Physiology for MRCEM Primary

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Basic cellular physiology


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.


Definition : “Ability of physiological systems to maintain a stable internal environment (regulating hormones, body temp., water balance, etc.) in a relatively constant state of equilibrium.”

Variable – The factor that is being regulated is called the variable (Like temperature or blood pressure or CO2 etc.).

Negative feedback mechanisms – The most common type of regulation in the body. A variable is moved in the opposite direction of the original deviation in negative feedback system.
Example – imagine the cold weather is trying to lower your body temperature and negative feedback tries to raise the body temperature.

Feedback comprises:

  1. Detectors (mostly neural receptors) measure the variable;
  2. Comparators (usually CNS centers) receive data from detectors and compares against the set point.
  3. Effectors (muscular / glandular tissue) are activated by the comparator to restore the variable towards 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 need not be a single optimum value. Most of the physiological set points are a narrow range which can be reset as per physiological requirements.
Eg: When you go to a high altitude location (some hill station) –> low partial pressure of O2 will lead to tachypnea ( breath rate increases) –> loss of CO2 is detected by the CNS and it will lower the respiratory rate. But, in 2–3 days, the brain stem lowers the set point for CO2 and allows respiratory rate to increase —  this is called “acclimatization” (Getting used to new conditions).

The principle of oscillations within the feedback loop based upon lag time in feedback.

Positive feedback as an amplification process: it’s instability and consequences of this.


Negative feedback systems induce oscillations in the variable. Let’s illustrate an example to make you understand.

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. Blood flow from lungs to brain takes time (Due to heart failure and low blood pressure) and these delayed signals will make the identification of abnormality late.
When there is apnea phase, the blood will have High CO2 levels and once it’s detected, the brainstem will induce rapid deep breathing. The rapid breathing will wash out the CO2 from body, and by the time low CO2 is detected, the body loses a lot of CO2 and this stimulates reduction in respiratory rate to the extent of apnea and this cycle continues.

Positive feedback causes rapid amplification. Eg: initiation of an Action potential / Depolarization.
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.

The role of homeostasis in protecting the form and function of proteins.

Consequences of the loss of this protective role upon protein function


The primary structure of a protein is determined by the amino acid sequence in that protein. The final results from folding of the amino acid chain, which takes the lowest energy conformation. Folding is made possible by weak electrochemical interactions (e.g. hydrogen bonds, van der Waals’ forces) between side-chains in multiple dimensions.

The cells have the ability to detect and destroy misfolded proteins. If the cell fails to do so, it can result in pathology, such as Alzheimer’s disease and Creutzfeldt–Jakob disease.

Factors that can change the shape of proteins:

  • Acidity
  • Osmotic potential
  • Temperature
  • Hydrostatic pressure

The modifications in tertiary shape of a protein are reversible to certain extent. However, beyond a point, proteins alter the shape permanently making them non-functional or irreversibly damaged (denaturation) (Eg: egg-white solidification in cooking).
Homeostatic systems ensure such factors are in check within the body, and thus preserve protein functionality.