Guyton Exam 2 prep

Skeletal Muscle Fiber Composition

• Each muscle fiber contains hundreds to thousands of myofibrils.
• Myofibrils consist of actin and myosin filaments.
• Myosin filaments are thick and create the dark A bands.
• Actin filaments are thin and create the light I bands.

Sarcomere Structure

• The sarcomere is the functional unit of muscle contraction.
• Sarcomeres are located between two Z discs.
• Titin connects the Z disc to myosin at the M line and is springy.
• Sarcoplasm is fluid between myofibrils containing potassium, magnesium, and phosphate.
• The sarcoplasmic reticulum regulates calcium storage, release, and uptake.

Myosin Filament Structure

• Myosin filaments consist of a tail, a hinge, and a head.
• Myosin molecule tails bundle to form the body of myosin.
• The arm and head is known as the crossbridge.
• Two hinges exist: one to create the arm and another to attach the head.
• Crossbridges extend in all directions around the body.

Actin Filament and Contraction Regulation

• Actin is strongly attached to the Z disc.
• Tropomyosin wraps around actin, covering active sites until contraction.
• Troponin, attached to tropomyosin, has a strong affinity for calcium, initiating contraction.
• In a relaxed muscle, a golf club-shaped myosin head is bound by ATP and detached from the thin filament.
• A complex composed of tropomyosin, troponin C, component I, and troponin T blocks myosin from binding to the active site.

Walk Along Theory (Contraction Process)

• An action potential releases calcium from the sarcoplasmic reticulum.
• Calcium causes myosin heads to attach to active sites on the actin filament.
• The crossbridge head tilts, dragging the actin filament along (power stroke).
• The head detaches, returns to the extended direction, and attaches to another active site for a new power stroke.
• After the neuromuscular junction transmits a signal, calcium concentration jumps sharply.
• The troponin complex has four calcium binding sites, two of which are low affinity.
• Once the two low affinity sites are filled, the complex undergoes a conformational change which moves it up and away.
• This movement allows tropomyosin to relocate, clearing the way for myosin to bind.
• Myosin remains detached if it is still bound by ATP, which hydrolyzes into ADP and inorganic phosphate.
• Before binding, the myosin head rotates to its cocked position, forming a cross bridge.
• The contraction begins when phosphate dissociates from myosin, triggering the power stroke.
• The myosin head rotates 45 degrees, pulling the actin along with it.
• Once the power stroke is finished, ADP leaves and the cross branch is stuck in the attached and contracted state.
• If ADP binds to the myosin head again, the cycle will start over at the relaxed stage.

Energy for Contraction

• Hydrolysis of ATP forms ADP during contraction.
• ATP is used to extend the head, and energy is stored for the power stroke.
• ATP is needed for the walk along mechanism, pumping calcium into the sarcoplasmic reticulum, and pumping sodium and potassium ions.
• ATP is formed through phosphocreatine, glycolysis, and oxidative metabolism.
• Phosphocreatine provides energy for 5-8 seconds.
• Glycolysis breaks down glycogen to pyruvic and lactic acid, maintaining contraction for about a minute.
• Oxidative metabolism combines oxygen and glycolysis products, providing over 95% of muscle energy.

Types of Muscle Contractions

• Isometric contraction: muscle length remains constant.
• Isotonic contraction: muscle shortens, tension remains constant.

Fast Versus Slow Fibers

• Muscles contain a mixture of fast and slow fibers.
• Slow fibers have more myoglobin (reddish), higher capillaries, more mitochondria, are smaller, have less strength, and longer contraction periods.
• Fast fibers have more strength, an extensive sarcoplasmic reticulum, large amounts of glycolytic enzymes, less blood supply, and fewer mitochondria.

Motor Units and Summation

• Each motor neuron innervates multiple muscle fibers, forming a motor unit.
• Fine motor control requires more nerve fibers.
• Summation: the addition of individual contractions.
• Summation: Increasing the number of motor units contracting simultaneously and/or increasing the frequency of those contractions.
• Size principle: Smaller units contract first, then larger units as signal strength increases.
• Tokenization: Contractions fuse together at a critical level, appearing smooth and continuous.

Muscle Strength and Fatigue

• Maximum strength of contraction is between 3 to 4 kg/cm².
• Staircase effect: Muscle strength increases rapidly after a long rest period.
• Muscle tone: Low rate of nerve impulses causing tightness.
• Muscle fatigue: Occurs in direct proportion to the depletion of glycogen.

Muscle Remodeling

• Hypertrophy results from increased numbers of actin and myosin filaments.
• A few strong contractions a day are needed for hypertrophy within 6-10 weeks.
• New sarcomeres are added when muscles are stretched.
• Sarcomeres are removed if a muscle remains shortened for an extended period.
• Denervation causes atrophy in as little as two months.
• Renovation can cause return of function, but typically with less capability.

Skeletal Muscle Contraction Overview

• Skeletal muscle makes up about 40% of the body, with smooth and cardiac muscle comprising another 10%.
• Skeletal muscles are composed of numerous fibers, each made of smaller subunits.
• Each fiber is typically innervated by a single nerve ending.
• The sarcolemma is the membrane enclosing a skeletal muscle fiber.
• Myofibrils contain actin and myosin filaments, essential for muscle contraction.
• Myosin filaments are thick, while actin filaments are thin.
• Titin molecules maintain the arrangement of myosin and actin filaments.
• The sarcoplasm is the intracellular fluid between myofibrils, containing potassium, magnesium, phosphate, protein enzymes, and mitochondria.
• The sarcoplasmic reticulum regulates calcium storage, release, and uptake, thereby controlling muscle contraction.
• Skeletal and cardiac muscles appear striated due to light and dark bands.
• Light bands, containing only actin filaments, are called I bands, while dark bands, containing myosin and overlapping actin filaments, are called A bands.
• The sarcomere is the portion of the myofibril between two successive Z disks.

Key steps in muscle contraction

• An action potential travels along a motor nerve to its endings on muscle fibers.
• The nerve secretes acetylcholine.
• Acetylcholine opens cation channels, allowing sodium ions to diffuse and causing depolarization.
• The action potential travels along the muscle fiber membrane.
• The sarcoplasmic reticulum releases calcium ions.
• Calcium ions initiate attractive forces between actin and myosin filaments, causing them to slide.
• Calcium ions are then pumped back into the sarcoplasmic reticulum, ceasing contraction.
• Myosin molecules have two heavy chains and four light chains.
• The heavy chains form a double helix tail, and each chain has a myosin head.
• The heads have hinged arms that allow them to extend outward.
• Actin filaments consist of two helical strands of F-actin molecules.
• Tropomyosin molecules are wrapped around the F-actin helix, and troponin complexes are attached to the tropomyosin.
• ATP is the energy source for contraction. binds to the myosin head, is cleaved into ADP and phosphate, with the energy used for the power stroke.
• The walk-along theory suggests that cross-bridges attach to actin filaments, tilt to drag the actin filament, detach, and reattach to a new active site, causing the filaments to slide.
• The amount of actin and myosin filament overlap determines the tension developed by the contracting muscle.

Work output during muscle contraction

• Work output during muscle contraction is W=L×D, where W is work output, L is the load, and D is the distance of movement against the load.
• Energy for muscle contraction includes phosphocreatine, glycolysis, and oxidative metabolism.
• Muscle contraction is isometric when the muscle does not shorten and isotonic when it shortens at a constant tension.
• Fast fibers are large, have an extensive sarcoplasmic reticulum, and rely on glycolytic enzymes.
• Slow fibers are smaller, have more blood vessels and mitochondria, and contain myoglobin.
• A motor unit consists of a motor neuron and the muscle fibers it innervates.
• Summation increases muscle contraction intensity by increasing the number of motor units contracting (multiple fiber summation) or increasing the frequency of contraction (frequency summation), leading to tetanization.
• Muscle fatigue results from the inability to maintain the required work output, often due to glycogen depletion.
• Agonist and antagonist muscles on opposite sides of a joint coordinate body movements.
• Muscles adapt through remodeling, including hypertrophy (increase in muscle mass) and atrophy (decrease in muscle mass).
• Muscle denervation leads to rapid atrophy.
• Muscular dystrophies, such as Duchenne muscular dystrophy (DMD), are inherited disorders causing muscle weakness and degeneration.

Physiological Anatomy of Skeletal Muscle

• Skeletal muscle comprises approximately 40% of body mass.
• Muscles consist of fibers (10-80 micrometers in diameter) made up of myofibrils.
• Myofibrils contain interdigitating myosin (thick) and actin (thin) filaments, creating light (I) and dark (A) bands.
• The sarcomere is the segment between two Z disks and represents the functional unit of muscle contraction.
• Titin molecules maintain the alignment of actin and myosin filaments.

Molecular Components and Their Roles

• Myosin: Thick filaments with cross-bridges that interact with actin.
• The protruding arms and heads together are called cross-bridges.
• Myosin heads have ATPase activity, which is crucial for energy released during contraction.
• Actin: Thin filaments containing active sites for myosin binding. Tropomyosin: Blocks the active sites on actin in the resting state.
• In the resting state, the tropomyosin molecules lie on top of the active sites of the actin strands.
• Troponin: Binds calcium ions, triggering a conformational change that moves tropomyosin and exposes the active sites on actin.

Sliding Filament Mechanism

• Muscle contraction occurs as actin filaments slide past myosin filaments, shortening the sarcomere.
• Cross-bridges on myosin bind to actin, pull the actin filaments, detach, and repeat the cycle ("walk-along" theory).

Excitation-Contraction Coupling

• Action potential travels along the muscle fiber membrane (sarcolemma).
• Depolarization causes the sarcoplasmic reticulum to release calcium ions.
• Calcium ions bind to troponin, initiating the contraction process.
• Calcium is pumped back into the sarcoplasmic reticulum to allow muscle relaxation.

Energy Sources

• ATP provides the immediate energy for muscle contraction.
• Phosphocreatine replenishes ATP quickly but is limited.
• Glycolysis (anaerobic breakdown of glycogen) provides energy for short-term, intense activity.
• Oxidative metabolism (using oxygen to break down carbohydrates, fats, and proteins) provides energy for sustained, long-term activity.
• More than 95% of all energy used by the muscles for sustained long-term contraction is derived from oxidative metabolism.

Types of Muscle Contraction

• Isometric: Muscle contracts without shortening.
• Isotonic: Muscle shortens while maintaining constant tension.

Motor Units

• A motor unit consists of a motor neuron and all the muscle fibers it innervates.
• Smaller motor units are recruited first for fine motor control; larger motor units are recruited for more forceful contractions ("size principle").

Summation and Tetanization

• Summation: Increased force of contraction due to multiple stimuli.
• Tetanization: Sustained, maximal contraction due to high-frequency stimulation.
• When the frequency reaches a critical level, the successive contractions eventually become so rapid that they fuse together.
• The whole muscle contraction appears to be completely smooth and continuous. This process is called tetanization.

Muscle Fatigue

• Caused by depletion of glycogen stores and the inability of contractile and metabolic processes to keep up with energy demands.

Muscle Remodeling

• Hypertrophy: Increase in muscle mass due to increased size of muscle fibers (increased actin and myosin filaments).
• Virtually all muscle hypertrophy results from an increase in the number of actin and myosin filaments in each muscle fiber.
• Atrophy: Decrease in muscle mass due to decreased protein synthesis or increased protein degradation.
• Muscle length can be adjusted by adding or removing sarcomeres.

Muscle Disorders

• Muscular Dystrophy: Genetic disorder causing progressive muscle weakness and degeneration due to defects in proteins like dystrophin.
• Denervation Atrophy: Muscle atrophy due to loss of nerve supply.

Neuromuscular Junction

• Large myelinated nerve fibers from the spinal cord's anterior horns stimulate skeletal muscle fibers.
• Action potentials travel along these fibers in both directions.
• The motor end plate is insulated by Schwann cells.
• The space between the nerve terminal and muscle fiber membrane is the synaptic space or cleft.
• This area has folds to increase the surface area for synaptic activity.

Acetylcholine Synthesis and Release

• ATP is used in the axon terminal to synthesize acetylcholine, stored in synaptic vesicles.
• There are roughly 300,000 vesicles in a nerve terminal of a skeletal muscle fiber.
• Each vesicle contains about 10,000 acetylcholine molecules.
• An action potential typically ruptures about 125 vesicles, releasing over 1.2 million acetylcholine molecules.

Mechanism of Acetylcholine Release

• When an action potential arrives at the nerve terminal, voltage-gated calcium channels open, allowing calcium ions to diffuse into the nerve terminal.
• Calcium facilitates the binding of acetylcholine vesicles to the neural membrane.
• Acetylcholine is released into the synaptic space via exocytosis.

Acetylcholine and Ion Channels

• Released acetylcholine stimulates ion channels on the post-synaptic muscle fiber.
• Two acetylcholine molecules bind to alpha subunit proteins on the acetylcholine-gated sodium ion channel.
• This enables 15,000 to 30,000 sodium ions to pass through in one millisecond.
• Despite the channel's width allowing negative ions to pass, strong charges prevent their diffusion.
• The muscle membrane's negative potential (-80 to -90 millivolts) pulls positively charged sodium ions into the muscle fiber.

Action Potential and Muscle Contraction

• The influx of sodium ions creates a local positive charge, opening neighboring voltage-gated sodium channels and allowing more sodium to flow inward.
• This positive charge spreads along the muscle membrane, leading to muscle contraction.
• Acetylcholine is rapidly broken down by acetylcholinesterase in the synaptic space, limiting its presence to a few milliseconds.
• Acetylcholine binds to connective tissue within the synaptic cleft.

Factors Affecting Action Potential

• The rapid diffusion of sodium ions causes a change in charge from -80 or -90 millivolts to a positive 50 to 75 millivolts, called the end plate potential.
• An action potential must reach a threshold to cause further action potentials.
• Curare poisoning and botulism toxin can weaken the potential, preventing it from reaching the threshold.

Drugs and Diseases

• Drugs that mimic acetylcholine can cause localized depolarization and muscle spasms.
• Drugs inhibiting acetylcholinesterase lead to acetylcholine accumulation in the neuromuscular junction.
• Diseases like Myasthenia Gravis reduce signaling from the nerve fiber or diminish receptors at the post-synaptic junction, impairing the ability to initiate a strong action potential.
• This condition can be treated with acetylcholinesterase inhibitors.

T Tubules

• Skeletal muscle fibers utilize T tubules to transmit action potentials into the muscle fiber's interior.
• These tubules are extensions of the cell membrane and communicate with the exterior of the muscle fiber.

Sarcoplasmic Reticulum and Calcium Release

• T tubules are closely associated with the sarcoplasmic reticulum, which stores large amounts of calcium ions.
• When an action potential occurs in the T tubule, calcium ions are released from the sarcoplasmic reticulum.
• A voltage change in the T tubule is detected by ryanodine receptor channels in the sarcoplasmic reticulum, leading to the opening of calcium release channels.
• Muscle contraction continues as long as calcium ion concentration remains high.

Calcium Pump and Relaxation

• A calcium pump in the sarcoplasmic reticulum wall pumps calcium back into the tubules.
• Each action potential stimulation increases calcium concentration significantly, which is then reduced by the calcium pump.
• This process, known as the calcium pulse, lasts about 1/20 of a second.

Excitation-Contraction Coupling Summary

• An action potential travels down the T tubule, stimulating the ryanodine receptor channel and causing the release of calcium ions from the sarcoplasmic reticulum, leading to muscle contraction.
• The calcium pump then restores calcium to the sarcoplasmic reticulum.

Malignant Hyperthermia

• Mutations in the ryanodine receptor channel can cause malignant hyperthermia, a hypermetabolic crisis triggered by certain anesthetics.
• These anesthetics cause unregulated calcium release from the sarcoplasmic reticulum, leading to excessive muscle fiber contraction, heat production, cellular acidosis, energy depletion, and rhabdomyolysis.

Neuromuscular Junction:

• Skeletal muscle fibers are innervated by myelinated nerve fibers from motor neurons.
• Neuromuscular junction forms near the muscle fiber's midpoint.
• The nerve fiber branches into terminals that invaginate into the muscle fiber surface, forming the motor end plate.
• The invaginated membrane is the synaptic gutter or trough, with a synaptic space (cleft) of 20 to 30 nanometers.
• Subneural clefts on the gutter's bottom increase the surface area for synaptic transmitter action.

Acetylcholine Release:

• When a nerve impulse reaches the neuromuscular junction, about 125 vesicles of acetylcholine are released into the synaptic space.
• Calcium ions entering the nerve terminal activate Ca2+-calmodulin–dependent protein kinase.
• Subsequently, synapsin proteins are phosphorylated freeing acetylcholine vesicles to move to the presynaptic neural membrane's active zone.
• The vesicles dock, fuse with the neural membrane, and release acetylcholine via exocytosis.

Acetylcholine-Gated Channels:

• Acetylcholine receptors are located near the mouths of subneural clefts.
• Each receptor has two alpha subunit proteins to which acetylcholine molecules attach, causing a conformational change that opens the channel.
• These channels allow positive ions like sodium, potassium, and calcium to move through.
• The channels repel negative ions like chloride.

End Plate Potential:

• The influx of sodium ions creates a local positive potential change called the end plate potential.
• If this potential is strong enough, it opens neighboring voltage-gated sodium channels, initiating an action potential.
• Acetylcholinesterase in the synaptic space destroys acetylcholine a few milliseconds after its release.

Safety Factor and Fatigue:

• Each nerve impulse normally causes three times as much end plate potential as needed to stimulate the muscle fiber, providing a high safety factor.
• Excessive stimulation can deplete acetylcholine vesicles, leading to fatigue of the neuromuscular junction.

T Tubule System:

• Action potentials spread along the muscle fiber membrane and into the T tubules.
• T tubules are extensions of the cell membrane that penetrate the muscle fiber.
• The T tubules transmit the action potential deep into the muscle fiber to stimulate the sarcoplasmic reticulum.

Calcium Release and Muscle Contraction:

• The sarcoplasmic reticulum stores calcium ions.
• When an action potential reaches the T tubule, it is sensed by dihydropyridine receptors.
• Which trigger the opening of calcium release channels (ryanodine receptor channels) in the sarcoplasmic reticulum.
• Calcium ions are released into the sarcoplasm, initiating muscle contraction.

Calcium Removal:

• A calcium pump (SERCA) in the sarcoplasmic reticulum wall pumps calcium ions back into the tubules.
• Calsequestrin, a calcium-binding protein inside the reticulum, can bind up to 40 calcium ions per molecule.

Neuromuscular Junction & Transmission:

• The neuromuscular junction (NMJ) is where a motor nerve fiber connects with a skeletal muscle fiber.
• The nerve fiber branches into terminals that invaginate into the muscle fiber surface, forming the motor end plate.
• The invaginated membrane is the synaptic gutter or trough.
• The space between the nerve terminal and muscle membrane is the synaptic space (cleft).
• Subneural clefts on the muscle membrane increase surface area.
• Each nerve ending makes a junction, called the neuromuscular junction, with the muscle fiber near its midpoint.
• Acetylcholine (ACh) is synthesized in the nerve terminal cytoplasm and then transported into synaptic vesicles (approx. 300,000 per terminal).
• When a nerve impulse arrives, voltage-gated calcium channels open, causing an influx of Ca2+ ions.
• This triggers the fusion of about 125 ACh vesicles with the presynaptic membrane and the release of ACh into the synaptic cleft via exocytosis.

ACh Receptors and End Plate Potential:

• ACh diffuses across the synaptic cleft and binds to ACh receptors.
• Receptors are ligand-gated ion channels on the muscle fiber membrane, primarily concentrated at the mouths of subneural clefts.
• The ACh receptors composed of five subunit proteins, open a central channel allowing Na+, K+, and Ca2+ to pass, but restrict the passage of negative ions like chloride.
• The influx of Na+ causes a localized depolarization called the end plate potential (EPP). The principle effect of opening the acetylcholine-gated channels is to allow sodium ions to flow to the inside of the fiber.
• This action creates a local positive potential change inside the muscle fiber membrane, called the end plate potential.

Action Potential Initiation:

• If the EPP reaches threshold, it opens voltage-gated sodium channels in the adjacent muscle fiber membrane.
• This initiates an action potential that propagates along the muscle fiber.
• Recall that a sudden increase in nerve membrane potential of more than 20 to 30 millivolts is normally sufficient.
• Sufficient enough to initiate more and more sodium channel opening, thus initiating an action potential at the muscle fiber membrane.

ACh Degradation:

• Acetylcholinesterase (AChE) rapidly hydrolyzes ACh into acetate and choline, terminating the signal.
• Choline is reabsorbed into the nerve terminal for ACh resynthesis.
• The acetylcholine, once released into the synaptic space, continues to activate acetylcholine receptors as long as the acetylcholine persists in the space.
• However, it is rapidly destroyed by the enzyme acetylcholinesterase.

Pharmacology & Pathology

• ACh-like drugs (methacholine, carbachol, nicotine): Stimulate muscle fibers by depolarizing the motor end plate.
• Anticholinesterase drugs (neostigmine, physostigmine, diisopropyl fluorophosphate): Inhibit AChE, prolonging ACh action and causing muscle spasm.
• Curariform drugs (d-tubocurarine): Block ACh receptors, preventing muscle fiber depolarization and causing paralysis. Myasthenia Gravis: An autoimmune disease where antibodies attack ACh receptors at the NMJ, leading to muscle weakness.
• Myasthenia gravis causes muscle weakness because of the inability of the neuromuscular junctions to transmit enough signals from the nerve fibers to the muscle fibers.

Drugs Affecting Neuromuscular Transmission:

• A T-Tubules: action potentials propagate along the muscle fiber’s surface membrane and also travel deep into the fiber via transverse tubules.
• Transverse tubules are invaginations of the cell membrane that ensure rapid and uniform excitation of the myofibrils.
• B Sarcoplasmic Reticulum (SR): the SR is an intracellular network that stores calcium ions.
• C Calcium Release: when an action potential reaches the Transverse tubules, voltage-sensitive dihydropyridine receptors (DHPRs) on the Transverse tubules membranes sense the voltage change.
• These are mechanically linked to ryanodine receptor channels (calcium release channels) on the SR membrane.
• DHPR activation triggers the opening of ryanodine receptors, releasing Calcium out of the SR into the sarcoplasm.

Smooth muscle types

• Multi-unit smooth muscle is composed of discrete, independent fibers, often innervated by single nerve endings and insulated by a basement membrane.
• These fibers are controlled mainly by nerve signals.
• Unitary smooth muscle consists of hundreds to thousands of fibers that contract together as a unit.
• Unitary smooth muscles have gap junctions, allowing action potentials to travel from fiber to fiber.
• Unitary smooth muscle is found in the walls of most viscera, including the GI tract, bile duct, uterus, and many blood vessels.

Smooth Muscle Contraction

• Smooth muscle contains actin and myosin, but their physical organization differs from that of skeletal muscle.
• Large numbers of actin filaments are attached to dense bodies, some attached to the cell membrane, while others are dispersed inside the cell.
• Dense bodies are bonded to adjacent cells by protein.
• Myosin filaments are interspersed among the actin filaments.
• Most smooth muscle contraction is prolonged lasting hours or even days.
• Smooth muscle requires low amounts of energy due to slow cross bridge cycling.
• Smooth muscle contraction begins 50 to 100 milliseconds after excitement, reaches full contraction in 0.5 seconds, and then declines in force for 1 to 2 seconds. Smooth muscle contraction is typically 1-3 seconds about 30x slower than skeletal muscle.
• Maximum force of contraction of smooth muscle is often greater than skeletal muscle due to the prolonged attachment of myosin cross bridges.

Latch Mechanism

• Refers to the prolonged attachment of myosin to actin filaments, requiring less energy and maintained for extended period.

Stress Relaxation

• Visceral unitary smooth muscle can return to its original force of contraction during elongation or shortening.
• When pressure increases, the muscle relaxes to maintain the same pressure and vice versa.
• An example is how the smooth muscle in the bladder wall relaxes to maintain pressure despite an increase in urinary volume.

Stimulus for Contraction

• The stimulus for smooth muscle contraction is an increase in calcium ion concentration, which can be caused by nerve stimulation, hormonal stimulation, stretch of the fiber, or changes in the chemical environment.
• Smooth muscle does not contain troponin; instead, calcium combines with calmodulin to initiate contraction.
• Increased cytosolic calcium concentration leads to calcium binding to calmodulin.
• Which subsequently activates myosin light chain kinase.
• Active myosin light chain kinase causes the attachment of the myosin head to the actin filament, resulting in contraction.

Sarcoplasmic Reticulum and Calcium Dependence

• The sarcoplasmic reticulum is less developed in smooth muscle compared to skeletal muscle.
• Most calcium ions that cause contraction come from the extracellular fluid.
• Smooth muscle contraction is dependent on extracellular calcium ion concentrations.

Smooth Muscle Relaxation

• Relaxation occurs when calcium is removed from intracellular fluids by calcium pumps, moving calcium ions back into the extracellular fluid or sarcoplasmic reticulum.
• Myosin phosphatase causes the myosin head to stop cycling, ceasing contraction.

Innervation and Receptors

• Autonomic nerve fibers innervate smooth muscle, branching diffusely onto a sheet of muscle.
• Acetylcholine and norepinephrine are the most important neurotransmitters.
• Local factors such as increased hydrogen ion concentration, lack of oxygen, or adenosine can cause contraction and dilation of pre-capillary sphincters, changing blood flow.
• Various circulating hormones, including norepinephrine, epinephrine, angiotensin II, endothelin, thromboxane, oxytocin, serotonin, and histamine, affect smooth muscle contraction.

Multi-Unit Smooth Muscle:

• Discrete, separate fibers that operate independently & are each innervated by a ending that's single nerve.
• The fibers are insulated from one another by a membrane-like substance.
• Examples are the ciliary muscle of the eye, the muscle of the eye, and muscles.
• Unitary Smooth Muscle: Known as or smooth muscle, this type consists of hundreds to thousands of fibers contracting as a unit.
• The fibers are arranged in with cell membranes to one another.
• Gap junctions facilitate flow between cells, enabling to spread.
• Examples are the of the tract, ducts, uterus, and blood vessels.

Contraction Mechanism

• Contraction begins when calcium ions bind to calmodulin [7].
• Muscle has act through or chemical.
• Actin filaments, which serve a function to the in muscle, are with protein bridges. Cross are. Smooth muscle cells can contract up to 80% of their length.
• A latch mechanism allows smooth muscle function with energy and minimal excitation.

Regulation by Calcium

• An smooth muscle can by stimulation, hormonal stimulation, fiber stretch, or chemical. Unlike skeletal muscle, is a to calmodulin. Calmodulin their contraction.
• Calcium concentration the cytosolic fluid due fluids or release from the reticulum. The calmodulin active.
• Extracellular calcium is critical for and relies on calcium ions extracellular fluid.

Nervous & Hormonal

• Can their membranes proteins that both the contractile process. Unlike skeletal, smooth respond via nerve signal
• There are neuromuscular which transmitter secreted. They neurotransmitters. This of smooth muscle's slow, contraction, makes it to involuntary bodily functions.

Smooth Muscle Overview:

• Small size muscle fibers, smooth muscle is various bodily muscle from by their calcium, speed of contraction and energy.

Types of Smooth Muscle:

• • Multi-unit muscles signals
• Unitary/single this form has gap junctions.

Contraction Mechanism

• Contains of and with actin filaments. Also of that are side polar which helps for greater contraction. Has the dense bodies that are found inside the cells.
• As, it is the force can maintain with which it needs. It's important contraction in the lumen organ.

Regulation of Contraction using Calcium Ions

• This lacks ions. It consists to the calcium influx where reticulum reticulum. In reticulum reticulum, ions are released. That's why there is longer or inhibition or receptors where depending the and the excitation or not.

Red Blood Cells

• Primarily transport hemogl0bin which itself carries oxygen.
• Carbonic anhydrase contains excellent acid based buffer. Normal red blood cells for men are 5.2 and for women 4.7

HemoGlobin

• Hemoglobin maxes out at 34g per 100m of blood cells Normal Hemoglobin levels; Men: 15g per 100ml Women 14g per 100ml.
• Early Embrionic Life Yolksac Middle Trimester spleen and lymph nodes, Last Month of Ge station Bone Marrow Below 5 years all bone marrow Over 20 membranous bones Erythropoietin: Is primarily responsible for red blood cell production.

Vitamin B12 and Folic Acid

• Vitamin b12 and folic acid have the deficiency to repair the DNA and lack the cell division
• Red Blood Cell lifespan is 120 days, self distract in the spleen.

HemoGlobin

Hemoglobin A has the combination of four hemoglobin chains

• Crucial for oxygen transport or reuse stored for the.
• High Dose Radiation results in blood loss with anemia, aplastic, megaloblastic anemia, and hemolytic anemia.

Blood Types

• Blood is grouped categorized into O/A/B based on their aggression
• This is blood type genetic locus that has three alleles

Anti A/ Anti B Blood

• If Type A the Anti B agglutinins are not present in the red blood cells, they will form
• Blood typing helps separate from the plasma when clumps occur it states antibody antigen

RH Blood Types

• There are six common times of Rh antigens.
• RH blood types work when the mother is negative and the father is positive. This has been proven to cause erythroblastosis fatalis or given Rh immunoglobulins or gestations
• Transfusions result in kidney failure of hypertension

Graft Rection

• Auto grafts survive because t cells suppress their action from drugs or therapy

O-A-B Blood Types

• The System, of that can cause reactions has: Type and on of cell is with these.
• Type their no a or b and. It that may have neither, one of its.
• There is blood types group group that that

O-Allele

• Genetic Determination is the Blood of group IA with IO.
• AA with OO group the is functionless, in no type on the type, while the while what is.
• The O is that is recess and, while the is

RH Blood Types

• Rh positive / negative:
• A negative exposure. This occurs after they developed through Rh system never occur so that the person must the anti gens

Transfusion Rections

• Lead to hemolysis of the blood by the complement system. This reaction will follow lead to kidney failure

Erythroblastosis Fetalis

• Is the condition where mothers will not usually have first arm, but the second is severe

Hemostasis Mechanisms

• 1. Blood Vessel - When blood vessels are cut smooth muscles are triggered.
• 2. Formation of Platelet- When damaged active factors become sticky adhering to collagen.
• 3. Blood clot- Blood has positive feedback to increase plotting Platelets - Contain protein fiber and are active for 18 to 12 days

HemoThrombin

• Hemo thrombin when a vessel is damaged can lead to factors or pathways of active and in active enzymes Almost all plotting factors are formed by the liber can cause poort absorption and that are fat soluble. Hemophilia is caused by an abnormality

Hemostasis

• Involves mechanisms, small cuts vascular, plug.
• Vasoconstriction
• Formation Blood Factors

Conversion of Fibrin

• High the molecules the in 2, 341 are. The is to, and their the broken Action or, positive feedback that the factors actions.

Extrinsic Pathway

• The extrinsic way is caused by trauma to the vascular wall or extavascular tissue. Calcium is required for all clotting