Session 1. 1 - Flow Flashcards
What is physiology
The physics of living systems
What is physiology at all levels
Involves the study of the flow of matter and energy within and between body systems
How does what happens at the whole body level reflect processes at a cellular level?
. What
What do physiologic processes such as flow require
Energy
What forms of energy flow between each other
Potential energy and kinetic energy energy
What are diseases processes
Disturbances to normal flow and utilisation of the body’s energy resources
Interactions are
Functional - systems interact to perform work
Dynamic
Very organised directed flow of matter and energy within bio-electrical fields
Flow requires precise control and regulation
Cellular activity is directed and regulated
Why is flow relevant to medicine
In every body system, flow is a clinical measurement to determine health and disease
Eg: pulmonary, CV, GI, renal
If blood stops or food blocked
What is the function of pulmonary flow
Enable respiratory gas flow
Supply of O2 + removal of CO2 - depending on level of activity
Flows through tracheal -> bronchial-> alveoli
Transfer matched to Cv flow - exercise, so increased demand increased flow
How to measure pulmonary flow
Lung capacity (volume)
Peak expiratiry flow rate - how fast gases can move through the airways
Airway resistance
What process do you think of when diagnosing all flow
Where is functional deficits?
Listen - measure - imaging - oximetry (eg: how saturated oxygen levels are)
Why might there be airway resistance
Accumulation of fluid
What are the possible causes of pulmonary deficit
Asthma
COPD
COVID 19
How to treat pulmonary flow
Steroids
Cell butamole - increase diameter
What is the function of cardiovascular flow
Supply of O2 and removal of CO2
Supply of nutrients to support metabolism, growth, repair
Removal of waste products
Flow matched to demand
Flows heart/lungs - arteries - arterioles - capillaries - venules - veins
Pulmonary flow matched to CV flow, increased demand, increased flow
How to measure CV flow
ECG - measure of pump efficiency(changes in electrical field), Heart rate x stroke volume = cardiac output (lub dug) Blood pressure Blood biochemistry (cholesterol and resistance to flow)
What are diseases associated with CV deficit
CHD
High BP
Cardiac related atherosclerosis
Could use stent
Diagnosis determines
Whether to use therapeutics - drugs
What are examples of flow at the molecular level
Membrane transporters/channels - regulate flow selectively
Nerve action potent toon - spatial-temporal control of Na+ and K+, type of electrochemical flow
Information
What is potential energy
Stored in chemical bonds
Energy released in reaction (ectothermic)
What is potential energy used for
Found in the phosphate bond in ATP
concentration gradients across cell membranes, electrochemical gradient I - generates membrane potential
Electrochemical gradient 2 - source for secondary active trasnport
Electric field - act on voltage sensitive proteins
Elastic PE - held in molecular structures for release as mechanical energy, directed movement of structure
The release of PE
needs to match the demand for KE - flow control
What is kinetic energy
Held in chemical bonds
When broken thermal energy from exothermic reactions is released which can be converted into random Brownian motion (disorganised flow)
What is KE used for
Chemical gradient - movement across membrane
Electrochemical gradient - current flow across membrane
Electrochemical energy 2 - current flow+ co transport = secondary active transport
Electrical field - field movement, when moved, there are conformational changes in voltage sensitive proteins
Elastic energy - released as mechanic energy, bring about conformation changes like in actin/myosin, when synchronised, macromolecular movement
Why is glucose considered high energy source
Due to the potential energy present in the C-H bonds and C-O
How much energy is given off as heat when mitochondria converts glucose to ATP
60% - keep core body temperature
What is potential energy in the form of
Chemical bonds
Concentration gradient across membrane
How do small molecules move around
Random motion
Eg: H2O, Na+ - rapid brownish motion
Fast
How do larger molecules move around
Slower
Eg: phospholipids, proteins
What type of substances can move across a membrane due to the energy provided by the electrochemical gradient
Lipid soluble hydrophobic or small polar - O2, CO2, H20 = diffusion
Large polar/ions = facilitated diffusion (need KE form and a protein to bind to)
Both some degree of random motion
Rate is proportional to temperature
How does the sodium/potassium ATPase work?
At rest - uses 30-35% of ATP
The chemical bond PE in ATP enables conformational change in ATPase to drive ions against their gradients
Carriers 3na out and 2k into cell
This is electrogenic - contributes to the electrochemical gradient across the cell
What drives the electrochemical gradient in primary active transport
The sodium/potassium ATPase
The electrical chemical chadienr is a important source of
PE
And has an associated Electric field - further source of PE
What is the Na+/K+ ATPase
Primary active transporter
All cells have a
Membrane potential
Outside the membrane
Positive
Inside the membrane
Negative
Due to the difference in electrochemical gradient
Current flow occurs
Movement of ions down the gradient (Na in, K out)= membrane potential
Causes localised changes in membrane voltage
How and why do sodium ion and potassium ion channels regulate flow in primary active transport
Precisely timed, sometime Na+ dominates (action potential) and sometime K+ dominates (hyper polarisation)
Action potential gives rises to non degrades signal carriage in excitable cells/tissues, which enables synchronous muscle contraction
Action potentials are also known as
Neuronal spikes
What drives the electrochemical gradient in xeoncdary active transport
Na+/K+ ATPase
Eg: in intestinal epithelial glucose transport
Lots of sodium ions travel out and cause confirmational change to drive co-transport of glucose inside the cell
What energy source is used for secondary active transport
Potential energy - more accessible than ATP and more sodium ions to do work than ATP so mobile
What happens as ions move down their gradient in secondary active transport
Use KE to drive conformational change in transporter protein (or can use specific trasnport proteins)
All cell have an
Electrical field across their membrane
Where do ions sit on an electrical field at rest
Negative inside
Positive outside - separated by a boundary
So large electrochemical gradient - source of PE
How do electrical fields allow specific ions through voltage sensitive channels
When ions move the electrical field moves within them, attached to current carrier, Na+, detected by voltage sensitive proteins, changes in electrical field causes voltage gated channels to depolarise and undergo conformational change which opens, allow specific ions through so current to flow
Electrical field change can bring about change in
Confirmation change in channels that are sensitive to it
How does ECG work
ECG reflects very large current and field changes
The shape of the ECG reflects ion movement and cardiac function
MEASURES FLOW
Elastic energy is released as
Mechanic energy when it springs back to lower ernegry confirmation, underpins storage in proteins
With phosphorylation of the protein what happens to PE and elastic energy
Both higher
Stages of potential energy -> kinetic energy
Phosphorylation - higher elastic energy
Elastic -> conformational change
Elastic -> released as mechanical energy (makes KE)-> release Na+
Uptake of K+ - loss of phosphate bond - mechanical energy return to lower energy state (uses KE)
Thus, a cycle and flow maintained
Elastic energy to mechanical energy
Muscle contraction - energy converted to mechanical energy
- ATP binds to myosin and out in high energy state in cocked position
- Myosin binds to exposed actin site losing ADP and P
- Myosin heads move and perform power stroke back to lower energy confirmation = mechanical energy
Synchronised so regulated flow of released elastic energy/PE which is then converted to ME
What is another example of PE-> KE or elastic -> mechanical
Release fo elastic energy stored in kinesin
What does signalling mean
Carry precise meaning within the system
Modulated by other signalling molecules and voltages
What is the classification of signalling molecules
Endogenous - within the body, eg: adrenaline, thyroid - neurotransmitters
Exogenous 1 - natural - plant based like morphine
Exogenous 11 - synthetic - man made
What is clinical pharmacology based on
Understanding of endogenous signalling molecules and their cellular targets
What are the main extracellular signalling groups
Endocrine
Paracrine
Autocrine
What are the purpose of extra cellular signalling molecules
Communication
Working in synchrony with a common purpose for the whole body
What is the endocrine system
A set of glands that produce hormones that act as signalling molecules into the blood - highly potent
Act over long distances
Cells need to express receptors for these hormones
What is the function of the neuroendocrine system
Regulation: Digestion Metabolism/respiration Growth Behaviours
What happens in disease to our endocrine system
The synthesis, release and degradation are no longer controlled and feedback mechanisms fails
What are the properties of amine hormones
Amino acid derivative
Small charged hydrophilic
Receptors in plasma membrane
What are the properties of peptides and proteins hormones
Hydrophilic
Short chain to many
Receptors in plasma membrane
What are the properties of steroid hormones
Common derivatives from cholesterol
Receptors are intracellular as lipid soluble (lipophilic)
Which type of hormone has the fastest plasma half life and time course of action
Catecholamines - seconds
Peptides and proteins - minutes
Steroids - hours
What are the mechanisms of catecholamines
Cause change in membrane potential
Trigger synthesis of second messengers
What are the mechanisms of peptides and proteins
Trigger synthesis of second messengers
Trigger protein kinase activity - change in DNA
What are the mechanisms of steroids
Receptor-hormones complex controls transcription and stability of mRNA
What are paracrine signalling molecules
Signalling from cell to cell
Released into extracellular environment and induce changes in receptor cell
Causes changes in behaviour or differentiation
What is an example of a paracrine signalling molecule
Neurotransmitter
How do neurotransmitters work as signalling molecules
Over a synapse
One way transmission of signal
There is an electrochemical signal which is proportional to the presynapric electrical field
What are the different types of neurotransmitter signalling molecules
Monamines, amino acids, acetylcholine
What are the primary signalling roles of neurotransmitters
Excitation - signal increase post synapticalky
Inhibitory - signal decrease post synapticalky
Neurones can summate to maintain fine control
What is the signalling function of acetylcholine
Excitably at the end of the organ
What are the types of neurotransmitter under the group monoamines
Adrenaline
Noradrenaline
Dopamine
Serotonin
What is the signalling function of adrenaline
Excitatory
What is the signalling function of noradrenaline
Excitatory
What is the signalling function of dopamine
Excitatory and inhibitory
What is the signalling function of serotonin
Excitatory
What are the types of neurotransmitter found under the group of amino acids
Glutamate
Glycine
GABA
What is the signalling function of glutamate
Excitatory
What is the signalling function of glycine
Mainly inhibitory
What is the signalling function of GABA
Inhibitory
What does receptor mean
Do not represent the only site for therapeutic drug action
To indicate a particular type of drug target
Has to be activated by a ligand or a signalling molecule
What happens when a signalling molecule binds with its target and what can signalling molecules do
Endogenous and exogenous signalling molecules - bring about change in functional status of target cells
This can cause another chemical or electrochemical signal to be produced which helps signal processing, perform a signal dependent task - transport or synthesis, direct interconversion between PE and KE
What is specific to endogenous signalling molecules binding to their target
Bind to receptors
Carry and transfer signal
Most are agonists - put receptor into an active state
What is specific to exogenous signalling molecules binding to their target
To carry imposter signal
Fit is less optimal
Act as antagonists - blocks or attenuated signal - important in therapeutics
Side effects are possible
Can be manufactured from endogenous molecules
What are the targets of signalling molecules in therapeutics (drug targets)
Receptors - different, ligand gated
Ion channels - voltage gated
Transporters
Enzymes
Gated channels governed by allosteric modulation
Exception - chemotherapy drug where target is a protein or DNA
What are the four drug target classes of receptors
Kinase linked receptors
Ion channels (ligand gated)
Nuclear/intracellular
G-protein coupled receptors
All receptors need a
Ligand or signalling molecule that activated them
How do ligand gated ion channels work
When bound with ligand - current - channel open and ions enter via facilitated diffusion - hyper polarisation or depolarisation - cellular effects
Milliseconds
Eg: nicotine can, ACh receptors
How do kinase linked receptors work
Mediate signals from a wide range of protein molecules such as hormones
Act via phosphorylation - signalling cascade - gene transcription - protein synthesis - cellular effects
Hours
Eg: cytokine receptors or hormones
How do nuclear receptors work
Lipid soluble steroid hormones bind to ligand receptor complex - enter nucleus and act as gene transcription factor - protein synthesis - cellular effects
Hours
Eg: oestrogen receptors
How do G protein coupled receptors work
3 types - GS, GI and GQ - activate different intercellular routes
Bring about changes in metabolism
Seconds
Eg: muscarinic receptors for acetylcholine
What are the targets of signalling molecules in voltage gated ion channels
Selective flow of ion currents down its electrochemical gradient Na K Ca Cl
How are voltage gated ion channels regulated
Modulated by phosphorylation - bring about change in conformation
The therapeutic effect occurs when binding using exogenous channel blockers
Eg: Na+/Ca+ channel blockers for epilepsy chronic pain, migraine
Opposite:
GABA Cl- channel agonists for epilepsy
What do transporter/carrier proteins do
Transport of ions/small molecules by facilitated diffusion
Active transport if needed when going against gradient, use ATP for energy or to establish gradient
Eg: many across GI tract, renal tubules
Serotonin when inhibited - treat mood disorders by targeting transporters
What do enzymes do
Signal processing
Transformation
Synthesis
Degradation
How do you target enzymes
Competitive inhibition - bind to active site, eg: aspirin reduces prostaglandin synthesis
ACE inhibitor - reduce levels of angiotensin - decrease BP
King Richard is the
RITE - four major groups
KLING - subdivision of receptors (to power) - L is ligand gated
