Fundamentals of Physiology and Cell Ions Flashcards
Define and identify physiology and pathophysiology in the human body
Physiology studies the characteristics (chemical, physical and mechanistic) that contribute to function and the processes of life.
- An understanding of the underlying physiological principles affords effective treatment in disease
- Allows monitoring of the patient
- Physiological knowledge, and its development, grants potentially more avenues towards optimised (and novel) treatments.
Pathophysiology studies pathology in the context of physiology. For example, this could be disease process or injury.
Explain signalling and homeostasis
Homeostasis
Most important form of homeostasis is negative feedback
- Stimulus -> Sensing -> Controller -> Effector -> Stimulus…..
Thermoregulation:
- A: thermal receptors detect the nominal set temperature – no action required – system at equilibrium.
- B: thermal receptors detect a higher temperature than nominal – action required to maintain equilibrium.
Explain negative and positive feedback and how they contribute to homeostasis
Negative feedback
Generally, when a variable moves beyond nominal the controller initiates negative feedback, via the effector, to return the variable to normal range.
Positive feedback
Positive feedback rapidly leads to system instability
This is a self-perpetuating cycle where the variable is amplified but not controlled leading to instability and loss of equilibrium
Positive application of a cycle
E.g. Birth:
- Stretching of the cervix causes the release of oxytocin
- Oxytocin stimulates the uterus to contract
- This increases pressure and stretching on the cervix
- Cycle amplifies
E.g. Blood loss:
- 1L blood loss: recoverable in terms of homeostatic control
- 2L blood loss: potentially non-recoverable.
- Too little blood to pump the heart effectively – arterial pressure falls, coronary blood flow reduces.
- Cycle amplifies resulting in further weakening of the heart, further reduced blood flow.
Describe fluid compartments in the human body, their composition and movement (diffusion and osmosis)
Diffusion
The movement of molecules down their concentration gradient
Factors affecting the rate of diffusion:
- Concentration - effective gradient
- Viscosity - movement
- Temperature - kinetic energy of molecules
- Mass - Affects kinetic energy; K = 1/2MV
Osmosis
- The net diffusion of water down its concentration gradient
- If the barrier is selectively permeable to water (significantly less to NaCl), there will be a net diffusion of water to areas of high ion concentration
Osmotic Pressure:
- measured using an U-tube
- The pressure required to halt the net diffusion of water (osmosis)
- Osmosis will continue until the pressure difference between A and B is sufficient to halt the flow of water
- This pressure difference is the osmotic pressure of the solution (chamber A)
- The principal factor that determines the osmotic pressure of a solution is concentration
- How much force is needed to stop the movement of water
Molecular level
If concentration is the same/No difference in
[H2O] between
inside and outside , isotonic solution = no net movement
Hypertonic: If [H2O] outside is LESS then found on the inside = movement of water out of the cell (shrink)
Hypotonic: [H2O] outside is MORE then found on the inside, water movement into the cell = swelling
Recognise what voltage is and define, give examples and differentiate between excitable vs non-excitable tissues
Voltage
- Voltage is the potential difference between two points in an electrical field
- Biologically relevant voltages are a consequence of membrane properties and ion concentrations
- Cell membranes are not normally permeable to charged ions
- Ions moved by various active and passive processes
- K+ forms the majority of cations inside the cell while Na+ forms the majority outside the cell, Cl- ions are also important.
Membrane potential = Membrane voltage
Most proteins inside the cell is negatively charged
helps to contribute to the negative charge of the cell
- Positive ions; not only concentration gradient but also attracted to the negative charge in the interior of the cell
- Electrochemical gradient with a membrane potential
- Repulsion of like charge, resists the movement of the concentration gradient
Excitable and non-excitable cells
- Excitable cells can produce OR respond to electrical signals
- Excitable cells can propagate action potentials
- Excitable: neurons, skeletal muscle cells, smooth muscle cells, cardiac myocytes
- Non-excitable: everything else
Recall functions and location of ions
Ca2+
Many enzymes or proteins that activated by increased intracellular calcium
The rules of ionic balance
- The concentration of positive and negative ions must “nearly” balance
- Any ion that leaves the cell must be replaced soon by another ion of that type coming into the cell
- Energy is always being used to re-establish the ionic gradients across membranes
Describe how ions cross the membrane: rules of ionic balance, gradient directions, electrical and chemical forces
Phospholipid Bilayer Transport Options
Different proteins:
Membrane-bound - extracellular site
Membrane channel:
- Making the membrane porous
Membrane spanning:
- Same principle as channel but allows movement against the concentration gradient
Passive transport: diffusion
Passive transport is always related to the diffusion of molecules down their concentration gradient. Diffusion may also be referred to as “simple diffusion”.
Passive transport: facilitated diffusion 1
- Channel proteins can be non-specific, or they can specific for a particular atom or molecule
- Cannot transport without the protein
- facilitating the transport from high to low concentration
Passive transport: facilitated diffusion 2
- Carrier proteins change conformation after binding to the target molecule and allow membrane passage
Passive transport: facilitated diffusion 3
- Carrier proteins change conformation after binding to the target molecule and allow membrane passage
- If the concentration of the diffusing molecule is high, then the rate of facilitated diffusion reaches a maximum rate as the carrier protein becomes saturated with its target molecule. Biochemically this is known as the Vmax.
- Facilitated diffusion is limited by the number of carrier proteins
2o Active transport: cotransport via symporters
- Channel proteins can transport molecules in same direction using the gradient of one component
- Couple energy from ions moving down its concentration gradient to allow for the passage of glucose against its gradient
2o Active transport : exchange via antiporters
- Channel proteins can transport molecules in opposite directions using the gradient of one component
1o Active transport : Na+ - K+ ATP pump
- PRIMARY active transport makes use of ATP as an energy source to drive the transport of molecules and atoms across the cell membrane.
- Exporting potassium to import sodium
- Hydrolyses ATP to ADP, using the energy released to conform protein to allow for the movement of sodium ions against its concentration
Appreciate the importance of carbonic anhydrase
Facilitates H2O +CO2 to H2CO3
An enzyme that catalysis the reaction of H2O and CO2 to generate carbonic acid and subsequently bicarbonate
H2O + CO2 <-> HCO3- + H+
The enzyme is involved in pH acid/base homeostasis and the direction of the reaction depends upon the environment
Appreciate the functions and mechanisms of ionic activities in a non-excitable cell
Importance of pH
pH_
pH is a measure is the negative logarithm of hydrogen ion concentration: pH= -log [H+]
- Intra- and extracellular pH tightly regulated, with extracellular fluid (pH 7.40) generally somewhat less acidic than the cytosol (pH 7-7.4)
- Plasma pH is tightly regulated by homeostatic mechanisms via the lungs and kidneys
- Formally pH = -log [H₃O+] since in water there will be no free protons an to be precise, we would generate these hydronium ions instead. In practice we just state pH= -log [H+] for convenience
- pH is important because it denatures or interferes with catalysis. PKA of amino acids, changing their charge
Transport and pH example: parietal cells
- Parietal cells release HCl into the stomach
- The Hcl concentration is ~160mM
- HCl can help digest food and protect the stomach from pathogens
- The low pH also stimulates proteolytic enzyme, sets up catalytic site
- CO2 enters the cell via passive transport (may also be generated via metabolism)
- CO2 and H2O react via the catalysis of CARBONIC ANHYDRASE
- H₂O + CO
- The dissociated proton (from H2CO3) is transported across the membrane via the H+/K+ ATPase pump
- Some protons may be acquired from the dissociation of H2O (will be minor)
- K+ ions are recycled across the membrane
- HCO3- is transported to the plasma via a Cl- antiporter
- Cl- ions are then transported across the membrane (lumen)
- The HCl concentration now rises in the lumen to approximately 160mM
Drug
- Omeprazole acts as a proton pump inhibitor (PPI)
- Forms a disulphide bond to target residues in the H+/K+ ATPase
- Oxonol dyes inhibit the chloride bicarbonate antiporter (and other transporters)
