Making Life Possible IV - Homeostasis Flashcards
Homeostasis
The state of steady internal physical and chemical conditions maintained by living systems.
Cellular Homeostasis
Cellular homeostasis: the process involved in the maintenance of an internal steady state at the level of the cell.
Steady State: Principles
Living systems are open dynamic systems:
Not at thermodynamic equilibrium
Continual through put of matter and energy
Yet remain remarkably constant in many respects
At steady state, sum of inputs = sum of outputs:
If not, the ‘pool size’ rises or falls until they do
This works at the level of the cell, organ and whole body.
Inputs and outputs need not match second-to-second:
In general inputs > outputs in the timescale of growth and development.
Negative Feedback
The aim is maintenance of a particular value of the controlled variable, in the face of perturbations
If the variable leaves the target range, a sensor is activated
A feedback signal is then sent to an effector
The effector then opposes the unwanted change
This is closed-loop negative feedback:
If something goes too high, this is sensed and processes are activated to bring it down
If something goes too low, this is sensed and processes are activated to bring it up.
Feedback Pathways in whole-body homeostasis
Sensors may report to a brain centre, which issues neural or hormonal signals to the effector organs
These mechanisms are often complicated and multiple
Keep the basic principles in mind:
Steady state
Error signals
Negative feedback
Negative Feedback vs Positive Feedback
Negative feedback - effectors act to minimise the perturbation so brings stability.
Positive feedback - effectors act to increase the perturbation so brings instability but is useful e.g. the nerve action potential.
Decompensation is commonly used to describe this or failures of homeostasis in disease.
Transport and Boundaries
Cell membrane is a lipid bilayer
Permeable to gases, small non-polar molecules
Polar solutes and larger molecules only permeate through specific transporters
Water can travel by diffusion through the lipid-bilayer and water-selective pores (aquaporins): net permeability
Osmosis is water transport across membranes in response to solute distribution: from lower to higher solute concentration until they equalise, if they ever do
Osmolality
Effective osmolality of a fluid is determined by total concentrations of solutes and their permeabilities, in relative to water.
Note: osmolality means mmol/kg water, molarity means mmol/l solution
Across the cell membrane, the osmolar gradient depends on concentration of salts, glucose and proteins (not urea, because this usually freely permeates).
Across the capillary epithelium, the oncotic pressure gradient depends on protein concentration, as small solutes can cross freely.
Passive Transport across the plasma membrane
a) Simple diffusion through the lipid bilayer
b) Facilitated diffusion through a nonspecific transporter
c) Facilitated diffusion through a specific transporter
Osmosis through the lipid bilayer and an aquaporin
Cell Volume
Set by osmotically active-cell contents, and osmolality of extracellular fluid (ECF):
ECF osmolality increases (hypertonic) = cell volume decreases
ECF osmolality decreases (hypotonic) = cell volume increases
ECF osmolality is set by whole body mechanisms:
Control of Na+ content: dominated by renal Na+ handling
Control of body water: thirst, sweating, renal water handling
‘Osmoles’ in cells = ions and metabolites e.g. amino acids
Can be regulated e.g. cerebral osmoregulation defence against cerebral swelling in water overload and cerebral shrinking in dehydration.
Membrane Potential: Principles 1
Gibbs-Donnan potential arises because negatively charged anions (proteins) are trapped in the cell: results in inside negative potential.
The Plasma Membrane Na+ K+ -ATPase
This uses metabolic energy (from ATP hydrolysis) to establish a highly non-equilibrium transmembrane ion distribution.
Membrane Potential: Principles 2
Effects of transmembrane ion gradients:
At equilibrium, membrane potential (Em) would settle at the ‘Nernst potential’.
Actual potential depends on permeabilities to back-leak of ions: the Goldman equation
When permeability to one ion is much larger, this dominates the membrane potential, which becomes closer to that ion’s Nernst potential.
The Action potential in Nerve and Muscle
Resting Em (membrane potential) set by K+ gradient established by Na+ K+ -ATPase, plus K+ outward leak: inside negative (-60mV) = K+ Nernst potential
Action potential results from transient increase in Na+ permeability (positive feedback): Na+ enters cell and Em (membrane potential) approaches Na+ Nernst potential, inside positive (+30mV): depolarisation.
Em (membrane potential) restored by K+ efflux: repolarisation: returns to -60mV
Regulation of cytosolic Ca2+ concentration
Equilibrium cellular concentration of Ca2+ would be very high, given negative membrane potential.
The energy of the Na+ gradient and of ATP directly is used to pump it out, keeping [Ca2+] approximately 100-300nM.
