Physiology Flashcards
What is the definition of osmosis?
The diffusion of solvent molecules into a region in which there is a higher concentration of solute to which the membrane is permeable
What is the definition of osmotic pressure?
The excess pressure required to maintain an osmotic equilibrium between a solution and the pure solvent seperated only to the solvent
What does the Van’t Hoff equation describe?
Osmotic Pressure
P = (nRT) / V
P - osmotic pressure
n - number of particles into which the substance dissociates
R - universal gas content, which is 0.082
T - absolute temperature
V - volume
In terms of proportionality, what does the Van’t Hoff equation mean?
Osmotic pressure is directly proportional to it’s absolute temperature, and at a constant temperature, it is directly proportional to the solute concentration
What is osmolarity?
The number of osmoles of solute per litre of solution.
What affects the osmolarity?
It depends on the volume of the solution, and therefore on the temperature and pressure of the solution
What is osmolality?
The number of osmoles of solute per kilogram of solvent
What affects osmolality?
Osmolality depends on the mass of the solvent which is independent of temperature and pressure
What is an osmole?
The amount of substance which must be dissolved in order to produce Avogadro’s number of particles (6.0221 x 10^23)
What is tonicity?
The osmotic pressure between two compartments, and is related to the difference in the concentration of ‘effective’ osmoles between them
What are effective osmoles?
Those substances which are unable to penetrate the membrane between compartments and therefore they are effective in their contribution to osmotic pressure
What are ineffective osmoles?
Substances which are able to equilibrate between compartments, and that are therefore unable to contribute to the osmotic pressure gradient
What is the reflective coefficient?
A measure of how permeable a membrane is to a given solute, where it equals 0 for a perfectly permeable membrane and 1 for a membrane which is perfectively selective
What is an isotonic solution?
Solution separated by a membrane that have equal osmolality on either side so there is no osmotic pressure and they are therefore isotonic
Describe how the movement of fluid between capillaries and tissues is governed by the balance of the hydrostatic pressure and the orthostatic pressure
- If the capillary hydrostatic pressure and blood oncotic pressure are equal, no net fluid movement occurs
- When capillary hydrostatic pressure is higher than oncotic pressure, blood is ultrafiltered out of the capillary and into the tissues
- When oncotic pressure is higher than intravascular hydrostatic pressure, tissue oedema fluid should be attracted back into the circulation
What is the Starling principle?
Hydrostatic pressure is higher than oncotic pressure in the post-arteriolar capillary segments, but as the pressure in the capillary decreases along its length, oncotic pressure ‘wins’ and attracts some of the ultrafiltered water back into the capillaries
On a basic general level, how are body water compartments measured?
Using indicator diluting techniques
Following equilibrium of the indicator into the compartment of interest, the blood level of the indicator can be measured
The volume of distribution of the indicator can then be calculated:
Volume of the compartment = dose of marker / concentration of marker
What are the features that make an ideal indictator to measure body water compartments?
- Safe
- Not metabolised or rapidly excreted
- confined to the compartment of interest
- not prone to changing the distribution of fluids within the compartment
What indicators can be used to measure
1. Total body water
2. Extracellular fluid
3. Plasma volume
4. Blood volume
- TBW - radioactive tritium
- ECF - bromine-82 or mannitol
- Plasma - albumin tagged with evans blue
- Blood - 53Cr labelled red cells
What is the volume of total body water and percentage of this of total body mass?
42L (60% of total body mass in men, 50% in women)
How does the total body water change in obesity?
The total body water is larger but the proportion of total body mass in less as adipose tissue is only 10-20% water
What is the volume of intracellular fluid and precentage of total body mass?
23.1L (33% total body mass)
This volume is regulated by the movement of free water
What is the volume of extracellular fluid and percentage of total body mass?
18.9L (27% total body mass)
This volume is regulated by the movement of sodium
What makes up extracellular fluid?
- plasma volume (2.8L)
- interstitial and lymph fluid
- dense connective tissue and bones
- adipose tissue
Intravascular Fluid
1. % of total body mass
2. % of total fluid
3. volume
Intravascular Fluid
* 4.5% total body mass
* 7.5% total fluid
* 3.15L
Blood Volume
1. % of body mass
2. % of total fluid
3. volume
Blood Volume
* 7% of total body mass
* 12% of total fluid
* 5L
Interstitial Fluid
1. % of body mass
2. % of total fluid
3. volume
Interstitial Fluid
* 12% of total body mass
* 20% of total fluid
* 8.4L
What is the volume of transcellular fluid and percentage of total body mass?
1050ml (1.5% total body mass)
Fluid formed by the secretory activity of cells
What makes up transcellular fluid?
- synovial fluid
- CSF
- aqueous humour
- bile
- bowel contents
- peritoneal fluid
- pleural fluid
- urine in the bladder
What is Fick’s Law of Diffusion?
The rate of diffusion is proportional to concentration and surface area
How come water can diffuse across the lipid bilayer despite it being very hydrophobic?
- The surface area of all the cells that interfere with the extracellular fluid is huge
- The concentration of water molecules is very high
- The lipid bilayer in very thin
Why does the thinness of the lipid bilayer affect diffusion?
Because diffusion rate in inversely proportional to the thickness of the membrane
What affects the water permeability of cell membranes?
The presence of embedded proteins and lipids which change the membrane properties (aquaporins)
What is the main mechanism that determines the balance of volume between the intracellular and extracellular compartments?
The equilibrium of osmolality of the compartments, therefore the most important osmotic agent is extracellular sodium, which is under tight regulation
Why is intracellular water important?
- it acts as a solvent
- its presence is essential for enzyme function
- it acts as a reagant itself
How is the volume of intracellular water determined?
- The first Gibbs-Donnan effect (passive), which is established by the equilibration of diffusable and non-diffusable solvents on either side of the cell membrane
- The second Gibbs-Donnan effect (active), which is maintained by the actions of the Na+/K+ATPase
What does the Gibbs-Donnan effect describe?
The unequal distribution of permeant charged ions of either side of a semi-permeable membrane, which occurs in the presence of impermeant charged ions
Equilibrium - both sides of the membrane will have equal charged ions
What is the concentration of total body sodium and how is it distributed?
60mmol/Kg
70kg man - 4200mmol
ECF - 50% total sodium
ICF - 5% total sodium
How does sodium move between the intravascular and interstitial fluid?
Due to the Gibbs-Donnan effect
How is sodium concentration inside the cell kept artificially low?
By the action of the Na+/K+ATPase, which exchanged 3 sodium atoms for every two potassium
What is the concentration of total body potassium and how is it distributed?
40mmol/Kg
70kg man - 2800mmol
ICF - 90%
ECF - 2%
Bone - 8%
How does potassium move between intravascular, interstital and intercellular fluid?
- It moves freely between intravascular and interstitial fluid due to low concentrations
- Na+/K+ATPase exchanges three sodium ions out of the cell and two potassium ions into the cell
What is the concentration of total body calcium and how is it distributed?
360mmol/kg
70kg man - 25mol
>99% is stored in bone
ECF - 30mmol
Intracellular calcium is minimal but it is an important secondary messenger
How does calcium move between intravascular, interstital and intercellular fluid?
- it moves freely between interstital and intravascular fluid
- it is actively transported by ATP-powered pumps, which is important because it is a second messenger
What is the concentration of total body magnesium and how is it distributed?
15mmol/Kg
70kg male - 1050mmol
60% is in bone
39% is intracellular
1% is ECF
How does magnesium move between intravascular, interstital and intercellular fluid?
- magnesium moves freely between ECF
- magnesium enters cells freely
- intracellular magnesium is bound to ATP, cell wall lipids and many various enzymes
What is the resting membrane potential?
The voltage (charge) difference between the extracellular and intracellular fluid when the cell is at rest
What are the mechanisms responsible for the resting membrane potential?
- chemical gradients created by ion transport pumps eg potassium, sodium, calcium
- selective membrane permeability - volatage-gated ion pumps
- electrical gradients - generated because potassium leak (via K2P channels) from the intracellular fluid creates a negative intracellular charge, attracting potassium back into cells (opposite to chemical gradient)
- electrochemical equilibrium develops when chemical and electrical gradients are equal (Nernst equation)
What is the Nernst potential for each ion?
The transmembrane potential difference generated when that ion is at electrochemical equilibrium
What value is the normal resting potential?
The net charge of the intracellular side of the cell is -70 - -90mV
What is the Nernst equation?
If you account the below as constants you will get:
Vk = -60mV log10 x (Kin - Kout)
What is the Nernst potential for:
K+
Cl-
Na+
Ca2+
K+ -94mV
Cl- -80mV
Na+ +60mV
Ca2+ +130mV
What is the Goldman-Hodgkin-Katz equation?
Most things are pretty constant so it basically equals out as the Nernst equation (just potassium)
What is the threshold potential?
The transmembrane potential required to produce depolarisation of the membrane =
-55mV
What is the all-or-nothing effect?
The finding that a subthreshold stimulus will produce no response, whereas a suprathreshold stimuli will produce an identical and maximal response.
What cell process occurs during depolarisation?
Depolarisation occurs as the result of voltage-gated sodium channels opening when the threshold potential is reached
- The result is an influx of sodium ions into the cell
- This rapidly depolarises the membrane (.5-1.0msec)
What cell process occurs during repolarisation?
Repolarisation occurs due to potassium channel opening and sodium channels closing
* Sodium channels enter a refractory period and cannot be activated again
* Potassium channels permit an outward potassium current, repolarising the cell
How does propagation of the action potential along a neuron occur?
Because the current generated locally by depolarization changes the transmembrane potential in adjacent areas of membrane, also depolarizing it
What are the factors which affect neuronal conduction?
- Myelination - myelinated fibres conduct faster
- Thickness of the fibre - thicker fibres conduct faster
- Properties of the membrane - the lower the capacitance and resistance the faster the conduction
- Properties of the extra-axonal environment e.g. electrolyte derangement (hyponatraemia, hypermagneseamia, acidosis and hypothermia all decrease the velocity of nerve conduction
What is ‘undershoot’ or afterhyperpolarisation?
Why does it happen?
It describes the post-spike negative dip in transmembrane poerital, which transiently falls below the normal resting membrane potential.
It happens because of persistent calcium-activated potassium channel activity, which are opened by the intracellular influx of calcium during the action potential
What is an axons capacitance?
The ability of the membrane to store charge; the greater the capacitance the more charge needs to be displaced by the local circuit and therefore the greater the current required in that local circuit.
In short, for faster conduction, you want a low-capacitance membrane that carries barely any charge
What is axial resistance?
The resistance to ion flow along the axon, measured between two flat cut ends of the axon.
Ion flow requires substrate to flow through, and therefore more axoplasm usually means better conduction
What is saltatory conduction?
- Most of an axon is covered in myelin sheath, not much action potential propagation happens over the myelinated length
- The sodium channels are concentrated at the unmyelinated regions between myelin segments (nodes of Ranvier)
- The action potential can propagate from one node to another
What is synaptic neurotransmission?
The phenomenon where the action potential of one neuron, through an intermediate signal molecule, facilitates a change in the state of another neuron, to which it is connected by a synapse.
What is a synapse?
A narrow (20-30nm) junction between two neurons
What are neurotransmitters and what are some of their shared properties?
They are molecules used for synaptic signalling. Some shared properties are:
* released from a presynaptic terminal in response to calcium-dependent depolarisation
* received by specific receptors on the postsynaptic neuron
* subsequently reabsorbed into the presynaptic neuron or glia, or metabolised into an inactive form by enzymes to terminate the stimulation
* a single neurotransmitter tends to be dominant in any given neuron (Dale’s principle), although this is not always true
What are some excitatory neurotransmitters?
Glutamate
Dopamine
Noradrenaline
Acetylcholine (nicotinic receptors)
What are some inhibitory neurotransmitters?
GABA
Serotonin
Acetylcholine (muscarinic receptors)
Describe synaptic neurotransmission on a basic level
- A nerve impulse is conducted to the presynaptic endplate of the neuron
- At the endplate, the neurotransmitter substance is stored in vesicles
- The arrival of an action potential and the depolarisation of the presynaptic membrane causes the release of the neurotransmitters into the synaptic cleft
- The release is generally mediated by intracellular calcium entry acting as a secondary messenger
- The released neurotransmitters cross the cleft and bind to their receptors
- The either alters the threshold potential or directly produces depolarisation
What are the proteins that calcium targets in synaptic neurotransmission? what are the responsible for?
They are broadly referred to as the SNARE family
* synaptotagmin
* synaptobrevin
* syntaxin
They are responsible for mediating the fusion of vesicles with the presynaptic membrane, and the exocytosis of vesicle contents
What are the two main things neurotransmitters do in the synapse?
- Bind to the post-synaptic receptors, producing some change in the other neuron
- Bind to the pre-synaptic receptors on the same neuron which had just released it, and therefore exerting some soft of feedback effect
How is the neurotransmitter cleared from the synaptic cleft?
Usually, by the action of various reuptake pumps or more rarely by the activity of a high-affinity enzyme that destroys the neuotransmitted molecule, like acetylcholinesterase
What is the mechanism of contraction of skeletal vs smooth vs cardiac muscle?
Skeletal and cardiac muscle
calcium-induced conformational change of tropomyosin and troponin, leading to exposure of actin sites
Smooth muscle
calcium induces calmodulin to activate MLCK, which phosphorylates myosin light chains
What is the mechanism of relaxation of skeletal vs smooth vs cardiac muscle?
Skeletal and cardiac muscle
calcium dissociation away from tropomyosin and troponin
Smooth muscle
dephosphorylation of myosin light chains by myosin light chain phosphatase
What is the role of calmodulin in skeletal vs smooth vs cardiac muscle?
Skeletal muscle
minor
Smooth muscle
central
Cardiac muscle
regulatory
What is a sarcoplasmic reticulum?
A specially organised organelle that mainly plays the role in coordinating calcium traffic
What is a motor unit of muscle?
It consists of a large anterior horn cell, its motor axon, and the skeletal muscle fibres innervated by that axon
How does smooth muscle contract?
- Intracellular calcium binds to calmodulin (there is no troponin)
- Calmodulin activates myosin light chain kinase
- Myosin light chain kinase phosphrylates the head of myosin
- Only phosphorylated myosin heads can participate in cross-bridge cycling
- Contraction then occurs via actin-myosin bridge formation
How does smooth muscle relax?
- When calcium concentration decreases, myosin light chain phosphatase dephosphorylates the myosin light chain kinase and puts an end to the contraction
- Myosin light chain phosphatase is activated by cGMP-dependent protein kinase, and is therefore responsive to nitric oxide
What does the reflex arc consist of?
A sense organ, an afferent neuron, one of more synapses of a central integrating system, an efferent neuron and an effector
Where do the afferent and efferent fibres travel through the spinal cord?
The afferent neurons enter via the dorsal roots or cranial nerves and have their cell bodies in the dorsal root ganglia or in the homologous ganglia of the cranial nerves.
The efferent fibres leave via the ventral route or corresponding motor cranial nerves.
What are the types of potentials created in the reflex arc.
- The sense organ generates a receptor potential whose magnitude is proportional to the strength of the stimulus
- The afferent nerve generates an all or nothing action potential, the number being proportional to the receptor potential
- In the CNS, the responses are graded in terms of excitatory post-synpaptic potentials (EPSPs) and inhibitory post-synaptic potentials (IPSPs) at synaptic juntions
- The efferent nerve is all or nothing potential
What is an adequate stimulus?
The stimulus that triggers a reflex. It is often very precise
What type of neurons are the efferent nerves in the reflex arc?
alpha motor neurons
What is the final common pathway?
All neural influences affecting muscular contraction ultimately funnel through the alpha motor neurons to the muscles, and they are therefore called the final common pathway.
What are monosynaptic and polysynaptic reflexes?
The simplest reflex arc is one with a single synapse between the afferent and efferent neurons, these are called monosynaptic reflexes.
Reflex arcs in which there interneurons are interposed between the afferent and efferent neurons are called polysynaptic reflexes
What is the stretch or myotactic reflex?
When a skeletal muscle with an intact nerve supply is stretched, it contracts. This response is called the stretch reflex.
What is the following in the stretch reflex:
* stimulus
* response
* sense organ
* neurotransmitter
* give an example of the stretch reflex
- Stimulus - stretch of the muscle
- Response - contraction of the muscle
- Sense organ - a small encapsulated spinkle-like structure called the muscle spindle
- Neurotransmitter - glutamate
- Example - knee jerk reflex
What are the three essential parts of a muscle spindle?
- A group of specialised intrafusal muscle fibres with contractile polar ends and a non-contractile centre
- Large diameter myelinated afferent nerves originating in the central portion of the intrafusal fibres
- Small diameter myelinated efferent nerves supplying the polar contractile regions of the intrafusal fibres
How are muscle spindles linked with proprioception?
Changes in muscle length are associated with changes in joint angle; thus muscle spindles provide information on position - proprioception
Where will you find muscle spindles?
The intrafusal muscles fibres are found parallel to the extrafusal muscle fibres (the regular contractile units of the muscle) with the ends of the spindle capsule attached to the tendons at each end of the muscle
What are the two types of intrafusal muscle fibres? Tell me a little bit about them
- Nuclear bag fibre contains many nuclei in a dilated central area. There are two types dynamic and static
- Nuclear chain fibre is thinner and shorter and lacks a definite bag.
Typically a muscle spindle has 2-3 bag fibres and 5 chain fibres
What are the two kinds of sensory endings in each spindle? What do they measure?
- A single primary (Ia) ending, which is very sensitive to the velocity of the change in muscle length during a stretch (dynamic response)
- Up to 8 secondary (II) endings, which provide information on the steady state length of the muscle (static response)
What nerves supply muscle spindles?
Gamma - motor neurons
How do the afferent nerves of the muscle spindles connect to the muscle they move?
Ia fibres end directly on motor neurons supplying the extrafusal fibres of the same muscle
In reflexes, what is the reaction time and the central delay? Give values for both
Reaction time is the time between the application of the stimulus and the response. Knee jerk - 19-24ms
Central delay is the time taken for the reflex activity to traverse the spinal cord. Knee jerk is 0.6-0.9ms
What scenario takes place to stop the muscle spindles from firing?
They stop firing when the muscle is made to contract by electrical stimulation of the alpha motor neurons to the extrafusal fibres because the muscle shortens when the spindle is unloaded.
What is the difference between alpha motor neuron and gamma motor neuron stimulation?
Stimulation of the gamma motor neuron does not lead directly to detectable contraction of the muscles because the intrafusal fibers are not strong enough. However, it does stretch the nucleur bag portion of the spindles, deforming the endings and initiating impulses to the Ia fibres. This can in turn lead to reflex contraction of the muscle.
How are the gamma motor neurons regulated?
From descending tracts from a number of areas of the brain that also control alpha motor neurons
What is reciprocal innervation?
When a stretch reflex occurs, the muscles that antagonise the muscle involved relax. This is called reciprocal innervation
What is the receptor for the inverse stretch reflex?
How does it work?
The Golgi tendon organ.
The fibres from the Golgi tendon organ make up the Ib group of myelinated, rapidly conducting sensory nerve fibers. Stimulation of these leads to production of IPSPs on the motor neurons from which the fibres arise. The Ib fibres end on the spinal cord on inhibitory interneurons that in turn directly terminate on the motor neurons. They also make excitatory connection with the antagonist muscle motor neurons.
What is the sensory pathway of vision?
- The axons of the ganglion cells pass caudally in the optic nerve and optic tract to end in the lateral geniculate body in the thalamus.
- The fibers from each nasal hemiretina decussate in the optic chiasm.
- In the geniculate body, the fibres from the nasal half of one retina and the temporal half of the other synapse on the cells who axons form the geniculocalcarine tract. This tract passes to the occipital lobe of the cerebral cortex.
What is the pathway that mediates the pupillary light reflex and eye movements?
Some ganglion cell axons bypass the lateral geniculate to project directly to the pretactal area.
How does the retina transmit information to the lateral geniculate body? How does this link with the structure of the lateral geniculate body?
The axons of retinal ganglion cells project a detailed spatial representation of the retina on the lateral geniculate body.
Each geniculate body has six well-defined layers (layers 1,4,6 from contralateral eye, 2,3,5 from ipsilateral eye). In each layer there is a point for point representation of the retina.
What are the two pathways from the lateral geniculate pathway to the primary visual cortex? Which P cells and M cells travel in each pathway?
- The M ganglion cells project to the magnocellular portion of the lateral geniculate, whereas the P ganglion cells project to the parvocellular portion.
- The magnocellular pathway, from layers 1 and 2, carries signals for detection of movement, depth and flicker.
- The parvocellular pathway, from layers 3-6. carries signals for colour vision, texture, shape and fine detail
What are the following lesions called and where is the lesion?
- A - A lesion that interrupts one optic nerve causes blindness in that eye
- B - Heteronomous (opposite sides of the visual fields) hemianopia - a lesion in the optic chiasm
- C - Homonomous (same side of the visual fields) hemianopia - a lesion in one optic tract
- D - Occipital lesions may spare the fibers from the macula because of seperation in the brain of these fibres from the other subserving vision
Label where these areas of the occipital region get their sensory nerves from
What does the reticular formation include?
The cell bodies and fibres of many of the serotonergic, noradrenergic, and cholinergic system.
It also contains many of the areas concerned with regulation of heart rate, blood pressure, and respiration.
It plays an important role in determining the level of arousal so is called the ascending reticular activation system
What is the reticular activating system?
A complex polysynaptic pathway arising from the brainstem reticular formation and hypothalamus with projections to the intralaminar and reticular nuclei of the thalamus which, in turn, project diffusely and non-specifically to wide regions of the cortex.
Collaterals funnel into it from the long ascending sensory tracts and the trigeminal, auditory, visual and olfactory systems
What are some important connections to and from the hypothalamus?
TO
* Norepinephrine-secreting neurons with their cell bodies in the hindbrain end in different parts of the hypothalamus
* Paraventricular neurons that secrete oxytocin and vasopressin project in turn to the hindbrain and the spinal cord
* Epinephrine-secreting neurons have their cell bodies in the hindbrain and end in the ventral hypothalamus
* Serotonin-secreting neurons project to the hypothalamus from the raphe nuclei
FROM
* An intrahypothalamic system composed of dompine-secreting neurons have their cell bodies in the arcuate nucleus and end on or near the capillaries in the median eminence.
For temperature regulation, where are the
1) afferents from
2) integrating areas
1) Afferents from temperature receptors in the skin, deep tissues, spinal cord, hypothalamus and other parts of the brain
2) Integrating areas include: Anterior hypothalamus responds to heat. Posterior hypothalamus responds to cold
For catecholamine regulation, where are the
1) afferents from
2) integrating areas
1) Afferents from limbic areas concerned with emotion
2) Integrating areas are dorsal and posterior hypothalamus
For vasopressin regulation, where are the
1) afferents from
2) integrating areas
1) Afferents from osmoreceptors and ‘volume receptors’
2) Integrating areas are supraoptic and paraventricular nuclei
For oxytocin regulation, where are the
1) afferents from
2) integrating areas
1) Afferents from touch receptors in breast, uterus, genitalia
2) Integrating areas are supraoptic and paraventricular nuclei
For TSH regulation, where are the
1) afferents from
2) integrating areas
1) Afferents from temperature receptors in infants and others
2) Integrating areas include paraventricular nuclei and other neighbouring areas
For ACTH regulation, where are the
1) afferents from
2) integrating areas
1) Afferents are from limbic system (emotional stimuli); reticular formation (systemic stimuli); hypothalamic and anterior pituitary cells sensitive to circulating blood cortisol levels; suprachiasmatic nuclei (diurnal rhythm)
2) Integrating areas are paraventricular nuclei
For FSH and LH regulation, where are the
1) afferents from
2) integrating areas
1) Afferents are from hypothalamic cells sensitive to oestrogens, eyes, touch receptors in skin and genitalia of reflex ovulating species
2) Integrating areas are preoptic area and others
For prolactin regulation, where are the
1) afferents from
2) integrating areas
1) Afferents from touch receptors in breasts
2) Integrating areas include arcuate nucleus
For thirst regulation, where are the
1) afferents from
2) integrating areas
1) Afferents are from osmoreceptors and angiotensin II uptake
2) Integrating areas include lateral superior hypothalamus and subfornical organ
For sexual behaviour regulation, where are the
1) afferents from
2) integrating areas
1) Afferents from cells sensitive to circulating oestrogen and androgen
2) Integrating areas from anterior ventral hypothalamus plus in the male, piriform cortex
For defense reactions regulation, where are the
1) afferents from
2) integrating areas
1) Afferents from sense organs and neocortex
2) Integrating areas are diffuse, in limbic system and hypothalamus
What are the ascending spinal tracts?
The neural pathways by which sensory information from the peripheral nerves is transmitted to the cerebral cortex.
There are three types of neuron in the dorsal column-medial lemniscal pathway. What are they?
- First order neurons - carry sensory information regarding touch, vibration and proprioception from the peripheral nerves to the medulla oblongata
- Second order neurons begin in the cuneate nucleus or gracilis - they decussate in the medulla oblongata and travel in the contralateral medial lemniscus to reach the thalamus
- Third order neurons transmit the signals from the thalamus to the ipsilateral primary sensory cortex
There are two types of first order neurons in the DCML pathway, what are they?
- Signals from the upper limb (T6 and above) - travel in the fasciculus cuneatus (lateral part of the dorsal column) - they then synapse in the nucleus cuneatus
- Signals from the lower limb (T6 and below) - travel in the fascilulus gracilis (medial part of the dorsal column) - they then synapse in the nucleus gracilis
What are the three neurons that make up the anterolateral spinothalamic tract and what are their paths?
- First order neurons arise from sensory receptors in the periphery, enter the spinal cord, ascend 1-2 vertebral levels, and synapse at the tip of the dorsal horn (the substantia gelatinosa)
- Second order neurons then decussate within the spinal cord and split to travel to the thalamus in two different pathways - the anterior and lateral spinothalamic tracts
- Third order neurons carry the signals from the ventral posterolateral nucleus in the thalamus to the ipsilateral primary sensory cortex of the brain
What are the spinocerebellar tracts?
The tracts that carry unconscious proprioceptive.
What is Brown-Sequard syndrome and what are the symptoms?
A hemisection of the spinal cord
DSML pathway - loss of ipsilateral proprioception and find touch
Anterolateral system - contralateral loss of pain and temperature sensation
It will also involve the motor tracts, causing a ipsilateral hemiparesis
What are upper vs lower motor neurons?
There are no synapses within the descending pathways. At the termination of the descending tracts, the neurons synapse with a lower motor neurone. Thus, all the neurons within the descending tract are called as upper motor neurons. Their cell bodies are found within the cerebral cortex of the brain stem, with their axons remaining in the CNS
Tell me about the journey of the corticospinal tract before it reaches the medulla?
It begins in the cerebral cortex, receiving input from the primary motor cortex, the premotor cortex and the supplementary motor area.
After originating from the cortex, the neurons converge, and descend through the internal capsule, the crus cerebri of the midbrain, the pons and into the medulla
Once the corticospinal tract reaches the medulla, it splits into two branches. What are these and what do they do?
- The lateral corticospinal tract decussates in the medulla, then descends into the spinal cord, terminating at the ventral horn. From the ventral horn, the lower motor neurons go on to supply the muscles of the body
- The medial corticospinal tract remains ipsilateral, descending into the spinal cord. They then decussate and terminate in the ventral horn of the cervical and upper thoracic segmental levels
What is the path of the corticobulbar tract?
The corticobulbar tracts arise from the lateral aspect of the primary motor cortex. They receive the same inputs as the corticospinal tracts. The fibres converge and pass through the internal capsule to the brainstem.
The neurons terminate on the motor nuclei of the cranial nerves. Here, they synapse with lower motor neurons, which carry the signals to the muscles of the face and neck.
Do the corticobulbar tracts innervate the motor neurons ispilaterally, contralaterally or bilaterally?
Bilaterally
Except for upper motor neurons for the facial nerve (CN VII) have contralateral innervation below the eyes and the upper motor neurons for the hypoglossal nerve (CN XII) only provide contralateral innervation
Label the tracts of the spinal cord
Where is the SA and the AV node?
- The SA node is at the junction of the superior vena cava with the right atria
- The AV node is located in the right posterior portion of the interatrial septum.
How many bundles of atrial fibres that contain Purkinje-type fibres and connect the SA and AV node are there? What are they called?
There are three:
* Anterior
* Middle (tract of Wenckebach)
* Posterior (tract of Thorel)
The AV node connects to the Bundle of His. What are the branches of the Bundle of His, where do they come off and where do they go?
- The Bundle of His gives off a left bundle branch at the top of the interventricular septum, and continues as the right bundle branch.
- The left bundle branch divides into an anterior fascicle and a posterior fascicle.
- The branches and fascicles run subendocardially down either side of the septum and come into contact with the Purkinje system, whose fibres spread to all parts of the ventricular myocardium.
What are the stages of the cardiac cycle in terms of repolarisation and ion channels? What happens in each one
- Phase 0 - the transmembrane action potential of single cardiac muscle cells is characterised by rapid depolarisation - rapid influx sodium through open sodium channels
- Phase 1 - an initial rapid repolarisation - inactivation of sodium channels
- Phase 2 - a plateau phase - slow influx of calcium through slower opening calcium channels
- Phase 3 - a slow repolarisation phase - slow potassium efflux
- Phase 4 - return to the resting membrane potential
What is the conduction rate in the following areas of the heart?
* SA node
* atrial pathways
* AV node
* Bundle of His
* Purkinje system
* Ventricular muscle
What is the pre-potential or pacemaker potential of cardiac rhythmically discharging cells?
Rhythmically discharging cells have a membrane potential that after each impulse, declines to the firing level. Thus, this pre-potential triggers the next impulse.
think ion changes and channels
What brings about the pacemaker potentials in rhythmically discharging cells in the heart?
- At the peak of each impulse, Ik begins and brings about repolarisation.
- Ik then declines, and a channel permeable to both sodium and potassium is activated. Because this channel is activated following hyperpolarisation, it is referred to as an** ‘h’ channel.**
- As Ih increases, the membrane begins to depolarise, forming the first part of the pre-potential.
- Calcium channels then open - the action potentials in the SA and AV node are largely due to calcium, with no contribution of sodium influx.
How is the action potential graph of rhythmically discharging cells different from the other parts of the conducting system? and why?
There is no sharp, rapid, depolarising spike before the plataeu, as there is in other parts of the conducting system and in the atrial and ventricular fibres.
In addition, pre-potentials are normally prominent only in the SA or AV nodes, unless the muscle fibres are abnormal or damaged.
What happens to the SA and AV node when the cholinergic vagal fibres to nodal tissues are stimulated?
- The membrane becomes hyperpolarised and the slope of the prepotentials is decreased because the acetylcholine released at the nerve endings increases the K+ conductance of the nodal tissues.
- This action is mediated by M2 muscarinic receptors, which, via the βγ subunit of a G protein, open a special set of K+ channels. The resulting IKAch slows the depolarising effect if Ih.
- In addition, activation of the M2 receptors decreases cAMP in the cells, and this slows the opening of Ca2+ channels.
- The result is a decrease in firing rate.
What happens to the SA and AV node when the sympathetic cardiac nerves are stimulated?
- It speeds the depolarising effect of Ih, and the rate of spontaneous dicharge increases.
- Noradrenaline secreted by the sympathetic endings binds to the β1 receptors and the resulting increase in intracellular cAMP facilitates the opening of the L channels, increasing ICa and the rapidity of the depolarisation phase of the impulse
What is the spread of excitation through the heart?
- Depolarisation initiated in the SA node spreads radially through the atria, then converges on the AV node.
- From the top of the septum, the wave of depolarisation spreads rapidly in the conducting Purkinje fibres to all parts of the ventricles.
- Depolarisation of the the ventricular muscle starts at the left side of the interventricular septum and moves to the right across the mid-portion of the septum
- It then spreads down the septum to the apex of the heart and returns along the ventricular walls to the AV groove, proceeding from the endocardial to epicardial surface
- The last parts of the heart to be depolarised are the posterobasal portion of the left ventricle, the pulmonary conus, and the uppermost part of the septum.
What is the Einthoven triangle?
In a volume conductor, the sum of the potentials at the points of an equilateral triangle with a current source in the centre is zero at all times.
A triangle (Einthoven’s), with the heart at the centre can be approximated by placing electrodes on both arms and the left leg. **These are the three standard leads of an ECG. **
What action creates the following waves in an ECG?
* P wave
* QRS complex
* T wave
* U wave
- P wave - atrial depolarisation
- QRS complex - ventricular depolarisation
- T wave - ventricular repolarisation
- U wave - an inconsistent finding that may be due to ventricular myocytes with long action potentials
What are the bipolar leads of an ECG? What do they represent?
The standard limb leads each measure the differences in potential between two limbs.
* In Lead I, the electrodes are connected so that an upward deflection is inscribed when the left arm becomes positive relative to the right (left arm positive).
* In Lead II, the electrodes are on the right arm and the left leg, with the leg postivity.
* In Lead III, the electrodes are on the left arm and left leg with the leg positive
What are the durations and events that occur during the following intervals in an ECG?
* PR interval
* QRS duration
* QT interval
* ST interval
- PR interval - 0.12-0.20 - AV conduction
- QRS duration - 0.08 - 0.10 - Ventricular depolarisation
- QT interval - 0.40 - 0.43 - Ventricular action potential
- ST interval - 0.32 - plateau portion of the ventricular action potential
What are the unipolar leads of an ECG?
Inclduing what an augmented limb lead is pls
Leads that record the potential difference between an exploring electrode and an indifferent electrode.
* There are six unipolar chest leads V1-V6 and three unipolar limb leads: VR (right arm), VL (left arm) and VF (left foot)
* Augmented limb leads put a before the above things, aVR, aVL and aVF. They are recording between the one, augmented limb and the other two limbs.
What aspects of the heart does aVR look at and therefore what should its normal pattern be?
aVR looks at the cavities of the ventricles and all waves should have negative deflections because all the pathways lead away from it
What aspects of the heart does aVL and aVF look at and therefore what should its normal pattern be?
aVL and aVF look at the ventricles and the deflections are either positive or biphasic because the pathways lead towards them
What aspects of the heart does V1 and V2 look at and therefore what should its normal pattern be?
- V1 and V2 should not have a Q wave and only has a small positive inflection at the start of the QRS, because ventricular depolarisation moves across the septum from left to right toward the exploring electrode.
- The wave of excitation then moves down the septum and into the left ventricle away from the electrode, producing a large S wave.
- Finally, it moves back along the ventricular wall toward the electrode, producing the return to the isoelectric line.
What aspects of the heart does V4-V6 look at and therefore what should its normal pattern be?
In the left ventricular leads, there may be a small Q wave (left to right septal depolarisation) and there is a large R wave (septal and left ventricular depolarisation) followed in V4 and V5 by a moderate S wave (late depolarisation of the ventricular walls moving back towards the AV junction)
How can the cardiac axis be calculated from two limb leads?
If it is assumed that the heart lies in the centre of the triangle, an approximate mean QRS vector is often plotted by using the average QRS deflection in each lead.
They can be approximated by measuring the net differences between the positive and negative peaks of the QRS.
What is the average heart rate for patients with 1) AV nodal heart block and 2) Infranodal heart block. Why?
- In patients with AV nodal block, the remaining nodal tissue becomes the pacemaker and the rate of the idioventricular rhythm is approx 45 bpm.
- In patients with infranodal heart block, the ventricular pacemaker is located more peripherally in the conduction system and the ventricular rate is slower, approx 30 bpm but can go down to 15bpm. The resultant cerebral ischaemia causes dizziness and fainting (Stokes-Adams syndrome)
What are the types of incomplete heart block?
- First-degree heart block is where all the atrial impulses reach the ventricles but the PR interval is abnormally long.
- Second-degree heart block is where not all the atrial impulses are conducted to the ventricles.
- Mobitz type 1 is where a ventricular beat may follow every second or third atrial beat (2:1 or 3:1 block)
- Mobitz type 2 - Wenckebach is where there are repeated sequences of beats in which the PR interval lengthens progressively until a ventricular beat is dropped.
What is increased automaticity of the heart?
Normally, myocardial cells do not discharge spontaneously, and the possibilty of spontaneous discharge of the His bundle and Purkinje fibres is low because the pacemaker discharge of the SA node is more rapid than their rate of spontaneous discharge.
However, in abnormal conditions, the His-Purkinje fibres or the myocardial fibres may discharge spontaneously.
In these conditions, increased automaticity is said to be present.
What happens if an irritable ectopic focus discharges?
If it discharges once, the result is a beat that occurs before the expected next normal beat and transiently disrupts the cardiac rhythm (atrial, nodal or ventricular extrasystole or premature beat)
If the focus discharges more than repetitively at a rate higher than the that of the SA node, it produces rapid, regular tachycardia (atrial, ventricular, or nodal paroxysmal tachycardia or atrial flutter)
What happens during re-entry pathways?
A defect in conduction that permits a wave of excitation to propagate continuously within a closed circuit.
If the re-entry is in the AV node, the re-entrant activity depolarises the atrium, and the resulting atrial beat is called an echo beat. In addition, the re-entrant activity propogates down to the ventricle, producing paroxysmal nodal tachycardia
What is the atrial rate in atrial flutter? How does it normally happen?
250-300/min
In the most common form, there is a large counterclockwise circus movement in the right atrium.
It is normally associated with at least 2:1 block because the ventricles can’t beat that fast.
What changes do you see on an ECG in ventricular arrhythmias?
- Premature beats that originate in an ectopic ventricular focus usually have bizarre shaped prolonged QRS complexes because of the slow spread of the impulse from the focus through the ventricular muscle to the rest of the ventricle.
- They are usually incapable of exciting the bundle of His, and retrograde conduction to the atria therefore does not occur. Meanwhile, the next succeeding normal SA node impulse depolarises the atria. Therefore, the P wave is usually buried in the QRS.
- If the normal impulse reaches the ventricles, they are still in the refractory period.
- However, the second succeeding impulse from the SA node produces a normal beat. Thus, ventricular premature beats are followed by a compensatory pause that is often longer than the pause after an atrial ectopic.
What is Torsades de Pointes?
A form of ventricular tachycardia where the QRS morphology varies
What happens to the electrical activity in the heart in VF?
The ventricular muscles contract in a totally irregular and ineffective way because of the very rapid discharge of multiple ventricular ectopic foci or a circus movement.
What does the ECG look like in WPW?
The manifestations of the Bundle of Kent activation merge with the normal QRS pattern, producing a short PR interval and a prolonged QRS deflection slurred on the upstroke, with a normal interval between the start of the P wave and the end of the QRS complex.
What happens in the cardiac cycle in terms of filling, volume and pressure?
- Atrial systole
- Isovolumetric ventricular contraction
- Ventricular ejection
- Isovolumetric ventricular relaxation
- Ventricular filling
What happens late in diastole during ventricular filling?
The mitral and tricuspid valves are open and the aortic and pulmonary valves are closed.
Blood flows into the heart throughout diastole, filling the atria and ventricles. The rate of the filling decreases as the ventricles become distended and, especially when the heart rate is low, the cusps of the AV valve drift toward the closed position.
The pressure in the ventricles remains low.
What happens during atrial systole?
- Contraction of the atria propels some additional blood into the ventricles
- Contraction of the atrial muscle narrows the orifices of the superior and inferior vena cava and pulmonary veins, and the inertia of the blood moving towards the heart tends to keep blood in it. However, despite these inhibitory influences, there is some regurgitation of blood into the veins.
What happens during isovolumetric ventricular contraction?
- The AV valves close.
- Ventricular muscle initially shortens relatively little, but intra-ventricular pressure rises sharply as the myocardium presses on the blood in the ventricle.
- During isovolumetric contraction, the AV valves bulge into the atria, causing a small but sharp rise in atrial pressure.
- The end of isovolumetric ventricular contracion is when he pressure in the ventricles excees the pressure in the aorta and pulmonary artery and the aortic and pulmonary valves open.
What happens during ventricular ejection?
- Ejection is rapid at first, slowing down as systole progresses.
- The intraventricular pressure rises to a maximum and then declines somewhat before ventricular systole ends.
- Late in systole, pressure in the aorta actually exceeds that in the left ventricle, but for a short period momentum keeps the blood flowing forward.
- The AV valves are pulled down by the contractions of the ventricular muscle, and atrial pressure drops.
What are the pressures in the aorta and pulmonary veins?
What are the peak pressures in the left and right ventricles?
Aorta - 80mmHg, 10.6kPa
Pulmonary artery - 10mmHg
Left ventricle - 120mmHg
Right ventricle - 25mmHg
What happens during protodiastole? How long does it last?
- Once the ventricular muscle is fully contracted, the already falling ventricular pressures drop more rapidly.
- It lasts for about 0.04 seconds
- It ends when the momentum of the ejected blood is overcome and the aortic and pulmonary valves close, setting up transient vibrations in the blood and blood vessel walls.
What happens during isovolumetric ventricular relaxation?
After the aortic and pulmonary valves close, pressure continues to drop rapidly during the period of isovolumetric volumetric relaxation.
Isovolumetric relaxation ends when the ventricular pressure falls below the atrial pressure and the AV valves open, permitting the ventricles to fill.
Which side of the heart contracts first?
Although events on two sides of the heart are similar, they are somewhat asynchronous. Right atrial systole precedes left atrial systole, and contraction of the right ventricle starts after that of the left.
However, since the pulmonary artery pressure is lower than aortic pressure, right ventricular ejection begins before that of the left.
What is the left ventricular ejection time (LVET)?
The period from the beginning of the carotid pressure rise to the dicrotic notch (a small oscillation of the falling phase of the pulse wave caused by vibrations set up when the aortic valve snaps shut, is visible if the pressure wave is recorded but is not palpable at the rest.)
What happens from points a-d in this normal pressure-volume loop of the left ventricle?
- During diastole, the ventricle fills and pressure increases from d to a
- Pressure then rises sharply from a to b during isovolumetric contraction and from b to c during ventricular ejection
- At c, the aortic valves close and pressure falls during isovolumetric relaxation from c back to d.
In recording of jugular pressure, what is the a wave, c wave and v wave?
- The a wave is due to atrial systole - some blood regurgitates back into the great veins and the resultant rise in JVP contributes to the a wave
- The c wave is the transmitted manifestation of the rise in atrial pressure produced by the bulging of the tricuspid valve into the atria during isovolumetric contraction
- The v wave mirrors the rise in atrial pressure before the tricuspid valve opens during diastole
What causes the first, second, third and fourth(!) heart sound?
- The first sound is caused by vibrations set up by the sudden closure of the AV valves at the start of ventricular systole
- The second sound is caused by vibrations associated with the closure of the aortic and pulmonary valves just after the end of ventricular systole.
- The third sound coincides with the period of rapid ventricular filling and is probably due to vibrations set up by the inrush of the blood - occurs in about 1/3 of young people through diastole.
- A fourth sound can sometimes be heard immediately before the first sound when atrial pressure is high or the ventricle is stiff in conditions such as ventricular hypertrophy. It is due to ventricular fillings and is largely pathological.
What is the length and frequency of the first, second and third heart sounds?
- First sound - duration 0.15 seconds, 25-45Hz - it is soft in bradycardia
- Second sound - duration 0.12 seconds, 50Hz - it is loud and sharp when the diastolic pressure in the aorta or pulmonary artery is elevated
- Third sound - when present duration 0.1 seconds
