Biology 212
Anatomy & Physiology II

Lecture Supplement

Tony Serino, Ph.D.

Associate Professor of Biology

MisericordiaUniversity

7th edition

©2015 Tony Serino, Ph.D.

Muscle

Sliding Filament Theory

Biomechanics of Force Production

Respiration

Breathing:

Acid-Base Balance

Circulatory System

Heart:

Blood:

Blood Vessels:

Lymphatic Circulation

Immunity

Digestive System

Fuel Homeostasis (Energy Metabolism)

Excretory System

Kidneys:

Endocrine function of the Kidneys

Acid Balance

Heredity

Muscle

Function: generate force and movement thus manipulating the internal or external environment

Attributes: contraction, excitability, extensibility and elasticity

Types: skeletalmoves the bones; cardiacheart muscle; smoothassociated with the internal environment; hollow organs and tubes

-Voluntary vs. involuntary; autorythmicity

Skeletal Muscle Cells

-long, cylindrical (non-branching), striated, multinucleated cells; muscle cell = muscle fiber

appear striated; due to arrangement of contractile proteins (actin and myosin); arranged in bundles known as myofibrils

-10-100 um in diameter; up to 35 cm in length

-voluntary, no spontaneous contractility
-Know Histology of muscle fiber

-terms: sarcosomes, sarcolemma, sarcoplasm, sarcoplasmic reticulum (SR), triads, motor unit and T-tubules
-innervated by motor neurons with acetylcholine (ACh) as the neurotransmitter

-nuclei displaced to side of cell due to arrangement ofmyofibrils (contractile proteins)

develop from fusion of myoblasts; satellite cells remain as reserve;

-each cell is wrapped in a CT sheath (endomysium) and aggregates of cells are grouped into bundles (fascicles) surrounded by another CT sheath (perimysium); the whole muscle is bound by CT sheath (epimysium) which is continuous with the tendon. This arrangement allows the efficient transmission of force across the tendon; and adds the elasticity of the tendon and CT sheaths to the muscle (known as series elastic component)

-all whole muscles are antagonistically arranged (that is; each group pair has the opposite action; for example: flexor and extensor). It is combination of this arrangement and the series elastic component which allows a muscle to return to its original length, without these a muscle cell would remain shortened after contraction.

Myofibril Arrangement:

Sarcomerefunctional unit of skeletal muscle

Know and understand arrangement of sarcomere (i.e. Aband, Iband, Zline, Mline, and Hzone)

Thick filaments consist of overlapping myosin molecules with their crossbridges projecting outward; each crossbridge has an actin and an ATPase binding site

Thin filaments consist of three proteins:

1. actin a helical chain of globular protein (drill bit shape)

2. Tropomyosin protein occupying actin's trench and blocks actin's binding site for myosin

3. Troponin globular protein; bound to actin and tropomyosin which can be allosterically modified by Ca++ to roll tropomyosin out of the trench

Sliding Filament Theory

contractionthe generation of tension and/or movement by sliding the thin filaments over the thick thus shrinking the sarcomere; tension is generated by binding myosin to actin. Myosin will bind to actin if it is first energized (which increases its affinity for actin) by ATP

MyosinActin interaction (crossbridge cycling):

Step 1: Attachment: crossbridge attaches to actin; begins tension development (A = actin, M = myosin, M* = energized myosin)

A + M*-ADP-Pi  A-M-ADP-Pi

Step 2: Power Stroke: the energy stored in myosin is used to swivel the crossbridge and ADP.Pi is released

A-M*-ADP-Pi  A-M + ADP + Pi

Step 3: Detachment: ATP binds to myosin allosterically lowering myosin's affinity for actin

A-M + ATP  A + M-ATP

Step 4: Reset: ATPase splits ATP which energizes (raises the crossbridge affinity for actin) and resets crossbridge position

M-ATP  M*-ADP-Pi

process continues to repeat as long as myosin can bind to actin and the ATP is resupplied

Cellular Control of Contraction: The Ca++ trigger

when the muscle is not contracting, tropomyosin blocks myosin from binding to actin

-however, when the muscle is stimulated to contract Ca ions are released which bind to troponin; then troponin changes its 3-D shape and pushes tropomyosin out of the way allowing myosin and actin to interact; removal of Ca++ reverses the process

ExcitationContraction Coupling

-therefore; to control contraction, intracellular Ca++ concentration must be regulated

skeletal muscle must be stimulated to contract; normally a motor neuron stimulates all skeletal muscle cells

an action potential arriving at the motor nerve ending triggers the release of ACh which diffuses across the neuromuscular junction and triggers a Motor End Plate Potential (MEPP) (analogous to a large EPSP); this is accomplished by the ACh binding to a receptor in the muscle membrane which opens Na channels which cause depolarization

normally each MEPP is large enough to trigger an AP in the muscle by affecting Na+ permeability (same as neuron)

the AP propagates (moves) along the sarcolemma (cell membrane) and into the interior of the cell via the Ttubules

each Ttubule is closely associated with the sarcoplasmic reticulum (SR) (which stores Ca++)

when the SR is depolarized, it release Ca++ which triggers contraction

in the absence of nerve stimulation, Ca++ are actively pumped into the SR, terminating contraction

NOTE: a single motor neuron may innervate several muscle cells (depending on the degree of control needed by that whole muscle); one motor neuron + all the muscle fibers it innervates = a motor unit

Biomechanics of Force Production

tension force exerted on an object by a contracting muscle

loadforce exerted on muscle by the weight of an object

therefore; tension must exceed load in order for an object to be moved

Twitchmechanical response of a muscle to an AP; consists of latent period, contraction and relaxation phases

isometric contractiontension may increase, but muscle does not shorten latent period here refers to delay due to excitationcontraction coupling; tension is less than or equal to the load

isotonic contractionlength of muscle may decrease, but tension remains constant; latent period here refers to delay for adequate tension to build to overcome the load; tension is greater than the load

Factors affecting muscle performance:

1. Frequency of stimulationAP last about 1-2 ms, whereas, twitches last 10100 ms; therefore a second stimulus would illicit a second contraction which would add to the remaining tension already developed by the previous twitch (mechanical summation)

dependent on muscle's ability to split ATP (fast or slow twitch) and the number of unblocked sites on actin. If stimuli are maintained at a fast frequency, a maximal tension may be produced (35X greater than single twitch tension) => tetanus maintained contraction without relaxation in response to high frequency stimulation

2. Initial length of muscle fiberdirectly affects the maximum tension which can be developed (see fig. 1214 in book)

3. Loadmay affect the velocity of contraction (how fast it shortens) increasing load : decreases velocity

4. Type of Muscle Fiber -there are three types which vary in size, strength, ATP splitting, and resistance to fatigue

-basis of type is speed of crossbridge cycling (fast or slow ATPase) and what pathway is primarily used in forming ATP (oxidative (red) or glycolytic (white))

a. slow twitch red -smallest diameter, weakest, slow ATPase, much myoglobin, abundant mitochondria and blood supply, high resistance to fatigue (SO)

b. fast twitch red -medium diameter, moderate strength, fast ATPase, much myoglobin, abundant mitochondria and blood supply fairly resistant to fatigue (FO)

c. fast twitch white -largest diameter, greatest strength, fast ATPase, little myoglobin, low in mitochondria and blood supply but high in glycolytic enzymes, least resistance to fatigue (that is, they tire quickly) (FG)

-a motor unit consists of only one fiber type

-most whole muscles are made of combinations of all three types

Control of Whole Muscle Tension

dependent on:

1. tension developed by each fiber (dependent on type of fiber and degree of mechanical summation)

2. amount of fibers stimulated to contract (recruitment and motor unit summation)

Energy Use:

stored ATP in muscle used up in first few twitches; therefore ATP resupply crucial

1. Creatine phosphate stored inside muscle fiber and can directly phosphorylate ADP to form ATP

2. Aerobic Respiration (Oxidative phosphorylation in mitochondria) first glycogen  glu; then glu and FA provided by blood; finally just FA is burned; these processes are very dependent on adequate oxygen supply

3. glycolysis -becomes increasingly more dominant as ATP consumption rises and oxygen becomes more unavailable to the cells

-after activity ceases, energy is still consumed to rebuild reserves (glycogen, myoglobin, CP and to transport lactate into blood; the lactate is transported to the liver where it is converted back into pyruvate and again used as energy source)---this need to consume oxygen after exercise is known as oxygen debt

Fatigueloss of tension while being stimulated

onset depends on fiber type, and intensity and duration of exercise

Cardiac muscle

-involuntary, striated, spontaneous contractility (autorhythmic)
-striated but can spontaneously contract (needs no innervation to contract); will be studied later with circulation

-contraction not dependent on outside stimulus; the autonomic nervous system (ANS) and hormones regulate rate of contraction only
-the ANS innervates special "pacemaker" regions

-cylindrical, branching cells with 1-2 nuclei centrally located; the cells are joined to one another by intercalated discs
-the discs anchor the myofibrils and spread the depolarization wave between cells

Smooth muscle -no sarcomeres hence smooth appearance

- 16:1 actin to myosin ration and the myosin is arranged in long filaments

-involuntary, non-striated, spindle shaped cells
-autorhythmic: spontaneous contraction, Ca++ is still the trigger ion but smooth muscle can maintain degrees of tension without further depolarization over very long periods of time

-specialized for continuous contraction and can relax when stretched

-contractions modulated by ANS, hormones and local metabolites
-associated with internal environment
-organs, vessels, ducts, arrectors of hair
-KNOW differences of myofibril arrangement
-Types:
1. visceral (single unit)
2. multiunit

Aging
-muscle cells are post-mitotic cells
-beginning at age 30 loss of muscle cells and mass

READ Muscle Mechanics and see Figures

Respiration

External - process of exchange of O2 and CO2 between the blood and the environment; usually includes ventilation

Internal - process of exchange of O2 and CO2 between the blood and the tissues

Cellular - burning of sugar to produce energy inside cells

Ventilation (Breathing) - movement of air in and out of the lungs

Respiratory Organs:

- primarily concerned with external respiration (getting O2 to respiratory (resp) surface (membrane) for exchange with blood)

- the upper resp. tract is above the pharynx, and the lower resp. tract is below the pharynx

-the lower resp. tract is derived from evaginations of the pharynx

Lungs and their Ducts

-develop as outgrowths of pharynx floor
-most tetrapods: the right lung is larger than left (or has more lobes)
consist of: nares, nasal passages, larynx, trachea, bronchi (primary, secondary, tertiary), bronchioles, and alveoli

Conducting Air Passages

- from nares to terminal bronchioles; conduct air to resp. membrane

- also condition the air (filter, warm, and moisten); trap particles in mucous and cilia move this debris toward the pharynx; in addition, the mucous contributes moisture. (see lecture notes for more detail)

-layers:

1. Mucosa -epith. + BM (pseudostratified ciliated columnar)

2. Submucosa - CT and mucous glands

3. Cartilage - incomplete rings with smooth muscle (trachealis) completing the ring

found in trachea and bronchi

4. Adventitia - loose and elastic CT

Respiratory Passages (carry on diffusion) -resp. bronchioles and alveoli

Alveoli: three layers

1. epith. + BM:

-type I pneumocytes - simple squamous cells function in exchange of gas

-type II pneumocytes - produce surfactant (a lipoprotein) which reduces surface tension in alveoli (preventing their collapse

2. CT - between alveoli; not involved in exchange of resp. gas

3. Capillaries - endothelium + BM (BM for resp. and capillary fuse)- dust cells (macrophage) engulf particles lodged in alveoli

- constitutes the thinnest diffusion membrane in body

-Respiration is affected by body size, age, gender, and health status

Breathing:

- mainly by developing vacuum pressure by depressing the diaphragm and rotating the ribs up and out (produced by contraction of external intercostal muscles) (Additional chest muscles may play a role in more forceful breathing)

- the expansion of the chest creates a drop in both intrapleural and intrapulmonary pressure below atmospheric pressure; the result is that air rushes down its pressure gradient into the lungs (Stretch receptors in lung and chest wall fire inhibitory signals to the medulla inspiratory center shutting down the inspiratory stimulus -the Hering-Breuer reflex)

- punctures of lungs or body wall can adversely affect breathing; resulting in pneumothorax

- normally expiration is a passive process; due to the elastic recoil of the lungs and chest and the relaxation of the inspiratory muscles the chest volume drops which creates a rise in lung pressure above atmospheric and the air rushes out

- forced expiration (internal intercostals + abdominal muscles) can further increase lung pressure by as much as 20-30 mm Hg

- lung capacities: tidal volume, residual volume, inspiratory reserve capacity, expiratory reserve capacity, vital capacity, total lung volume

Control of Respiratory Rate and Depth

- rate and depth of breathing controlled by circulating levels of carbon dioxide and H+ concentrations (monitored in the aortic and carotid bodies and in the brain itself); high levels stimulate brain inspiratory center to trigger increased ventilation.

- Also, low 02 concentration can be detected, but only functions when levels are extremely low

Transportation of gases

Oxygen- mainly transported by combining with Hemoglobin (Hb) (a large globular protein with four heme molecules each carrying an iron atom which combines with the oxygen); some of the oxygen dissolves into the plasma and can be measured as the partial pressure of oxygen (pO2)

- H+, pCO2 and temperature affect Hbs affinity for oxygen; increases in these parameters lowers the Hb affinity for oxygen; a decrease in these parameters has the opposite effect

Carbon Dioxide -some combines with hemoglobin (carboxyhemoglobin), some dissolves into plasma (pCO2), most combines with water (by the action of carbonic anhydrase) to make carbonic acid which is in equilibrium with its ions:

CO2 + H2O  H2CO3  H+ + HCO3-

NOTE: effects of increase and decrease CO2 and/or H+ on resp. rate

also effects of hyper and hypoventilation on CO2 and H+

Acid-Base Balance

Respiratory acidosis -decreased respiration causes retention of CO2 which allows plasma pH to drop

Respiratory alkalosis -increased respiration leads to CO2 loss which causes a rise in plasma pH

Metabolic acidosis -drop in plasma pH due to other than resp. causes; resp. alkalosis can compensate

Metabolic alkalosis -rise in plasma pH due to other than resp. causes; resp. acidosis can compensate

Circulatory System

General Circulatory System

1.Cardiovascular - moves the blood

-two circuit system (systemic and pulmonary); arteries move blood away from the heart; veins move blood toward the heart

-the flow of blood is usually:

artery  arteriole

heart capillaries

veins  venules

-consists of a closed system of vessels which transports the blood. It includes the heart, arteries, arterioles, capillaries, venules, and veins.

-the arterioles, venules and capillaries make up the microcirculation

2.Lymphvascular -moves lymph

-consists of blind ending tubes which return interstitial fluid lost from capillary beds back to the cardiovascular system. It includes lymphatic capillaries, lymphatic vessels, lymph nodes, and lymph organs.

Heart:

-4 chambers: 2 atria and 2 ventricles

-systole = ventricular contraction; diastole = ventricular relaxation

-dual pump (double circuit): pulmonary and systemic circulation

Cardiac Muscle:

-has sarcomeres; therefore, striations; the thin and thick filaments have the same arrangement as in skeletal muscle, sarcoplasmic reticulum is well developed and plays the same role as in skeletal muscle

-the cells are short, branched uninucleated and are joined to the next cell by intercalated discs (areas of interdigitation with many gap junctions); thus the atria and ventricles act as a single unit

-their depolarization differs from normal action potentials; the uplimb is due to Na+ permeability increase, the down limb is due to K+ flow; but these are separated by a plateau region due to the movement of Ca++ into the cell

-this type of depolarization increases the refractory period for the muscle (which lasts about as long as contraction) and prevents cardiac muscles from summating their contractions

-depolarization releases Ca++ from the SR (allowing contraction); additionally Ca++ enters through the cell membrane. Unlike skeletal muscle in response to depolarization, cardiac cells do not release enough Ca++ to completely saturate the troponin binding sites. Therefore, any event which would increase the cytosolic Ca++ increases the rate and force of contraction

Cardiac Muscle Cell Action Potential
Development of Heart:

-develop from mesoderm

-the human heart begins pumping fluid at day 23 starts off as a single tubular structure which receives blood caudally and pumps it cranially to the ventral aorta

-the tube twists to the anatomical right into an S-shape; moving the atrium more cephalad and dorsal

-the twisting continues until the atrium lies cephalad to the ventricles; the atrium then enlarges forming two chambers divided by a septum

-the ventricle splits and forms an interventricular septum

Fetal circulation -Know variations in adult
-specialized structures for respiratory and nutrient exchange for the fetal environment
-anatomy: placenta, umbilicus, umbilical a&v, ductus venosus, foramen ovale, ductus arteriosus