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What is homeostasis?

- the ability to maintain a constant internal environment despite stressors in the external environment (e.g. a rat's blood pressure in a cage, high sodium diet doesn't affect bp in the short term)


What changes in order to maintain blood pressure?

- heart rate


What happens if the reflexes that control heart rate are lost (Synoaortic denervation)?

- heart rate relatively stable
- BP cycles all over the place - dramatic changes to everything


How are glucose levels maintained?

- insulin and glucagon
- glucose levels rise after eating - go down with insulin
- maintained at a pretty constant level during periods of fasting ~4.2


How do we have cellular homeostasis of neuronal activity?

- in general, the neurons you are born are the neurons that you die with (at approx. age 100)
- you don't get many new ones
- the ones that you do have to maintain their activity/normal activity throughout your life
- can't have massive changes in the levels of excitability of neurons
- apart from learning and memory, you don't want activity/synaptic strength etc to change over the course of your life e.g. breathing pattern circuits
- for the majority of neurons it is about maintenance of normal activity (years, decades)
- every few days, the ion channels that determine the activity of the neurons are recycled
- the channels are not life-long
- activity within the neuron is changing but overall activity is maintained at a homeostatic level over the course of years
- if you alter channel expression you get changed activity, this leads to expression of channels that return cell to normal, happens very quickly i.e. activity-dependent regulation
- activity-independent coupled expression (monitoring gene expression)


How does water flow across a semipermeable membrane?

- osmotic flow across a membrane will have water moving from a place of low solute concentration to a place of high solution concentration in order to try and balance the concentration


What is a consequence of water flow via osmosis?

- if in a fixed compartment, as the water flows into the area of higher solute concentration, pressure will increase


What are regulatory volume increase and regulatory volume decrease?

- if a cell gains solute it will also gain water resulting in regulatory volume increase
- if a cell loses solute it will also lose water resulting in a regulatory volume decrease
- these are regulatory mechanisms - can be brought about by adding or taking away solute channels


What are consequences of increased/decreased volume?

- swelling can cause the cell to burst e.g. putting blood cells in hypotonic water, swelling of the brain cells results in brain damage because of limited capacity of blood to perfuse into the brain
- decreased - cell shrinkage


What is a consequence of RVI/RVD?

- can change ion concentration that is necessary for neuron function/excitability


How can we induce long term changes?

- proteins that represent an osmotic component: osmolytes e.g. some amino acids (alanine, proline, taurine), polyols (glycerol, sorbitol, myo-inositol), methylamines (TMAO, betaine, GPC)
- cell can respond to osmotic changes by changing the amounts of these components


Is homeostatic control tight or loose?

very tight


What changes to activity can be caused by changes in plasma osmolality?

- 10 mOsm/k
- lead to reduced learning, headaches,
- in the other direction - delirium


Can washing mouth restore changes in osmolality?

- no, makes you feel less dehydrated but no difference to not being able to replenish fluids


What homeostatic pathways enable us to maintain osmolality?

- we have a set point ~290 mOsm/kilo
- hypertonicity: increase thirst (water intake), increase vasopressin (water retention), decrease Na+ appetite (no salt intake), increase Natriuresis (Na+ excretion)
- hypotonicty: decrease thirst (no water intake), decrease vasopressin (water excretion), maybe increase salt appetite, decrease natriuresis

- important to maintain volume as well as solute concentration


Where do we have sensors that pick up osmolality?

- gastrointestinal tract
- liver (Hepatic portal vein)
- splanchnic mesentery
- pharynx/oesophagus

e.g. drink water, sensors in pharynx and oesophagus will sense that, send info to the brain to inform it that you have just ingested something of a particular osmolality

- also sensors that sense osmolality of blood


Which regions of the brain are activated in response to hypertonic saline?

- ACC: anterior cingulate cortex – I'm thirsty
- lamina terminalus: in the hypothalamus – more involved in sensation

- ACC activity decreases as soon as you drink some water even if osmolality isn't changing i.e. a decrease in perception of thirst
- lamina terminalus barely changes in response to intake of water


What is the lamina terminalus?

- contains cells that are responding to very small changes in plasma osmolality
- faithful representatives
- signal through other pathways to tell the brain that behaviours need to change in order to restore plasma osmolality
- seem to respond to volume of the cell - swelling and shrinking seems to change its response
- swelling causes a decrease in conductance
- TRPV1 essential channel that links a change in volume with a change in osmolality


What is special about circumventricular organs?

- they have no blood brain barrier thus allowing them to sense plasma


What is vasopressin?

- a hormone that acts in the kidney and causes retention of fluid
- secreted at night to allow you to sleep
- alcohol suppresses expression of vasopressin
- secreted by magnocellular neurosecretory cells in the hypothalamus
- connected to the OVLT