This action might not be possible to undo. Are you sure you want to continue?
Contents........................................................................................................................................1 Sensory Nerve Conduction and Carpal Tunnel Syndrome..........................................................2 Skeletal Muscle Physiology.........................................................................................................3 Membrane Potentials.................................................................................................................4 Somatosensory System..............................................................................................................5 Motor Systems Physiology..........................................................................................................6 Female Reproductive Hormones and Their Effects.....................................................................7 Thyroid Gland Physiology...........................................................................................................9 Toad Heart...............................................................................................................................12 Recording and Interpreting an ECG..........................................................................................14 Body Temperature and Cutaneous Circulation.........................................................................24 Exercise Physiology 1...............................................................................................................28 Exercise Physiology 2...............................................................................................................30 Drug Metabolism......................................................................................................................32 Renal Physiology......................................................................................................................33 Spirometry and Respiratory Mechanics....................................................................................38 Respiratory Gas Exchange.......................................................................................................41 Control of Respiration...............................................................................................................45
SENSORY NERVE CONDUCTION
CARPAL TUNNEL SYNDROME
Axons conduct signals to/from periphery neurons to CNS as either motor [efferent] or sensory [efferent] signals. They are classified into groups based on their conduction speed – A-beta, Adelta and C. Conduction velocity depends on axon diameter, myelination and temperature. Diseases such as carpal tunnel syndrome and peripheral neuropathy slow action potentials or block conduction.
Describe how sensory nerve action potentials can be elicited by transcutaneous electrical nerve stimulation and recorded as a compound sensory nerve action potential. Compound action potentials are a response of an entire nerve to a stimulus, being the summation of the many action potentials of different fibres. With increasing distance, differences in the conduction velocity of the fibre types separate the signal in the action potential. They are the result of all-or-nothing AP’s firing and do not occur in real life as it involves externally stimulating an entire nerve. The types of fibres recruited depend on intensity of the stimulus. Whilst single neurons exhibit all-or-nothing responses to a stimulus, CAP show a graded response due to different axons having different thresholds. Large axons have low thresholds [ Aα axons>Aβ>Aγ>Aδ >B>C] Measurement: It is measured through 2 electrodes – proximal and distal. When the CAP arrives at the proximal electrode, it becomes transiently negative to the distal electrode [upward deflection]. In between, the CAP has no effect. When it arrives at the distal electrode negative compared to proximal causing downward deflection. Q1 - The amplitude of the compound sensory action potential is very small (<20µV), which is much smaller than electromyogram potentials (a few mV). This is because muscles fibres are much larger than neurons; therefore they possess a larger membrane. With an increased area of membrane, there is the possibility for a greater number of ion channels to be formed, thus creating a larger potential difference. Q2 - The amplitude of the compound sensory action potential is much smaller than the depolarisation generated by a typical action potential due to the distance between the compound sensory action potential and the recording device, as well as the presence of various tissues in between. Q3 - The potential recorded at the elbow (5µV) is smaller than at the wrist (20µV), due to the dispersion of the components that make up the compound action potential. The median nerve is also more superficial at the wrist. Q4 - The subject feels the sensation throughout the entire digit, even distal to the stimulating electrodes due to the tonotopic organisation of the nervous system. The stimulus is not something the brain encounters regularly; therefore the referral of the sensation occurs, with the brain believing it to be from a wide range of areas. Conduction Velocity of the sensory axons in the median nerve The conduction distances are the distances between the cathode on the stimulating
electrode and the active electrode at the wrist and elbow. The latency of onset is the time it takes for the start of a response to be recorded at each point from the time the stimulus is initiated. The conduction velocity is calculated by dividing the conduction distance by the conduction time. For the fastest axons, the time will be the latency to the onset of the compound nerve potential. For the slowest contributing axons, the conduction time will be at the end of the compound nerve potential. The median nerve at the wrist is a mixed nerve with both motor and sensory axons, while the nerves at the digits are purely sensory. When measuring the conduction velocity of the neurons that are being stimulated at the digits, it is only the conduction velocity of the sensory neurons that is being measured. When stimulating the median nerve at the wrist, which has both motor and sensory neurons, the conduction velocity being measured is for both motor and sensory. If the fastest conduction velocity is increased when stimulating the wrist as opposed to the digits, then the motor neurons are faster than sensory neurons. If the slowest conduction velocity is decreased when stimulating the wrist compared to the digits, then the motor neurons are slower than sensory neurons. In the experiment, only the fastest conduction time was recorded, so the only conclusion was that the motor neurons are not faster than sensory neurons. Thermal and nociceptive (pain) afferents do not contribute to the recorded sensory compound nerve potential as they are not activated due to their high threshold. Also, the conduction velocities of these neurons are so slow that they would not be recorded in the same field. Clinical Correlations
Muscle contraction is through depolarisation of a nerve releasing ACh into the neuromuscular junction causing an endpoint potential and triggering an AP in the muscle and contraction. The strength of the contraction is due to (i) the number of muscle fibres activated; (ii) frequency of activation; (iii) initial length of the muscle fibre. This was studied through the sciatic nerve and the gastrocnemius muscle (Achilles’ tendon). Graded stimulation of the sciatic nerve-recruitment of motor units
By increasing the stimulus strength (ie. the electrode voltage), an increasing number of nerve fibres were recruited. There was a graded stimulation of the sciatic nerve due to different thresholds of nerve fibres and low voltages only recruited nerve fibres near the electrode. Any stimulus above maximum tension is a supra-maximal stimulus.
Effect of varying the frequency of the trains of supra-maximal stimuli When a second stimulus occurs close a first one without allowing relaxation [increasing frequency], tension is additive. 'Tetanus:twitch' ratio is the ratio of the peak tension during the tetanus to the peak tension during a single twitch. 'Tetanus' is a sustained muscular contraction resulting from a rapid series of nerve impulses As the frequency of the pulses increases, the tension between the twitches does not return to baseline, so they fuse (tetanus). The peak tension during the tetanus is greater than the tension of a single twitch (because in a single twitch there is not enough time to prestretch the elastic elements and produce a full force), so as the frequency increases, the tetanus:twitch ratio also increases. Tetanus is 4x a single twitch strength. The fusion frequency is when tension vs time is a smooth increase. Influence of length on isometric contractions As the muscle length (and therefore also the passive tension) increases, the force of the muscle contraction increases to a point, reaches a peak and then decreases again. This observation is evidence supporting the sliding filament binding hypothesis, as it could be due to sarcomere length -there is an optimal length at which most of the actin and myosin are overlapping (so maximum force can be produced by the myosin heads in the actin binding sites), whereas if the muscle was stretched too much or not enough, there would be fewer binding sites available for the myosin heads to attach [less interference]. This is calculated by measuring passive tension in the muscle [due to elastic properties] and subtracting from total tension to find twitch/active tension.
Concentration differences across membranes of living cells are energy differences. If a membrane was impermeable, no electrolytes can move between the two partitions and no potential difference builds up. Semi-permeability allows selective diffusion, transmembrane potentials can develop. This experiment creates two chambers to emulate the ICF [150 mmol/L] and the ESF [variable] separated by a polysuphonic resin membrane that is selectively permeable. Electodes are
AgCl – coated with Ag and a salt bridge of 3M KCl in agar. It shows how different concentrations of electrolytes give different transmembrane potentials. Both chambers were filled with 150 mM KCl with the ECF after double washouts filled with 100mM to 1.5mM KCl measuring the potential. Using the Nerst equation, we can determine if its more selective for K(+) or Cl (-). Plots of membrane potential vs KCl in ECF were made.
From this we can see as we reduce the concentration of KCl in the outside bath, either K+ or Cl- has to cross to balance the concentrations. If K+ crosses into the outside bath, there would be a negative charge in the ICF and a negative membrane potential. Hence Membrane 1 is permeable to cations as it gives a negative charge. Likewise, if Cl- crossed, it would leave a positive charge in the ICF. Hence Membrane 2 is permeable to anions.
SOMATOSENSORY SYSTEM Texture Discrimination – an active sense as it is easier to compare the roughness of two pieces of sandpaper through active rubbing rather than passive touch, with passive touch relying on physical distortion of the skin only whilst active rubbing creates vibrations which rapidly changes and more easily recognised by the brain. Weight discrimination – tested through judging comparative weights with hand resting on table as well as when elevated. When resting, sensory perception is only through tactile response whilst elevation allows proprioceptive sense (joints and muscle length) to assist in discriminating weights Illusions Parchment skin illusion - with headphones on, fingers are rubbed in front of a microphone. Adjusting the tone to treble creates a sensation of roughness, as the auditory information is integrated in the cortex to create an illusion of roughness. Phantom hand – One hand of a person is under the table, with the other hand resting next to a rubber hand. Brushes and probes are used to touch both the rubber hand and the persons hand under the table. The person then identifies the rubber hand as their own, with numbness. This is due to combination of visual and tactile information. Archimedes’ Illusion – Crossed fingers touch a small bead. This creates an illusion of two beads as sensory information is sent in a somatotropic fashion with the brain
assuming the touching of opposite sides two fingers means there are two objects. However, open eyes adds visual information which may override this. Kinaesthetic Sensations Proprioceptive Illusions –a blindfolded subject attempts to touch their nose with a normal arm and an arm which has the biceps tendon stimulated [struck]. The vibrations cause the arm to appear extended and thus failure to touch the nose. Visual information can override this. Transfer of wrist flexion sensation –in a blindfolded subject, the wrist extensor tendons are stimulated, making the person feel like their wrist is flexing. If the palms of both hands are brought together, this sensation is transferred to the non-stimulated hand as the cortex integrates the vibration to believe both hands are flexing. Postural illusion / Achilles tendon –with eyes closed, the person stands straight and their Achilles tendon is stimulated and repeated with leaning against the bench. The brain believes the ankle is flexing and contracts the gastrocnemius muscle to extend the knee. If against the bench, heels feel like they are digging into the floor. Vestibular / balance system is not able to overcome the proprioceptive senses in postural control. MOTOR SYSTEMS PHYSIOLOGY
FEMALE REPRODUCTIVE HORMONES
During a normal menstrual cycle there are varying levels of estrogen and progesterone. Estrogen from the developing follicle dominates the first half the cycle. Following evolution, the corpus luteum secretes progesterone. Negative feedback from both hormones on the hypothalamic-pituitary reduces levels of Follicle Stimulating Hormone and Luteinising Hormone causing degeneration of the corpus luteum. The drop in Estrogen and Progesterone causes shedding of the endometrium leading to menstruation. Fertilisation maintains levels of Estrogen and progesterone to maintain the endometrium. This experiment looks at the effect of estrogen and progesterone on the uterus and vaginal epithelial cells in non-pregnant rats. A vaginal spear is taken using a cotton bud soaked in saline. A Papanicolaou stain is used involving ethanol, distilled water, haematoxylin with acetic acid, HCl, Orange G, EA 50 and SlideBrite. The types of cells are: nucleated epithelial cells [blue-green with pink/mauve nuclei], large squamous cornified epithelial cells [orange-red] and PMN leucocytes [green, smaller than nucleated epithelial cells]. 4 phases – Oestrus [cornified epithelial cells, heat]; Early Diestrus [leucocytes in cornified cells], Late Diestrus [regression of corpora lutea, mainly PMN’s] and Pre-estrus [nucleated epithelial cells]. Oestrogen cornified cells; Progesterone inhibits. Looking at treated rats:
The experiment then looks at the weight of the uterus as a % of total body weight in normal and treated rats. Higher weight in estrogen as it increases endometrial thickness, vascularity and glandular secretion.
Pregnancy Testing: Uses an antibody test against the Beta subunit of human chorionic Gonadotrophin (hCG) hormone. FSH, LH, TSH and hCH all share the same alpha subunit with only differences being beta subunit, which determines biological function hCG is initially secreted by the blastocyst as it implants 6 days following ovulation / day 20 of cycle. Concentration till day 60, and then declines. It helps maintain pregnancy and supplements the low LH at the end the cycle and prevents luteal regression, thus allowing it to secrete oestrogen and progesterone until the placenta takes over. of
THYROID GLAND PHYSIOLOGY The thyroid gland is made up by masses of balls of cells (follicle). Each follicle has a space which is filled with protein and fluid (colloid). Around the colloid are follicular cells which accumulate iodine, synthesise thyroglobulin, a hormone storage and precursor molecule, and regulate the secretion of thyroid hormones. The colloid contains the stored hormones attached to the thyroglobulin. 1) Iodide is transported into the follicular cell by secondary active transporter (Na2+/I-) using the [Na2+] gradient. The Na/K/ATPase pump maintains the sodium gradient. 2) After it moves across the apical membrane via an anion exchanger into the colloid space, iodide gets converted to iodine by thyroid peroxidase, which combines with the thyroglobulin synthesised by the follicular cells. The iodine combines by binding to the tyrosine amino acids on the thyroglobulin. [Iodide can continue to move across the apical membrane because there is a low concentration of iodide but not iodine in the colloid space thanks to the peroxidase.] 3) The binding to tyrosine amino acids forms multiple thyroid hormone molecules (predominantly thyroxine) which are all still attached to the thyroglobulin. Thus lipophilic thyroid hormone is stored in the colloid space in this manner to stop it escaping. 4) When thyroid hormone needs to be released, (as triggered by the release of TRH from the hypothalamus which stimulates release of TSH from the anterior pituitary), TSH acts on a receptor on the basal membrane and increases cAMP levels. This causes the release of proteases by the follicular cell into the colloid space. The proteases break thyroid hormone off the thyroglobulin, and the hormone is then easily secreted due to its lipophilic nature. Two hormones are produced thyroxine aka tetra-iodothyronine (T4) and tri-iodothyronine (T3). T3 is more active, but more T4 is released. Since they are both lipophilic, to get around to the body via the bloodstream, they need transport molecules e.g. TBG for T4 or albumin which binds stuff in general. Once they reach the target tissue most of the T4 is converted to the active T3 by deiodinases.
The point of the practical is to prove that thyroid peroxidase, which converts iodide to iodine, is susceptible to competition/inhibition through examining (a) histological slides (b) uptake and distribution of radioactive iodine I131 when administered as NaI131, of thyroid glands of rats which received different treatments. Thyroxine (T4) is the major thyroid hormone synthesised by the thyroid gland, exerts most of the negative feedback on the thalamus and anterior pituitary, and is converted to T3 in target tissues. Thiouracil interferes with the synthesis of thyroxine, and is used in the treatment of hyperthyroidism.
Deduce the mechanism of action of perchlorate upon the thyroid gland Comparing A, D and G, clearly NaClO inhibits the uptake of iodide by follicular cells from the blood. When dissociated, compeetes with iodine for Na/I symporter.
Determine the mechanism of action of thiouracil, and determine the effects of the preexperimental treatments upon the levels of HP and anterior pituitary activity and hence the secretion of TSH Thyroxine has an inhibitory effect on TSH (negative feedback loop). This decreases iodide uptake by follicular cells, the secretion of thyroid hormones and endocytosis of the thyroglobulin storage molecule from the colloid. Hence, the cells are less active and more hormone is stored than released. From the results, it can be deduced that thiouracil increases uptake of iodine by follicular cells, either through the blood or from the colloid space, or both (which is the case). TSH must be high to cause the thyroid glands to get so big and for the cells to be so active, yet the colloid spaces are small. This is because thiouracil inhibits thyroid peroxidase. This causes iodide to stay as iodide and move out of the colloid space into the follicular cell. Due to the high concentration of iodide in
the cell vs blood, iodide will move out into the blood. As a result, there will be low amounts of thyroid hormone being produced, which stimulates the release of TRH/TSH, leading to a more active follicular cell. Determine the relative level of activity of the thyroid glands from the rats of the different pretreatment groups by the iodide distribution. The thyroid glands of the rats that got thiouracil were the most active, followed by the normal thyroid glands, followed by the thyroid glands which received thyroxine. Find out the half-life for I131 using semi log paper and compare it to I123 and the 60 day halflife of I125. What advantages does the former have in this experiment and in clinical practice? I131 has a half-life of 17 days. I123 has a half-life of 13.57 hours. In clinical practice, I131 would be useful if you wanted to destroy thyroid gland cells e.g. thyroid cancer. If we were to do this experiment on humans to determine thyroid activity though, we would probably use I123 due to its shorter half-life. TOAD HEART The cardiac muscle tissue of the heart has four main functions: - It forms the physical structure of the heart - It provides the contraction necessary to pump blood - It conducts the impulses which co-ordinate each beat of the heart, and - It generates the rhythmic signals which trigger each beat In order to continuously beat 70 bpm for up to a 100 years, cardiac muscle has specific properties different from skeletal muscle. Like skeletal muscle, cardiac muscle has an all-ornone response to a stimulus. A stimulus / depolarisation at any point in the muscle spread throughout the cardiac muscle so they all twitch. The heart generates its own rhythm through cells which depolarise spontatneously regularly – Sino-atrial node [SA node], Atrio-ventricular node [AV node] and the bundle of HIS. The SA beats the fastest thus having control. The nervous system alters the frequency of the SA node to control heart rate. This experiment uses a toad heart to demonstrate some mechanical and electrical properties. Electrical events in the heart are large enough to be detected on limbs through an ECG. A force transducer measures the mechanical contraction of the heart. A – Surgical procedure – Cut the toad up to see the heart B – Examination of the Heart – Single ventricle, two atria C – Recording ECG – 50mV, Low pass filter 20-50Hz D – Sequence of contraction during heart beat – sinus contractsatriaventriclebulbus arteriosus E – Attach force transducer using a clip to ventricle F – Artificial stimulation of the ventricle of the toad heart.
Toad Heart Results from Stimulation
In electrocardiography, the term “lead” refers to a pair of electrodes and the signal recorded from them. Over the cardiac cycle the myocardium depolarizes and repolarizes. These waves of depol/repol generates extracellular currents that alter the electric potential difference (voltage) across the electrodes of a lead (since current is proportional to voltage, i.e. V=IR). The direction of current flow is important as current is a vector. A conventional current (+ve charge) flowing in the direction of the +ve electrode will lead to an increase in recorded voltage across the electrodes (i.e. an upwards spike), but the same current flowing in the opposite direction will instead lead to a reduction in recorded voltage (i.e. a downwards spike). This changing potential difference over time is the signal recorded by the amplifier, which represents it as a paper trace. The sites of our electrodes that we place on the test subject (i.e. pie) are: Limb electrodes LA (left arm) RA (right arm) LF (left foot) RF (right foot: note this electrode is only used as a filter) Chest(precordal) electrodes 6 electrodes placed at various locations running from the sternum to the left side of the chest (see prac book pg 33 for details). From these electrodes we can obtain 12 leads (12 different pairs of electrodes). These leads can be divided into either bipolar or unipolar leads: Bipolar leads: consists of two “active” electrodes on different sides of heart. Both electrodes are “active” in that they both respond to currents in the heart, and the ECG measures the changes in difference between potentials of both electrodes. Note that these electrodes, together with their connecting wires and the ECG, form a complete circuit involving the chest wall. Leads I, II, III are bipolar leads. Unipolar leads: Has one active electrode (+ve) which responds to currents in the heart. The potential of this active electrode is measured against a baseline potential of an “indifferent electrode” (its potential never alters). The “indifferent electrode” is obtained by combining the outputs from RA, LA and LL into a single electrode which will not vary in potential over the cardiac cycle (I dun quite know how this works…will think about it). Leads V1-6 are unipolar chest leads. Each of the active electrodes measures the electric
potential of the heart muscle directly underneath and abnormalities will produce significant changes in particular leads. Leads aVR, aVL, aVF are unipolar limb leads. They compare the potential measured in a limb electrode against the indifferent electrode. In modern ECGs, the amplitude of the recording is magnified 50% (shape of recording does not change)by disconnecting the part of the indifferent electrode from the limb being measured by the active electrode (i.e. if you are measuring a potential in the LA with an active electrode, you remove the LA component of the indifferent electrode). This amplification results in the leads given the prefix “a” for “augmented”. Summary table of all leads Lead Lead Type I Bi II Bi III Bi Electrode combination LA (+ve), RA (-ve) LF (+ve), RA (-ve) LF (+ve), LA (-ve) Active electrode (always+ve) aVR Uni RA aVL Uni LA aVF Uni LF V1 Uni V1 V2 Uni V2 V3 Uni V3 V4 Uni V4 V5 Uni V5 V6 Uni V6 Task A: Record a 12 lead ECG from one member of each group Leads: 10mm/mV (amplitude of recording. i.e. each 10mm of height in the printout is 1mV) 25mm/s (speed of recording. i.e. every second the paper rolls for 25 mm) Muscle filter: 35hz (not sure what this means. Maybe it means that the ECG is measuring the muscle interference from the RL lead and deducting it from the curve, updating 35 times per sec?).
Indifferent electrode (treated as the –ve) LA+LF RA+LF LA+RA LA+RA+RF LA+RA+RF LA+RA+RF LA+RA+RF LA+RA+RF LA+RA+RF
P wave QRS T wave
QRS P wave T wave
P, QRS, T similar to above. This one was a bit weird. Pie must have been moving. aVR:
This seems to be a weird upside down version of things, but fits the textbook shape
QRS P wave T wave
Task B: Observe and note the effects of the following technical problems 1) Muscle filter removed:
Jumpy/fuzzy line indicating noise
There is an increased amount of noise in the lead (trace), as shown by the “jumpy” nature of the trace compared to normal. 2) Voluntary muscle movement, with and without muscle filter.
Voluntary movement with filter Can’t notice much difference from normal, save that the shape of the trace is slightly irregular
Voluntary movement without filter A high amount of noise, shape of the trace is irregular This is a demonstration of why keeping still and using filter is essential 3) Effect of incorrect cable connections – arm cables (LA, RA) reversed. Effect in lead I:
Looks like normal lead I, but with vectors reversed in direction. This is because the +ve and –ve poles of the trace are reversed (their electrodes are swapped around).
Effect in lead II:
Looks like normal lead III Effect in lead III:
Looks like normal lead II This swapping between the traces of lead II and III is a direct result of the reversal of the LA and RA electrodes. When the machine reads lead II, instead of reading input from the RA and LF electrodes it is actually reading from the LA and LF electrodes. This is the normal method of reading from lead III, and hence the new lead II resembles a normal lead III trace. In effect, the machine is just being tricked into thinking lead III is now lead II, and vice versa. Effect in lead aVR:
Looks like normal lead aVL Effect in lead aVL:
Looks like normal lead aVR
Effect in lead aVF
Lead aVF is normal and unchanged. Effect in V1-V6: The prechordal leads will not be affected as it compares the chest electrode with an indifferent electrode. Leads I and II are both parts of the indifferent electrode, and hence swapping them around will not change any measurements at all. Remember Kirkoff’s law. Task C: Measurements on the ECG done by group Note that at usual paper speed, (25mm/s), 1mm = 0.04 Measurement Value (normal range) Heat Rate (bpm) 75 (60-80) P wave duration (sec) 0.12 (0.08 -0.1) [Atrial depolarisation] PR interval (sec) 0.16 (0.12-0.21) [Conduction from SA to AV node and ventricles] QRS duration (sec) [Depolarisation of the ventricles] QT interval (sec) [Ventricul depolarisation and repolarisation ventricular AP / refractory period] Electrical axis (degrees) [Direction of depolarisation and where cardiac muscle is -> changed in MI and ventricular hypertrophy] 0.10 (<0.12) 0.32 sec Comment (e.g. is this value normal?) Usually not measured clinically PR too long = first degree heart block PR too short: may be due to accessory conducting bundles may run from LA to LV (Wolff-Parkinson-White syndrome) QRS too long: depolarization of ventricles along an abnormal route Measure the total duration of the action potential in the ventricle. It varies with heart rate and gender. Women and children have a longer interval. QT interval also increases as heart rate reduces *see later
Determining heart rate Can be done through 3 different methods 1) Measuring the R-R interval in seconds and dividing this value by 60
2) Use a calibrated ruler 3) Divide by 300 the number of large squares between consecutive beats: 1 large square = 5mm 25 mm = 1 second Therefore 1 square = 0.2 second Time between each beat = number of large squares x 0.2 HR = 60 / time between each beat = 60 / (number of squares x 0.2) = (60/0.2)/number of squares = 300/number of squares (ok this was a waste of time, but I had to prove to myself that their equation made sense =P)
For all three methods its better to measure the heart rate over severalbeats instead of using just two beats. This is because measuring over several beats will negate the variation in heart rate due to sinus arrhythmia (variation with breathing). Determining the electrical axis of the heart The mean electrical axis of the heart indicates the general direction of depolarization in the ventricles (usually from base towards apex), is during and is often of clinical value. It is given as an angle θ from a line parallel to the ground when the patient is standing upright. Vectors pointing below this line has a +ve value for θ, while vectors pointing above this line has a –ve value for θ.
The electrical axis of the heart can be measured simply by triangulation of two instantaneous vectors of depolarization. These two vectors are found by taking values from two different leads. For simplicity, we use values from two leads that measure at right angles to each other so that we can use a simple right angled triangle to work things out. Hence, leads I and aVF are used.
Value from lead I
Angle of mean electrical axis, derived by trigonometry Mean vector (mean electrical axis of the heart) Value from lead aVF
Steps for determining the mean electrical axis (vector) of the heart 1) Examine the QQRS complex in leads I and aVF
2) Calculate the algebraic sum of the R and S deflections in mm (R wave height – S wave depth) I lead:
R height (above the think red line delineating big squares)
S depth (below the think red line delineating big squares)
R height = 2.5, S depth = -1 R – S = 2.5-(-1) = 3.5 aVF lead:
R height = 11, S depth = -1 R – S = 11-(-1) = 12 3 ) Draw lines of the calculated lengths in the appropriate direction for each lead
4) Join the origin of the line for lead I to the end of the line for lead aVF (i.e. adding vectors)
5) Calculate angle θ θ = tan-1 (12/3.5) = 73˚44’ Hence Pei’s heart’s mean electrical axis is 73˚44’ Normal range of the mean electrical axis is from -30 to 120 degrees. <-30˚ = Left axis deviation; can be due to left anterior hemiblock (one of the branches of the bundles of purkinje fibres is defective?) >120˚ = Right axis deviation; can be due to right ventricle hypertrophy (great bulk of muscle there generates more electrical activity and shifts the axis towards the right).
Myocardial infarction: The ECG can show ST-segment depression (subendocardial ischemia), ST elevation (transmural ischemia), or symmetrically inverted (flipped) T waves in the area of ischemia (eg, inferior ischemia in II, III, and F; anterior ischemia in V1 to V6; lateral ischemia in I, aVL; anterolateral ischemia in I, aVL, V5, and V6; anteroseptal ischemia in V1, V2, V3, and V4. BODY TEMPERATURE AND CUTANEOUS CIRCULATION Body temperature is well controlled in homeothermic animals, including man. This control is not absolute in that there can be fluctuations by up to about 2°C over 24 hours, ie, a circadian oscillation. The mean is, however, sufficiently well controlled for significant deviation from it to be used as an index of disease. Body temperature is purposely raised during fever to match the raised hypothalamic "set-point" temperature [reduces bacterial growth] and its measurement is an important part of clinical practice and experimental physiology. There are various instruments available for temperature measurement amongst which are alcohol or mercury-in-glass thermometers (including the special version known as the clinical thermometer), thermocouples and other devices which have temperature dependent electrical properties. In the steady state of heat flow, the heat produced in the body is balanced by the heat lost to the external environment so that internal body temperature tends to remain near 37°C. A. Calibration Use the water baths to check the accuracy of the digital thermometer. Use the certified thermometer (water bath thermometer) as reference standard. Plot a calibration curve, with the independent variable (the certified reading) on the x-axis.
Discussion 1. What are the structural and functional differences between clinical and laboratory thermometers? Why are they different? What range of errors did you find? Lab thermometers have a much larger range, commonly going from -10°C to 50°C. Their gradations tend to be by 0.5°C. Clinical thermometers tend to have a physiological range, i.e. about 35°C to 42°C, and their gradations are much finer, which is made possible because of the thin mercury column. 2. a) What water vapour pressure gradient did you have available to lose body heat by evaporation? For evaporation to occur, the water vapour pressure of the skin must exceed water vapour pressure of atmosphere b) What is the common reason for feeling hot on a hot Sydney summer day? What is almost invariably a person’s first line of defence. Reason you feel hot is because the hotter it is, the less effective the body is at losing heat, and so the more the core body temperature diverges from its ideal value. Lines of defence include: lying in a cool shady area, sitting near a fan, avoiding intense physical activity (as this generates heat) 3. Why did core and skin temperature differ from each other at different sites? The closer the site is to the actual site of core body temperature, the more it will resemble the core body temperature. Hence, the oral temperature is higher than the axillary, and thus a better measure of core body temperature. 4. What precautions might you take when attempting to measure the temperature of: a) a patient who was in danger of becoming hypothermic? o Make sure you shake down the thermometer so you get an accurate reading o Make sure it is a functioning thermometer b) a patient in bed in an un-air-conditioned house during the day in high summer? o May have to cool the thermometer down (e.g. under a cold tap) before shaking it down o Read the thermometer while it is still in the patient’s mouth (don’t take it out, since the ambient temperature might be hot enough to change the reading!) 5. What other factors (i.e. apart from ambient temperature, core temperature and cutaneous circulation) determine skin temperature? o o Clothing and other insulation Subcutaneous fat (more fat means less conduction, so you lose less heat)
6. Describe reactive hyperaemia. How is it caused? Reactive hyperaemia is the transient increase in organ blood flow that occurs following a brief period of ischemia (e.g., arterial occlusion). It is caused by the build-up of vasodilator metabolites (e.g. NO, K+, H+, CO2, adenosine) during the period of ischaemia. 7. What happened to core and skin temperatures during exercise? Why? The data shows that there was a small increase in core body temperature (as measured by oral temperature), and big increase in peripheral temperature (as measured by finger pulp temperature). This is in keeping with the steady state of heat flow, which states that heat generated by the body (as in exercise) is lost to the environment to maintain a relatively constant core body temperature.
The heat lost would have been by conduction, convection, and evaporation/sweating. It is primarily the increase in convection to the skin (via peripheral vasodilation) that raises the skin temperature.
EXERCISE PHYSIOLOGY 1 Is aerobic fitness important for health? • Most important variable • 80% of population do not exercise, or exercise at a level with no health benefits Decrease in leisure & occupational physical activity • Studies: If physically active, = less morbidity, less angina, less cardiovascular disease. • As these people exercise, morbidity decreases. Moderately fit people with conditions = at least half incidence of mortality. • The fitter you are, the less the heart disease. What is VO2max? (maximal oxygen uptake) • Maximum amount of oxygen used by your muscles during exercise. • Athletes utilise oxygen better in the muscles, higher VO2 max à lots of mitochondria, lots of slow twitch fibres, lots of oxidative enzymes in mitochondria, good lungs. The limiting factors for VO2max • Measurement of VO2max • Submaximal fitness tests; LifeSprints • Demonstration • Health Profile laboratory Lifestyle risk factors • Obesity • Dyslipidemia • Smoking • Genetic inheritance • Blood pressure • Physical inactivity Criteria for attaining VO2max (maximal oxygen uptake) • VO2 max = A plateau of oxygen when exercise is raised. • Respiratory Exchange Ratio (RER) > 1.10 • Ratio of O2 and CO2 = respiratory exchange ratio à tells us what nutrient they’re using. • RER usually 0.8 --> shows burning up a fair amount of fat. Obese people will not burn up this fat as has more carbs to burn from diet. • Blood lactate > 10 mmol • Truly maxed out when starting to use glycolytic pathways • Max heart rate is: 220 – age. However, 12% of population is higher or lower than this value. Limiting Factors For VO2max In normal people = cardiac output = heart rate x stroke volume = producing Ian Thorpe has 50L = cardiac output. Therefore, pushing around 50L of blood around body. Pulmonary Diffusing Capacity The major factors that determine VO2max: the ability of the heart to pump blood (CO) and the muscles’ ability to use oxygen and produce energy. Measurement of VO2max • Subject’s expired air • Air volume breathed • O2 and CO2 analyzer • Oxygen and carbon dioxide ratio measured --> can see if they are using more carbs or fat, etc. • Traditionally done with Douglas bags, measure volume of gas (O2, CO2) exhaled into Douglas bags. • Amount of CO2 is usually a bit more than O2. • VCO2 = amount of CO2 used. • Spirometer • Mixing chambers • High speed gas analysers VO2max values • · Absolute in litres (e.g., 5.2 litres) • Big males have big absolute VO2 max, but does not mean they are fit, as they have a lot of body weight to carry around.
· Relative to body mass in ml.kg.min (e.g., 70 ml.kg.min = an elite runner; below 30 ml.kg.min is unfit) • Better way than absolute value in assessing fitness. Uses of O2 assessment • · Best assessment of aerobic power (cardiopulmonary fitness) • · One of the best predictors of disease • Resistance exercise also important for preventing osteoporosis etc. • · Substrate use (fat versus carbohydrate) • · Resting metabolic rate (e.g. indicates thyroid function) • · Stress testing (used fore testing arrythmias and cardiovascular) • · Expensive equipment • · Trained personnel Disadvantages • · Exhausting • · Stresses cardiovascular system • · Crash cart, defibrillator (as stress testing may result in heart attack/problems) Submaximal testing Subject’s estimated VO2max (80 kg) is: • - 3.8 litres • - 47.5 ml.kg.min • - Gases not collected, only HR collected. • - Calculate max HR by 220-age. HR is linear to O2 consumption, therefore can estimate. Exterpolate/continue from the graph line until maximal HR reached. • - Start off with light exercise with low resistance, then gradually increases resistance/stress. • - But don’t max the subject out, therefore no problems with breathing, heart problems etc. • - Useful if used in comparison: i.e. ‘before and after’ submaximal testing. One test is useless. Fat loss and intermittent exercise (LifeSprints) • High intensity • Intermittent • Lost a lot of fat. • 8 seconds hard sprint, 12 seconds slowing down. • 20 minutes • 8 min sprint, 12 min easy • Heart rates >160 bpm during this exercise. • When sprinting = body has lots of catacholomines (burning fat), when stopped = body starts oxidizing. • Improves VO2 max despite this being lots of anaerobic running. • 40 min steady exercise: did not lose fat. • If this is done for 6 months: only half kg weight (not necessary fat). Trunk fat • - Women not much trunk fat, men = more. Insulin • - LifeSprints greatly reduced insulin resistance. Ageing changes • - When reach 30 yrs: VO2 comes down at linear rate. • - If you exercise a lot, doesn’t stop this process, but delays this deterioration rate. • - As people age, they do less physical activity at work and for leisure. Laboratory – Health Profile (five components) • - Blood pressure • - Body composition • - Flexibility • - Strength
- Posture Laboratory – Health Profile (body composition) • BMI o underweight <18.5 o Normal 18.5-24.9 o Overweight 25-29.9 • Waist circumference WC (high risk when BMI >25): o Men >102 cm (overweight 94 cm) o Women > 88 cm (overweight 80 cm In obese male, subcutaneous fat. Obese female has far more subcutaneous fat amount, but far less visceral fat. Subcutaneous fat is benign and is useful because it stores and traps our fat. However, visceral fat = much more metabolically active and dangerous. Far more dangerous chemicals produced à insulin resistance, etc. • Waist-hip-ratio o Women = 0.80 or less o Men = 0.95 or less • Body fat • Skinfolds Measure of skin fold containing fat. Laboratory – Health Profile (posture) • Head poking (Too much work on computer --> muscles will change. Tight back muscles) Rounded shoulders Scoliosis Kyphotic curve Lordotic curve Muscle imbalance
Laboratory – Health Profile (blood pressure) Systolic and diastolic Mean arterial pressure Rate pressure product (HR x systolic, divided by 100) o If high, then heart is using much more O2 than usual. Pulse pressure (>50 problematic) o Systolic – diastolic. o Usually 40, high = 50. o Measure cardio problems. • Resting heart rate • Heart rate variability (record HR for 10 sec breathing in, then 10 seconds breathing out; should be >8 bpm difference) o High sugar levels e.g. diabetic neuropathy --> nerve deterioration --> this variability is less than 8bpm. Parasympathetic nerve slows HR down. When inhale, HR accelerates due to nerve response, when exhale HR slows.
Laboratory – Health Profile (flexibility) • Sit-and-reach • Hamstring (Indicates stiff calf muscles/hamstrings/calves, short hamstrings, etc.) • Short adductors (groins & knees should be close to ground) • Sit-and-reach test • Fall over more, lack of balance = old age inflexibility
Laboratory – Health Profile (strength) • • • • • Hand grip Abdominal stage test (predictor of back pain) Lower abdominal test Lateral lift test (quadratus lumborum, predictor of back pain) Abdominal and handgrip tests
• • • • •
EXERCISE PHYSIOLOGY 2 Blood Pressure • Blood pressure is the amount of force supplied by the arteries = how hard your heart is working in order to deliver blood around the body. • A high blood pressure means that your heart has to work harder than it should à possible complications later in life. • Very important to detect high blood pressure early on, so that it can be controlled by altering eating behaviours, participating in aerobic exercise, and controlling stress in your everyday life.
Cholesterol • There are two types of cholesterol in your body, high levels of one of the types of cholesterol in your blood can cause your arteries to harden, which increases your blood pressure. By analysing the different types of cholesterol and free fatty acids in your blood, we can assess your risk of developing high blood pressure
Body Composition • Too often in weight loss programs, people use their weight as a guide for their progress. What’s more important to your health is your body composition = proportion of your weight made up by fat, muscle, and bone. • A lot of the time, people find they don’t lose any weight during a fitness program. In fact, they may gain some weight as muscle and lose body fat. • By analysing your current body fat, we can observe any changes over the course of the program. • Girth measurements are an accurate indicator for risk of strokes and heart attacks later in life, and so will also take hip and waist measurements. Posture • Walk up and down the room. • Observe: o Are shoulders level? o Rounded shoulders? o Is the spine straight from the back? o Excessive curvature of thoracic spine? à wall test o Excessive curvature of lumbar spine? o Normal curves of back too flat? o Head poking? Aerobic Power (sub-maximal cycle ergometry) • Aerobic capacity is assessed by a sub-maximal cycle ergometry test. • Determines cardiovascular fitness level use this to determine types of exercise and intensity of subject’s fitness regime.
In order to assess VO2max, subject is placed on an exercise bike with a heart rate monitor attached around your chest. • Asked to continue pedalling at a set speed for approximately 10mins. • During this time the workload will be adjusted according to the changes in subject’s heart rate. • During the test, patient will also be asked at regular intervals to rate their exertion levels. This will be done with the assistance of a RPE scale (rate of perceived exertion). • At the end of the 10mins, results will be graphed, and estimated VO2max calculated. • This test is 90% accurate, and subject’s heart rate should not exceed 160 beats per minute at any stage. Flexibility • Flexibility refers to the ability to move limbs in wide ranges, without pain or injury. • Poor flexibility indicates tight muscles and ligaments surrounding the joint, which can lead to chronic pain and possibly predispose to injury. • The sit-and-reach test is a simple test for general flexibility of the hamstrings and lower back. • Areas of poor flexibility = determined by score and shape of body during the test • Range of movement tests allows assessing of joint specific flexibility throughout the body. The score will identify the specific areas of the body that should be targeted by a stretching training program.
Strength • Upper body strength is assessed using a hand-grip dynamometer. • Strength in general declines with age, so it is important to ensure your grip is strong enough at younger ages, to enable you to maintain your ability to do certain things when you are older (open bottles, turn door handles, etc) • Your abdominal strength will be assessed by using a 5stage sit-up test. Abdominal strength is vital for the maintenance of correct posture, and to aid in supporting the lower back during lifting and bending movements. DRUG METABOLISM Explanation • Ingesting sodium bicarbonate (NaHCO3) alkalises urine, increasing its pH • • • • • Ingesting ammonium chloride (NH4Cl) acidifies urine, lowering its pH Lowest urine pH possible – 4.4 Normal urine pH – 4.6-8.5 1. What effect does urine pH have on salicylate clearance? Stomach – low pH, acidic o Salicylate will be unionised, therefore absorbed across stomach o Stomach has small surface area, so not much will be absorbed Intestines – pH 7-8 o Salicylate will be more ionised, therefore harder to cross membrane o Intestines have large surface area and some salicylate will be unionised still, so significant amount will be absorbed Kidney o Ultrafiltrate of plasma passes through kidneys from circulation o Blood is well buffered, and hence can’t change pH o The glomerulus filters the plasma. Drug is filtered out, and some cross membrane. Proximal tubule o Urine is alkali pH ionised salicylate won’t be reabsorbed, and more is excreted o Urine is acidic pH unionised salicylate reabsorbed, and less is excreted o Salicylate is a weak acid. In a basic drug, the opposite is true.
2. What are the advantages and disadvantages of increasing the rate of salicylate clearance? Advantages o In an overdose, give patient something alkali to drink to make urine more alkali, and increase rate of clearance Disadvantages o Increased clearance rate a problem when you want to maintain drug in a therapeutic range (i.e. plasma concentrations where drugs work). E.g. cardiac glycoside has narrow range 3. What clinically relevant applications relate to your results? A dosing schedule should consider a person’s diet to work out the effects of food on elimination of drugs.
Further Questions 1. List as many drugs as you can that are weak acids: • Neurofen 2. What factors (e.g. diet, drugs) may result in an altered urine pH? For each factor identified, describe how you may modulate the dose schedule of a drug that is a weak acid. • Acidic foods • Meat and animal products (starch and protein) – fish, fowl, eggs, liver, yoghurt, buttermilk • Alcohol - wine • Sugar • Corn, beans, grains, asparagus • Vinegar • Coffee • Distilled or filtered water • Alkali foods • Orange and lemon juice – metabolites of ascorbic acid are alkali • Fruits and vegetables – bananas, figs, potatoes, spinach, water melon • Mineral water • Other factors that make urine more acidic • Acidosis – blood pH decrease, therefore urine more acidic • Diabetes • Diarrhoea • Starvation, dehydration • Respiratory problems – more CO2 in blood makes urine more acidic • Kidney stones • Tobacco • Aspirin • Probiotics • Soft water • Other factors that make urine more alkali • Respiratory problems – get rid of too much CO2 leads to alkalosis • Urinary tract infections and urinary tract obstructions • Antibiotics • Most mineral supplements – calcium, potassium, iron and magnesium • Antacids • Hard water RENAL PHYSIOLOGY Osmolarity (Osm/l) = dissociation constant * conc (mol/l) Osmolality (Osm/kg) = dissociation constant * conc (mol/kg) Note: Plasma osmolality reference range = 275 - 299 mOsm/kg
1. What is the osmolality of a 0.9% saline solution? (Note: mw of NaCl = 58.5) 1 mole = 58.5 g 1g/l of saline = 1/58.5 mol/l ∴ 9g/l of saline = 9 * 1/58.5 ≈ 154 mmol/l Dissociation of NaCl ≈ 1.88 ∴osmolality = 154 * 1.88 ≈ 290 mOsm/kg (∵1l H2O = 1 kg H2O) 2. What is the osmolality of a 1.8% urea solution (Note: mw of urea = 60) 1 mole = 60g 18g/l solution = 18 * 1/60 = 300 mmol/l Urea undergoes no dissociation ∴ osmolality = 300 mOsm/kg 3. Is 0.9% saline isotonic? Why? 0.9% saline is isotonic ∵ impermeant and iso-osmotic Size of cells stay the same. 4. Is 1.8% urea isotonic? Why? No. Urea permeates cells down concentration gradient ∵ [extracellular urea] > [intracellular urea] and thus is followed by water. 1.8% urea is hypotonic. Cells swell. 5. When a subject drinks 20 ml/kg of water, a) What happens to their total body water, extracellular volume and intracellular volume? b) What happens to the osmolality of their body fluids? (Assume that prior to drinking water, TBW = 600 ml/kg, ECV = 200 ml/kg, ICV = 400 ml/kg and plasma osmolality = 300 mOsm/kg) a) TBW from 600 ml/kg to 620 ml/kg ECV from 200 ml/kg to 207 ml/kg ICV from 400 ml/kg to 413 ml/kg (By osmosis as 1/3 solutes is extracellular and 2/3 solutes is intracellular) b) Osmoles in BW = 0.6 l x 300 mOsm/l = 180 mOsm/kg After drinking, 180 mOsm is contained in 0.62 l ∴ osmolality = 180/0.62 = 290 mOsm 6. When a subject drinks 7 ml/kg of 0.9% saline, a) What happens to their total body water, extracellular volume and intracellular volume? b) What happens to the osmolality of their body fluids? (Assume that prior to drinking water, TBW = 600 ml/kg, ECV = 200 ml/kg, ICV = 400 ml/kg and plasma osmolality = 300 mOsm/kg) a) TBW from 600 ml/kg to 607 ml/kg ECV from 200 ml/kg to 207 ml/kg (does not permeate cells) ICV remains at 400 ml/kg b) Osmolality remains unchanged (can be inferred from Q3). Initially 180 mOsm/kg of BW Added 300 x 0.07 = 2.1 mOsm/kg Now, 182.1 mOsm in a volume of 0.607l, ∴ Osmolality = 182.1/0.607 = 300 mOsm/kg 7. Why were subjects who drank 0.9% saline given only 7 ml/kg to drink instead of 20 ml/kg? To get the same amount of volume expansion as 20 ml/kg of water. 8. On the graph paper provided, plot 5 graphs showing average (i) urine flow rate (ml/30 min) and (ii) urinary osmolality (mOsm/kg) as a function of time (30 mins, 60 mins, 90 mins, 120 mins) for each of the 5 groups of subjects.
9. What was the effect of drinking 20 ml/kg of water on urine flow rate and osmolality? Urine flow rate up & osmolality down. 10. Which of the other test solutions produced urine flow rates similar to water load? 1.8% urea 11. Why did the 1.8& urea solution produce a greater urine flow than that produced by drinking 0.9% saline? Cells producing ADH swell with 1.8% urea whereas they don't change in size with 0.9% saline. This inhibits release of ADH by the posterior pituitary. AQP2 is withdrawn from the apical membrane of the principal cells of collecting ducts. No reabsorption ∴ more urine is excreted 12. Which test solution produced the maximum osmolar excretion? Why? (Note: osmolar excretion per 30 min calculated as urine flow x osmolality) Calculate osmolar excretion for: Control = 114 mOsm Water = 165 mOsm (more than control ∵ excreting more water = more urea) Saline = 172 mOsm Urea = 276 mOsm Water + ADH = 161 mOsm 13. (a) Was the diuresis in water loaded subjects primarily a response to volume expansion of body fluid or to a change (dilution) of osmolality of body fluids? Why do you conclude this? Yes. Saline subjects did not have diuresis unlike water & urea subjects. (b) Where are the receptors which detect these changes? Supraoptic & paraventricular nuclei in the hypothalamus Volume is detected in baroreceptors in carotid & aortic arch (high pressure) and right atrium, great veins & pulmonary vessels (low pressure) 14. What effect did administration of ADH have on the response to a water load? Why? ADH inhibited the diuretic effect of water load. Endogenous ADH in normal subjects caused diuresis. 15. Summarise the mecahnisms via which water loading causes a diuresis. Inhibition of ADH Release of Atrial Natriueitc Peptide (ANP) Inhibition of Sypathetic Nervous System (SNS) causing inhibition of renin release and renal vasodilation Additional Exercises 1. Where would the following distribute if (hypothetically) transfused into the plasma space of a normal person? (a) water Throughout TBW (IV water lyses RBC) (b) "normal saline" ie. 9g NaCl/l of total solution or 0.9% (W/V) saline. Stays in ECV (c) 1.8% urea solution (in water) Throughout TBW (cannot IV) (d) 5.5% mannitol (polysaccharide) solution
Distributed in ECV (e) plasma Distributed in vascular compartment then to ECV Increases blood pressure quickly (f) 10% albumin solution in 0.9% saline Distributed in vascular compartent then slowly to ECV (g) whole blood Distributed in vascular compartment (RBC; plasma slow turnover into ECV) (h) 5.4% glucose solution ECV ---insulin action----> ICV IV for hydration without causing cells to lyse How would these values change if the following were added to ECF? (a) 3L of pure water - New ICV = 30l - New osmolality = 300*28/30 = 280 mOsm/kg - New [K+] = 150*28/30 = 140 mmol/l - New ECV = 15l - New osmolality = 300*14/15 = 280 mOsm/kg (or simply 280 mOsm ∵ distribution until same) - New [Na+] = 140*14/15 = 131 mmol/l (b) 3l of 0.9% NaCl - ICV stays the same (NaCl does not permeate cells) - Osmolality unchanged - [K+] unchanged - New ECV = 17l - Osmolality unchanged ∵ same osmoles - New [Na+] = (140*14 + 3*154)/17 ≈ 142.5 mmol/l o Na increases when saline infused unlike plasma (c) 420 mmol NaCl 420 mmol NaCl = 840 mOsm (or use 1.88 dissociation factor) New osmolality (ICV & ECV) = [300*42 + 840]/42 = 320 mOsm/kg - New ECV = (300*14 + 840)/320 = 15.75l - New ICV = 42 - 15.75 = 26.25l - New [Na+] = (140*14 + 420)/15.75 ≈ 151 mmol/l - New [K+] = (150*28)/26.25 = 160 mmol/l
SPIROMETRY AND RESPIRATORY MECHANICS Respiratory mechanics is the study of volumes, flows and forces of gas movements in the respiratory system. Methods of studying respiratory mechanics: Bell Spirometer – a floating tank measuring changes in lung volume This is differentiated to find Flow = dV / dt Pneumotachometer – measures small pressure differences in a flow head containing a fine wire mesh. P Pressure differences are proportional to flow rate which is interpreted by PowerLab. This is integrated to find Volume = ʃ F dt This is complicated by differences in volume due to differences in temperature between the air and the body. This is corrected through the BPTS [Body Temperature, Atmospheric Pressure, Saturated with water vapour] factor. Inspiratory Inspiratory reserve Volume – Capacity – primary max gas in Vital capacity Max air breathed after breathing in after normal – max normally expiration expiration after M: 3000ml F: 1900ml max inspiration Total lung capacity – gas in lungs after max inspiration
Tidal Volume – primary measurement 500-600ml at rest Functional Residual Capacity – gas left after normal expiration Expiratory Reserve Volume – primary Max air breathed after breathing out normally M: 1200ml F: 800ml
Residual Volume – primary Gas in lungs after end of max expiration – CANNOT be measured in spirometry M: 1200ml There F:1000ml are also forced parameters which are valuable clinically. FEV1 – Forced Expiratory Volume in One Second – Like FVC but in how much in one second. It can be used for a ratio of FEV1/ FVC for obstructive disorders [Bronchitis, Emphysema, and Asthma]. PIF – Peak Inspiratory Flow – affected by airway resistance PEF – Peak Expiratory Flow – affected by airway resistance FVC – Forced Vital Capacity – Like VC, but measured from a single breath – indicates restrictive disorders [Pulmonary Fibrosis] Method and Results
Familiarise with apparatus with two full expirations and a minute of tidal breathing Note the volume correction to make the measurements of the two full expirations equal.
Lung Volumes and Capacities – measure tidal breathing and IRV and ERV whilst noting the respiratory rate converted to HZ through dividing respiratory rate by 60. Note: Inspiration is followed immediately by expiration, with a pause in between.
Calculate minute volume by multiplies respiratory rate by tidal volume. Calculate IRC by measuring the difference peak of previous tidal volume and peak of IRV. Calculate IC [ IC = IRV + Tidal volume] Calculate ERV by measuring difference between trough of previous tidal volume and ERV. Calculate VC = IRV + ERV + Tidal volume. Use table to find predicted VC [varies with height, age and sex] Predict Residual Volume using RV = predicted VC x 0.25 L Calculate Total Lung Capacity: TLC = VC + RV or ERV + IRV + Tidal + RV Calculate Forced Residual Capacity: FRC = RV + ERV [air remaining after normal expiration]
Pulmonary Function Tests: Breathe normally and then inspire maximally, and expire forcefully and maximally. Repeat 3 times. Peak Inspiratory Flow – read the max positive absolute value. Multiply by 60 to get L/min Peak Expiratory Flow – read the max negative value. Multiply by 60 to get L/min. Forced Vital Capacity – read from top of peak to lowest value. Measure = Litres. FEV1 – Measure from peak to the value on the curve 1 second after. Note: Can also use program to do this.
RESPIRATORY GAS EXCHANGE Air that is expired during respiration is a mixture of dead space gas [atmospheric air] and alveolar gas. In using a respiratory valve, we can take air from beyond the expiratory valve during inspiration, alveolar gas samples can be obtained. These are collected in a Douglas bag. I Inspired Gas E Expired gas A Alveolar gas T Tidal gas D Dead space gas SPTD Standard temperature and pressure Dry BTPS Body temperature and pressure saturated with water vapour ATPS Ambient temperature and pressure saturated with water vapour a arterial blood c capillary blood v venous blood F P C [mM] S V f P Q R time Fractional concentration of dry gas [no water vapour] Pressure of a gas [Partial pressure]. Usually in mmHg / torr [equivalent] Content of a gas per unit volume in liquid. Either in ml (STPD) per 100ml or millimole/litre Saturation. Fractional / percentage saturation of blood with O2 or CO2 Gas volume (L or ml) Respiratory frequency (min) Volume per unit time Mean pressure [line above = average] Volume of blood (L or ml) Volume per unit time Respiratory exchange ratio –CO2 output per unit time divided by O2 uptake per unit
Oxygen Content of a Sample: This is the amount (in Vols STPD percent or millimoles per litre) of molecular oxygen, in solution or combination, that can be released from the sample after destroying the oxygen binding power of haemoglobin and subjecting the sample to a vacuum. It thus includes both oxygen in physical solution and oxygen combined with haemoglobin. Oxygen Capacity of a Sample: This is the amount (in Vols STPD percent) of oxygen which is combined with the haemoglobin in the sample when the haemoglobin is fully saturated. Note it does not include dissolved oxygen. Hence, when a sample is fully saturated, its oxygen content may be higher than its oxygen capacity. Oxygen Saturation of a Sample: This is the ratio of the amount of oxygen combined with the haemoglobin in the sample to the amount which could be combined at full saturation.
It can be expressed as a percentage, say 65%; or as a fraction, say 0.65. Carbon Monoxide Content, Capacity and Saturation: Defined as for oxygen content etc. Carbon Dioxide Content of a sample: This is the amount of CO2 (in Vols STPD per cent or mmoles per litre) that can be released from the sample after treatment with acid, and extraction of the gas under a vacuum. Carbon Dioxide Capacity and Saturation: Carbon dioxide exists in different combined forms in the blood and there is a significant amount of dissolved carbon dioxide. As CO2 tension of a sample is increased, we do not have any clear stage at which CO2 content reaches a plateau and for this reason the term "carbon dioxide capacity" is not used. Thus it is also meaningless to speak of the carbon dioxide saturation of a sample.
Correcting to STPD Note: this applies to gases – water vapour does not obey this law. Hence we take water vapour out of our total pressure first. We know the pressure of water at certain temperatures and pressure and use that to remove it
When ATPS to STPD [note: from vapour], we know that water [23°/766mmHg]
converting between water vapour to no water vapour takes up 21mmHg
The correction factor is between 0.88 and 0.92 for most sea level laboratory conditions. Correcting to BTPS Body temperature is higher than the environment, increasing the volume of the gases which also become saturated with water vapour. Body temperature is 37/310K. Note we subtract water vapour from both pressures since water doesn’t obey the gas laws.
The conversion factor is about 1.09 and falls with rises in temperature of the room [less difference between body temperature and air temperature so the gases expand less]. Bohr Formula Amount of a gas ‘X’ expired is equal to the amount from dead space and the amount from the alveoli. This amount is equal to the volume of the gas ‘X’ multiplied by the fractional concentration of ‘X’. Hence:
But the Volume Expired (VE) is the same as a normal tidal volume (VT). And the fraction of X in the dead space is the same the fraction of X in the inspired gas as the dead space [before an expiration] is filled with air that you just inspired. Hence the equation becomes:
tensions/pressures: And using the respiratory frequency we can get in terms of ventilation of dead space and tota ventilation.
Rearranging for alveolar ventilation: Note: VE - VD is equal to alveolar volume.
But since in air has a concentration and pressure of 0 for CO2. We can rearrange VD / VT. VD = PECO2 - PACO2 VT = PICO2 - PACO2 VD = VT = Hence: Oxygen PECO2 - PACO2 0 - PACO2 and Consumption
The volume of air expired is measurable. The fraction of oxygen in inspired and expired air is also measurable. The volume of air inspired is not directly measurable since air in ≠ air out for oxygen since we don’t produce the same number of molecules of carbon dioxide as we do for molecules of oxygen breathed in. However, Nitrogen is not metabolised in the body so the volume and fraction in is the same as the volume and fraction out.
Hence: Applying the same thing BUT, CO2 in inspired air is 0 Hence: Respiratory exchange ratio: to CO2:
Now the actual practical: Composition of dry air
Method: Breathe normally, then close hole making expired air go into the Douglas Bag. Record time of expiration into the Douglas bag and respiratory rate After 1 minute take a sample of alveolar air by withdrawing air as the person breathes in [the last bit of expiration from previous breath is alveolar air] After 5 minutes, stop the Douglas bag expiration and record time. Mix the bag and take samples of expired air. We know: alveolar air, expired air and inspired [dry] air, as well as total ventilation and tidal volume.
Results PAO2 (mmHg) PACO2 (mmHg) Volume expired per unit time (BTPS) (L/min) Alveolar ventilation per unit time (BTPS) (L/min) How much gas alveolar are producing/min Our Results 120 [higher since forced breathing in experiment] 30 7 [bigger in larger person] 6 (This value is less than the result above (V-dotE) because that includes dead space + alveolar air, whereas this just measures alveolar ventilation) 700mL [larger person] 200mL (60-70mL higher than ideal value because the apparatus we use also uses air) Ideal 100 40 7-8 5-6 Equation used -
VT (BTPS) Tidal volume VD (BTPS) Volume of dead space
Volume of O2 consumed/min Volume of CO2 produced/min R Respiratory exchange ratio
250L/min (not how this is less than the O2 value) 250/300 = 0.8
CONTROL OF RESPIRATION Control of respiration is linked to the blood levels of the respiratory gases carbon dioxide and oxygen. Changes in tensions are stimuli for receptors in the medullary chemoreceptors, and the carotid and aortic bodies. During breath holding, CO2 is produced and O2 is consumed with the difference in the alveoli of PO2 and PCO2 decreasing. The changes in the chemoreceptors eventually force the subject to breathe. Factors influencing the breaking point to breathing include: subject motivation, change in gas volume in the lungs [O2 uptake is greater than CO2 release decreasing lung volume]. The proprioceptive collapsing of the alveoli quicken the reflex to breathe. This is true when breathing 100% air. • To calculate PAO2 and PACO2 o PAX = FAX x (PB-47) o PB = 767 o TA= 22oC = 295 K o FAX = reading off the meter (converted into a fraction)
Task 1 • PAO2 and PACO2 are normally 100 and 40 respectively. • Our experimental results were a bit higher for PAO2 and a bit lower for PACO2 • This is because the subject took in a deep breath, which was a mini-hyperventilation. Hence, there was more O2 and less CO2, and so PAO2 increased while PACO2 decreased. • These values were used as control values, as every experiment began with a deep breath Task 2
• • •
Compared with Task 1, the first sample of Task 2 shows PAO2 ↓and PACO2 ↑ This is because during breath-hold, alveolar oxygen was been used up and carbon dioxide was coming out of blood and into alveolar air After exhalation into the bag, the subject was able to hold their breath for longer. However, note that breathing air out into the bag and breathing the same air back in does not actually change the air composition in the lung. o Hence, hypercapnia and hypoxia hasn’t changed o The reason we can breathe longer is that we give our lung muscles a chance to relax before going back to work (see stimulus three in answer for question 1)
1) Why are you no longer able to hold your breath at the breaking point? The 3 stimuli for breaking point are: 1) ↑CO2 – hypercapnia 2) ↓O2 – hypoxia 3) Proprioceptive inputs from collapsing thorax – Lung volume decreases when we hold our breath. Receptors sense this in the diaphragm and sends input to the respiratory centre. The brain then tells the lungs to breathe. 2) Why could you extend the period of holding after air expiration? Proprioceptive inputs are removed, and the sense of discomfort due to collapsing thorax is relieved. This method works in the same way as breathing out into the bag. 3) Did hyperventilation allow a prolonged breath-hold? Why? Yes. Hyperventilation flushes out CO2, but does not increase O2 to a great degree. Hence, you can tolerate a higher PACO2 as the hypercapnia stimulus is reduced. Also, when you remove the hypercapnic stimulus, chemoreceptors can tolerate a greater degree of hypoxia (i.e. lower PAO2) before you need to take a breath. 4) Did oxygen breathing allow a prolonged breath-hold? Why? Yes, in fact breath-hold was doubled. This is because oxygen breathing reduces the hypoxic stimuli. Also, when you remove the hypoxic stimulus, chemoreceptors can tolerate a greater degree of hypercapnia (i.e. higher PACO2) before you need to take a breath. 5) Why are you warned not to hyperventilate on pure oxygen before starting to hold your breath? If you had unwisely ignored this warning, can you calculate how long you might have been able to hold your breath? Breathing in 100% oxygen means that there is no nitrogen intake. Hyperventilation leads to the blowing off of carbon dioxide and nitrogen. Then, as you hold your breath, reduction in hypercapnia and hypoxia stimuli (due to hypoventilation) means breath-hold will go on for an extended period of time. The only trigger for breathing would be the decrease in lung volume leading to proprioceptive inputs from the collapsing thorax. Hence, the extended breath-hold means that you will hold your breath until the alveoli collapse (because there is no nitrogen to support them and keep them open). You will need resuscitation with ventilator. To calculate: TLC = 5L V02 (with dot i.e. normal resting consumption) = 250mL/min Hence, time = 5000 / 250 = 20 minutes 6) Why do some swimmers hyperventilate before they swim underwater for any distance? To increase breath-hold time. However, this is actually a bad idea, as shown by the following underwater diving scenario: • Hyperventilation causes your partial pressures to become: o PAO2 = 120 o PACO2 = 20 • As you dive, each 10m depth is equivalent to adding 1atm of pressure. Hence, diving 10m down will lead to 2x the pressure. Therefore, the partial pressures also double o PAO2 = 240 o PACO2 = 40 o Therefore, the person has a lot of oxygen, and the carbon dioxide levels will not cause in to break. • The diver stays at 10m depth for a period of time. The partial pressures will become:
o PAO2 = 75 o PACO2 = 50 diver wants to return to surface Diver rises, and pressure halves. o PAO2 = 37.38 SHALLOW WATER BLACKOUT! o PACO2 = 25 Blackouts are why hyperventilating to stay underwater for longer is dangerous.
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue listening from where you left off, or restart the preview.