Human Physiology

Chapter 3 - Cellular Level of Organization

Learning Outcomes

Describe the processes of cellular diffusion and osmosis, and explain their role in physiological systems.

Describe carrier-mediated transport and vesicular transport mechanisms used by cells to facilitate the absorption or removal of specific substances.

Explain the origin and significance of the cell membrane potential.

Diffusion + Osmosis

The plasma (cell) is a barrier, but nutrients must get in and products and wastes must get out

Permeability determines what moves in and out of a cell, and a membrane that

Let's nothing in or out is deemed impermeable
Lets anything pass through is freely permeable
restricts /controls movement is selectively permeable

Cell plasma is selectively permeable

Diffusion

Net movement of a substance from area of HIGHER concentration to an area of LOWER concentration

Diffusion is a process where a molecule moves from high concentration to low concentration
Extracellular outside the cell

Osmosis

Diffusion of water across a selectively permeable membrane
Water molecules diffuse across a membrane toward the solution with more solutes

Osmolarity and Tonicity

A cell in an isotonic solution, stays the same size and shape
The cell in a hypotonic solution - in water, may rupture (hemolysis)
A cell in hypertonic solution - loses water and shrinks

Carriers and Vesicles

Carrier-mediated Transport

Proteins transport ions of organic substrates across plasma membrane and exhibit:

Specificity - one transport protein for one set of substrates
Saturation Limits - transport rate dePends on availability of transport proteins and substrates
Regulation - cofactors such as hormones affect activity of carriers
Symport (cotransport) - two substances move in the same direction at the same time
Antiport (countertransport) - one substance moves in while another moves out

FACILITATED DIFFUSION

Is a passive process (no energy required)

Carrier proteins transport molecules too large to fit through channel proteins (like glucose and amino acids)
Molecules bond to receptor site on the carrier protein
Carrier protein changes shape, allowing molecule to pass through
The receptor site is specific to certain molecules

ACTIVE TRANSPORT

Proteins move substrates against concentration gradient
Requires energy, such as ATP and include
Ion pumps that moves ion (Na+, K+, Mg2+) in our out, OR
Exchange pumps moves two ions in opposite simultaneously

Primary Active Transport

Pumping solutes against against a concentration gradient using ATP

Sodium-potassium exchange pump

One ATP powers the movement of 3 sodium ions (Na+) out, and two potassium ions (K+) in

Secondary Active Transport

ATP is required to establish a concentration gradient of one substance in order to passively transport another
Example: Na+ concentration gradient of one substance in order to passively transport another
ATP is used to pump Na+ back out

Vesicular Transport (bulk transport) is an active transport process that requires ATP

Materials move in (endocytosis) or out of (exocytosis) via vesicles (small bubbles of plasma membrane)

Endocytosis (endo = inside) is the importation of extracellular material

Receptor-Mediated Endocytosis - bind target molecules (ligands) and envelop them in a vesicle

Pinocytosis

Endosomes “drink” extracellular fluid

Phagocytosis

Cytoplasmic extension envelope large objects which are engulfed in phagosomes

Exocytosis (exo = outside)

Granules or droplets are released from the cell as vesicles fuse to a plasma membrane

Chapter 12 - Nervous Tissue

Learning Outcomes

Explain how the resting potential is created and maintained.

Describe the events involved in the generation and propagation of an action potential.

Discuss the factors that affect the speed with which action potentials are propagated.

Describe the structure of a synapse and explain the mechanism of synaptic activity.

Describe the major types of neurotransmitters and neuromodulators and discuss their effects on postsynaptic membranes.

Discuss the interactions that enable information processing to occur in neural tissue

Membrane Potential

All plasma (cell) membranes produce electrical signals by ion movements

Membrane potential is particularly important to neurons

Resting membrane potential

The membrane potential of a resting cell

Graded Potential

Temporary, localized change is resting potential
Caused by a stimulus

Action Potential

Is an electrical impulse
Produced by graded potential
Propagates along surface of axon to synapse

Resting Membrane Potential

3 important concepts

The extracellular fluid (ECF) and intracellular fluid (cytosol) differ greatly in ionic composition

Extracellular fluid contains high concentrations of Na+ and Cl-
Cytosol contains high concentrations of K+ and negatively charged proteins

Cells have selectively permeable membranes
Membrane permeability varies by ion

Passive Process acting across cell membrane

Current is the movement of charges to eliminate a potential difference

Resistance is how much the membrane restriction movement

If resistance is high, current is small

Chemical gradients are formed by the concentration gradients of ion Na+, K+

Electrical Gradients are charges that are separated by the cell membrane

Cytosol within the cell is negative relative to extracellular fluid

Electrochemical gradient is the sum of chemical and electrical forces acting on an ion across the membrane

Equilibrium Potential

Membrane potential at which there is no net movement of a particular ion across the cell membrane

-K+ = -90mV

-Na+ = +66mV

- plasma membrane is highly permeable to K= which accounts for most of the resting potential (-70mV)

- resting membranes permeability to Na+ is very low so Na+ has a small effect on resting potential

Active process across the membrane

sodium -potassium exchange pump

Powered by ATP
Ejects Na+ for every 2 K+ brought in (REMEMBER KIN like the program)
Balances passive forces diffusion
KIN 220 The Nervous System
Human Physiology
11
• Active processes across the membrane
o Sodium–potassium exchange pump
Powered by ATP
Ejects 3 Na + for every 2 K+ brought in (REMEMBER KIN, like the program!)
Balances passive forces of diffusion
• Resting membrane potential exists because the cytosol differs from extracellular fluid in chemical and ionic composition and plasma membrane is selectively permeable
Membrane potential changes in response to temporary changes in membrane
permeability
Results from opening or closing of specific membrane channels in response to stimuli
Na + and K+ are the primary determinants of membrane potential
Na + and K+ channels are either passive or active
Passive ion channels (leak channels) are always open
Permeability changes with conditions
Active ion channels (gated ion channels)
o Open and close in response to stimuli
o At resting membrane potential, most are closed

Changes in Resting Membrane Potential

Leak channels (passive channels)

Gated channels (active channels)

Chemically gated channels

Also called ligand-gated ion channels
Open when they bind specific chemicals like acetylcholine (ACh)
Found on the cell body and dendrites neurons

Voltage-gated channels

Respond to changes in membrane potential
Found in axons of neurons and sarcolemma of skeletal and cardiac muscle cells
Activation gate opens when stimulated
Inactivation gate closes to stop ion movement
Three possible states are: closed but capable of opening, open (activated), closed and incapable of opening (inactivated)

Mechanically-gated channels

Respond to membrane distortion
Found in sensory receptors that respond to touch, pressure or vibration

**figure 12-8 for summary

Graded Potentials (local potentials)

Changes in membrane potential that cannot spread far from site of stimulation
Produced by any stimulus that opens gated channel

Example: a resting membrane is exposed to a chemical

Chemically gated Na+ channels open
Sodium ions enter cell
Membrane potential rises (depolarization)
Sodium ions move parallel to plasma membrane producing local current which depolarized nearby region of plasma membrane (graded potential)
The change in potential is proportional to stimulus

Repolarization

When the stimulus is removed, membrane potential returns to normal

Hyperpolarization

Results from opening potassium ion channels
Positive ions move out, not into cell
Opposite effect of opening sodium ion channels
Increases the negativity of the resting potential

Characteristics of graded potentials

Membrane potential is most changed at site of stimulation; effect decreases with distance
Effect spreads passively, due to local currents
Graded change in membrane potential may involve depolarization or hyperpolarization
Stronger stimuli produce greater changes in membrane potential and affect a larger area of the membrane
Often trigger specific cell functions like exocytosis of glandular secretions
ACh causes graded potential at motor end plate at neuromuscular junction

Action Potential (nerve impulses)

Propagated changes in membrane potential that affect an entire excitable membrane
Begin at initial segment of axon and do NOT diminish as they move along the axon
Stimulated by a graded potential that depolarizes the axolemma to threshold - threshold for an axon is -60 to -55mV

Quiz #2 Info

All-or-none principle

Any stimulus that changes the membrane potential to threshold will cause an action potential
All action potentials is either triggered or not

Generation of Action Potentials

Any stimulus that changes the membrane potentials to threshold - will cause an action potential
All action potentials are the same - no matter how large the stimulus - action potentials is either triggered or not

Step 1: depolarization to threshold (-60mV)

Step 2: activation of voltage-gated Na+ channels

Inner membrane surfaces changes from negative to positive
Results in rapid depolarization

Step 3: inactivation of Na+ channels and activation of K+ channels

At +30mV, inactivation gates of voltage-gated Na+ channels close
K+ moves out of cytosol
Repolarization begins
Generation of action potentials

Step 4:

Return to resting membrane potential
voltage -gated K+ channels begin to close
As membrane reaches normal resting potential
K+ continues to leave cell
Membrane is briefly hyperpolarized to -90mV

After all voltage-gated K+ channels finish closing

Resting membrane potential is restored
Action potential is over

Important Class Notes - Monday January 13th

Sodium Channel Open at -60mV and close at a positive number

Potassium leaks out and makes cell repolarize

Refractory period is inplace to ensure that the propagation of the cell body doesn't go back the other way

-70mV A graded dePolarization brings an area of excitable membrane to threshold (-60mV)
Voltage-gated sodium channels open and sodium ions move into the cell, the transmembrane potential rises to +30mV
+30mV Sodium channels close around +10, voltage gated potassium channels open, and potassium ions move out of the cell. REPOLARIZATION BEGINS
Potassium channels close, and both sodium and potassium channels return to their normal states

Refractory Period:

From start of action potential to return to resting state
During which the membrane will not respond normally to additional stimuli

Absolute Refractory Period:

during absolute refractory period, the membrane cannot respond to further stimulation

Relative Refractory Period:

during the relative refractory period, the membrane can respond only to a larger than normal stimulus
Begins when Na+ channels regain resting condition
Continues until membrane potential stabilizes
Only a strong stimulus can initiate another action potential
Depolarization: from Na+ coming in - getting warmer
Repolarization: involves LOSS of K+ - back to normal losing potassium makes it colder

During flushing a toilet - absolute refractory period

Forcing another flush while toilet water fills up - relative refractory period

Propagation

Movement of the action potential along a neuron

Continuous Propagation: slower type of conduction, opening one channel at a time; one person telling another, takes more time

This happens in UNMYELINATED AXONS
Step 1: Action potential develops at initial segment, depolarizes membrane to +30mV
Step 2: Local current develops, depolarizes second segment to threshold
Step 3: Action potential occurs in second segment to threshold, initial segment begins repolarization
Step 4: local current depolarizes next segment, cycle repeats, action potential travels in one direction (1m/sec)

Saltatory Propagation: message is delivered but skips a little bit, the physical properties of the neuron are causing the skip (schwann cells) - form the myelin sheath on neurons

Red= active action potential, causes graded potential in next section
Pink = graded potential, which causes action potential in next section

Propagation Speed:

Type A fibres: large diameter & myelinated, up to 268 mph

Type B fibres: smaller diameter and myelinated, average 40mph
Type C fibres: smaller diameter and unmyelinated, average 2mph (1m per sec)

Synapse - are specialized sites where a neuron communicates with another cell

Presynaptic neuron sends the message
Postsynaptic neuron receives the message

What are the types of synapses?

Electrical
Chemical
Cholinergic

Electrical Synapse - direct physical contact between cells

“Gap junction” where presynaptic and postsynaptic membranes are locked together
Action potentials move quickly and efficiently
Ions pass between cells through pores
Local current affects both cells
Action potentials are propagated quickly
uncommon , but found in some areas of brain, eye, ciliary ganglia

Chemical Synapse - most Common and have signal transmitted across a gap by neurotransmitters

Neurotransmitters: excitatory - causes depolarization and inhibitory - causes hyperpolarization which means its less likely to reach threshold
Receptors: specific for the chemical being released and different cells have different receptors
Only type between neurons and cells
Cells are separated by synaptic cleft

What are the types of Chemical Synapses?

Neuromuscular Junction: synapse between a neuron and skeletal muscle cell
Neuroglandular Junction: synapse between a neuron and a gland cell

Neurotransmitters

Chemical messengers contained within a synaptic vesicles in axon terminal of presynaptic cell
Released into synaptic cleft affecting receptors of postsynaptic membrane
Broken down by enzymes, reabsorbed and reassembled by axon terminal

Function of Chemical Synapses

Axon terminal releases neurotransmitters that bind to postsynaptic plasma membrane
produces localized change in permeability and graded potentials

Action potentials may or may not be generated in postsynaptic cell, depending on

Amount of neurotransmitter released
Sensitivity of postsynaptic cell

Cholinergic Synapse

Neurotransmitter = acetylcholine - releases it at:

All neuromuscular junctions involving skeletal muscle fibres
Many synapses in CNS
All neuron-to-neuron synapses in PNS
All neuromuscular and neuroglandular junctions in parasympathetic divisions of ANS

What are the events at a cholinergic synapse?

Step 1: action potential arrives at axon terminal and depolarizes membrane

Step 2: extracellular calcium ions enter axon terminal and trigger exocytosis of ACh

Step 3: ACh binds to receptors on postsynaptic membrane and depolarize it

Step 4: ACh is removed from synaptic cleft by acetylcholinesterase (AChE)

Synaptic Delay

A synaptic delday of 0.2-0.5 msec occurs between

Arrival of action potential at axon terminal
And effect on postsynaptic membrane
Mostly due to time required for calcium ion influx and neurotransmitter release
Fewer synapses lead to faster responses
Some reflexes involve only one synapse

Synaptic Fatigue

Happens when neurotransmitter cannot be recycled fast enough to meet demands on intense stimuli
Response of synapse weakens until ACh is replenished

Some Ganglionic neurons ACh

Called cholinergic neurons

Effect of sympathetic stimulation caused by the specific receptor activated

Alpha-1 receptors

More common type
Found primarily in smooth muscle cells
Stimulation has excitatory effect

Alpha-2

Found on preganglionic sympathetic neurons
Stimulation lowers cAMP levels in cytoplasm and has inhibitory effect
Coordinated activities of ANS

Beta Receptors

Located on membranes of cells in skeletal muscles,

Neuromuscular junction (skeletal muscle)
Many CNS synapses
All neuron-neuron PNS synapses
All neuromuscular & neuroglandular junctions in PNS

Classes of Neurotransmitters

Excitatory Neurotransmitters cause depolarization of postsynaptic membranes

Promote action potentials in the postsynaptic cell

Inhibitory Neurotransmitters cause hyperpolarization of postsynaptic membranes

Suppress action potentials in the postsynaptic cell

The effect of a neurotransmitter on postsynaptic membrane

Depends on properties of the receptor, not on the nature of the neurotransmitter

Major Classes of Neurotransmitters include

Biogenic amines
Amino acids
Neuropeptides
Dissolved gases

Biogenic Amines

Norepinephrine (NE)

Released by adgrenicguc synapses and has an excitatory/depolarizing effect
Widely distributed in brain and portions of ANS

Dopamine

A CNS neurotransmitter that may be excitatory or inhibitory
Involved in Parkinson's diseases and cocaine use

Serotonin

CNS neurotransmitter that affects attention and emotional states

Amino Acids

Gamma-aminobutyric acid (GAGA)
Inhibitory effect in the CNS that are not well understood

Neuropeptides

Small peptide chains synthesised and released by axon terminal
Many act as neuromodulators
Chemicals released by axon terminals that alter the rate of neurotransmitter release or the response by post-synaptic cell
Effects are long-term and slow to appear
Responses involve multiple steps and intermediary compounds
Affect presynaptic membrane, postsynaptic membrane or both
Released alone or with a neurotransmitter

Dissolved Gases

Nitric Oxide (NO)
Carbon Monoxide (CO)

Neurotransmitters and Neurimodulators may have:

A direct effect on membrane potentials

By opening or closing chemically gated ion-channels
Example: ACh, glutamate, aspartate

An indirect effect through G proteins

Example: E, NE, dopamine, serotonin, histamine, GABA

An indirect effect via intracellular enzymes

Example: lipid-soluble gases (NO, CO)

Indirect effects by second messengers

G Protein links
First messenger (neurotransmitter)
Ans second messengers (ions or molecules in cell)

G proteins include an enzyme that is activated when an extracellular compound binds

Example adenylate cyclase
Produces the second messenger cyclic-AMP (cAMP)

Indirect effects by intracellular enzymes

Lipid-soluble gases (NO,CO)
Diffuse through lipid membranes
Bind to enzyme inside of brain cells

Information Processing is the response of postsynaptic cell (integration of stimuli)

At the simplest level (individual neurons)
Excitatory + inhibitory stimuli can be received simultaneously
Net effect on axon hillock determines if an action potential is produced

Postsynaptic Potentials

Graded potentials developed in a postsynaptic cell in response to neurotransmitters

Types of postsynaptic potentials

Excitatory Postsynaptic Potential (EPSP)

Graded dePolarization of postsynaptic membrane

Inhibitory Postsynaptic Potential (IPSP)

Graded hyperpolarization of postsynaptic membrane
Neuron that receives many IP's is inhibited from producing an action potentials because the stimulation needed to reach threshold is increased

To trigger an action potential

One EPSP is not enough
EPSP (and IPSPs) combine through SUMMATION
Temporal Summation - rapid, repeated stimuli at a single synapse
Spatial Summation - simultaneous stimuli arrive from multiple synapses
A neuron becomes facilitated as EPSPs accumulate and raise membrane potentials closer to threshold, therefore a small stimulus can trigger an action potential
Summation of EPSPs and IPSPs
Neuromodulators and hormones can change membrane sensitivity to neurotransmitters, shifting balance between EPSP’ and IPSP

Summary

Information is relayed in the form of action potentials
Neurotransmitters released at a synapse may have excitatory or inhibitory effects
Neuromodulators can alter rate of neurotransmitter release or response of a postsynaptic neuron
Neurons may be facilitated or inhibited by chemicals other than neurotransmitter so neuromodulators

Response of post-synaptic neuron can be altered by

Neuromodulators or other chemicals that cause facilitation or inhibition
Activity underway at other synapses
Modification of rate of neurotransmitter release through facilitation or inhibition

Chapter 16 - The Autonomic Nervous System and Higher Functions

16-1 Compare the organization of the autonomic nervous system with that of the somatic nervous system, and name the divisions and major functions of the ANS.

16-2 Describe the structures and functions of the sympathetic division of the autonomic

nervous system.

16-3 Describe the types of neurotransmitters and receptors and explain their mechanisms

of action.

16-4 Describe the structures and functions of the parasympathetic division of the

autonomic nervous system.

16-5 Describe the mechanisms of parasympathetic neurotransmitter release and their

effects on target organs and tissues.

16-7 Discuss the functional significance of dual innervation and autonomic tone

AUTONOMIC NERVOUS SYSTEM

Somatic nervous system (SNS) innervates voluntary control of skeletal muscles
Corticospinal pathway controls all voluntary movement

Initiated in the Primary Motor Cortex (aka pRe-central gyrus of the frontal lobe)

Upper motor neuron carries motor info through the CNS and synapse with a lower (aka alpha) Motor Neuron
alpha-MN innervate (control) skeletal muscle and initiate muscle contraction at the neuromuscular junction (NMJ)
Upper and lower motor neurons both release Ach as the primary neurotransmitter

Autonomic Nervous System (ANS) innervates involuntary control of visceral effectors

Visceral Motor Neurons

Preganglionic Neurons (cell bodies) in brainstem and spinal cord
Preganglionic Fibres - axons of preganglionic neurons
After leaving CNS, they synapse on ganglionic neurons (postganglionic neurons)

Autonomic Ganglia

Contain many ganglionic neurons that innervate visceral effectors
Postganglionic Fibres - axons of ganglion neurons

2 divisions of ANS

Sympathetic

Fight or flight
Prepares body to deal with emergencies
Increases alertness, metabolic rate, and muscular abilities

Parasympathetic

Rest and digest
Conserves energy and maintains resting metabolic rate

*Sympathetic and Parasympathetic division usually have opposing effects

If sympathetic division causes excitation, the parasympathetic causes inhibitions
May also work independently
Only one division innervates some structures
May work together with each controlling one stage of a complex process

Responses to increased sympathetic activity

Heightened mental alertness
Increased metabolic rate
Reduced digestive and urinary functions
Activation of energy reserves
Increased respiratory rate and dilation of respiratory passageways
Increased heart rate and blood pressure
Activation of sweat glands

Responses to increased parasympathetic activity

Decreased metabolic rate
Decreased heart rate and blood pressure
Increased secretion by salivary and digestive glands
Increased motility and blood flow in digestive tract
Stimulation of urination and defecation

Sympathetic Division (thoracolumbar division)

Short preganglionic fibres in thoracic and lumbar segments of spinal cord
Preganglionic neurons located between segments T1 and L2
Cell bodies in ;lateral horns of spinal cord with axons entering the anterior roots
Ganglionic neurons in ganglia near spinal cord, except for ADRENAL MEDULLA
Long postganglionic fibres to target organs

Sympathetic chain ganglia are found on either side of vertebral column

One preganglionic fibre synapses on many ganglionic neurons
Superior and inferior fibres interconnect sympathetic chain ganglia, making the chain look like a string of pearls
Each ganglion innervates a particular body organ or group of organs

Ganglionic neurons synapse in 3 locations

Sympathetic Chain Ganglia

On both sides of vertebral column and control effectors in

Body wall
Thoracic cavity
Head
Neck
Limbs

Collateral Ganglia

Anterior to vertebral bodies
Conaton ganglionic neurons that innervate abdominopelvic tissues and visceral organs
All 3 ganglia are named after nearby arteries

Celiac Ganglion

Innervate stomach, liver, gallbladder, pancreas, and spleen

Superior Mesenteric Ganglion

Innervate small intestine and proximal two-thirds of large intestine

Inferior Mesenteric Ganglion

Innervate kidneys, urinary bladder, terminal segments of large intestine and sex organs

ADRENAL GLAND

The center of each adrenal gland is modified sympathetic ganglion
Ganglionic neurons have very short axons
When stimulated, they release neurotransmitters into bloodstream (NOT at synapse) that function as (neuro-) hormones to affect target cells throughout body

Innervated by preganglionic fibres that synapse on cells that secrete

Epinephrine (aka adrenaline)
norepinephrine (aka noradrenaline)
Epinephrine makes up 75-80% if secretory output

The sympathetic division can change the activities of specific effectors

Called sympathetic activation
Occurs during a crisis when stressed or during exercise
The entire division responds
Controlled by sympathetic centers in hypothalamus
Affects peripheral tissues and CNS activity

Changes caused by sympathetic activation

Increased alertness
Feelings of energy and euphoria
Increased blood pressure, heart rate, breathing rate, and depth of respiration
Elevation in muscle tone
Mobilization of energy reserves

**Parasympathetic = ACETYLCHOLINE all the time

SYMPATHETIC EFFECTS

Stimulation of sympathetic preganglionic neurons
Released acetylcholine (ACh) at synapses with ganglion neurons
Effect is always excitatory

Ganglionic Neurons

Release neurotransmitters at target organs
Telodendria form branching networks with swollen segments called varicosities
packed with neurotransmitter vesicles
Membrane recePtors are scattered across target cells

Most Sympathetic Ganglionic Neurons

Release norepinephrine (NE) at varicosities
They Are called adrenergic neurons

Some Ganglionic Neurons Release ACh

Called cholinergic neurons

Alpha Receptors

Alpha-1

More common type
Found primarily in smooth muscle cells
Stimulation has excitatory effect

Alpha-2

Found on preganglionic sympathetic neurons
Stimulation lowers cAMP levels in cytoplasm and has inhibitory effect
Coordinates activities of ANS

Beta Receptors

Located on membranes of cells in skeletal muscles, lungs, heart, liver, etc
Stimulation increases intracellular cAMP levels and triggers metabolic changes
Major types of beta receptors

Beta 1

Stimulation increases metabolic activity

Beta 2

Stimulation triggers relaxation of smooth muscles along respiratory tract

Beta 3

Stimulation leads to lipolysis, the breakdown of triglycerides in adipocytes

PARASYMPATHETIC DIVISION (craniosacral division)

Long preganglionic fibres in brainstem and sacral segments of spinal cord
Ganglionic neurons in peripheral ganglia within or adjacent to target organs
Short postganglionic fibers in or near target organs

Ganglionic neurons in peripheral ganglia

Terminal ganglia are located near target organs and are usually paired
Intramural ganglion are embedded in tissues of target organ

Organization of parasympathetic division

Cranial parasympathetic preganglionic fibers leave the brain via cranial nerves and control visceral structures in the head
III Oculomotor
VII Facial
IX Glossopharyngeal

Vagus nerve provides 75 percent of all parasympathetic outflow and innervates structures in the neck, thoracic and abdominopelvic cavities, including distal portion of large intestine

Branches intermingle with fibers of sympathetic division

Sacral preganglionic fibers carry parasympathetic output through pelvic nerves to innervate intramural ganglia in kidneys, urinary bladder, portions of large intestine, and sex organs

Major Effects of Parasympathetic Division

Constriction of pupils and focusing on near objects
Secretion by digestive glands
Absorption and use of nutrients by peripheral cells
Changes associated with sexual arousal
Increased smooth muscle activity in digestive tract
Stimulation and coordination of defecation
Contraction of respiratory passageways
Reduction in heart rate and force of contraction

PARASYMPATHETIC EFFECTS

All parasympathetic neurons release Ach
Effects on postsynaptic cell vary widely based on receptors activated or the second messengers involved

Effects on parasympathetic stimulation of cholinergic receptors are localized and short lived

Most ACh is inactivated at synapse by acetylcholinesterase (AChE)
ACh that diffuses into surrounding tissues is inactivated by tissue cholinesterase

Cholinergic Receptors

NICOTINIC RECEPTORS

On ganglion cells of sympathetic and parasympathetic divisions
Also occur at neuromuscular junctions of somatic NS
Exposure to ACh causes excitation of ganglion uc neuron or muscle fiber

Muscarinic Receptors

At cholinergic neuromuscular or neuroglandular junctions in parasympathetic divisions
At cholinergic junctions in sympathetic division
G protein-coupled receptors
Effects are longer lasting than nicotinic receptors

Response is excitatory or inhibitory depending on activation or inactivation of specific enzymes

SUMMARY of ANS

Sympathetic division has WIDESPREAD EFFECTS

Two sets of sympathetic chain ganglia, three collateral ganglia, and two adrenal medulla
Short preganglionic fibers, long postganglionic fibers
Extensive divergence
Preganglionic neurons release ACh; most postganglionic fibers release NE
Effector response depends on second messengers

Parasympathetic division has SPECIAL EFFECTS

Visceral motor nuclei are associated with cranial nerve III, VII, IX, X and with S2-S4
Ganglionic neurons are located in ganglia within or next to target organs
Innervates regions serviced by cranial nerves and organs in thoracic and abdominopelvic cavities
One-fifth the divergence of sympathetic division
All neurons are cholinergic
Effects are generally brief and restricted

DUAL INNERVATION

Most vital organs are innervated by both division of ANS
Two divisions commonly have opposing effects
Parasympathetic postganglionic fibers travel by cranial nerves to peripheral detection
Sympathetic innervation reaches for same structures - from superior cervical ganglia of sympathetic chain

Anatomy of dual innervation

Autonomic Plexuses

Nerve networks in the thoracic and abdominopelvic cavities
Formed by mingled sympathetic postganglionic fibers and parasympathetic preganglionic fibers

Travel with blood and lymphatic vessels that supply visceral organs

Cardiac plexus

Pulmonary plexus

Esophageal plexus

Celiac plexus (aka solar plexus)

Inferior mesenteric plexus
Hypogastric plexus

Autonomic tone

Autonomic motor neurons have resting level of activity, even without stimulation

Important aspect of ANS function

Because nerves maintain background level of activity, they can increase or decrease activity
Provides greater range of control

Significant where dual innervation occurs, more important where it does not occur

The heart receives dual innervation

Acetylcholine released by parasympathetic postganglionic fibers slows heart rate
NE released by varicosities of sympathetic division accelerates heart rate
Small amounts of both are released continuously, producing autonomic tone

Parasympathetic division dominates at rest

Crisis speeds heart rate by stimulating sympathetic and inhibiting parasympathetic nerves

Some organs are innervated by only one division

Example: sympathetic control of blood vessel diameter
NE is released from sympathetic fibers at smooth muscle cells in blood vessel walls
Sympathetic tone keeps smooth muscles partially contracted

When more blood flow is needed,

Rate of NE release decreases

Sympathetic cholinergic fibers are stimulated

Smooth muscle cells relax and blood vessel dilates

Important Class Notes from Wednesday January 15th

Neurotransmitters and Neuromoduluators

Neurotransmitters

Excitatory neurotransmitters cause depolarization of postsynaptic membranes
Promote action potentials in the postsynaptic cell

Inhibitory neurotransmitters cause hyperpolarization of postsynaptic membranes

Suppress action potentials in the postsynaptic cell
If inhibitory and excitatory postsynaptic potentials come together they cancel each other out

Chapter 18 - Endocrine System

Explain the importance of intercellular communication,describe the mechanisms

involved, and compare the modes of intercellular communication that occur in the

endocrine and nervous systems.

18-2 Compare the cellular components of the endocrine system with those of other systems,

contrast the major structural classes of hormones, and explain the general mechanisms

of hormonal action on target organs.

18-3

Describe the location, hormones, and functions of the pituitary gland, and discuss the

effects of abnormal pituitary hormone production.

18-4

Describe the location, hormones, and functions of the thyroid gland, and discuss the

effects of abnormal thyroid hormone

production.

18-6

Describe the location, structure, hormones, and general functions of the adrenal glands,

and discuss the effects of abnormal adrenal hormone production.

18-8

Describe the location, structure, hormones, and functions of the pancreas, and discuss

the effects of abnormal pancreatic hormone production.

18-10

Explain how hormones interact to produce coordinated physiological responses and

influence behavior, describe the role of hormones in the general adaptation syndrome,

and discuss how aging affects hormone production and give examples of interactions

between the endocrine system and other organ system

Quiz 3

Nervous System vs. Endocrine System

Both Systems:

Rely on chemicals binding to specific receptors on target cells
Share many chemical messengers (ex: epinephrine, norepinePhrine)
Rely on negative feedback for regulation
Share a common goal of preserving homeostasis by regulating activities in cells, tissues, organs and systems

Negative feedback loop

Set point
Stimulus change
Sensor/detector
Comparator/integrator
Effector

Classes of Hormones

Based on Chemical Structure

Amino acid derivatives
Tyrosine is the precursor to thyroid hormones
tryotisohan is the precursor to

Learning Outcomes

18-1Explain the importance of intercellular communication, describe the mechanisms

involved, and compare the modes of intercellular communication that occur in the

endocrine and nervous systems.

18-2

Compare the cellular components of the endocrine system with those of other systems,contrast the major structural classes of hormones, and explain the general mechanisms of hormonal action on target organs.

18-3

Describe the location, hormones, and functions of the pituitary gland, and discuss the effects of abnormal pituitary hormone production.

18-4

Describe the location, hormones, and functions of the thyroid gland, and discuss the

effects of abnormal thyroid hormone production.

18-6

Describe the location, structure, hormones, and general functions of the

adrenal glands, and discuss the effects of abnormal adrenal hormone production.

18-8

Describe the location, structure, hormones, and functions of the pancreas, and discuss the effects of abnormal pancreatic hormone production.

18-1 0

Explain how hormones interact to produce coordinated physiological responses and influence behavior, describe the role of hormones in the general adaptation syndrome, and discuss how aging affects hormone production and give examples of interactions between the endocrine system and other organ systems.

18-1 Intracellular Communication

Mechanisms of intracellular communication

Direct Communication

Exchange of ions and molecules between adjacent cells across gap junctions
Occurs between two cells of the same type
Highly specialized and relatively rare

Paracrine Communication

Chemical signals transfers information from cell to cell within a single tissue
Mechanisms of intercellular communication
Chemicals involved are paracrines

Autocrine Communication

Messages affect the same cells that secrete them
Chemicals involved are autocrines
Example: prostaglandins secreted by smooth muscle cells cause the same cells to contract

Endocrine Communication

Endocrine cells release chemicals (hormones) that are transported in bloodstream
Alters metabolic activities of many organs

Target Cells

Have receptors needed to bind and “read” hormonal messages

Hormones

Changes types, quantities, or activities of enzymes and structural proteins in target cells
Can alter metabolic activities of multiple tissues and organs at the same time
Affect long-term processes like growth and development

Both endocrine and nervous systems rely on release of chemicals that bind to specific receptors on target cells

Share many chemical messengers (ex: epinephrine and norepinephrine)
Are regulated mainly by negative feedback
Function to preserve homeostasis by coordinating and regulating activities

Endocrine System

Includes all endocrine cells and tissues that produce hormones or paracrines
Endocrine cells release secretions into extracellular fluid (unlike exocrine cells which release through a duct)
Endocrine organs are scattered throughout body

Classes of Hormones

Amino Acid Derivatives
Peptide Hormones
Lipid Derivatives

Amino Acid Derivatives (biogenic amines)

Small molecules structurally related to amino acids

Derivatives of tyrosine include:

Thyroid hormones
Catcholimes (epinephrine, norepinephrine, and dopamine_

Derivatives of tryptophan

Serotonin and melatonin

Peptide Hormones

Chains of amino acids
Ost are synthesized as inactive prohormones
Inactive molecules converted to active hormones before or after hey are secreted

Glycoproteins

Proteins more than 200 amino acids long that have carbohydrate side chains (eg.TSH, LH, FSH)

Short Polypeptides/Small Proteins

Short-Chain Polypeptides

ADH and OXT are each 9 amino acids long

Small Proteins

Insulin (51 amino acids)
Growth hormone (191 amino acids)
Prolactin (198 amino acids)

Includes all hormones secreted by hypothalamus, heart, thymus, digestive tract, pancreas, posterior lobe of pituitary gland etc

Not lipid soluble, so they are unable to penetrate plasma membrane

Bind to receptor proteins on outer surface of plasma membrane (extracellular receptors)

Lipid Derivatives

Eicosanoids - derived from arachidonic acid, a 20-carbon fatty acid

Paracrines that coordinate cellular activities and affect enzymatic processes (such as blood clotting)
Some eicosanoids (such as leukotrienes) have secondary roles as hormones
Prostaglandins coordinate local cellular activities
Converted to thromboxanes and prostacyclins in some tissues

Steroid Hormones - derived from cholesterol, remain in circulation longer than peptide hormones and include:

Androgens from testes in males
Estrogens and progesterone from ovaries in females
Corticosteroids from adrenal
Calcitriol from kidneys
Steroids are lipid soluble, allowing them to diffuse across plasma membrane and bind to receptors inside cell (intracellular receptors)

Transport and Inactivation of Hormones

Hormones may circulate freely or travel bound to special carrier proteins

Free hormones remain functional for less than an hour an hour and are inactivated when they:

Diffuse out of bloodstream and bind to receptors on target cells
Are absorbed and broken down by liver, or kidneys or
are broken down by enzymes in blood or interstitial fluid

Mechanisms of hormone action

Binding of a hormone may

Alter genetic activity
Alter rate of protein synthesis

Hormone Receptors

Protein molecules to which a particular molecules binds strongly
Different tissues have different combos of receptors
Presence or absence of a specific receptor determines hormonal sensitivity of a cell

Down-Regulation

Presence of a hormone triggers a decrease in the number of hormone receptors
When levels of a particular hormone are high, cells become less sensitive to it

Up-Regulation

Absence of a hormone triggers an increase in the number of hormone receptors
When levels of a particular hormones are low, cells become more sensitive to it

Hormones and extracellular receptors

First messengers are the hormones that bind to extracellular receptors

Promote release of a “second messenger” inside the cell

Second Messenger

Intermediary molecule that appears due to hormone - receptor interaction
May act as enzyme activator, inhibitor, cofactor
Results in change in rates of metabolic reactions

Process of amplification

When a small number of hormone molecules binds to extracellular receptors
Thousands of second messengers may appear
Magnified effect of hormone on a target cell

G Proteins and cAMP

Steps involved in increasing cAMP levels, which accelerates metabolic activity of cell

Activated G Protein activates adenylate cyclase
Adenylate cyclase converts ATP to cyclic AMP
Cyclic AMP functions as a second messenger
generally , cyclic AMP activates kinases that phosphate proteins

Increase in cAMP level is usually short-lived
Phosphodiesterase (PDE) converts cAMP to AMP
G Proteins and calcium ions

G Protein activates phospholipase C (PLC)
Triggers receptor cascade beginning with production of diacylglycerol (DAG) + inositol triphosphate (IP3) from phospholipids
IP3 diffuses into cytoplasm and triggers release if Ca+ from intracellular reserves
Calcium ion channels open due to activation of protein kinase C (PKC) and Ca2+ enters cell
Ca2+ binds to calmodulin activating enzymes

Hormones and Intracellular Receptors

Steroids hormones can alter rate of DNA transcription in nucleus
Alterations in synthesis of enzymes or structural proteins

Thyroid hormones bind to receptors within nucleus and on mitochondria

Activate genes or change rate of transcripTION
Increases rates if ATP production

Hormone Secretion

Mainly controlled by negative feedback
Stimulus triggers production of hormone that reduces intensity of the stimulus

Can be triggered by

Humoral Stimuli - glandular cells detect a change in extracellular fluid and respond to maintain homeostasis
Hormonal Stimuli - glandular cell that gets stimulated by arrival or removal of a hormone
Neural Stimuli - glandular cell is stimulated by the arrival of neurotransmitters at the neuroglandular junction (ex: epinephrine)

Control of Hormone Secretion

May involve only one hormone

Humoral Stimuli

Control hormone secretion by heart, pancreas, parathyroid gland, and digestive tract

Hormonal Stimuli

May involve one or more intermediary steps
Two or more hormones involved

Neural Stimuli

Hypothalamus provides highest level of control

Pituitary Gland - (hypophysis)

Lies within sella turcica of the sphenoid bone
Hangs inferior to hypothalamus and is connected by infundibulum

Releases 9 important peptide hormones that:

Bind to extracellular receptors
Use cAMP as second messenger

2 distinct portions of pituitary gland:

Anterior Lobe (adenohypophysis)

Adenohypophysis has endocrine function
Is regulated by the hypothalamus
Produces 6 hormones that “turn on” endocrine glands or support functions of other organs

Posterior Lobe (neurohypophysis)

Neurohypophysis is neural tissue
Contains unmyelinated axons of the hypothalamic neurons that produce 2 hormones

HYPOTHALAMUS

Regulates functions of the pituitary g;alnd
Synthesizes antidiuretic hormone (ADH) & oxytocin (OXT) and transports the to the posterior pituitary gland for release
Secretes regulatory hormones that control secretory activity of anterior pituitary gland
Contains autonomic centres that exert direct control over adrenal medulla release norepinephrine and epinephrine

Portal Vessels

Blood vessels that link two capillary networks
Entire complex is a portal system

Hypophyseal Portal System

Ensures that regulatory hormones reach cells in anterior pituitary before entering general circulation
Another important portal system delivers blood from the absorptive surfaces of the intestines to the liver and is called the hepatic portal system

Hypothalamic control of Anterior Lobe

Two classes of hypothalamic regulatory hormones

Releasing Hormones (RH)

Stimulate synthesis and secretion of one or more hormones at anterior lobe

Inhibiting Hormone (IH)

Prevent synthesis and secretion of hormones from anterior lobe
Rate of secretion is controlled by negative feedback

Hormones of the Anterior Lobe

Thyroid-Stimulating Hormone (TSH)

Released by thyroid releasing hormone

Adrenocorticotropic Hormone (ACTH)

Released due to corticotropin-releasing hormone (CRH) from hypothalamus

Prolactin (PRL)

Release INHIBITED by prolactin-inhibiting hormone (PIH)
Release STIMULATED by prolactin-releasing hormone (PRH)

Growth Hormone (GH) or somatotropin

Growth hormone stimulates:

Liver cells to release somatomedins that stimulate tissue growth
Skeletal muscle fibers and other cells increase uptake of amino acids
Stem cells in epithelia and connective tissues to divide
Breakdown of triglycerides in adipocytes, which leads to glucose sparing effect
Breakdown of glycogen by liver cells causing diabetogenic effect

Production of growth hormone is regulated by:

Growth hormone-releasing hormone (GH-RH)
Growth hormone-inhibiting hormone (GH-IH)

Gonadotropins are a class of hormones

Are stimulated by gonadotropin-releasing hormone (GnRH)

Follicle-Stimulating Hormone (FSH)
Luteinizing Hormone (LH)

In females, it induces ovulation and stimulates secretion of estrogens and progesterone
In males, it stimulates production of androgens

Hypogonadism

Caused by low production of gonadotropins

Hormones of the Posterior Lobe

Antidiuretic Hormone (ADH)

Stimulates water retention in kidneys

Oxytocin (OXT)

Stimulates contraction of uterus during labour
Promotes ejection of milk after delivery

Pars Intermedia is the area between the anterior and posterior lobes and secretes:

Melanocyte-Stimulating Hormone (MSH)

Stimulates melanin production
Virtually nonfunctional in adults except in rare cases and pregnancy

Thyroid Gland

Lies inferior to thyroid cartilage of larynx
Consists of 2 lobes connected by isthmus

Thyroid Follicles

Hollow spheres filled with a fluid called colloid
Surrounded by capillaries
Cells absorb iodide ions (I-) from blood

C (clear) Cells

Produce calcitonin (CT)
Helps regulate concentrations of Ca2+ in body fluids
Stimulates Ca2+ exertion by kidneys
Prevents Ca2+ absorption by digestive tract

Thyroid Hormones

Thyroxine (T4) or tetraiodothyronine

Contains four iodine atoms

Triiodothyronine (T3)

Contains 3 iodine atoms

Thyroid-binding globulins (TBG’s)

Proteins that bind about 75% of T4 and 70% of T3 entering the bloodstream

Thyroid-Stimulating Hormone (TSH)

Absence causes thyroid follicles to become inactive
Neither synthesis nor secretion occurs
Binds to plasma membrane receptors
Activates key enzymes in thyroid hormone production

Thyroid Hormones

Affect almost every cell in body
Enter target cells by transport system

Bind to intracellular Receptors

In cytoplasm
On surfaces of mitochondria
In nucleus
In children, essential to normal development of skeleton, muscles and nerves

Thyroid Hormones activate genes involved in glycolysis and ATP production

Results in calorigenic effect

Increased energy consumption and heat generation of cells
Responsible for strong, immediate, and short-lived increase in rate of cellular metabolism

Effects of thyroid hormones

Elevate oxygen and energy consumption; in children, may cause rise in body temperature
Increase heart rate and force of contraction
Increase sensitivity to sympathetic stimulation
Maintain normal sensitivity of respiratory centers to oxygen and carbon dioxide concentrations
Stimulate red blood cell formation
Stimulate activity in other endocrine tissues
Accelerate turnover of minerals in bone

Adrenal Glands

Lie along superior border of each kidney

Adrenal Medulla - Inner Part

Secretory activities controlled by sympathetic division of ANS
Produces epinephrine & norepinephrine (Catecholamines)

Contains 2 types of secretory cells

One produces epinephrine, 75-80% of medullary secretion
other produces norepinephrine (NE) 20-25% of medullary secretion

Results of activation of Adrenal Medulla

SKELETAL MUSCLES: epinephrine and norepinephrine trigger mobilization of glycogen reserves and increase glucose breakdown

ADIPOSE TISSUE: stored fats are broken down into fatty acids
LIVER: glycogen molecules are broken down
HEART: stimulation of BETA 1 receptors speeds and strengthens cardiac muscle contraction

Adrenal Cortex - Superficial Part

Stores lipids, especially cholesterol and fatty acids
Manufactures steroid hormones (Corticosteroids)

HAS 3 ZONES

Outer Zona Glomerulosa
Middle Zona Fasciculata
Inner Zona Reticularis

Outer Zona Glomerulosa (outer region of adrenal cortex)

Produces mineralocorticoids like aldosterone
Stimulates conservation of sodium ions and elimination of potassium ions increases sensitivity of salt receptors in taste buds

Secreted in response to:

Drop in blood Na+, blood volume, or blood pressure
Rise in blood K+ concentration

Zona Fasciculata (middle region of the adrenal cortex)

Produces glucocorticoids like cortisol
Secretion is regulated by negative feedback

Glucocorticoids have inhibitory effect on production of

Corticotropin-releasing hormone (CRH) in hypothalamus
ACTH in anterior pituitary

Effects of glucocorticoids

Accelerate glucose synthesis and glycogen formation, especially in liver
Have anti-inflammatory effects
Inhibits activities of white blood cells and other components of immune system

Zona Reticularis (inner region of adrenal cortex)

Produces small quantities of androgens under stimulation by ACTH
Some are converted to estrogen in bloodstream
Stimulate development of pubic hair before puberty

PANCREAS

Large gland
Lies in loop between inferior border of stomach and proximal portion of small intestine
Mostly retroperitoneal
Contains both exocrine & endocrine cells

Exocrine Pancreas

Consists of clusters of gland cells called pancreatic acini and their attached ducts
Takes up roughly 99% of pancreatic volume
Gland and duct cells secrete alkaline, enzyme-rich fluid which pass through a network of ducts to lumen of digestive tract

Endocrine Pancreas

Consists of cells that form clusters know as pancreatic islets (islets of Langerhans)
Alpha cells produce glucagon
Beta cells produce insulin

When blood glucose level increases, beta cells secrete insulin stimulated transport of glucose INTO target cells

When blood glucose level decreases, alpha cells secrete glucagon stimulating glycogen breakdown and glucose release by liver

Insulin

Peptide hormone released by beta cells

Effects on Target Cells

Accelerating glucose uptake
Accelerating glucose use and enhancing ATP production
Stimulating glycogen formation in liver and skeletal muscle
Stimulating amino acid absorption and protein synthesis
Stimulating triglyceride formation in adipocytes

Glucagon

Released by alpha cells
Mobilizes energy reserves

Effects on target cells

Stimulating breakdown of glycogen in skeletal muscle fibers and liver cells
Stimulating production and release of glucose in liver cells (gluconeogenesis)

Hyperglycemia

Abnormally high glucose levels in the blood

Diabetes Mellitus

Characterised by high glucose concentration that overwhelm reabsorption capabilities of kidneys
Glucose appears in urine
Polyuria - urine volume becomes excessive

Type 1 Diabetes Mellitus

Characterised by inadequate insulin production by pancreatic beta cells
Patients require daily injections or continuous infusion of insulin
Approximately 5 percent of cases
Usually develops in children and young adults

Type 2 Diabetes Mellitus

Most common form
Usually normal amounts of insulin are produced, at least initially
When tissues don’t respond properly its called insulin resistance
Associated with obesity - weight loss is an effective treatment

Complications of untreated or poorly managed diabetes mellitus includes:

Kidney degeneration
Retinal damage (diabetic retinopathy)
May lead to blindness
Early heart attacks (3-5 times more likely)
Peripheral nerve problems (diabetic neuropathies)
Peripheral tissue damage due to reduced blood flow
Tissue death, ulceration, infection and amputation

HORMONE INTERACTIONS

When a cell receives instructions from 3 hormones at the same time, 4 outcomes are possible

Antagonistic Effect

Result depends on balance between 2 hormones - insulin & glucagon

Synergistic Effect

Additive effect
Testosterone and follicle-stimulating hormone (FSH)

Permissive Effect

One hormone is needed for another to produce effect
estrogen/progesterone and prolactin

Integrative Effect

Hormones produce different but complementary results
Secretion and cholecystokinin (CCK)

Stress

Any condition that threatens homeostasis
General Adaptation Syndrome (GAS) aka stress response
How body responds to stress-causing factors

Divided into 3 phases

Alarm phase
Resistance phase
Exhaustion phase

General Adaptation Syndrome

Alarm Phase

Intermediate response to stress
Directed by sympathetic division of ANS
Energy reserves (mainly glucose) are mobilized
Body prepares “fight or flight” responses
Epinephrine is dominant hormone

Resistance Phase

Occurs if stress lasts longer than a few hours
May last for weeks or months
Glucocorticoids are dominant hormones
Lipids and amino acids are mobilized for energy
Glucose is conserved for use by nervous tissue

Exhaustion Phase

Begins when homeostatic regulation breaks down
Drop in K+ levels due to aldosterone produced in resistance phase
Failure of one or more organ systems will be fatal