Phys Midterm #1

• Homeostasis maintains 7 key variables within a specific range

• Body temperature

• Blood sugar levels

• Blood pH

• Oxygen and Carbon Dioxide levels

• Blood pressure

• Electrolyte balance

• Water balance

• Feedback loop components work together to maintain homeostasis

• Regulated variable

• Sensor

• Control center

• Effectors

Body Fluid Compartments

• Intracellular fluid makes up 67% of total body fluid, is high in potassium and protein, featuring a negative charge inside the cell membrane
• Blood plasma, 6.6% of body fluid, consists mainly of water (98%) and various substances, facilitating transport of blood cells
• Interstitial fluid bathes cells, allowing for nutrient and gas exchange, comprising 26.7% of body fluid, and contains more sodium, chloride, and calcium than intracellular fluid

Chemical Composition Maintenance

• Non-charged molecules freely cross cell membranes
• Charged molecules require protein channels
• The phospholipid bilayer is hydrophobic and lipophilic

Sodium/Potassium Pump

• Pumps 3 sodium ions out and 2 potassium ions in, requiring ATP

Osmosis

• Osmosis is the movement of water across a semi-permeable membrane down a concentration gradient
• Water crosses membranes via aquaporins
• Solvent: the liquid in which a substance is dissolved
• Solute: the substance being dissolved
• Solution: the combination of dissolved solute in a solvent

Factors Affecting Osmosis

• Permeability
• Concentration gradient of solutes in intracellular and interstitial fluids
• Pressure gradient can affect osmosis

Units of Osmosis

• Osmolarity: number of osmoles per kilogram of water
• Osmolality: number of osmoles per liter of water

Calculating Osmolality

• A 1 molar solution of NaCl dissociates into Na+ and Cl- in water, resulting in 2 osmotically active particles, equaling 2 osmoles per kilogram of water

Osmotic Pressure and Tonicity

• Osmotic pressure is the force needed to halt water movement
• Tonicity describes a solution's ability to cause water movement into or out of a cell

Protein Roles and Functions

• Proteins ensure systems function properly
• Proteins build other proteins, such as DNA polymerase
• Proteins provide structure (actin)
• Proteins act as messengers for signaling (neurotransmitters, hormones)
• Proteins control chemical reactions (enzymes)
• Proteins regulate substance movement across cell membranes

Membrane Proteins

• Cell identity markers distinguish self from non-self cells
• Cell surface receptors receive extracellular signals and transmit intracellular messages
• Ion channels allow specific ions to move across membranes
• Cell-cell adhesion proteins mediate cell interactions and maintain tissue integrity
• Transporters facilitate molecule movement across membranes, either along or against a concentration gradient
• Enzymes catalyze reactions for signaling, transport, or breakdown

Hypertonic, Isotonic, and Hypotonic Solutions

• Hypertonic solution: higher solute concentration outside of a cell, causing water to rush out and shrink the cell
• Isotonic solution: equal solute concentration inside and outside the cell, resulting in no net water movement
• Hypotonic solution: lower solute concentration outside of a cell, causing water to rush in and swell the cell

Resting Membrane Potential

• The resting membrane potential is the electrical charge difference across the cell membrane when the cell is at rest
• Primarily caused by uneven ion distribution, generating a negative charge
• Typically -70 millivolts
• Electrochemical gradient is created by chemical concentration and electrical potentials

Excitable Cells

• Use resting membrane potential to generate electrochemical impulses (action potentials)
• Includes neurons, muscle cells, and some endocrine cells

Depolarization Events

• Resting potential: Potassium channels are leaky, sodium and chemically gated potassium channels are closed
• Depolarization: Sodium rushes in as voltage-gated sodium channels open, making the cell more positive
• Repolarization: Voltage-gated potassium channels open and voltage-gated sodium channels close.
• Hyperpolarization: Chemically gated potassium channels open, causing the cell to become too negative and preventing action potential

Excitatory Post-Synaptic Potentials (EPSPs)

• Localized depolarizations that do not trigger an action potential alone
• Strength depends on stimulus size
• Can combine to reach threshold for an action potential
• Diminish as they move from the stimulus
• Neurotransmitters cause sodium and potassium channels to open, increasing the likelihood of reaching action potential threshold

Inhibitory Post-Synaptic Potentials (IPSPs)

• Localized hyperpolarizations, making the inside of the cell more negative
• Graded and can summate
• Inhibit action potentials by moving the neuron further from threshold
• Diminish over distance like EPSPs
• Results from opening potassium (out) or chloride (in) channels

Graded Potentials Properties

• Size depends on stimulus, and decay over distance

• Can be summed through:

• Temporal summation: repeated input from one neuron

• Spatial summation: input from multiple neurons at once

• Summation at the axon hillock determines whether an action potential is triggered

AP Propagation

• Action potentials propagate from the soma down the axon towards the axon terminals
• This unidirectionality is due to refractory periods, which prevent another action potential from being elicited while ion channels are inactive

Synapse

• Neurons communicate via synapses

• Impulses passed from one cell to the next

• Electrical: directly exchange info through channels

• Chemical: excitable cells release chemical called neurotransmitters to communicate (presynaptic neuron, synaptic cleft, postsynaptic neuron)

• The action potential reaches the axon terminal and depolarizes the pre-synaptic membrane

• Voltage-gated calcium channels open, triggering biochemical reactions that allow synaptic vesicles to fuse with the pre-synaptic membrane

• Neurotransmitters release into the synaptic cleft

Neurotransmitters

• Neurotransmitters bind to receptors on the post-synaptic membrane

• Diffuse out of the synapse down concentration gradients

• Broken down by enzymes that are located in the synaptic cleft or on the post-synaptic membrane

• Re-uptake into the pre-synaptic cell to be recycled

• Neurotransmitters bind to ligand-gated receptors on the post-synaptic membrane

• Can be ion channels

• Can trigger events that lead to opening of ion channels

• Binding neurotransmitters to receptors

• Leads to depolarization

• Leads to hyperpolarization

Neuromuscular Junction (NMJ) Overview

• Signals travel from CNS -> upper motor neuron -> lower motor neuron -> skeletal muscle.
• Neurotransmitters are released at chemical synapses into the synaptic cleft
• The post-synaptic cell is a muscle cell

Steps of Neuromuscular Transmission

• Action potential arrives at the axon terminal of the pre-synaptic neuron
• Voltage-gated Calcium channels open allowing calcium to enter the pre-synaptic neuron
• Calcium causes synaptic vesicles to fuse with membrane and release acetylcholine(ACH)
• ACH binds to ligand-gated nicotinic receptors on the muscle cell -> Na and K -> depolarization
• ACH is degraded by acetylcholinesterase into acetate and choline choline is recycled

Types of ACH Receptors

• Nicotinic
  • Found at NMJs and autonomic post-ganglionic cells
  • Ligand-gated ion channels (ionotropic)
  • Allow direct ion flow after ACH binding
• Muscarinic
  • Found on smooth and cardiac muscle
  • G-protein coupled receptors (metabotropic)
  • ACH binding triggers intracellular signaling to open ion channels indirectly

Myasthenia Gravis

• Autoimmune neuromuscular disorder causing skeletal muscle weakness
• The immune system produces antibodies against nicotinic receptors
  • Blocks acetylcholine binding
  • Reduces number of receptors
  • Flattens motor end plate folds, reducing surface area
• Result: Decreased muscle cell excitation = muscle weakness

Therapeutic Approach

• No cure, but symptoms can be managed
• Acetylcholinesterase inhibitors are used
• Slow Ach breakdown
• Keep Ach in synaptic cleft longer
• Increases chance ACH binds to the remaining nicotinic receptors
• Nicotinic receptors are all ACH-binding receptors

Case Study: Highlights

• Patient Marr
• Experiences: Generalized muscle weakness and fatigue
• Notable signs:
  • Cogan's lid twitch (diagnostic indicator)
• Electrical stimulation shows reduced muscle response -> supports Myasthenia Gravis diagnosis

Neuromuscular Junction (NMJ)

• Acetylcholine is the neurotransmitter that motor neurons release to communicate with skeletal muscle cells
• The NMJ consists of the motor neuron, synapse, and motor end plate(folded for more surface area)
• Synaptic vesicles in the axon terminal store and release acetylcholine into the synaptic cleft

Properties of Skeletal Muscle cells

• Cylindrical, multinucleated, and striated
• Contain numerous mitochondria for ATP production
• Myofibrils within muscle cells are bundles of myofilaments

Myofilaments

• Thin Filaments: composed of
  • actin(with myosin binding sites)
  • tropomyosin( covers binding sites at rest)
  • troponin(binds actin,calcium and tropomyosin)
• Thick Filament:
• made of myosin with heads that bind actin and ATP
• Myosin heads perform a "power stroke" during contraction

Sarcomere:

• the functional contractile unit of muscle, defined by 2-lines
• contains
  • Thin filaments anchored to 2-lines
  • Thick filaments anchored to M-lines
  • Band: at rest, band (thin filaments only)
  • Band: (length of thick filaments)
  • Band: (gap between thin filaments)
• Shortens during contraction as thin filaments slide over thick filaments

Sliding Filament Theory:

• Contraction occurs as myosin heads bind to actin,perform power strokes and pull thin filaments toward the M-line.
• 2-lines move closer together without changing the length of the filaments.

Excitation-Contraction Coupling

• Action potentials trigger calcium release from sarcoplasmic reticulum.
• Calcium binds troponin exposing to myosin sites on actin
• ATP is required for cross-bridge cycling and calcium reuptake

Rigor Mortis

• Occurs after death due to lack of ATP -Prevents the detachment of actin-myosin cross-bridge,preventing calcium from going back up

Motor Unit and Muscle Twitch

• Motor unit consists of motor neuron an all the muscle fibers it innervates.

Muscle Twitch Phases

• Latent Period (calcium release)
• Contraction Period (cross-bridge cycling)
• Relaxation period (calcium reuptake)
• Smooth movement is achieved through asynchronous firing of motor units

Graded Muscle Contractions

Increased force is achieved Through

• Motor unit recruitment (activating more units)
• Summation(reduce relaxation time)
• Complete tetanus occurs (so frequent no relaxation)

Somatic Nervous System Overview

• Part of the Peripheral Nervous System(PNS) responsible for voluntary movement
• Coordinates skeletal muscle activity via motor neurons at the neuromuscular junction
• Includes
  • Primary motor cortex
  • Premotor area
  • Supplementary Motorarea
  • Basal ganglia -Spinal Pathways -Motor nerves
  • Muscle Receptors

Motor Cortex Function

• Premotor Cortex: plans movement strategies
• Supplementary Motor Cortex: Programs Complex repetitive movements
• Primary Motor Cortex:
  • Located in the pre-central gyrus
  • Controls specific muscles via topographical map of body parts
  • Sends Signals to muscles through the corticospinal tract

Corticospinal Tract

• Major pathway in motor cortex to muscles
• Divides in contralateral (80%) and ipsilateral (20%) fibers at the medulla
• Synapses with lower motor neurons in the spinal cord to activate muscles

Proprioception- ability to sense the body position and movement without visual input

• Rilies on
• Muscle Spindles: detect length changes
• Golgi tendon Organs:Measure force to muscles

Muscle Spindles

• Infrafusal fibers within muscles signal length or velocity changes to CNS
  • Primary afferents detect the speed
  • Second afferents detect strength change

Golgi Tendon Organs.

• Located between muscle fibers and tendons
• Detect force/load applied to muscles and send signals to the CNS

Alpha- Gamma Coactivation

• Ensure muscle spindles remain sensitive during contraction
• A motor neurons contract extrafusal fibers that adjust in frafusa fibers

Reflex arcs

• Involve afferent (sensory) pathways sending signals to the Cns and efferent(motor) pathways activating muscles
• Example stretch relfex