Homeostasis

• Homeostasis refers to maintaining steady states in the body through coordinated physiological mechanisms.
• These mechanisms restore normal internal conditions after disruption.
• The goal is the maintenance of the stable environment for cells.

Internal Environment of the Body

• Includes extracellular fluids (ECFs) like transcellular fluid (TCF), plasma, and interstitial fluid (ISF).
• ECFs do not directly communicate with the surrounding environment, but provide a surrounding bathing fluid for cells.
• The digestive, respiratory, urinary systems, skin, and sensory organs are in direct contact with the external environment.
• Large contact areas with the external environment pose a potential threat to the stability of the internal environment.

Factors Affecting Homeostasis

• The stable composition of extracellular fluid is constantly disturbed by the external environment and metabolic processes in cells.
• According to Claude Bernard, stability of the internal environment is essential for free and independent existence.

Homeostatic Mechanisms

• Negative feedback, positive feedback, and feedforward control are key mechanisms.

Feedback Control Components

• A regulated variable, a vital parameter, is maintained within a set range.
• Sensors (detectors) detect deviations from a set point (internal reference value).
• An integrating center (controller, comparator) is a region of the brain or spinal cord, or cells of endocrine glands.
• Effectors (generally muscles or glands) defend the set point against deviations.

Negative Feedback

• It's a simple or complex feedback loop.
• Involves a controller, effector, sensor, and regulated variable.
• The output reduces the original stimulus effect.
• The activity of the effector is affected negatively by its product.
• Examples of negative feedback include regulation of blood glucose and calcium levels, heart rate, and blood pressure.

Complex Negative Feedback

• Involves several components such as the CNS, hypothalamus, anterior pituitary, peripheral gland, and tissues.
• Examples include hormones of the thyroid gland, glucocorticoids, and sex hormones.

Positive Feedback

• Effector activity is influenced positively by its product.
• It does not lead to stability or regulation and results in a progressive change in one direction.
• Secretion of estrogens (follicular phase) and calcium-induced calcium release are examples.

Feedforward Control

• It's based on continuous prognosis of the system's output when a change with time is desired and can be anticipated.
• Moment-to-moment operation is open loop, and the regulated variable is not sensed.
• Correction can be achieved through feedback control.
• For example, the CNS anticipates a higher O2 demand before physical exercise and sends a command to the respiratory center to increase ventilation.

Complex Regulation

• Homeostasis is maintained by negative, rather than positive, feedback mechanisms.
• Effectiveness of some negative feedback mechanisms is increased by positive feedback loops to enhance the efficiency of feedback control systems, examples being blood clotting and activation of digestive enzymes.
• Correction remains possible even if regulatory loops are disturbed or destroyed because several cooperating mechanisms come into action simultaneously or successively, called redundancy.
• Control functions can adapt based on past experience (learning) or long-term administration of disturbing stimulus, which can result in more efficient regulation, as in the secretion of digestive enzymes elicited by the thought of food.
• Baroreceptors, however, may adapt on long-term elevation of arterial blood pressure, resulting in impaired regulation.
• Efficiency of homeostatic mechanisms varies over a person's lifetime, especially during critical periods just after birth and advanced age.

Regulated Variables

• pH, mineral concentrations (Na, K, Mg, Ca, Cl), and organic compounds (e.g., glycemia, urea concentration) are regulated variables.
• Body fluid volumes and osmolality are also regulated, where TBW = ECF + ICF = ISF + plasma + TCF + ICF.
• Blood pressure, body temperature, and partial pressures of O2 and CO2 are regulated variables.

Hydrogen Ion (H+) and pH

• Hydrogen ion concentration [cH+] cannot be easily measured in body fluids, is always higher than the activity of H+ ions ([aH+]).
• Hydrogen ion activity [aH+] = 0.000 000 035 – 0.000 000 045 mol/kg water or 10-7.44 – 10-7.36 mol/kg = 35 – 45 nmol/kg
• pH = -log [aH+] mol/l (H2O)
• Increase/decrease in pH by 0.301 (log2) results in decrease/increase in H+ activity to 50%/200%.

Acids and Bases

• An acid can release a proton (H+).
• A base can accept a proton.
• Amphoteric substances, like amino acids, peptides, and proteins, can act as either acids or bases.

Dissociation

• General reaction for dissociation is: HA ↔ H+ + A-
• Dissociation constant (Henderson's equation): K = [H+] x [A-] / [HA], which can be rearranged to [H+] = K x [HA] / [A-]
• Henderson’s-Hasselbalch’s equation: pH = pK + log [HCO3-] / [H2CO3]

Acid-Base Balance of Body Fluids

• H+ concentration in plasma is 40 nmol/l, pH 7.4, and in ICF is approximately 100 nmol/l, pH 7.0.
• Body produces volatile (CO2): 13,000 – 20,000 mmol/24 hours.
• Production of non-volatile acids (H2SO4, H3PO4, lactate): 40 – 80 mmol/24 hours.
• pH stability is maintained through buffering systems, lung function, and kidney function.

Buffering Systems of the Blood

• 53% Bicarbonate: [HCO3-] / [H2CO3] = 20/1
• 5% Phosphate: [HPO42-] / [H2PO4-] = 4/1
• 35% Hemoglobin: Hb/HbO2
• 7% Protein: AA could serve as bases or acids, with an isoelectric point of majority of proteins at pH < 7.0.

Bicarbonate Buffer Function

• Increase in strong acid (HA) concentration: [H+] + [A-] + [Na+] + [HCO3-] ultimately leads to [Na+] + [A-] + [H2CO3], and then [H2O] + [CO2].
• Lungs expire excess CO2 to maintain pCO2 at normal levels, with ventilated systems increasing bicarbonate buffering efficiency tenfold.
• Increase in strong base (NaOH) concentration: [OH-] + [Na+] + [H2CO3] leads to [Na+] + [HCO3-] + H2O.
• Alkalosis is more frequently caused by loss of strong acid or loss of strong acid anions (replaced by bicarbonate from carbonic acid).

Ions

• Ionic composition of the internal environment is maintained in relatively narrow limits (Na, K, Ca, Mg, Cl).
• The balance between intake (food) and output (kidney, GIT, sweating) is more easily disturbed in critical periods (newborns, advanced age).
• Endocrine control includes:
  • Ca - parathyroid hormone, calcitonin, calcitriol
  • Na - aldosterone, ANP
  • K - aldosterone

Osmosis

• Osmotic pressures on semipermeable membranes are maintained stable.
• Osmolality (molality, molal concentration) is the total amount of dissolved, osmotically active particles in 1 kg of the solvent (mmol/kg).
• (Os)molarity (molar concentration) is the total amount of dissolved, osmotically active particles in 1 L of the solution (mmol/l).

Osmolarity and Osmotic Pressure

• Normal osmolality of the plasma is 275 – 295 mmol/kg; its osmolarity is slightly lower, approx. 270 mmol/l.
• Calculated osmolality = 2 Na + 2 K + Glucose + Urea
• Plasma density is 1025 kg/m³.
• Osmotic pressure = approximately 270 (mmol/l) x 8.314 (J.K-1.mol-1) x 310.15 K = 696 kPa
• Effective osmotic pressure is always lower than the calculated value since biological membranes are partly permeable to many substances.
• Oncotic pressure is the osmotic pressure on the membrane impermeable exclusively to protein macromolecules (capillary wall), and is only 3.3 kPa .