Possible 2 mark questions (all topics, not including definitions) Flashcards
1
Q
what four words does ADME stand for? (a useful term in pharmacokinetics)
A
Absorption
Distribution
Metabolism
Excretion
(things that the body does to the drug - pharmacokinetics)
2
Q
describe the process of first pass metabolism
A
when a drug is administered orally, it is absorbed by the gastrointestinal tract and transported via the hepatic portal vein to the liver where it is metabolised. as a result, only a small portion of the drug is passed into systemic circulation.
3
Q
list the four organs of the body where first pass metabolism takes place
A
liver and gut (stomach, small intestine, large intestine)
4
Q
list the four main routes of drug administration
A
enteral (via the gut): can include orally or rectally
parenteral (not via the gut): can include injections or topical administration
5
Q
what are the pros and cons of oral drug administration?
A
pros:
- low infection risk
- self administration is possible
cons:
- comes up against issues of first pass metabolism
- stomach is a harsh environment so drugs need to be formulated appropriately for this.
6
Q
what are the pros and cons of topical drug administration?
A
pros:
- local effect
- low infection risk
- bypass first pass metabolism
- low systemic effects/side effects
cons:
- long period of administration
- must be lipid soluble in order to permeate skin. must also be a drug with small molecules so they can be transported by carrier proteins
- often the carrier molecule used in drug formulation is a mild irritant in order to better permeate skin
7
Q
what are the pros and cons of injection as a method of drug administration?
A
pros:
- rapid bioavailability
- can be targeted
- bypasses first pass metabolism
cons:
- infection risk is high
- targeting risk if the needle misses.
8
Q
what is the difference between enteral and parenteral drug administration?
A
enteral is administration of a drug via the gut (orally or rectally) and so the drug is subject to first pass metabolism, meaning bioavailability is likely to be lower. parenteral methods bypass the gut and therefore bypass first pass metabolism.
9
Q
what are the processes that affect drug absorption?
A
- route of administration
- permeation (the ability of the drug to cross cell membranes)
10
Q
list the properties in Ficks law that determine how fast a drug is able to be absorbed.
A
- surface area
- distance
- concentration gradient
11
Q
what are the three main processes that affect drug distribution in the body?
A
- protein binding (only free, unbound drug can pass through cell membranes or bind to receptors. those bound to plasma proteins cannot)
- blood flow (higher blood flow = more drug in that area of the body)
- membrane permeability (a more permeable membrane will allow more drug into or out of a cell)
12
Q
describe phase I metabolism
A
phase I metabolism is the first stage of breaking down a drug, it often involves creating toxic metabolites. the product of phase I metabolism is called the derivative. Phase I metabolism usually involves enzymes such as cytochrome P450 in the liver. phase I changes the chemical structure of the drug through processes such as oxidation or deamination.
13
Q
describe phase II metabolism
A
phase II metabolism is the second stage of drug metabolism. (although can happen without phase I preceding it.) it involves the conjugation of the phase I metabolite with an endogenous substance, via covalent bonding, this makes the drug water soluble and biologically inactive. following phase II metabolism, the conjugate can be excreted from the body safely.
14
Q
name the four main protein targets for drugs
A
receptors
ion channels
carrier molecules
enzymes
15
Q
describe the process of pro-drug conversion using codeine as an example
A
codeine is a mild opioid in its original form, some other pro-drugs have no physiological effect in their original form. however, when codeine is metabolised in the liver, a portion of it becomes morphine, which is a much stronger opioid. it is this morphine that then passes into systemic circulation. pro-drugs can be activated by metabolism in the liver through interaction with enzymes. genetic differences determine how fast codeine is metabolised in the liver, and it can be dangerous for fast metabolisers as they end up with high doses of morphine in their blood.
16
Q
describe the difference between an ion channel blocker and an allosteric modulator
A
an ion channel blocker is a drug that sits in the pore of an ion channel, physically blocking it by being there. alternatively, an allosteric modulator binds to the ion channel at another site and changes the shape or function of the ion channel by doing so (so the channel is left open, but the molecule may change function or structure to change what comes into/out of the cell)
17
Q
describe the different ways that drugs can interact with enzymes
A
- enzyme inhibitors: normal action of an enzyme is blocked by the drug sitting in the binding site of the enzyme as they are substrate analogues (same shape as the intended substrate)
- false substrate: the drug binds to the enzyme and is broken down by it, this creates abnormal metabolites
- pro-drug: the drug binds to the enzyme and when it is broken down by the enzyme, it becomes a biologically active drug
18
Q
what is the difference between an orthosteric antagonist and a allosteric antagonist
A
both drugs block the action of a receptor. orthosteric antagonists bind to the intended ligand binding site and block the intended ligand from binding. allosteric antagonists bind to somewhere else on the receptor and change the shape or charge of the intended ligand binding site, deactivating it.
19
Q
describe the difference between an agonist and an antagonist
A
an agonist is a molecule which activates a receptor. an antagonist either blocks a receptor or reduces a response caused by an agonist. they oppose each other.
20
Q
what is the difference between a drug and a medicine
A
a drug is a chemical substance of known structure that has a biological effect. a medicine is one or more drugs combined (usually with excipients such as bulking agents or coatings) and administered for desired therapeutic effect. most medicines will contain at least one drug but a drug can exist without being a medicine.
21
Q
what are the three different names that can be given to a drug?
A
- chemical name (describes the drugs chemical structure)
- generic name (class of drug to which the molecule belongs)
- proprietary name/manufacturers name (what the drug is sold as)
22
Q
describe the mechanism of action of NSAIDs
A
NSAIDs inhibit COX enzymes, which convert arachidonic acid into intermediaries which then become prostanoids such as prostoglandin. by blocking COX enzymes, no prostoglandin is created so free nerve endings are not activated.
23
Q
briefly outline the desired effects of NSAIDs
A
- anti-inflammatory agent (prostoglandin is a vasodilator, but also no prostoglandin means less substance P so less neurogenic inflammation and less vasodilation = less swelling and oedema)
- analgesic agent (blocking COX 1 leads to no prostoglandin so less peripheral sensitisation. blocking COX 2 in the spine also stops central sensitisation)
- antipyretic effect (pyrogens stimulate prostoglandin E2 in the hypothalamus, this sends signals to regulate temperature. NSAIDs block COX 2 so no prostoglandin i made and so nothing interferes with pyrogens in the hypothalamus)
- platelet aggregation (platelets produces thromboxane A2 which alters surface proteins on platelets and allows them to bind together. COX 1 inhibition reduces thromboxane A2 and reduces blood clotting)
24
Q
explain how NSAIDs work as anti-inflammatory agents
A
prostoglandins derived from COX 2 enzymes are powerful vasodilators. inhibition of COX 2 removes these prostoglandins so no vasodilation occurs. lack of prostoglandin also prevents peripheral sensitisation and the production of substance P, which causes vasodilation and neurogenic inflammation. so the use of NSAIDs reduces swelling, oedema and redness.
25
explain how NSAIDs work as analgesic agents
NSAIDs block COX enzymes, which create prostoglandins. prostoglandins are early activators of free nerve endings and so lack of prostoglandin means that free nerve endings are not stimulated, preventing peripheral sensitisation also. NSAIDs also inhibit COX 2 in the dorsal horn of the spine, which prevents central sensitisation.
26
explain how NSAIDs work as antipyretic agents
pyrogens stimulate prostoglandin E2 in the hypothalamus, PGE2 inhibits temperature sensitive neurons, which means that the body can keep heating up with no signal of this reaching the hypothalamus. when the production of prostoglandin is stopped by NSAIDs blocking COX enzymes, temperature sensitive neurons can once again communicate with the hyppothalamus and homeostatic temperature control is restored.
27
explain how NSAIDs work in preventing platelet aggregation (blood clotting)
thromboxane A2 is produced by COX enzymes and changes surface proteins on platelets to allow them to bind to one another and create blood clots. when COX 1 is inhibited, thromboxane A2 production is stopped, which means platelets do not bind to one another and blood clots do not form. Aspirin has strong COX 1 selectivity and binds irreversibly to COX 1 in platelets so they never recover the ability to clot so new platelets must be produced in their place
28
when and where are COX 1 and COX 2 enzymes found?
COX 1: present in most tissues, primary roles are within gastrointestinal system and blood clotting
COX 2: usually undetected in tissues but is produced at the site of injury in response to inflammatory cytokines. also present in the CNS (spine).
29
list the potential unwanted side effects of NSAIDs
- gastrointestinal (COX 1 selective NSAIDs such as aspirin)
- respiratory (both, but common with COX 1 selective NSAIDs such as aspirin)
- Renal side effects (both COX1 and COX2 selective NSAIDS)
- liver damage (both, less common side effect but more severe)
30
list the intentional and unintentional side effects of aspirin
intended effects:
COX 1 inhibition leads to reduction in blood clotting/platelet aggregation. even though aspirin is COX 1 selective, it will still bind to some COX 2 so will also have analgesic, antipyretic and anti-inflammatory effects
unintended side effects:
COX 1 inhibition leads to potential for gastrointestinal issues, through the removal of protective mucous, and respiratory side effects such as aspirin induced asthma.
however through the inhibition of COX enzymes more generally could also have renal and hepatic side effects.
31
how can aspirin lead to gastrointestinal problems?
prostoglandins promote the production of strong alkali mucous which lines the stomach so that stomach acid doesn't start destroying the stomach itself. when COX 1 is inhibited by a COX 1 selective NSAID such as aspirin, prostoglandin production decreases and so less alkali mucous is produced. this may lead to aspirin induced gastritis and stomach ulceration.
32
how can aspirin use lead to respiratory side effects
arachidonic acid is also converted into leukotrienes which are bronchoconstrictors. when COX 1 is not inhibited, only some arachidonic acid is converted into leukotrienes, however when COX 1 is inhibited by NSAIDs such as aspirin, this leaves a large amount of arachidonic acid in the tissues of the lungs as none is being converted into other substances such as prostanoids, therefore, more arachidonic acid is converted into leukotrienes, so more bronchoconstriction takes place. this is an issue if the person already suffers with a respiratory condition such as asthma as it can induce symptoms of an asthma attack.
33
how can use of NSAIDs lead to renal damage?
prostoglandins promote vasodilation and glomerular filtration. when prostoglandins are not present, reduced renal filtration occurs, which leads to increased sodium retention. this in turn reduces the efficacy of the kidney and leads to damage.
34
how can NSAIDs use lead to liver damage?
the mechanism of this is not particularly well understood.
- retention of bile as a result of NSAID use could lead to liver damage
- mitochondrial damage which eventually leads to programmed cell death
- inhibition of prostoglandin E2 which is cytoprotective (stops programmed cell death)
- reactive metabolites - some of the metabolites of NSAIDs may cause an autoimmune response which eventually leads to the immune system destroying healthy liver cells.
35
outline the mechanism of action for opioids
at the dorsal horn in the spine, a nociceptive neuron meets a second order neuron. here, neurotransmitter is released to signal an action potential in the second order neuron and the nociceptive signal can then travel up the spine. however, endogenous opiates can reduce the transmission of neurotransmitter by binding to the synapse on the first order neuron. Opioids are drugs which artificially bind to the site of endogenous opiates and prevent the transmission of nociceptive stimuli to the second order neuron.
Opioids also have central effects within the brain but these are more complex and less well understood. overall opioids seem to depress the activity of neurons.
36
what are the potential side effects of opioids?
- constipation (activity of nerve cells in gut is downregulated)
- depression of cough reflex
- depression of respiration (neurons in brain stem responsible for inspiration, breathing in, are depressed)
- nausea/vomiting
- tolerance effects
- physical dependence and addiction
- euphoria
37
what are the potential long term effects of opioid use?
- immune suppression
- decreased sex hormone production
- opiate induced hyperalgesia (hypersensitivity to pain rather than pain suppression)
38
outline the mechanism of action of paracetamol
the mechanism of action of paracetamol is poorly understood. it is almost an nSAID but not technically. it may inhibit COX 2 within the CNS or even act on COX 3 which is very poorly understood in humans. alternatively it may activate descending inhibitory pathways or activate cannabinoid receptors.
- either way it is an analgesic and antipyretic
39
outline the process of metabolising paracetamol
phase I: this involves the breaking down of paracetamol into the toxic metabolite, NAPQI
phase II: glutathione breaks NAPQI down into the biologically inactive glutathione conjugate which can then be excreted from the body.
- unfortunately there is only enough glutathione in the body to cope with 4g worth of paracetamol per day, hence this is the maximum dose.
40
what are the potential side effects of paracetamol?
- overdose is very harmful and cause liver and kidney damage. it can also cause low blood cell count including low white blood cell count and low platelet count
- allergic reactions
- low blood pressure as the metabolites of paracetamol are vasodilators
41
what is the WHO analgesic ladder?
a treatment strategy for the management of pain. low levels of pain should be treated with no opioids, as pain increases the strength of opioid prescribed should increase.
- issues with this include the potential for over-reliance on opioids (addiction and possibility that they stop working) and lack of biopsychosocial approach (better ways of managing long term pain)
42
describe the difference between A delta and C fibres
both fibres are nociceptive fibres. but they have different properties. A delta fibres are large and myelinated and therefore transmit information much quicker (this is why you feel a sharp pain first). whereas C fibres are much thinner and non-myelinated, meaning they transmit much slower (why the dull, aching pain comes after the sharp pain). there are more C fibres in the body, making up about 70% of all nociceptive fibres.
43
describe the pathway of nociceptive information from the site of damage to the brain
A delta and C fibres both collect nociceptive information and carry information to the spine.
once in the spine, both fibres travel up the spinothalamic tract, which decussates in the spine, although carry slightly different information and target different areas of the brain.
- faster A delta fibres travel via the direct spinothalamic tract (lateral) to the cortical areas of the brain to allow for conscious awareness of pain. this allows for distinct spatial discrimination of the injury as well.
- slower C fibres travel via the indirect spinothalamic tract and target areas of the brain that are involved with the unconscious processing of pain including the hypothalamus, limbic system and reticular formation. this pathway has far worse spatial discrimination (a general ache in your foot rather than a pinprick pain)
44
describe the direct spinothalamic tract
the direct spinothalamic tract is an afferent sensory spinal pathway that carries information regarding pain/nociception to the conscious areas of the brain (cortical areas). the pathway decussates in the spinal cord. it travels through the lateral branch of the spinothalamic tract (which carries pain sensation). this branch of the spinothalamic tract primarily contains A delta fibres which carry fast, sharp pain and allow for clear spatial discrimination of the location of the injury.
45
describe the indirect spinothalamic tract
the indirect spinothalamic tract is an afferent sensory spinal pathway that carries information regarding pain/nociception to the unconscious areas of the brain such as the hypothalamus, limbic system and reticular formation. this pathway decussates in the spine. this pathway primarily contains slower C fibres which carry slow, aching pain with poor spatial discrimination for the site of injury.
46
briefly describe the pain gate theory
this is a theory proposed by Melzack and Wall whereby there is a 'gate' in the spinal cord that can be open (more experience of pain) or closed (less experience of pain). this gate can be closed by ascending physiological input such as the mechanoreceptor fibre, interneuron and nociceptor interaction that underlies the 'rub it better' principle (to summarise this, the activation of a mechanoreceptor allows an inhibitory interneuron to inhibit nociceptive signals reaching a second order neuron in the spine). however the gate can also be controlled by descending modulation from the cortical areas of the brain. for example if someone is happy and relaxed, descending signals from the brain can close the pain gate to reduce nociceptive signals. A biopsychosocial model of pain perception.
47
describe the process of peripheral sensitisation
When there is damage to an area of the body, early activators of free nerve endings include histamines, bradykinins, H+, K+ etc can trigger action potentials and lead to pain sensations.
when injury is persisting, free nerve endings release substance P. substance P activates mast cells to release more histamine, which in turn leads to greater activation of the free nerve ending. this creates a kind of feedback loop. substance P is also a powerful vasodilator and causes neurogenic inflammation at the site of injury.
48
describe the process of central sensitisation
central sensitisation, also known as spinal hyperexcitability, follows the principles of a process called long term potentiation, whereby a one time maximal stimulation of a second order neuron in the spine can lead to increasing sensitivity to lower levels of stimuli.
normal stimuli level = activation of AMPA receptors which causes a depolarisation/action potential as normal
maximal/large stimuli level = unblocking of NMDA receptors which allow for the entry of Ca2+ ions into the neuron, this starts an intracellular cascade whereby more AMPA receptors are made and AMPA receptors are made more sensitive. this means that the neuron itself becomes more sensitive to lower levels of stimulation.
49
list/describe some real world application of the pain gate theory
- 'rub it better' (also i think sometimes when someone is experiencing dermal injection into the skin, the clinician may rub the skin to reduce the sensation of the needle)
- psychological coping techniques (relaxation and meditation exercises, healthy coping strategies, distraction can all close the pain gate)
- social techniques (social support and lack of social isolation can close the pain gate)
biopsychosocial viewpoint is more important for individuals dealing with chronic pain as they will need long term self-management techniques outside of the use of drugs.
50
list some of the psychosocial factors which open or close the pain gate
closing the pain gate:
- social support
- healthy coping strategies
- distraction
- happiness
opening the pain gate:
- unhealthy coping strategies or pain catastrophising
- boredom
- anxiety
- lack of social support/social isolation
51
describe the descending modulatory pain pathways
descending modulatory pain pathways stem from the periaqueductal gray. they are a top down control mechanism of pain. broadly they act on endogenous opioid receptors and stop first order neurons from releasing neurotransmitter in the dorsal horn. there are two descending pathways. the serotonergic pathway releases serotonin and the noradrenergic pathway which releases noradrenaline.
52
why is pain a useful sensory modality?
pain warns us of an actual or potential risk to the body. it provides an alert of actual or potential damage so that the body can react (either consciously or unconsciously in the case of spinal reflex arcs) to remove itself from danger or away from noxious stimuli. pain largely prevents damage or further damage to the body.
53
briefly describe the different types of pain
acute = less than 3 months
chronic = longer than 3 months
neuropathic = no longer/no biological cause
superficial = skin level, localised
somatic = within the body, deeper, longer lasting
visceral = within organs or organ systems, dull, long lasting ache.
54
identify the main structures of a nerve cell
dendrites
soma (cell body) containing nucleus
axon hillock
axon (myelinated or non-myelinated)
terminal branches
terminal boutons
55
identify the structure of a nerve
axons, surrounded by the endoneurium membrane
axons in bunches called fascicles, surrounded by the perineurium membrane
fascicles bunched together are surrounded by the epineurium
nerves have their own blood supply (vasi nervorum) and nerve supply (nervi nervorum) which run between fascicles.
56
explain the functional classification of sensory, interneurons and motor neurons
sensory neurons = afferent neurons which receive signals from internal or external stimuli and pass information towards the CNS
interneurons = found within the CNS/spinal cord. connect sensory neurons to motor neurons but can also form complex networks of interneurons between themselves. sometimes act as inhibitors like in the pain gate theory
motor neurons = efferent neurons which receive input from the CNS and travel to effector organs where movement (or other response) is stimulated.
57
what is the difference between a graded potential and an action potential?
graded potential = local change in membrane potential which depends on the strength of the incoming stimuli and can either be a depolarisation or a hyperpolarisation.
action potential = an all or nothing event which is a depolarisation of a set magnitude that travels in one direction down the axon of a neuron. does not depend on the strength of incoming stimuli
58
describe the stages of an action potential and what happens
1. resting membrane potential (maintained by ion channels allowing k+ out and Na+ in, with ion pumps also maintaining a balance of about -70mv)
2. depolarisation occurs (all Na+ channels open, allowing Na+ to flood in down the concentration gradient (facilitated diffusion), K+ channels are closed so the membrane potential becomes positive, +30mv)
3. repolarisation (K+ channels open on a delay in response to depolarisation so after +30mv is reached, K+ channels open and Na+ channels close, K+ leaves the neuron and membrane potential restores to resting state)
4. hyperpolarisation (ion channels overshoot slightly and the neuron becomes more negative than resting potential, this is the refactory period. ion pumps then slowly restore membrane to resting potential)
59
how does the refactory period effect direction of action potentials?
the refactory period is a short period of hyperpolarisation where the resting membrane potential is more negative than resting state. this ensures that straight after an action potential has occurred in one segment of the neuron, another one cannot occur, meaning that the action potential travels in one direction down the axon and not both.
60
describe the structure and function of schwann cells
schwann cells are glial cells found in the peripheral nervous system (PNS). they form the myelin sheath of axons by wrapping their cell membrane in concentric layers around the axon. they speed up the conduction of action potentials as they are made of fatty non-conductive materials.
61
describe the structure and function of satellite cells
these are glial cells found in the PNS which maintain the shape and structure of neurons (stopping them from touching each other) and surround the cell bodies of neurons. they act like astrocytes in the CNS and maintain the chemical environment needed for neurons, provide nutrients etc by connecting to nearby capillaries.
62
describe the structure and function of astrocytes
these are star shaped glial cells found in the CNS which perform a number of supportive roles for the neurons there. they maintain chemical environment, provide nutrients through their branching connections to capillaries. they perform homeostatic, metabolic and neuroprotective tasks and may even communicate with one another through electrical synapses.
63
describe the structure and function of microglia
microglia are small glial cells which act as the immune system of the CNS. they are able to phagocytose foreign bodies and waste products and multiply when a person is experiencing disease
64
describe the structure and function of oligodendrocytes
oligodendrocytes are the myelinating cells of the CNS, they produce myelin sheaths along axons in a very similar way to Schwann cells in the PNS. they increase conduction speed of action potentials and guide neuronal growth and regrowth.
65
describe the structure and function of ependymal cells
these are ciliated glial cells which form along the ventricles of the brain and spinal cord. they secrete and maintain homeostasis of cerebrospinal fluid.
66
describe seddons classification scheme of nerve damage
neuropraxia = compression or stretch of axons without causing any actual damage. some loss of function and sensation may occur distal to point of stretch or compression but full recovery happens quickly
axonotmesis = severance of axons, but connective tissues of nerve remain in tact. loss of function or sensation distal to point of damage occurs but recovers fully over time.
neurotmesis = full severance of a nerve and the axons within it. full distal loss of function or sensation in areas innervated by that nerve occurs and is unlikely to recover even over time. recovery may lead to painful nerve regrowth in the wrong location leading to bundles of nerves where they shouldn't be.
67
list the main causes of age related neuronal deterioration
- natural lessening of myelination occurs with age, leading to slower reactions
- lessening of neurotransmitter produced leads to weakening of signals within nervous system
- nerves and neurons are less able to regenerate or recover after injury, leading to worsened nervous connectivity and communication.
68
what is the role of the SNARE complex?
Ca2+ enters the terminal bouton when an action potential reaches it, Ca2+ binds to the SNARE complex and this causes the release of neurotransmitter from the terminal bouton through the process of exocytosis.
69
how does botulinum toxin work?
botulinum inhibits SNARE proteins in pre-synaptic terminal boutons and prevents release of neurotransmitter into the synapse. this leads to paralysis as no action potentials can reach effectors.
70
how does tetanus toxin work?
tetanus toxin binds to SNARE proteins specifically in neurons which inhibit lower motor neurons, preventing the release of neurotransmitters here. this means that lower motor neurons are not inhibited and continually fire, leading to muscle rigidity or spasms and can lead to respiratory failure.
71
outline the structure of a chemical synapse
- axon travels down axon to terminal bouton
- depolarisation of terminal bouton causes voltage gated Ca2+ ion channels to open, allowing Ca2+ into the terminal bouton
- Ca2+ binds to SNARE complex causing exocytosis of neurotransmitter into the synapse
- neurotransmitter diffuses across synaptic cleft
- neurotransmitter binds to specific receptors on the post-synaptic neuron and causes a wave of local depolarisation here (graded potential).
72
what is the difference between a chemical synapse and an electrical synapse?
chemical synapse = slow transmission but adaptable in that it can be inhibitory or excitatory. one way transmission. physical gap between two neurons. found in human nervous system.
electrical synapse = fast transmission but fixed effect. transmission occurs both ways. physical ion channel connection between the two neurons. only found between glial cells in human body
73
describe how an action potential is triggered in a post-synaptic membrane
if the input is excitatory, neurotransmitter binds to a specific membrane receptor which then opens voltage gated ion channels that allow Na+ into the cell and K+ out of the cell. this will cause a slight depolarisation of the post-synaptic membrane, which then travels to the axon hillock where summation will take place.
74
describe how a neurotransmitter such as ACh is removed from the synapse
- diffusion away from the synapse (where it will likely be taken in by glial cells such as astrocytes or satellite cells depending on where the synapse is)
- reuptake into the pre-synaptic neuron via ion channels
- degradation by enzymes in the synaptic cleft
75
describe the structure and function of free nerve endings
these are unencapsulated sensory receptors which are found in the skin. they are like branched endings to a nerve fibre. they are sensitive to nociceptive stimuli, but also hot and cold, and light touch.
76
describe the structure and function of pacinian corpuscles
these are encapsulated sensory receptors which are found in the deeper layers of the skin (dermis), bone periosteum, joint capsules, pancreas and other viscera. they consist of many layers of circular membrane around a central fibre. they detect transient pressure and vibration.
77
describe the structure and function of Meissner's corpuscles/tactile corpuscles
these are fluid filled, encapsulated sensory receptors which are found in the epidermis, particularly in the fingertips. they are sensitive to fine touch and pressure, and some level of vibration
78
describe the structure and function of Ruffini endings/bulbous corpuscles
these are encapsulated sensory receptors found in the epidermis and within joint capsules. they detect stretch and deformation within joints and skin and also detect warmth within the skin
79
describe the structure and function of Merkle cells/Merkle's discs
these are an unencapsulated sensory receptor which are found in high concentration in the lips and fingertips. they are very sensitive to light/discriminative touch, hence they are found in such touch sensitive locations.
80
describe the structure and function of golgi tendon organs
these are sensory receptors enclosed in spindle-like capsules that are found near the junction of a tendon and a muscle. they are sensitive to muscle tension.
81
describe the structure and function of muscle spindles
these are unencapsulated sensory receptors which are found embedded within skeletal muscle. they detect the stretch and length of a muscle.
82
which sensory receptors are found in joints/muscles and send proprioceptive information back to the CNS?
- golgi tendon organs
- muscle spindles
- Ruffini endings
- Pacinian corpuscles
83
how can motor units make movement smooth?
motor units are the muscle fibres that are innervated by the same motor neuron. if all motor units were fired simultaneously (the whole muscle), there would be one strong 'twitch' before the muscle relaxed, making movements jerky and twitchy. however, when smooth movement is required, motor units are turned on asynchronously which means that by the time one motor unit is relaxing, another has begun to contract and taken over so the muscle as a whole can contract smoothly without relaxing in between stimuli.
84
describe the main steps in E-C coupling
- An action potential is triggered on the sarcolemma of a muscle cell
- the action potential travels down a T tubule, where voltage controlled receptors change shape, which causes Ca2+ molecules to be released into the sarcoplasm by terminal cisterns
- Ca2+ binds to troponin molecules, which causes tropomyosin to shift and expose the myosin binding sites present on actin
- energised myosin heads can then bind to actin and start the cross bridge cycle
85
describe the stages of the cross-bridge cycle
- energised myosin head binds to actin
- ADP and P are released as myosin 'cocks' moving actin filament closer to the M line
- ATP binds to Myosin and it detaches from actin
- myosin hydrolyses ATP into ADP and P and returns to the 'ready' position
- energised myosin head binds to the next binding site along on actin
86
describe the microscopic anatomy of a muscle
muscle cells are also called muscle fibres. they are striated and multinucleate. they contain organelles called myofibrils which are composed of end to end sarcomeres. sarcomeres are the contractile unit of muscles and consist of thin filaments, thick filaments and elastic fibres.
87
describe the molecular structure of a sarcomere
sarcomere = the space between two Z discs, there is an M line in the centre and it consists of the light I band (doesn't include myosin fibres) and the dark A band (contains myosin). contains different filaments.
thick filaments = myosin, long molecule with bulbous heads
thin filaments = primarily actin, with troponin and tropomyosin
elastic fibres = primarily made of titin
88
describe the histological (cellular) structure/make up of different types of muscle
skeletal = long striated, multinucleate cells containing myofibrils consisting of many sarcomeres end to end. contains many mitochondria.
smooth muscle = cells are spindle shaped, have one central nucleus per cell. they also have no sarcomeres but contain overlapping thick and thin filaments so they can still contract.
cardiac = branching chains of cells with one or two nuclei, they are striated but less regular in shape than skeletal muscle. they have very similar contractile units to skeletal muscle.
89
describe the structure and function of a neuromuscular junction
a neuromuscular junction is a synapse between a motor neuron and a muscle cell. the sarcolemma folds into the sarcoplasm (draw diagram in an exam). ACh is released from the motor neuron, it then diffuses across the wiggly synaptic cleft and binds to specific receptors on the sarcolemma where an end plate potential (graded potential) is created.
90
what factors contribute to ageing effects in skeletal muscle
- natural loss of strength (sarcopenia)
- loss of contractile tissue and non-contractile connective tissue
- reduction in number of muscle fibres
- loss of muscle fibres leads to loss of motor units
91
describe the concept of frequency coding in skeletal muscle
one action potential in a motor neuron causes a muscle to twitch once. if another action potential follows after the muscle has relaxed from the original contraction, the contraction as a result of the second action potential will be of equal force/size/strength. however, if the second action potential fires before the muscle is finished relaxing from the first contraction, it will produce a larger/stronger contraction. this principle continues until the muscle reaches maximal contraction. basically maximal contraction requires many action potentials to arrive at the neuromuscular junction in quick succession.
92
explain the role of spinal reflexes
spinal reflexes allow the body to respond to stimuli unconsciously. this could be to achieve constant unconscious tasks such as maintaining balance or to protect the body from danger such as the withdrawal reflex. in this case, thinking about an appropriate response would take too much time and the body would sustain more damage, although reflex arcs can be overridden by conscious processes such as being ready for a painful stimuli
93
describe the withdrawal/flexor reflex
- noxious stimuli triggers a sensory receptor (lets say on the bottom of the foot)
- signal travels through afferent sensory neuron to the dorsal horn of the spine
- sensory neuron synapses with an interneuron in the dorsal horn
- interneuron synapses with two different alpha motor neurons
- one motor neuron leaves the dorsal horn via the ventral column and stimulates flexors in the leg
- simultaneously another motor neuron inhibits the extensors of the same leg.
happens ipsilaterally (does not cross the spine)
94
describe the crossed extension reflex
this happens at the same time as the withdrawal reflex.
- noxious stimuli triggers a sensory receptor (lets say on the bottom of the foot)
- withdrawal reflex is triggered ipsilaterally
- sensory neuron synapses with interneurons in the dorsal horn which then decussate (Cross the midline of the body)
- motor neurons in the contralateral leg stimulate extensors and inhibit flexors which keeps the leg grounded and the body balanced as the other foot leaves the floor.
95
describe the golgi tendon reflex/inverse stretch reflex/inverse myotatic reflex
- increased contraction within a muscle activates the golgi tendon organ
- the sensory neuron carries this information to the dorsal horn of the spine
- in the dorsal horn the sensory neuron synapses with two interneurons.
- one interneuron inhibits motor neurons to the contracted muscle and causes the contracted muscle to relax
- one interneuron activates motor neurons to the antagonist muscle, causing it to contract and counter the other contraction.
96
describe the muscle spindle reflex/stretch reflex/myotatic reflex
- muscle spindle detects stretch in a muscle
- sensory neuron carries information to the dorsal horn of the spine
- in the dorsal horn, the sensory neuron synapses with a motor neuron which causes the stretched muscle to contract
- the sensory neuron also synapses with an inhibitory interneuron which causes a second motor neuron to inhibit the action of the antagonist muscle, allowing the originally stretched muscle to contract
97
describe the structure and function of muscle triads
these are a T tubule (infolded tube of sarcolemma) flanked by two terminal cisterns which are structures made of sarcoplasmic reticulum. before muscle contraction can occur, an action potential from an efferent motor fibre spreads along the sarcolemma and down the T tubule. this causes voltage controlled receptors to change shape, this deformation of the receptors in the T tubule causes Ca2+ ions to be released into the sarcoplasm by terminal cisterns. this Ca2+ then binds to troponin to move tropomyosin out of the way of myosin binding sites on actin filaments.
98
summarise the sensory receptors responsible for limb proprioception, the information they encode, and the pathways this information takes through the spine to the brain
receptors include = pacinian corpuscles (which encode pressure and vibration in joint capsules) and Ruffini endings (which encode tension and stretch within joints) additionally, muscle spindles detect stretch of muscles and golgi tendon organs detect tension in muscles.
pathways = pacinian corpuscles and ruffini endings travel through the spine via the dorsal column pathway which is held in the dorsal white column of the spine and decussates at the brain stem. it travels to the cortical areas of the brain so is involved in conscious processing.
information from muscle spindles and golgi tendon organs travels by the spinocerebellar pathway which is an ipsilateral pathway that ultimately reaches the cerebellum
99
describe the role of proprioception in the control of normal movement
proprioception is the ability to be aware of the placement and movement of the body in space without being able to see the body itself. it involves information from receptors in the joint capsules (pacinian corpuscles, ruffini endings) which detect position and rate of position change as well as unconscious information from muscle spindles and golgi tendon organs. proprioceptive information reaches both conscious (cortical areas such as somatosensory and motor cortices) and unconscious regions (cerebellum and basal ganglia) of the brain. this allows for motor planning and control, and provides feedback on where the body is and how it is moving.
100
describe the structure and function of otolith organs
otolith organs (utricula macula and saccular macula) detect horizontal acceleration of the head. they are found in little bulbous structures above the cochlear in the ear. they consist of otoliths (calcium carbonate stones) in a gel like substance. otoliths have inertia so when the head moves, the gel lags a second behind. this causes hair cells underneath the gel, which have ciliated surfaces with one kinocilium and many stereocilia, to move, movement of these cilia cause the hair cells to depolarise, sending signals to the vestibular nuclei via vestibular nerve fibres.
101
describe the structure and function of semi-circular canals
the three semi-circular canals and their corresponding ampullares detect rotational acceleration of the head. ampullares consist of a layer of hair cells covered by a large feather like ampullary cupula in a cavity filled with endolymph (inner ear fluid). when the head rotates, endolymph, which has inertia, lags slightly and deforms the ampullary cupula. this then moves the kinocilium and stereocilia on the hair cells underneath and causes them to depolarise, this signal is then sent to the vestibular nuclei via the vestibular nerve fibres attached to the hair cells.
102
list the ways that the basal ganglia influences motor activity
caudate nucleus = integrates motor information
putamen = regulates movement, movement sequencing and learning of repetitive movement
globus pallidus = smoothing out movement and initiating movement
subthalamic nucleus = stimulates rest of basal ganglia to inhibit unwanted movement
substantia nigra = selects appropriate motor commands and inhibits inappropriate motor commands.
103
describe the role of the visual system in facilitating normal movement
the visual system primarily provides data about the external environment which is necessary for movement planning both on a local (reaching for something) and global level (route planning). visual information regarding where the body is also integrates with proprioceptive information. visual information is sent to the cerebellum, where it is used to compare actual and intended movement and maintain smooth engagement with the environment. it is also sent to the vestibular nuclei. from here, proprioceptive, vestibular and visual information is integrated and signals are sent to the oculomotor complex to control eye movement in relation to the rest of the head, as well as to the cervical spine to control head movement.
- visual input is important in the control of movement but other modalities (proprioception and vestibular) can compensate for lack of visual information (blind people can still move)
104
predict the likely functional consequences of impaired proprioception
- impaired balance, difficulty walking or standing
- uncoordinated movement
- clumsiness
- poor postural control and limb control.
105
describe the functional consequences of losing all proprioceptive sensory neurons within the dorsal root ganglia
- no communication with proprioceptive receptors in the body
- no afferent proprioceptive signals
- lack of ability to move the body without seeing its location in space
- poor balance, coordination, postural control. potential lack of ability to walk.
106
describe the consequences of lesions in the basal ganglia including those found in parkisons disease
general damage to the basal ganglia = lack of inhibition of inappropriate motor commands, jerky irregular movement, poor movement sequencing, impaired ability to initiate motor movement
parkinsons disease involves a loss of dopamine from the substantia nigra. this leads to symptoms such as bradykinesia (action selection inhibited), festinating gait (scaling issues and struggling to initiate movement), tremors and rigidity in the body. Parkinsons can be managed with L-Dopa to counteract the loss of dopamine from the basal ganglia.
107
describe the general anatomy of the cerebellum
cerebellum is a feather-like structure underneath the parietal lobe and behind the brain stem
functional divisions of the cerebellum include:
vestibulocerebellum (connections with the vestibular system/vestibular nuclei)
spinocerebellum (connections with proprioceptors from the spinocerebellar tract)
corticocerebellum (connections with the motor cortex)
108
what are some possible effects of cerebellar lesions?
- issues with balance or posture
- ataxia = abnormal uncoordinated movement
- asynergia = difficulty creating smooth movement
- dysmetria = lack of ability to judge distance or scale
- scanning speech = uncoordinated development of speech
- decomposition of movement = component parts of movement rather than smooth movement
109
what are the main outputs for the vestibular nuclei?
- the cerebellum
- the cervical spine to control head movement
- the oculomotor system to control eye movement
- lower extensors to keep the body balanced
110
what are the main targets for proprioceptive information in the CNS?
- somatosensory cortex and primary motor cortex for conscious control of movement
- basal ganglia for scaling and action selection
- cerebellum for refinement of motor movement
- spinal cord for reflex arcs
111
what are the two pathways within the basal ganglia?
direct = excitatory pathways for movement initiation
(cortex --> striatum --> globus pallidus --> thalamus --> motor cortex --> spinal cord)
indirect = inhibitory pathway for for movement termination/inhibition
(cortex --> striatum --> globus pallidus --> subthalamic nucleus --> globus pallidus --> thalamus --> motor cortex --> spinal cord)
112
describe the pyramidal motor tracts
pyramidal motor tracts are efferent, descending motor tracts which carry conscious motor control signals from the brain to lower motor neurons. the corticobulbar tract controls movement of the face and head whereas the corticospinal tract controls limb and trunk movement. the fibres travel through the pyramids in the brain stem (hence the name) and decussate shortly afterwards (although 90% of fibres decussate, 10% remain ipsilateral)
113
describe the extrapyramidal motor tracts
extrapyramidal motor tracts are efferent, descending motor pathways which carry unconscious motor signals. these do not pass through the pyramids within the brain stem (hence the name) and different tracts decussate at different points in the brain stem and spinal cord. extrapyramidal tracts include the rubrospinal tract, tectospinal tract, vestibulospinal tract and reticulospinal tract. each tract controls different processes such as balance or coordination but all are unconscious
114
why are sensory pathways important for normal functioning?
ascending/afferent sensory pathways carry information from sensory receptors to the brain. they can carry either conscious or unconscious information. they are important for movement and proprioception (via the spinocerebellar pathway) which allows the brain to know where the body is in space and respond appropriately. they also provide conscious information about touch, pressure and other sensory stimuli so that the brain can register these and respond appropriately. this can help the body respond to the environment, avoid noxious stimuli etc.
115
describe the route taken by pain signals through the body in a healthy person
nociceptive nerve ending --> afferent A delta (fast) and C fibres (slow) reach the spinal cord. --> C fibres ascend via the indirect spinothalamic tract (--> unconscious information processing via hypothalamus, reticular formation etc) A delta fibres ascend via the direct spinothalamic tract (--> conscious processing via cortical areas)
116
describe a generic sensory pathway (neurons, cell bodies, synapses etc)
first order neuron = one end connects with a sensory receptor, its cell body is in the dorsal root ganglion and its axon extends into the dorsal horn where it synapses with...
second order neuron = interneuron with cell body in the dorsal horn or brain stem, axon extends up the spine where it synapses with...
third order neuron = cell body is found in the thalamus, axon extends into another region of the brain such as somatosensory areas
117
how does the spinocerebellar pathway differ from the dorsal column pathway?
both pathways carry proprioceptive information but..
- spinocerebellar pathway is ipsilateral, dorsal column pathway decussates in the medulla.
- dorsal column pathway carries conscious information as it has a projection into the somatosensory area, whereas the spinocerebellar pathway is unconscious and does not project into the cortical areas
- dorsal column pathway begins to somatotopically organise information from different limbs, spinocerebellar pathway does not do this.
- dorsal column pathway travels up the spine through the dorsal white column whereas spinocerebellar is found on lateral aspects of spinal cord.
118
outline the anatomical details of the spinothalamic tract
- two divisions of this tract (lateral carries info about pain and ventral about touch)
- nociceptive receptor sends signals through an afferent sensory neuron with cell body in dorsal root ganglion, axon enters the dorsal horn.
- interneuron with cell body in dorsal horn extends up the spine, here the tract decussates/crosses the midline
- third order neuron with cell body in the thalamus then projects to the cerebellum (indirect) or the somatosensory cortex (direct)
119
outline the anatomical details of the spinocerebellar tract
this tract is an ascending sensory tract which carries unconscious proprioceptive information. it has only two neurons rather than three like most sensory tracts.
- first order neuron with cell body in dorsal root ganglion enters the dorsal horn
- second order neuron with cell body in spine extends to the cerebellum.
The tract is ipsilateral (does not decussate) and travels up the spine on the lateral aspect of the dorsal horn. information on the right of the body travels up the right of the spine (for example)
120
describe a generic motor pathway (neurons, cell bodies, synapses)
upper motor neuron = cell body in the motor cortex, axon extends down the spine
lower motor neuron = cell body in ventral grey matter, axon leaves through ventral nerve root
121
describe the structure and function of the corticospinal tract
corticospinal tract (direct pyramidal pathway) which controls conscious motor output.
- fibres originate from motor cortex
- fibres pass through the pyramids within the brain stem
- 90% of fibres decussate after pyramids, 10% remain ipsilateral
the 90% that decussate control limbs and trunk (corticospinal) and 10% that don't control neck and shoulder movement (corticobulbar)
- lower motor neurons run from spine to control musculoskeletal movement.
122
what is the structure and role of the rubrospinal tract?
information = unconscious fine motor control/coordination of upper limb and modulates reflexes
origin = red nucleus in midbrain of brain stem
pyramidal = nope
decussation = almost immediately after origin in red nucleus
123
what is the structure and role of the tectospinal tract?
information = neck muscles, head eye coordination and visual/auditory feedback
origin = midbrain of brain stem
pyramidal = nope
decussation = occurs in the midbrain also
124
what is the structure and role of the vestibulospinal tract?
information = modulating extensors and controlling balance in the lower limb
origin = vestibular nuclei, pons, brain stem
pyramidal = nope
decussation = N/A doesn't decussate
125
what is the structure and role of the reticulospinal tract?
information = autonomic functions, pain modulation
origin = reticular formation.
pyramidal = nope
decussation = consists of one ipsilateral and one contralateral tract. contralateral tract decussates at brainstem level.
126
where are the paravertebral and prevertebral trunks of the autonomic nervous system located?
paravertebral = parallel to the spine on either side, laterally
prevertebral = in front of the aorta anterior to the aorta and spine
127
what area of the brain stem is primarily responsible for regulating heart rate?
the reticular formation
128
what are the 4 nuclei in the reticular formation that control heart rate and what do they do?
solitary nucleus = receives input from baroreceptors and sends output to nucleus ambiguous and depressor area
nucleus ambiguous = sends out parasympathetic signal/fibre to slow/maintain steady heart rate
depressor area = sends signals to pressor area to depress action of the sympathetic nervous system
pressor area = sends sympathetic fibres out to the sympathetic trunk and lowers activity in sympathetic fibres. these fibres connect to heart and blood vessels
129
what area of the brain stem is primarily responsible for regulating respiratory rate
the pons
130
what are the three nuclei in the pons that control respiration rate and what do they do?
ventral respiratory group = generates a pattern of inspiration and expiration
dorsal respiratory group = receives input from solitary nucleus and other sources and regulates the activity of the ventral respiratory group i.e. speeding it up or slowing it down
pontine nucleus = regulates and smooths action of both respiratory groups, allows for smooth breathing and regulation of breathing whilst talking etc.
131
explain the higher brain areas that regulate the autonomic nervous system
cerebral cortex (cognitive aspects of stress/relaxation, can be consciously controlled to some extent) --> limbic system (emotional responses/aspect) --> hypothalamus (main integration and command centre for autonomic output) --> brain stem (reticular formation and pons which send the actual fibres out) --> spine --> effectors
132
describe the difference in anatomy between the sympathetic and parasympathetic nervous systems
sympathetic = fibres pass through and synapse in sympathetic trunk ganglions in the sympathetic trunk so they have short pre-ganglionic axons and long post-ganglionic axons. they release norepinephrine as a NT
parasympathetic = long pre-ganglionic axons extend to ganglions just before the target organs and short post-ganglionic axons release ACh as a NT.
133
describe the path of sympathetic fibres to the effector organs they target (blood vessels and glands etc)
spinal cord --> out via ventral root --> white ramus --> paravertebral sympathetic trunk ganglion --> grey ramus --> spinal nerve --> effector
134
describe the path of sympathetic fibres to the effector organs they target (kidney)
spinal cord -->out via ventral root --> white ramus --> paravertebral sympathetic trunk ganglion --> splanchic trunk --> celiac ganglion --> kidney/adrenal medulla
