Homeostasis Flashcards
What is homeostasis?
Literally staying the same; more broadly, maintaining the internal conditions and
physical integrity of the body in the face of thermodynamic laws, changing internal
demands and changing stresses originating from outside.
Examples of responses to changing internal demands:
Muscle demands for oxygen (raised pulse, raised breathing)
Examples of responses to changing external stresses:
Temperature; in heat, skin capillaries dilate to increase blood flow (reddening of skin
visible in fair-skinned people), more sweat is produced, activity tends to reduce. In
cold, skin capillaries carry less blood (fair skin turns blue-grey), little sweat is
produced, muscles shiver, exposure reduced by folding limbs in and seeking clothing,
shelter and/ or artificial heat.
Standing up to the second law
The second law of thermodynamics tends to iron out differences, to make everywhere
the same (a drop of ink spreads in water; the system never reforms its original
order). The body depends on having different concentrations of things in different
places, so has to expend energy (obtained from food) to overcome/ reverse the
dissipative effects of the second law.
Handling energy:
Cell’s main source of energy is glucose, a molecule that has 29eV of energy locked up
in it (compared to the energy of the carbon dioxide and water into which it
decomposes on oxidation). This is almost 100x the energy change of typical
biochemical reactions, most of which are powered by the 0.3eV change of ATP -> ADP
+ Pi, or a small multiple of this by using more than one ATP. Cells therefore oxidize
glucose not in one step, but in a long series of steps, each of which creams off a little
energy and uses it to ‘recharge’ ATP, either directly or via intermediates such as
NADH, which ‘recharge’ ATP via the mitochondrial electron transport chain and the
membrane ATPase. Some of the energy of ATP is used to power the Na+
K+
ATP-ase,
to create electrochemical gradients across membranes. These can be used to ‘pay for’
active transport.
Membranes
Are made of phospholipid biyayers, hydrophilic heads outermost, hydrophobic tails
innermost; cholesterol is used to prevent freezing, and various proteins are embedded
in or cross the membranes.
Transport across membranes:
Sufficiently non-hydrophilic molecules (CO2, steroids, many drugs) can cross the
membrane directly. Hydrophilic molecules, including water itself, need to pass through
channels, made of proteins. Each channel has specificity about what it will allow to
pass. Channels can pass only one thing (eg aquaporins), or two things (cotransporters). Co-transporters either transport things together in the same direction
(symporters) or in different directions (antiporters). In general, this is passive flow
but, if there is a concentration difference across a membrane of one ion to be
transported, then flow of that ion down-gradient (reducing the free energy of the
system) can ‘pay for’ transport of the other thing up-gradient, as long as the overall
effect is still reduction in free energy. The Na+
gradient produced by the Na+
K+
ATPase
is often used this way.
Information and signals:
Meanings of signals (and whether something is a signal) are defined by the receiver.
The same thing can be interpreted as having a different meaning by different
receivers. Information has an entropy associated with it, and making and handling it
requires energy. Signals with little information have lower energy demands than
information-rich ones. The body therefore often uses simple signals, and relies on rich
information already being in the receiving cell. This is useful, because the signals are
often simple enough for us to mimic or block them with drugs. `
Types of signal
Signals are autocrine or paracrine, and paracrine includes juxtacrine and endocrine.
Some signals are encoded in media that can cross membranes directly (eg steroid
hormones). Most cannot; they are detected by receptors in plasma membranes, that
relay news of the signal (but not the signalling molecule itself) to the inside of the
cell. Typically, they interact with enzyme systems to generate second messengers.
This can involve amplification, which makes systems fast and sensitive but is
energetically costly. Signalling systems can have any two of sensitivity, speed and
energy economy, but not all three.
More info needed
Different signals can converge on the same second messenger systems, combining
positively or antagonistically; the cytoplasm can be viewed as an analogue computer
making decisions based on data coming from all active receptors.
Using signals to mediate homeostasis in the face of change:
Homeostatic systems use closed-loop control, in which a measurement of what has
been achieved is compared to a set-point, and the error signal (the difference) is used
to control an effector. For example, plasma concentration of Ca2+ is compared to its
target value by cells in the parathyroid gland and, if it is less, these produce PTH that
increases reabsorption from bone and urine (proportional control). It also increases
production of DHCC from vitamin D; this is a long-lived regulator of gut uptake of Ca2+
,
and adds integrative control to the proportional control of PTH. In people with
insufficient vitamin D, this cannot happen properly. Vitamin D can be taken in diet/
dietary supplements or made in skin under sunlight. In Scotland, many people have
insufficient exposure to sun and mild vitamin D shortage is common.
Anticipatory homeostatic events
While many homeostatic systems are purely reactive, some show anticipation.
Typically, the brain notices a pattern that suggests a specific physiological activity is
about to be needed, and it triggers physiological responses to support this even before
they are actually needed. Examples include the fight-or-flight response to something
scary (many changes made in preparation for strenuous muscle activity), salivation in
response to things associated with food, or vaginal mucus secretion in response to
stimuli potentially followed by coitus (the ‘three Fs’; fighting, feeding and mating).
Understanding homeostatic systems, we can trigger them deliberately to prepare for
something, for example exposure to cold air to prepare for immersion in cold water.
Failures of homeostasis are a major part of medicine
When effectors of homeostasis fail, doctors normally replace their function with an
artifical equivalent either to allow the body to heal and properly restore its own
function, or if healing will not happen, forever. Examples include plasters/ bandages to
seal off a hole in the integument, dialysis machines to substitute the function of
damaged kidneys and artificial pacemakers to substitute failure of the natural one.
When regulators of homeostasis fail, doctors normally mimic their signalling with an
appropriate drug. Examples are metraleptin to substitute leptin an a patient with
mutations preventing him making the natural regulator of feeding, fludocortisone
acetate to substitute for aldosterone that cannot be made due to Addison’s disease,
and anti-histamines to block inappropriately released histamine in hay fever.
Notice that in almost all of these cases, doctors do not actually fix the problem - they
provide a work-around.
