Homeostasis and Physiological Control Mechanisms

Fundamentals of Physiology: Principles of Homeostasis

• Homeostasis Overview: Homeostasis is defined as the dynamic maintenance of physiological variables within a predictable range.

• Learning Objectives:

  • Explain the underlying principles of physiological homeostasis, including the importance of negative feedback.

  • Describe the role of the autonomic nervous system in physiological control.

  • Describe the role of hormonal systems in physiological control.

  • Describe the role of paracrine homeostatic signaling in physiological control.

  • Describe feed-forward and positive feedback control mechanisms.

Fundamental Terminology and Concepts

• Physiological Variable: A measure of a bodily condition or bodily function.

• Set-point: The normal "basal" or "at rest" value for a physiological variable within a predictable range.

  • Set-points are not fixed; they may be temporarily overridden or adjusted to suit changing external or internal circumstances.

  • Core Temperature Set-point: $37^\circ\text{C}$.

  • Arterial Carbon Dioxide ($CO_2$) Set-point: $5.3\,\text{KPa}$.

• Negative Feedback: This is the most common mechanism used for the maintenance of physiological variables. It involves a change being sensed and a response being initiated to reverse that change, thus maintaining variables within a predicted range.

The Rationale for Homeostasis

• Health and Survival: If a physiological variable strays too far out of its normal range for too long, it leads to illness, disease, or death.

  • Short-term: Critical for immediate survival.

  • Medium-to-long term: Critical for health, well-being, and reproductive capability.

• Clinical Implications of Homeostatic Failure:

  • Acidosis/Alkalosis: Failure to regulate pH.

  • Hyperglycemia: Leads to Diabetes.

  • Hypertension: Chronic high blood pressure.

  • Hypoxemia: Insufficient oxygen in the blood.

  • Excess Cortisol: Leads to Cushing Syndrome.

  • Hyperthyroidism: Leads to Grave's disease.

Illustrative Physiological Variables

• Blood Glucose Concentration:

  • The standard set-point is approximately $90\,\text{mg/ml}$.

  • Glucose levels rise after meals (e.g., Breakfast at 08:00, Lunch at 12:00, Dinner at 18:00) and are subsequently brought back toward the set-point through homeostatic control.

• Blood Pressure (Arterial Pressure):

  • Mean Values (At rest/awake): Diastolic pressure = $80\,\text{mmHg}$; Systolic pressure = $120\,\text{mmHg}$.

  • The set-point is notably lower during sleep.

  • Short-term influences include physical activity and mood, but blood pressure remains predictable over the long term.

Interdependence and Hierarchy of Variables

• Interdependence: Physiological variables are often linked. A change in one affects others to ensure the optimal functioning of all cells. Key variables include:

  • Blood Flow Rate and Plasma Volume.

  • Temperature and Metabolic Rate.

  • Sodium content, Plasma osmolality, and Water content.

  • Tissue $O_2$, $CO_2$, and pH levels.

  • Breathing rate and Growth rate.

• Hierarchy of Importance: Some variables are prioritized over others for immediate survival.

  • Example: Osmolarity (Salt/Water Balance) vs. Blood Pressure: If there is excessive salt in the diet, plasma osmolality increases. To maintain osmolality (which is more critical for immediate survival), the body increases water intake and plasma volume.

  • Outcome: Plasma osmolality is maintained, but this results in increased blood volume and consequently Hypertension (increased blood pressure).

  • While high blood pressure is dangerous in the long term, maintaining osmolality is prioritized in the short term.

Types of Control Mechanisms

• Negative Feedback: Senses change and initiates a response to reverse it (maintain physiological variables within a predicted range).

• Feed-forward: Anticipates a change and brings about a response before the change can be detected by negative feedback sensors.

• Positive Feedback: A change triggers a response that causes further change in the same variable, resulting in amplification of the change rather than normalization.

The Negative Feedback Loop Architecture

• Standard Components:

  1. Stimulus: A variable drifts away from the set-point.

  2. Sensors: Detect the change in the variable.

  3. Afferent Pathway: Carries signals from sensors to the integrating centre.

  4. Integrating Centre: Compares inputs against the physiological set-point and elicits a response.

  5. Efferent Pathway: Carries signals from the integrating centre to effectors.

  6. Effectors: Produce responses that bring the variable back toward the set-point (negative feedback).

• Signalling Pathways: Negative feedback uses three primary types of signalling depending on the variable being controlled:

  • Neuronal

  • Hormonal

  • Paracrine

Neuronal Feedback Control

• Integrating Centres: Many are located in the midbrain or brain stem, specifically the Hypothalamus, Pons, and Medulla.

• Essential Functions: Temperature control, osmolality control, blood pressure/flow control, and blood gas/breathing control.

• Communication with Effectors: Primarily via the autonomic nervous system:

  • Sympathetic Nervous System: Uses noradrenaline.

  • Parasympathetic Nervous System: Uses acetylcholine.

  • These systems often have opposing actions, allowing for the fine-tuning of variables such as cardiac output, lung ventilation, GI tract motility, bladder control, and secretions (exocrine and endocrine).

• Example: Body Temperature Regulation:

  • Stimulus: Drop in ambient temperature leading to a drop in core temperature.

  • Sensor: Hypothalamus senses the change.

  • Afferent Pathways: Neurons communicate within hypothalamus.

  • Integrating Centre: Hypothalamus compares temperature to the $37^\circ\text{C}$ set-point.

  • Efferent Pathways: Neuronal signals within the hypothalamus and out to effectors.

  • Effectors and Response:

    • Muscles trigger shivering to increase heat production.

    • Skin blood vessels reduce blood flow to decrease heat loss.

Feed-Forward Control Mechanisms

• Usually neuronal in nature, these mechanisms prepare the body for future demands.

• Anticipation of a Meal: Stimulates saliva and gastric juice production in preparation for food intake begins.

• Anticipation of Physical Exertion: Increases heart rate and blood flow to muscles to prepare for increased oxygen and fuel demands by muscles.

Hormonal Homeostatic Control

• Endocrine Organs: Include the Hypothalamus, Pituitary (Anterior and Posterior), Thyroid, Adrenal glands, Pancreas, Kidneys, Ovaries, and Testes.

• Hormone Classes:

  • Tyrosine Derivatives: Thyroxine ($T_4$) from the Thyroid; Adrenaline from the Adrenal medulla.

  • Peptides, Polypeptides, and Glycopeptides:

    • Peptides: Anti-diuretic hormone (ADH) and Oxytocin (from the posterior pituitary).

    • Polypeptides: Insulin (Pancreas) and Growth Hormone (Anterior pituitary).

    • Glycopeptides: LH, FSH, and TSH (all from the anterior pituitary).

  • Steroids: Derived from Cholesterol. Examples include Cortisol and Aldosterone (Adrenal cortex), Estradiol (Ovaries), and Testosterone (Testes).

• Hormone Receptors and Action Mechanisms:

  • Peptides/Catecholamines: Bind to cell surface (plasma membrane) receptors. They use second messengers to change enzyme activity. Responses are rapid and often transient.

  • Steroids/Thyroid Hormones: Bind to intracellular receptors (cytoplasm or nucleus). They alter gene transcription. Responses are slow and prolonged.

  • hormones act on target cells by binding to receptors

• Example: Blood Glucose Control via Insulin:

  1. Stimulus: Eating a meal increases blood glucose.

  2. Sensor/Integrating Centre: Pancreatic $\beta$-cells detect change and compare it to the set-point.

  3. Afferent Pathway: Intracellular pathway within the $\beta$-cell.

  4. Efferent Pathway: Pancreas secretes more insulin into the blood.

  5. Effectors: Other tissues (e.g., Liver) absorb more glucose, lowering blood levels.

Paracrine Homeostatic Control

• Mechanism: Sensors, integrating centres, and effectors are all located within the same tissue. The efferent pathway involves the secretion of diffusible substances from one group of cells to act on another group of cells nearby

  • may be part of negative feedback or feed-forward pathways.

• Stimulus: may operate in parallel or independently of neuronal and endocrine control

• Effect: Diffusible substances may act on cell surface receptors or intracellular targets of effector cells

• Examples:

  • Nitric Oxide (NO): Released by endothelial cells in blood vessels; diffuses to nearby smooth muscle cells to cause vasodilation and relaxation, controlling blood flow and pressure.

  • Histamine: Released by mast cells during inflammation; acts on nearby vessels to increase permeability for immune cell access. Facilitates access of immune cells to affected tissue

  • Neurotransmitter Release: Diffusion at synapses to adjacent neurons or muscle cells.

  • Growth Factors: Various growth factors such as Fibroblast Growth Factor (FGF), released at injury sites to promote cell division and matrix regeneration.

Positive Feedback Control

• Rare but required for specific functions where normalization is not the goal.

• Example: Parturition (Birth):

  1. Initiation: Pregnancy shifts the estrogen/progesterone balance, increasing uterine excitability.

  2. Cycle: Uterine contractions cause the fetus to press on the cervix sending ignals to the hypothalamus.

  3. Signal: This triggers oxytocin secretion from the pituitary.

  4. Augmentation: Oxytocin causes further, stronger contractions and increased excitability of uterus.

  5. Termination: The birth of the baby terminates the positive feedback loop.

Quiz: Control of Blood Pressure

• Question: Control of blood pressure…

  • A. Occurs consciously

  • B. Combines elements of neuronal, hormonal and paracrine signalling

  • C. Is a type of positive feedback control

  • D. Is controlled entirely by hormones

  • E. Always involves negative feedback

• Answer Analysis: Control of blood pressure is a complex process utilizing negative feedback loops and a combination of all three signaling mechanisms (neuronal, hormonal, and paracrine).