patho exam 3

Question 1

INTRODUCTION

Answer 1

Compose ~50% of human body weight
* Muscles contract (develop tension & shorten) to achieve:
– Purposeful movement
– Manipulation of external objects
– Propulsion of contents through hollow internal organs (circulation, digestion)
– Emptying contents of certain organs to external environment (urination, child birth)

Question 2

SKELETAL MUSCLE STRUCTURE

Answer 2

Skeletal muscle: many muscle fibers lying parallel to one another, bundled together by connective tissue
* Muscle fiber = muscle cell
– Relatively large, elongated & cylindrical shape, extending the
entire length of the muscle
– 10-100m in diameter; up to 750,000 m long
– Multi-nucleated: multiple cells fuse together during development – Multiple mitochondria: production of energy

Question 3

SKELETAL MUSCLE STRUCTURE

Answer 3

tendon

epimysium - on top
perimysium - between
endomysium - with

muscle fiber

Question 4

STRUCTURE OF MUSCLE CELL/FIBER

Answer 4

Consists of contractile elements: myofibrils
– Constitute 80% of muscle fiber volume, 1 m diameter
– Regular arrangement of thick and thin filaments
* Thick filaments (myosin): 12-18 nm in diameter, 1.6 m long * Thin filaments (actin ): 5-8 nm in diameter, 1.0 m long

muscle fiber

myofibril

Whole muscle to Muscle fiber to Myofibril to Thick filaments (myosin) thin filaments (actin)

Question 5

STRUCTURE OF MUSCLE CELL/FIBER

Answer 5

Sarcomeres: functional unit of the myofibril, found between two Z- lines, consists of actin & myosin, 2.5 m
* Regions of sarcomeres:
– A band: myosin (thick) filaments stacked along with parts of
the actin (thin) filaments
– H zone: myosin in center of A band devoid of actin
– M line: extends vertically down the center of the A band; provides support
– I band: has section of actin that doesn’t project into A band

Question 6

STRUCTURE OF MUSCLE CELL/FIBER

Answer 6

thin filament

thick filament

sarcomere

m line

cross bdriges

H zone

A band

I band

Z line

Question 7

STRUCTURE OF THICK FILAMENT

Answer 7

Composed of several hundred myosin molecules
* Myosin: two identical subunits, shaped like a golf club, heads form cross bridges, tail ends are intertwined, oriented to center
* Cross bridges:
– Seen under electron microscope
– Extend from thick to thin filaments
– Attach to actin binding sites
– Possess myosin ATPase activity

Question 8

STRUCTURE OF THIN FILAMENT

Answer 8

Composed of three proteins: actin, tropomyosin, troponin
* Actin: spherical; joined into 2 twisted strands to form filament backbone, each molecule has binding site for myosin cross bridge
* Tropomyosin: thread-like, covers the actin binding sites, preventing their association with myosin cross bridges
* Troponin: has three polypeptide units for binding to tropomyosin, actin, and Ca ions
* Latter two are regulatory proteins

Question 9

STRUCTURE OF THIN FILAMENT

Answer 9

G actin

F actin

actin molecules

binding sites for attachment within myosin cross bridges

tropomyosin

troponin

Question 10

relaxed vs excited muscle

Answer 10

relaxed
- no excitiation
- no cross bridges bnding because cross bdrge binding site on actin is physcially covered by troponn-tropomyosin complex
- muscle fber is relaxed

excited
- muscle fiber is excited. and ca2+ is relased
- released Ca2+ binds with troponin. pulling troponn-topomyosin complex aside to expose cross bdirge binding ste
- cross bridge binding complex

Question 11

SKELETAL MUSCLE CONTRACTION

Answer 11

Muscle contraction:sliding filament mechanism – Cycles of cross-bridge binding & bending pull thin
filaments inward (power stroke)
– Z-lines come closer, sarcomere shortens & so muscle shortens (contracts)
– H-zone and I-band decrease, A-band unaffected – Movie!

Question 12

SKELETAL MUSCLE CONTRACTION

Question 13

SKELETAL MUSCLE CONTRACTION

Answer 13

Muscle contraction:sliding filament mechanism
– Repeated cycles of binding, power stroke & detachment
BINDING Myosin cross-bridge binds to actin molecule.
POWER STROKE Cross bridge bends, pulling thin myofilament inward.
DETACHMENT Cross bridge detaches at the end of the power stroke and returns to the original conformation.
BINDING Cross bridge binds to more distal actin molecule; cycle repeated.

Question 14

SKELETAL MUSCLE CONTRACTION

Answer 14

Muscle contraction: sliding filament mechanism
– Binding of actin & myosin: tropomyosin and troponin expose
actin cross bridge binding sites in response to Ca2+
– Power stoke: conformation of cross bridge altered, bends
inward like stroking of a boat oar (rowing)
– Detachment: at the end of power stroke, link betweenw actin & myosin broken (small movement achieved)
– Muscle contraction: repeated cycles of binding, power stroke & detachment (climbing a rope)
– Power stroke directed towards the center of the thick filament
– All six thin filaments pulled inwards simultaneously

Question 15

SKELETAL MUSCLE CONTRACTION

Answer 15

Excitation-contraction coupling: series of events linking muscle excitation to muscle contraction, Ca2+
– ACh released at NMJ generation of AP in muscle  role of transverse (T) tubules & sarcoplasmic reticulum
– Transverse tubules: dips of surface membrane into muscle fiber at the junction of A-band and I-band, AP travels rapidly, inducing permeability changes in SPR
– Sarcoplasmic reticulum: modified EPR, forms a network around myofibrils, lateral sacs (terminal cisternae) store Ca2+ which is released by AP

Question 18

ryanodine receptors

Answer 18

RyR1
- for skeletal muscles
- causes a conformational change (physical)
- mutations can cause malignant hyperthermia

RyR2
- for the heart
- for calcium-induced release
- mutations can cause cardiac arrhythmias

RyR3
- for the brain

Question 20

SKELETAL MUSCLE CONTRACTION

Answer 20

Excitation-contraction coupling:
– AP at NMJ releases ACh w/c binds to receptors at MEP
– AP generated & propagated across muscle & down T tubule – AP in T tubule releases Ca2+ from SPR
– Ca2+ binds to troponin, moves tropomyosin aside
– Myosin cross-bridges attach to actin, power stroke
– Ca2+ actively taken up by SPR in the absence of AP
– Tropomyosin slips back, actin slips back to resting position

Question 21

steps

Answer 21

1 - an action potential arriving at a terminal button of the neuromuscular junction stimulates the release of acetylcholine, which diffuses across the cleft and triggers an action potential in the muscle fiber

2 - the action potential moves across the surface membrane and into the muscle fiber interior through the T tubules, An action potential in the T tubules triggers releases of Ca2+ from the sarcoplasmic reticulum into the cytosol

3 - Ca2+ binds to troponin thin filaments

4 - Ca2+ binding to troponin causes tropomyosin to change shape, physically moving it away from its blocking position; this uncovers the binding sites on actin for the myosin cross-bridges

5 - myosin cross bridges attach to actin at the exposed binding sites

6 - the binding triggers the cross bridge to bend pulling the thin filament over the thick filament toward the center of the sarcomere. This power stroke is powered by energy provided by ATP

7 - After the power stroke, the cross bridge. detaches from actin. If Ca2+ is still present, the cycle returns to step 5

8 - when action potentials stop, Ca2+ is taken up by the sarcoplasmic reticulum. With no Ca2+ on troponin, tropomyosin moves back to its original position, blocking myosin cross-bridge binding sites on actin. Contraction stops and the thin filaments passively slide back to their original relaxed position

Question 22

SKELETAL MUSCLE CONTRACTION

Answer 22

Role of ATP: myosin cross-bridge has ATPase activity, ATP  ADP + Pi + energy, Mg2+ important! ADP & Pi bound to myosin, energy used to store in the cross bridge, power stroke on the binding of actin  ADP & Pi released
* Rigor mortis: stiffness of skeletal muscles that begins 3-4 hrs after death, complete in 12 hrs, due to the inability of the actin-myosin complex to dissociate due to lack of ATP

Question 23

SKELETAL MUSCLE CONTRACTION
role of ATP

Answer 23

1 - energized: ATP split by myosin ATPase; ADP and Pi remain attached to myosin; energy stored in cross bridge (that is, energy “cocks” cross bridge)

2a - binding: Ca2+ released on excitation; removes inhibitory influence from actin, enabling it to bind with cross bridge

2b - resting: no excitation, no Ca2+ released actin and myosin prevented from binding; no cross-bridge cycle; muscle fiber remains at rest

3 - bending: power stroke of cross-bridge triggered on contact between myosin and actin; Pi released during and ADP released after power stroke

4a - detachment: linkage between actin and myosin broken as a fresh molecule of ATP binds to myosin cross bridge; cross bridge assumes original conformation; ATP hydrolyzed (cycle starts again at step 1) - fresh ATP available

or

4b - rigor complex: if no fresh ATP is available (after death), actin and myosin remain bound in rigor complex

Question 24

SKELETAL MUSCLE RELAXATION

Answer 24

Return of Ca2+ into the SPR:
– Absence of ACh at NMJ terminates AP at muscle cell – Ca2+ actively taken up by SPR via Ca2+ ATPase pump – Troponin-tropomyosin complex slips back
– Actin-myosin no longer able to bind at cross bridges – Actin slips back to resting position
Contractile activity outlasts electrical activity
– AP lasts only 1-2 msec, latent period b/w AP & muscle contraction, muscle contraction lasts for 100 msec
– Important for contractions of variable strength

Question 25

SKELETAL MUSCLE MECHANICS

Answer 25

A single AP produces a brief, weak contraction: twitch, too short & too weak to be useful

• Muscles work cooperatively to produce useful contractions of varying strength by adjusting the following two factors:
  – Number of muscle fibers contracting within a muscle: depends on the extent of motor unit recruitment
  – Tension developed by each fiber: frequency of stimulation, length & thickness of fiber, extent of muscle fatigue

Question 26

CONCEPT OF MOTOR UNITS

Answer 26

Motor unit: one motor neuron & innervated muscle fibers, distributed evenly
* Muscle tension depends on:
– Size of the muscle
– Extent of motor units involved
– Size of motor units (fine vs coarse)
* Muscle fatigue prevented by asynchronous recruitment of motor units (shifts)

Question 27

CONCEPT OF MOTOR UNITS

Answer 27

3 motor units

the muscle with more motor units generates more strength than the muscle with no motor units

Question 28

TENSION DEVELOPED BY FIBER

Answer 28

Frequencyofstimulation
– Twitch summation: two twitches from different APs added together to produce greater tension than one alone, possibly b/c of a discrepancy between the duration of AP & the resultant twitch
– Tetanus: smooth, sustained contraction of maximal strength (3X-4X twitch); caused by rapid stimulation of muscle fiber allowing no time for relaxation between stimuli
– Results from a sustained elevation in Ca2+, CB cycling

Question 29

TWITCH SUMMATION

Answer 29

single twitch
- if a muscle fiber is restimulated after it has completely relaxed, the second twitch has the same magnitude as the first twitch

twitch summation
- if a muscle fiber is restimulated before it has completely relaxed. the second twitch is added on to the first twitch, resulting in summation

tetanus
- if a muscle fiber is stimulated so rapidly that it does not have an opportunity to relax at all between stimuli, a maximal sustained contraction known as tetanus occurs

Question 30

TENSION DEVELOPED BY FIBER

Answer 30

Length of fiber at onset of contraction (resting muscle length is the optimal length):
– Offers the maximal opportunity for cross-bridge interaction
– At lengths other than the optimal length, not all cross bridges are able to interact for muscle shortening, so less optimal
* Extent of fatigue
* Thickness of the muscle fiber

Question 31

FIBER LENGTH & TENSION

Question 32

TYPES OF CONTRACTION

Answer 32

Isometric contraction:
– Muscle tension developed is less than its opposing load – Muscle cannot shorten and lift the object with that load – No change in length, despite developing tension
* Isotonic contraction:
– Muscle tension developed is greater than its opposing load
– Muscle usually shortens and lifts an object
– Muscle changes length, but maintains a constant tension throughout the period of shortening
– Two types: concentric (muscle shortens) and eccentric (muscle lengthens)

Question 33

SKELETAL MUSCLE METABOLISM

Answer 33

Skeletal muscle contraction & relaxation requires ATP (energy) for the following three steps:
– Power stroke of cross bridges by myosin ATPase
– Detachment of cross bridges from actin filaments at the end
of power stroke
– Active transport of Ca2+ back into SPR during relaxation
Limited amount of ATP present, additional pathways: – From creatine phosphate
– From oxidative phosphorylation
– From glycolysis

Question 34

SKELETAL MUSCLE METABOLISM

Question 35

TYPES OF SKELETAL MUSCLES

Answer 35

3 types of skeletal muscle fibers: based on the pathway used for ATP synthesis (oxidative/glycolytic) & the rapidity by which they split ATP & contract (fast/slow)
* Slow-oxidative (type I) fibers - Red,  myoglobin & mitochondria
* Fast-oxidative (type IIa) fibers
* Fast-glycolytic (type IIb) fibers - White (little myoglobin)  glycogen conc.
- Fast fibers have higher myosin ATPase activity than slow fibers

Most humans have a mixture of all three types, genetics play a role

Question 36

TYPES OF SKELETAL MUSCLES

Question 37

SMOOTH MUSCLES

Answer 37

Composes the internal, contractile organs (the walls of hollow organs and tubes) except the heart
Exert pressure and regulates forward movement
Elongated, spindle shaped, single nucleus & small
Arranged in sheets, unstriated, filament types:
Thick myosin filaments (longer than skeletal muscles)
Thin actin filaments (more than skeletal), have tropomyosin, no troponin Intermediate size filaments (support, not contractile)
Cellular arrangement is not organized into sarcomere pattern of skeletal muscle, so, do not show banding (they are “smooth”)
Dense bodies have same proteins as Z-lines of skeletal muscles Innervated by both sympathetic and parasympathetic NS (ANS)

Question 38

SMOOTH MUSCLES

Question 39

SMOOTH MUSCLES

Question 40

SMOOTH MUSCLES

Answer 40

has:
thin/thick filament
dense bodies
actin (thin filament) myosin head
myosin (thick filament)
actin (thin filament)

Question 41

SMOOTH MUSCLE CONTRACTION

Answer 41

Smooth muscle cells contract when Ca2+ ions enter the cells from the ECF and from intracellular stores
Ca2+ release activates signaling cascade leading to myosin cross bridge movement

Question 42

SMOOTH MUSCLE CONTRACTION

Question 43

SMOOTH MUSCLE CONTRACTION

Question 44

TYPES OF SMOOTH MUSCLES

Answer 44

Based on level of ongoing contractile activity:
– Phasic SM:
* Contracts in bursts
* AP  Ca2+ levels
* Pronounced increase in contractile activity
* Walls of hollow organs e.g. digestive organs
– Tonic SM:
* Partially contracted at all times (tone)
* Low RMP (-55 to -40 mV), so some VGCCs opened * Tone dependent on Ca2+ levels, not on AP activity * Walls of arterioles: maintains blood pressure

Question 45

PHASIC/TONIC SMOOTH MUSCLES

Question 46

TYPES OF SMOOTH MUSCLES

Answer 46

Based on how the muscle becomes excited:
– Single-unit SM:
* Most common SM, aka visceral SM
* Forms a functional syncytia, works as a unit
* Myogenic (self-excitable): pacemaker or slow-wave potentials
* May be phasic or tonic
– Multi-unit SM:
* Properties similar to skeletal and smooth muscles * Multiple discrete units, functioning independently * Neurogenic: nerve produced
* Phasic only

Question 47

TYPES OF SMOOTH MUSCLES

Answer 47

Single-unit smooth muscle: most common, visceral
– Form functional syncytia: a group of interconnected cells (gap junctions)
* When an AP develops in one cell, it quickly spreads to other cells
* Contract as a single, coordinated unit
– Myogenic (self-excitable): does not require nervous stimulation for contraction
* Pacemaker cells generate AP
* Pacemaker cells display spontaneous
electrical activity of one of two types: – pacemaker potentials
– slow-wave potentials

Question 48

SINGLE UNIT MUSCLE POTENTIALS

Answer 48

Pacemaker potentials:
– Automatic shifts in ion concentrations in the ECF and ICF cause spontaneous depolarizations
to threshold potential
* Slow-wave potentials:
– Gradually alternating hyperpolarizing and depolarizing swings in potential caused by automatic cyclical changes in rate that sodium ions are actively transported across membrane
– If threshold is reached, a burst of AP occur at the peak of depolarization

Question 49

TYPES OF SMOOTH MUSCLES

Answer 49

Multi-unit smooth muscle
– Consists of multiple discrete units functioning independently
– Properties partway b/w skeletal & single-unit smooth muscle
* Neurogenic (“nerve produced” excitation, similar to skeletal muscle)
* Supplied by the involuntary ANS
– Found in: walls of large blood vessels, large airways of lungs, ciliary muscle, iris of the eye, base of hair follicles

Question 50

SMOOTH MUSCLE GRADED CONTRACTION

Answer 50

Graded contraction possible in single-unit smooth muscle mechanism different from skeletal muscle
– Varying the level of
– Increased Ca2+ concentrations cause increased numbers of
Ca
2+ ions in the cytosol cross bridges formed and increased tension
– Many factors influence Ca2+ concentration
* Tone: low level of tension maintained by many single-unit smooth muscle cells that have enough calcium in the cytosol, occurs in the absence of APs
* ANS and hormones: alter the strength of self-induced, smooth muscle contractions via signaling
* Other factors (e.g., local metabolites and certain drugs): alter the contraction of both single unit and multi-unit smooth muscle

Question 51

SMOOTH MUSCLE ADVANTAGES

Answer 51

Smooth muscles can develop maximal tension even when stretched 2.5x their resting length
– Resting length is shorter than lo
– Thin & thick filaments overlap even when stretched
– Hence, smooth muscles can exist at different lengths with little change in tension
* Stretching a smooth muscle inherently relaxes it – Hence, smooth muscles do not exert any pressure on
the contents until it is ready to be emptied
* Smooth muscle is slow & economical
– Slow CB cycling maintains tension with less ATP use

Question 52

CARDIAC MUSCLE

Answer 52

Found in the walls of the heart, has properties of skeletal and smooth muscle
– Skeletal:
* Highly organized and striated
* Troponin and tropomysoin
* Clear tension-length relationship
* T tubules and SR
* Mitochondria and myoglobin
– Smooth:
* Can generate APs which spread throughout the walls of the heart,
i.e., pacemaker potentials
* Innervated and modified by ANS (hormones/local factors)