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Tissues

  • Connective Tissue (CT) binds to and supports body parts
  • Muscle Tissue protects joints, produces movement and heat
  • Nervous Tissue responds to stimuli and transmits impulses from one body part to another
  • Epithelial Tissue covers body surfaces and lines body cavities
  • Skin is an organ
    • Epidermis of skin is made of stratified squamous epithelium
    • New cells are pushed outward, become keratinized, die and are rubbed off

Classification of Epithelium

  • Simple epithelium: Composed of a single cell layer
    • Found in the alveolar (air sacs) wall of the lung
    • Increases rate of diffusion by increasing surface area and reducing diffusion pathway
  • Stratified epithelium: Composed of multiple cell layers
    • Provide protection
  • Squamous: Cells have a flattened appearance, with a flattened nucleus
  • Cuboidal: Cells appear as a cube, the nucleus is spherical
  • Columnar: Cells are column shaped with an elongated nucleus
  • Cilia: Small projections that can move small substances
    • Lines the respiratory tract
    • Cleans impurities by moving them upwards, towards the throat

Blood

  • Is a connective tissue containing different cell types (erythrocytes, lymphocytes, monocytes, granulocytes)

Blood Plasma

  • Plasma is aq containing proteins, inorganic salts, amino acids, vitamins, hormones
  • Main plasma proteins are albumin, globulins, and fibrinogen
    • Albumin maintains osmotic pressure and acts as a transport protein for various substances
    • Globulins are mainly antibodies
    • Fibrinogen is involved in clotting process

Erythrocytes (red blood cells) are filled with O2 carrying haemoglobin

  • Contain the respiratory pigment haemoglobin which carries oxygen
  • Biconcave discs 7.5 µm in diameter
    • Biconcave shape provides large surface-to-volume ratio for O2 delivery
    • Also allows greater flexibility in thin capillaries
  • Maturation in bone marrow takes 24-48h
    • Loose mitochondria, nucleus during maturation for O2 carrying
    • Thus, No aerobic respiration possible → depends on anaerobic respiration
    • Proteins serve as acid-base buffers //anaerobic respiration produces lactic acid
  • Survive in circulation for ≈120 days
  • Old cells are removed by phagocytic cells of spleen and bone marrow
  • Decrease of red blood cells is called anaemia

Leukocytes (white blood cells)

  • Involved in cellular and humoral defence of organism
  • [MECHANISM] Leave circulatory system to enter tissues
    • Margination: Leukocytes flow in plasmatic zone (next to the tunica intima)
    • Adhesion: They randomly contact or "roll over" the endothelium
    • Emigration: Migration through the wall of venules and small veins
    • Diapedesis: Passive escape of red cells from vessels
  • Classified into granulocytes and agranulocytes
    • Based on the presence or absence of visible granules within the cellular cytoplasm
    • Granulocytes / presence of granules / neutrophils, eosinophils, and basophils
    • Agranulocytes / absence of granules / monocytes and lymphocytes

Lymphocytes (6-18µm)

  • Spherical nucleus and shape, very little cytoplasm
  • Memory cells have specific antigen receptors on the cell surface
  • Lymphocytes vary in life span. Some live few days, others many years
  • Only white blood cells that return to blood stream after migrating to tissues

Monocytes (12-20µm)

  • Oval, horseshoe or kidney shaped nucleus; more cytoplasm than lymphocytes
  • Nucleus does not stain as darkly as lymphocytes in blood smears
  • After leaving circulatory system, they differentiate into macrophages in connective tissues

Granulocytes

  • Lobed nucleus and granular cytoplasm
  • Different functions: some engulf bacteria; others are involved with allergies and inflammation

Blood clotting

  • If blood vessels are damaged a series (cascade) of enzyme-control reactions occurs to form a clot
    • Prevents further blood loss
    • Prevents invasion by pathogens
  • IMG 3-12-3
  • Clotting depends on clotting factors which are plasma enzymes
  • They are present as an inactive form in blood plasma
  • They are named with roman numerals e.g. Factor V
  • Haemophilia is an inherited disease. Patients make non functional Factor VIII
  • Serotonin causes smooth muscle of the arterioles to contract / narrows blood vessels, cutting off the blood flow to damaged area

Blood vessels

Arteries

  • Pulmonary artery
    • Transport deoxygenated blood from the right ventricle into lungs
  • Systemic arteries
    • Transport oxygenated blood from left ventricle to body tissues
    • About 10% of total blood volume is in systemic arterial system at any given time
    • Blood is pumped from the left ventricle into large elastic arteries
    • Elastic arteries become smaller muscular arteries
    • Muscular arteries branch into smaller arterioles (smallest arteries)
    • Arterioles regulate blood flow into tissue capillaries
  • Arterial wall consists of 3 layers:
    • Innermost layer, tunica intima, is simple squamous epithelium / surrounded by a connective tissue basement membrane with elastic fibres
    • Middle layer, tunica media, is smooth muscle and usually thickest layer / changes vessel diameter to regulate blood flow and blood pressure
    • Outermost layer, tunica adventitia, attaches vessel to surrounding tissue / connective tissue with varying amounts of elastic and collagenous fibers
  • Arteries have a relatively small lumen (compared to veins)
  • During exercise, supply of blood to muscle and skin increases; blood to digestive system decreases / middle layer muscles of smaller arterials and arterioles change their diameter to adjust blood supply

Veins

  • Pulmonary veins
    • Transport oxygenated blood from lungs to left atrium
  • Systemic veins
    • Carry deoxygenated blood towards the heart
    • After blood has passed through the capillaries, it runs into venules (smallest veins)
    • Afterwards, veins become progressively larger until they reach the heart (right atrium)
    • Medium and large veins have valves that help to keep blood flowing toward heart
    • This is important in arms and legs to prevent backflow of blood due to gravity
  • Walls of veins have same three layers as arteries
    • BUT less smooth muscle and connective tissue
    • Makes walls of veins thinner with less pressure → Larger lumen
    • Can hold more blood than arteries
  • Almost 70% of total blood volume is in veins at any given time

Capillaries

  • Smallest, most numerous blood vessels
    • Carry blood from arteries to veins
    • Blood flows from arterioles into the capillaries, then from them into venules
    • Size of lumen is roughly equal to diameter of erythrocytes
    • Thin wall is composed of endothelium (single layer of overlapping flat cells)
  • Function: exchange of materials between blood and tissue cells (e.g. O2, CO2, nutrients, wastes)
  • Capillary distribution varies with metabolic activity of body tissues
    • Skeletal muscle, liver, and kidney have extensive capillary networks
    • They are metabolically active and require an abundant supply of oxygen and nutrients
    • Connective tissue have less abundant supply of capillaries
    • Epidermis of skin and lens, and cornea of eye completely lack a capillary network
  • Flow of blood is controlled by structures called precapillary sphincters
    • Located between arterioles and capillaries
    • Muscle fibres allow them to contract
  • Hydrostatic pressure is created by the heart which pumps blood into arteries
  • At the arteriole end
    • Hydrostatic pressure > water potential
    • As plasma proteins lower water potential
    • H2O, small molecules, fluid are forced out through the permeable capillary wall
    • Plasma proteins are not forced out as they are too large
  • At the venule end
    • Water potential > hydrostatic pressure (due to lower volume)
    • Fluid tends to flow back into the blood with waste products produced by cells

Lungs and Respiration

Diffusion and gas exchange

  • All organisms exchange food, waste, gases, heat with their surroundings by diffusion
  • Rate of diffusion is given by Fick's law and depends on
    • Thickness of the membrane the molecules must diffuse across,
    • Surface area for gas exchange
    • Mass and solubility of molecule
    • Rate of diffusion is proportional to (surface area x conc. difference) / distance
  • Large organisms have a small surface area : volume ratio
    • Decreases the rate of diffusion
    • More difficult to exchange materials (e.g. waste) with surroundings
  • Organisms also need to exchange heat with their surroundings
    • Large animals lose less heat than small animals
    • Small mammals lose heat very readily → have a high metabolism to maintain body temp
    • Large mammals feed once every few days while small mammals must feed continuously
  • Plant cells respire all the time, chloroplasts causes photosynthesise / plants exchange gases
    • Main gas exchange surfaces in plants are spongy mesophyll cells in leaves
    • Leaves have large surface area / loosely-packed spongy cells further increase area

Structure of the lungs

  • Air is
    • filtered in nostrils with small hairs
    • moistened and warmed by nasal cavities
    • mucus traps foreign particles while cilia propels particles towards the throat
  • Air passes into the pharynx → larynx → trachea
    • The epiglottis is found within the larynx
    • Breathing: epiglottis projects upwards → larynx is open
    • Swallowing: larynx pulled up / epiglottis blocks larynx / prevents food from entering airway
  • Trachea
    • Contains C-shaped cartilage rings / prevents collapsing of tube
    • Trachea divides into 2 tubes with smaller diameter called bronchi
    • To prevent microorganisms, a bronchus is supported with ciliated epithelia
    • Right bronchus is bigger than the left one → common site for inhaled foreign objects
  • Bronchi further divide into bronchioles
    • Their diameter can be controlled by smooth muscles
    • Bronchial tubes form a system called alveoli (100µm in diameter)

Alveolar Gas Exchange

  • Greater partial pressure of O2 in alveolar air / more O2 dissolves in blood (Henry's Law)
  • Alveoli walls are composed of endothelium → gases diffuse through 2 thin cells
    • Alveoli is constantly moist
    • O2 can dissolve and diffuse through the cells into the blood
    • It is then taken up by haemoglobin
  • Alveoli contain phagocytes to kill bacteria that have not been trapped by mucus
  • O2 diffuses down its conc. gradient from air to blood; CO2 diffuses from blood to air
  • Ventilation: Flow of air in and out of alveoli

Ventilation

  • Tidal volume, VT, volume of air inhaled and exhaled in a normal single breath (≈0.5 L)
  • Functional residual capacity, FRC, volume remaining in lungs after exhalation of tidal volume (≈2.5 L)
  • Expiratory reserve volume, ER, volume of a maximal exhalation (≈1.5 L)
  • Residual volume, RV, volume remaining in lung after maximal exhalation (≈1L)
  • Inspiratory reserve volume, IR, additional volume that can be inhaled after inhalation of tidal volume
  • Vital capacity, VC, maximum volume of exhalation after lungs are maximally filled
    • best clinical indicator of breathing
  • Minute ventilation is the overall flow of air into lungs (analogous to cardiac output)
    • Minute Ventilation = Tidal Volume x Respiratory Rate
    • (0.5 litre/breath * 10 breaths/min = 5 litres per minute)
  • "Dead space" - not all O2 available in air is available to alveoli
    • Fresh air mixes with exhaled air during inspiration
    • Alveolar ventilation takes dead space into account
    • Alveolar ventilation = (Tidal Volume - Dead Space) x Respiratory Rate
    • (350 ml x 10 breaths per minute = 3500 ml or 3.5 litres)

Measurements of Ventilation

  • A spirometer is used to measure expired breath
  • Restrictive disorders, such as pulmonary fibrosis, reduce compliance and vital capacity
  • Four measures are called respiratory volumes
    • Tidal volume
    • Inspiratory reserve volume
    • Expiratory reserve volume
    • Residual volume
  • Others, called respiratory capacities, are calculated by adding 2 or more of the respiratory volumes

Coordination of breathing

  • Breathing centre in the medulla of the brain consists of
    • Inspiratory centre (dorsal respiratory group, DRG)
    • Expiratory centre (ventral respiratory group, VRG)
  • The purpose of respiration is to maintain pH, oxygen, and carbon dioxide levels in the blood within homeostatic limits. Brainstem respiratory centers monitor these conditions in the blood by various means

Inspiration (inhalation)

  • Inspiratory centre sends impulses to intercostal muscles and diaphragm via intercostal and phrenic nerves
  • Muscles contract, ribs raise, diaphragm moves down
  • Volume of alveoli increases / pressure decreases below atmospheric / air flows in
  • Inhalation requires muscular effort, thus burning calories and ATP

Normal expiration

  • Stretch receptors are stimulated, send impulses to expiratory centre via vagus nerve
  • Diaphragm (moves upwards) and external intercostal muscles relax
  • Volume of alveoli decreases / pressure increases above atmospheric / air flows out

Forced expiration (exercise)

  • Abdominal muscles contract, pushing diaphragm upwards
  • Internal intercostal muscles contract, pulling ribs downward
  • Gives larger and faster expiration

Control of breathing - Respiratory control

Breathing rate is monitored by

  • CO2 conc. - increases when more CO2 is produced as a waste product
  • O2 conc. - decreases as it is used in respiration to produce ATP
  • More sensitive to changes in CO2

Sensory nerves send information to the medulla via cranial nerves

  • Chemoreceptors, aortic and carotid bodies, are located in the aorta and carotid arteries
  • Primarily monitor pH and CO2 level (homeostasis control)
  • Aortic bodies send signals via vagus nerves about breathing reflexes, blood pressure and cardiac activity
  • Carotid bodies send signals about sensations of breathing and blood pressure

Motor nerves send commands to muscles or organs

  • Phrenic nerve innervates diaphragm
    • Originate from cervical plexus, high in neck
    • Stimulate breathing by carrying messages from medulla
  • Intercostal nerves enter intercostal muscles and run along the rib cage

Heart

  • Heart pumps blood through arteries that branch into smaller arterioles, capillaries, then from a network of venules to veins and back to the heart

Cardiac Anatomy

  • The heart consists of 4 chambers: right atrium, right ventricle, left atrium, left ventricle
  • Right atrium receives blood from superior and inferior vena cava
  • Blood flows from right atrium, across tricuspid valve, into right ventricle
  • Muscle of right ventricle is not as thick as left ventricle
  • Blood enters pulmonary artery from right ventricle. Backflow prevented by semilunar pulmonic valve
  • Blood returns to heart from lungs via 4 pulmonary veins that enter left atrium
  • Blood flows from left atrium, across mitral valve, into left ventricle
  • Left ventricle has a thick muscular wall / generate high pressures during contraction
  • Blood from left ventricle is ejected, across aortic valve, into aorta
  • Tricuspid and mitral valves (atrioventricular AV valves)
    • Have fibrous strands (cordae tendinae) that attach to papillary muscles
    • The papillary muscles contract during ventricular contraction
    • Generate tension on valve via cordae tendinae to prevent AV valves from bulging back into atria
  • Semilunar valves (pulmonic and aortic) do not have these attachments

The Cardiac Cycle

  • Atria receive blood from veins and store it prior to each heart beat
  • Right atrium receives blood from main body veins called "vena cava"
    • Superior vena cava SVC carries blood from head, upper chest and arms
    • Inferior vena cava IVC carries blood from lower chest, abdomen and legs
  • Left atrium receives blood from lungs via 4 separate pulmonary veins
  • Systole refers to a period of contraction by heart muscle
  • Diastole refers to a period of relaxation by heart muscle

Atrial systole

  • Both atria contract and push stored blood across AV valves into ventricles, to help fill them
  • Atrioventricular (AV) valves include
    • Mitral valve located between left atrium and left ventricle
    • and tricuspid valve which separates right atrium from right ventricle
  • Reduces the volume of atria and increases pressure

Ventricular systole

  • After atria contracts, ventricles begin to contract
  • Pressure in ventricles increases, blood is forced against AV valves
  • Valves close to prevent backflow → first heart sound
  • Volume is reduced
  • Blood is ejected into arteries through aortic and pulmonary valves

Ventricular diastole

  • End of cardiac cycle, all chambers relax
  • Aortic and pulmonary valves close (second heart sound) / prevents backflow into heart
  • Atria begin to fill up again to start next cycle
  • Volume increases and pressure decreases

Electrophysiology

  • Sinus node is located at the top right atrium
    • Also known as the "natural pacemaker" controlling heart rate
    • Increases with physical activity and decreases when relaxing
    • Electrical signal rapidly spreads from the Sinus node across the right atrium and left atrium
  • Only one area where atria and ventricles are electrically connected
    • Atrioventricular node or AV node deep in center of heart
    • All electrical signals from atrium must pass through AV node in order to get to ventricles
    • AV node is connected to the Bundle of His
    • Branches into a right bundle (to right ventricle) and left bundle (to left ventricle)
  • Fibers that branch out to distant ventricular tissues are called Purkinje Fibers

Blood pressure

  • Baroreceptors near aorta and carotid arteries monitor blood pressure
  • Abnormal blood pressure → signal send to medulla
  • Cardiac center changes heart rate → cardiac output
  • Vasomotor center changes diameter of blood vessels
  • Shock: blood pressure too low
    • Insufficient nutrients for cells with a high metabolism (heart, brain)
    • Caused by excessive bleeding or extensive vasodilation
    • Treated with vasoconstrictors such as epinephrine (adrenaline), atropine
    • [NOTE] International name for adrenaline is now epinephrine

Regulation of the Cardiac Cycle

  • Heart has unique ability to beat (contract) on its own
  • Assisted by nerves and hormones in blood but functions without them
  • Impulse leaves SA node and passes through both atria → causing them to contract
  • From AV node impulse passes down to the Bundle of His
  • Bundle of His branches and spreads through both ventricles via Purkinje fibers → ventricles contact

Cardiac output as a function of stroke volume and heart rate

  • The volume of blood pumped by one ventricle during one beat is called the stroke volume
  • Cardiac Output = Stroke Volume x Heart Rate (number of ventricular contractions/min)
  • ↑Force of contraction → ↑Stroke volume → ↑Cardiac output

Regulation of heart rate → Cardiac output is influenced by several factors

Autonomic Nervous System

  • Heart is innervated by the autonomic nervous system (ANS)
    • The autonomic nervous system has 2 divisions
    • These division are called parasympathetic and sympathetic
    • Parasympathetic fibres decrease heart rate via the vagus nerve
    • Sympathetic fibres increase heart rate
  • Cardiac Inhibitory Centre
    • Found in the medulla oblongata of the brain stem
    • Sends signals via the vagus nerve, which is parasympathetic, to the heart
    • Signal reaches SA and AV nodes to trigger a release of neurotransmitter acetylcholine
    • This slows down the heart rate
  • Cardiac Accelerating Centre
    • Found in the medulla and the upper thoracic spinal cord
    • Sympathetic fibres run towards the myocardium
    • There they also innervate the SA and AV nodes, but also cardiac cells
    • When stimulated, the sympathetic fibres cause a release of norepinephrine
    • [NOTE] The international name for noradrenaline is now norepinephrine
    • Norepinephrine increases heart rate and strength of ventricular and atrial contraction
  • Cardiac centres balance stimulatory and inhibitory effects of the ANS

Hormonal influence

  • Stress releases epinephrine and norepinephrine from the adrenal medulla into the circulation.
  • Both hormones increase the heart rate.

Electrolyte Balance

  • Excess K+ in the extracellular environment reduces heart rate and strength of contraction
  • Only a fraction of a KCl infusion is required to kill a patient
  • Spastic contraction of the heart results from excess Ca2+
  • Heart can be defibrillated by applying an electrical current to the chest wall
  • Stimulates depolarisation of all cardiac muscle fibres simultaneously
  • As a result, all contractions cease
  • If the SA node then begins to function, normal cardiac rhythm may be re-established

Pressure Changes During the Cardiac Cycle

  • Ventricles begin to contract, intraventricular pressure rises causing AV valves to close. Ventricles are neither being filled with blood (AV valves are closed) nor ejecting blood (intraventricular pressure has not risen sufficiently to open semilunar valves). This is the phase of isovolumetric contraction.
  • Pressure in the left ventricle becomes greater than pressure in the aorta, phase of ejection begins as semilunar valves open. Pressure in left ventricle and aorta rises to about 120 mm Hg when ejection begins and ventricular volume decreases
  • Pressure in left ventricle falls below pressure in the aorta, back pressure causes semilunar valves to shut. Pressure in aorta falls to 80 mm Hg
  • During isovolumetric relaxation AV and semilunar valves are closed. This phase lasts until pressure in ventricles falls below pressure in atria
  • When pressure in ventricles falls below pressure in atria, ventricles are filled
  • Atrial systole empties final amount of blood into ventricles immediately prior to next phase of isovolumetric contraction of ventricles