Circulatory, Lymphatic and Immune Systems

Circulatory System

  • Functions (circulation of oxygen, nutrients, hormones, ions, and fluids; removal of metabolic waste)
    • Oxygen delivery to tissues
      1. diffuses into the blood in alveolar (lung) capillaries
      2. binds to hemoglobin in red blood cells
      3. gets transported to tissues
      4. used in cellular respiration
    • Carbon dioxide delivered out
      1. cellular respiration makes CO2: carbonic anhydrase converts it to bicarbonate.
      2. CO2 gets transported by blood: dissolved CO2, dissolved bicarbonate ion (major), bound to hemoglobin and plasma proteins
      3. diffuses out of the alveolar capillaries
      4. exhaled out
    • Nutrients
      • nutrients absorbed (either by diffusion or active transport) into blood stream in the small intestines.
      • nutrients can also be released into the blood stream by cells. For example, glucagon causes glucose to be released into the blood stream.
      • nutrients can be taken up by cells. For example, insulin causes cells to take in glucose from blood.
    • Hormones released by endocrine glands, circulate the blood in order to reach their target cells.
    • Fluids and ions circulate the blood and are regulated by how much reabsorption of water and salt occurs in the kidney.
    • Urea = metabolic waste, travels in the blood to the kidneys, where it is filtered out and passed in urine.
  • Role in thermoregulation
    • Vasoconstriction conserves heat. When it's cold, vasoconstriction occurs in the arterioles that feed the skin. Less blood flows near the surface of the skin, less heat lost.
    • Vasodilation cools you down. When it's hot, vasodilation occurs in the arterioles that feed the skin. More skin blood flow, more heat lost to the surroundings.
  • Four-chambered heart (structure, function)
    systemic and pulmonary circulation through the heart
    1. Deoxygenated blood returns to the heart: superior/inferior vena cava → right atrium
    2. Deoxygenated blood gets pumped to the lungs: right atrium → right ventricle → pulmonary artery → lungs
    3. Blood arrives at the lungs and gets oxygenated.
    4. Oxygenated blood returns to the heart: lungs → pulmonary vein → left atrium
    5. Oxygenated blood gets pumped to the body: left atrium → left ventricle → aorta
  • Blood going through the heart including the valves
    1. Vena cava
    2. Right atrium
    3. Tricuspid valve
    4. Right ventricle
    5. Pulmonary valve
    6. Pulmonary artery
    7. Lung
    8. Pulmonary vein
    9. Left atrium
    10. Bicuspid (Mitral) valve
    11. Left ventricle
    12. Aortic valve
    13. Aorta
  • Systolic and diastolic pressure
    • blood pressure = pressure blood exert on the walls of the blood vessel.
    • systolic pressure = blood pressure when blood is being pumped (the ventricles are contracting).
    • diastolic pressure = blood pressure when blood is not being pumped (the ventricles are relaxing).
  • Pulmonary and systemic circulation
    • Pulmonary circulation = heart → lungs → back to heart = oxygenates blood
    • Systemic circulation = heart → body → back to heart = delivers oxygenated blood to body
    • Pulmonary circulation = shorter than systemic circulation = less resistance = less blood pressure.
    • Systemic circulation: vasodilation when oxygen levels are low → more blood flow to oxygen-starved tissue.
    • Pulmonary circulation: vasoconstriction when oxygen levels are low → less blood flow to low oxygen/blocked alveoli → more blood flow to good alveoli where gas exchange can occur.
  • Arterial and venous systems (arteries, arterioles, venules, veins)
    comparison of blood vessels
    • structural and functional differences
      • Blood flows from artery → arteriole → capillary → venule → vein.
      • Artery
        • Elastic artery
          • Aorta and its major branches.
          • Major function = provide elastic pipe for blood straight out of the heart.
          • Lots of elastic tissue.
          • Layers: endothelium, smooth muscle, connective tissue.
          • Not active in vasoconstriction.
        • Muscular (distributing) arteries
          • Major function = distribute blood to specific organs.
          • Lots of muscle.
          • Layers: endothelium, lots of smooth muscle, connective tissue.
          • Some activity in vasoconstriction.
      • Arteriole
        • Ranges from being like a smaller version of the artery, to being a larger version of the capillary with smooth muscles spiralling around it.
        • Major function = controls blood flow to the capillaries.
        • Active in vasoconstriction. The arterioles allow the body to control which tissues gets more blood.
        • The arteriole is the most important site for vasoconstriction. Although other vessels are capable of vasoconstriction, you should always think of the arteriole when you see vasoconstriction.
      • Capillary
        • Layer: single cell thick endothelium.
        • Major function: blood-tissue solute exchange.
        • Not active in vasoconstriction.
      • Venule
        • Ranges from being like a large capillary to being like a small vein.
        • Major function: merge of capillaries to be conducted to veins.
        • No vasoconstriction.
      • Vein
        • Layers: endothelium, smooth muscle, connective tissue.
        • Major function: returns blood back to the heart.
        • Has valves to prevent the back flow of blood.
        • Breathing, skeletal muscles, and smooth muscle adaptations help blood flow through the vein at low pressure.
        • Vasoconstriction can occur in the vein.
      • You can argue that the aorta has a single aortic valve right where it connects to the heart. But for the purposes of the MCAT, arteries don't have valves, veins do.
      • Thickness: artery > vein > arteriole > venule > capillary
      • Differences between arteries and veins
        • arteries are thicker, more muscular than veins.
        • veins have valves, arteries don't.
        • arteries carry blood away from the heart (oxygenated except for pulmonary artery). Veins carry blood back into the heart (deoxygenated except for pulmonary vein).
      • Differences between artery and arteriole
        • arterioles are smaller.
        • vasoconstriction occurs predominantly at the arterioles.
    • pressure and flow characteristics
      • Blood pressure of arteries > arterioles > capillaries > venules > veins
      • Blood pressure is highest in the arteries (specifically the aorta) because the heart pumps directly into the aorta.
      • Blood pressure is lowest in the veins (specifically the vena cava) because flow resistance brings the pressure down.
      • Blood pressure is also lower when you elevate a blood vessel (think physics, P = ρgh, where h is the depth - raising your arm like taking it to shallower water)
      • Blood pressure can be regulated by vasoconstriction (increase bp), vasodilation (decrease bp), and hormones (ADH, aldosterone, renin, adrenaline all increases bp).
      • Blood flows from artery → arteriole → capillary → venule → vein.
      • Blood squirts from arteries, flows from veins, and oozes from capillaries.
      • The elasticity of arteries causes blood to flow even when the heart is resting between pumps (this is why your diastolic blood pressure is not zero)
      • Adaptations that help blood flow through the vein at low pressure:
        • Respiratory pump: when you inhale, your stomach squeezes on the veins, and your chest sucks on it.
        • Muscular pump: skeletal muscle squeezes on the veins when you exercise.
        • When you're scared, smooth muscles around veins constrict and squeezes blood.
  • Capillary beds
    • mechanisms of gas and solute exchange
      • Diffusion is the major mechanism of gas and solute exchange, whether it is diffusion as a free molecule, or bound to carrier proteins.
      • Continuous capillary
        • No pores on endothelial cells. May have clefts at cell boundaries.
        • Exchange may occur through the clefts, or by vesicle trafficking through endothelial cells.
        • Found in skin and muscles.
        • Blood-brain barrier = sealing of clefts by tight junctions.
      • Fenestrated capillary
        • Small pores, large enough for molecules, but not blood cells to leak through.
        • Found in small intestines to facilitate nutrient absorption.
        • Found in endocrine organs to allow passage of hormones.
        • Found in kidneys to allow blood filtration.
      • Sinusoidal capillary
        • Large pores, large enough for blood cells to leak through.
        • Found in lymphoid tissues, liver, spleen, bone marrow.
        • Large pores facilitate lymphocyte travel to tissues.
        • Large pores also facilitate blood cell modifications.
    • mechanism of heat exchange
      • radiation - your body gives off IR signal.
      • conduction - you touch something cold, or take a hot bath.
      • evaporative cooling - you sweat, and it cools you as it evaporates.
    • source of peripheral resistance (no longer tested)
      • Blood viscosity: blood cells and plasma proteins give blood a higher resistance to flow compared to water. Diseases that increase the amount of blood cells increase resistance.
      • Total blood vessel length: more blood vessels you have, the more resistance to flow. Overweight = more blood vessels to service the fat cells = more resistance.
      • Blood vessel diameter: vasoconstriction increases resistance, vasodilation decreases it. Obstruction from plaques inside blood vessels also increases resistance.
  • Composition of blood
    blood composition and components
    • plasma, chemicals, blood cells
      • plasma = water and chemicals = mostly water, plasma proteins, electrolytes, gases, nutrients, wastes, hormones.
      • blood cells
        • red blood cells (RBCs or erythrocytes)
          • contain hemoglobin, transports O2 and CO2
          • no nucleus, which gives it a biconcave disk shape
          • most abundant cell in blood.
        • white blood cells (WBCs or leukocytes)
          • larger than RBCs
          • lobed or irregular shaped nuclei
          • fights off pathogens
        • platelets
          • technically not cells, but cell fragments
          • responsible for clotting blood
    • erythrocyte production and destruction (spleen, bone marrow)
      • Bone marrow = makes RBCs from stem cells.
      • Spleen = destroys aged and damaged RBCs.
      • Other sites for RBC destruction include the liver and bone marrow.
      • Components of hemoglobin from destroyed RBC gets recycled
        • iron = recycled
        • heme → bilirubin → bile → excreted in feces
        • protein (globin) = broken down to amino acids
    • regulation of plasma volume
      • Blood osmolarity
        • Higher blood osmolarity → water goes into blood → higher blood volume
        • Lower blood osmolarity → water goes into tissues → lower blood volume
      • ADH (vasopressin): ↑ water reabsorption in kidney.
      • Aldosterone: ↑ salt reabsorption, leads to ↑ water reabsorption in kidney.
    • coagulation, clotting mechanisms, role of liver in production of clotting factors
      • Platelets contain enzymes and chemicals needed involved in the clotting process.
      • Liver produces clotting factors (eg. fibrinogen), which circulates in blood plasma.
      • Coagulation = liquid blood → gel
      • Clotting mechanism:
        • Platelet plug formation: wound + platelets → platelets clump at wound, release chemicals, activates clotting factors.
        • Coagulation: series of clotting factor/enzyme activation that ends in fibrinogen → fibrin. Fibrin being the fiber mesh that seals the clot.
        • Retraction and repair: clot contracts, gets compact, but after the wounded blood vessel repairs itself, the clot dissolves.
  • Oxygen and carbon dioxide transport by blood
    • hemoglobin, hematocrit
      • hemoglobin = (heme + globin) x 4
        • heme = chemical ligand binding iron
        • globin = protein that surrounds heme
        • 4 subunits of the heme-globin complex form a tetramer called hemoglobin.
        • hemoglobin can bind oxygen and carbon dioxide
      • hematocrit = % volume of blood that is red blood cells, usually ~ 45%
    • oxygen content
      • each iron atom in hemoglobin can bind one oxygen.
      • hemoglobin has 4 subunits containing 4 iron atoms.
      • each RBC has hundreds of millions of hemoglobin molecules.
    • oxygen affinity
      • hemoglobin has a sigmoidal oxygen binding curve. This is because oxygen binding to one subunit "relaxes" the conformation of the other subunits, and makes it easier for additional oxygen to bind.
      • carbon monoxide binds hemoglobin tighter than oxygen.
      • fetal hemoglobin binds oxygen tighter than adult hemoglobin.
      • myoglobin binds oxygen tighter than hemoglobin.
  • Details of oxygen transport: biochemical characteristics of hemoglobin
    hemoglobin binding curve for oxygen
    • modification of oxygen affinity
      • Higher levels of carbon dioxide → lower oxygen affinity of hemoglobin.
      • Lower pH → lower oxygen affinity.
      • Higher temperature → lower oxygen affinity.
      • Working muscle = hot, acidic, high CO2, needs oxygen. So, hemoglobin must unload its oxygen, and it does this by lowering its oxygen affinity.

Lymphatic System

  • Major functions
    • equalization of fluid distribution
      • Interstitial fluid pressure > lymphatic pressure → lymph vessel flaps open → interstitial fluid enters lymphatic capillaries → lymphatic circulation merges with veins → returns the fluid to blood
      • Interstitial fluid pressure < lymphatic pressure → lymph vessel flaps close → prevents lymph from leaking back out.
    • transport of proteins and large glycerides
      • fats get absorbed into the lacteals in the small intestine.
      • lacteal = lymphatic capillary in the small intestine.
      • plasma protein that leaked into interstitial fluids get returned to the blood via the lymphatic system.
    • production of lymphocytes involved in immune reactions
      • technically, lymphocytes are produced in the bone marrow from blood stem cells.
      • however, lymphoid tissues provide a place where lymphocytes can reside, proliferate, and differentiate.
      • lymphoid tissue is found in lymph nodes, thymus, and scattered throughout various organs.
      • lymph tissue contains many lymphocytes that cleans/filters lymph.
      • thymus is the place where T cells mature.
    • return of materials to the blood
      • cells and plasma proteins that leak out of the blood capillaries gets collected by the lymphatic capillaries and returned to the vein.
    • Composition of lymph (similarity to blood plasma; substances transported)
      • Lymph = stuff that leaks out of the capillaries = mostly water, plasma protein, chemicals, and white blood cells.
    • Source of lymph (diffusion from capillaries by differential pressure)
      • blood plasma from capillaries → interstitial fluid → lymph → returned to blood
    • Lymph nodes (activation of lymphocytes)
      • Lymph nodes are concentrated with white blood cells.
      • When pathogens or foreign antigens get inside a lymph node, lymphocytes that reside there get activated.
      • Activation = lymphocytes start releasing chemicals that stimulate an immune response = proliferation, antibody production, release of cytokines.

Immune system: Innate and Adaptive Systems

  • Cells and their basic functions
    white blood cells
    • macrophages, neutrophils, mast cells, natural killer cells, dendritic cells
      • macrophages = phagocytose pathogen and then act as antigen presenting cell.
      • neutrophils = Polymorphonuclear leukocytes = PMNs = phagocytose pathogen and destroys it.
      • mast cells: release histamine during an allergic response, bring about inflammation.
      • natural killer cells: kills infected/abnormal cells.
      • dendritic cells: the best antigen presenting cells.
    • T-lymphocytes
      • Matures in the Thymus.
      • cytotoxic T cells recognize antigen on infected cells, and signal for apoptosis.
      • helper T cells recognize antigen on antigen-presenting cells, and signal for activation of B cells, T cells, and macrophages.
    • B-lymphocytes, plasma cells
      • Matures in Bone marrow.
      • B cells form plasma cells and memory cells when exposed to antigen.
      • plasma cells = secrete antibody.
      • memory cells = stick around in case the same antigen attacks in the future.
  • Tissues
    • bone marrow
      • all blood cells arise from stem cells in the bone marrow.
      • B lymphocytes differentiate in the bone marrow.
    • spleen
      • Provides a site for WBCs to reside and proliferate.
      • Removes pathogens from blood.
      • Removes old RBCs and platelets.
    • thymus: T lymphocytes differentiate in the thymus.
    • lymph nodes
      • Provide a site for WBCs to reside and proliferate.
      • Removes pathogens from lymph.
      • Residing lymphocytes monitor lymph for foreign antigens, and initiate an immune response when exposed to foreign antigens.
  • Basic aspects of innate immunity and inflammatory response: Innate = first line of defense = kills anything that doesn't look right = not specific to a particular pathogen / antigen
    • Skin: natural flora, layer of keratin.
    • Mucus membranes: traps pathogen in mucus, and cilia moves it out.
    • Phagocytes: engulf pathogen.
    • Natural killer cells: destroy infected cells.
    • Antimicrobial proteins: tears (lyse bacteria), interferons (interfere with virus replication), complement (punches holes in cell/pathogen membrane).
    • Fever/inflammation: WBCs are more active at higher temperature, and inflammation recruits WBCs to site of infection by sending out chemical signals and making capillaries more permeable.
  • Adaptive immunity = highly specific for a particular pathogen / antigen.
    • antigen presenting cells present foreign antigen on their surface.
    • antigen is recognized by T and B cells.
    • cytotoxic T cells kill infected cells.
    • helper T cells activate macrophages, T and B cells.
    • B cells produce antibodies.
    • antibodies bind to antigens and bring about
      • neutralization: pathogen can't adhere to host cell
      • opsonization: makes it easier for phagocytosis
      • complement activation: kills infected cell by punching holes in cell membrane.
    • memory cells are made that are much more efficient (does not need T cell activation) in proliferating and making antibodies in case the same infection strikes in the future.
    • memory cells allow the body to mount a greater, and more sustained response against the same pathogen during secondary response.
      primary and secondary immune response
  • Concept of antigen and antibody
    • Antibody = lock, Antigen = key. Each antibody is specific to the binding of an antigen.
    • Antibody is like a Y, the tips of the fork bind antigen.
    • The tips of the fork are called hypervariable regions because they are unique to each antigen-specific antibody.
    • The antibody consists of 2 light chains and 2 heavy chains linked together by disulfide bonds.
  • Structure of antibody molecule
    antibody molecule
  • Mechanism of stimulation by antigen; antigen presentation
    • pathogen enters antigen-presenting-cell (APC)
    • pieces of the pathogen gets displayed at the surface of APCs.
    • T cell receptors recognize the presented antigen, and activates various immune responses.
  • scenario 1: extracellular pathogen
    1. macrophage engulfs pathogen.
    2. pieces of the pathogen becomes the antigen and gets presented at the macrophage's cell surface.
    3. helper T cells recognize the presented antigen, and activates macrophages to destroy pathogen. Helper T cells also activate B cells to produce antibodies against the pathogen.
  • scenario 2: intracellular pathogen
    1. pathogen invades host cell.
    2. pieces of the pathogen gets presented on the host cell surface.
    3. cytotoxic T cells recognize the presented antigen, and signals the infected cell to self-destruct.