Lecture 1 (slides 11,12,14-24)
Homeostasis = a relatively constant internal environment
Study of body functions in a disease state = pathophysiology
One of the first physiologists
-was around the late 1800’s
Fluid matrix [extracellular fluid & related fluid in the body] = he’s talking about the fluid within
Temperature change or bacteria invasion in the body – we’re still able to cope.
- Our bodies allows us to function and carry out our daily tasks. - it does this by maintaining
Some of Bernard’s discoveries:
- So he showed the mechanism of muscle contraction. [@ curare]
- Carbon monoxide – that is why smoking is so bad!
Physiology: How the body maintains homeostasis
Homeostasis & the mechanism that the body uses to regulate homeostasis: [Fig. 1.3]
-Protective layer – which is the skin for us
-contained within this protective layer [skin] is loads of fluid
Within this fluid are cells – which also contain fluid
-homeostasis is the balance between the fluid within the cells compared to the fluid within the
It’s not like chemical equilibrium – where the body is trying to balance out the two systems or
the two fluids so that they are identical. it’s to make them similar where it allows us to
function in a way to detect the changes in movement/smell/sound.
-all of our abilities to do that is all to do with changes in homeostasis.
@ Fig. 1.2 - Complicated version of Fig. 1.3
- Shows all the diff. Compartments in the body – where although they are essentially
different & are compartments – they do interact – e.g. diffusion across
barriers/membranes – which allows movement of fluid
- The body is not a completely closed system = we have a mouth & a nose! & we also
excrete things through barriers/systems within our bodies!
- - the ability of different systems to interact in our body – the ones mentioned in the
Physiology = Homeostasis; Pathologies arise when homeostasis fails
So when homeostasis fails = we get ill/sick!
Environment toxins that get into our body - & the body copes with them [sometimes fails]
-our bodies can deal with it to a certain extent!
so – with something like the examples listed on the slide
1)So the toxin enters the body
2) then there is an internal change
3) which results in a loss of homeostasis
4) Then the organism can compensate [usually] - & we remain healthy.
BUT what if that FAILS?!
e.g. Glucose – so when a healthy person takes glucose in the form of a chocolate bar.
- So they have the chocolate
- - they’re fine
1) their body has an increase in glucose
2) Their body changes the salt/ water balance
3) Then insulin is excreted
4) Then the insulin breaks down the glucose – so body returns to homeostasis!
- BUT what about a diabetic person - when there is NO INSULIN [so external change]
1) so blood glucose continues to rise 2) It leads to huge changes in the body – changes in salt balance btwn intracellular &
3) Eventually – what this can cause in a diabetic person [with no insulin] is: slurred speech,
fainting, coma, blindness & loss of blood to outer extremities.
[this was an example of when the body is NOT able to compensate for the external change –
therefore compensation fails = & illness arises]
What about an INTERNAL CHANGE?
- FEVER – causing internal change in body temp.
- Concentration of neurotransmitters (e.g. Increase in dopamine = schizophrenia or a
decrease = depression)
- Cell growth (too much = cancer)
- Cell death (too much = neurodegeneration)
[e.g. Neuro-degenerative diseases = Parkinson’s & Alzheimer's disease]
So how do we understand mammalian physiology?
-Genome project: thought that once completed – that we could cure & treat ALL diseases
-unfortunately – THAT DID NOT OCCUR !
1) It was found that there are fewer genes than proteins in the body: so each gene encodes
several proteins [not the only problem discovered]
2) It’s that the diff. Proteins have diff. Functions in diff. Pathways in diff. Cells in diff.
Tissues. = so body is extremely complicated
& to really understand how it works right down from the protein level to the organism
level = we’ve to take the top down research approach [so going from the organism to the
organ to tissues & so on]
BUT we also have to think about what the proteins do to the diff. Pathways. = so we also have to
take the Bottom up approach as well! 2. Requirement for a Hypothesis
Physiologists require a hypothesis to further our understanding of the body.
- Hypothesis – although it’s quite artistic in the fact that it’s creative but it can’t be abstract
[whereas art can be] – there has to be logic behind it!
3.Experimental design, e.g choice of the correct system (i.e MODEL)
As scientists – when designing things – have to take diff. Things in account – with the first one
being the choice of model.
- Test tube/ Cell Culture : so you can control the diff. Variables within a test tube or a
cell culture - & everything that can happen is controlled for – whereas when you use
animals or humans – that’s not necessarily always the case.
- Understand cellular + molecular mechanisms = to do this is humans/ rats – you would
have to take apart the parts to understand the cellular/molecular mechanisms.
- Relatively quick - but with humans – it could take years.
- [RMR – WE CAN’T DESIGN A PERFECT EXPERIMENT]
- Note: physiologically – you won’t use feelings as a measure!`
- OVERALL: we NEED to do choose all of these models – so use test tubes – then cell
culture – then animals & then move eventually to humans!
Lecture 2 –RESTING MEMBRANE POTENTIAL (print slides 3-18)
Typical concentration of ions in intracellular (IC) and extracellular (EC) solutions:
In Extracellular (EC) Solution: (=concentration)
- Large  of sodium ions
- High  of chloride ions
- Relatively low  of potassium ions.
BUT in Intracellular (IC) Solution:
- High  of potassium ions
- Not so much of chloride or sodium ions - so the chemical gradient between these 2 compartments exists b/c of the
difference in the  of sodium, potassium and chloride ions between the two
[So EC is high in sodium ions
While IC is high in potassium ions]
- So it is the  of sodium ions outside and the  of potassium ions inside that’s crucial with
regards to controlling resting membrane potential and subsequent changes in potential of the
There is a chemical gradient between the IC and EC
because of the properties of the plasma membrane that separates them
A crucial aspect that controls the distribution of ions between the two compartments is the
properties of the PLASMA MEMBRANE.
-can’t pass through the membrane itself (as membrane is non-polar)
- Need to pass through (protein) channels
Why is there a chemical gradient between the IC and EC?
The Na / K ATPase pump located on the cell membrane
Transports 3 Na ions out of the cell and simultaneously transports 2 K ions into the cell
-> that itself establishes a difference in charge between the 2 compartments
-> it’s taking out more +ve ions outside than taking inside
Therefore - this ELECTROGENIC pump produces net movement of positive charge
outside the cell.
Ions pass through the membrane via ion channels
The actual mechanisms that control’s RMP
- One the crucial things that controls this is the presence of ion channels within the
membrane [=these are voltage-gated]
- So at rest – the sodium channel is closed! - & a from of potassium channel (2 types of potassium channels) is open = so b/c there is
lots of potassium inside the cell -> there is a tendency for the potassium to move out of
the cell, down it’s  gradient!
What generates the resting membrane potential (-70mV)?
1. K leak channels
So there are three main factors that govern RMP are:
1) K leak channels
2) Na/K ATPase pump
3) The properties of the plasma membrane
*[2) & 3) on next slides]*
So Na+ & Cl- channels are closed and at rest.
- The K+ channels are open! (leak K+ channel = a form of potassium channel open at
So while the potassium is moving out of the cell – you still have these negatively charged
proteins within the cell
Negatively charged proteins = are BIG – so they can’t escape the membrane.
- So the level of potassium movement is controlled somewhat by the negatively charged
- So, the net negative charge within the cell – > retaining these potassium ions within the
Forces controlling the movement of ions between IC and EC compartments
- this doesn’t mean that there is an equal  of ions between the compartments - it’s the
balance of electrical charges and the chemical gradient that governs this
-you calculate it – you measure it using EQUILIBRIUM POTENTIAL.
EQUILIBRIUM POTENTIAL = the time at which there is NO movement of ions between the 2
compartments is when equilibrium potential is reached. -> so – this is the actual voltage that has to be applied inside the cell using recording electrode to
prevent movement of ions [only in artificial situations]
-the equilibrium potential can only be measured in artificial models!
- Or in our bodies – physiologically - we measure this when the cell is permeable to only
- E.g. So if we are interested in potassium equilibrium potential – so that’s when only the
K+ channel would be open!
Lecture 3 -The Action Potential (1) print slides 3-16,18,19,21
Nerve and muscle cells are excitable cells:
Nerve and muscle cells are excitable = meaning they’ve the ability to change in their membrane
Remember – there is lots of potassium INSIDE the cell
-while there is lots of sodium OUTSIDE the cell.
-& the inside of the cell is NEGATIVE to outside of the cell
-so when sodium comes in – so that’s movement of positive charge into the cell – that makes the
cell more POSITIVE!
& that increases the excitability of the cell = so the movement of sodium into the cell
increases the excitability of the cell!
-So when potassium moves out of the cell – that causes an increase in the negative charge of the
cell (inside the cell)
[so that relative increase in the negative charge DECREASES the excitability of the cell!]
- & we measure these changes in excitability using electro-physiology equipment
discussed in previous lecture! (in picture on the slide)
- ->so the electrode placed inside the cell & another placed outside the cell.
- & the vol