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Core
Homeostasis
Homeostasis is the maintenance of a stable internal environment within a dynamic equilibrium (a balance that is constantly adjusted rather than fixed) via negative feedback mechanisms.
The endocrine system and the nervous system are responsible for maintaining homeostasis. This is achieved via the following pathway:
- Stimulus - This is a change in the environment which causes the variable (the thing being controlled, such as body temperature) to deviate from its normal value (the set point).
- Receptors - These are specialised cells which detect stimuli. They communicate with the control centre via afferent pathways (nervous/endocrine), which carry information towards the control centre. Examples include:
- Chemoreceptors - Detect chemical changes such as CO2, O2 and pH levels.
- Thermoreceptors - Detect changes in temperature.
- Proprioceptors - Detect changes in position and movement.
- Mechanoreceptors - Detect mechanical stimuli, such as pressure and stretch.
- Nociceptors - Detect potentially dangerous stimuli, such as extremes in temperature or pressure. They are found in the skin and in other tissues, such as muscles, joints and internal organs.
- Control centre - This is often located in the brain (within the hypothalamus or medulla oblongata, the lowest part of the brainstem), but also in other areas of the body. The role of the control centre is to:
- Determine the set point - Core body temperature = about 37°C
- Analyse the afferent input - Thermoreceptors detecting a rise in core body temperature
- Determine the appropriate response - Lower the core body temperature (the response needed when the body is too hot)
- Effectors - These are the organs/tissues which bring about the change to return the variable to the set point. They receive signals from the control centre via efferent pathways (nervous/endocrine), which carry signals away from the control centre.
- Feedback - The process by which the output of the effector (its response) influences the overall function of the control system.
- Negative feedback - This is the most common type of feedback loop. Here, the output acts to oppose the stimulus in order to bring the variable back towards the set point. This allows the variable to be kept within tight limits. For example, if the body is too hot, the effector will act to reduce the temperature and maintain homeostasis.
- Positive feedback - This type of feedback is much rarer. Here, the output amplifies the stimulus, causing the variable to deviate even further from the set point. One example of this is during labour. Stretching of the cervix (the lowest part of the uterus) triggers the release of oxytocin (a hormone released by the pituitary gland), which strengthens the uterine contractions. This stretches the cervix even more, so the loop continues until the baby is born.
Diagram: A negative feedback loop, using thermoregulation as an example
Creative commons source by OpenStax [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
The set point in a human can vary over time, which gives rise to biological rhythms. The human biological clock is found in the hypothalamus in the form of a small group of neurones collectively known as the suprachiasmatic nucleus. These neurones set the body’s circadian rhythm (around 24 hours). The biological clock receives input from environmental cues or zeitgebers (light, temperature, physical activity etc.) and a hormone called melatonin. Melatonin is secreted by the pineal gland (a small gland deep in the brain) and helps to regulate the sleep-wake cycle in humans. A mismatch between environmental cues and the body clock (e.g. after a long-haul flight) results in jet lag.
Examples of biological rhythms include:
- Cortisol - Follows a circadian rhythm, peaking in the early morning (around waking) and reaching its lowest levels around midnight.
- The menstrual cycle - Involves a number of hormones (e.g. oestrogen, progesterone, follicle-stimulating hormone or FSH, and luteinising hormone or LH), whose set points vary according to a monthly cycle.
Note: the time labels along the bottom of this graph are out of order. Read from left to right, they should be 12pm, 4pm, 8pm, 12am, 4am, 8am and 12pm. Melatonin production is low during the day, rises from the evening, is highest during the night and falls again by the morning.
Graph: The rise and fall of melatonin levels (made by the pineal gland) in the body across the day. The suprachiasmatic nucleus (the biological clock) drives the pineal gland to release more melatonin at night. Melatonin helps to regulate the sleep-wake cycle and promotes sleep. Disruption of the body clock is linked with sleep disorders.
SimpleMed original by Dr. Thomas Burnell
A hormone is a molecule which is secreted by an endocrine gland (or by other cells with an endocrine function, such as cells in the heart, kidneys or fat tissue) into the bloodstream to act on a distant target cell. Hormones are normally present in the blood at very low concentrations (often between picomolar and micromolar levels, that is, between a trillionth and a millionth of a mole per litre). It is usually a change in the concentration of the hormone that produces a response in a target cell.
Hormones can be classified according to their chemical structure:
Table: Classification of hormones
SimpleMed original by Dr. Joshua Bray
The endocrine glands that produce the polypeptide hormones and catecholamines (such as adrenaline) typically store their hormonal products within the cell in discrete storage vesicles prior to secretion. The steroid-producing tissues do not normally store hormones, but store cholesterol as cholesterol esters (cholesterol joined to a fatty acid). The thyroid gland is an exception to both of these patterns, as it stores its hormonal products outside the cell as colloid (the fluid in the centre of each thyroid follicle, one of the small sacs that make up the gland).
The secretion of hormones is generally controlled by negative feedback, but in many cases the secretion of one hormone is controlled by another. In this arrangement, the hormone that controls the release of the other is known as the tropic hormone (not to be confused with trophic hormone: a hormone that stimulates growth in the target tissue). Tropic hormones are mostly secreted by the anterior pituitary gland. One example of this is the hypothalamic-pituitary-gonadal (HPG) axis (the chain of control from the hypothalamus to the pituitary gland to the ovaries or testes), shown in the diagram below.
Diagram: Action of tropic hormones using the hypothalamic-pituitary-gonadal (HPG) axis as an example. Gonadotrophin-releasing hormone (GnRH) is released from the hypothalamus, stimulating the anterior pituitary to release FSH and LH, which act on target cells within the ovaries/testes.
Creative commons source by Neil Smith [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Hormones exert their effects by binding to receptors on the target cell. The type of receptor depends on the type of hormone.
Lipophilic (fat-soluble) hormones (e.g. cortisol) bind to intracellular receptors located within the cytoplasm or nucleus. Due to their lipophilic nature, they can pass through the phospholipid bilayer of the cell. They exert their effects by modulating gene transcription.
Hydrophilic (water-soluble) hormones cannot cross the cell membrane, so they bind to cell-surface receptors (receptors on the outer surface of the cell membrane). These include:
- G-protein coupled receptors (receptors linked to a G-protein, a protein just inside the cell membrane that relays the signal) - Hormone binding modulates the generation of a second messenger (a chemical inside the cell that passes the hormone's signal on, such as cyclic adenosine monophosphate or cAMP), which activates various intracellular signalling pathways. Examples include the receptors for glucagon and thyroid-stimulating hormone (TSH).
- Tyrosine kinase receptors (receptors that are enzymes which add phosphate groups to proteins) - Hormone binding results in protein phosphorylation (adding a phosphate group to a protein). This activates a signalling cascade (a chain of steps that passes the signal on) and influences gene transcription. An example is the insulin receptor.
Inactivation of hormones occurs in the liver and kidney, and sometimes in the target tissues themselves. Steroid hormones are inactivated by a small change in chemical structure that increases their water solubility, enabling them to be excreted from the body in urine or via the bile. Protein hormones undergo more extensive chemical changes and are degraded to amino acids that are reused for protein synthesis.
Reviewed by: Dr. Marcus Judge
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