HOMEOSTASIS

Y1 SEMESTER 1

Homeostasis and Principles of signalling

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Homeostasis

What is homeostasis?

Maintaining the internal conditions and physical integrity of the body in the face of thermodynamic laws, changing internal demands and changing stresses originating from the external environment

Examples of responses to changing internal demands- Muscle demands for oxygen during strenuous exercise (Increase heart rate and respiration)
Examples of responses to changing external stresses-
- Temperature
  - High temperature- Skin capillaries dilate to increase blood flow to the surface (reddening of skin is visible in fair-skinned people) and increased perspiration.
  - Low temperatures- Skin capillaries constrict, reducing blood flow to the surface (fair skin turns blue-grey) and can cause shivering and goosebumps.

Regulating body temperature - Homeostasis - GCSE Biology (Single Science) Revision - BBC Bitesize

Standing up to the second law of thermodynamic:

The second law is the total entropy (measure of disorder) of an isolated system can never decrease over time.

It 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. To fight back against the action of the second law it has to expend energy (obtained from food) to maintain its organisation and order (non-equilibrium state). Hence, biological systems must minimise free energy and are not a closed system (in which disorder inevitably decreases) and restricts itself to a limited number of states.

When a drop of blue ink is put in water the blue Colour spreads and the whole solution becomes blue name the phenomenon due to which this happens?

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.
Cells therefore oxidize glucose not in one step, but in a long series of steps, each of which creams off a little energy so that we don't release all the energy of the glucose in one destructive moment.
Some steps pass this energy directly to 'recharge' ATP, either directly or via intermediates such as NADH. These 'recharge' ATP via the mitochondrial electron transport chain and the membrane ATPase.
Furthermore, some of the energy of ATP is used to power the Na+ K+ ATP-ase (sodium-potassium pump), to create electrochemical gradients across membranes. These can be used to 'pay for' active transport.

Membranes- are made of phospholipid bilayers and are selectively permeable. Hydrophilic heads outermost, hydrophobic tails innermost. Cholesterol is used to prevent freezing, and various proteins are embedded in and cross the membranes.

https://ibiologia.com/phospholipid-bilayer/

Transport across membranes

Non-hydrophilic molecules- (CO2, steroids, many drugs) can cross the membrane directly.
Hydrophilic molecules- Glucose, amino acids, urea, ions, water can pass the membrane but very slowly. The membrane needs selective channels.
Co-transporters either transport things together in the same direction (symporters) or in different directions (antiporters). Ions such as sodium, potassium and chlorine can diffuse passively down a concentration gradient.

Active transport- Uses ATP to transport molecules across membranes and decreases free energy.

For example a maintained non-equilibrium is seen with Na+ and K+ where extracellular fluids have a higher concentration of Na+ and intracellular fluids have a higher concentration of K+.

Na+/K+ ATPase moves unequal amounts of ions, with 3 Na+ out and 2 K+ into the cell, against a concentration gradient and so requires energy to do this which is hydrolysed from ATP.
This creates a difference in voltage across the membrane which can be used by co-transporters to transport ions. For example used in the Na+/ glucose symport

https://www.ahajournals.org/doi/full/10.1161/circulationaha.116.021887

Principles of signaling

The same signal can have different effects on different receivers e.g. oestrogen on bone (epiphyseal closure) as well as the uterus (thickening).
Making and transmitting information requires energy. Some biological systems have to carry vast amounts of information.
Drugs work by making alterations to how well these signals are received.
- Autocrine- sends signals to itself or a group of cells that are the same.
- Paracrine- one cell signal to a different type of cell
- Juxtacrine- signal very close to a different type of cell so is a very short-lived molecule
- Endocrine- signal is longer range and travels in the blood to different types of cell where hormones can go to the whole body.

https://biologydictionary.net/how-do-cells-maintain-homeostasis/

Steroid mediated signal alters gene expression. Steroid hormone (testosterone) hormones are derived from cholesterol. Consequently, steroid hormones are generally poorly soluble in water and, following secretion, are transported bound to plasma-binding proteins. Steroids diffuse across the plasma membrane and bind to a cytoplasmic binding protein.They then control gene expression by activating transcription factors. This kind of pathway is efficient but slow. Eg sex determination (life-long), regulating puberty(years), mestraul cycles (months) stress and inflammation (days-years)

http://studyblue.com/notes/note/n/endocrine-system-3/deck/10386766

A huge number of signals are mediated by hydrophilic molecules and require receptors to bind to to induce a conformational change and allow the passage of ions, neurotransmitters, peptide hormones(e.g. insulin) and growth factors.

http://what-when-how.com/molecular-biology/phospholipases-c-molecular-biology/

Enzymes on the intracellular side can be targets for signalling molecules. For example G-protein coupled receptors.

A signalling molecule binds to the receptor and the G-protein can activate enzyme phospholipase C which activates PIP2 which further activates DAG and IP3. DAG functions as secondary messenger in other pathways. IP3 diffuses through cytosol and binds IP3 gated calcium channel in the ER causing it to open. Calcium ions flow out (down gradient) into cytosol and ions activate next protein in one or more pathways.

Different receptors activate different G-proteins and once the enzyme is activated it acts as an amplifier.

Signal- receptor- enzyme channels- secondary messengers- ultimate effects

Energetics and dynamics of signalling

There is an inevitable compromise in signalling where you can have 2 but not all 3 of sensitivity, speed, and energy efficiency.

Sensitivity can be increased by amplification which can be achieved by using a lot of ATP. There is a risk of cells being triggered when they shouldnt be and the ways to avoid false signals is to:

Average signals over time (where speed of response is compromised) and Average over a group of cells (requires communication between them)
Speed- For high speed in both directions (on and off) it requires rapid production of secondary messengers and activated effectors which costs a lot of energy. Rapid destruction of the secondary messengers and activated effectors cost more energy. Destruction keeps pace with synthesis.

Challenges of long-distance communication

A low speed has the choice between producing lots of a signal or the receiver having high sensitivity to a signal. Generally, it's more energy efficient to produce small amounts of a signal and having the receiving cells sensitive to the signal. Hence, we can use averaging overtime to avoid being triggered by extra signals.
Advantage of nervous communication: same chemical signals and same response systems to make the body do many different things according to which nerve axons are activated.
Hormones can have a wide range of effects and neurotransmitters have a single effect (eg contract a muscle)

http://www.quia.com/jg/2550021list.html

Feedback loop- using signalling for body-level homeostasis

The body must keep its proper internal environment in the face of internal and external changes.

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.

A differential control allows for fast restoration.

Positive feedback- encourage an increase in response e.g., cell division

Negative feedback- reversal of an original response from a stimulus.

Pictures Of Calcium Metabolism (healthiack.com)

Using signalling for body-level homeostasis

If a parameter is critical to health and well-being letting it get worse can be detrimental.
Some physiological changes are anticipative as soon as we know a problem is likely we invoke a solution e.g. fight or flight responses when the brain recognises danger. Releasing signals from the sympathetic nervous system and the adrenal medulla releases adrenaline which in turn increases heart rate, blood flow to muscle and converts glycogen to sugars.

https://www.health.qld.gov.au/news-alerts/podcast/my-amazing-body-the-adrenal-glands

Eating- the brain uses cues such as smell and sound to anticipate food and trigger extra saliva production which is needed to begin digestion of starch
Systems can be driven from not showing anticipation to anticipative behaviour by pre-exposure eg cold water swimming.
Anticipatory changes involve the brain doing some pattern recognition.

Failures of homeostasis

Damage to effectors

When effectors of homeostasis have failed, artificial mechanisms can provide an adequate replacement function.

For example:

Breach of integumentary barriers and of blood vessels fluids can flow where they should not be. Restore the barrier by providing a temporary barrier while natural homeostatic responses (clotting) take place.
Renal failure- inability to regulate fluids to remove some toxins such as urea. Main treatment is dialysis to remove toxins from the blood

Pacemaker of the heart mediates between feedback controls and heart muscle contraction. If the pacemaker is damaged it does not beat properly and an artificial one is implanted to regulate electrical signals.

http://medimoon.com/2014/03/small-wireless-pacemaker-is-safe-effective-in-early-testing/

Damage to control systems

When there is a failure in a control system it is often because of a gene mutation.

Congenital defects absence of a regulator e.g. leptin for hunger and fat storage
Damage to a critical feedback system (Addison’s disease)
Inappropriate activation of a homeostatic signal (allergy)
Cell wrongly interpreting valid signals (cancer)
Mimic or missing a signal by a drug or a blocked pathway.

Summary

Homeostasis is essential to life, achieved only with expenditure of energy. It is usually achieved using feedback loops, proportional, integrative and sometimes differential control. It also may be anticipatory. Lastly, may diseases are failures in some aspects of homeostasis of systems or effectors.