Regulation & Integration of the Human Body

physiology

the study of function in all living organisms and their underlying components, including processes such as respiration, circulation, and digestion.

anatomy (structure) determines function, so a change in structure…

changes function

ex. a typical heart can fill and pump, but a ddilated cardiomyopathy heart can fill but cannot pump

homeostasis

dynamic state of equilibrium

what does homeostasis do?

maintains a relatively constant internal environment

requirements of life

oxygen/atmospheric pressure (Hb), nutrients (macro/micro/energy), water (50-60% of body), temperature (pH)

nervous system

fast acting and hardworking

endocrine system

slow acting through diffusing chemical messengers

what’s the flow of information in a nerve?

The dendrites receive the message, and there is a transmission of electrical impulses (AP) along the axon, which are generated by changes in membrane potential and propagated to the axon terminals, where neurotransmitters are released to signal adjacent neuron dendrites or target tissues

what’s the flow of information in a blood vessel?

hormones diffuse or are actively transported to a receptor cell (target) and are transcribed into an action (effect)

compartmentalization

separate functional areas of our body

how do we manage transport from internal/external environments?

compartments → separate distinct functional areas → buffer changes in the local internal environment

excitable membrane

any plasma membrane that can hold an electrical charge and propagate an electrical signal

ex. neurons (transport electrical impulses) and muscles (contract and produce force)

neurons

transport electrical impulses

muscles

contract and produce force

simple diffusion

the motive force for passive transport is the concentration gradient (relative difference in gradient energy)

fick’s law of diffusion

V = (D × (P₁ - P₂) × A) / T

D =

diffusion coefficient

P

partial pressure

A

surface area

T

thickness of barrier

the speed of diffusion is influenced by

concentration (higher concentration difference increases speed), molecular size (smaller molecules diffuse faster), and temperature (↑ temp ↑ speed ↑ diffusion)

simple diffusion works well…

over short distances, it facilitates greater effect (chemical gradient, electrical gradient, pressure gradient)

resting membrane potentials

the electrical charge across a cell's membrane when it is not actively sending signals. all excitable membranes have a non-zero potential at rest.

what is a neuron’s resting membrane potential?

-70 mV

what is a muscle cell’s resting membrane potential?

-85 mV

at rest, the membrane is more permeable to…

K+ than to Na+

nernst equation

Ecell = E° - (RT/nF)

used to calculate the cell potential under normal conditions

Goldman-Hodgkin-Katz (GHK) equation

explains how multiple ions contribute to the resting membrane potential, considering their permeability and concentration gradients

What affects the resting membrane?

K+ leaky channels (high permeability and a high concentration gradient at rest), Na+ leaky channels (entry through a few leaking channels helps maintain -70 mV), Na+/K+ pump (maintains concentration gradient)

important ratio?

3 Na+ out, 2 K+ in

steps of the Na+/K+ pump

1) ATP binds to pump: 3 Na+ enter pump

2) ATP is hydrolyzed (ATP → ADP + phosphate, phosphate attaches to pump and changes its shape), transfer of electrical charge (change of Na+/K+ ATPase, opens to ECF instead of ICF), 3 Na+ released to ECF, 2 K+ enter ICF

3) Na+/K+ returns back to original shape, K+ transported to ICF

action potential

depolarization of an excitable membrane in response to a threshold stimulus

“all or none”

if a threshold stimulus excites the membrane, you get an action potential

step 1

Rest at polarized state (separation of + and -)

voltage-gated Na+ and K+ gates are closed

K+ leaky channels are allowing K+ to exit

-70 mV

step 2

Depolarization

Na+ voltage-gated channels allow Na+ entry into the cell → cell becomes more +

K+ voltage-gated channels are opening slowly, basically closed

step 3

Repolarization

K+ voltage-gated channels open slowly → K+ leaves and cells become more -

Na+ activation gates are open, but inactivation gates are closed

Na+ permeability is low, K+ has high permeability

step 4

Hyperpolarization

K+ voltage-gated channels close slowly, but K+ still exits so we overshoot our resting potential

cell more -

refractory period

period of time where an excitable membrane cannot be reexcited or stimulated

absolute refractory period

activation gate of Na+ channels is open (depolarization to hyperpolarization)

another AP cannot be generated because Na+ inactivation gates close so Na+ can’t enter the cell

relative refractory period

activation gate of Na+ channel is closed, but we can’t re-fire the cell normally because the stimulus cannot get the cell back up to the voltage needed to reopen voltage-gated Na+ channels

a suprathreshold stimulus is needed to overcome hyperpolarization

how do voltage-gated channels reach threshold voltage?

1) an electrical stimulus is applied, causing small amplitude fluctuation in voltage → reach threshold

2) stimulus applied chemically or mechanically gated channel allows ions to flow across membrane causing graded potentials

two kinds of binding/receptor sites

ligand-gated channels (chemically gated) and voltage-gated

ligand gated channels (chemically gated)

neurotransmitter required to open the ion channel

neurotransmitter attaches to receptor, opens the channel, ions move in response to gradient

voltage-gated channel

at -70 mV (resting potential): activation gates are closed, so Na+ can’t enter

at -55 mV (threshold): activation gates open, Na+ rushes into the cell, causing depolarization

characteristics of voltage-gated channel

amplitude is proportional to stimulus strength

change in voltage can be - = hyperpolarization, thus inhibitory OR + = depolarization, thus excitatory

summation: close successive stimuli can add up

graded potentials

small changes in membrane voltage can lead to a neuron reaching threshold (+ together: summation)

temporal graded potentials

multiple AP come from a single cellfiring at a rapid rate, leading to cumulative effects on the postsynaptic neuron

spatial graded potentials

multiple inputs to one neuron

action potentials from presynaptic neurons send excitatory signals to the postsynaptic neuron

several graded potentials arrive at different dendrites at the same time

EPSP (excitatory postsynaptic potential) and IPSP (inhibitory postsynaptic potential) can…

balance each other out so they never reach threshold

EPSP

ligand-gated Na+ channels open, depolarizing currents, increasing likelihood of an AP occurring at our post-synaptic cell

IPSP

ligand gated Cl- channels (outside → in) or K+ channels (inside → out) open, hyperpolarizing, decreasing likelihood of AP occurring

How does an AP cause neurotransmitter release at a chemical synapse?

1) Action potential travels down the presynaptic neuron (the electrical signal moves along the axon to the terminal)

2) Voltage-gated Ca2+ channels are triggered open once the action potential reaches the terminal

3) Ca2+ enters the presynaptic terminal (because of its concentration gradient)

4) Ca2+ binds to synaptic vesicles (triggers neurotransmitters to move toward the membrane)

5) Neurotransmitters are released into the synaptic cleft, vesicles fuse with the presynaptic membrane and release neurotransmitters by exocytosis

6) Neurotransmitters bind to ligand-gated channels on the postynaptic neuron (this causes Na+ to enter to postsynaptic cell, produced a graded potential (EPSP or IPSP)

7) Postsynaptic effect - if the graded potentials are strong enough to reach threshold, the postsynaptic neuron fires an action potential (or in muscle/gland cells, it triggers contraction or secretion)

Neuromodulation

a process where a collateral neuron modifies how another neuron fires

it does not directly cause the neuron to fire; it changes how the neuron responds once the signal arrives

what are the two effects of neuromodulation?

facilitation: collateral neuron causes more neurotransmitter release, making the postynaptic neuron more likely to fire

inhibition: collateral neuron causes less neurotransmitter release, making the postsynaptic neuron less likely to fire

homeostasis feedback loop

an input signal leads to a controller, which generates an output signal

feedback can be negative or positive