[box type=”bio”] Appreciation of the fundamental role of homeostatic mechanisms in physiology:
— Negative feedback via receptors, comparators & effectors based upon a ‘set point’
— The ‘set point’ as being a narrow range of values within which normal function occurs [/box]
“Ability of physiological systems to maintain conditions within the body in a relatively constant state of equilibrium.”
The factor that is being regulated is called the variable (Like temperature or blood pressure etc.).
The most common type of regulation is by negative feedback (a variable is moved in the opposite direction of the original deviation) ~Imagine the cold weather is trying to lower your body temperature and negative feedback tries to raise the body temperature.
- Detectors (mostly neural receptors) measure the variable;
- Comparators (usually CNS centres) receive data from detectors and compares against the desired level.
- Effectors (muscular / glandular tissue) are activated by the comparator to restore the variable to its set point.
Eg: When the partial pressure of CO2 in blood rises over 5.3 kPa (40mmHg), brain stem increases the rate of ventilation to clear the excess gas, and vice versa.
Set point could be a single optimum value or a narrow range which can be reset as per physiological requirements.
Eg: High altitude –> low partial pressure of O2 –> ventilation rate increases –> loss of CO2 tries to lower ventilation rate.
But, in 2–3 days, the brain stem lowers the set point for CO2 and allows ventilation to increase — this is called “acclimatization”
[box type=”bio”] — The principle of oscillations within the feedback loop based upon lag time in feedback.
— Positive feedback as an amplification process: its instability and consequences of this. [/box]
Negative feedback systems induce oscillations in the variable.
Patients with congestive heart failure show Cheyne–Stokes’breathing (periods of deep breathing interspersed with apnoea). Breathing alterations require chemical signals to be detected by brain-stem. Slow blood flow from lungs to brain causes a delay in detecting CO2 levels.
Positive feedback causes rapid amplification. Eg: initiation of an action potential/depolarisation
Positive feedback is unstable requiring some kind of mechanism to break the feedback loop and stop the process such as time-dependent inactivation of sodium channels.
[box type=”download”] — The role of homeostasis in protecting the form and function of proteins.
— Consequences of the loss of this protective role upon protein function.[/box]
The primary structure of a protein is determined by the amino acid sequence. The final shape of the molecule (the tertiary structure), results from folding of the amino acid chain in its lowest energy conformation. Folding is aided by weak electrochemical interactions between side-chains (e.g. hydrogen bonds, van der Waals’ forces) which is overseen by molecular chaperones, such as the heat shock proteins.
In healthy tissue, cells can detect and destroy misfolded proteins, a failure in this can result in various pathological conditions, including Alzheimer’s disease and Creutzfeldt–Jakob disease. Folding ensures a proper orientated to allow the protein to serve its function.
Alterations in acidity, osmotic potential, concentrations of specific molecules/ions, temperature or even hydrostatic pressure can modify the tertiary shape of a protein (usually reversible). For instance CO2 chemoreceptors possess ion channel proteins that open or close to generate electrical signals when the acidity(Change in CO2) surrounding the receptor is altered.
However, there are limits to the degree of fluctuation that can be tolerated by proteins before their shape alters permanently making them non-functional or irreversibly damaged (denaturation) (Eg: egg-white solidification in cooking). Homeostatic systems prevent such conditions from arising within the body, and thus preserve protein functionality.
[box type=”download”] — Compartments and fluid spaces in health.[/box]
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