Week 2 - Muscles + Cell Adaptation Flashcards
Muscular System Function
- body movement
- maintenance of posture
- respiration
- communication
- constriction of organs and vessels
- heart beat
- production of body heat
Properties of Muscle
- excitability
- contractility
- extensibility
- elasticity
Excitability
capacity to respond to a stimulus (A.P)
Contractility
ability to shorten and generate a pulling force
Extensibility
ability to stretch
Elasticity
ability of a muscle to recoil to its resting length after being stretched
Skeletal Muscle
attached to bones via tendons
- striated with multiple nuclei
- 40% body weight
- locomotion (voluntary control)
- capable of rapid contraction
Skeletal muscle is controlled by:
somatic motor neurons
Muscle group is made up of ______ separated by perimysium
fascicles
Muscle fascicles composed of multiple _______ , each surrounded by endomysium
muscle fibers
Myofibrils
multiple repeating units within sarcomere that are responsible for muscle contraction
-contain thick filament (myosin) and thin filament (actin)
Epimysium
surrounds entire muscle
- dense, regular connective tissue
- connects to deep fascia and separates the muscle from surrounding organs
Perimysium
surrounds group of muscle fibers
- primarily collagen and elastic fibers
- contains BV and nerves
Endomysium
surrounds each individual muscle fiber
- loose connective tissue
- contains BV, nerves, satellite cells
Epimysium, Perimysium and Endomysium all come together to form a ________
tendon or aponeurosis (connects muscle to bones)
Sarcolemma
surrounds sarcoplasm
-where change in membrane potential and muscle contraction begin
Sarcoplasm
membrane around each muscle fiber
Transverse Tubules (T tubules)
transmit A.P. through the cell so that the entire muscle contracts at the same time
-encircle the sarcomere near the zones of overlap
Sarcoplasmic Reticulum (SR)
brings transmission of A.P. to the t-tubules
-forms chambers called cisternae that are also attached to the t-tubules
-releases Ca2+, causing myosin and actin to interact → muscle contraction
Triad
1 tubule + 2 terminal cisternae
Cisternae
concentrate Ca2+ and release Ca2+ into sarcomeres for muscle contraction
Sarcomere
contractile unit of muscle
-striations
A Band
overlap of thick and thin filaments
-stays the same during contraction
I band
thin filaments + “spring/coil” of thick filaments present (missing the body of the thick filaments)
-shortens with contraction
M Line
midline of sarcomere
Z Line
differentiates one sarcomere (borders)
Zone of Overlap
thick and thin filaments overlap
-at rest, only contains thick filaments (myosin)
Titin
protein stabilizing thick filament and connects it to Z line
Filaments responsible for muscle contraction
actin and myosin
H Band
has thick filaments only at rest
- contracted state: shortens
- relaxed state: wide H zone
Thin Filament (Actin) Proteins
F-Actin - 2 twisted rows of G-Actin molecules
Nebulin - holds strands together so they do not fall apart
Tropomyosin - regulates access of actin binding proteins to the filament
Troponin - under control of Ca2+; binds to thick filament
Thick Filaments (skeletal)
- myosin heads and tails attached → move as one to contract muscle
- each thick filament is surrounded by 6 thin filaments
- each thin filament is surrounded by 3 thick filaments
Low Ca2+ → _______ covers troponin complex so that it CANNOT interact with the myosin head
tropomyosin
High Ca2+ → it will bind to a subunit of ________ so that tropomyosin moves away from the binding sites to allow for muscle contraction
troponin complex
Each actin molecule has a binding site for a _________
Myosin head
Cross Bridge Theory
sufficient Ca2+ → myosin head will bind to the nearest actin molecule
→ myosin head hinges over, draws thin filaments towards each other (shortens sarcomere)
→ shortening of sarcomere generates a force within muscle fiber
→ each myosin head has a binding site for ATP + actin
→ ATP binds → hydrolyzed to ADP + P to energize the myosin cross bridge
Rigor Mortis
occurs when there is no ATP left to unhinge the myosin head
-no more ATP = contracted state
Sliding Filament Theory
when a muscle cell contracts, the thin filaments slide past the thick filaments and the sarcomere shortens
→ Ca2+ increase → actin attaches to myosin
→ ATP hydrolyzes
→ causes cross bridge
→ ATP binds to myosin head again, causing bridge to detach
When all sarcomeres within a muscle group shorten, it causes _______
muscle contraction
Sliding Filament Mechanism
- ATP binds to myosin head
- Myosin head cleaves ATP molecule (into ADP + P - they stay bound until another ATP molecule releases it)
- Troponin-Tropomyosin complex binds with Ca2+ ions that come from SR → pulls tropomyosin so that the active sites on actin filaments are uncovered for binding with myosin
- Myosin head binds to active site on actin molecule
- Bond between head of the cross bridge (myosin) and the actin filaments cause the bridge to change shape (hinge inwards)
- Power stroke pulls thin filament inward only a small distance
- Head tilt causes release of ADP + P ions
- A new ATP binds at the active site of release → binding causes detachment of myosin head
- New cycle of attach-detach-attach begins → dependent on available ATP, Ca2+, O2
- Repeated cycles
Force Generation
A.P. has a short duration of 1-2 msec
- membrane repolarized when Ca2+ reaches max
- Ca2+ peak = 10 msec after initial depolarization
Power Stroke
attach-detach-attach cycle
- myosin head bridges along actin and pulls it inward
- thick filament is STATIONARY
- brings attachment towards center of sarcomere
- detachment of myosin head cannot take place unless new ATP attaches to myosin head
- thick and thin filaments do not shorten (cross over one another)
Skeletal Muscle Relaxation
- Ca2+ is taken back up into the SR
- ATP dependent Ca2+ pump
- Ca2+ binds to Calsequestrin in SR
- Ca2+ dissociates from troponin → tropomyosin recovers the binding sites
*stays relaxed if there is no more Ca2+ or ATP stimulation
Neuromuscular Junction
end of motor neuron that attaches to a muscle fiber
- A.P. arrives at nerve ending, depolarizes the membrane and allows Ca2+ influx
- ACh diffuses into post junctional nicotinic cholinergic receptors → receptors open ion channels + permit movement of Na+ and K+ (allows A.P. to continue into sarcolemma and muscle)
- A.P. sarcolemma → t-tubule
- ACh is reversible bound to cholinergic receptors
- free ACh is hydrolyzed into choline and acetate
- Choline is taken back to terminal and can be used to synthesize new ACh → stored in presynaptic cleft for new A.P.
- Free ACh diminishes → receptors no longer stimulated → membrane repolarizes → ready for new A.P.
Action Potential Frequency is determined by ______
force
Low frequency A.P.
muscle twitches
High Frequency A.P.
summation effect → leads to A.P.
-fused tetanic force of contraction → no rest = tetanus
Intermediate Frequency A.P.
unfused tetanic contractions
Determinants of Muscle Force
- frequency: increased stimulation to muscle fiber
- recruitment: addition of motor units (the force of one motor unit adds to the fibers of the second; progresses from small alpha motor neurons to large ones)
Motor Unit
the muscle fibers innervated by axons arising from a single alpha motor neuron
Isometric Muscle Contraction
generating a force without shortening the muscle
ex. lifting a small weight without flexion; maintaining position
- max velocity at no load weight
Isotonic Muscle Contraction
shortening the muscle at constant tension/force
Length Tension Property
upper plot: shows total tension = sum of active force generation due to the cross bridge formation + passive tension due to shortening due to stretching of the muscle fiber
lower plot: shows optimal length of sarcomere at which maximum tension can be generated by cross bridge cycling
ATP has 2 functions:
- hydrolysis by myosin ATPase as energy for muscle contraction
- hydrolysis of Ca2+ ATPase for pumping Ca2+ into SR
3 Ways to Regenerate ATP
- Increase energy phosphate bond from creatine phosphate (fast but limited)
- Glycolysis of glucose (slower and dependent on availability of glucose - anaerobic exercise)
- Oxidative Phosphorylation in mitochondria (slow - aerobic exercise)
Slow Oxidative Muscle Fibers
dependent on oxidative phosphorylation
-abundant mitochondria (dark)
Fast Glycolytic Muscle Fibers
dependent on glycolytic metabolism
-fewer mitochondria (light)
Fast Oxidative Glycolytic Muscle Fibers (intermediate)
dependent on mixture of oxidative phosphorylation and glycolytic metabolism (mix dark/light)
Types of Skeletal Muscle Fibers
- Slow oxidative
- Fast glycolytic
- Fast oxidative glycolytic
*determines duration of muscle contraction
Where Smooth Muscle is Found:
in the walls of hollow organs, blood vessels, eyes, glands, uterus and skin
Functions of Smooth Muscle
- repel urine
- mix food in digestive tract
- dilate and constrict pupils
- regulate blood flow
- control involuntary movements of endocrine and autonomic nervous system
Smooth Muscle Characteristics
- substantially smaller than skeletal muscle fibers
- spindle shaped fibers
- actin and myosin are NOT arranged at sarcomeres
- actin fibers radiate from dense bodies NOT filaments
- myosin dispersed 1 to every 15 actin
- structure: dense bodies inside the cell are connected by desmin (thin filament protein) from which actin radiates
2 Types of Smooth Muscle
Multiunit and Single Unit
Multiunit Smooth Muscle
fibers operate independently of one another
- no gap junctions
- autonomic nervous system
- innervated by a single nerve
- rarely exhibit spontaneous contraction
- found in walls of large BV + lungs
Single Unit Smooth Muscle
multiple fibers act as a single unit
- gap junctions in plasma membrane so that fiber groups contract together
- slow / energy efficient
- found in walls of hollow organs (ex. bladder)
- spontaneous action potentials
Smooth Muscle Contraction Steps
- Ca2+ binds to Calmodulin
- Ca2+-Calmodulin Complex joins with myosin kinase + activates phosphorylating enzyme
- Activated myosin kinase transfers phosphate to the head of myosin light chain
- Phosphorylated myosin head binds to actin
- Contraction occurs
Smooth Muscle Contraction vs. Skeletal Muscle Contraction
Smooth Muscle
- Ca2+ mostly from ECF
- Series of biochemical events following Ca2+ influx
- Phosphorylation
- Ca2+ regulation by Calmodulin in myosin light chains
- Slower rate of cross bridging → lower ATPase activity
Skeletal Muscle
- Ca2+ from ICF (SR)
- Physical repositioning of troponin-tropomyosin complex following Ca2+ influx
- Uncovering of cross bridge
- Regulation site of Ca2+ is in myosin thick filaments
Smooth Muscle Relaxation
- Removal + reduction Ca2+
- Hydrolysis of myosin phosphate by myosin phosphatase
Smooth Muscle Regulation of Ca2+
-Ca2+ triggers contraction (comes from extracellular sources)
- Enters smooth muscle cells via slow gated channels (open slow, but stay open longer = prolonged A.P.)
-
Entry is mediated by:
1. neural signals and hormonal stimulation → do not cause A.P.; leads to Ca2+ entry then chain of events occur (ACh, angiotensin, oxytocin, histamine, serotonin, epinephrine, norepinephrine)
2. stretching of smooth muscle fiber
3. change in chemical environment
Factors Affecting Smooth Muscle Contraction
- PO2
- PCO2
- H+ or pH
- Adenosine
- Lactate
- increased temperature
- K+
- Change in Ca2+ permeability
- Activated second messengers (cAMP or cGMP)
Smooth Muscle Characteristics vs. Skeletal Muscle Characteristics
Smooth Muscle
- no striated banding pattern
- no distinct sarcomeres
- no t-tubules
- very few SR
- actin and myosin filaments
- Ca2+ dependent excitation-contraction coupling
- site of Ca2+ regulation = myosin
- source of Ca2+ = SR and ECF
- connections between SM cells = single unit and multiunit
Skeletal Muscle
- striated muscle
- distinct sarcomeres
- t-tubules
- site of Ca2+ storage = SR
- myofibrils contain actin and myosin filaments
- site of Ca2+ regulation - troponin
- source of Ca2+ = SR
- individual muscle fibers are electrically separate
Cardiac Muscle Characteristics
- exhibit their own electrical impulses (designed to help the body)
- controlled involuntarily by endocrine and autonomic N.S.
- arranged in a branching pattern with striations
- cells arranged in 1-2 nuclei (not as many as skeletal)
- SLOWER speed of contraction than skeletal muscle but FASTER than smooth muscle
- connected by intercalated discs
Cardiac Muscle Contraction Steps
Phase 0: rapid depolarization
Phase 1: sudden inactivation of the fast Na+ channels; depolarization, K+ moving out and Cl- moving in
Phase 2: plateau phase; voltage of cell changes; slower opening of Ca2+ L-channels, opening of some special delayed K+ channels
Phase 3: rapid depolarization phase; Ca2+ L channels close and slow delayed K+ channels stay open (RMP = -85 mV)
Phase 4: Na+/K+ pump; no overshoot / hyperpolarization → waste of time to generate new A.P., hence why channels are slow
- stops at -85 mV
- slow K+ channels responsible for no overshoot
- Na+/K+ pump brings cell back to RMP
Cardiac Muscle Conductivity
pacemaker cells have an automatic rhythm → spontaneously fires A.P.
-pacemaker cells cause cardiac muscles to reach threshold voltage to initiate A.P. (gradient potential)
Structures of Pacemaker Cells (Nodes)
-SA node: 60-80 A.P./min
-AV node: 40-60 A.P./min
-Bundle of HIS: 20-40 A.P./min
-Bundle Branches: 10-20 A.P./min
*serve as backups to to one another for electrical conductivity
Cardiac Muscle Contraction Characteristics
- Requires Ca2+ to allow actin to bind to myosin
- 20% of Ca2+ is required from ECF and 80% required from ICF
- Ca2+ enters L-channels
- 20% ECF Ca2+ is taken up by troponin C
- influx of Ca2+ from ECF occurs during cardiac muscle A.P. (occurs at the same time)
L-Channels
voltage dependent, slow Ca2+ channels only present in cardiac muscle
Functions of Ca2+ in Cardiac Muscle
- excites cell A.P.
- contracts muscle
*Ca2+ more important in cardiac muscle than skeletal muscle
Ca2+ Blockers
primarily act within L-Channels to decrease force of contraction
-since L-Channels are only present in cardiac muscle, Ca2+ blockers will not affect skeletal muscle (ex. Verapamil)
Absolute Refraction Period
where no other A.P. can be generated
- longer period in cardiac muscle
- Na+ increases A.P. (depolarization)
- Ca2+ initiates contraction (enters cell)
- plateau phase provides a longer refractory period (lasts 200 msec), preventing A.P. from summation → decrease chances of tetany rising)
- K+ exits the cell (repolarization)
- A.P. and muscle contraction end at the same time
Cellular Adaptation
changes made in a cell in response to adverse or varying environmental changes
-atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia
Atrophy
decrease in cell size (use it or lose it)
ex. skeletal muscle, cardiac muscle, brain, secondary sex organs
patho → thymus gland atrophies from childhood to adulthood because you no longer need it
Hypertrophy
increase in cell size, caused by mechanical signals (stretching) or tropic (growth) factors
-ex. sustained weight bearing exercises
→ heart muscle secondary to HTN
Hyperplasia
increase in cell number, secondary to mitosis or cell division
-Compensatory: regeneration of tissue (epithelial surfaces - skin, mouth, RBC, bone marrow)
Hormonal: organs dependent on estrogen (during pregnancy - hyperplasia of cells)
patho → endometriosis
Metaplasia
one cell type replaces by another; can be reversible
-more differentiation = increase risk (cancer)
-can turn dysplastic if irritant is not removed (ex. bronchiole cells can convert from mucus secreting to non-mucus secreting due to constant exposure of irritants - cigarette smoke)
Dysplasia
progression of hyperplasia + metaplasia combined; abnormal change in cell shape, size or organization
Cellular Injury
changes to the cell made by continuous stress from internal and external environment
-includes adaptation and cell death
Cell Death
injury is too severe; dependent on length and severity of exposure
-includes necrosis and apoptosis
Necrosis
cell uncontrollably explodes, causing inflammation
- swelling of organelles, membrane ruptures, all cellular content spills into surrounding tissue → tissue damage
- affects surrounding cells and tissues
- Types: Coagulative, Liquefactive, Caseous, Fat, Fibroid, Gangrenous
Apoptosis
controlled cell death by shrinking / breaking
- rids the body of cells that are beyond repair
- remnants taken up by immune system
- does not cause inflammation or affect surrounding cells
Mechanisms of Cell Injury
Hypoxia
Chemical
Free Radicals
Hypoxia: Mechanism of Cell Injury
inadequate flow of oxygen and nutrients to a cell
- O2 demand exceeds supply
- decreased ATP
- progression = cell death
- symptoms: AMS, pins + needles, coolness, cyanosis
-ex. Reperfusion Injury: result of blood flow restoration to ischemic or hypoxic tissues; must be careful how fast you bring back O2
→ restoring blood flow = bringing back Ca2+ into the cell → cytotoxic damage
→ ischemia damages mitochondria → rapid increase O2 → increase in free radicals
Chemical: Mechanism of Cell Injury
direct damage to cells by caustic agents or toxins
-targets plasma membrane + mitochondria → results in difficulty producing A.P., RMP, disregulates ion channels
Free Radicals: Mechanism of Cell Injury
waste products from chemical reactions in cell harm other cell of the body
- unpaired single electron in the outer shell
- highly reactive and very non-specific → rapidly attack other cells while looking for another electron to fill outer shell
- widespread derangement of cell components
- normal biological functions cannot be performed
-associated with: cancer, atherosclerosis, Alzheimer’s, Parkinson’s
*intense aerobic exercise can induce oxidative stress → free radical production
Substances that generate free radicals:
fried foods
alcohol
tobacco smoke
pesticides
air pollutants
Antioxidants
prevent free radicals from taking electrons
- body produces on its own but in insufficient amounts
ex. Beta-Carotene (carrots), Vitamin C, Vitamin E, Lycopene (tomatoes)
Unintentional Cellular Injuries
- blunt force trauma (BFT)
- contusion
- abrasion
- laceration
- puncture (nail in the foot - diabetics)
- gunshot wound (GSW)
- asphyxiation (unintentional)
Degeneration
abnormal functioning of the cell, structural and biochemical changes
- sometimes follows cell nonlethal cell injury; reversible if injury subsides
- necrosis if injury persists
Coagulative Necrosis
caused by ischemia or infarction
- cell architecture preserved for a few days
- usually does not occur in the brain
Liquefactive Necrosis
inflammatory cells release proteolytic enzymes that destroy surrounding tissue
- usually occurs in high concentration lipid tissues or those prone to abcess
- most common cause is bacterial infection
ex. brain or lungs
Caseous Necrosis
cell death that causes tissues to appear “cheese-like”
- preventable and treatable
- most common: Tuberculosis (TB)
Fat Necrosis
inflammation causes decrease in O2 and blood supply to fat cells
- occurs after surgery or radiation
ex. breast tissue
Fibroid Necrosis
dead cells of BV form fibrin, which blocks blood flow through vessels
- irreversible
- usually occurs as a result of chronic HTN
ex. Vasculitis
Gangrenous Necrosis
circumferential cell death around a digit or extremity
-discoloration, pain, discharge, numbness
→ Dry Gangrenous: peripheral vascular disease (usually arterial), no fluid accumulation
→ Wet Gangrenous: decreased blood flow, cannot be returned via venous pathway; poor prognosis; stagnant blood flow promotes rapid bacterial growth; high risk for amputation
→ Gas Gangrenous: infection producing gas between tissues; most fatal (ex. subcutaneous emphysema)
Apoptosis Mechanism
- Cells shrink
- Cell fragments within shrunken cells form blebs
- Nucleus and organelles collapse (cannot function)
- Apoptotic bodies form
- Cell releases apoptotic bodies to macrophages to rid of them
Cellular Aging
aka cellular senescence
permanent cell growth arrest
-caused by oxidative stress, DNA damage, decreased autophagy (ability to recycle damaged parts decrease as we age)
-so many cell divisions → error signal → stops making new copies of itself
Inflammation
nonspecific response to tissue injury; always the same response regardless of triggering event
- goal: to bring phagocytes and plasma proteins to invaded/injured areas
- defense: tissue macrophages
- types: serous, suppurative, membranous, granulomatous
Inflammation Mechanism
- Resident macrophages
- Increased redness (vasodilation) and heat, increased swelling (increased fluid with increased antibodies) - local edema (interstitial) - discharge may form or leak
- Immigration of leukocytes
- Histamine released
- Plasma proteins leave blood and enter the inflamed area
Serous Inflammation
exudate production
Suppurative Inflammation
secondary to bacterial infection
-hemotoxins produced by bacteria → dense increase of neutrophils
Fluid accumulation causes 4 types of inflammation
- Heat (calor)
- Pain (dolor)
- Redness (rubor)
- Swelling (tumor)
Neutrophils/monocytes emigrate from the blood to the inflamed area and form:
- Margination - adhere to the surface of capillaries
- Diapedesis - neutrophils enter interstitial space
- Chemotaxis - neutrophils guided to areas in need
Leukocyte Proliferation
within a few hours of inflammation response
- Neutrophils increase 4-5x in size
- Monocytes increase at a slower rate
- Bacteria marked for destruction by opsonins → more susceptible to phagocytosis → complement system activated → allows phagocytes to determine foreign vs. normal
Mediation of inflammatory response by phagocyte secreted chemicals:
- Nitric oxide
- Lactoferrin
- Histamine
- Kinins
- Endogenous pyrogen
- Leukocyte endogenous mediator
- Acute phase proteins from the liver
Scar Tissue
No regeneration of tissue
Leukocytes destroy bacteria by
Phagocytosis
Neoplasia
formation of new, abnormal growth of tissue
-cell adaptations: hyperplasia, hypoplasia, hypertrophy, atrophy
Anaplasia
loss of specialized cell features
-usually seen in malignant tumors
Carcinogens
cancer causing agents
-agents: chemical (radiation, asbestos), physical and infections (HPV, Esptein-Barr, Hep B - hepatocellular carcinoma)
Malignancy
cells that grow uncontrollably and rapidly
-spread through bloodstream and lymphatic system
-most common: breast, bone, liver, brain
Carcinoma
malignant
-epithelial origin
Sarcoma
malignant
-mesenchymal origin
Oncogene
mutated gene with potential to cause cancer
→ breast cancer = BRCA 1, BRCA 2
Criteria for Malignancy
- many cells that are not in groups
- variable shape/size nucleus
- nuclei not in the center
- inhomogeneous chromatin
Tumor Classification
→ by tissue (1)
→ specific type (2)
→ grading (3)
→ spread according to node metastases (4): amount of spread and where
- T = size of primary tumor
- N = degree of lymph node involvement
- M = presence of metastasis
Metastasis Formation
invade local tissue, then to other body parts (close to circulation)
→ circulates → extravasation (leaves blood circulation)
- can lie dormant for months (scans clear but metastases in hiding)
- metastatic colonization
Paraneoplastic Syndrome
consequence of cancer but not due to the cancer cells (before primary tumor is discovered)
-abnormal immune system response
