intended learning outcomes - all Flashcards
The processes required for synaptic transmission including;
a) Neurotransmitter synthesis
b) The action potential
c) Vesicular release
d) Receptor activation
a) chemical precursors, acetylcoA and choline, are used to synthesise acetylcholine by choline acetyl transferase
b) the action potential triggers release of neurotransmitters at the nerve terminal due to an increase in Ca2+ ion concentration
c) neurotransmitters are released via exocytosis due to the action potential and increase in Ca2+ ion concentration, in the presence of receptors on the postsynaptic membrane
d) neurotransmitters carry the signal across the synaptic cleft where they act on receptors expressed on the post-synaptic cell and can either cause excitation or inhibition. acetylcholine binds to receptors on the postsynaptic membrane causing a conformational change leading to a cellular response. acetylcholinesterase enzymes inactivate acetylcholine by breaking it down to acetate and choline. choline returns to the presynaptic cell.
Identify potential synaptic targets for drug, or, toxin action at the neuromuscular junction
enhance synaptic transmission by; direct stimulation of post-synaptic receptors - the natural transmitter, analogues (carbachol) - or indirect stimulation - increasing transmitter release, inhibition of transmitter removal.
inhibit synaptic transmission by blocking synthesis, storage or release from the presynaptic neurone, or by blocking postsynaptic receptors
Understand receptor agonist and antagonist
agonist > activate receptor by causing a conformational change resulting in a biological response. show affinity and efficacy.
antagonist > block the action of the agonist. bind to receptors but do not activate them. possess affinity but lack efficacy. competitive antagonist - competes with the agonist for the agonist binding site on the receptor, block is reversible by increasing the agonist concentration.
Understand the meaning of drug affinity and drug efficacy
affinity > the ability of an agonist to bind to a receptor
efficacy > the ability of an agonist, once bound to a receptor, to initiate a biological response. the ability of an agonist to activate a receptor.
Understand how acetylcholine nicotinic receptors operate and how the patch-clamp technique can be used to record the functional properties of single receptors
nAchRs > activated by acetylcholine or nicotene. ligand gated- ion channels. agonist binding causes the pore of the channel to open which allows cations to enter which causes depolarisation
understand the use of electrophysiology to record synaptic transmission at the neuromuscular junction
electrophysiology is used to record and measure MEPPs to understand how neurotransmitters are released, how synaptic transmission works under normal and diseased conditions, and the effects of drugs or toxins on nerve-muscle communication.
Understand the quantal theory of neurotransmitter release & how the measurements of EPPs and MEPPs permits the determination of quantal content
neurotransmitters are released in fixed packets (quanta), not continuously
EPPs and MEPPs are how synaptic signals are measured to calculate how many quanta are released
EPPs > the electircal signal in the muscle caused by nerve stimulation. many quanta of neurotransmitter are released
MEPPs > tiny spontaneous signals that happen without nerve stimulation. caused by the random release of a single vesicle.
QC > mean EPP amplitude/mean MEPP amplitude
Describe drugs or toxins that influence synaptic transmission by modifying;
a) The synthesis, storage, and release of neurotransmitter
b) The function of the nicotinic receptor
⍺-latrotoxin > influences spontaneous transmitter release - massive Ach release
tetrodotoxin > blocks Na+ channels, no activation of VG Ca2+ channels, no action potential, no release, no EPP.
conotoxins > block VG Ca2+ channels, decreased Ca2+ influx = decreased release. EPP amplitude decreases, no change in MEPP = decreased QC
dendrotoxin > block VG K+ channels, prolonged action potential, increased Ca2+ influx = increased release, EPP amplitude increases, no change in MEPP = increased QC
botulinum toxin > blocks vesicle fusion by cleaving a vesicular protein required for exocytosis = decreased release. EPP amplitude decreases, no change in MEPP = decreased QC
compare and contrast how tubocurarine, suxamethonium, and ⍺-bungarotoxin produce skeletal muscle relaxation at the neuromuscular junction
tubocurarine > a muscle relaxant. blocks nAchR. reversible competitive antagonist that is overcome by increasing acetlycholine concentration. reversed by neostigmine (an antagonist of acetylcholinesterase). reduce the EPP. no depolarisation, no action potential, no contraction.
suxamethionium > nAchR agonist that causes skeletal muscle paralysis. metabolised by plasma cholinesterase. depolarising blocker.
⍺-bungarotoxin > an irreversible nAchR antagonist. decreases the EPP and MEPP
Understand the clinical uses of tubocurarine, and suxamethonium
tubocurarine > used clinically as a skeletal muscle relaxant. muscle block reversed by anticholinesterases.
suxamethonium > used for rapid tracheal intubation and during electro-convulsant therapy
Understand the role of acetylcholinesterase enzymes at the neuromuscular junction
breaks down acetylcholine into acetate and choline to terminate signal
inhibited by anticholinesterases
Understand the clinical uses of anticholinesterases, e.g. neostigmine
inhibit acetylcholinesterases to increase the effects of acetylcholine
reverse non-depolarising skeletal muscle relaxants
diagnosis and treatment of myasthenia gravis
describe the structure and function of the musculoskeletal system
comprised of two systems - skeletal system and muscular system
skeletal system > bone and cartilage. homeostasis and blood production.
muscular system > heat production and peristalsis.
functions > movement, stability, shape and support
Distinguish between the axial and appendicular skeleton
axial > head, neck and trunk
appendicular > limbs and girdles
Describe different types of bones, providing examples
- flat bones - protection of the heart. sternum
- long bones - tubular. provide leverage. femur
- sesamoid bones - develop in tendons. protect tendon. patella
- irregular bones - complex shape. protection of the spinal cord. vertebrae
- short bones - cuboidal. stability, support and some movement. tarsals
Describe bone structure
periosteum - outer surface. bone forming cells. fibrous connective tissue coverings of bone
endosteum - inner surface. bone forming cells. fibrous connective tissue coverings of bone
perichondrium - at joints. fibrous connective tissue covering articular cartilage
cortical bone - rigid outer shell
trabecular bone - interconnected struts
medullary cavity - hollow part of bone containing bone marrow
Describe different types of joints, providing examples
- cartiliaginous joints - primary >covered by hyaline cartilage. epiphyseal/growth plate. 1st sternocostal joint. secondary >permanent unions by fibrocartilage. pubic symphysis
- fibrous joints - bones united by fibrous tissue. stability.
- synovial joints - joint capsule spans and encloses joint. lined by synovial membrane and articular cartilage. filled with a lubricating synovial fluid for mobility.
a) pivot joints - atlanto-axial joint
b) hinge joints - ulnohumeral (elbow joint)
c) saddle joints - carpometacarpal joint of 1st digit
d) ball and socket joints - hip joint
e) condyloid joints - wrist joint
f) plane joints - acromioclavicular joint
Distinguish between ligaments and tendons
ligaments > connect bone to bone. fibrous bands of dense regular connective tissue. stabilise articulating bones and reinforce joints.
tendons > connect muscle to bone. dense regular connective tissue. transmits mechanical force
Describe and classify skeletal muscle
voluntary. striated. gross named muscles. organs of locomotion. provide support and form, and heat.
pennate - fasicles attach obliquely
convergent - arise from a broad area and converge to form a single attachment
circular/sphincter - surround opening. constrict when contracted
fusiform - spindle shaped with thick round bellies and tapered ends
flat - parallel fibres
Outline muscle contractions
reflexive - automatic. diaphragm
tonic- muscle tone. posture.
phasic - isotonic contractions > muscle changes length. eccentric = muscle lengthening. concentric = muscle shortening. isometric contractions > muscle length remains the same
antagonistic muscle pairs
Explain what is meant by the sliding filament hypothesis of muscle contraction
action potential from motor neuron reaches motor end plate. Acetylcholine is released and diffuses across the synaptic cleft and binds to receptors opening ligand-gated cation channels, allowing Na+ ions to enter and K+ ions to exit the muscle fibre increasing the membrane potential. The action potential travels along the sarcolemma and its transverse tubules once the threshold potential is reached, this releases Ca2+ ions from the sarcoplasmic reticulum into the sarcoplasm.
troponin and tropomyosin form a protein complex that at low Ca2+ ion concentration binds to actin blocking the myosin-actin binding site. When calcium is present, troponin is released revealing the myosin-actin binding site. calcium is released.
ATP binds to the myosin head before dissociating into ADP and Pi, activating the myosin head by forming the activated myosin and ADP complex. The energy released from ATP hydrolysis is used to allow the myosin head to cock and bind to the binding site on actin. ADP and Pi is released from the myosin head initiating a power stroke to pull the actin inwards, shortening the sarcomere. Myosin then binds to ATP and releases from actin, this ATP also hydrolyses to ADP and Pi to reactivate the myosin head so it can bind to actin once again.
Explain the role of ATP in the cross bridge cycle
myosin II heads bind to actin and the cross-bridges become distorted, and the myosin heads detach from actin. energy comes from the hydrolysis of ATP. an increase in intracellular calcium concentration triggers contraction by removing the inhibition of cross-bridge cycling
Describe the source and role of calcium ions in skeletal muscle contraction
Action potential arrives at the NMJ and spreads into the muscle via T-tubules.
This triggers the release of Ca²⁺ from the sarcoplasmic reticulum.
Calcium binds to troponin, a protein on the thin actin filament.
This moves tropomyosin, exposing myosin-binding sites on actin.
Myosin heads attach to actin, forming cross-bridges, and begin the power stroke (muscle contraction).
Describe the arrangements of major proteins such as actin and myosin within skeletal muscle
thin filament - a relaxed skeletal muscle fibre composed of actin, troponin and tropomyosin. a double stranded alpha-helical F-actin with a myosin binding site
tropomyosin - a thread-like coil wrapped around actin to cover the myosin binding site.
troponin - a heterotrimer consisting of troponin T, C and I. each heterotrimer of troponin interacts with a single molecule of tropomyosin, which in turn interacts directly with 7 actin molecules
thick filament - composed of multiple myosin II molecules > a double trimer (2x alkali light chains, 2x regulatory light chains, 2x intertwined heavy chains that each possess a binding site for actin and a site for binding and hydrolysing ATP)
Describe the involvement of troponin and tropomyosin in skeletal muscle contraction
troponin T - binds to a single molecule of tropomyosin
troponin C - binds Ca2+
troponin I - binds to actin and inhibits contraction
tropomyosin - the heads of the heavy chains each possess a binding site for actin and a site for binding and hydrolysing ATP
Understand how and when rigger mortis occurs
’ stiffness of death’
begins 3-4 hours after death and completes in approx 12 hours.
an increase in intracellular calcium ion concentration lets the regulatory proteins move aside, allowing actin to bind myosin cross-bridges that were already charged with ATP. dead cells cannot produce ATP, so actin and myosin, once bound, cannot detach
Understand that there are differences between the calcium trigger and response for skeletal and cardiac muscle contractions
skeletal muscle - Action potential travels down T-tubules. Ca2+ release channel opens, releasing calcium from the sarcoplasmic reticulum (SR). Calcium binds to troponin, triggering contraction. calcium is pumped back into SR → muscle relaxes.
cardiac muscle - Action potential activates L-type calcium channels in T-tubules. Extracellular calcium enters the cell, triggering Ryanodine receptor (RyR2) to release more calcium from the SR. Calcium binds to troponin, allowing contraction.Calcium is pumped back into SR and out of the cell via Na-Ca (sodium-calcium exchanger) → muscle relaxes.
Explain the term “excitation-contraction coupling”
the process that links a nerve signal to muscle contraction (action potential > muscle contraction)
1. an action potential arriving at a terminal button of the NMJ stimulates release of Ach, which diffuses across the cleft and triggers an action potential in the muscle fibre
2. the action potential moves across the surface membrane and into the muscle fibres interior through the T tubules. an action potential in the T tubules triggers release of calcium from the SR into the cytosol
3. calcium binds to troponin on thin filaments
4. calcium binding to troponin causes tropomyosin to change shape, physically moving it away from its blocking position; this uncovers the binding sites on actin for the myosin cross-bridges
5. myosin cross-bridges attach to actin at the exposed binding sites
6. the binding triggers the cross bridge to bend, pulling the thin filament over the thick filament toward the centre of the sarcomere. this power stroke is powered by energy provided by ATP
7. after the power stroke, the cross bridge detaches from actin. if calcium is still present, the cycle returns to step 5
8. when action potentials stop, calcium is taken up by the SR. with no calcium on troponin, tropomyosin moves back to its original position, blocking myosin cross-bridge binding sires on actin contraction stops and the thin filaments passively slide back to their original relaxed positions.
Describe the components of muscles which are vital to E-CC > the T-tubules and SR
T-tubules - penetrate all the way through the muscle fibre, from one side to the other
SR - sarcoplasmic reticulum - the intracellular store of calcium
Describe how calcium is the link between excitation and contraction in skeletal muscle
A nerve impulse reaches the neuromuscular junction, releasing acetylcholine (ACh).
ACh binds to receptors on the muscle cell membrane (sarcolemma), generating an action potential
The action potential travels across the sarcolemma and into the T-tubules
The action potential activates voltage-sensitive receptors (DHP receptors) in the T-tubules.
This triggers the release of calcium (Ca²⁺) from the sarcoplasmic reticulum (SR) into the muscle fiber’s cytoplasm.
The released calcium ions bind to troponin, a protein on the actin filaments.
This causes tropomyosin to shift and expose myosin-binding sites on actin.
With the myosin-binding sites exposed, myosin heads can attach to actin, forming cross-bridges.
The myosin heads then pivot, pulling actin filaments toward the center of the sarcomere - this causes muscle contraction.
After the nerve signal stops, calcium is actively pumped back into the SR by calcium pumps.
As calcium levels drop, troponin and tropomyosin return to their original positions, blocking myosin-binding sites on actin.
The muscle relaxes.
Describe how named proteins are used to develop force in a controlled manner within muscle cells
actin
troponin
tropomyosin
myosin
appreciate that the autonomic nervous system is essential to life due to its fundamental role in homeostasis
sympathetic and parasympathetic divisions of the ANS often work simultaneously in a reciprocal and complementary manner maintaining homeostasis
sympathetic - orchestrates the stress response and energy consumption. associated with ‘fight or flight’ reactions, but also has very important ongoing activity
parasympathetic - regulates many functions, some of which are restorative and energy conserving, ‘rest and digest’
skin - thermoregulation by controlling contraction and relaxation of smooth muscle vasculature
liver/pancreas - metabolism of glucose and lipids
lungs - ventilation to control partial pressures and pH
heart & vasculature - blood pressure by contraction and relaxation of smooth muscle in the vasculature
kidneys - osmoregulation (water and electrolyte balance), acid-base balance, blood pressure regulation
homeostasis generally involves a negative feedback loop which has three parts; a sensor, a comparator/integrator (in the CNS, initiates an effector response via efferent neurons) and an effector
Describe the functional anatomy of the motor ANS utilising the terms;
a) Pre-ganglionic fibre
b) Post-ganglionic fibres
c) Ganglia
d) Paravertebral ganglia
e) Pre vertebral ganglia
a) cell bodies arise in the central nervous system, project axons which leave the CNS and synapse at pre- and post-vertebral ganglia
b) cell bodies arise in ganglia
c) collections of cell bodies
d) chain of nerve cell clusters that run alongside the spinal cord. sympathetic NS
e) clusters of nerve cells located in front of the spinal column. sympathetic NS.
Name the ‘classic’ neurotransmitters synthesised and released by pre- and post- ganglionic fibres in the sympathetic and parasympathetic divisions of the ANS, and the receptors they act upon
sympathetic - pre-ganglionic neurons = acetylcholine > nicotinic Ach receptor. post-ganglionic neurons = noradrenaline > adrenoceptor (⍺1,⍺2, beta1, beta2)
parasympathetic - pre-ganglionic neurons = acetylcholine > nicotinic Ach receptor. post-ganglionic neurons = acetylcholine > muscarinic Ach receptor.
Understand the meaning of the terms cholinergic, cholinoceptor, adrenergic, adrenoceptor, and non-adrenergic,non-cholinergic (NANC)
cholinergic - acetylcholine. parasympathetic
cholinoceptor - Ach is the endogenous agonist of nicotinic/muscarinic Ach receptors. nAchR > ligand-gated ion channel. mAchR > G-protein coupled receptor
adrenergic - adrenaline/noradrenaline. sympathetic.
adrenoceptor - noradrenaline and adrenaline are the endogenous agonists. G-protein coupled receptors.
NANC - sympathetic > ATP. neuropeptide Y. parasympathetic > nitric oxide. vasoactive intestinal peptide.
State the effect of sympathetic and parasympathetic stimulation upon selected targets noting their frequently reciprocal, but in some instances unopposed, effects
sympathetic:
increased vascular tone = vasoconstriction
1. ATP produces a fast contraction of the smooth muscle
2. noradrenaline produces a moderately fast response
3. neuropeptide Y produces a slow response
pupil dilation - ⍺1 - noradrenaline
airway relaxation - β2 - noradrenaline
increased rate and force of heart contraction - β1 - noradrenaline
sweat gland secretion - mAchR - acetylcholine
penile ejaculation - ⍺1 - noradrenaline
Parasympathetic:
decreased vascular tone = vasodilation
1. acetylcholine and nitric oxide produce a rapid relaxation
2. vasoactive intestinal peptide can produce a slow, delayed response
pupil contraction - mAchR - acetylcholine
airway contraction - mAchR - acetylcholine
decreased heart rate - mAchR - acetylcholine
penile erection - mAchR - acetylcholine
Provide a simple description of neurochemical transmission in the sympathetic and parasympathetic divisions of the ANS noting their exemplar organ distribution and physiological actions.
sympathetic:
short myelinated pre-ganglionic neuron
pre-ganglioinc fibres synapse in pre- and para-vertebral ganglia
long unmyelinated post-ganglionic neurons
pupil dilation - ⍺1 - noradrenaline
airway relaxation - β2 - noradrenaline
increased rate and force of heart contraction - β1 - noradrenaline
sweat gland secretion - mAchR - acetylcholine
penile ejaculation - ⍺1 - noradrenaline
parasympathetic:
long myelinated pre-ganglioinc neurons
pre-ganglionic fibres synapse in or on target tissues/organs
short unmyelinated post-ganglionic neurons
pupil contraction - mAchR - acetylcholine
airway contraction - mAchR - acetylcholine
decreased heart rate - mAchR - acetylcholine
penile erection - mAchR - acetylcholine
Describe the overall organisation of the somatic motor system
a branch of the peripheral nervous system
consists of the skeletal muscle and their neural control elements > RESPONSIBLE FOR MOTOR CONTROL OF SKELETAL MUSCLE
voluntary
motor neurons of the somatic NS - upper motor neurons. lower motor neurons.
upper motor neurons - arise in the cerebral cortex > central nervous system in the brain. uses glutamate as a neurotransmitter
lower motor neurons - arise from the spinal cord > axons synapse directly on skeletal muscle (force generation). uses acetylcholine as a neurotransmitter.
CONTROL IS FACILITATED BY UPPER MOTOR NEURONS WHICH SYNAPSE ON AND DRIVE LOWER MOTOR NEURONS WHICH ACT AS THE FINAL COMMON PATHWAY IN INITIATING SKELETAL MUSCLE CONTRACTION
Understand the segmental organisation of lower motor neurons (LMNs)
lower motor neurons exit the spinal cord in spinal nerves, and are organised into motor units with skeletal muscle fibres. provide both motor and sensory supply to skeletal muscle, and sensory input from skin and visceral receptors
30 spinal nerves which innervate muscles roughly at the spinal segment.
Understand the distinction between a motor unit and motor pool
motor unit > ⍺-motor neuorn and all of the skeletal muscle it innervates
motor pool > single muscle innervated by group of ⍺-motor neurons
Appreciate the factors that contribute to force of contraction
motor unit recruitment
changes in the frequency of action potentials generated
Describe the features of motor units
motor units vary in size
smaller motor units control finer movements and are innervated by smaller ⍺-motor neurons
larger motor units control postural muscles and are innervated by larger ⍺-motor neurons
Discuss the different types of skeletal muscle fibres, their characteristics and functions
red muscle:
slow twitch. slow myosin ATPase activity. high fatigue resistance. high oxidative capacity. high myoglobin. low glycolytic capacity.
white muscle:
fast twitch. fast myosin ATPase activity. low fatigue resistance. low oxidative capacity. low myoglobin. high glycolytic capacity.
Appreciate the importance of the size principle of motor neuron recruitment
starts with slow motor units, then, fast, fatigue-resistant units, finally, fast, fatiguable units
understand the sensory components of skeletal muscle
two types of muscle fibres; 1. extrafusal - bulk of skeletal muscle fibres that create force generation and are innervated by ⍺-motor neuron. 2. intrafusal - the remaining specialised fibres (muscle spindles) that are innervated by 𝛄-motorneuron and sensory afferents
sensory innervation:
afferent information (travels upto the spinal cord where it synapses) provided by either the group 1a afferents or the group II afferents
motor innervation:
𝛄-motorneuron
generates contraction
Apply understanding of the following reflexes;
a) Stretch (myotatic) reflex
b) Golgi tendon (inverse myotatic) reflex
c) Flexion-withdrawal reflex
a) knee jerk. muscle is stretched and group 1a afferent fibres in the muscle spindle start firing. these synapse on ⍺-motorneurons in the spinal cord (the ⍺-motorneurons innervate the same muscle from which the group 1a afferent relayed the sensory information). ⍺-motorneuron induces contraction of skeletal muscle. muscle returns to resting length and firing frequency of group 1a decreases. THE REFLEX STIMULATES IN THE SPINAL CORD, THE MOTOR NEURONS TO THE EXTENSOR MUSCLE, AND, INHIBITS THE MOTOR NEURONS TO THE FLEXOR MUSCLE.
b) clasp knife. muscle contracts and the extrafusal fibres shorten, and this stimulates the golgi tendon organ. group 1b afferents start firing and send sensory information to the inhibitory interneurons they synapse on, in the spinal cord. inhibitory interneurons synapse on the ⍺-motorneurons. muscle returns to resting lrngth and firing frequency of group 1b decreases. synergistic muscles also relax and antagonistic muslces contract. THE REFLEX INHIBITS IN THE SPINAL CORD, THE MOROT NEURONS TO THE EXTENSOR MUSCLE, AND, STIMULATES THE MOTOR NEURONS TO THE FLEXOR MUSCLE.
c) stubbing toe. when something painful/noxious is detected, there are multiple afferent fibres that are activated which then synapse on multiple interneurons in the spinal cord. on the same side as the painful/noxious stimuli, flexors are contracted and extensors are relaxed. on the opposite side as the painful/noxious stimuli, flexors are relaxed and extensors are contracted. IN THE LEG THAT FEELS THE PAIN, THE REFLEX INHIBITS IN THE SPINAL CORD, THE MOTOR NEURONS TO THE EXTENSOR MUSCLE, AND, STIMULATES THE MOTOR NEURONS TO THE FLEXOR MUSCLE. IN THE OPPOSITE LEG, THE REFLEX STIMULATES IN THE SPINAL CORD, THE MOTOR NEURONS TO THE EXTENSOR MUSCLE, AND, INHIBITS THE MOTOR NEURONS TO THE FLEXOR MUSCLE.
state the varied functions of smooth muscle
vasculature - controls diameter, regulates flow and pressure
airways - controls diameter, regulates flow and resistance
urinary system - propulsion of urine into ureters, bladder tone, tone of internal sphincter of bladder
gastrointestinal tract - controls tone, motility, opening/closing of sphincters
male reproductive tract - secretion, propulsion of semen
female reproductive tract - propulsion (fallopian tubes), partuition (uterus)
skin - pilli erection
Describe the major classes of smooth muscle
tonic - multi-unit. electrical isolation of cells allows finer motor control. function individually. e.g. iris and vas deferens
phasic - unitary. gap junctions permit coordinated contraction. function as a syncytium. e.g. stomach, urinary bladder and bronchioles
Provide a summary of the structure of a smooth muscle cell
individual muscle fibres are relatively small, spindle shaped, and possess one nucleus
Explain the mechanisms responsible for contraction and relaxation of smooth muscle, noting the role of calmodulin, in particular
smooth muscle relies on sliding filament mechanism generated during actin-myosin cross-bridge formation to facilitate contraction.
1. driven by a rise in intracellular calcium concentration which binds to calmodulin (Ca2+ is released from sarcoplasmic reticulum, or an influx across the plasma membrane)
2. Ca2+-calmodulin complex activated myosin light chain kinase (MLCK)
3. myosin light chain is phosphorylated on the myosin head
4. phosphorylation of myosin head ‘cocks’ it and increases its ATPase activity readying it to interact with actin to form a cross-bridge
calmodulin:
a multifuncitonal Ca2+ binding protein present in the cytoplasm of all eukaryotic cells.
Describe the process of excitation contraction coupling in smooth muscle, detailing pharmacomechanical and electromechanical coupling
pharmacomechanical coupling:
the process by which an agent causes a change in smooth muscle tone without a change in membrane potential. involves the production of intracellular second messengers that either contract or relax, the muscle (IP3 > causes contraction. cGMP and cAMP > causes relaxation)
electromechanical coupling:
the opening of plasma membrane voltage-activated L-type Ca2+ channels in response to depolarisation with, or, without action potential generation.
Describe the contractile elements of smooth muscle
sliding filament mechanism
actin-myosin cross-bridge formation
Describe the innervation of smooth muscle and the control of its activity
innervated by the autonomic nervous system
arterial smooth muscle - sympathetic innervation with noradrenaline
other smooth muscle - sympathetic and parasympathetic innervation with noradrenaline and acetylcholine
Describe the effects of organic nitrates (e.g. GTN) on the systemic circulation as well as the coronary circulation and understand their role in the treatment of angina and acute coronary syndromes
the primary action of organic nitrates is to induce venodilation to reduce venous pressure and the venous return to the heart which reduces work of the heart by Starlings law to overall reduce oxygen demand.
nitrate dilates collateral and increases blood flow to ischaemic myocardium.
organic nitrates act directly on the smooth muscle cell to increase nitric oxide production causing relaxation and therefore vasodilation where they act on veins to reduce preload and oxygen demand in the myocardium, secondary action on the coronary collaterals to improve oxygen delivery to the ischaemic myocardium
describe the regulation of vascular smooth muscle contraction
increase in intracellular calcium concentration by release from SR or by opening of L-type Ca2+ channels
intracellular calcium binds to calmodulin forming a Ca2+-calmodulin complex which activated MLCK to phosphorylate MLC which causes contraction.
cGMP activated protein kinase G which activates additional MLCP to dephosphorylate MLCp which causes relaxation
Outline the mechanism of action and limited clinical uses of Katp channel openers
open Katp channels in the smooth muscle cell membrane and hyperpolarise the smooth muscle cell
can be used in severe hypertension alongside beta blocker and diuretics
Appreciate the important role of the endothelium in regulating vascular smooth muscle tone
vasodilating substances cause an increase in intracellular calcium concentration in an endothelial cell which binds to calmodulin forming a calcium-calmodulin complex. L-arginine and O2 bind with endothelial nitric oxide synthase to form nitric oxide and citrulline. nitric oxide enters the smooth muscle cell which with the aid of guanylate cyclase catalyses the formation of cGMP from GTP which activates protein kinase G causing relaxation.
protein kinase G:
stimulates MLCP
stimulates plasma membrane Ca2+ ATPase
stimulates sarcoplasmic.endoplasmic reticulum Ca2+ATPase
activates K+ channels that cause hyperpolarisation and inactivate Ca2+ channels.
Explain why calcium channel blockers are used in the treatment of hypertension, angina, and certain disturbances of cardiac rhythm
act at L-type Ca2+ channels on vasclar smooth muscle and in cardiac myocytes
block calcium channels so there is no increase in intracellular calcium ion concentration which leads to relaxation of the vascular smooth muscle.
Explain why ⍺-blockers may be used in the treatment of hypertension
⍺1 adrenoceptors are the first part of the signalling cascade that leads to smooth muscle contraction following activation of the sympathetic nervous system
⍺1 antagonists prevent this signalling cascade and leads to vasodilation
describe the function of the cardiovascular system
blood transportation network. blood carries nutrients, oxygen and waste products to and from cells.
Differentiate between pulmonary and systemic circulation
pulmonary circulation > between the heart and the lungs. deoxygenated blood enters the lung capillaries and then exits oxygenated through the diffusion of O2 in the alveolus.
systemic circulation > between the heart and all organs and tissues. oxygenated blood is distributed to the brain, skin, kidneys, muscles, liver and then back to the heart deoxygenated.
Describe the location of the heart
located within the middle mediastinum
situated pbliquely, with 2/3rds of the heart left to the mid-sternal line, and 1/3rd to the right
sits within the pericardium
Identify the structures of the heart
the pericardium > fibrous and serous
the heart wall > the epicardium - outer layer. the myocardium - middle layer, cardiac muscle. the endocardium - inner layer. the purkinje fibres - distribute excitatory activity for ventricular contraction.
atrioventricular valves
semilunar valves
Relate the structure of the heart to its function
deoxygenated blood flow:
vena cava > right atrium > tricuspid valve > right ventricle > pulmonary valve > pulmonary artery > lungs
oxygenated blood flow:
lungs > pulmonary vein > left atrium > mitral valve (bicuspid) > left ventricle > aortic valve > aorta
during diastole which is when the heart muscles relax as it fills with blood, the AV valves open during ventricular diastole due to relaxed papillary muscles.
during systole which is when the heart muscles contract and blood is pumped out, AV valves close during ventricular systole due to contraction of papillary muscles creating tension of chorae tendinae
the pulmonary valve is between the right ventricle and the pulmonary trunk
the aortic valve is between the left ventricle and aorta
semilunar valves prevent backflow of blood into the ventricles
conducting system of the heart:
generates and transmits impulses to produce coordinated contractions
excitation signal is created by the sinoatrial node. the wave of excitation spreads across the atria, causing them to contract. upon reaching the atrioventricular node, the signal is delayed. signal is conducted into the bundle of His, down the intraventricular septum. the bundle of His and the purkinje fibres spread the wave of impulses along the ventricles, causing them to contract.
Distinguish between arteries and veins
arteries of the heart supply the heart with oxygenated blood. left and right coronary arteries emerge from the aortic sinus of the ascending aorta.
veins drain the heart of deoxygenated blood. drain into the coronary sinus which then empties into the right atrium
blood vessel structure:
1. tunica intima - single layer of cells
2. tunica media - smooth muscle
3. tunica adventitia - outer connective tissue
arteries vs veins:
share the same three layers. arteries have thicker walls and smaller lumen due to higher blood pressure. veins often contain valves.
Name the 2 specialised types of cardiac cell.
contractile cells - normally do not initiate action potentials
autorhythmic cells - initiate or conduct action potentials
Define pacemaker activity and pacemaker potential.
cardiac autorhythmic cells display pacemaker activity, they cyclically initiate action potentials which then spread through the heart to trigger contraction without any nervous stimulation.
autorhythmic cells do not have a resting membrane potential. the cells membrane slow drift to threshold is called the pacemaker potential.
List the 4 sites where specialised cells that demonstrate autorhythmicity are found in the heart.
- the sinoatrial node
- the atrioventricular node
- the bundle of His (atrioventricular bundle)
- purkinje fibres
For specialised cardiac cells that have pacemaker potential state their spontaneous rate of firing.
SA node - 70-80 action potentials per minute
AV node - 40-60 action potentials per minute
Bundle of His and purkinje fibres - 20-40 action potentials per minute
atrial and ventricular myocardium - 0 action potentials per minute
Draw a simple diagram to illustrate the spread of excitation across the heart.
DRAW
Sketch a typical action potential in a SA node pacemaker cell, labelling both the voltage and time axes accurately.
GRAPH
Briefly summarise the ionic mechanism of pacemaker automaticity and rhythmicity.
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Sketch a typical action potential in a ventricular muscle cell, labelling both the voltage and time axes accurately.
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Briefly describe how ionic currents contribute to the 5 phases of the cardiac action potential.
cycle of voltage changes across cardiac myocytes
occurs in five distinct phases;
1. depolarisation
2. early repolarisation
3. plateau phase
4. late repolarisation
5. resting potential
Explain what accounts for the long duration of the cardiac action potential, and the resultant long refractory period.
the long duration of the cardiac action potential is primarily due to the plateau phase, caused by the balance of calcium influx and potassium efflux, which prolongs the depolarisation.
The long refractory period ensures that the heart cannot be re-stimulated before it has fully relaxed, preventing dangerous continuous contractions and allowing proper filling and pumping of blood.
What is the advantage of the long plateau of the cardiac action potential, and the long refractory period?
prevention of tetany and ensures proper heart function
prevents premature contraction and allows full heart relaxation
The long plateau makes sure the heart muscle contracts long enough to pump blood effectively, while the long refractory period makes sure the heart has time to relax and refill before the next beat
Describe the electrode positions for recording standard limb leads I, II and III.
limb leads I, II, III are bipolar leads
lead I > right arm to left arm
lead II > right arm to left leg
lead III > left arm to left leg
Identify the major components of the ECG (P wave, QRS complex, T wave).
P wave = atrial depolarisation moving towards the recording electrode
QRS complex = ventricular depolarisation and atria repolarisation.
T wave = ventricular repolarisation moving in a direction opposite to that of depolarisation, accounts for the usually observed upward deflection.
Relate the electrical activity in the heart to these major components.
Explain the time relationships between the electrical activity of the heart (as recorded in the ECG) and the mechanical activity of the heart.
an ECG is not a direct recording of the actual electrical activity of the heart.
Define and calculate cardiac output (CO).
CO is the volume of blood pumped by each ventricle per minute
CO =HR x SV = l/min
SV = the volume of blood ejecter per contraction
Give approximate minimum and maximum values for CO in untrained and trained adults.
young adult at rest = 5 l/min
young adult exercising = 23 l/min
marathoner = 30 l/min
Understand that CO is regulated by intrinsic and extrinsic mechanisms.
CO is controlled according to physiological requirements - via control of HR and SV
1. intrinsic control - varying the initial length of the cardiac muscle fibres, which in turn depends upon EDV
2. extrinsic control - varying the extent of sympathetic stimulation
3. end diastolic volume - an increase in EDV increases SV > as more blood returns to the heart, the heart pumps out more.
Draw and describe the length-tension relationship of a single cardiac cell (Frank-Starling curve).
an increase in tension = an increase in length
cardiac muscle does not normally operate within the descending limb of the length-tension curve
degree of diastolic filling causes muscle fibres to vary in length before contraction. increased EDV, the more the heart is stretched, the longer the initial cardiac fibre length before contraction, resulting in greater force on the subsequent cardiac contraction, a greater SV
Define preload.
the amount of blood that fills the hearts ventricles at the end of diastole
the volume of blood in the ventricles before the heart contracts
Define afterload.
the resistance the heart must overcome to pump blood out of the ventricles.
Predict the consequence of an increase or decrease in arterial pressure on the cardiac workload.
increase in arterial pressure = higher cardiac workload
decrease in arterial pressure = lower cardiac workload
Define contractility and explain why dP/dt is a useful index of contractility.
contractility is the hearts ability to contract with force
dP/dt is a measure of how quickly the pressure inside the heart increases during contraction
Explain the cellular basis for the effects of Ca2+ on cardiac muscle contractility.
extrinsic control - sympathetic stimulation and adrenaline - enhance the hearts contractility due to increased Ca2+ entry triggered by noradrenaline/adrenaline. increased inward Ca2+ influx during the plateau phase enhances the intracellular calcium ion concentration store. Ca2+ is required for excitation-contraction coupling in cardiac muscle cells. increase the rate of relaxation of cardiac muscle cells by stimulating Ca2+ pumps to take up more Ca2+ from the cytoplasm more rapidly and therefore shortening systole.
Explain how changes in sympathetic activity alter ventricular work and cardiac output.
Increased sympathetic activity causes the heart to work harder, leading to increased ventricular work and higher cardiac output. This is useful during times of stress or exercise when the body needs more oxygen and nutrients delivered through the blood
Describe the major functions and features of each major vessel type (arteries, arterioles, capillaries, veins).
arteries - low resistance vessels conducting blood to the various organs with little loss in pressure. act as pressure resevoirs for maintaining blood flow between ventricular contractions. several hundred. thick, highly elastic walls. large radii. passageway from heart to organs. serve as pressure resevoirs.
arterioles - makor sites of resistance to blood flow. responsible for the pattern of blood flow distribution. participate in the regulation of arterial blood pressure. half a million. highly muscular, well-innervated walls. small radii. primary resistance vessels. determine distribution of cardiac output.
capillaries - site of exchange between blood and tissues. ten billion. thin walled. large total cross-sectional area. site of exchange. determine distribution of extracellular fluid between plasma and interstitial fluid.
veins - low resistance vessels for blood to flow back to the heart. their capacity for blood is adjusted to facilitate flow. several hundred. thin walled. highly distensible. large radii. passageway to heart from organs. serve as blood resevoir.
Draw a simple, labelled diagram to illustrate the 3 layered, basic structure of a blood vessel wall.
adventitial layer - connective tissue
medial layer - smooth muscle cells
intimal layer - endothelial cells
Describe the composition of each layer of the blood vessel wall.
elastic artery:
5% endothelium. 25% smooth muscle. 40% elastic tissue. 30% connective tissue.
arteriole:
10% endothelium. 60% smooth muscle. 10% elastic tissue. 20% connective tissue.
capillary:
95% endothelium. 0% smooth muscle. 0% elastic tissue. 50% connective tissue.
venule:
20% endothelium. 20% smooth muscle. 0% elastic tissue. 60% connective tissue.
Describe the key differences in composition of walls of different blood vessel types.
aorta:
internal radius = 12mm
wall thickness = 2mm
medium artery:
internal radius = 2mm
wall thickness = 1mm
arteriole:
internal radius = 15µm
wall thickness = 20µm
true capillary:
internal radius = 3µm
wall thickness = 1µm
venule:
internal radius = 10µm
wall thickness = 2µm
vein:
internal radius = 2.5mm
wall thickness = 0.5mm
vena cava:
internal radius = 15mm
wall thickness = 1.5mm
State the units used for blood flow and blood pressure.
blood flow = volume per unit time = l/min
pressure = ΔP (mmHg)
Define resistance in relation to blood flow through a vessel.
a measure of how difficult it is for blood to flow between two points at any given pressure difference
a measure of the friction impeding flow
F=ΔP/R
resistance is proportional to 1/r^4
dependent on 3 factors; 1. viscosity of the blood, 2. vessel length, 3. vessel radius
State the relationship between flow, pressure and resistance.
resistance is proportional to 1/r^4
flow is proportional to r^4
Describe why diastolic pressure is not 0 mmHg.
the arteries maintain a certain level of pressure to keep blood flowing between heartbeats
Describe the effect on blood flow of an increase in resistance.
an increase in resistance causes a decrease in blood flow
Describe the effect on blood flow of a decrease in resistance.
as resistance decreases, blood flow increases
Know how to calculate pulse pressure.
pulse pressure = end systolic volume - end diastolic volume
With reference to Poiseuille’s equation, state what would happen to flow rate in response to changes (ie increase or decrease) in pressure gradient, radius, or viscosity.
pressure gradient:
increase = flow increases
decrease = flow decreases
radius:
increase = flow increases
decrease = flow decreases
viscosity:
increase = flow decreases
decrease = flow increases
Know how to calculate mean arterial pressure.
mean arterial pressure = diastolic blood pressure + 1/3(pulse pressure)
List the 3 factors that give rise to resistance to blood flow. Which of the 3 is most important?
blood viscosity
blood vessel length
blood vessel radius - most important
Draw a labelled plot to show changes in arterial blood pressure over time.
DRAW
Draw a labelled plot to show changes in blood pressure throughout the systemic circulation.
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Describe the relationships between blood flow rate, total cross sectional area and velocity of flow across all levels of the circulatory system.
blood flow rate stays the same throughout the circulatory system
total cross-sectional area is small in arteries and veins, but is very large in capillaries
velocity of flow is fastest in arteries and slowest in capillaries
Briefly describe why arterioles are the major resistance vessels.
as the small radius of arterioles offers considerable resistance to blood flow which causes a marked drop in mean pressure as blood flows through arterioles. this pressure gradient helps drive blood from the heart to the tissue capillary beds
State which nerves innervate the smooth muscle found in the walls of arterioles.
arteriolar walls include a thick layer of smooth muscle that is richly innervated by nerves of the sympathetic nervous system
Know that smooth muscle cells are sensitive to local chemical changes and certain circulating hormones.
smooth muscle is also sensitive to many local chemical changes and certain circulating hormones
Define vascular tone and state the 2 factors that contribute to this
arteriolar smooth muscle displays a state of partial constriction which is vascular tone
1. myogenic activity
2. sympathetic activity
tonic activity makes it possible to either decrease or increase contractile activity
any changes in contractility of arteriolar smooth muscle will substantially change resistance to flow in these vessels
Describe what happens to radius, resistance and flow during arteriolar i) vasoconstriction and ii) vasodilation.
i) contraction. decreased radius, increased resistance. decreased local blood flow.
increased contraction of smooth muscle. increase in resistance
decreased flow through the vessel
ii) relaxation. increased radius, decreased resistance. increased local blood flow.
decreased contraction of smooth muscle
decrease in resistance
increased flow through the vessel
Define tachycardia and bradycardia.
tachycardia - increased activity in the sympathetic nerves to the heart to increase heart rate
bradycardia - increased activity in the parasympathetic nerves to the heart to decrease heart rate
Describe the effects of the autonomic transmitters acetylcholine and noradrenaline (norepinephrine) and the hormone adrenaline (epinephrine) upon heart rate, contractility and electrical conduction within the heart.
parasympathetic:
the vagus nerve releases acetylcholine to muscarinic receptors
alter the activity of the cAMP second messenger pathway in innervated cardiac cells
Ach is coupled to an inhibitory G-protein that reduces activity of the cAMP pathway
decreases heart rate through 2 effects on pacemaker tissue - hyperpolarisation of the SA node membrane so it takes longer to reach threshold - decreases the rate of spontaneous depolarisation (Ach increases K+ permeability by G-protein-coupled inwardly-rectifying potassium channels)
decreases the AV nodes excitability which prolongs transmission of impulses to the ventricles
shortens the plateau phase of the action potential in atrial cotractile cells, weakening atrial contraction
has little effect on ventricular contraction
parasympathetic activity arises in the cardioinhibitory centre of the medulla
neurotransduction through the vagus nerve mediates inhibitory input
Ach increases SA node permeability to K+ (slow closure of K+ channels) and so increased leakage of +’ve charge. SA node hyperpolarises between contraction cycles resulting in fewer action potentials at the SA node, does not alter AV node function
heart rate decreases
sympathetic:
releases noradrenaline to beta1 adrenergic receptors
alter the activity of the cAMP second messenger pathway in innervated cardiac cells
NorAd is coupled to a stimulatory G-protein that accelerates activity of the cAMP pathway
speedsup heart rate through its effect on pacemaker tissue (tachcardia) - speeds up depolarisation, so threshold is reached more rapidly (NorAd augments funny channels, If, and transient-type Ca2+ channels, T)
reduces AV nodal delay by increasing conduction velocity
speeds up spread of action potential throughout the specialised conduction pathway
increased contractile strength of the atrial and ventricular contractile cells - heart beats more forcefully and squeezes out more blood - increase Ca2+ permeability through prolonged opening of L-typed Ca2+ channels
speeds up relaxation
sympathetic activity arises in the cardioacceleratory centre of the medulla
motor neurons linking to T1-T5 level of the spinal cord synapse with ganglionic neurons located in cervical and upper thoracic symoathetic chain ganglia. postganglionic fibres innervate the SA and AV node to raise HR and CO
NorAd accelerates closure of K+ channels so reducing K+ permeability. SA and AV node membrane potential moves closer to threshold due to accumulation of +’ve charge in the cell between depolarisation cycles. increase in Na+ and T-type Ca2+ channel activity further accelerates depolarisation and raises action potential frequency
heart rate increases
Define afterload.
the resistance the heart must overcome to pump blood out of the ventricles.
Predict the consequence of an increase or decrease in arterial pressure on the cardiac workload.
increase arterial pressure = increases cardiac workload
decrease arterial pressure = decreases cardiac workload
Describe the neural and hormonal control of arterial blood pressure
short term control - mediated by the baroreceptor reflex - neural control
long term control - renin-angiotensin-aldosterone system - hormonal control
neural control
negative feedback loop of stretch-sensitive baroreceptors acting as the sensors (afferents), cardiovascular control centre in the medulla oblongata acting as the integrator, and autonomic neurons acting as the effectors (efferents)
Describe how baroreceptor activity changes in response to changes in arterial blood pressure and the influence this has upon sympathetic and parasympathetic outflow to the heart and vasculature
increased BP
increase in BP activates stretch receptors in the carotid sinus and impulses are transmitted to the glossopharyngeal nerve and then to nuclei tractus solitarii causing stimulation, this stimulation inhibits sympathetic activity causing a reduction in smooth muscle contraction leading to vasodilation and a fall in blood pressure
Identify the location of the baroreceptors and the corresponding nerves involved in communication between these and the cardiovascular centre in the brain
arterial baroreceptors
afferent nerve fibres relay information to the brain about blood pressure
are ideally located stretch receptors
located at the carotid sinus and aortic arch
cardiopulmonary baroreceptors
afferent fibres of four types - myelinated veno-arterial mechanoreceptors, non-myelinated mechanoreceptors, coronary artery baroreceptors, chemosensors
located in the heart and pulmonary artery
Understand the therapeutic applications of control of blood pressure
hypertension = BP of 140/90mmHg
angiotensin-converting enzyme inhibitor
angiotensin-II receptor blocker
calcium channel blocker
thiazide-like diuretic
Recognise and describe the regulation of blood volume in long term control of blood pressure
a) Renin - angiotensin - aldosterone system
a decrease in renal perfusion pressure (a decrease in effective circulating volume) causes a decrease in stretch on afferent arterioles and an increases in renin, as well as a rise in sympathetic activity and a decrease in NaCl concentration
renin is produced by juxtaglomerular cells in the kidney, renin cleaves angiotensinogen to angiotensin I which travels thorugh the blood stream, when it reaches the lungs ACE enzymes convert it to angiotensin II which is a vasoconstrictor peptide that stimulates thirst and ADH release in the hypothalamus and the release of aldosterone from the adrenal cortex, aldosterone increases Na+ absorption which increases water uptake to increase the blood volume and therefore increases bloop pressure.
Describe the principles of the mechanisms of action and indications for use of;
a) angiotensin - converting enzyme (ACE) inhibitors and,
b) angiotensin II receptors antagonists
a) blocks ACE in the lungs from converting angiotensin I into angtiotensin II resulting in a decrease in circulating blood volume and therefore decreases blood pressure. used as a first line treatment in hypertension with type two diabetes and without type 2 diabetes but over 55 years of age and not of a black African or African-Caribbean family origin
b) blocking of angiotensin II causes a decrease in veno-and atrioconstriction and a subsequent decrease in blood pressure. used as a first line treatment in hypertension with type two diabetes and without type 2 diabetes but over 55 years of age and not of a black African or African-Caribbean family origin
Describe the dynamic and static responses of baroreceptors to changes in mean arterial blood pressure and pulse pressure
an increase in mean arterial pressure increases carotid sinus firing frequency
Understand the effectors mediated changes in blood pressure facilitated by changes in the heart and vasculature
increased BP
parasympathetic activation slows the heart to reduce BP
vasodilation occurs to lower BP
the heart > increased sympathetic drive, increased noradrenaline release from postsynaptic neurons , binds to β1 adrenoceptors on the myocardium, increased chronotropy, increased dromotropy, increased inotorpy, decreased lusitropy, increased cardiac output, increased arterial BP.
the vasculature >increased sympathetic drive, increased noradrenaline release from postsynaptic neurons, binds to ⍺1 adrenoceptors on the myocardium, increased vasoconstriction, increased total peripheral resistance, increased arterial BP.
decreased BP
sympathetic activation increases heart rate and contractility to raise BP
vasoconstriction to increase resistance and raise BP
the heart >increased parasympathetic drive, increased acetylcholine release from postsynaptic neurons, binds to muscarinic M2 receptors on the myocardium, decresed chronotropy, decreased dromotropy, decreased inotorpy, increased lusitropy, decreased cardiac output, decreased arterial BP
the vasculature > increased parasympathetic drive, increased acetylcholine release from postsynaptic neurons, binds to muscarinic M3 receptors on the myocardium, increased vasodilation by endothelium dependent mechanism, decreased total peripheral resistance, decreased arterial BP
Describe the stages of lung growth in the fetus which give rise to adult lung structure
- embryonic - establishes basic lung structure as a template for further growth
- pseudoglandular - establishes the branched network of gas conducting airway
- canalicular - formation of the blood-gas barrier
- saccular - formation of the respiratory acinus > the zone of gas exchange
- alveolar - formation of the alveolus and high surface area for gas exchange
Review lung volumes and capacities and describe their measurement.
tidal volume - the air inhaled/exhaled in a normal breath
inspiratory reserve volume - extra air that can be inhaled after a normal breath
expiratory reserve volume - extra air that can be exhaled after a normal breath
residual volume - air that remains in lungs after full exhalation - measured by spirometry
functional residual capacity - air left in lungs after normal exhalation - measured by plethysmography
vital capacity - max air that can be exhaled after deep inhalation
total lung capacity - max air lungs can holr
Review gas movement between phases and the importance of partial pressure. Describe the structure of the lungs and airways and their relation to respiratory function.
gas follows partial pressure not concentration gradients
partial pressures tells the direction of movement of gas
gas moves from high partial pressure to low partial pressure both within and between phases
review respiratory function tests and respiratory disorders.
spirometry
plethysmography
obstructive lung diseases - asthma, COPD
restrictive lung diseases - pulmonary fibrosis
Describe the basic anatomical features of the lung from trachea to alveolar blood gas barrier
branch generation 1 >16
conductive zone, conducting airways. trachea > mainstream bronchi > terminal bronchioles
branch generation 17 >23
respiratory zone, alveolar air spaces. alveolus > respiratory bronchioles > alveolar ducts > alveolar sacs
Explain the process of gas movement over the blood gas barrier
Gas exchange across the blood-gas barrier happens by diffusion, where gases move from high partial pressure to low partial pressure:
Oxygen (O₂) moves from the alveoli (high O₂) into the blood (low O₂) to be delivered to the body.
Carbon dioxide (CO₂) moves from the blood (high CO₂) into the alveoli (low CO₂) to be exhaled.
The process is affected by: Barrier thickness (thicker barriers slow diffusion), Surface area (larger surface area improves gas exchange), and Gas solubility (CO₂ diffuses faster than O₂).
Identify the causes of resistance to gas movement into and out of the lung
airway restriction
reduced lung compliance
Name the respiratory muscles involved in quiet and forced breathing and describe the processes of inspiration and expiration
quiet breathing - during inspiration the diaphragm and external intercostal muscles work, during expiration no active muscles as elastic recoil of the lungs is sufficient
forced breathing - during inspiration the diaphragm, external intercostals, sternoceliromastoid and scalenes work, during expiration the abdominal muscles and internal intercostal muscles push air out of the lungs.
Define oxygen content, haemoglobin saturation and oxygen carrying capacity of blood.
oxygen content - determined by the amount of haemoglobin and oxygen in the blood
oxygen saturation - the proportion in percentage of oxygen
oxygen carrying capacity of haemoglobin is 1.34x15 = 20mls O2/100ml of blood
Interpret the consequences of different oxygen-haemoglobin dissociation curves for oxygen loading at the lungs and off-loading to tissues.
normal p50 = 27mmHg at pH7.4 and pCO2 of 40mmHg
left-shift p50 = increased Hb-O2 affinity, reduced O2 off-loading to tissues
right-shift p50 = decreased Hb-O2 affinity, raised O2 offloading to tissues
Define and understand the term compliance
Understand how surface tension affects elastic recoil
Describe the relationship between compliance and elastance
Describe components contributing to elastic recoil in the lung
Know how lung diseases affect lung compliance
Recognise the relationship between surface tension and surface free energy
Pressure volume curves.
Know how surfactant affects surface tension in the alveoli and thereby stabilises smaller alveoli
Static and dynamic resistances in respiratory mechanics. Airway resistance (AWR) its locations, measurements and factors affecting its value.
Mechanism of airway collapse during forced exhalation.
Work of breathing.
Differentiate between static and dynamic (non elastic) resistances
Describe/quantify the dynamic resistances
Explain why AWR is not collectively highest in the smallest diameter ‘tubes’
Describe how, in principle, AWR is measured
Draw a graph showing how the relationship between AWR and tubular diameter varies throughout the respiratory tree
Indicate factors affecting AWR
Draw & explain dynamic pressure-volume curves
Show graphically a normal Flow-Volume loop
Describe the mechanism of airway collapse in asthma
Review of sensory inputs, brainstem structures and efferent outputs involved in breathing.
Define ‘work of breathing’
Illustrate different patterns of breathing through use of pressure-volume graphs and indicate the most efficient (optimum) pattern
Describe the results of ablation experiments designed to identify brainstem regions controlling breathing
Description of ablation experiments.
Consideration of rhythmicity and pattern generators
Describe the role of the phrenic and vagus nerves in breathing
Review current theories concerning the neuronal structures involved in generating and modifying breathing patterns
Identify important features of neuronal pattern generators
Review of central and peripheral chemoreceptors. Oxygen and acid-sensitive potassium channels
Describe the location, characteristics and function of respiratory chemoreceptors
Identify the main chemical stimuli for increased ventilation under normal and pathological circumstances
Review recent evidence concerning the identity and role of oxygen- and acid- sensitive potassium channels
Describe what changes occur to heart rate, stroke volume, cardiac output, systolic pressure, diastolic pressure during exercise.
Quote sensible normal values for the above variables at i) rest and ii) at maximal work load.
Explain the mechanisms that underlie the above changes.
Explain the origin and consequences of “metabolic hyperaemia” in skeletal and cardiac muscle.
Explain the mechanisms responsible for the redistribution of cardiac output during exercise.
With reference to the underlying mechanisms, briefly explain what happens to TPR during heavy exercise.
Describe what happens to VE, VO2 and VCO2 at rest and during moderate and severe exercise
Describe what brings about the disproportionate rise in VE during heavy exercise.
Explain briefly how the respiratory exchange ratio can exceed 1 during heavy exercise.
Describe the concept of “O2 deficit” and “O2 debt”
Define VO2 max and how this can be determined.
Describe how gas transfer between the lungs and blood is enhanced.
Describe possible mechanisms whereby ventilation is driven during exercise.
Describe how working muscles acquire extra O2
