Unit 3 Lecture Objectives

Describe the functions of different layers of connective tissue that surround and are associated with the skeletal muscles

• Epimysium

  • Surrounds entire muscle

• Perimysium

  • Surrounds fascicles (bundles of muscle fibers)

  • Contains blood vessels and nerves

• Endomysium

  • Surrounds individual muscle cell

  • Contains capillaries

Describe the unique features of the skeletal muscle compared to a typical cell

• multinucleated

• Develop through embryonic cells called myoblasts

• Contains myofibrils

• Smooth ER is sarcoplasmic reticulum

• T-tubules

Describe the structural and functional unit of the muscle

• sarcomere

• Between Z lines

• Has thick filaments (myosin) and thin filaments (actin)

• Dark band is called the A band

• Light banned is the I band

Explain how the proteins in the thick and thin filaments regulate muscle contraction and relaxation

• thin (actin)

  • Tropomyosin (Tm)

  • Troponin (Tn)

  • TnI

    • C-terminus

      • Helps anchor the troponin complex to actin and tropomyosin, holding filament in a blocked state and preventing muscle contraction

    • Switch region

      • Binds the hydrophobic pocket in TnC

  • TnC

    • N-terminus

      • contains calcium-binding sites; key calcium sensor

  • TnT

    • N-terminus

      • Helps regulate function of troponin complex

Compare and contract the three functional states of the thin filaments with the three states in which the myosin heads can exist

• thin

  • Blocked state

    • Unbound/detached myosin crossbridge

  • Closed state

    • weakly bound XB

  • Open state

    • Strongly bound XB

Distinguish between the calcium-mediated activation of the thin filaments and crossbridge-mediated activation of the thin filament

• calcium-mediated activation

  • Electrical signal (like an action potential) causes release of calcium ions

  • Calcium ions bind to troponin, causes tropomyosin to move

  • Movement of tropomyosin exposes myosin-binding site

  • Blocked state to closed state

• Crossbridge-mediated activation

  • Closed state to open state

  • Crossbridge forms, holds tropomyosin in “on” position

  • Initiates power stroke, where myosin head pulls actin filament and muscle contraction occurs

Describe the various steps involved in excitation-contraction coupling and relaxation of the skeletal muscles

• excitation-contraction coupling

  • Action potential arrives, ACh released into synaptic cleft. Binds to receptors on sarcolemma

  • action potential travels along T-tubules

  • Action potential activates dihydropyridine (DHP) receptors

  • Triggers opening of ryanodine receptors (RyRs), causes rapid release of Ca2+

  • Ca2+ binds to troponin, causing movement of tropomyosin and exposure of myosin-binding sites

  • Crossbridges form, hydrolysis of ATP fuels power stroke, shortening the sarcomere and causing muscle contraction

• Relaxation

  • Nerve stimulation stops, RyRs close

  • Ca2+ pumped back into SE by SR Ca2+ pumps (SERCA)

  • Troponin returns to original shape, tropomyosin moves back to block myosin-binding sites

  • Cross-bridges detach, muscle relaxes

Why does rigor mortis occur

SERCA can’t function ‘

Describe some of the structural and functional differences between skeletal vs cardiac muscles, skeletal vs smooth muscles, and between cardiac vs smooth muscles

• Smooth

  • Involuntary control

  • Spindle-shaped

  • Single, central nucleus

  • No tendons, T-tubules, myofibrils, or sarcomeres

  • NOT striated

    • Scattered thick filaments with many myosin heads

    • Thin filaments attached to dense bodies

  • Function

    • No neuromuscular junction. Instead, neurotransmitters are released into synaptic cleft from varicosities in axons that course through muscle

    • Ca2+ ions trigger contraction when released from SR and enter through voltage-gated calcium channels

    • Calcium binds to calmodulin (not troponin like in skeletal muscle), activates myosin light-chain kinase (MLCK)

  • Control of contractions

    • Multi-unit smooth muscle cells are innervated by a motor neuron

    • Visceral smooth muscle cells are interconnected

      • Mechanical stretch controls activity

• Cardiac muscle

  • Ordered myofibrils like smooth muscle

  • Structural differences

    • smaller

    • Branched

    • Intercalated discs

      • Desmosomes

      • Gap-junctions

  • Conduction system and gap junctions rapidly propagate action potentials across entire myocardium, enabling heart to contract and relax as a single unit

Describe the various fuels used by muscles depending on the intensity and duration of physical activities

• aerobic activity - carbs, fats, protein if on short supply of other fuels

• Anaerobic - carbs

• Rest - carbs and fat

Predict the type of activity and the substrate used to make ATP based on the RQ values (0.7, 0.8, 1)

• 0.7

  • Fats

• RQ of 0.8

  • Either rest or protein

• 1

  • Carbs

Compare and contrast between the physiological relevance of fast, slow, and intermediate muscle fibers

• Fast

  • Anaerobic

  • Easily fatigued

  • Large diameter

• Slow

  • Darker color due to myoglobin (stores oxygen in muscles)

  • Fatigue resistant

  • Aerobic

  • Smaller diameter

• Intermediate

3 mechanisms proposed to explain DOMS (also what’s DOMS)

DOMS - delayed-onset muscle soreness

1. Tears in the muscle tissue permits the loss of enzymes; myoglobin may stimulate nearby pain receptors

2. Muscle spasms

3. Connective tissue and tendon tears

Explain how muscle contractions are classified based on muscle length and the load

• isotonic contraction

  • Concentric - muscle shortens

  • Eccentric - muscle lengthens

• Isometric contraction - length doesn’t change

• Speed of shortening is inversely proportional to the load

Describe the three ways in which the force generated by skeletal muscle can be regulated/fine-tuned

1. Recruitment of motor units

   1. More force = more motor units recruited

2. Twitch summation

   1. More action potentials in quick succession is more force (does eventually plateau - called tetanic contraction)

3. Force-length relationship

Describe action potentials in cardiac muscles

1. Stimulus

2. Rapid depolarization due to opening of Na+ channels and Na+ influx

3. Plateau due to slow Ca2+ influx balanced by K+ efflux

   1. This is the refractory period

4. Repolarization due to rapid K+ efflux and closure of Ca2+ channels

Compare and contrast between the physiological relevance of force-length relationship in cardiac and skeletal muscles

• cardiac muscle on ascending limb (change in sarcomere length causes greater change in force percentage)

  • Allows it to adjust force output to volume of blood in ventricle (Frank-Starling law)

• Skeletal muscle on plateau region

Describe the blood flow through the various chambers of the heart, the cardiac valves, and cardiac blood vessels to the systemic and pulmonary circuit.

• Right atrium

  • Coronary sinus receives deoxygenated blood from superior and inferior vena cava, empties into right atrium

• Blood goes through tricuspid valve to right ventricle

• Right ventricle

  • Discharges deoxygenated blood

• Blood goes through pulmonary trunk to lungs

• ^ pulmonary circuit

• \/ Systemic circuit

• Left atrium

  • Receives oxygenated blood from pulmonary veins (one exception - veins usually carry deoxygenated blood)

• Blood goes through bicuspid valve to left ventricle

• Left ventricle

  • Discharges oxygenated blood

• Oxygenated blood leaves through aorta to rest of the body

What happens when ventricles relax vs contract

• relax

  • Right and left atrioventricular (AV) valves open but aortic and pulmonary valves close

• Contract

  • Right and left AV valves close, aortic and pulmonary valves open

• Describe the various components and the functioning of the cardiac conduction system

• autorhythmic cells

  • Found in the nodes and in the internodal pathways

  • Produce action potential spontaneously

  • Smaller

  • Few contractile fibers

  • No organized sarcomeres

• Hyperpolarization and Cyclic Nucleotide (HCN) channels

  • Generate “funny” pacemaker current (I sub f)

  • Activated by hyperpolarization and cAMP binding

• Unstable resting potential; slow inflow of Na+ without compensating outflow of K+

• Process

  • I sub f/HCN channels spontaneously depolarize cell to threshold

  • Voltage-gated Ca2+ channels open, Ca2+ flows into the cell

  • At peak, K+ channels open, K+ flows out to hyperpolarize the cell

• Nodes

  • Sinoatrial (SA) node

    • Fired 75-100 action potentials/min

  • Atrioventricular (AV) node

    • 50 impulses/min - delayed about 100 ms to allow for full contraction of atria

  • Right and left bundle branch

    • Fires 20-40 times/min

Explain how the various layers of the heart aid in its function

• pericardium - membrane enclosing the heart, consisting of an outer fibrous layer and an inner double layer of serous membrane

  • Endocardium

    • Endothelium

    • Areolar tissue

  • Myocardium

    • Cardiac muscle cells

    • Connective tissues

  • Pericardial cavity

  • Visceral layer of serous pericardium

    • Mesothelium

    • Areolar tissue

  • parietal layer of serous pericardium

    • Dense fibrous layer

    • Areolar tissue

    • Mesothelium

Compare and contrast between the physiological relevance of autorhythmic and contractile cells in the heart

• autorhythmic

  • Produce action potential spontaneously

  • Smaller

  • Few contractile fibers

  • No organized sarcomeres

  • HCN channels depolarize to threshold, then rapid depolarization occurs bc of voltage gated Ca2+ channels

• Contractile

  • Na+ channels depolarize to threshold

  • Plateau phase due to Ca2+ influx balanced by K+ efflux

Explain how the various parts of the electrocardiogram (ECG/EKG) relate to the cardiac cycle

• SA node fires

• P wave

  • Atria depolarize/atrial contraction (atrial systole begins)

• PR segment

  • Conduction of signal through AV node

• QRS complex

  • Depolarization of ventricles

  • Q - isovolumetric contraction

  • R - ventricular contraction/first phase of ventricular systole

  • S - ventricular ejection/second phase of ventricular systole

• ST segment

  • Cardiac muscle AP plateau

• T wave

  • Repolarization of ventricles

  • Isovolumetric relaxation/early ventricular diastole

• Right after T wave

  • Ventricular filling/late ventricular diastole

• R to R is one heartbeat

Explain with examples how the electrocardiogram readings can indicate various pathologies of the heart

• Bradychardia - slow heart rhythm

• Tachycardia - fast heart rhythm

• Heart block - interruption in the normal conduction pathway

  • First-degree AV block

    • Delay in conduction between SA and AV nodes

  • Second-degree

    • Only some impulses from SA node reach AV node (only P wave present occasionally)

  • Third-degree

    • No correlation between atrial and ventricular activity (P waves and QRS complex)

• Fibrillation- rapid, irregular out-of-phase contractions; useless for pumping blood

Difference between a heart attack and cardiac arrest

• heart attack

  • Clogged artery disrupts blood flow to your heart

  • Common cause of cardiac arrest

• Cardiac arrest

  • Rapid, abnormal impulses override heart’s natural rhythm

Describe how the blood pressure and blood volume changes in the ventricles and atria during the cardiac cycle

• ventricle diastole/atrial systole (P wave)

  • Atrial pressure slightly greater than ventricular

  • Ventricular volume rising until end-diastolic volume

• After QRS complex

  • Aortic valve opens, left AV valve closes

  • Ventricular pressure much greater than atrial pressure but slightly less than aortic

  • Ventricular blood volume drops significantly, then stays the same for a period bc pressure lower than aortic pressure but higher than atrial

• After T wave

  • Aortic valve closes, then left AV valve opens

  • Ventricular pressure drops. After left AV valve opens, pressure is less than atrial

  • Blood volume steadily rises

Explain how the cardiac cycle is represented using a pressure-volume loop

• preload - stretch of myocardium or end-diastolic volume of the ventricles

• After load - force or load against which the heart has to contract to eject the blood

• Contractility - relative ability of the heart to eject a stroke volume (SV) at a given prevailing afterload (arterial pressure) and preload (end-diastolic volume; EDV)

• Ejection fraction - percentage of EDV represented by stroke volume

  • Stroke volume (SV) = EDV - ESV

• Slope constructed using the end systolic volume in the PV loop indicates contractility/inotropy

Predict how changes in heart rate and stroke volume can affect the cardiac output

CO = HR x SV

CO = HR x (EDV - ESV)

Explain how the autonomic nervous system regulates the increase and decrease of heart rate by impacting the action potentials of autorhythmic cells

• To decrease HR, parasympathetic neurons release ACh which opens K+ channels. K+ leaves the cell, cell hyperpolarizes, thus slowing the rate of depolarization (slowing the heart rate)

• To increase HR, sympathetic neurons release norepinephrine, which opens HCN channels, causes Na+ influx → rapid repolarization, which accelerates reaching threshold, thus increasing HR

Explain the relationship between pressure, flow, and resistance

• Resistance has a direct relationship with blood viscosity

• Resistance has a direct relationship with total blood vessel length

• Resistance has an inverse relationship with vessel radius and cross-sectional area

• Site of greatest resistance is arterioles

Describe the role of smooth muscles in blood vessels

• regulate blood flow and maintain blood pressure by contracting and relaxing to change the vessel’s diameter

Explain how the progressive branching of blood vessels between the aorta and capillary beds influences the cross-sectional area of the vessels, rate of blood flow, resistance to blood flow, and the blood pressure in the vessels

Cross-sectional area least at elastic arteries and venae cavae

Vessel diameter greatest at elastic arteries and venae cavae, least at capillaries

Describe the various components of blood and their proportions

• plasma (55%)

  • Water (92%)

  • Plasma proteins (7%)

  • Other solutes (1%)

• Formed elements (45%)

  • Buffy coat

    • white blood cells and platelets (<0.1%)

  • Red blood cells (RBC)/erythrocytes (99.9%)

Describe the structural features and functions of red blood cells (RBCs), white blood cells (WBCs), and platelets

• red blood cells (RBCs)

  • Biconcave discs

  • Large surface-area-to-volume ratio to quickly absorb and release oxygen

  • Small, highly specialized disks

    • Lack organelles

    • Short lifespan bc can’t synthesize proteins or repair damage

  • Form stacks called rouleaux that allow for smooth blood flow

• White blood cells (WBCs)

  • Also called leukocytes

  • Have nuclei and other organelles

  • Lack hemoglobin

  • Most are in connective tissue proper and organs of lymphatic system

  • Small fraction circulates in the blood

  • Functions

    • Defend against pathogens

    • Attracted to specific chemical stimuli (positive chemotaxis)

    • Some phagocytic

    • Remove toxins and wastes

    • Attack abnormal or damaged cells

Different kinds of WBCs

• Neutrophils

  • 50-70% circulating WBCs

  • Multilobed nucleus

  • Pale cytoplasmic granules containing lysosomal enzymes and bactericidal compounds

  • Mobile, active, phagocytic

• Eosinophils

  • 2-4% circulating WBCs

  • Bi-lobed nucleus

  • Involved in allergic reactions and parasitic infections

• Basophils

  • Less than 1% circulating WBCs

  • Enhance local inflammation by releasing

    • Histamine - dilates blood vessels

    • Heparin - prevents blood clotting

• Monocytes

  • Spherical and large cells

  • 2-8% circulating WBCs

  • Aggressive phagocytes - enter peripheral tissues to become macrophages

• Lymphocytes

  • Thin cytoplasm around nucleus

  • 20-40% circulating WBCs

  • Continuously migrate in and out of blood stream (found in lymphatic organs and connective tissues)

  • Part of body’s specific defense system

    • B cells complete development in bone marrow

    • T cells develop and mature in the thymus

Describe the steps involved in heme recycling, breakdown, and synthesis of red blood cells

• synthesis

  • Macrophage secretes IL-3, which influences differentiation of a hematopoietic stem cell into a proerythrocyte

  • Pericytes (cells on blood vessels) release erythropoietin (EPO)

  • EPO binds to receptor on proerythrocyte

  • Proerythrocyte becomes a normoblast

  • Normoblast loses nucleus and organelles, becomes a reticulocyte

  • In bone marrow capillaries, reticulocyte matured into an erythrocyte (RBC)

• breakdown

  • Red pulp of spleen has macrophages that inspect the glycoproteins on erythrocytes for oxidation

  • If oxidized, death by phagocytosis

• Recycling

  • Old and damaged RBCs broken down into amino acids and heme

  • Heme converted into biliverdin then bilirubin

  • Bilirubin binds to albumin in bloodstream, taken to liver, excreted in bile

  • Hemoglobin that’s not phagocytized after hemolysis (rupture of RBCs in bloodstream) breaks down. Alpha and beta chains eliminated in urine

Predict how exogenous administration erythropoietin (EPO) can impact athletic performance

• increases VO2 max

• Increases time to exhaustion

Describe the structure and functions of hemoglobin

• Hemoglobin

  • Protein that transports O2 and CO2

  • Heme - iron-containing pigment in each hemoglobin

  • O2 binds Fe

  • CO2 binds alpha and beta chains

Distinguish between the regulation of red blood cell and white blood cell production

• RBC production largely regulated by hormone erythropoietin (EPO)

• WBC production regulated by colony-stimulating factors (CSFs)

  • Multi-CSF

    • Granulocytes, monocytes, platelets, RBCs

  • GM-CSF

    • granulocytes and monocytes

  • M-CSF

    • Monocytes

  • G-CSF

    • Granulocytes

Describe the major functions of blood

• transports dissolved gases, nutrients, hormones, and metabolic wastes

• Regulated pH and ion composition of interstitial fluids

• Restricts fluid losses at injury sites

• Stabilizes body temp by redistributing heat generated by muscles

• Defends against toxins and pathogens

Describe the functions of cytokines, CDs, PAMPs, and DAMPs with examples

• cytokines

  • Secreted proteins that function as signaling molecules in an autocrine, paracrine, or endocrine fashion

  • Growth factors, interleukins, chemokines (induce chemotaxis)

  • Can cause cell motility (chemotaxis), differentiation, cell division, altered gene expression, etc.

• CDs

  • Cluster of differentiation molecules

  • Surface molecules/markers expressed on blood cells which are used for cell-cell signaling and identifying cells

  • CD4 and CD8

• PAMPs

  • Pathogen associated molecular patterns

  • Signal presence of pathogens to immune system

• DAMPs

  • Damage associated with molecular patterns

  • Damage signaled by unusual molecules in the extracellular spaces

Describe the function of primary and secondary lymphoid tissues with a few examples

• primary - sites where lymphocytes are formed and mature in the

  • Red bone marrow

  • Thymus

    • Primary lymphoid organ that atrophies after puberty

    • Regulates T cell lymphocyte development and maturation

      • T cells divide in the cortex, maturing migrate into medulla, matured leave by medullary blood vessels

    • Selection is done at thymi’s epithelial cells for:

      • Efficacy - ability to recognize proteins (positive selection)

      • Specificity - should not recognize self proteins (negative selection)

• Secondary - where lymphocytes are activated

  • Tonsils

  • Mucosa associated lymphatic tissue (MALT)

  • Lymph nodes

    • Cortex contains follicles (collections of lymphocytes)

      • Naive B cells

      • Germinal centers - activated B cells are generating daughter cells (plasma cells, which release antibodies)

    • Medulla contains macrophages

    • Paracortex contains dendritic cells

  • Spleen

    • Red pulp - contains many red blood cells

    • White pulp - resembles lymph nodes

    • Functions

      • Filter blood to remove abnormal blood cells and other blood components by phagocytosis

      • Storage of iron recycled from RBCs

      • Initiate immune responses to antigens in blood by macrophages, B cells, T cells

Compare and contrast between innate and adaptive immunity by listing the various types of cells responsible for them

• innate

  • Neutrophil

  • Eosinophil

  • Mast cell

• Adaptive

  • T lymphocyte

  • Memory B cells

  • B lymphocyte

  • Plasma cell

What cells are most directly responsible for humoral branch of immunity

Plasma cells

Describe the various steps involved in innate immune response to a bacterial vs viral infections

• bacterial

  • Bacteria damages dermis

  • PAMPs and DAMPs presented, activate mast cells

  • Mast cells degranutes to release histamines

  • Damaged cells secrete cytokines and chemokines

    • Cytokines dilate capillaries, heparin is anticoagulant

    • chemokines induce chemotaxis of neutrophils to damaged tissue

  • Chemotaxis of neutrophils triggers expression of selectin receptors on endothelial cells

  • Neutrophils bind to selectin receptors to enter damaged tissue via diapedesis

  • Neutrophils phagocytose bacterial and damaged cells until it explodes - contains free radicals, hydrogen peroxide, killing both healthy cells and bacteria

  • Chemokines recruit monocytes from bone marrow

• Viral

  • Cell becomes infected with H1N1

  • Viral fragment displayed on MHC I, triggering death by cytotoxic/killer T cells

  • Interferons released, bind with receptors on nearby cells, trigger decrease in endocytosis, exocytosis, transcription, translation (triggers closing up) until viral infection no longer a threat

Steps of adaptive immune response for bacterial vs viral infections

• bacterial

  • Macrophage presents antigen on MHC II

  • CD4 of naive T cell binds MHC

  • Antigen recognition - T cell receptor interacts with antigen

  • Co-stimulation - B7 from macrophage interacts with CD28 from T cell,

  • Proliferation/colonial expansion - IL2 released by T cell engages in autocrine signaling, becomes activated helper T cell that can recognize the antigen. Many copies form

  • B cell activation

    • Naive B cell presents antigen on MHC II

    • CD4 of naive T cell binds MHC

    • Antigen recognition

    • Co-stimulation - CD40 from B cell interacts with CD40L from T cell

    • Paracrine stimulation - T cell releases IL4, binds on B cell. Naive B cell becomes plasma B cell that produce antibodies that bind to pathogens and target them for phagocytosis

• Viral

  • Macrophage presents antigen on MHC I

  • CD8 of naive T cell binds MHC I

  • Antigen recognition

  • Co-stimulation - B7 from macrophage interacts with CD28 from T cell

  • Proliferation/clinal expansion - IL2 released, autocrine signaling, becomes activated killer T cell that will kill cells that are infected

Explain the purpose of an interferon response to the viral infection of a cell

Alerts cells in the nearby vicinity to close up until virus is no longer a threat

List the four cardinal signs of inflammation and explain the factors that cause them

• pain - nociceptors

• Redness - histamine

• Swelling - histamine

• Heat - histamine

Explain how the innate inflammatory response leads to an adaptive immune response

Immune recruits monocytes, which become macrophages

Describe the various steps involved in activation of a T cell vs a B cell

• both CD4, MHC II

• B7 of macrophage is like CD40 on B cell

• CD28 for macrophage from T cell is CD40L for B cell

• T cell releases IL2 for autocrine signaling for activating T cell, releases IL4 for activating B cell

Explain how antibodies perform their function based on their structure

• variable segments of light and heavy chains form antigen-binding sites

• Heavy chain is site of binding to macrophages

Describe where T-cells mature and how they are activated

Thymus

Compare and contrast how CD4 and CD8 cells are related to MHCI and MHCII receptors, respectively

CD4 and MCHII interact to activate helper T cells

CD8 and MCHI interact to activate killer T cells