unit 11- 15

The Lymphatic System

Consists of two main components:

• Lymphatic Vessels: Transport lymph throughout the body.

• Lymphoid Tissues and Organs: Include lymph nodes, spleen, and thymus, and play key roles in immune response.

Functions of the Lymphatic System

• Fluid Transport:

  • Returns escaped fluids from the cardiovascular system back to the blood.

  • Prevents edema by picking up excess tissue fluid and plasma proteins carried by lymphatic vessels.

• Immune Function:

  • Circulates lymphocytes (white blood cells) for immune responses.

  • Filters toxins, pathogens, and cellular debris from lymphatic fluid.

• Fat Absorption:

  • Absorbs fats and fat-soluble substances from the digestive tract via lacteals.

Balance Between Hydrostatic and Osmotic Pressure

• Hydrostatic Pressure:

  • Pushes fluids out of capillaries into tissue spaces.

• Osmotic Pressure:

  • Pulls fluids back into capillaries.

• Achieving balance between these two forces is crucial for normal circulation and fluid exchange.

Edema

• Occurs when excess fluid accumulates in tissues due to failure in lymphatic drainage.

Lymphatic Vessels

• Structure: Form a one-way system where lymph flows only toward the heart.

• Comparison to Blood Vessels: Similar to veins but specifically designed to transport lymph.

Lymph Capillaries

• Serve as pores for gas and nutrient exchange.

Lymph Components

Lymph

• A clear, colorless fluid carrying white blood cells, proteins, and waste products.

  • Important for immune defense and maintaining fluid balance.

Lymphatic Vessels

• Network of Tubes: Transport lymph throughout the body, ensuring unidirectional flow through valves.

Lymphoid Organs

• Types:

  • Primary Lymphoid Organs (Sites of Lymphocyte Production & Maturation):

    • Bone Marrow: Produces B and T lymphocytes (B-cells mature here, T-cells migrate to thymus for maturation).

    • Thymus: Located in upper chest, matures T-lymphocytes, shrinks in adults.

  • Secondary Lymphoid Organs (Sites of Immune Response):

    • Lymph Nodes: Filter lymph fluid, trapping pathogens and housing immune cells.

    • Spleen: Filters blood, removes old red blood cells, stores white blood cells.

    • Tonsils: Fight infections from airborne or ingested pathogens.

    • Peyer’s Patches: Found in intestines, detect microbes in the digestive system.

    • Mucosa-Associated Lymphoid Tissue (MALT): Protects mucosal areas.

Differences Between Primary and Secondary Lymphoid Organs

Lymph Transport Mechanism

• Lymphatic vessels form a low-pressure system similar to veins.

• Transport aided by:

  • Milking Action of Skeletal Muscles: Helps push lymph.

  • Pressure Changes During Breathing: Assist in drawing lymph towards the heart.

  • Smooth Muscle in Lymphatic Walls: Contracts to help move lymph.

Lymph Nodes and Immune Defense

• Components:

  • Macrophages: Engulf and destroy bacteria and viruses.

  • Lymphocytes: Monitor lymph for foreign substances.

• Structure:

  • Typically kidney-shaped, less than 1 cm long, divided into compartments by trabeculae.

  • Contains follicle structures where lymphocytes proliferate and germinal centers form.

Types of Lymphocytes

1. B cells: Produce antibodies against antigens.

2. T cells: Defend the body against diseases directly by killing infected cells.

3. Natural Killer Cells: Attack virus-infected and cancerous cells.

Lymph Flow Through Nodes

• Pathway:

  • Lymph enters through afferent lymphatic vessels, flows through sinuses, and exits via efferent lymphatic vessels.

  • Slowed Flow: Fewer efferent vessels compared to afferent vessels slows down lymph flow, enhancing filtration.

Inflammation and the Immune Response

First Line of Defense

• Physical & Chemical Barriers:

  • Skin, mucous membranes, and other barriers prevent pathogen entry.

  • Stomach acid kills harmful microbes, while tears and saliva contain antimicrobial enzymes.

Second Line of Defense (Innate Immune Response)

• Fights back against pathogens if they enter the body, through:

  • Phagocytosis: Engulfing and ingesting pathogens by specific cells (e.g., macrophages).

  • Inflammation: Increases blood flow and attracts immune cells to the injury site.

  • Fever: Elevates body temperature to hinder pathogen growth.

Third Line of Defense (Adaptive Immunity)

• Specific Recognition: Includes actions of T-cells and B-cells:

  • T-Cells activate B-cells and can directly kill infected cells.

  • B-Cells produce antibodies that attach to pathogens.

Adaptive Immunity Mechanics

• Memory Cells: Long-lasting cells that remember previous invaders for faster immune response upon re-exposure.

• Immunological Memory: Maintains a bank of data about past infections for efficient future responses.

Overview of Immune Disorders

• Allergies: Overreactions to harmless substances.

• Autoimmune Diseases: Body's immune system attacks itself, mistaking parts of the body as foreign.

• Immunodeficiencies: Abnormalities in immune function leading to higher susceptibility to infections

• Antibodies prepared for clinical testing in diagnostics.

• Produced from descendants of a single cell line, exhibiting specificity for one antigen.

• Uses: Cancer treatment, autoimmune diseases, and infectious diseases.

Antibodies (Immunoglobulins, Igs)

• Constitute gamma globulin part of blood proteins and are soluble proteins secreted by activated B cells (plasma cells).

• Formed in response to various antigens.

Antibody Structure

• T- or Y-shaped molecules with four polypeptide chains linked by disulfide bonds.

• Each chain has:

  • Variable regions (V): Antigen-binding sites.

  • Constant regions (C): Determine antibody class.

Antibody Classes: MADGE

1. IgM: First class released; can fix complement.

2. IgA: Found in secretions like mucus and tears.

3. IgD: Important for B cell activation.

4. IgG: Most abundant; crosses placental barrier.

5. IgE: Involved in allergies.

Antibody Functions

• Inactivation of Antigens:

  • Complement fixation: Antibodies bind, fixing complement.

  • Opsonization: Tags antigens for phagocytosis.

  • Neutralization: Binds to toxins or viruses.

  • Agglutination: Clumping of cells.

  • Precipitation: Antigen-antibody complexes settle out of solution.

Adaptive Immune Response

• B Cells: Secrete antibodies.

• T Cells: Fight antigens directly, activated by antigen presentation from APCs.

  • Helper T Cells: Stimulate B cells; release cytokines.

  • Cytotoxic T Cells: Kill infected cells using perforin and granzymes.

  • Regulatory T Cells: Suppress immune activity.

  • Memory Cells: Long-lived, aid in subsequent responses.

Transplants and Grafts

• Types of Grafts:

  • Autografts: Same person.

  • Isografts: Identical twin.

  • Allografts: Different person (most common).

  • Xenografts: Between different species (usually unsuccessful).

• Tissue matching and immunosuppressive therapy are crucial to prevent rejection.

Immune System Disorders

• Allergies: Hypersensitivity responses.

  • Immediate: IgE-mediated (e.g., hives, anaphylaxis).

  • Delayed: Involving T cells (e.g., contact dermatitis).

• Autoimmune Diseases: Body attacks itself (e.g., rheumatoid arthritis, multiple sclerosis, lupus).

• Immunodeficiencies: Increased susceptibility to infections due to immune system dysfunction.

Blood Circulation

Oxygenated Blood vs. Deoxygenated Blood

Flow of Blood in the Body

1. Lungs: Oxygen is absorbed into the blood.

2. Oxygenated Blood: Travels via pulmonary veins to the left heart.

3. Heart Pumps It: Through the aorta to the whole body.

4. Body Uses Oxygen: Blood becomes deoxygenated.

5. Deoxygenated Blood: Returns to the right heart via veins.

6. Heart Sends It to Lungs: Through pulmonary arteries for oxygenation.

7. Cycle Repeats!

Heart Conductive Pathway (Electrical System of the Heart)

Step-by-Step Flow of Electrical Signals

1. Sinoatrial (SA) Node: Pacemaker located in the right atrium, generates electrical impulses (normal: 60-100 bpm).

2. Atrioventricular (AV) Node: Located between the right atrium & ventricle, delays impulse for atrial contraction.

3. Bundle of His: Inside the interventricular septum, carries impulses to ventricles.

4. Right & Left Bundle Branches: Direct signals to right and left ventricles.

5. Purkinje Fibers: Spread through ventricles, causing contraction to pump blood.

Summary Flowchart

🟢 SA Node → AV Node → Bundle of His → Right & Left Bundle Branches → Purkinje Fibers → Ventricular Contraction🔄

Importance of the Conductive Pathway

• Maintains steady heartbeat

• Ensures proper blood circulation

• Prevents heart rhythm disorders (arrhythmias)

Heart Wall Structure and Function

The heart wall has four layers:

1. Pericardium (Outer Protective Layer): Reduces friction, protects heart from infections and over-expansion.

2. Epicardium (Outermost Layer): Thin layer, part of the heart wall.

3. Myocardium (Thick Muscular Middle): Contracts to pump blood.

4. Endocardium (Inner Lining): Smooth lining to reduce friction.

Operation Process of the Heart Wall

• Systole: Myocardium contracts, pushing blood into arteries.

• Diastole: Myocardium relaxes, allowing heart chambers to fill.

• Electrical Signals: Ensure coordinated muscle contraction for steady rhythm.

• Blood Circulation: Maintains oxygenated blood flow to body and deoxygenated blood return to lungs.

Detailed Explanation of Cardiac Circulation

Cardiac circulation consists of two main circuits:

1. Pulmonary Circulation: Moves deoxygenated blood from heart to lungs for oxygenation and back.

2. Systemic Circulation: Delivers oxygenated blood to the body and returns deoxygenated blood to heart.

Step-by-Step Blood Flow Through the Heart

1. Deoxygenated blood from the Superior & Inferior Vena Cava enters the right atrium.

2. The right atrium contracts, sending blood to the right ventricle... (continue this process as needed).

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• The right ventricle then contracts, pumping the deoxygenated blood through the pulmonary valve into the pulmonary arteries.

• From there, the blood travels to the lungs, where it receives oxygen and releases carbon dioxide.

• Oxygenated blood returns to the heart via the pulmonary veins into the left atrium.

• The left atrium contracts, pushing blood into the left ventricle.

• Finally, the left ventricle contracts, sending oxygen-rich blood through the aortic valve into the aorta, distributing it to the rest of the body.

  • Vessels That Return Blood Toward the Heart

    • Venules and Veins: Responsible for returning blood to the heart.

    Three Layers (Tunics) in Blood Vessels (Except Capillaries)

    • Tunica Intima: Friction-reducing lining.

      • Endothelium

    • Tunica Media:

      • Smooth muscle and elastic tissue.

      • Controlled by the sympathetic nervous system.

    • Tunica Externa:

      • Protective outermost covering composed mostly of fibrous connective tissue, which supports and protects the vessel.

    Structural Differences in Arteries, Veins, and Capillaries

    • Capillaries:

      • Only one cell layer thick (tunica intima).

      • Allow exchanges between blood and tissue.

      • Form networks called capillary beds.

      • Blood flow through a capillary bed is known as microcirculation.

      • Pathway: Blood flows from terminal arteriole → exchange vessels of capillary bed → postcapillary venule.

    • Special Capillary Beds:

      • The mesentery has precapillary sphincters and vascular shunts:

      • When precapillary sphincter is open, blood flows through and exchanges with cells can occur.

      • When closed, blood flows through the shunt, bypassing cells in that region.

    Major Arteries of Systemic Circulation

    • Aorta: Largest artery in the body, leaves from the left ventricle of the heart.

      • Regions:

        • Ascending aorta: Leaves the left ventricle.

        • Aortic arch: Arches to the left.

        • Thoracic aorta: Travels downward through the thorax.

        • Abdominal aorta: Passes through the diaphragm into the abdominopelvic cavity.

    • Arterial Branches of the Aortic Arch:

      • Brachiocephalic trunk splits into:

        • Right common carotid artery.

        • Right subclavian artery.

      • Left common carotid artery splits into:

        • Left internal and external carotid arteries.

      • Left subclavian artery branches into:

        • Vertebral artery.

      • In the axilla, the subclavian artery becomes the axillary artery → brachial artery → radial and ulnar arteries.

    • Arterial Branches of the Abdominal Aorta:

      • Celiac trunk is the first branch. Three branches are:

        1. Left gastric artery (stomach).

        2. Splenic artery (spleen).

        3. Common hepatic artery (liver).

      • Superior mesenteric artery supplies most of the small intestine and first half of the large intestine.

      • External iliac arteries enter the thigh → femoral artery → popliteal artery → anterior and posterior tibial arteries.

    Major Veins of Systemic Circulation

    • Veins Draining into the Superior Vena Cava:

      • Radial and ulnar veins drain into → brachial vein → axillary vein.

      • Cephalic vein drains the lateral aspect of the arm and empties into the axillary vein.

      • Basilic vein drains the medial aspect of the arm and empties into the brachial vein.

      • Basilic and cephalic veins are joined at the median cubital vein (elbow area).

      • Brachiocephalic veins join to form the superior vena cava → right atrium of heart.

      • Azygos vein drains the thorax.

      • Posterior tibial vein drains into → popliteal vein → femoral vein → external iliac vein.

    Arterial Supply of the Brain and the Cerebral Arterial Circle (Circle of Willis)

    -Posterior cerebral arteries form from the division of the basilar artery, supplying the posterior cerebrum.

    • Anterior and posterior blood supplies are united by small communicating arterial branches, resulting in the cerebral arterial circle.

    Vital Signs

    • Measurements of arterial pulse, blood pressure, respiratory rate, and body temperature.

    • Arterial Pulse: Alternate expansion and recoil of a blood vessel wall due to heartbeats, monitored at pressure points in superficial arteries.

      • Normal pulse: averages 70 to 76 beats per minute at rest in a healthy person.

    • Blood Pressure: The pressure blood exerts against blood vessel walls.

      • Pressure decreases as the distance from the heart increases; higher in arteries, lower in capillaries, and lowest in veins.

      • Expressed as systolic pressure over diastolic pressure (mm Hg) (e.g., 120/80 mm Hg).

      • Auscultatory Method: An indirect method of measuring systemic arterial blood pressure, typically in the brachial artery.

    Effects of Various Factors on Blood Pressure

    • Arterial Blood Pressure (BP) is directly related to cardiac output and peripheral resistance.

      • Cardiac Output (CO): Amount of blood pumped out of the left ventricle per minute.

      • Peripheral Resistance (PR): Amount of friction blood encounters as it flows through vessels.

      • Formula: BP = CO × PR.

    • Renal Factors: The kidneys regulate blood pressure

      • If blood pressure is too high, kidneys release water in urine.

      • If too low, kidneys release renin to form angiotensin II (vasoconstrictor).

      • Angiotensin II stimulates release of aldosterone, enhancing sodium (and water) reabsorption by kidneys.

    • Temperature Effects:

      • Heat: Vasodilating effect.

      • Cold: Vasoconstricting effect.

    • Chemical Effects:

      • Various substances can raise or lower blood pressure (e.g., epinephrine increases heart rate and blood pressure).

    Variations in Blood Pressure

    • Normal human range varies:

      • Systolic pressure: 110 to 140 mm Hg.

      • Diastolic pressure: 70 to 80 mm Hg.

      • Hypotension: Low blood pressure.

    Replace my note with thisAdd to the bottom of my noteTry againCancelSickle Cell Anemia (SCA)

    • SCA results from abnormally shaped hemoglobin, affecting its function of binding and carrying oxygen due to its quaternary structure.

    • The structure of globular proteins is vulnerable to pH changes and can be denatured by extreme pH levels, which impairs hemoglobin's ability to bind oxygen.

    Homeostatic Imbalance of RBCs

    • Polycythemia: Disorder resulting from excessive or abnormal increase of RBCs due to:

      • Bone marrow cancer (polycythemia vera)

      • Life at higher altitudes (secondary polycythemia)

    • An increase in RBCs slows blood flow and increases blood viscosity.

    Leukocytes (White Blood Cells, WBCs)

    • Crucial in the body’s defense against disease.

    • Complete cells with a nucleus and organelles.

    • Able to move into and out of blood vessels (diapedesis).

    • Respond to chemicals released by damaged tissues (positive chemotaxis).

    • Move by amoeboid motion through cytoplasmic extensions.

    • Normal range: 4,800 to 10,800 WBCs per mm³ of blood.

    Homeostatic Imbalance of WBCs

    • Leukocytosis: Normal response to infection, but excessive production of abnormal WBCs (e.g., in infectious mononucleosis or leukemia) is pathological.

    • Leukopenia: Abnormally low WBC count, commonly caused by certain drugs like corticosteroids and anticancer agents.

    • Leukemia: Cancer of the bone marrow leading to excessive production of immature WBCs.

    Types of WBCs

    • Granulocytes:

      • Granules can be stained; possess lobed nuclei.

      • Types include:

        • Neutrophils: Most numerous, multilobed nucleus, function as phagocytes; 3,000–7,000 per mm³ (40-70% of WBCs).

        • Eosinophils: Stain blue-red with brick-red granules, function in killing parasitic worms and allergies; 100–400 per mm³ (1-4% of WBCs).

        • Basophils: Rarest, with large histamine-containing granules, contain heparin; 20–50 per mm³ (0-1% of WBCs).

    • Agranulocytes:

      • Lack visible granules; include:

        • Lymphocytes: Large dark nucleus, important in immune response; 1,500–3,000 per mm³ (20-45% of WBCs).

        • Monocytes: Largest WBCs with kidney-shaped nucleus; functions as macrophages; 100–700 per mm³ (4-8% of WBCs).

    Platelets

    • Fragments of megakaryocytes, essential for clotting

    • Normal count: 300,000 platelets per mm³ of blood.

    Hematopoiesis

    • Process of blood cell formation in red bone marrow (myeloid tissue).

    • All blood cells derive from a common stem cell (hemocytoblast), forming:

      • Lymphoid stem cells: Produce lymphocytes.

      • Myeloid stem cells: Produce all other formed elements.

    • RBCs are anucleate, have a lifespan of 100-120 days, and are replaced by division of hemocytoblasts in the red bone marrow.

    • Reticulocytes are young RBCs which enter the blood to
      become oxygen-transporting e

    Erythropoietin

    • Rate of RBC production is controlled by erythropoietin, produced by kidneys in response to low oxygen levels, maintaining homeostasis through negative feedback.

    • WBC and platelet production is regulated by hormones:

      • Colony stimulating factors and interleukins for WBCs.

      • Thrombopoietin stimulates platelet production.

    Hemostasis

    • Hemostasis is the process of stopping bleeding from a broken blood vessel and involves three phases:

      1. Vascular spasms.

      2. Platelet plug formation.

      3. Coagulation (blood clotting).

    Coagulation

    • Injured tissues release tissue factor (TF); PF3 interacts with TF, clotting factors, and calcium ions to trigger a clotting cascade, converting prothrombin to thrombin.

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    Thrombin then catalyzes the conversion of fibrinogen to fibrin, forming a mesh that stabilizes the clot and ultimately leads to wound healing. Hemophilia

    • Hereditary bleeding disorder.

    • Normal clotting factors are missing.

    • Minor tissue damage can cause life-threatening prolonged bleeding.

    Blood Antigens

    • Blood contains genetically determined proteins known as antigens.

      • Antigens are substances recognized as foreign by the body and may be attacked by the immune system.

      • Most antigens are foreign proteins.

      • The body tolerates its "self" antigens.

      • Antibodies are the “recognizers” that bind foreign antigens.

      • Blood is “typed” using antibodies that cause blood with certain proteins to clump (agglutination) and lyse.

    Blood Group Antigens

    • There are over 30 common red blood cell antigens.

    • The most vigorous transfusion reactions are caused by ABO and Rh blood group antigens.

    ABO Blood Group

    • Type AB: Presence of both antigens A and B.

      • Can receive A, B, AB, and O blood (universal recipient).

    • Type A: Presence of antigen A.

      • Can receive A and O blood.

    • Type B: Presence of antigen B.

      • Can receive B and O blood.

    • Type O: Lack of both A and B antigens.

      • Can receive O blood (universal donor).

    Rh Blood Group

    • Named for one of the eight Rh antigens (agglutinogen D) identified in Rhesus monkeys.

    • Most Americans are Rh+ (Rh-positive), meaning they carry the Rh antigen.

    • Anti-Rh antibodies are not automatically formed in Rh-negative individuals (unlike in the ABO system).

    Rh Sensitization and Pregnancy Issues

    • If an Rh− (Rh-negative) person receives Rh+ blood:

      • The immune system becomes sensitized and produces antibodies; hemolysis does not occur immediately, as antibody production takes time.

      • Subsequent transfusions result in an immune response where antibodies attack donor Rh+ RBCs, causing hemolysis.

    • Rh-related problem during pregnancy:

      • Danger occurs when the mother is Rh−, the father is Rh+, and the child inherits the Rh+ factor.

      • RhoGAM® shot can prevent the buildup of anti−Rh+ antibodies in the mother’s blood.

    Blood Typing

    • Blood samples are mixed with anti-A and anti-B serum.

      • Agglutination or lack thereof leads to identification of blood type.

    • Typing for ABO and Rh factors is done similarly.

    • Cross Matching: Testing for agglutination of donor RBCs by the recipient’s serum and vice versa.

    Congenital Blood Defects

    • Include various types of hemolytic anemias and hemophilia.

    • Incompatibility between maternal and fetal blood can result in fetal cyanosis from the destruction of fetal blood cells.

    • Fetal hemoglobin differs from hemoglobin produced after birth.

    • Physiologic jaundice occurs in infants when the liver cannot rid the body of hemoglobin breakdown products fast enough.
      

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