Understanding Homeostasis

Homeostasis

• Is the body's ability to maintain a stable internal environment despite external changes.
• Requires cells, tissues, organs, and organ systems to maintain variables within compatible ranges for life.
• Involves dynamic equilibrium with continuous changes while maintaining steady conditions.
• Employs physiological mechanisms for proper body functioning amidst external dynamism

Origin and Definition

• Coined in 1962 by American physiologist Walter Bradford Cannon.
• Derived from Greek words: "hómoios" (similar), "hístēmi" (standing still), and "stásis" (standing).
• The human body is structured hierarchically: cells to tissues to organs to systems, all functioning in unison.
• Organs collaborate to maintain internal conditions within an ideal or normal range.
• Variables have a set-point, which is the physiological optimum value or normal range.
• Variables body temperature, pH, electrolyte levels (sodium, potassium, calcium), and blood sugar are kept within the homeostatic range.
• Homeostatic range is defined by allowable upper and lower limits. For example, body temperature is between 36.5 to 37.5 °C.
• Dysfunction occurs if these ranges are exceeded.

Components of Homeostasis

• Receptor
• Control center
• Effector

Functionality of Components

• Receptors gather information (stimuli) from the surroundings and transmit it to the control center.
• The control center processes this information, determines the appropriate response, and sends signals to the effector.
• The effector generates a response based on control center signals to restore the normal homeostatic range.

Homeostatic Mechanisms

• Respond to perturbations via feedback mechanisms.
• Feedback loops bring the body back to a steady internal state. When deviations from homeostasis occur, signaling processes trigger mechanisms to restabilize.

Positive Feedback

• Accelerates/promotes a stimulus' effect to maintain its direction.
• Positive feedback includes labour contractions, blood clotting and action potential generation.

Blood Clotting (Example of Positive Feedback)

• Blood clot formation is a positive feedback mechanism.
• The conversion of blood from liquid to solid involves a series of clotting factor activations.
• Activated clotting factor activates more, forming a fibrin clot and maintaining the stimulus's direction.

Action Potential Generation (Example of Postive Feedback)

• Demonstrates positive feedback in neuron signaling during membrane depolarization.
• Voltage-gated sodium channels open in series down the axon as a nerve impulse travels.
• Initial channel opening leads to sodium influx, depolarizing the surrounding area and causing the next channel set to open.

Negative Feedback

• Inhibits stimulus source or slows metabolic processes, reversing the stimulus's direction.
• Examples of negative feedback include, thermoregulation, blood glucose regulation, baroreflex in blood pressure, osmoregulation.

Thermoregulation

• Example of negative feedback involving homeostatic regulation of body temperature.
• The human body maintains an internal temperature between 36.1 – 37.2°C
• Body temperature is regulated by the nervous system, specifically the anterior hypothalamus and the preoptic area of the brain.
• The thermoregulatory center receives impulses from the hypothalamus, brain, spinal cord, internal organs, great veins, and skin.
• Thermoreceptors are located in the hypothalamus, brain, spinal cord, internal organs, great veins, and skin.
• Brain thermoregulatory center initiates control mechanisms returning core temperature to its set point.
• The thermoregulatory center sends signals for muscle shivering and autonomic nervous system vasoconstriction, especially in the skin.
• Body gains heat when temperature is higher than skin temperature increasing the core temperature.
• When temperature is less than skin temperature, heat loss occurs, lowering the core temperature.
• The thermoregulatory centre stimulates sweat secretion for evaporative cooling and vasodilation

Blood Pressure Homeostasis

• Negative feedback regulates blood pressure.
• The cardiovascular center receives information about BP changes from baroreceptors in carotid sinus and aortic arch.
• Baroreceptors also signal atrial heart muscle cells to release atrial natriuretic peptide (ANP).
• ANP regulates blood pressure by managing blood volume through the renin-angiotensin-aldosterone system, inhibiting renin production.

Homeostatic Imbalance

• Homeostatic mechanisms fail and homeostasis is lost.
• The result becomes cellular deficiencies and toxic accumulation
• Lack of restored balance leads to disease or death.

The Cell

• Cell is the basic living unit of the human body.
• The human body has an organized structure composed of cells.
• Trillions of specialized cells carry out defined functions.
• Although cells share a general structure, the specific structure depends on its function.

Contents of the Cell

• Different substances make up the cell are called protoplasm.
• Protoplasm consists of water, electrolytes, proteins, lipids, and carbohydrates.
• Cells contain intracellular organelles, which are highly organized physical structures.

Cell Membrane

• Most cell organelles are covered by membranes, such as the cell membrane, nuclear membrane, endoplasmic reticulum membrane, mitochondria, lysosomes, and Golgi apparatus.
• Membranes consist of lipids and proteins but each one has differing features based on the organelles of the function.
• Each cell is enclosed by cell membrane.
• A thin, elastic structure (7.5 – 10 nanometers) composed proteins, lipids and carbohydrates.

Lipid Bilayer

• The basic structure of the membrane is the lipid bilayer
• The lipid bilayer consists of phospholipid molecules (phosphatidylcholine and phosphatidylethanolamine) arranged with hydrophilic ends exposed to water-rich surfaces while hydrophobic ends face each other.
• The phosphate end of the phospholipid is hydrophilic
• The fatty acid portion is hydrophobic.
• The lipid layer is impermeable to water-soluble substances like ions, glucose, and urea.
• Fat-soluble substances, such as oxygen, carbon dioxide, and alcohol, can penetrate the membrane more easily.

Role of Cholesterol

• Cholesterol in the membrane helps in determining the permeability of the bilayer to water-soluble constituents of body fluids.
• Cholesterol controls membrane fluidity and influences activity of membrane-associated enzymes and aging processes.

Cell Membrane Fluidity

• Is the freedom of movement of protein and lipid constituents within the cell membrane.
• Reduced membrane fluidity impairs normal cellular functions and increases susceptibility to injury and death

Membrane Proteins

• Proteins, integral and peripheral, are embedded in the membrane.
• Integral proteins pass through the membrane.
• Peripheral proteins are found on the inside or outside membrane surface.
• Proteins function as cell adhesion molecules, pumps, carriers, ion channels, receptors, and enzymes.

Transport across Cell Membranes

• ICF volume and the composition remains separate from the ECF.
• Membrane permeability and the transport controls the the specific substances by its selective permeability.
• Cell membranes allow passage of small, lipid-soluble substances like oxygen, lipids, Co2, and alcohol.

Types of Transport Mechanisms

• Passive transport
• Active transport

Passive Transport

• Movement of substances across the membrane does not required cellular energy.
• Substances move down concentration or electrical gradients to form an electrochemical gradient.
• Movement proceeds from high to low chemical concentration.
• Cell membranes are polarized, with a negative interior and a positive exterior.
• Positively charged particles moving from positive outside to negative inside are drawn to negative charges and moves down concentration gradient

Types of Passive Transport

• Simple diffusion via the lipid layer which allows lipid-soluble substances (oxygen, carbon dioxide, alcohol) to pass through.
• Simple diffusion via protein layer allows water-soluble substances (water, electrolytes) to occurs via integral protein channels.
• Some channels are ion-specific, continuously open (ungated), or closed and require opening signals (gated).

Facilitated/ Carrier Mediated Diffusion

• Water-soluble substances with large molecules (glucose, amino acids) are transported using specific carrier proteins.
• Differs from simple diffusion as it shows competitive inhibition.
• Its shows saturation kinetics: the amount of carrier protein limits transport rate, achieving transport maximum (Tm).

Types of Carriers

• Uniport: transport one substance.
• Symport: transport two or more substances in the same direction (glucose and sodium ions from intestinal lumen to cells).
• Antiport: transport substances in opposite directions (sodium-potassium pump).

Sodium-Potassium Pump

• Sodium ions(Na⁺)-potassium ions (K⁺) (ATPase operates as an antiporter.
• Actively transports 3 Na⁺ out and 2 K⁺ into cells for each ATP molecule hydrolyzed.

Osmosis

• Is diffusion of solvent molecules (water) into a higher concentration of a non-permeable substance.
• Requires an imbalance of solutes between the ECF and ICF

Types of Osmosis

• Endosmosis: water moves into the cell.
• Exosmosis: water moves out of the cell.

Osmotic Pressure

• Pressure is applied to a solution to stop fluid movement across a semipermeable membrane.
• Its amount of pressure is required to prevent water flow.
• Lower water concentration and a higher concentration of solute generates a higher osmotic pressure of a solution.
• The osmotic pressure of a solution is proportional to concentration of osmotically active particles.
• Colloid osmotic pressure (oncortic pressure) is the osmotic force created by macromolecules within the intravascular compartment.

Key Quantities Definitions

• Mole: standard SI unit describing molecular weight (MW) of a substance in grams.
• Osmole: unit for osmotically active particles, total particle number in solution.
• Milliosmole: one-thousandth of an osmole.
• Osmolality: number of osmoles dissolved in a kg of water.
• Osmolarity: number of osmoles in one litre of plasma.

Active Transport

• Is the movement of substances against gradient (chemical or electrochemical gradient).
• Requires energy from the breakdown of ATP.
• Requires carrier proteins or pumps.

Types of Active Transport

• Primary Active Transport: Energy comes directly from ATP breakdown.
• Secondary Active Transport: Utilizes primary active transport of one substance (Na) to facilitate the passive transport of another (glucose/amino acids or hydrogen ions).
• Vesicular Transport

Primary Active Transport

• The energy liberated is from the breakdown of ATP.
• Transport substances like electrolytes, sodium, potassium,calcium, hydrogen and chloride.

Secondary Active Transport

• Primary transport of sodium ions from the cell facilitates the diffusion of sodium and other molecules from the lumen.
• Sodium and glucose/amino acids symport and sodium and hydrogen antiport exists.

Vesicular Transport: Pinocytosis

• Transports 'Cell drinking' of large molecules, such as proteins, through membrane invagination and vesicle formation enclosing ECF and macromolecules.
• Vesicles fuse with lysosomes.
• This process allows enzymes to digest the substances.
• The products of digestion diffuse into cytoplasm, while undigested material is removed by exocytosis.

Vesicular Transport: Phagocytosis

• Transports 'Cell eating' of large particles.
• It follows similar steps to pinocytosis process and occurs in larger particles such as macromolecules engulfed into the cell, pathogens, tumor or senescent cells.
• Cells that perform this function are called phagocytes.

Vesicular Transport: Exocytosis

• Is the reverse of pinocytosis as it expels waste products out of the cell.
• It exports synthesized proteins stored in granules fuse with cell membrane and granules are discharged.

Body Water Compartments

• Cells exist in an “internal sea” of extracellular fluid (ECF), which is the internal environment.
• In animals with closed vascular systems, ECF consists of interstitial fluid and blood plasma.
• Interstitial fluid surrounds cells by bathing it and also being outside the vascular system..
• Transcellular fluid is a smaller compartment within the extracellular fluid.
• The total body water is one third extracellular and the remaining two thirds is intracellular fluid (ICF).
• Intracellular component is 40% of body weight, ECF is 20% in adults.

Fluid Volumes and Percentages

• Approximately 25% of ECF is in the vascular system, and 75% is in the interstitial space
• Total body fluid is divided between: extracellular fluid (ECF). intracellular fluid (ICF).

Measuring Fluid Volumes

• Indicator-Dilution Principle is used for measuring fluid volumes
• Indicator substance must be injected, allowing it to mix/distribute.
• Measure dilution determines compartment volume based on mass conservation.
• Calculation for total mass: Volume B x Concentration B = Volume A x Concentration A

Ideal Indicator Substance Characteristics

• An indicator has to be non-toxic
• The indicator has to disperses evenly in compartment being measured.
• The indicator has to be dispersing exclusively to the compartment of measure.
• The indicator should not be metabolized or excreted.

Acid-Base Balance

• Requires a balance between the concentrations of acids and bases in the body fluids.
• Lungs excrete acid in the form of Co2 and Kidneys excrete hydrogen ions and conserve bicarbonate.
• Non-volatile acids are mainly regulated by the kidneys.
• Changes in [H+] affect all cell and body functions due to enzyme system sensitivities.

Actions of Acid and Base

• Acids release H+ in solution (e.g. HCl, H2CO3).
• A base accepts H+ (e.g. HCO3, HPO4=).

Acid-Base Balance Regulators

• In the body fluids acidosis/alkalosis can be regulated:
• Chemical acid-base buffer systems: (1) proteins, (2) hemoglobin, (3) carbonic acid-bicarbonate system, (4) phosphate, and (5) ammonium-ammonia.
• The respiratory centre
• The kidneys

Chemical Buffers

• Minimises pH fluctuations in fluid.
• The normal blood pH is 7.35 to 7.45.
• Buffers reversibly bind H+.
• Weak acid/base pairs capture free ions.

Key Buffer Actions

• Buffers do not add/remove H+ from body.
• Buffers tie-up free H+ until homeostasis is reestablished.

Definition of pH

• pH is the expression of H+ concentration on a logarithm scale.
• The Henderson-Hasselbalch equation represents it: pH=pK +Log [base]/[acid].
• Buffers in a biological system follow the isohydric principle, where multiple acid/base pairs reach equilibrium through the hydrogen ion interaction.

Implications of the Isohydric Principle

• All buffers in a system contribute in the pH levels.
• The pH can be calculated via an individual the buffer system.

Buffer Power

• effectiveness of a buffer determined by the pH of the solution and the pK of the buffer.
• Buffer system is the most effective when their pH is near the pK.
• Buffer system retains effectiveness at 1.0pH unit on other side of pk.
• The concentration of the buffer determines the buffer power.
• The addition of acid or the base on to the buffer would cause a shift in the pH.

Bicarbonate Buffer System

• Bicarbonate buffer is considered the most powerful buffer in the ECF
• HCO3- and CO2 are regulated by the kidneys and lungs,

Phosphate Buffer System

• Plays a major role in buffering renal tubular fluid and intracellular fluids.
• The dihydrogen phosphate (H2PO4-) (weak acids) and monohydrogen phosphate (HPO4=) (weak base) are the component of the buffer system.
• Can be described by the equations, HCl + Na2HPO4 → NaH2PO4 + NaCl, and NaOH + NaH2PO4 → Na2HPO4 + H2O

Properties of the Phosphate Buffer

• Phosphate has a pK of 6.8 close to the 7.4 pH, system operates with max power.
• Phosphate remains lower in the ECF.
• However, the phosphate is abundant in the tubular fluids of the kidneys and increased in buffering power.
• The phosphate is important for buffering tubular fluids.

Protein Buffers

• Most abundant buffers but uneven distribution.
• Protein buffers are made of amino acids, contatining positively(+) changed carboxyl/amino acids
• Charged regions can also bind hydrogen/hydroxil ions and function as buffer.
• Proteins are buffers and carboxy/amino groups dissociate.
• Nearly all proteins function as buffers, and help regulate in fluid ( ECF/ICF
• 60-70% of buffering is located inside cell result in intracellular proteins.
• Protein concentrations in cells are high, system is fairly closer to 7.4.
• Haemoglobin is a protein found in a RBC.

Isohydric Principle

• Chemical buffer system act in the isohydric principle.
• Buffer system changes the same, when fluid changes due to the H+ concentrations.
• System also will act together since it has a common reaction of all system.

Respiratory Regulation of Acid-Base Balance

• Second tier defence against acid-base related disturbances with CO2 regulation of the ECF.
• A response happens by roughly 3-12 minutes.
• Increase in aeration removes CO2, while the decrease then will increase CO2,
• If there is metabolic formation for CO2, the other factor affecting Extracellular fluid (Pco2) is in the rate of alveolar.

Actions of Respiration in Acid-Base

• Acts as a negative feedback for H+ concentration controller, regulation is a buffer system and its overall buffer power is then the buffer for chemicals. For metabolic regulation is inadequate to have control for the pH disturbance.

Acidosis and Alkalosis

• Acidosis happens the pH levels is falling at 7.4, or if it has alkalosis then pH levels will raise 7.4. Limit is between pH and a person can be alive is at roughly 6.8 and 8.0.