Main Final Exam Content Flashcards
6 Steps of Protein Synthesis
- Rough ER synthesises proteins to be secreted to exterior or to be incorporated into plasma membrane or other cell components
- Smooth ER packages protein into transport vesicle, which bud off and travel to Golgi complex
- Transport vesicle fuses with Golgi complex and empties contents into Golgi sac
- Proteins travel through layers of the Golgi complex
- Secretory vesicles containing finished protein bud off Golgi complex and remain in cytosol to store until signalled
- On appropriate stimulation, secretory vesicles fuse with plasma membrane, open and empty protein into cells exterior for use
Describe Desmosomes (Cell Junctions)
- join two cells together without touching
- bound by glycoprotein filaments attached to thickened cytoplasm
- prevents tearing of the tissue when stretched
- e.g. epidermis cells, cardiac cells
Describe Tight Junctions (Cell Junctions)
- membrane proteins from adjacent cells fuse together
- prevents passage of molecules between adjoining cells
- e.g. nephrons in kidney, intestine cells
Describe Gap Junctions (Cell Junctions)
- tunnels from one cell to another
- transport of ions and small molecules between cells
- e.g. some nervous system cells, cardiac cells
Describe Passive transport and list the 3 different types of passive transport
Passive transport = doesn’t require energy (ATP)
- simple diffusion
- osmosis
- facilitated diffusion (channels & carriers)
Describe Active transport and list the 3 different types of active transport
Active transport = requires energy (ATP)
- primary active transport
- secondary active transport
- vesicular transport (endocytosis & exocytosis)
Describe Diffusion
- movement of molecules from an area of high concentration to an area of low concentration
- molecules diffuse down a concentration gradient in order to reach equilibrium
Describe Osmosis
- diffusion of water across a selectively permeable membrane
- movement of water from an area of low solute concentration to an area of high solute concentration
- osmolarity = number of solute particles per litre of solution
- most body fluids are 300 mOsm/L
Describe Facilitated Diffusion
- down concentration gradient
- does not require ATP
- two types: channel or carrier
Describe Channels (Facilitated Diffusion)
- transport of small ions (Na, K, Ca, Cl) and water (aquaporins)
- can be open or closed
- open to both sides of membrane simultaneously
- allows rapid transport of molecules
Describe Carriers (Facilitated Diffusion)
- transport for larger hydrophilic molecules (glucose and amino acids)
- always open
- only open to one side of membrane
- allows slower movement of molecules
List and describe 5 things that affect Diffusion Rate
- The size of the concentration gradient
- bigger gradient = faster diffusion - Membrane surface area
- bigger surface area = faster diffusion - Size of the molecule
- small molecules diffuse more quickly than large molecules - Diffusion distance
- decreasing diffusion distance = increasing diffusion rate - Lipid solubility of the molecule
- whether the molecule can pass through the lipid part of the membrane
Describe Tonicity
Tonicity = the ability of a solution to change the shape of a cell
Isotonic = solution concentration is equal to ICF concentration = no cell change
Hypertonic = solution concentration is higher than ICF concentration = cell shrivels/shrinks
Hypotonic = solution concentration is lower than ICF concentration = cell bursts/swells
List the 6 Steps of Primary Active Transport: Na/K ATPase
- Binding of cytoplasmic Na to the pump protein stimulates phosphorylation of ATP
- Phosphorylation causes the protein to change its shape
- The shape change expels Na to outside and extracellular K binds
- K binding triggers release of the phosphate group
- Loss of phosphate restores the original conformation of the pump protein
- K is released and Na sites are ready to bind Na again,; the cycle repeats
List the 3 Steps of Secondary Active Transport: Sodium Glucose Transport
- Na/K pump creates ion gradient
- Na - glucose symport transporter loading glucose from ECF
- Na - glucose symport transporter releasing glucose to the cytoplasm
Describe Vesicular Transport
- transfer of materials between ECF and ICF within vesicles
- requires energy from ATP
- endocytosis = vesicular transport into cell
- exocytosis = vesicular transport out of cell
List the 7 Steps of Receptor - Mediated Endocytosis
- Target molecules (ligands) bind to receptors in plasma membrane
- Areas coated with ligands form deep pockets in plasma membrane surface
- Pockets pinch off, forming endosomes known as coated vesicles
- Coated vesicles fuse with primary lysosomes to form secondary lysosomes
- Ligands are removed and absorbed into the cytoplasm
- The lysosomal and endosomal membrane separate
- The endosome fuses with the plasma membrane and the receptors are again available for ligand binding
List the 3 Steps of Pinocytosis (Endocytosis)
- Solute molecules and water molecules are outside the plasma membrane
- Membrane pockets inward, enclosing solute molecules and water molecules
- Pocket pinches off as endocytic vesicle containing sample of ECF
List the 5 Steps of Phagocytosis (Endocytosis)
- Cell engulfs large solid particles (e.g. bacterium)
- The cell extends pseudopods (cytoplasmic extensions) around the object
- The resulting vesicle (phagosome) can fuse with a lysosome containing enzymes
- The enzymes break down the object
- The object is then killed and digested within the vesicles
Describe Exocytosis
- reverse of endocytosis
- secretory vesicles are released from the Golgi complex. They bind to the cell membrane, releasing their contents
Describe Membrane Potential
- difference in electric potential between the interior and the exterior of a biological cell
- separation of opposite charges across the membrane
- the resting membrane potential is negative because the Na/K ATPase pumps 3Na out and 2K in
- resting membrane potential is approximately -70mV in a human neuron
Describe the Effect of Na/K pump on membrane potential
- Na/K pump transports 3Na out for every 2K it transports in
- most of the membrane potential results from the passive diffusion of K and Na down concentration gradients
Describe an Action Potential
- occurs when the membrane potential of a specific cell location rapidly rises and falls: this depolarisation then causes adjacent locations to similarly depolarise
- action potentials assist in the propagation of signals along the axon
List the 5 Steps of an Action Potential
- Voltage gated ion channels closed
- Some Na channels open, Na in
- Many Na channels open, Na in
Depolarisation: decrease in potential; membrane less negative - K channels open, K out, Na inactivated
Repolarisation: return to resting potential after depolarisation - Na/K ATPase restore Na and K concentrations during this time it is more difficult to generate AP.
Hyperpolarisation: increase in potential; membrane more negative
Describe Graded Potential
- local changes in membrane potential that occur in varying grades or degrees of magnitude or strength
- vary in magnitude
- proportional relationship between graded potential and triggering event
List the 9 Steps of Synaptic Neurotransmission
- Nerve implies is propagated along the pre-synpatic neuron until it reaches the pre-synaptic membrane
- Depolarisation causes Ca to diffuse through channels in the membrane
- This causes vesicles containing neurotransmitter to fuse with the membrane
- Neurotransmitter is released into the synaptic cleft via exocytosis
- Neurotransmitters diffuse and bind to receptors on the post-synaptic membrane
- Binding of neurotransmitter to receptor open Na channels
- Na diffuses down the concentration gradient into the post-synaptic membrane, causing it to reach threshold potential (-50mV)
- An action potential is triggered in the post-synaptic membrane and propagated along
- Neurotransmitter is broken down
Describe the 2 types of Direct Intercellular Communication
- Gap Junctions
- specialised intercellular connection between a multitude of cell types
- they directly connect to the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regulated gate between cells - Transient Direct Linkup of Cells Surface Markers
- direct linkup of cells surface markers
- cells are not in constant contact with each other
Describe the 4 types of Indirect Intercellular Communication Via Extracellular Chemical Messengers
- Paracrine Secretion
- local chemical messengers
- effect is exerted only on neighbouring cells in the immediate environment of their site of secretion - Neurotransmitter Secretion
- short range chemical messengers
- in response to electrical signals (APs) - Hormonal Secretion
- long range chemical messengers specifically secreted into the blood by endocrine glands in response to an appropriate signal - Neurohormone Secretion
- hormones released into blood by neurosecretory neurons
- respond to and conduct electrical signals
- distributed through blood to distant target cells
Describe Skeletal Muscle
- striated muscle tissue
- under voluntary control of somatic nervous system
- most skeletal muscles are attached to bones by bundles of collagen fibres known as tendons
- abundance of mitochondria, as is expected with the high energy demands of a tissue as active as skeletal muscle
Describe A and I bands
- myofibril displays alternating dark bands (A bands) and light bands (I bands)
- parallel line up of A and I bands leads to striation
- contraction of A and I bands leads to muscle contraction
List the 7 Steps of Excitation - Contraction Coupling
- Acetylcholine released from the axon terminal binds to receptors on the muscle cell plasma membrane
- An AP is generated and travels down the T-tubule
- Ca is released from the sarcoplasmic reticulum in response to the change in voltage
- Ca binds to troponin; cross-bridges form between actin and myosin
- Acetylcholinesterase removes acetylcholine from the synaptic cleft
- Ca is transported back into the sarcoplasmic reticulum
- Tropomyosin binds active sites on actin causing the cross-bridge to detach
Describe Twitch Summation
- addition of a second twitch, resulting in greater tension and results from stimulating the muscle before it has a chance to relax completely
Describe Tetanus
- prolonged contraction without relaxation and results from repeating stimulation before the muscle has a chance to relax at all
Describe Smooth Muscle
- found in the walls of hollow organs and tubes
- contraction exerts pressure on and regulates forward movement of the contents of structures
- no striation
Describe Cardiac Muscle
- found only in heart
- striated
- has clear length-tension relationship
- many mitochondria and myoglobin
- have T-tubules
- slender and short
- displays pacemaker activity
- interconnected by gap junctions
- joined in a branching network
- cardiac APs last much longer before repolarising
Describe the 3 Steps of Receptor Potential in Specialised Afferent endings
- In sensory receptors that are specialised afferent neuron endings, stimulus open stimulus-sensitive channels, permitting net Na entry that produces receptor potential
- Local current flow between depolarised receptor ending and adjacent region opens voltage-gated Na channels
- Na entry initiates action potential in afferent fibre that self-propagates to CNS
Describe the 6 Steps of Receptor Potential in Separate Receptor Cell
- In sensory receptors that are separate cells, stimulus opens stimulus-sensitive channels, permitting net Na entry that produces receptor potential
- This local depolarisation opens voltage-gated Ca channels
- Ca entry triggers exocytosis of neurotransmitter
- Neurotransmitter binding opens chemically gated receptor-channels at afferent ending, permitting net Na entry
- Resultant depolarisation opens voltage-gated Na channels in adjacent region
- Na entry initiates action potential in afferent fibre that self-propagates to CNS
Describe Labelled Line Theory
= the CNS determines the type of stimulus based on receiving input from all sensory cells activated by that stimulus
i.e. the brain can decode the type and location of stimulus by determining which ascending pathway the information travelled up via
Describe Tonic Receptor
- do not adapt, or adapt slowly
- these receptors are useful when it is valuable to maintain information about a stimulus
- Examples: muscle stretch receptors and joint proprioceptors
Describe Phasic Receptor
- rapidly adapting receptors
- quickly adapts by no longer responding to a maintained stimulus
- these receptors are useful when it is important to signal a change in stimulus intensity rather than to relay status quo information
- Examples: Pacinian Corpuscle
Describe Tactile Receptors and list the 5 types
- sensory input from these receptors informs the CNS of the body’s contact with objects in the external environment
- types:
1. Hair receptors
2. Merkel’s disc
3. Pacinian Corpuscle
4. Ruffini Endings
5. Meissner’s Corpuscle
Describe Hair Receptors
- rapidly adapting
- senses hair movement and very gentle touch
Describe Merkel’s Disc
- slowly adapting
- detects light, sustained touch and texture
Describe Pacinian Corpuscle
- rapidly adapting
- responds to vibrations and deep pressure
Describe Ruffini Endings
- slowly adapting
- respond to deep, sustained pressure and stretch of skin
Describe Meissner’s Corpuscle
- rapidly adapting
- sensitive to light, fluttering touch
List the 4 Steps of Chemically Gated Receptor Channels
- Extracellular messenger binds to receptor
- Binding of messenger leads to opening of channel
- Ions enter
- Ion entry brings about desired response
List the 4 Steps of Receptor Enzymes
- Extracellular messenger binds to receptor
- Binding of messenger leads to activation of protein kinase enzyme site
- Protein kinase activates designated protein
- Active designated protein brings about desired response
List the 7 Steps of G-Protein Coupled Receptors
- Extracellular (first) messenger binds to receptor
- Receptor activates G-protein
- G-protein activates effector protein
- Effector protein produces second messenger
- Second messenger activates protein kinase
- Protein kinase activates designated protein
- Active designated protein brings about desired response
List the 9 Steps of Intracellular Receptors
- Free lipophilic hormone diffuses through plasma membrane
- Hormone binds with intracellular receptor specific for it
- Hormone receptor complex binds with DNAs hormone response element
- Binding activates gene
- Activated gene transcribes mRNA
- New mRNA leaves nucleus
- Ribosomes “read” mRNA to synthesis new proteins
- New protein is released from ribosome and processed into final folded form
- New protein brings about desired response
List and describe 7 points of comparison between the Nervous System and Endocrine System
- Wired or Wireless
NS= anatomically linked to target cells (wired)
ES= anatomically separated from target cells (wireless) - Type of Chemical Messenger
NS= neurotransmitter, neurohormone
ES= hormones - Distance of Action
NS= short distance (across the synaptic cleft)
ES= long distance (into blood) - Specificity
NS= specificity depends on the closeness of neurons and target cells
ES= specificity depends on the presence of the target receptor - Speed of Response
NS= rapid (ms)
ES= slow (mins to hours) - Duration of Action
NS= short (ms)
ES= long (mins, days or longer) - Major Function
NS= rapid, precise receptors
ES= activities that require a long duration
List the 5 Steps of the Cardiac Cycle
- Ventricular & Atrial Diastole
- blood entering atrium. Atrial pressure > ventricular pressure
- AV open (passive flow of blood into the ventricles) - Atrial Contraction
- atrial pressure increases and ventricular volume increases until EDV - Isovolumetric Ventricular Contraction
- ventricular pressure > atrial pressure = AV open (1st heart sound)
- ventricular pressure < aortic pressure = SL closed - Ventricular Ejection
- ventricular pressure > aortic pressure = SL open
- ventricular volume decreases until ESV - Isovolumetric Ventricular Relaxation
- ventricular pressure < aortic pressure = SL closes (2nd heart sound)
- ventricular pressure > atrial pressure = AV closes
Describe Heart Sounds
Closing of Valves
- lub dub (pause)
First Sound (S1)
- closure of the AV valve
- beginning of ventricular systole
Second Sound (S2)
- closure of SL valve
- ventricular diastole
Describe Cardiac Output and give the formula
- volume of blood pumped by each ventricle per minute
- indicates blood flow through peripheral tissues
Cardiac Output = Heart Rate (beats/min) x Stroke Volume (ml/beat)
where:
Heart rate = how fast the heart is beating
Stroke volume = volume of blood pumped out of ventricle during each contraction
Describe Stroke Volume and give the formula
- volume of blood pumped out of ventricle during contraction
- different between EDV and ESV
where:
EDV = End Diastolic Volume = volume of blood in the ventricle during relaxation
ESV = End Systolic Volume = volume of blood in the ventricle after systole
Stroke Volume = EDV - ESV
Describe Venous Return
- volume of blood returning back to the heart each minute
- increasing venous return will:
- increase EDV
- cause heart muscle to stretch
- as cardiac muscle stretches, the next contraction will be stronger
Describe the Frank Starling Law of the Heart
- the greater the EDV/venous return, the greater the force of contraction during systole (within limits)
- if increase in EDV, stroke volume also increases. At rest, heart muscle is not at optimal length to produce contraction. When increase EDV, muscle and cell stretches, creating more optimal overlap between actin and myosin, therefore, creating a stronger contraction
List the 4 factors affecting venous return
- Cardiac suction
- Skeletal muscle pump
- Venous valves
- Respiratory pump
- Sympathetic Nervous system
Describe Cardiac Suction and its affect on venous return
- heart acts as suction pump
- occurs in both systole and diastole
- contraction (systole) of ventricles: sucks blood from veins into atria
- relaxation (diastole) of ventricles: sucks blood from veins and atria into ventricles
Describe Skeletal muscle pump and its affect on venous return
- large veins lie between skeletal muscle/run through muscle
- muscle action compresses the vein and pushes blood through vein
Describe Venous valves and its affect on venous return
- valves control the direction of blood flow and prevent back flow
Describe Respiratory pump and its affect on venous return
Inspiration:
= expansion of thoracic cavity and decreased pressure in thoracic cavity
= increase venous return
Expiration:
= compression of thoracic cavity and increased pressure in thoracic cavity
= decrease venous return
Describe Sympathetic Stimulation and its affect on venous return
- causes vasoconstriction of veins and increases venous return
List the 6 Steps of fainting
- Standing at attention
- Decreased venous return
- Decreased cardiac output
- Decreased blood to brain
- Fainting - loss of consciousness
- Fall over - venous return and cardiac output return to normal
Describe Sphygmomanometry
- cuff is inflated
- cuff pressure > arterial pressure
- when the pressure in cuff is higher than in artery, the artery closes
- artery is completely blocked
- no sound due to no blood flow
- cuff pressure is reduced until first sound is heard
- systolic pressure
- blood passes through turbulently when arterial pressure transiently is greater than cuff pressure
- no sound heard when cuff pressure is less than diastolic pressure
- last sound heard is diastolic pressure
Describe Mean Arterial Pressure and give the formula
- average blood pressure in the arteries
- closer to diastole because heart spends longer in diastole
Mean Arterial Pressure = Diastolic Pressure + 1/3 Pulse Pressure
Describe Flow and resistance
- friction between blood and vessel causes resistance
- resistance to blood flow is controlled by:
- blood viscosity (constant)
- vessel length (constant)
- vessel diameter (only factor we can regulate)
- double the radius, increased blood flow by 16 times
Describe Flow and Pressure
- contraction of heart gives pressure to blood
- pressure in cardiovascular system decreases from arteries to veins
- blood flows from high pressure to low pressure
- blood flow is directly proportional to the pressure gradient
Describe Arteriolar Radius
- total peripheral resistance is controlled by blood
vessel radius
*radius of arterioles can be increased (dilated) or decreased (constricted)
*arterioles are the major resistance vessels - can be controlled by extrinsic and local factors
*local = changes at the level of muscle/vessel
*extrinsic = changes at level of nervous and endocrine systems
Describe Local Metabolic Changes
- local metabolic changes in a tissue control arteriolar diameter and allow blood flow to meet the needs of the tissue
- i.e. during exercise an increase in metabolism stimulates the dilated of local arterioles
List the 6 Steps of Local Metabolic Changes
- Exercise
- Increase in tissue metabolism
- Decrease in Oxygen, increase in Carbon dioxide and increase in hydrogen ions
- Arterioles dilate
- Decrease resistance = increase blood flow
- Increase oxygen and nutrients supplied to metabolising tissue
Describe Capillaries
- site of exchange between blood and tissue and gases (oxygen and carbon dioxide), nutrients and wastes
- exchange occurs primarily by diffusion
Describe Pre-capillary sphincters and arterioles
- blood supply to a capillary bed can be controlled by a pre-capillary sphincter
- on average, only 25% of the capillaries are open
- opening is controlled by local metabolic changes
- pre-capillary sphincters open when we need them to
Describe Bulk Flow
- continuous flow of fluid and solutes between capillaries and interstitial fluid
- driven by two forces:
1. Capillary Hydrostatic Pressure (CHP)
2. Blood Colloid Osmotic Pressure (BCOP)
Describe Capillary Hydrostatic Pressure
- hydrostatic pressure of blood flowing into capillaries
- pushes fluid out of capillaries
- higher at arteriolar end than venular end
Describe Blood Colloid Osmotic Pressure
- plasma proteins too large to exit capillary
- more solutes in the capillary than the interstitial fluid
- osmosis draws the fluid back into the capillary
Describe Net Filtration Pressure (NFP)
= the difference between the capillary hydrostatic pressure and blood colloid osmotic pressure
- Positive (+) NFP favours filtration
- Negative (-) NFP favours reabsorption
Describe the Baroreceptor Reflex
- baroreceptors = mechanoreceptors that respond to stretch
- carotid sinuses = monitor blood flow to the brain
- aortic arch = monitor blood flow to systemic circulation
List the 8 Steps of the Baroreceptor Reflex: Decreased Blood Pressure
- When blood pressure falls below normal
- Decrease carotid sinus and aortic arch receptor potential
- Decrease rate of firing in afferent nerves
- Cardiovascular centre
- Increase sympathetic cardiac nerve activity, increase sympathetic vasoconstrictor nerve activity, decrease parasympathetic nerve activity
- Increase heart rate, increase stroke volume and arteriolar and venous vasoconstriction
- Increase cardiac output and increase total peripheral resistance
- Blood pressure increased towards normal
List the 8 Steps of the Baroreceptor Reflex: Increased Blood Pressure
- When blood pressure becomes elevated above normal
- Increase carotid sinus and aortic arch receptor potential
- Increase rate of firing in afferent nerves
- Cardiovascular centre
- Decrease sympathetic cardiac nerve activity, decrease sympathetic vasoconstrictor nerve activity, increase parasympathetic nerve activity
- Decrease heart rate, decrease stroke volume and arteriolar and venous vasodilation
- Decrease cardiac output and decrease total peripheral resistance
- Blood pressure decreased towards normal
Draw the process of Haemorrhage: Short term: Baroreceptor Reflex
- see notes for diagram
Draw the process of Haemorrhage: Long term: Endocrine response
- see notes for diagram
List the 4 Steps of External Respiration
- Ventilation or gas exchange between the atmosphere and alveoli in the lungs
- Exchange of oxygen and carbon dioxide between air in the alveoli and the blood in the pulmonary capillaries
- Transport of oxygen and carbon dioxide by the blood between the lungs and the tissues
- Exchange of oxygen and carbon dioxide between the blood in the systemic capillaries and the tissue cells
Describe the equation for Cellular respiration
food (energy) + oxygen -> carbon dioxide + water + ATP
Describe the 3 types of alveoli
1. Type 1 Alveolar Cell = squamous cells lining the alveoli 2. Type 2 Alveolar Cell = produce surfactant 3. Alveolar Macrophages = phagocytose foreign material
Describe the 3 Pressures Influencing Ventilation
- Atmospheric Pressure
- 760 mmHg - Intra-Alveolar Pressure
- pressure inside lungs (alveoli)
- atmosphere and alveoli are linked by conducting airways - intra-alveolar pressure quickly becomes the same as atmospheric pressure
- 760 mmHg - Intrapleural Pressure
- pressure inside pleural sac
- less than atmospheric pressure (sub-atmospheric)
- 756 mmHg (also expressed as -4 mmHg)
Describe Transmural Pressure Gradient
- is the pressure difference between the lungs and the pleural cavity
- pushes lungs out towards the thoracic wall
List the 4 Steps of the Process of Inspiration
- Diaphragm and external intercostals contract
- Lung volume increases
- Slight drop in intra-alveolar pressure
- Air enters lungs
List the 4 Steps of the Process of Expiration
- Diaphragm and external intercostals relax
- Lung volume decreases
- Slight rise in intra-alveolar pressure
- Air leaves lungs
Describe Forced Breathing - Inspiration
- further contraction of external intercostals and diaphragm (as much as 10cm)
- contraction of accessory muscles in neck
- Inspiration is muscle activity working AGAINST elastic recoil
Describe Forced Breathing - Expiration
- internal intercostals draw in ribs
- abdominal muscles contract and push the diaphragm upwards
- forced expiration is not passive
- Forced Expiration is muscle activity working WITH elastic recoil
Describe Airway Resistance and give the formula
F = (delta P) / R where: F = airflow rate (delta P) = air pressure gradient = difference between atmospheric and intra-alveolar pressure R = airway resistance
- airway resistance is very low in healthy individuals
- friction of air against walls of airways
- increased resistance = slower air flow
- main factor increasing resistance is reduced bronchiole radius
- bronchoconstriction
- mucous
- fluid
e. g. asthma
Describe Surfactant
- breaks the surface tension of water
- produced by Type 2 alveolar cells
- mixture of proteins and lipids
- breaks hydrogen bonds between water molecules
- stops alveoli from collapsing
- easier to expand alveoli during inspiration
Describe Lung Compliance
- stretchability of the lungs during inspiration
- high compliance = easily stretched
- low compliance = hard to stretch
- factors reducing compliance:
- high surface tension (reduced surfactant)
- scarring of lung tissue
- restrictive diseases
Describe Elastic Recoil
- ability of lungs to rebound (shrink)
- important during expiration
- influenced by two factors:
1. Elastic fibres
2. Surface tension - decreased surface tension = decreased elastic recoil
List and describe the 8 Healthy Respiratory Volumes
- Tidal Volume (TV)
- air inspired or expired during quiet breathing
- 500ml - Inspiratory Reserve Volume (IRV)
- extra air inspired during forced inspiration
- 3000ml - Expiratory Reserve Volume (ERV)
- extra air expired during forced expiration
- 1000ml - Residual Volume (RV)
- air left in the lungs after forced expiration
- 1200ml - Inspiration Capacity (IC)
- maximum volume of air that can be inspired
- TV + IRV
- 3500ml - Vital Capacity (VC)
- maximum amount of air expired after maximum inspiration
- TV + IRV + ERV
- 4500ml - Functional Residual Capacity (FRC)
- volume of air in lungs after normal expiration
- ERV + RV
- 2200ml - Total Lung Capacity (TLC)
- maximum volume of air that the lungs can hold
- VC + RV
- 5700ml
Describe Pulmonary Ventilation and give the formula
- also called minute ventilation
- volume of air breathed in and out per minute (ml/min)
Pulmonary Ventilation (ml/min) = Tidal Volume (ml/breath) x Respiratory Rate (breath/min)
Describe Alveolar Ventilation and give the formula
- volume of air exchanged between the atmosphere and alveoli
- air available for gas exchange
- takes dead space into account
Alveolar Ventilation (ml/min) = (Tidal Volume - Dead Space) (ml/breath) x Respiratory Rate (breath/min)
Describe Anatomical Dead Space
- the volume of air available for gas exchange is less than the tidal volume -> this is because some of the tidal volume never makes it into the alveoli
- anatomical dead space = air stuck in the airways
List the 4 Steps of Anatomical Dead Space
- End of inspiration. Dead space filled with fresh air
- Exhale 500ml (tidal volume). The first exhaled air (150ml) comes out of the dead space. Only 350ml leaves the alveoli
- At the end of expiration, the dead space is filled with “stale” air from alveoli
- Inhale 500ml of fresh air (tidal volume)
Describe Obstructive Lung Diseases
- difficulty with exhalation
- increased airway resistance
- e.g. asthma, emphysema, chronic conditions, cystic fibrosis
Describe Restrictive Lung Diseases
- difficulty with inhalation
- impaired lung expansion
- e.g. pleural effusion, pleurisy, atelectasis, fibrosis
Describe Pulmonary Fibrosis
- restrictive disease resulting in reduced lung compliance
- caused by exposure to irritants (e.g. asbestos, silica), these irritant fibres don’t break down causing scarring
- inflamed lung tissue becomes ‘scarred’
- because lung tissue is scarred, the composition of lung tissue changes leading to reduced lung compliance
Describe Chronic Obstructive Pulmonary Disease (COPD)
- asthma (reversible)
- emphysema and chronic bronchitis (tend to co-occur and are irreversible)
Describe Chronic Bronchitis
- hyper secretion of mucous and chronic productive cough for at least three months of the year for at least two consecutive years
- chronic productive cough = including phlegm or fluids
- cause: cigarette smoking, air pollutants
- chronic inflammation of lungs
- bronchial oedema (swelling) and increased mucous production
- impaired mucous clearance
- mucous accumulation in lungs and recurrent infections
Describe Emphysema
- permanent enlargement of airways in the respiratory region
- causes: cigarette smoking and pollutants and very rarely 1-3% genetic causes
- increased enzymatic activity - breakdown of lung elastic fibres
- reduced elastic recoil
- difficulty during expiration
- air trapping (increased residual volume)
Draw the process of Smoking/Irritants and Emphysema
- see notes for diagram
Describe asthma
- periods of increased airway resistance due to three main changes in the bronchioles:
1. Inflammation - thickening of airway walls
2. Increased mucous secretion
3. Airway hyper-responsiveness - bronchoconstriction
Describe Normal Expiration
- resistance to airflow is low
- frictional loss of airway pressure is minimal
- airway pressure higher than intrapleural pressure
- airways remain open during normal quiet breathing
Describe Dynamic Airway Closure
- intrapleural and intra-alveolar pressures increase
- at low lung volume:
- loss of pressure in the airways
- dynamic airway closure:
- equal pressure in airways and pleural sac
- airways collapse
- remaining volume = residual volume
- only at low volumes in healthy people
Describe Spirometry
- measures volume and flow of air
- two readouts:
1. Volume-time curve
2. Flow-volume loop
Describe Volume-Tim Curve
FVC = forced vital capacity = maximum volume forcefully exhaled after maximum inspiration
FEV1 = forced expiratory volume in 1 second
FEV1/FVC = provides information about resistance to airflow
Describe Flow-Volume Loop
- maximum inspiration beforehand
- maximum fast expiration followed by maximum fast inspiration
- measures:
PEF = peal expiratory flow rate
FVC= forced vital capacity
PIF = peak inspiratory flow rate
Describe Respiratory Control Centre
- breathing is controlled through respiratory control centres (brain stem: medulla and pons)
- medullary centres:
- quiet breathing
- forced breathing
- respiratory rhythm
- pons centre:
- smooth transition between inspiration and expiration
Describe the Medullary Control Centres
- the rate and rhythm of breathing is controlled by the medullary control centres
Dorsal Respiratory Group (DRG)
- inspiratory neurons
- contraction of inspiratory muscles
- quiet breathing
Ventral Respiratory Group (VRG)
- inspiratory and expiratory neurons
- contraction of inspiratory and expiratory muscles
- forced breathing
Pre-Botzinger Complex
- auto rhythmic cells
- control rate of DRG inspiratory neurons
Draw the Process of Chemical Control Oxygen Process
- see notes for diagram
Draw the Process of Chemical Control Carbon Dioxide and Hydrogen Ions Process
- see notes for diagram
Describe Agonist
= a substance that promotes a receptor-mediated biological response often by competing with another substance at the same receptor
- on the molecular level, agonists bind to receptors
Describe Receptor
= a molecular (usually protein) structure or site on the surface or interior of a cell that binds with substances such as hormones, antigens, drugs or neurotransmitters with specificity
Describe Antagonists
= a substance that binds to, but does not activate the receptor
- competitive antagonists = bind to the same area on the receptor as the agonist does or did
- irreversible competitive antagonists = permanently bind to the same area on the receptor as the agonist does or did
Describe Ligand Gated Ion Channels (Inotropic Receptors)
- milliseconds
- e.g. nicotinic receptor
Describe Nicotinic Receptor
- 5 transmembrane units
- endogenous agonist is acetylcholine (Ach)
- 2 molecules of ACh bind, opening Na channel
- ions flow down concentration gradient
Describe G-protein Coupled Receptors
- seconds
- e.g. B-adrenoreceptors
Describe B-Adrenoreceptors
- 7 transmembrane domains
- largely composed of alpha helices
- endogenous agonist is adrenaline
- agonist binding activates G-protein
- extracellular domain interacts with agonist
- intracellular domina interactions with G-protein
Draw the process of Amplification of GPCR Signalling
- see notes for diagram
List the 5 Steps of Nuclear Receptors
- The steroid hormone testosterone passes through the plasma membrane
- Testosterone binds to a receptor protein in the cytoplasm, activating it
- The hormone receptor complex enters the nucleus and binds to specific genes
- The bound protein stimulates the transcription of the gene into mRNA
- The mRNA is translated into a specific protein
Describe EC50
= Effective Concentration for 50% response (EC50)
= the concentration at which 50% of the receptors are bound to the agonist/drug
Describe Potency
= concentration/strength of dose needed to get effect
Describe Efficacy
= how effective is the drug, given its potency
Describe ADME
A: Absorption = how a drug gets into the body
D: Distribution = how a drug moves around the body
M: Metabolism = how a drug is changed in the body
E: Excretion = how a drug is removed from the body
List 3 Advantages and 5 Disadvantages of Oral Administration
Advantages:
- convenient
- ~75% absorbed in 1-3 hours
- slow release formulations
Disadvantages:
- some drugs not well absorbed
- irritation to gastric/intestinal mucosa
- food can delay/affect absorption
- much slower absorption than parental
- inactivation by ‘first-pass’ metabolism by liver
List 4 Advantages and 2 Disadvantages of Rectal Administration
Advantages:
- avoids ‘first-pass’ metabolism
- reduces vomiting/nausea
- good when patient is unconsciousness/seizures
- local inflammation (e.g. haemorrhoids)
Disadvantages:
- inconvenient
- absorption often incomplete
Describe Metabolism by Liver Hepatocytes
- drugs that are absorbed from the gut reach the liver via the hepatic portal vein before entering the systemic circulation. Some drugs may have low bioavailability/distribution due to this first-pass effect
- some drugs can be given as pro-drugs, relying on the body’s metabolic processes to make an active metabolite
- some metabolites are active, most are inactive
Describe 3 Advantages and 3 Disadvantages of Avoiding First Metabolism
via: intramuscular (i.m.), subcutaneous (s.c.), intravenous (i.v.), intradermal (i.d.)
Advantages:
- rapid onset, compared to oral (i.v. > i.m. > s.c.)
- drugs are not broken down by acid/enzymes as in the gut
- ‘first-pass’ metabolism in the liver is less of a problem
Disadvantages:
- less convenient (needs a skilled person)
- risk of infection
- more toxicities (higher peak blood levels)
Describe Sublingual Non-Needled Administration
- dissolve tablet under the tongue:
- good vascularisation
- rapid absorption into bloodstream
- no ‘first-pass’ metabolism in the liver
- e.g. anti-anginal drug nitroglycerin (vasodilator)
- absorbed rapidly
- straight to the heart
- can’t be given orally
Describe Topical Non-Needled Administration
- direct application to diseased or injured site
- require lower overall doses
- reduced systemic toxicity
- skin: few drugs penetrate skin readily
- patches work well: nicotine, scopolamine, fentanyl
- eyes, ears, nose, vagina
- local effect required (e.g. corticosteroids)
Describe Enzymatic Reactions
- Phase 1 Reactions
- oxidations (cytochrome p450s)
- reduction (reductase)
- hydrolysis (esterases) - Phase 11 Reactions
- add water-soluble moiety to drug
* glucuronide
* glutathione
* sulfate
* acetate
Describe Phase 1 Reaction: Oxidation (Cytochrome P450s)
- more than 50 different forms of cytochrome P450 enzymes exist, with different substrate specificities and mechanisms
- most lipophilic drugs and environmental chemicals are substrates for one or more forms of P450
Describe Phase 1 Reaction: Reduction (reductase) and Hydrolysis (esterases)
- each reaction, whether oxidation, reduction or hydrolysis, increase the water solubility of the resulting metabolite
Describe Phase 11 Reactions
- glucuronidation
- sulfation
- acetylation
- glutathione conjugation
- methylation
*Addition of a water-soluble moiety (therefore, involves a co-factor)
Describe AntiHypertensives
= a very large range of diverse drugs can be used to assist and usually a combination of drugs is best approach
- diuretics
- directly acting vasodilators
- calcium channel blockers
- sympathetic antagonists (peripheral and central)
- beta blockers
Describe Calcium Channel Blockers (e.g. Nifedipine and Verapamil)
- inhibit calcium ion movement into vascular and cardiac muscle
- interferes with inwards movement of calcium ions
- affects depolarisation and contraction processes
- relaxant effects mainly on arteriole smooth muscle
- results:
- peripheral and coronary vasodilation
- decrease heart rate and contractility
Describe Beta Blockers
- the beta drugs act predominantly on the heart tissue, if they are selective for antagonists for beta-1 adrenergic receptors
- results:
- reduce heart rate
- reduce ventricular contractility
Describe Myocardial Ischaemia
- reduced blood flow through coronary arteries, leading to inadequate oxygenation of heart myocytes
- this leads to chest pain (short term) and to myocyte cell death (long term)
Describe Coronary Artery Disease
- atherosclerosis
Describe Stable Angina and how to treat it
= predictable chest pain experienced with exertion due to underlying narrowing of the coronary vessels by atheroma (accumulated fatty deposits and scar tissue)
Treat by:
targeting cardiac work and blood supply (organic nitrates, vasodilators and beta blockers), underlying atherosclerosis (statins), anti-thrombotic therapy (aspirin)
Describe Unstable Angina and how to treat it
= pain occurring with reduced exertion, culminating in pain at rest. Similar pathology to an MI
Treat By:
antiplatelet drugs, organic nitrates, etc
Describe Myocardial Infarction and how to treat it
= sudden occlusion of a coronary vessel leading to death of cardiac tissue due to oxygen deprivation. The location and size of the block determines the extent of the damage
Treatment:
restore myocardial flow by physical and pharmacological means
Describe Stents, along with pros and cons
= a tube placed inside a duct or canal to reopen it or keep it open
Pros:
best treatment if emergency
Cons:
facilities and personnel are needed
Describe Coronary Artery Bypass Grafting
- surgical procedure performed to relieve angina and reduce risk of death
- arteries and veins from elsewhere in the body are grafted to coronary arteries to bypass atherosclerotic narrowing and improve blood supply to the coronary circulation to the myocardium
Describe Congestive Heart Failure
- the inability of the heart to supply adequate nutrients to the metabolising tissues of the body; it simply cannot pump effectively or efficiently
- cardiac output decreases
- short term strategy is to increase adrenaline, this is not a good long term plan as vasoconstriction is increased along with cardiac output and the workload on the heart is increased
- activation of adrenal medulla leads to activation of reninangiotensin system (RAS)
- long term, not a good idea as RAS leads to retention of salt and water, leading to congestion and oedema
List the 4 drugs used in Heart Failure
- Positive Inotropic Agents: Digoxin/Digitalis
- Vasodilators: ACE inhibitors, nitrates
- Diuretics
- Beta Blockers
Describe Positive Inotropic Agents: Digoxin/Digitalis
- inhibition of the Na-K pump impairs exchange between Na and Ca ions indirectly; elevated Ca ions increase the force of myocyte contraction; stronger myocardial contraction - improved cardiac efficiency = increased cardiac output
Describe Vasodilators: ACE Inhibitors
- lower blood pressure and increase blood to heart
- opens coronary arteries; dilated artery = lower blood pressure
- ACE inhibitors stop angiotensin production
Describe Diuretics
- improve kidney function such that oedema is relieved
- by reducing swelling in the organs and limbs, the work of the heart is reduced significantly
- diuretics are often combined with all other forms of heart failure treatment
Describe Beta blockers
- evidence of effect is uncertain
- however, it has been suggested that the use of beta blockers may somehow protect the heart of harmful stimulatory effects of noradrenaline and adrenaline
Describe Asthma triggers
- allergens: molds, dust, animal dander, pollen, food, pests (dust mites, cockroaches)
- irritants: secondhand smoke, strong odours, ozone, chemicals, perfume
- exercise: cold and dry air
- viral infections:
- some causes are unknown and are “non-allergic”
- genetic factors also play a role in our response to potential allergens
- one of the best methods of allergic asthma management is simply minimising exposure to allergens
Describe Asthma Pathogenesis: Early and Late Phase
Early Phase
- bronchoconstriction
Late Phase
- inflammation
- mucous hyper secretion
- eosinophilic infiltration
- elevated IgE levels
- subepithelial fibrosis
- airway hyper-responsiveness
Describe Delivery methods of asthma medication
Pressurised Metre-dose Inhalers (pMDIs)
= propellant gas is likely to be HFA (ozone compliant)
Nebuliser
= drug is inhaled during tidal breathing and higher doses can be given; good in case of attacks
Spacers
= used between the inhaler and patient; allows for inhaled particles to slow in speed and for propellant to drug, rendering the medication smaller in volume. Reduces swallowing of drug and increases the depth of the airways reaches
Dry Power Inhalers (DPI)
= tablet is crushed and inhaled
**Inhaled Route is preferred
List all Pharmacological Interventions for Asthma
Relievers/Controllers (bronchodilators):
- Beta-2 adrenergic agonists: SABAs and LABAs
- Methylxanthines
- Muscarinic Receptor Antagonists
Preventers (anti-inflammatory antagonists):
- Leukotriene Receptor Antagonists
- corticosteroids
- anti-Ige antibodies
Describe Short-Acting Beta-2 Agonists (SABAs)
- agonist
- MOA = short term stimulation of beta-2 receptors on smooth muscle lining of the bronchioles. Effective in early phase asthma
- DOA = 3-5 hours, with 1-5 minutes onset of action
- Outcome = symptomatic relief of bronchospasms and constriction
- Possible Side Effects = increase heart rate, muscle tremors, feeling light-headed or shaky, headache
- Active Drug = Salbutamol
Describe Long-Acting Beta-2 Agonists (LABAs)
- agonist
- MOA = long term stimulation of beta-2 receptor on smooth muscle lining of the bronchioles
- DOA = 12+ hours, with 30-45 minutes onset of action
- Outcome = used prophylactically for asthma treatment
- Possible Side Effects = increase heart rate, muscle tremors, feeling light-headed and shaky, headaches
- Active Drug = Salmeterol
Describe Methylxanthines
- antagonist
- MOA = inhibits phosphodiesterase (PDE), may reduce transcription of inflammatory genes. Stimulates the CNA and increases breathing rate
- DOA = 12+ hours
- Outcome = increase cAMP, promotes bronchodilation
- Possible Side Effects = cardiac dysrhythmia, GI disturbances, seizures -> narrow therapeutic window, P450 metabolism
- Active Drug = Theophylline
Describe Muscarinic Antagonist
- antagonist
- MOA = blocks M3 receptors, preventing parasympathetic contraction of smooth muscle. Used with beta-2 agonists or steroids in acute severe asthma
- DOA = 2-3 hours
- Outcome = short acting bronchodilator, inhibits bronchoconstriction and mucous sceretion
- Possible Side Effects = limited side effects, as not permeable into systemic circulation. Bitter in taste. Nebulised patients of age may develop glaucoma if using face mask
- Active Drug = Ipratropium
Describe Leukotriene Receptor Antagonist (LTRAs)
- antagonist
- MOA = taken orally to reduce leukotriene activity. Relaxation of smooth muscle. No effect on inflammation
- DOA = 12+ hours
- Outcome = relaxes airways
- Possible Side Effects = GI irritation
- Active Drug = Montelukast
Describe Inhaled Corticosteroids (ICS)
- antagonist
- MOA = inhibition of release of immune mediators from macrophages, T-cells and eosinophils. Reduction of mucous secretion and reduced inflammation
- DOA = 18 - 36 hours
- Outcome = reduces mucous secretion and inflammation
- Possible Side Effects = oral thrush, cataract risk, reduced bone density, glaucoma, reduced growth rate in children
- Active Drug = Beclomethasone, Fluticasone, Prednisone
Describe Anti-IgE Antibodies
- antagonist
- MOA = reduces stimulation of mast cells, and releases anti-inflammatory mediators
- DOA = 2-4 weeks
- Outcome = controls/reduces inflammation
- Possible Side Effects = rash, itching, joint pain, nausea, dizziness, cold-like symptoms
- Active Drug = Omalizumab
Describe Vitalograph
= measures the amount of air that can be forcefully exhaled over a period of time
- a vitalograph reads FEV1, FVC and FEV1/FVC
FEV1 = air expired in 1 second
FVC = forced vital capacity = maximum amount of air we can possibly expire
(FEV1/FVC) x 100 = of all the air you can expire, how much of it gets out in the first second
= how fast the air is coming out in expiration
- An FEV1/FVC value less than 75% suggests an obstructive disease, such as asthma or emphysema
- FEV1 and FVC are dependent on age, gender and height
Describe Flow-volume Loop
= measures airflow rate during forced expiration and forced inspiration
- a flow-volume loop reads, Flow 0, PEF, 100% Vital Capacity and PIF
Flow 0 = beginning of expiration (0L/sec)
PEF = peak expiratory flow; should be achieved before 15% of vital capacity has been exhaled
100% vital capacity= the end of forced expiration when all air has been exhaled (when flow is 0L/sec)
PIF = peak inspiratory flow; should be achieved at about 50% of volume inhaled
Draw a typical vitolgraph and flow-volume loop
- see notes for diagram
Define Large Airway Obstruction
= the large airways include the trachea and bronchi, whereas, the bronchioles are small airways. A tumour in a trachea is an example of a large airway obstruction.
Cartilage is found in large airways, but not in small airways
Draw a Vitalograph and Flow-Volume Loop of a patient with Large Airway Obstruction
- see notes for diagram
Describe the changes in a vitalograph and flow-volume loop of a patient with Large Airway Obstruction
- large airway obstruction affects inspiratory and expiratory flow
- decrease FEV1/FVC
- decrease PEF
- decrease PIF
- no early closure of small airways
- normal dynamic airways closure in large airway obstruction
- increased large airway resistance
- increased loss of pressure in large airways
- dynamic airway closure still occurs, just at a normal stage of breathing process
- decreased FEV1/FVC, normal FVC, normal RV
Define Asthma
= reversible episodes of increased resistance to airflow in the small airways (bronchioles). There is a reduction in the diameter of the small airways because of:
- inflammation: the lining of the airways becomes red and swollen
- increased mucous production
- bronchoconstriction: the smooth muscle in the bronchioles contracts
Draw a Vitalograph and Flow-Volume Loop of a patient with Asthma
- see notes for diagram
Describe the changes in a vitalograph and flow-volume loop of a patient with Asthma
- asthma affects expiration:
- increase small airway resistance
- increase early small airway closure process
- decrease FVC
- decrease FEV1/FVC
- decrease PEF
- early airway closure in asthma (early in lung volume, not time)
- increased airway resistance
- increased loss of pressure in small airways
- early small airway closure, decreased FVC, decreased FEV1/FVC, increased RV
- PIF is normal as asthma affects expiration, not inspiration and because the expanding of bronchioles allows inspiration to remain normal
Define Emphysema
= causes permanent enlargement of the smallest airways and alveoli
Draw a Vitalograph and Flow-Volume Loop of a patient with Emphysema
- see notes for diagram
Describe the changes in a vitalograph and flow-volume loop of a patient with Emphysema
- emphysema affects expiration and inspiration:
- increased intrapleural pressure
- increased early small airway closure
- decreased FVC
- decreased FEV1/FVC
- decrease PEF
- increase PIF due to decrease elastic recoil
- early airway closure in emphysema (early in lung volume, not time)
- loss of lung tissue
- decreased lung elastic recoil
- increased intrapleural pressure
- early airway closure, decreased FVC, decreased FEV1/FVC, increased RV
- PIF increases because there is reduced elastic recoil which leads to the fact that the lungs inflate more easily and quickly
- the only difference between asthma and emphysema is that emphysema has an increased PIF
Define Restrictive Diseases
= reduce the lungs capacity to expand, which affects inspiration. An example is asbestos, which is a type of pulmonary fibrosis. Inhaled asbestos fibres cause an immune response which initiates the production of scar tissue. This scar tissue is not as stretchy (or compliant) as normal lung tissue, so the lungs cannot expand easily
Draw a Vitalograph and Flow-Volume Loop of a patient with Restrictive Diseases
- see notes for diagram
Describe the changes in a vitalograph and flow-volume loop of a patient with Restrictive Diseases
- restrictive diseases affect inspiration:
- decrease FVC
- decrease PIF
- lungs are less compliant
- increase FEV1/FVC
- no early closure of airways in restrictive diseases
- reduced FVC
- reduced PIF
- decreased compliancy
- very high (>95%) FEV1/FVC can suggest a restrictive disease (more tests are required)
