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Introduction to Physiology

  • Physiology is the study of the functions of living organisms
    • Concerned with the question “how does an organism perform its various activities”
    • Built on several fundamental principles and underlying physical laws. It is largely a quantitative science
    • Seeks to explain function from behaviour down to the molecular level

Homeostasis

The Principles of Homeostasis
  • Homeostasis is the term we use to describe the constant state of the internal environment. The processes and activities that help to maintain homeostasis are referred to as homeostatic mechanisms.
    • There is a set variable to be maintained (a STIMULUS)
    • A change the variable is detected by a receptor
    • The receptor passes information of the change back to a control centre
    • The control centre sends a message to an effector (to do something that counteracts the change)
    • The effector does something to counteract the change (a RESPONSE)
  • Homeostasis involves a loop with negative feedback

In a young adult male human of 70kg:

  • 42 kg water (60%)
  • 13 kg protein (18%)
  • 10 kg fat (15%)
  • 5 kg minerals (7%)

Fluid compartments

Fluid Compartments within the Body
  • Intracellular compartment
    • Fluid inside cells (inside membrane), including red and white blood cells
    • (Blood is a mixture of cells; plasma is the extracellular fluid)
  • Extracellular compartment (outside cells)
    • Interstitial space (the environment of most cells)
    • (Extracellular fluid = solution that bathes all cells)
    • Transcellular – pools of special fluids such as aqueous humour, synovial fluid, cerebrospinal fluid, urine in bladder
    • Plasma – the fluid of blood, excluding the contents of blood cells
    • Aqueous fluid in eyes
    • Synovial fluids in joints
    • CSF in spine

Electrolyte distribution in body compartments

  • We evolved from ocean creatures. As we moved onto land, we took ocean water with us. By extrapolating measurements of ocean salinity back in time (to the point where we left the ocean), we get the salinity of our CSF.
  • Note that the total osmoles in each area is the same, as water does not spontaneously rush from one area to another
  • Some basic ion concentrations:
    • Na high outside cell, low inside cell
    • K high inside cell, low outside cell
    • Protein high inside cell, low outside cell
    • Ca zero inside cell, some outside cell
    • Mg high inside cell, low outside cell
  • Gradients across a membrane work like a (backwards) hydroelectric power plant
    • Dam = membrane
    • Water level = ion concentration
    • Turbine and generator = pumps and carriers
    • Via the sodium pump, the cell has a way to store energy and quickly use it again (flooding)
      • Na+ wants to get inside the cell very badly
      • Flooding of Na+ inside the cell is analogous to a capacitor discharging
      • High current for a brief period of time
  • Use of the gradients
    • Store energy in a readily accessible form
    • An essential part of the cellular respiration cycle in mitochondria
    • Drive uptake and excretion of metabolites
    • Fast signalling: action potentials in neurones
    • Preventing multiple sperm fertilisation of a single egg
  • (No gradient => dead. – E.g. rigor mortis)
Phospholipid Bilayer
  • Separating the intracellular compartment is done through the phospholipid bilayer that is the cell membrane.
  • The constituent phospholipids have a head (which is hyprophilic – polar end) and a tail (which is hydrophobic – made of C-H… a fatty chain).
  • Spheres formed out of a phospholipid bilayer are called “micelles”, a low energy configuration that is stable under most conditions
Epithelial Cells
  • Separating the extracellular compartment is achieved via epithelial cells only.
  • There are various different sorts of junctions between cells that regulate fluid movement:
    1. Tight junctions
      • Critical to control fluid flow between cells
      • In most of the body, they’re very loose
      • They stop fluid leaking back between cells, allowing us to produce a filtrate on one side of the epithelium (e.g. kidneys)
    2. Adhering junction
      • Regulate how fluid moves between cells
      • Various proteins connect the cells
    3. Gap junctions
      • Enable intercellular fluid communication through little tubes (connexons) between the cells
      • Essential in the heart, where intercalated discs spread contractions and cause entire groups of myocardium to contract together
    4. Desmosomes
      • Hold cells together (specialised in cell-cell adhesion)

Movement of Fluid between Body Compartments

  • Movement of fluid around compartments occurs via the circulation of blood, which is a form of bulk flow.
    • Bulk flow is where all molecules flow in one direction (net simple movement along 1 axis only).
    • Since we exponentially expand the number of vessels, we get relatively little resistance, so in face most resistance comes from the arterioles.
    • It is impossible to do bulk flow across a membrane.
    • Hence we have diffusion.
  • Diffusion is the movement of molecules from an area where they are at a high concentration to an area where they are at a low concentration
    • Each molecule still does its own thing
    • Any individual particle is free to go back and forth, but in the long run we get equal movement in both directions across a membrane UNLESS there is a higher concentration of particles on one side of the membrane
    • In this case, there is a mathematically higher chance that we get movement from a high to a low concentration
    • Diffusion is very fast over short distances, but is very slow over long distances
    • Many molecules won’t be able to diffuse into a cell because:
      • They do not easily dissolve into the membrane (Na doesn’t diffuse into a cell as it hates the interior of the membrane)
      • The concentration gradient is against them
      • They are too big to diffuse well (Brownian motion)
    • Cells have molecular machinery to cope with these problems:
      • Pores and channels to make aqueous diffusion paths for ions
      • Pumps to move molecules against a gradient (harness the Na gradient to pull sugar in etc)
      • Carriers for facilitated diffusion of bigger molecules and pinocytosis (drinking) and phagocytosis to ingest really big molecules
    • Micro-organisms have devices to get material through our membranes, too
      • E.g. they have hollow protein tubes to inject material through the membrane (like a mosquito’s proboscis)
  • What drives water across the membrane?
    • Water is driven across the membrane by its concentration gradient (water moves from an area where it is at a high concentration to where it is at a low concentration)
    • This is based on the number of osmoles (total number of moles) of dissolved solutes inside and outside the membrane
    • E.g. if a rbc is placed in a hypotonic solution, it swells. If placed in a hypertonic solution, it shrinks
    • If the solution outside the membrane is distilled water, then water will move across the membrane indefinitely (or until the cell lyses; or in the case of column of water, osmosis is balanced by hydrostatic pressure) (since you can’t ever dilute a solution that has a finite concentration down to one with zero concentration)

Osmolarity/osmotic pressure

  • Osmoles (Osm) = total number of moles of solute particles (ions or molecules). One osmole is 6.022 * 10^23 particles (Avogadro’s number)
  • Osmolarity = number of osmoles per litre of solution (e.g. 5 mol/L of NaCl corresponds to 10 osmol/L)
  • Osmosis is the flow by diffusion of solvent across a semi-permeable membrane. It can be counter-balanced by hydrostatic pressure. A difference of 1 mosm/L exerts a pressure of about 20 mmHg
  • Capillary exchange depends on the difference between hydrostatic and osmotic pressure
    • Arteriole end of a capillary:
      • Hydrostatic pressure exceeds osmotic pressure, so there is net filtration (fluid leaving the blood vessel)
      • We have both high pressure and a small amount of solute, so that water leaves due to both osmotic and hydrostatic pressure.
    • Venule end of a capillary:
      • The remaining plasma has a higher osmolarity (because of retained protein; a lot of fluid has left) and hydrostatic pressure is lower, so there is net reabsorption
      • We have lower pressure and a higher concentration in the blood (water left the vessel but proteins and cells remained). Hence water is absorbed by osmosis.