Comprehensive Study Notes on Homeostasis and Physiological Control Systems

Introduction to Homeostasis

• Historical Concepts and Definitions:
  • Claude Bernard introduced the concept of the internal environment (milieu intérieur) in the 19th century.
  • Walter Cannon introduced the term "Homeostasis" in 1929 to describe the maintenance of nearly constant conditions within the internal environment.
• Nature of the Internal Environment:
  • The internal environment of the body is specifically the Extracellular Fluid (ECF), within which cells live.
  • The ECF is the fluid located outside of cells that constantly moves around the body.
  • The ECF comprises blood plasma and interstitial fluid.
  • The ECF contains nutrients, ions, and all other substances necessary for cellular survival.
• Systemic Integration:
  • All organs and tissues of the body perform functions that help maintain the internal environment.
  • Organ systems involved in maintaining homeostasis include the Respiratory system, Gastrointestinal Tract (GIT), Liver, Kidneys, Nervous systems, Hormone systems, and Genetic control systems.
• Physiological Limits:
  • Ions, nutrients, waste products, and other body constituents are normally regulated within a dynamic range of values rather than a fixed value.
  • These ranges are defined as physiological limits or set limits.

Normal Ranges of Important ECF Constituents

• Quantitative Parameters (Adapted from Guyton and Hall):
  • Oxygen (Venous):
  • Normal Value: $40\,\text{mm Hg}$
  • Normal Range: $35\text{--}45\,\text{mm Hg}$
  • Short-Term Non-Lethal Limit: $10\text{--}1000\,\text{mm Hg}$
  • Carbon Dioxide (Venous):
  • Normal Value: $45\,\text{mm Hg}$
  • Normal Range: $35\text{--}45\,\text{mm Hg}$
  • Short-Term Non-Lethal Limit: $5\text{--}80\,\text{mm Hg}$
  • Sodium Ion:
  • Normal Value: $142\,\text{mmol/L}$
  • Normal Range: $138\text{--}146\,\text{mmol/L}$
  • Short-Term Non-Lethal Limit: $115\text{--}175\,\text{mmol/L}$
  • Potassium Ion:
  • Normal Value: $4.2\,\text{mmol/L}$
  • Normal Range: $3.8\text{--}5.0\,\text{mmol/L}$
  • Short-Term Non-Lethal Limit: $1.5\text{--}9.0\,\text{mmol/L}$
  • Calcium Ion:
  • Normal Value: $1.2\,\text{mmol/L}$
  • Normal Range: $1.0\text{--}1.4\,\text{mmol/L}$
  • Short-Term Non-Lethal Limit: $0.5\text{--}2.0\,\text{mmol/L}$
  • Chloride Ion:
  • Normal Value: $106\,\text{mmol/L}$
  • Normal Range: $103\text{--}112\,\text{mmol/L}$
  • Short-Term Non-Lethal Limit: $70\text{--}130\,\text{mmol/L}$
  • Bicarbonate Ion:
  • Normal Value: $24\,\text{mmol/L}$
  • Normal Range: $24\text{--}32\,\text{mmol/L}$
  • Short-Term Non-Lethal Limit: $8\text{--}45\,\text{mmol/L}$
  • Glucose:
  • Normal Value: $90\,\text{mg/dl}$
  • Normal Range: $75\text{--}95\,\text{mg/dl}$
  • Short-Term Non-Lethal Limit: $20\text{--}1500\,\text{mg/dl}$
  • Body Temperature:
  • Normal Value: $98.4\,^{\circ}\text{F}\ (37.0\,^{\circ}\text{C})$
  • Normal Range: $98\text{--}98.8\,^{\circ}\text{F}\ (37.0\,^{\circ}\text{C})$
  • Short-Term Non-Lethal Limit: $65\text{--}110\,^{\circ}\text{F}\ (18.3\text{--}43.3\,^{\circ}\text{C})$
  • Acid-Base Balance:
  • Normal Value: $7.4\,\text{pH}$
  • Normal Range: $7.3\text{--}7.5\,\text{pH}$
  • Short-Term Non-Lethal Limit: $6.9\text{--}8.0\,\text{pH}$

Physiological Pathologies from Range Deviations

• Effects of Temperature Deviations:
  • An increase of $11\,^{\circ}\text{F}$ ($7\,^{\circ}\text{C}$) above normal leads to a vicious cycle of increasing cellular metabolism that destroys cells.
• Effects of Potassium Ion ($\text{K}^+$) Deviations:
  • A decrease to less than $\frac{1}{3}$ of normal leads to paralysis due to the inability of nerves to transmit signals.
  • An increase to $2\times$ normal or more severely suppresses heart muscle contraction.
• Effects of Calcium Ion ($\text{Ca}^{2+}$) Deviations:
  • A decrease below $\frac{1}{2}$ of normal causes spontaneous generation of excess nerve impulses in peripheral nerves, inducing tetanic muscle contractions throughout the body.
• Effects of Glucose Deviations:
  • A decrease below $\frac{1}{2}$ of normal produces extreme mental irritability and convulsions.

Characteristics of Control Systems

• Negative Feedback Mechanism:
  • Most control systems operate via negative feedback.
  • Consists of a series of changes that return an elevated or deficient factor toward a mean value to maintain homeostasis.
  • Detects a change (stimulus) in a physiological condition and initiates a response that reverses the changed variable back to normal.
  • Mechanics (Effect Reverses Cause):
  • Sensors detect a change in the condition.
  • The integrator of the Control center compares the change to a set point.
  • Effectors initiate a response to correct the deviation.
• Gain of a Control System:
  • Measures the degree of effectiveness with which a control system maintains constant conditions.
  • Defined mathematically as:     $\text{Gain} = \frac{\text{Correction}}{\text{Error}}$
• Positive Feedback System:
  • Non-homeostatic mechanism, also known as a "vicious cycle".
  • An initiating stimulus causes more of the same stimulus or response.
  • Most positive feedback mechanisms cause systemic instability and eventually lead to death.
  • When useful, positive feedback operates as part of an overall negative feedback process (e.g., blood clotting operates to preserve total blood volume).
• Adaptive Control Systems:
  • Also termed Feed-forward control or Delayed negative feedback.

Negative Feedback Control Examples

• Regulation of ECF Oxygen and Carbon Dioxide:
  • Oxygen Regulation (Oxygen-Buffering Function of Haemoglobin):
  • Haemoglobin combines with oxygen during passage through pulmonary capillaries in the lungs.
  • Haemoglobin exhibits strong chemical affinity for oxygen.
  • As blood passes through tissue capillaries, oxygen is not released if local tissue oxygen concentration is already high.
  • When tissue oxygen concentration is low, haemoglobin releases sufficient oxygen to restore adequate tissue concentration.
  • Carbon Dioxide Regulation:
  • Carbon dioxide is a primary end product of cellular oxidative metabolic reactions.
  • High blood carbon dioxide concentrations excite the respiratory center.
  • Respiratory center excitation increases pulmonary ventilation, causing deeper and rapid breathing.
  • Increased ventilation removes excess carbon dioxide from blood and tissue fluid, decreasing its concentration back to normal.
• Regulation of Arterial Blood Pressure:
  • Regulated via multiple physiological mechanisms, including the Baroreceptor system.
  • Baroreceptors are nerve receptors located in:
  • The wall of the bifurcation region of the carotid arteries in the neck.
  • The arch of the aorta in the thorax.
• Thyroxine Control System Loop:
  • Increased thyroxine secretion inhibits Thyroid-Stimulating Hormone (TSH) secretion.
  • Reduced TSH secretion leads to decreased thyroxine secretion, returning thyroxine to normal levels (no deviation).
  • Decreased thyroxine secretion stimulates TSH secretion.
  • Elevated TSH secretion leads to increased thyroxine secretion, returning thyroxine to normal levels (no deviation).
• Maintenance of Water Balance:
  • Decreased Body Water Content Loop:
  • Low water content stimulates osmoreceptors in the hypothalamus.
  • Osmoreceptor stimulation triggers thirst, causing increased water intake.
  • Osmoreceptor stimulation simultaneously increases Anti-Diuretic Hormone (ADH) secretion from the posterior pituitary.
  • Increased ADH secretion causes increased water retention by the kidneys.
  • Both intake and kidney retention restore normal water content (no deviation).
  • Increased Body Water Content Loop:
  • High water content results in no stimulation of hypothalamic osmoreceptors.
  • Absence of osmoreceptor stimulation results in no thirst, causing decreased water intake.
  • Absence of osmoreceptor stimulation leads to decreased ADH secretion from the posterior pituitary.
  • Reduced ADH secretion leads to decreased water retention by the kidneys.
  • Both decreased intake and reduced retention restore normal water content (no deviation).

Positive Feedback Control Examples

• Blood Clotting:
  • Injury to a blood vessel causes bleeding.
  • Vessel injury initiates the formation of prothrombin activator.
  • Prothrombin activator converts prothrombin into thrombin.
  • Thrombin converts fibrinogen into fibrin, resulting in the stoppage of bleeding.
• Parturition (Childbirth):
  • Onset of labor causes movement of the fetus into the cervix.
  • Fetal movement causes dilatation of the cervix.
  • Cervical dilatation stimulates stretch receptors in the cervix.
  • Receptors discharge nerve impulses.
  • Impulses are transmitted to the hypothalamus.
  • Hypothalamus stimulates the release of oxytocin.
  • Oxytocin induces contraction of the uterus.
  • Uterine contraction forces further movement of the fetus through the cervix, amplifying the cycle until delivery.
• Generation of Nerve Signals:
  • During an action potential, initial influx of sodium ions causes opening of additional voltage-gated sodium channels.
  • Channel opening drives further influx of sodium ions until an action potential is fully generated and propagated.

Key Principles and Nuances

• Differentiation of Negative Feedback and Homeostasis:
  • Not all negative feedback systems are homeostatic.
  • A negative feedback system is only considered homeostatic if it successfully returns a changed variable back to within its normal physiological range.