regulated in terms of constriction and dilation by the autonomic nervous system.

② Vein: Consists of three layers (intima, media, and outer membrane). Valves and muscle fibers (smooth muscle) are present. The vena cava and the venules (61% blood)

○ More than the artery and larger in diameter, holding more than half the blood in the circulatory system

○ The smallest blood flow resistance due to the largest radius among blood vessels

○ The walls are thinner and less elastic than those of arteries, and because the blood pressure is lower, valves are present to prevent backflow.

○ In addition to smooth muscle, there is a regulatory action of adjacent skeletal muscle

③ Capillaries

○ Capillary wall consists of a very thin layer of epithelial cells. No smooth muscle

○ Capillary pore (opening): Pores in a tube of endothelial cells. Not in the brain with strict control of BBB

○ Basal layer: Surrounded by endothelial cells, allowing for easy permeability, which facilitates the exchange of substances.

○ Hydrophobic substances and small hydrophilic substances: pass through the endothelial cell membrane by simple diffusion. Examples include carbon dioxide, water, glucose, and amino acids.

○ Large hydrophilic substances: Cross via transcytosis. In the liver and intestines, the gaps between endothelial cells are wide enough for proteins to pass through.

○ Cells located more than 100 μm away from capillaries will undergo cell death.

○ The diameter of alveolar capillaries is approximately 8 μm.

④ Blood pressure, total cross-sectional area, blood flow rate

</center>

Figure 11. Blood pressure, total cross-sectional area, blood flow rate

○ Blood pressure: Arteries> Capillaries> Veins

○ Total cross-sectional area: Capillaries> Veins> Arteries

○ Blood flow rate: Arteries> Veins> Capillaries (∵ Continuous Equation)

○ Blood flow rate of arteries: 10 cm/s

○ Blood flow rate of veins: 0.05 cm/s

⑵ Blood pressure

Figure 12. Blood pressure

① Ventricular Contraction Pressure (Max): One heart rate, release rate

○ Increased ventricular contraction pressure when the aorta decreases in distensibility

○ Increasing volume of single stroke increases ventricular contraction pressure

② Ventricular relaxation pressure (lowest): Peripheral circulation resistance, time to next systolic period

○ Decreased distensibility of the aorta reduces ventricular diastolic pressure

○ The volume of single stroke does not affect ventricular relaxation.

③ Pulse pressure (= systolic blood pressure-diastolic blood pressure) ← 1 stroke volume, elasticity of the aorta

④ Cardiac output = The volume of blood ejected from the ventricle for 1 minute = The volume change of the ventricles × heart rate for 1 minute

⑤ Blood pressure 120/80 (mmHg) is the pressure exerted in addition to the existing atmospheric pressure

⑥ Measurement of blood pressure

Figure 13. Measurement graph of blood pressure

Figure 14. How to measure blood pressure

⑦ Blood pressure changes according to the cardiac cycle (CV physiology)

Figure 15. Blood pressure changes according to the cardiac cycle

○ The diastolic phase is approximately twice as long as the systolic phase.

○ The MAP (mean arterial pressure) is commonly calculated using the formula: MAP = (2 × diastolic + systolic) / 3

⑧ Blood pressure = Full load × Posterior load

○ Full load: Proportional to blood volume, long-term regulation, regulation in the kidneys

○ Posterior load: Proportional to capillary perfusion resistance, etc. Short-term regulation, controlled through contraction and relaxation of arterioles.

○ Vascular resistance

○ The body’s peripheral blood pressure is greater than the pressure of the heart because it has to go against gravity, and skeletal muscle is involved.

○ Figure 15. Is not identified because is a major vessel

⑶ Material transport through the walls of capillaries

① Capillaries have a single layer of cells and have the largest cross-sectional area, which is advantageous for mass exchange.

② Mass exchange method

○ Simple diffusion or facilitated diffusion: Oxygen, carbon dioxide, small molecules, some ionic material

○ Transcytosis: When moving large molecules (blood cells, proteins, etc.)

○ Movement through capillary pores

○ Active transport

○ Osmotic pressure

③ Driving force for mass exchange

○ Blood pressure

○ Blood osmotic pressure: Formed by large molecules remaining in the capillaries

⑷ Mechanism of blood flow to the heart through veins

① Disruptors of Vein Blood Flow

○ Veins have low blood pressure, which can reverse intravenous pressure depending on external conditions

○ Example. Gravity: Obstruct the flow of blood from bottom to top through an artery or vein

② Vein Blood Flow Mechanism: Helps blood flow to the heart

○ Valve: Prevent blood flow in the vein from reversed → Prevent blood flow reversed during muscle contraction and relaxation

○ Periodic contraction of smooth muscles surrounding the veins

Figure 16. Vein Blood Flow Mechanism

○ When muscles contract, blood moves towards the heart

○ When the muscles relax, the valve closes to prevent blood backflow

○ Skeletal muscle contracting during exercise

○ Example. Efficacy in removing blood clots formed in veins when traveling long distances

○ Pressure changes in the chest cavity (negative pressure) dilate the vena cava around the heart

○ ↑ Venous pooling → ↑ Capillary pressure → ↑ Filtration → ↑ Interstitial fluid (tissue cells)

③ If an abnormality occurs in the valve of a vein, varicose veins develop: Blood stagnation, increased load, risk of pulmonary blood

⑸ Exchange of blood and tissue fluid

① Tissue fluid and lymphatic fluid

○ Tissue fluid

○ No plasma components, white blood cells, red blood cells and platelets from capillaries

○ Tissue fluid is secreted from the capillaries to supply the cells with the nutrients and materials they need

○ Function: Substance exchange with cells and immune function

○ Return of tissue: About 85% of tissue fluid goes to capillaries, and about 15% of tissue fluid goes to lymphatic vessels

○ Lymphatic fluid

○ Tissue fluid entering the lymphatic vessel

○ No blood cells, protein, etc.

② Exchange of blood and tissue fluid through capillaries

○ Hydrostatic pressure (capillary pressure) (P_c): Blood pressure acts as a force to push liquid

○ Plasma osmotic pressure (π_p): High osmotic pressure acts as a force to draw water from tissue fluid

○ Tissue Fluid Hydrostatic Pressure (P_IF)

○ Tissue Fluid Osmotic Pressure (π_IF)

○ Frank-Starling law: Interstitial fluid (tissue exudate) = K_f(P_c - P_IF) - σ_r(π_p - π_IF) ≒ (P_c - P_IF) - (π_p - π_IF)

○ Net Filtration Pressure at End of Artery = (P_c-P_IF)-(π_p-π_IF) = (35-0)-(28-3) = 10 mmHg

○ Net Filtration Pressure at End of Vein = (P_c-P_IF)-(π_p-π_IF) = (15-0)-(28-3) = -10 mmHg

③ Return of liquid components through the lymphatic system: Lymph circulation is 1/3000 of cardiac output

Figure 17. Blood and Lymphatic Exchange

○ Formation of the lymphatic system: The amount of water that has drained into the tissue fluid is greater than the amount of water that has entered the blood

○ Function

○ Lymph nodes: Exist along the main lymphatic vessels of birds and mammals. Various immune cells are located. Swelling upon infection.

○ Absorption of fat-soluble nutrients: Lymphatic system has thin walls and high permeability, allowing fat-soluble nutrients to move

○ Return to blood: Tissue fluid → blood

○ Lymph fluid recovery: Lymphatic capillaries → Thoracic duct → Superior vena cava → Subclavian vein → Heart

○ Backflow prevention mechanism

○ Lymphatic vessels have valves, like veins, that prevent backflow and ensure lymph flows into the thoracic duct.

○ Movement is driven by pressure from surrounding skeletal muscle contractions.

○ A phenomenon that occurs in the lymphatic system

○ Lymphocytes in lymph nodes enter the bloodstream through the thoracic duct.

○ Lymphocytes exit capillary walls, pass through interstitial spaces, and enter the lymphatic system.

○ Lymphatic vessels serve as pathways for nutrient transport from the small intestine to the bloodstream.

○ Blood cells cannot enter the lymphatic system.

④ Edema: An increase in interstitial fluid due to an imbalance in fluid recovery or abnormalities in the lymphatic system.

5. Blood flow control

⑴ Overview

① Neural signals, hormones, and chemicals serve as signals for blood flow regulation.

② The brain requires a constant and stable blood flow at all times.

⑵ Overall control: Blood flow control

Figure 18. Global blood flow regulation mechanism

The dashed line represents the feedback circuit associated with the specified blood pressure adjustment

① Medulla oblongata: the autonomic nervous system control center

○ PH detection of cerebrospinal fluid → control of breathing and circulation

○ Since H⁺ does not pass through BBB, pH change is detected through simple diffusion of CO₂ and carbonate acid-base reaction.

② Arterial Baroreceptors

○ Located in the aortic arch and carotid sinuses, they send signals to the medulla oblongata.

○ The carotid sinus is a more effective baroreceptor than the aortic arch.

③ Blood Flow Control Process

○ 1^st. Increased blood pressure → Arterial baroreceptors act on the medulla oblongata.

○ 2^nd. The medulla oblongata directly stimulates the parasympathetic nervous system.

○ Parasympathetic nerve terminals: release acetylcholine, resulting in delayed heart rate.

○ 3^rd. The medulla oblongata acts on inhibitory interneurons in the spinal cord to suppress the sympathetic nervous system.

○ Sympathetic nerve terminals: release epinephrine, which increases heart rate.

○ Cardiotonic agent: epinephrine

○ 4^th. ↑ Parasympathetic activity, ↓ Sympathetic activity: arteriolar dilation, delayed pacemaker activity, decreased cardiac output.

④ Example 1. Astronauts

○ Although the actual water volume is low, the body is misled into thinking there is excess fluid → increased urine output.

○ Recovery mechanism: ↑ Sympathetic activity → prevents peripheral blood pooling → conserves body fluids.

⑤ Example 2. Orthostatic Hypotension

○ Due to gravity, venous return ↓ → cerebral blood flow ↓ → symptoms of dizziness/faintness.

○ Recovery mechanism: ↑ Sympathetic activity → prevents peripheral blood pooling → conserves body fluids.

⑶ Local regulation: Contraction and Relaxation of Arterial Smooth Muscle

① Arterial smooth muscle is controlled by the autonomic nervous system

② General: When the sympathetic nervous system is activated, arterioles leading to visceral organs constrict, while arterioles leading to skeletal muscles dilate.

③ Transient hyperemia: Arterioles near tissues with low oxygen partial pressure and high carbon dioxide partial pressure dilate, increasing blood flow.

④ Active hyperemia: Blood flow supply is proportional to metabolic changes caused by local activity (e.g., exercise).

⑤ Reactive hyperemia: Increased blood flow in response to a prior reduction in blood flow.

○ Endothelin: A vasoconstrictor

Figure 19. Aortic smooth muscle regulation mechanism

⑷ Local regulation: Capillary Microcirculation Control

① Contraction and Relaxation of Total Capillary Sphincter or Endothelial Cells

○ Relaxation of the arterioles increases full load → increases capillary blood pressure

Figure 20. Mechanisms of Microcirculation Control of Capillaries

② Quantitative explanation: Blood flow resistance (R) is inversely proportional to the fourth power of the vessel radius (r).

③ Even a slight adjustment of the radius of a specific capillary can easily regulate the blood flow through that vessel as well as other associated capillaries.

⑸ Local regulation: Histamine

① Capillary dilation during inflammatory response

② Increased vascular permeability

③ Increased blood flow to the injured area (↑ complement protein influx)

④ Relaxation of smooth muscle

6. Blood Coagulation

⑴ Exogenous coagulation: Coagulation outside the vessel. General coagulation process

① 1^st. Endothelial Surface Changes: Exposure of collagen on the endothelial cell surface

② 2^nd. Primary hemostasis

○ 2^nd-1^st. Platelets adsorb to collagen in connective tissue and physically block

○ 2^nd-2^nd. Secretion of substances by bound platelets that promote the adhesion of nearby platelets

③ 3^rd. Secondary hemostasis: Clumps blood cells in the blood while forming fibrin aggregates. Platelet plug formation

Figure 21. Blood clotting process

○ 3^rd-1^st. Fibrin Formation by Multistage Enzyme Reaction of Platelets, Damaged Cells, and Plasma Coagulation Factors

○ 3^rd-1^st-1^st. Secretion of clotting factors such as thrombokinase from damaged tissue cells

○ 3^rd-1^st-2^nd. Blood coagulation factor is activated by Ca²⁺.

○ 3^rd-1^st-3^rd. Activated coagulation factor activates prothrombin to thrombin together with Ca²⁺.

○ 3^rd-1^st-4^th. Thrombin activates fibrinogen (in the sol state) into fibrin (in the gel state).

○ In blood coagulation, thrombin and other plasma proteins are proteolytic enzymes.

○ 3^rd-2^nd. As fibrin clumps together, a fibrin clot (thrombus) forms, creating a platelet plug that seals the wound site.

④ 4^th. Vasoconstriction: Aggregated platelets contract smooth muscle, synthesizing thromboxane A2 and releasing chemical mediators

○ 4^th-1^st. Arachidonic acid → prostaglandins: cyclooxygenase is involved

○ 4^th-2^nd. Prostaglandins → Thromboxane: thromboxane synthetase is involved

⑤ 5^th. Wound closure

○ 5^th-1^st. PDGF secretion from platelets

○ 5^th-2^nd. PDGF receptors on epithelial cells show tyrosine kinase activity

○ 5^th-3^rd. Increased collagen fibers in fibroblasts → wound closure

⑵ Endogenous coagulation: Coagulation within blood vessels

① Involves Hageman factor.

② Generally speaking, blood coagulation refers to exogenous coagulation, not endogenous coagulation.

⑶ Regulation of blood clotting

① Vitamin K: Essential for blood clotting; other vitamins are independent of blood clotting

② Prostacyclin (PGI₂), Nitric Oxide (NO): Inhibit platelet aggregation

○ Generated from endothelial cells

○ Prevention of platelet plug formation in areas other than the site of injury

③ Aspirin

○ Exerts an anticoagulant effect by inhibiting cyclooxygenase, which is involved in thromboxane synthesis

○ Positive effects: antipyretic and analgesic action, prevention of heart attacks, thrombolytic effect

○ Side effects: gastric ulcers (related to mucous membrane formation), cases of death due to inability to stop bleeding during surgery, gastrointestinal bleeding, cerebral hemorrhage

④ Heparin, hirudin: Anticoagulant action by inhibiting the activation of protein lyase

○ Heparin: synthesized by mast cells, with most of its carboxyl groups carrying a negative charge; present in the liver.

○ 1^st . Heparin and anti-thrombin III bind

○ 2^nd. The three-dimensional structure of antithrombin changes

○ 3^rd. Heparin and antithrombin conjugates irreversibly bind to thrombin

○ 4^th. When antithrombin binds to thrombin, its binding affinity for heparin decreases, causing it to dissociate.

○ 5^th. Heparin is recycled and combined with another antithrombin

○ Types: Unfractionated heparin, Enoxaparin, Daltaparin, Tinzaparin

○ Hirudin: an anticoagulant substance found in leeches, secreted to prevent the ingested blood from clotting.

⑤ Warfarin: Competitive inhibitor of vitamin K, anticoagulant action by inhibiting prothrombin formation

⑥ EDTA, sodium citrate, sodium oxalate: Anticoagulant by removing calcium

⑦ Plasmin: Blood clot removal

⑧ Xa inhibitor

○ Fondaparinux

○ Rivaroxiban

○ Apixaban

⑨ Direct inhibitor to thrombin

○ Dalbigatran

○ Bivalirudin

○ Argatroban

⑷ Blood type and blood coagulation

① ABO Blood Type

○ Type A standard serum (anti-B): contains antigen A and agglutinin β.

○ Type A blood recognizes substances similar to antigen B—produced by Escherichia coli—as foreign, and produces agglutinin β.

○ Type B standard serum (anti-A): contains antigen B and agglutinin α.

○ Type B blood recognizes substances similar to antigen A—produced by Escherichia coli—as foreign, and produces agglutinin α.

○ Reaction with standard sera:

○ Agglutination occurs between antigen A and agglutinin α, and between antigen B and agglutinin β.

○ Type A blood: has antigen A and a trace amount of agglutinin β, and agglutinates with type B standard serum (anti-A).

○ Type B blood: has antigen B and a trace amount of agglutinin α, and agglutinates with type A standard serum (anti-B).

○ Type AB blood: has both antigen A and antigen B but no agglutinins; agglutinates with both type A and type B standard sera.

○ Type O blood: has no antigens but has both agglutinin α and agglutinin β; does not agglutinate.

○ Transfusion:

○ Type A can donate only to types A and AB.

○ Type B can donate only to types B and AB.

○ Type AB can donate only to type AB.

○ Type O can donate to types AB, A, B, and O.

○ Example 1: Transfusing type O blood into type A

○ Antibodies in type O blood are in trace amounts, so they do not cause a major problem.

○ From the type A recipient’s perspective, there are no foreign antigens, so it is not problematic.

○ Example 2: Transfusing type A blood into type O

○ Antibodies in type A blood are in trace amounts, so they do not cause a major problem.

○ From the type O recipient’s perspective, the foreign antigen A is introduced, leading to the production of large amounts of α antibodies, causing an agglutination reaction → death.

○ Plastic blood: not dependent on blood type.

○ Structure of blood type antigens: determined by the sugar attached after adding fucose to the red blood cell surface.

② MNS Blood Type

③ Lutheran Blood Groups

7. Cardiovascular disease

⑴ Arteriosclerosis: Oil in blood vessels causes arteries to harden

Figure 22. Arteriosclerosis

① Definition: a condition in which fat builds up inside blood vessels, causing arteries to harden.

○ CAD (coronary artery disease): a disease of the coronary arteries.

○ Heart attack: caused by blockage of the coronary arteries, which stops the supply of oxygen to the heart muscle and leads to the death of heart muscle cells.

② 1^st. Lipoproteins, such as LDL, become entangled in the arterial endothelium

○ case 1: Cholesterol deposits on damaged sites after damage to the vessel’s inner wall

○ case 2: Cholesterol deposition around the inside of blood vessels: Decreased elasticity of blood vessels

③ 2^nd. Macrophages ingest it and transform into lipid-rich foam cells.

④ 3^rd. Plaque (atheromatous deposit) formation: when extracellular matrix components (such as collagen) are secreted, the lipoprotein mass enlarges.

⑤ 4^th. T lymphocytes and smooth muscle cells of the vessel wall also join the plaque.

⑥ 5^th. Part of the smooth muscle cells form a fibrous cap that separates the plaque from the blood

⑦ 6^th. Foam cells in plaque die and release cellular residue and cholesterol

○ If a plaque ruptures, a thrombus forms in the artery.

○ If a plaque does not rupture but continues to grow, it can block the artery.

○ When the coronary artery is blocked, it causes angina pectoris.

⑧ 7^th. It takes about 40 years for hematoma and thrombus formation to occur. ChatGPT에게 묻기

⑨ Type 1. Atherosclerosis: CD40-CD40L is involved.

⑩ Type 2. Gaucher’s disease

⑪ Type 3. Niemenn-Pick disease

⑵ Primary hyperlipidemia: One of genetic diseases

① Type Ⅰ: Lipoprotein lipase deficiency

② Type Ⅱa: Defective LDL receptor

③ Type Ⅱb: Unknown cause

④ Type Ⅲ: Abnormal apoplipoprotein E

⑤ Type Ⅳ: Unknown cause

⑥ Type Ⅴ :Deficiency of apoplipoprotein C

⑶ Stroke

① Definition: A condition in which blood cannot flow through the cerebral blood vessels, causing tissue death due to lack of oxygen.

○ Ischemic stroke: Occurs when an artery in the head becomes blocked → blood supply to downstream tissue is cut off.

○ Hemorrhagic stroke: Occurs when an artery in the head ruptures.

○ If treated within three hours, the effects of a stroke can be completely reversed.

② Can also be caused by a blood clot (thrombus).

⑷ Hypertension

① Defition: Symptoms with a contraction pressure of at least 140 mmHg and a relaxation pressure of at least 90 mmHg

② Cause: Increased cardiac output, increased peripheral resistance

③ Characteristic: In patients with hypertension, the pressure receptors (baroreceptors) in the carotid artery and aorta perceive the high blood pressure as normal, resulting in a failure to initiate the baroreceptor reflex to lower blood pressure.

⑸ Anemia

① Overview

○ Definition: A condition in which red blood cells are unable to effectively carry oxygen.

○ More specifically, it refers to cases where the hemoglobin level or hematocrit level in the blood — in other words, the concentration of red blood cells — is lower than normal.

② Anemia due to impaired hematopoiesis: Includes hemolytic anemia (e.g., sickle cell anemia) and other conditions with a reduced number of red blood cells. Red blood cell production can also decrease after blood transfusions.

③ Iron-deficiency anemia

④ Pernicious anemia (e.g., caused by a deficiency of vitamin B12)

⑤ Aplastic anemia: Anemia resulting from damage to bone marrow production function. It cannot be treated with medication and requires blood transfusions.

⑥ Renal anemia: Anemia caused by kidney failure; it cannot be treated with medication and requires blood transfusions.

⑹ Cardiomyopathy

① Type 1. DCM (Dilated Cardiomyopathy): Left ventricular dilation with normal left ventricular wall thickness.

② Type 2. HCM (Hypertrophic Cardiomyopathy): Increased left ventricular wall thickness; associated with mutations in sarcomere genes.

⑺ Lymphatic System–Related Diseases

① CLL (Chronic Lymphocytic Leukemia): Characterized by small lymphocytes.

② FL (Follicular Lymphoma):

○ Grade I: Between 0 and 5 centroblasts

○ Grade II: Between 6 and 15 centroblasts

○ Grade III: More than 15 centroblasts

○ Grade III-A: Centrocytes are present

○ Grade III-B: Centroblasts form clusters

③ MCL (Mantle Cell Lymphoma)

⑻ Brugada Syndrome: A rare disorder in which the heart suddenly stops beating (sudden cardiac arrest).

8. Cardiovascular Diagnosis

⑴ Diagnosis of CAD (Coronary Artery Disease)

① Invasive methods

○ Invasive coronary angiography: Traditional gold standard; offers high resolution.

○ FFR (Fractional Flow Reserve): Distal coronary pressure ÷ proximal coronary pressure.

○ IVUS (Intravascular Ultrasound): The catheter tip emits ultrasound waves.

○ OCT (Optical Coherence Tomography): Detects lesions at a higher resolution than IVUS; more advanced than NIRS.

② Direct visualization methods among non-invasive techniques

○ CAC (Coronary Calcium Score)

○ EBCT (Electron Beam CT)

○ MDCT (Multidetector CT)

○ Magnetic Resonance Angiography

③ Functional imaging techniques among non-invasive methods

○ Myocardial perfusion scintigraphy: Uses SPECT and PET.

○ SE (Stress Echocardiography)

○ CMR (Cardiac MRI)

○ CT Angiography: Performed after intravenous injection, followed by image reconstruction.

⑵ Cholesterol level assessment: Measure LDL/HDL levels.

⑶ Inflammatory response assessment: Inflammation plays a critical role in atherosclerosis and thrombus formation.

① Treatment: Aspirin → prevents recurrence of heart attack and stroke.

② CRP (C-reactive protein) measurement: Synthesized in the liver; blood levels increase during inflammatory responses.

⑷ Blood pressure assessment: In hypertension, arterial wall damage promotes plaque formation.

⑸ Myocardial perfusion agents

Table 2. Myocardial perfusion agents

⑹ Coronary Flow Reserve (CFR)

① A compensatory mechanism in which blood vessels dilate in response to changes in pressure to maintain a constant blood flow.

② Because there is a limit to how much the vessels can dilate, there is a certain pressure at which blood flow can no longer remain constant and instead decreases.

③ In people with angina, coronary flow reserve is reduced.

Input: 2015.7.18 00:07

Modify: 2019.2.10 22:34