Surgical Physiology

For MRCS part 3

By Dr. MMM

Surgical Physiology 2

.C.N.S

Surgical Physiology 3

Membranes
What is the main function of the cell membrane? To control the entry and exit of molecules from the cell and so regulate the interacellular environment. Describe the basic structures of a cell membrane? The cell membrane consists of a continous lipid bilayer studded with protein molecules. How does this structure allow control of the movement of molecules into and out of the cell? The lipid bilayer has hydrophilic groups facing outwards while hydrophobic groups face each other across the middle. Most large water soluble molecules, charged molecules and ions cannot cross the lipid barrier. Size, charge and water solubility all decrease the ability of a molecule crossing the fatty membrane. These substances depend on the membrane proteins for their entry and exit from the cell. These patients can act as channels sensitive to voltage or ligand binding or as energy dependent pumps. !at soluble substances li"e oxygen and carbon dioxide can cross easily as can water. What is the overall charge of the outer surface of the cell membrane? #egative. What art of the membrane structure is res onsible for this negative charge? The cell has a $glycocalyx$ formed by membrane carbohydrates, which are negatively charged. These carbohydrates also act as receptor substrates and can bind to carbohydrates on other cells.

!on channels
What is the basic structures of an ion channel? They are proteins, which form tubular structures with a central pore which transverse the cell membrane and can allow communication between the extracellular fliud and the intracellular compartment. "re they sim le ores? #o, they are selectively permeable to specific ions and can be opened and closed. What would be the conse#uences for nerve conduction if they were sim le ores? %f they were open all the time there could be no electrical potential across the cell membrane and cells would be isoelectric with the extracellular environment. The lac" of ion gradient would remove the power source for the action potential to be generated when ion channels open and so nerve conduction would not be possible.

Surgical Physiology & What features of an ion channels ma$e it selective for sodium or otassium ions? This is determined by the pore diameter and the charge within the channels. ' sodium selective channel is highly charged and narrow. %n a charged environment ions dehydrate and the dehydrated #a( ion is smaller than dehydrated )( and so can selectively pass through. The potassium selective channel is less charged so the ions are hydrated, a hydrated )( ion is smaller than hydrated #a( and the pore is the right size to let the hydrated )( through. How can mechanism of channel gating be classified? Please give e%am les. *hannels can be voltage or ligand gating. 'n example of a voltage gated channel is the #a( channel in the membrane of a nerve fibre where the gate is strongly shut when the intracellular charge is negative. %f the cell becomes less negative the gate opens allowing #a( ions to flood in and generate the action potential. 'n example of a ligand gated channel is the acetylcholine receptor at the neuromuscular +unction. 'cetylcholine interacts with the channel leading to a conformational change which opens the central pore to allow #a( ion to flood into the cell.

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&ece tors
What is a rece tor? The specific molecular site to which a pharmacological agent binds and mediates its effect. '% lain how binding to a rece tor can lead to a cellular res onse? ' receptor has two components The binding part which protrudes from the cell membrane. 'n ionophore component which passes through the membrane to the intracellular compartment. The ionophore can be an enzyme or an ion channel. %n the case of an ion channel, binding of a ligand leads to the opening of a gate and influx or efflux of ions as is the case at the neuromuscular +unction when acetylcholine binds. .nzyme lin"ed receptors alter the metabolic activity of the cell often via second messengers. *yclic adenosine monophosphate /'M01 production by adenyl cyclase is mediated by ligand binding followed by 2 protein activation. 0rotein "inase can lead to altered gene expression in the nucleus. %n general, enzyme lin"ed receptors lead to slow, prolonged changes in cell activity and ion channels to rapid, short lived response binding. What is a neurotransmitter? ' chemical which binds to a receptor and leads to an effect on a synapse function in nerve conduction. (ive an e%am le of an e%citatory neurotransmitter and inhibitory neurotransmitter? 'cetylcholine is an excitory neurotransmitter at muscarinic receptors. 2amma amino butyric acid /2'3'1 is the main inhibitory neurotransmitter in the brain. When is mani ulation of the acetylcholine rece tor of interest to the surgeon? 3loc"ing transmission at the neuro muscular +unction by bloc"ing the acetylcholine receptor with a muscle relaxant paralyses the patient. How do atients with myasthenia gravis behave differentially to muscle rela%ants? They are resistant to depolarizing agents li"e suxamethonium but more senstives to non depolarizing agents such as atracurium.

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"ction otentials
What is an action otential? %t is a rapid change in the membrane potential followed by rapid return to the resting membrane potential. %t is due to voltage dependent ion channel proteins. %n the plasma membrane5 the size and shape of action potential differ considerably from one tissue to another. What tissue have an action otential? The tissues which have an action potential include neurons and all types of muscle cell. Draw and describe a neuronal action otential ? There are three phases 6. 7esting phase- negative charge maintained by #a(8)(8 'T0ase. 2. 9epolarization phase- after a threshold is reached #a( channels open and the cell becomes more positively charged and actually overshoots beyond neutral. 3. 7epolarisation phase- #a( channels close and )( channels open leading to the cell returning to a negative state. ' gain there is overshoot and the cell become hyperpolarized.

What determines the conduction velocity of an action otential? Two factors determine action potential velocity6. 9iameter of the axon, large cells a faster conduction velocity 2. Mylination increases velocity because the action potential is propagated from one node of 7anvier to the next because the intervening membrane is non excitable and cannot fire an action potential. This +umping of potential from node to node is termed salutatory conduction. /' node of 7anvier is the gap between two ad+acent schwann cells1. What affects the magnitude of the action otential along the length of a neuron? The action potential is an all or nothing phenomenon. %t has the same magnitude along the entire length of the neuron. %nformation is therefore coded in terms of fre:uency of impulses.

Surgical Physiology ; What do the terms )threshold)* all or none and summation mean with reference to the action otential ? The cell membrane has a resting potential across it, with the inside usually ;< m= negative compared to the outside. 'pplication of a current will decrease this difference depolarization up to a point "nown as the $threshold$ after which an action potential is generated by reversing the membrane polarity, i.e. the inside now becomes positive with regard to the outside. This generates an action potential which is then propagated, without decrement, down the entire length of the fibre. 9epolarization occurs because opening of #a( into the cell changing its polarity. 'lmost as soon as the sodium gate is opened, it begins to close and a potassium gate opens to allow repolarization. The all or none phenomenon indicates that a larger depolarizing current does not create a larger action potential5 similarly, once initiated an action potential will spread across the whole membrane. %f the current is big enough to create an action potential in one small corner of the membrane, it will depolarize the whole membrane. %f the current is big enough to create an action potential in one small corner of the membrane, it will depolarize the whole membrane, if it is not sufficient, none of the membrane depolarizes, i.e. all or none. Summation refers to a phenomenon of muscle fibres whereby the addition of individual muscle twitches creates a stronger and more concerted twitch. %t occurs by firstly, increasing the number of motor units contracting stimultaneously and secondly by increasing the fre:uency with which they contract. What is the difference between the action otential of a neuron and cardiac muscle? *ardiac muscle cells have an additional voltage channel which creates the characteristic cardiac action potential. This is the slow *a (2 channel. This channel opens and the muscle is depolarized. %t maintains the depolarized state so creating a plateau phase. 9uring this phase, contacting is stimulated by release of more *a(( from the sacroplasmic reticulum. The cell is also refractory to further stimulus during this phase and therefore tetany is not possible.

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Cardiac action otential

Can you describe the hases of the cardiac action otential ? 6. The resting potential of ventricular muscle cells is ?< m=. 2. The action potential commences when the membrane of the ventricular muscle is brought to a threshold of a round ;, m= by excitation from ad+acent muscle cells. 3. @nce the threshold has been reached, the action potential proceeds in three phases 0hase6 /rapid depolarization1- at the threshold, =oltage regulated fast sodium channels open and. The membrane rapidly becomes permeable to sodium resulting in a rapid depolarization of the sarcolemma /duration 3 , ms1. 0hase2 /plateau phase1- as the membrane potential approaches (3< m=, The voltage regulated sodium channels close. 't the same time, The slow voltage regulated calcium channels open. 3ecause calcium channels are slow channels, they remain open for lomger /6;, ms1 and, as result, the membrane potential remains near < m= for an extended period of time "nown as the $plateu phase$. 0hase3 /repolarization1- as the plateau continues, The slow calcium channels begins to close and The slow potassium channels begin to open. The result is a period of rapid repolarization that restores the resting potential &. 7efractory period- following an action potential, the muscle will not respond to a second stimulus. 9uring the absolute refractory period the muscle cannot respond at all to any stimulus /duration 2<< ms1. This is followed by a relative refractory period, during which the muscle will only respond to a stimulus that is stronger than normal /duration ,< ms1. What is the main difference between the cardiac action otential and the s$eletal muscle action otential? *ardiac muscle demonstrates a plateau phase but s"eletal muscle does not %n s"eletal muscle cell, rapid depolarization is immediately followed by a period of rapid repolrization. Draw and describe a ty ical cardiac action otential? ' typical cardiac action potential is "nown in figure . there are four phases to the cardiac action potential6. depolarization and overshoot due to #a( channels opening 2. repolarization as #a( channels shut. 3. plateau phase as *a(2 enter. &. repolarization as )(2 effluxes ,. slow upwards drift due to #a( entry. *ell is refractory during this period.

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Draw and describe the action otential in the sino+atrial node. There are three phases to the nodal action potential6. Apwards drift due to lea" of #a( ions into the cell. 2. Bhen threshold of &< m= reached rapid entry of *a(( ions occurs. 3. 7epolarization due to )( efflux.

Do you $now of any drugs that act on the cardiac action otential? 'nti arrythmic drugs act by altering the flux of ions across the membranes of excitable cells in the heart. The primary mechanisms of action correspond to the mechanisms used in the $=aughan Billiams$ classification system *lass % drugs act via inhibition of sodium channels %'- :uinnidine and procainamide /prolong repolarization1. %3- lidocine and phenytoin /shorten repolarization1. %*- flecainide and propafenone /little effect on repolirization1. *lass %% drugs bloc" 3 adrenergic receptors in the heart 0ropanol and esmolol. *lass %%% drugs inhibit potassium channels- sotalol, amiodarone and bretylium. *lass %= drugs inhibit calcium channels =erapamil and diltiazem. o 'drenaline- this increases the rate of sodium lea", decrease the time between action potentials and hence increases heart rate. o 'cetylcholine- this decreases the rate of sodium lea" which has the opposite effect to adrenaline, and hence slows down the heart rate.

Surgical Physiology 6< o *alcium channel bloc"ers- these shorten the plateau phase and hence decrease the force of contraction of cardiac muscle.

Nerve action otential

Can you draw and label a nerve action otential?

Can you describe the se#uence of events that occur during a nerve action Potential? The resting membrane potential in a neurone is approximately ;< m= /due to the different concentrations of sodium, potassium is mostly intracellular and potassium is mostly extracellular1. ' stimulus activates the fast sodium channels, causing rapid influx of sodium ions into the cell and subse:uent depolarization of the membrane potential. 9epolarization overshoots the zero to (3<m=, which inactivates the sodium channels and therefore stops further influx of sodium ions. =oltage dependent potassium channels open, causing influx of potassium ions and repolarization bac" to the resting membrane potential of ;< m=. Bhen sodium channels are inactivated, the cell is refractory to any further stimulius The #a(8)( 'T0ase pump plays an important role in maintaining intra and extracellular concentrations of sodium and potassium ions. What influences the s eed of neural conduction? 9iameter of the nerve- speed increases with increasing diameter. Myelination 0ropagation of the action potential between the nodes of 7anvier /salutatory conduction1 The node of 7anvier is an unmyelinated gap between ad+acent Schwann cells.

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Muscle
What are the different ty es of muscle found in the body? S"eletal /striated1 Cong, cylindrical, non branching fibres. 0arallel or obli:ue. Smooth /non striated1 #arrow, parallel, spindle shaped cells. Slow but sustained contraction. 'utonomic nerves5 gap +unctions. *ardiac /striated1 Cess powerful than s"eletal muscle but more prone to fatigue. What is the structure of s$eletal muscle and how does it contact? .pimysium /around muscle bundles1. 0erimysium ,around muscle fascicles-. .ndomysium / around individuals myofibrils1. Sarcomeres contain actin/%1 and mysosin /D15 actin is attached to E lines and myosin is attached to M lines. 'cetylcholine is released at the synapse when the depolarization impulse arrives at the neuromuscular +unction. This leads to a cascade of events which results in depolarization of the sarcoplasmic reticulum and release of calcium. The calcium binds to troponin on the thin filaments, changing the position of tropomysin on the thin filaments. This expose actin and leads to the formation of cross bridge. What is the difference between the muscles of marathon runners and the muscles of s rinters? Marathon runners have predominately slow twitch fibres /red1 'erobic more mitochondria, enzymes and triglyceride. Cow concentration of glycolytic enzymes /'T0ase1 and glycogen. 3est remembered by the expression $slow red ox$. Sprinters have predomintaley fast twitch fibres /white1 Carger, stronger motor units. 'T0 creatine phosphate system.

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Peri heral nerves

What are the different layers within a eri heral nerve? .xternal epineurium surrounding internal epineurium, surrounding fascicular groups /consisting of endoneuruium1, surrounding nerve fibres /consisting of schwann cell8myelin sheath1 surrounding the axon. What hysiological changes occur in the nerve following in.ury? 0roximal stump undergoes wallerian degeneration to the proximal node of 7anvier. *ell body increases 7#' synthesis. Multiple axonal sprouts growth cones with filipodia. 9istal pump undergoes Ballerian degeneration /leaving empty neural tubes, schwann cells and basal lamina1. 'xonal sprouts reaching distal schwann cells continue to grow /6 mm8day1, others degenerate. How do you classify nerve in.uries? #eurapraxia 7eversible conduction bloc". Cocal ischaemia and selective demyelination of axon sheath. 2ood prognosis. 'xontmesis 9isruption of axon and myelin sheath, leaving epineurium intact. !air prognosis. #euronotmesis *omplete nerve division with disruption of the endoneurium. 0oor prognosis.

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Muscle contraction
What is the motor unit? The motor unit is the basic element of motor control. %t contains of an F motor neuron, its motor axon, and all the s"eletal muscle fibres that it innervates. The number of muscle fibres supplied by a single F motor neuron is determined by the type of movement that the muscle performs, so muscles performing coarse movements /such as :uadriceps femoris1 will have a large number, and muscles performing fine movement such as extraocular muscles1 will have a small number. What is the structure and function of muscle stretch rece tors? Muscle stretch receptors /muscle spindles and golgi tendon organs1 are specified sensory receptors that discharge when the muscle is stretched. They are vital for motor control and proprioception. The most complex is the muscle spindle, which is composed of two types of fibres %ntra fusal muscle fibres- are richly innervated and enclosed within a connective tissue capsule. They contain two types of fibre- nuclear bag and nuclear chain fibres. '. The nuclear bag fibres are innervated by large, myelinated group%a fibre. 3. The nuclear chain fibres are innervated by medium sized, myelinated group %% fibres. 2amma motor neurons innervated the intra fusal muscle fibres to regulate the sensitivity of the muscle spindles to stretch. .xtra fusal fibres- lie between the regular muscle fibres. The contractile unit of a striated muscle cell is the sarcomere. Bithin one striated muscle cell are large numbers of sarcomers lin"ed end to end by E dis"s There are two types of sliding muscle filaments, thic" and thin. Thic" filaments are composed of myosin, consisting of a head pro+ecting from a tail. The head forms the crossbridge to the thin filaments. The thin filaments are composed of actin, tropomyosin and troponin. What is the structure of striated muscle? The contractile unit of a striated muscle is the sarcomere. Bithin one striated muscle cell are large numbers of sacromers lin"ed end to end by E dis"s. There are two types of sliding muscle filaments, thic" and thin. What is the mechanism of e%citation+contraction cou ling? Muscle cells contract by the sliding filamenrt cross bridge mechanism. There are four steps to this cross bridge mechanism6. The 'T0 bound to myosin is hydrolyzed to form a myosin '90 phosphate complex with high energy enabling binding to the actin of thin filament.

Surgical Physiology 6& 2. The '90 and phosphate are released after myosin binds to actin. This causes a conformational change in the myosin head that results in sliding of the thin fibres towards the centre of the sacromer /i.e. contraction1. 3. The actin myosin complex binds 'T0 to release the cross bridge. &. The myosin '90 0 complex is formed to complete the cycle. What is the im ortant difference between s$eletal and cardiac e%citation+ contraction cou ling? The important difference is that is that no tetany in cardiac muscle because the action potential is longer than the contractile response.

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Neuromuscular .unction
What do you understand about the neuromuscular .unction? The neuromuscular +unction is the synapse between the presynaptic motor neurone and the postsynaptic muscle membrane. The axon divides into terminal buttons that invaginate into the muscle fibre. The synaptic cleft is ,< ;< nm wide and filled with extracellular fluid. The orifices /synaptic cleft1 lie opposite the release points for acetylcholine and contain high concentrations of acetylcholinestrase. The action potential concluded along the motor nerve causes depolarization and an influx of calcium. The influx of calcium stimulates the release of acetylcholine from storage vesicles into the synapse5 acetylcholine binds to nicotinic receptors on the motor end plate. Stimulation of the acetylcholine receptors results in opening of sodium channels /and some potassium channels1, and influx of sodium and potassium into the cell results in depolarization. 9epolarization is called the end plate potential if the end plate potential is sufficiently large, an action potential is produced and muscle contraction occurs. 'cetylcholine is hydrolyzed by acetylcholinesterase and the product choline is ta"en bac" up through the presynaptic membrane to re produce acetylcholine. Do you $now any to%ins that bloc$ neuromuscular transmission? 3otulinum toxin 3otulinum toxin is an exotoxin produced by clostridium botulinum, a 2ram positive spore forming bacillus. The toxin is internalized in the presynaptic membrane and binds to the veicle membrane. This prevents the release of the vesicle and therefore acetylcholine at the neuromuscular +unction. Do you $now any anaesthetic agents that bloc$ neuromuscular transmission? 9epolarizing muscle relaxant 0roduce what appears to be a presistant depolarization of the neuromuscular +unction. *ause depolarization by mimic"ing the effect of acetylcholine but without being rapidly hydrolysed by acetylcholineesterase. .xamples include suxamethonium and decamethonium. #on deplolarizing muscle relaxant *omplete with acetylcholine for nicotine receptor binding sites. The bloc"ade is competitive, so muscle paralysis occurs gradually. .xamples include tubocurium and vecuronium.

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What is the molecular basis of myasthenia gravis and how is it diagnosed? 'nti body mediated destructions of acetylcholine receptors. This results in wea"ness and faiguability of s"eletal muscle /e.g. fatigueable ptosis of eyelid clinically on prolonged upward gaze1. .drophonium /Tensilon1 is a short acting acetylcholinestrase inhibitor, and its adminstration briefly reverses the wea"ness, by increasing the amount of available acetylcholine in the neuromuscular +unction. Thiss is used as a diagnostic tool. T+ymectomy can be curative.

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S inal cord and refle%es

Describe in general terms the internal organi/ation of the s inal cord The internal architecture of the spinal cord consists of grey and white matter'. The grey matter forming proportionally more of the content at cervical and lumbar enlargements. %t is arranged in a butterfly shape centrally and is organized as ten numbered laminate each side Camina % lying posteriorly. The posterior laminaea % =%, receive the cutanous and visceral primary affrent fibres. Caminae =%%, =%%% and G lie centrally and not receive peripheral fibres. Camina %G occipies the anterior horn and contains the F and H motor neurons. 3. The white matter contains the ascending and descending long tract. The descending, corticospinal, vestibulospinal and reticulospinal tracts lie in the lateral white fibres. The corticpspinal tract is the principal descending motor tract and is also "nown as the pyramidal tract, thus The other two ascending tracts constitute the extrapyramidal networ" and are responsible for controlling posterior columns, and the anteriorly situated spinoreticular and spinothalmic tracts.

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Where do motor and sensory athways decussate? The descending motor pathways of the corticospinal tract decussate as they exit the medulla and so travel down the cord on the $ the opposite side$. 'scending spinothalamic and spinoreticular tracts cross obli:uely in the cord before ascending. The obli:uity increases the more cranial the segment. What would ha en if you hemisected the cord? Demisection of the cord gives rise to the well described entity of 3rown Se:uard syndrome %psilateral spastic wea"ness due to division of corticospinal tracts, and dorsal column division gives loss of point position sense and vibration sensation. There is a contralateral loss of pain and temperature sensation due to division of the crossed spinothalamic tract, this loss is noted between 2 and 4 dermatomes lower than the level of the lesion owing to the obli:uity of the crossing fibres. What is a refle%? %t is defined as a stereotypical response to a sensory input. %t must involve as a minimum, a sensor, an afferent neuron and an efferent neuron. 'll reflexes except the stretch reflex also include interneurons. Describe the athway of the sim le refle%? The simplest reflex of all is the stretch reflex, which is monosynaptic. Stri"ing the patellar tendon with a tendon hammer activates muscle spindle endings that are $stretched$. The stimulus travels by 6F afferent fibres into the posterior horn of the spinal cord, where they synapse with H motor neurons anteriorly that travel to the neuromuscular +unction in the :uadriceps which contracts. What is a crossed refle%? 3efore describing the crossed extensor reflex, it is necessary to describe the flexor or withdrawal reflex. Standing on a drawing pin with an unshod right foot sends pain stimuli into the dorsal horn via nociceptive pathways. Dere, the stimulus passes into the interneurons, which eventually sends the stimulus to the motor neurons of both the hip, causing iliopsoas flexion, and "nee, resulting in hamstring flexion to withdraw the foot. 't the same time, inhibitory motor stimuli are sent to the opposing muscle group to allow the flexion to occur unhindred. This is the withdrawal reflex. %n addition, interneurons pass to the collateral cord at the same segmental levels to stimulate the motor neurons of the left leg to cause extension, thus allowing the right foot to come off the ground, and the drawing pin, whilst the left leg supports the body weight.

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0hermoregulation
How are changes in body tem erature detected? The hypothalamus and spinal cord have thermoreceptors for core temperature. S"in has receptors for peripheral temperature. 'll signal are sent to the hypothalamus. How do we regulate our body tem erature? *ore body temperature is normally maintained fairly rigidly within fine limits. The central control of thermoregulation is the hypothalamic thermostat, which not only contains its own thermosensory cells that are ex:uisitely sensitive to temperature change, but also receives the input from s"in temperature receptors. There are many more cold receptors than warm ones, hence we recognize cooling of our environment much more easily. There are 3 principal mechanisms for heat loss as follows6. =asodilatation of the cutaneous venous plexuses, which are tonically constricted under sympathetic control. !ull vasodilatation compared with full constriction has an eightfold increase in heat conductance. 2. Sweating allows a significant increase in the amount of evaporative losses. %nitially, in a hot environment, this is maximal at about ;<< ml of sweat per day with a heavy salt loss but, after & wee"s of acclimatization, this system will produce up to 2<<< ml of low sodium sweat, increasing the efficiency of the evaporative loss system by tenfold. Sweating is under the control of sympathetic cholinergic receptors, although circulating catecholamines can also influence sweating. 3. The final mechanism of heat production and mechanisms such as shivering and chemical thermogenesis are inhibited There are 3 mechanisms of heat production6. S"in vasoconstriction- reduces radiant heat loss from the s"in. 0ilorection- although somewhat rudimentary in humans, is an attempt to create a larger air poc"et around the body, and decrease conductive and convective losses. Shivering- under direct hypothalamic control, which increases muscle production of heat. 2. *hemical thermogenesis results in uncoupling of oxidative phosphorylation in the cells regulated by catecholamines to produce an increased rate of cellular metabolism. 3rown fat is extremely important in this mechanism owing to the large number of mitochondria in its cells. 3. The final mechanism is a general up regulation of metabolism by the increased secretion of the thyroid gland, again mediated by the hypothalamus,

Surgical Physiology 2< which increases secretion of thyrophin releasing hormone and is perhaps another form of the chemical thermogenesis. ' side from these inherent physiological systems for controlling body temperature humans posses an even more potent mechanism behavioral control. ' human adult can increases its temperature by putting on warm clothes, getting out of the cold environment, drin"ing hot drin"s and turning the central heating up. The converse is obviously true for the human in the warm environment. Can you describe the body1s res onse to hy othermia? The response is mediated via the autonomic and somatic nervous systemsSomatic response %ncreased voluntary muscle activity and curling up. Shevering /can increase basal metabolic rate /3M71 fourfold. 'utonomic response =asoconstriction /directly, via s"in thermoreceptors1. Dair stands up /horripilation1. Sweat glands inhibited. t3rown fat activated /in infants1. The thermoregulatory centre is situated in the pre optic region and the anterior hypothalamus The body has central and peripheral receptors *entral receptors monitor core temperature. whereas The peripheral receptors consist of warm and cold receptors whose discharge increases with increasing and falling temperature repectively. The other mechanisms involved in the control and maintaince of temperature, include *ontrol of s"in blood flow. =enous circulation. Shivering and sweating. How does thermoregulation differ in 's$imos and children ? 3rown fat plays an important role in chemical thermogenesis. Anfortunately, adult humans posses almost no brown fat5 only infants do, in small patches between the scapulae. %n children chemical thermogenesis can increase heat production by 6<< I, which may be in compensation for the inability of babies to shiver. .s"imos have very high basal metabolic rates mediated by thyroid gland in an attempt to maintain ade:uate heat production. *hildren lac" the behavioral control to allow them to modify their environment as circumstances dictate. Which anatomical sites are commonly used for measuring tem erature and are there variations according to site? The most commonly used sites and their normal readings are @ral /3; o*1. Tympanic /3;., o*1. 'xillray /3, 34 o*1. 'nd these variations should be borne in mind when examining patient charts.

Surgical Physiology 26 More accurate readings of core temperature /3; o*1 can be obtained by rectal and oesophageal measurements5 an oesophageal probe is often used intraoperatively.

How do you mange a hy othermic atient? *hec" airway, give oxygen and ventilate if needed. Set up an intravenous infusion of warm fluids and send off blood. Monitor the patient 'ccurate per rectal temperature probe .*2 + waves and arrhythmias Arinary catheter 'ctively rewarm at half a degree *elsius per hour unless rapidly cooled. Thermal blan"et, 3air hugger, infusion of warm fluids into the peritoneal cavity of bladder, haemodialysis, cardiopulmonary bypass. %nvestigate the reason for the hypothermia and deal with this /including home or social situation if applicable1. What is sweat? Sweat is a hypotonic solution containing approximately 4< mmol of sodium chloride. What controls its roduction ? %ts secretion is stimulated by the sympathetic system. How much sweat can one roduce? Ap to 6., C of sweat may be secreted in one hour, but this may be rise to &C per hour in a heat acclimatized sub+ect. What hysiological changes occur following acclimation in a hot climate? !ollowing acclimation there is %ncreased rate of sweating. 9ecreased core temperature. 9ecreased heart rate. .xpansion of plasma volume. 9ecreased sodium content of sweat. What hormonal changes are seen following changes in tem erature? %n the cold, the adrenal medulla is stimulated so releasing catecholamines into the circulation. There is also inhibition of anti diuretic hormone, /#3. Thyroid function does not change1. !s human body tem erature constant?

Surgical Physiology 22 The temperature of the resting body varies throughout the day, exhibiting a diurnal or circadin rhythm. %t is lowest at night often falling to 34 o* and rises by up to 6., o* during the day. Bomen have a monthly rhythm of temperature and the basal temperature rises by a bout <., o* at ovulation and remains at this high level until the onset of the next menstruation.

Pyre%ia
What conditions can cause a rise in body tem erature? %nfection /swinging pyrexias from abscesses1, eg subpherenic abscess. %nflammation / radiotherapy, chemotherapy, thrombombolism, post surgical1. Malignancy. 9rug reactions. Menstrual cycle. Malignant hyperplasia. How is yre%ia mediated? *irculating pyrogens reset the thermostatic mechanism in the hypothalamus .ndogenous pyrogens /macrophage activate and release interleu"in 6, 4 promoting the production of endogenous pyrogenic proteins from liver, brain and other organs1 or .xogenous pyrogens /eg bacterial debris1. What is malignant hy erthermia and how is it treated? ' genetic muscle disorder of muscle, presenting at the time of operation. 'ffects 6 in 6,.<<< paediatric patients and 6 in &<.<<< adult patients. *an have either autosomal dominant or autosomal recessive inheritance /,<I have a mutation of the calcium release channel gene on chromosome 6?1. 'cute onset of s"eletal muscle rigidity, metabolic, acidosis and malignant hyperpyrexia1. Triggered by halogen containing anaesthetic agents. %mmediate treatment with dantrolene prevents tissue damage and death.

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Pain
How ain sensed and tranmitted? 0ain is sensed free nerve endings. %n the s"in, they are widespread and densely pac"ed5 in most internal tissues, however, they are more widely dispersed. They react to different types of painful stimuli thermal, mechanical or chemical and there is often much overlap between receptors. %nvolved chemical mediators include brady"inin, serotonin, prostaglandins, histamine, potassium and acetylcholine. %t should be noted that the body recognize 2 different types pain acute and slow pain. 'cute pain is that pain which begins within <.6 second of the stimulus and is typified by a needle puncture of the s"in. %t is transmitted ' J pain fibres, which are small and transmit at between 4 and 3< m8s. Slow pain begins a second or so after application of the stimulus, but continues to increase over seconds and minutes. %t is typified by a throbbing pain and is transmitted in larger diameter * fibres at speed of <., 2.< m8s. .ach type of pain fibre ends in different parts of the posterior horn grey matter before mostly crossing over and ascending in the anterolateral sensory pathway to the brainstem reticular formation before further ascending into the thalamus and higher cortical areas for processing and integration. 2y what mechanisms can we modify the ain res onse? Stimulation of peripheral tactile receptors, perhaps by rubbing the s"in, transmits sensory input in large sensory fibres and depresses the transmition of pain signals from the locality5 it is this mechanism that is invo"ed when footballers have linament rubbed on in+uries and is probably the basis for acupuncture. %n a similar fashion, T.#S /transcutaneous electrical nerve stimulation1 has much the same effect. The body has an intrinsic analgesia system that allows damping down of pain signals direct stimulation of these areas5 the peria:ueductal grey area of the mesencephalon, raphe nucleus magnus and part of the dorsal horn of spinal cord will bloc" pain transmission. %mplicated in this pathway are arises of optiate cord substances which are naturally secreted and loosely grouped as endorphins and encephalins.

Surgical Physiology 2& Bhen these are in+ected experimentally into the peria:ueductal grey area, they produce profound analgesia. What is the ain relief ladder? The pain relif ladder is a stepwise approach to controlling pain /BD@1. 'dditional drugs are added until pain is fully controlled. The first step of the ladder uses non opioid drugs, such as paracetamol or non steroidal anti inflammatory drugs/#S'%9s1. %f this is insufficient to control the pain, then wea" opioid drugs, such as codeine are added. %n the final step of the ladder, strong opioid drugs are used such as morphine. What other drugs can be used in con.unction with the ain relief ladder? 'nti emetics to ease nausa and vomiting particularly with opioid drugs. 'nxiolytics such as diazepam. #eurological pain use drugs such as carbazepine, amitriptyline or gabapenitin. Steroids such as prednisolone or dexamethasone, increase the efficacy of analgesia especially for terminally ill patient. What are the goals of treatment in the terminally ill atient? The aim of terminal care is to provide appropriate relief and support from physical and psychological discomfort when cure is not possible. The important areas are to 0rovide the patient with as much control over their symptoms as possible. )eep the patient comfortable. Delp the patient, their families and careers organize their lives and deal with issues and concerns. 0repare them for death. How do local anaethetics wor$? 'll local anaesthetic are esters or amides of benzoic acid and are membrane stablizers. They plug the membrane sodium channels, prohibiting generation of an action potential and stopping transmission of sensory signals. This is reversible. 's they are non specific membrane stablizers, they will also stabilize other excitable tissues, such as myocardium, if inadvertently in+ected intravenously. What is the safe dose of lignocaine and bu ivacaine? Maximum dosage is designed to ta"e account of inadvertent intravascular in+ection5 thus in theory a patient can have an intravenous in+ection of up to the maximum safe dose of local anaesthetic without side effects. 's these anaethetics diffuse into the surrounding tissue and are then gradually absorbed, and are, in general, vasodialatory, addition of a vasoconstrictor, such as adrenaline, will slow down the rate of diffusion and conse:uently increase the safe maximum dose. !or lignocaine, the safe dose is 3 mg8"g body weight increasing to ; mg8"g with the addition of 6-2<<<<< adrenaline. <., I lignocaine contains , mg8ml of lignocaine.

Surgical Physiology 2, 6 I contains 6< mg8ml, and 2 percent contains 2< mg8 ml. 3upivacaine has a maximum dose of 2 mg8"g or 2., mg8"g with adrenaline.

What ha ens in overdose and why is the described thera eutic range for bu ivacaine much less than for lignocaine? %n systemic toxicity, all excitable tissues become membrane stabilized. The earliest features are 0arasthesia around the nouth and on the tongue. followed by Cight headedness, drowsiness and anxiety. Tinnitus is not uncommon. %f untreated and serum concentration continue to rise Coss of consciounsness. *onvulsions supervene. .ither as a conse:uence of this or due to a direct myocardial effect cardiovalcular collapse and cardiac arrest may follow. 3upivacaine has a tendency to be more cardiotoxic than other local anaesthetics and deosnot have the warning neurological signs before cardiovascular collapse occurs. 'dditionally, the myocardial depression tends to be more resistant to treatment compared to that initiated by lignocaine.

Surgical Physiology 24

Micturition
Can you briefly describe the structure of the bladder? The bladder may be anatomically described in two parts the trigone and the fundus. o The trigone is a relatively fixed triangular base of the bladder nec" at the internal urethral meatus. @ne of the ureters enters the bladder at the upper to angles. %t is supported by stout fibro muscular ligaments which extend from the inferior aspect of the pubic bones in the region of the bladder nec". There are pubo prostatic ligaments in the male and pubourethral ligaments in the female which aid fixation of the trigone and maintain the osition of the bladder as the fundus expands and contracts. o The fundus of the bladder consists of 3 layers, an outer adventitial, a middle muscular and an inner mucosal layer. The adventitial layer is mainly composed of loose connective tissue. The bladder mucosa is of the transitional type of epithelium. The smooth muscle of the bladder, called the destrusor and is the principle component of the bladder wall. Can you briefly describe the initiation and control of voiding? @nce the threshold of filling has been reached in the bladder, there is increased afferent activity which reaches conscious level and one becomes aware that the bladder is filling. The spinal cord integrates this afferent information from the bladder and also receives afferent inputs from the pelvic, hypogastric and lumbar nerves which run to the brain stem. The centres responsible for the co ordination of micturition lie in the brain stem, impulses that facilitate reflex are throught to originate in the pontine micturtion centre. There is a complex series of reflexes which involve many areas of the brain with inputs to the brain stem micturition centre. There are ma+or descending pathways that led from the brain stem and converge on the sacral micturition centre, which is a group of cells lying in the grey matter /@nufKs

Surgical Physiology 2; nucleus1 in the ventral horn of the sacral spinal cord/S21. These cell bodies are the motor neurons which supply the external uretheral sphincter. The cerebral cortex is important in the control of micturtion having an overall inhibitory effect on the desrusor muscle. What is the innervation of the detrusor muscle? The detrusor muscle receives 0arasympathetic innervation via the pelvic nerves /S2 S&1 and is responsible for bladder contraction. Sympathetic innervation via the hypogastric nerves T6< C2 which produces destrusor relaxtion. How does the bladder store urine? The bladder is able to store urine because it possesses intrinsic tone and exhibits receptive relaxation, i.e. the vesical lumen can expand without a concomitant rise in intra vesical pressure. These viscoelastic properties of the bladder and intrinsic ability of muscle to retain a constant tension over a wide range of stretch allow the bladder to store urine. The other ma+or factor controlling bladder storage is neural inhibitory control.

Surgical Physiology 2>

Cerebros inal fluid

Discuss the formation of cerebros inal fliud? *erebrospinal fliud is mainly produced by the choroid plexuses, which line the third, fourth and lateral ventricles with some being generated from the other cerebral capillaries. 'lthough the total volume of *S! is only 63< ml or so, about ,<< ml per day is produced, reflecting a constant circulation and resorption of fliud. %t can exchange substances with the extracellular fliud, but this is regulated by the tight +unctions of blood brain barrier5 the overall composition of *S! is determined by the secretory role of the choroids plexus. Describe the athways by which CS3 flows and is resorbed? The *S! flows in a caudal direction from the lateral ventricles into the third ventricle via the interventricular foramen of Monro, and then

Surgical Physiology 2?

through the Sylvian a:ueduct of the midbrain into the fourth ventricle from here, *S! then reaches the subrachnoid space via the foramina of Cusch"a and Magendie, passing into the pontine cistern and cerebromedullary cistern, respectively. @nce within the subrachnoid space, it circulates around the surface of the brain and spinal cord before being resorbed into the venous circulation by the arachnoid villi. These herniate through the arachnoid mater and lie within the ma+or venous sinuses, especially the superior sagittal sinus, and thus lie in the subdural space. @ver time, the discrete arachnoid villi coalesce into clumps "nown as arachnoid granulation.

What are the contents of the CS3? #ormal *S! is crystal clear and contains Bater. 0rotein- <.6, <.&, g8l. 2lucose- <.&, <.; g8l. Small numbers of white cells /leucocytes, neutrophils and monocytes1 L , white cells8mm3. What are the functions of the CS3? 6. %t acts as a shoc" absorber for the brain. 2. %t reduces the effective weight of the brain. %t provides a route for excretion of waste products from the brain. 3. %t delivers glucose to the brain, M is important in its homeostasis. What are the abnormalities of the CS3?

Surgical Physiology 3< %n meningitis*S! samples are turbid in bacterial meningitis. The *S! contains several neutrophil polymorphs and depleted glucose levels. %n subarachnoid DgeThere is xanthochromia /*S! loo"s yellow when spun down in the lab1. What is hydroce halus? How is it classified and how is it caused? Dydrocephalus is defined as an increase in the volume of *S! within the cerebral ventricles. %t is usually although not always, caused by impaired absorption rather than excessive secretion. %t may be classified as an obstructive or communicating hydrocephalus, depending on the site of absorption to flow%. The obstructive type- there is a bloc"age to *S! flow within the ventricular system itself. %%. The communication type- whereby the bloc"age is outside the ventricular system. Dydrocephalus may also be described as congenital or ac:uired.

Table- causes of hydrocephalus 0y es Pathology ':uired o ':ueductal stenosis obstructive o Mass effect8 compression

Cause %nfection. Daemorrahge. Tentorial herniation. Tumors. 'bscess. 2ranulomata. %ntraventricular haematom. 'rachnoid colloid cyst. *hiari %% malformation 9andy wal"er syndrome atresia of %=th ventricle oulet foramina ':ueductal stenosis

o @bstructing lesion *ongenital obstructive o Structural anomalities

Surgical Physiology 36 *ommunicating o Ceptomeningeal thic"ening o %ncreased *S! production o Dypersensitivity of *S!. %nfection Daemorrhage carcinomatous depositis *horoid plexus papllimoa

How would you obtain a sam le of CS3 for analysis? 3y performing a lumbar puncture. The patients is placed on left side with "nee drawn up and the nec" flexed. The preferred level is at C3,C&. This level is easily identified as being level with the iliac crests. %t can be chec"ed by counting up from the lumosacral +unction, and is mar"ed. %t is essential that lumber puncture is a sertile procedure. The s"in is prepared with antiseptic solution. Dand scrubbing, mas"ing and gowning are as for any other sterile procedure. Ap to , ml of 6 I lignocaine are in+ected into the s"in and paravertebral muscles as local anaesthetic. ' spinal needle is advanced forward, aiming for the previously identified vertebral space. ' $give$ is felt as the needle pierces the tough ligamentum flavum and then passes through dura and arachnoid layers to enter the spinal canal. The stylet is withdrawn from the needle and the *S! specimen/s1 collected, noting its colour and turbidity. The needle can now be connected to a manometer, if re:uired to measure the pressure within the cerebrospinal system.

The blood brain barrier%t selectively controls the entry of substances into the extracellular fluid of the *#S and the rate of their entry. This limits access of toxins but also of immune mechanisms. %t is located in the smallest capillaries supplying the brain and consists of tight +unctions and transport mechanisms. !at soluble drugs /e.g. diamorphine1 cross :uic"ely, andd glucose and anaesthetic agents can also cross. Dydrogen ions donKt usually cross and this has implications for control of respiration and acid base balance. The blood brain barrier is absent in a number of areas6. Median eminence of the hypothalamus- where hypothalamic neurons release hormones that act on the anterior pituitary into the portal system of capillaries.

Surgical Physiology 32 2. 0osterior pituitary- where '9D and oxytocin secreting neurons secrete directly into the blood. 3. *ircumventricular organs- ad+acent to the 3rd M &th ventricles. This areas is ad+acent to the chemotrigger zone. The blood brain barrier may be compromised in severly raised %*0 and is often disrupted in the context of aggressive intra axial tumours.

Surgical Physiology 33

C.4.S.

Surgical Physiology 3&

Cardiac cell hysiology

Which 5 ions are associated with the cardiac action otential? #a(, )( and *a((. What are the intracellular and e%tracellular conteration of each of these? %ons .xtracellular %ntracellular concentration /mM1 concentration /mM1 ) & 63, #a 6&, 6< 2 *a 2 6< & What is the resting otential of a cardiac cell and how do you account for this? 'pproximately >< ml. The cell membrane is permeable to )( but less permeable to anions /e.g. proteins1 within the cells. %n the resting state )( ions leave the cell and anions are left behind, ma"ing the anterior of the cell electronegative. Can you describe the movement of these ions across the cardiac cell membrane during de olari/ation? Triggering of the action potential by the pacema"er cells results in a brief increase in cell membrane permeability to #a ions. There is rapid influx of #a( ions ma"ing the transmembrane potential positive. )( then diffuse out of the cell to restore negative transmembrane potential /repolarization1. 7estoration of membrane potential is delayed by influx of *a(( ions /plateau phase of action potential1. This means that there is an obligatory period during which the cell cannot be depolarized this prevents tetany. What are the effects of hy o$alamia on the heart? ' large increase in extracellular )(( results in loss of cell excitation, decreased rate of conduction and slowing of the heart with dysrythmias.

Surgical Physiology 3,

Cardiac cycle
What is the cardiac cycle? The cardiac cycle relates events within the heart to simple body surface measurements. The opening and closing the heart valves and pressure changes within the chambers of the heart /and aorta and +ugular vein1 are drawn in relation to the timing of the heart sounds and changes on an electrocardiography /.*21 trace
N=olume, pressure changes in ', =, great vessels in each cycle ( heart sounds (.*2O

How long is the cardiac cycle in seconds? %t is <.& seconds.

With regard to the left ventricle* what are the hases of the cardiac cycle Ceft ventricular contraction and relaxation. Ceft ventricular contraction can be further divided into phases of %sovolumetric contraction. 7apid e+ection. Slow e+ection. Ceft ventricular relaxation can be further subdivided into phases of 7educed e+ection. %sovolumetric relaxation. 7apid filling and slow flling.

Surgical Physiology 34 What is the difference between cardiological and hysiological left ventricular systole? *ardiological left ventricular systole is defined as the period between closure of the mitral and aortic valve. 0hysiological left ventricular systole is defined as isovolumetric contraction to the end of the rapid e+ection phase. 6n an 'C(* what do the P wave and 7&S com le% re resent? The 0 wave represents atrial depolarization. 'trial systole begins shortly after the onset of the 0 wave. The P7S complex represents ventricular depolarization. =entricular systole begins at the pea" of 7 wave and ends +ust after T wave. What does the dicrotic notch re resent? The dicrotic notch is seen on the descending limb of the aortic pressure curve and mar"s the division between ventricular systole and diastole. The aortic valve closes at this point. Can you desribe the o ening and closing of the mitral valve in relation to the cardiac cycle? *losure %t closes at the end of artrial systole when the pressure in the left ventricle exceeds that of the left atrium. This mar"s the beginning of the ventricular systole /the pea" of the 7 wave1. @pening %t opens in early ventricular diastole, when the pressure in the left ventricle is below that of the atrium. %t is the end of isovolumetric relaxation of the ventricle. @pening of the mitral valve results in rapid ventricular filling. Can you describe the o ening and the closing of the aortic valve in relation to the cardiac cycle? @pening %t opens in early ventricular systole when the pressure in the left ventricle exceeds that of the aorta. This mar"s the end of the period of isovolumetric contraction of the left ventricle a short period at the start of ventricular systole when both the mitral and aortic valves are closed1. *losure %t closes when the pressure in the aorta in greater than the left ventricle. This mar"s the end of ventricular systole.

Surgical Physiology 3;

What roduces the heart sounds ? Simplicitically, the closing of the coronary valves produces the heart sounds. To be more precise, after the valves have snapped shut, a bac"flow of blood against them causes them to bulge taut into the ad+acent chambers and then rebound, forcing blood bac" into the chamber in turbulent flow. %t is the rebound of the taut valve cusps and turbulent flow that causes the heart sounds. 61 The first sound is caused by the closure of the atrioventricular valves, namely the tricuspid and mitral valves. 21 The second heart sound is caused by the closure of the semilunar /aortic and pulmonary1 valves. 31 The third heart sound is caused by the inrush of blood into the ventricles in the mid third of diastole. &1 !ourth heart sounds is caused by the inrush of blood into the atirum during atrial contraction,

Surgical Physiology 3>

Cardiac function
What other ways can you investigate cardiac function ? *ontinuous ambulatory .*2 monitor. .*2 with exercise /treadmill1. .chocardiology utilizes ultrasound to give dynamic information about ventricular wall thic"ness and movements, flow across valves and "inetics segments. Thallium scanning uses a radioisotopes, which is ta"en up by myocardial muscle in proportion to its blood supply5 thus well perfused areas show up brightly on the gamma camera, whilst infracted areas show up as holes. *oronary artery angiography has revolutionized pre operative assessment of ischaemic heart disease. 'ccess is either by placement of a transvenous catheter to give information about the right heart or arterial catheter placement allwing angiography of the coronary arteries and exact visualization of occlusive disease, which is studied closely by the cardiac surgeon prior to coronary artery bypass grafting. What are the differences between the right and left ventricles? Ansurprisingly, the differences between the two ventricles are a representation of their differing functions and re:uirements. The right ventricle %tKs thin walls are a reflection of the low afterload, i.e. the low pressure pulmonary circulation. %t is able to cope with large changes in preload. @ne example being the changes in venous return between lying and standing. %t is not, however, very good at coping with an increase in afterload, and rises in pulmonary pressure badly affect right heart function. The left ventricle %t is thic" walled because of the high afterload. and conse:uently, %t can deal with changes in afterload relatively easily but it is sensitives to change in preload, i.e. it needs filling. This description of the right ventricle explains some of the problems of ventilating asthmatics. To overcome the high airway pressures associated with intermittent positive pressure ventilation of an asthmatic, high pressures are needed. This will compress the pulmonary blood vessels, resulting in an increased right heart afterload, this in turn, can lead to right heart failure in this group of patients

Surgical Physiology 3?

Cardiac out ut
How do you calculate cardiac out ut ,C6- and what ercentage is delivered to each organ system? *@Q stri"e volume x rate /usually ;< ml x ;< bpm Q ,6 minute1. Deart ,I 3rain 6&I Muscle 2<I )idney 22I Civer 2,I The rest 6&I What formula is ty ically used to re resent this value? P Q D7 x S= Bhere P Q *@ /68 minute1 D7 Q Deart rate /beats8 minute1 S= Q Stro"e volume /61

What governs cardiac out ut? *ardiac output is the product of heart rate and stro"e volume, i.e. how much blood does the heart e+ect at each contraction and how many times a minute does it do itR *ardiac ouput is also related to the blood pressure /301 and systemic vascular resistance /S=71 according to the e:uation. 30Q *@8 S=7 How can the contractility of the heart be described? %t is the amount of force generated for a given inotropic state. %t is described by starling curves that plot force generated against initial fibre length. ' rise in the inotropic state will move the curve into a higher position, indicating greater contractility. %t is an intrinsic property of the myocardium. What are the effects of sym athetic stimulation and C6? %ncreased myocardial contractility and increased heart rate and therefore, a rise in *@. How is cardiac out ut regulated? *ardiac output is regulated through factors that affect heart rate and stro"e volume. These include #eural mechanisms- sympathetic, parasympathetic. %ntrinsic mechanisms to the heart- starlingKs law of contractility /preload is proportional to vardiac output1. Dormonal mechanisms- adrenaline, glucagons /less important1, thyroxine.

Surgical Physiology &<

How can you measure the cardiac out 6. *linically through*onscious level. Deart rate. Arine ouptput. *apillary refill.

ut? 3lood pressure. Temperature. 0eripheral perfusion.

2. !ic" principle7e:uires samples of mixed veous and arterial blood *ardiac output /litres8 minute1@2 absorbed per minute by lungs /mC8min1 'rtetiovenous @2 difference /ml8l of blood1

The fic" principle states that the amount of a substance ta"en up by an organ per unit of time is e:ual to the arterial level of the substance minus the venous level multiplied by the blood flow. The fic" principle can be used to calculate blood flow /cardiac output1 and *@2 consumption. 3. 9ilution techni:ue /using a Swan 2anz cardiac catheter1'. 9ye dilution )now amount of dye is in+ected and its concentration measured peripherally /photoelectric spectrometer1, indocyanine green /low half and toxicity1 3. Thermodilution %t uses cold saline infused through a *=0 line and analysed via a modified arterial line containing a thermistor. 9ata represented as temperature drop against time5 cardiac output is inversely proportional to the area under the curve. Thermodilution method based on thr fic" principle. o *@Q D7 x S= o 30Q *@ x S=7
/*@- cardiac output5 S=- stro"e volume5 D7- Deart rate5 30- 3lood pressure5 S=7- Systemic vascular resistance1.

&. .chocardiology#ot a continous techni:ue and operator dependent but allows direct visualization of the myocardium and an assessment of e+ection fraction. ,. .cho 9opplerMeasures blood flow in the aorta using an oesophageal probe. *@ can be derived from the doppler waveform.

Surgical Physiology &6

"re you aware of any other methods of measuring cardiac out ut? 6. %mpedance plethysmography. 2. .chocardiography. 3. .lectromagnetic flow measurement /probe on aortic root during surgery1. &. *ardiac catheterization. ,. @esophageal 9oppler 9oopler probe into the oesophagus to measure blood flow velocity in the descending aorta. ' velocity time waveform is created and the total ventricular stro"e can be calculated from the area under the waveform. !rom this, cardiac output may be determined. What is Straling1s law? The force of contraction of the heart is proportional to the length of its muscle fibres, i.e. increasing venous returm to the heart results in increase stretch of the muscle fibres and in turn a greater force of contraction, therefore increasing S=. There is, however, an optimum fibre length and excessive stretch will depress pumping capacity. !n the trans lanted heart* does Straling1s law a ly? What is resting heart rate? Ses, StarlingKs law of the heart force generated is proportional to initial fibre length is a local mechanosensitive mechanism that is intrinsic to the cardiac muscle fibres. The resting rate is about >< ?< beats per minute, which represents the intrinsic rate of the pacemar"ers without any vagal slowing. How well does a cardiac trans lant function? What is the rate of develo ing angina? 0ostoperative function is usually good5 enabling normal day to day activity. Survival rates are ?< I at 6 year and ;< I at , years. There is no angina, because by definition the the transplanted heart has been completely disconnected from any nerves and as such, there is no pain pathway to transmit the sensation of angina5 that is not to say that coronary ischemia does not occur. What facctors affecting the wor$ing of the trans lanted heart? 's stated StarlingKs law still holds, as does the 3ainbridge reflex /increased venous return causing right atrail distension and a reflex increase in heart rate1. 'lthough separated from neural autonomic influences, the heart will respond to circulating catecholamines and may mount a response to stress or exercise. What are the cardovascularn effects of cross+clam ing the aorta in """ re air? 6. *@ Q S= D7. 2. 30 Q *@ S=7. T07 increases mar"edly, pushing up blood pressure. To compensate, there is a reflex bradycardiacto reduce *@ and hence 30.

Surgical Physiology &2

What ha ens to your ca illaries when you stand u 8 erform valsalva manouever? 6. *@ Q S= D7. 2. 30 Q *@ S=7. 3. 9raw StarlingKs curve. Standing up leads to pooling of blood, and a decrease in venous return. This leads to a decrease in S= and hence *@ /StarlingKs curve1. This leads to a decrease in 30. This drop in 30 is sensed by the baroreceptors and there is a reflex constriction of the capillaries and arterioles to maintain 30 as the *@ component of e:uation has dropped. There is also a reflex bradycardia and an increase in contractility caused by sympathetic activation of the heart. ' valsalva manoeuver /forced expiration against a closed glottis1 causes increased intrathoracic pressure and hence a decrease in venous return as above. Why would an anaestheist be worried about a atient with heart bloc$? 6. *@ Q S= D7. 2. 30 Q *@ S=7. 3. 9raw StarlingKs curve. This e:uation needs lateral thin"ing. %nduction agents cause vasodilation and a decrease in S=7. This causes the 30 to drop. To maintain reflexly the 30, S=7 M D7 need to increase, but the heart bloc" prevent a reflex tachycardia.

Surgical Physiology &3

6%ygen flu% e#uation

What is the o%ygen flu% e#uation? This e:uation represnts the amount of oxygen delivered to the tissue per minute. 9o2 Q *@ x arterial content. Q *@ x /@2 bound to Db ( @2 dissolved in plasma1 Q *@ x /6<x Dbx Sao2x 6.3&1( /6< x 0ao2 x <.<22,1 Bhere Q *ardiac output *@ Q Daemoglobin concentration in g8 dl Db Q 'rterial oxygen saturation of haemoglobin Sao2 Q DufnerKs constant 6.3& Q 'rterial partial pressure of oxygen 0ao2 Q ml of oxygen dissolved8 6<< ml plasma8 " 0a /<.<<3 mm Dg1 <.<22, #ormally, the 9o2 is >,< 62<< ml8minute. The factor of 6< is included to ensure uniformity of units as haemoglobin is in g8dl but cardiac output is in C8min. %n practice, the amount of oxygen in direct solution is minimal /T 6 I 1 and is generally ignored in this calculation. What is shoc$? Shoc" can be defined as an acute circulatory disturbance resulting in inade:uate tissue perfusion and tissue hypoxia. What is the revelence of the o%ygen flu% e#uation to the management of shoc$? The oxygen flux e:uation tells you how much oxygen is being delivered to the tissue. Shoc" is by definition an inade:uate amount of oxygen delivered to the tissues, thus the management of s"oc" is the maximization of the flux e:uation in practice. Se:uential analysis of the e:uation and comparison to clinical events will ma"e sense of this. %n order to maximize 9@2, any one of the individual terms could be maximized, hence %f the shoc" is haemorrhagic in nature, there will be a decrease in the haemoglobin concentration and the /Db1 term of the e:uation will be lower than previously. The solution would be transfuse blood to restore the haemoglobin concentration, thus increasing the value of 9@2. similarly, giving the patient supplemtal oxygen will serve to increase the Sa@2 phrase of the e:uation. *ardiac output is defined as heart rate multiplied by stro"e volume , thus maximization of these parameters by manipulation of inotropes is another important method of increasing oxygen delivery. 'dditionally, if cardiac output is considered mathematically as blood pressure over systemic vascular resistance /308S=715 then inotropic manipulation of these will also allow manipulation of 9@2. in occasional situations, hyperbaric therapy may be used to increase the final. 'nd normally ignored, part of the flux e:uation, although this is

Surgical Physiology && more li"ely to be in a case such as carbon monoxide poisoning than hypovolaemic shoc" management.

Discuss the role of )goal+directed thera y) in the of the critically ill? 2oal directed therapy stems from wor" by Shoema"er in the early 6?><s when he noted that patients in intensive treatment units who achieved a certain level of oxygen delivery according to the flux e:uation did better than those who did not. This led to patients being aggressively fluid filled and inotropically driven to cheive preset goals of oxygen delivery, and was the vogue in many %TAs for a while. Cater wor" has shown that achievement of these goals in itself does not improve outcome and the current view is that patients who reach these goal without heavy inotrope support do indeed do better5 this is more li"ely a natural reflection of the fact that they are physiologically able to reach that target. !orcing physiologically incapable patients to meet preset goals by inotropic manipulation has a deletrious effect. What is an inotro e? What do they do and give e%am les? 'n inotrope is a substance that alters the inotropic state of the heart i.e. it affects the myocardial contractility. The phrase is commonly used to refer to those agents that increase contractility, although negative inotropes do exist. .xogenous inotropes are analogues or derivatives of endogenous catecholamines and act on variety of receptors including the F, 36, 32 adrenergic and dopamine receptors. 'drenaline acts mildly at F receptors, but mainly at 36 and 32 receptors to increase heart rate and contractility and causes vasodialtion because of relaxation of smooth muscle. #oraderaline acts predominantly at te F receptor causing peripheral vasoconstriction and increase in systemic vascular resistance. %t also has some mild 36 stimulatory properties. 9obutamines is a synthetic derivatives of dopamine and causes mainly 36 effects.

Surgical Physiology &,

2lood ressure
What is blood ressure ? 3lood pressure is the force exerted by the blood against any unit area of the vessel wall and is traditionally measured in millimeters of mercury. %t may be expressed as ' mean arterial pressure /M'01 about which there are oscillations. or ' systolic and diastolic pressure. These represent the biphasic output of the heart with high pressure on ventricular contraction and a lower pressure due to vascular recoil while the ventricles refill. 's the blood pressure is closer to diastolic pressure for a greater proportion of the cardiac cycle, the mean arterial pressure is not simply an average of the diastolic and systolic pressures5 it is given by the e:uationM'0Q /2G diastolic pressure1 ( systolic pressure 3

How can blood ressure be monitred? #on invasive6. Traditional shygnomanometer %ntermittent, cumbersome and time consuming. #on invasive method is mannual /using stethoscope1 2. 9ynamap system /still uses arm cuff but based on oscillometry1 'utomatic, :uic"er, less time consumeing. 0robably slightly less accurate than manual measurment. %ntermittent but can be set to reta"e 30 every minute. 3. 7adia artery tonometry 3ased on superficial pressure sensors and therefore highly positional. #ew technology but may eventually replace an arterial line for short term monitoring /e.g. in local anaesthetic procedures such as carotid endarterectomy1. *ontinous monitoring, produces 30 waveform as with an arterial line. &. !inometer Cargely for research, based on measurement of $finger blood pressure$. %nvasive6. 'rterial line =ommonly a 2< 2 catheter inserted into the radial artery. %nvasive U ris"s of clotting of liine, infection. Most accurate, beat to beat assessment of Map and 30.

Surgical Physiology &4 'llows assessment of arterial waveform to see if it is swinging, indicating underfilling. 'llows regular aspiration of arterial blood for '32s. What factors determine arterial blood ressure? %n broad terms, the factors determining arterial pressure can be divided into 0hysical factors /blood volume and compliance1. 0hysiological factors /cardiac output /*@1, heart rate, stro"e volume /S=1, vascular resistance, etc1. Can you define mean arterial ressure using a sim le e#uation? M'0 Q *@G T07 Bhere *@ Q cardiac output T07Q total peripheral resistance /dyne seconds8*m,1

Which sites account for the ma.ority of resistance in the circulation? The capillaries- have a narrow caliber, a large surface area and are numerous. The arterioles- are lined with smooth muscle which can contact, narrowing the vessel and increasing resistance. How can C6 and systemic vascular resistance ,S4&- affect blood ressure? .ssentailly , in any given artery the M'0 will be proportional to the volume of blood. *@ and S=7 can be understood to affect M'0 by how they might alter the volume of blood. *@ is the inflow of blood to the artery /*@Q inflow1 and S=7 is inversely proportional to the outflow of blood from the artery /S=7Q 68 outflow1. 'n increase in either *@ or S=7 will, therefore, increase blood volume and therefore M'0. @r the other words, M'0Q *@GS=7. What is ulse ressure ,PP00 is the difference between S30 and 930 /00Q S30 9301. What dactors affect PP and why they are im ortant? Two main factors determine 00 S=. *ompliance. 's pressure is proportional to the volume of the blood in the artery, an increase in S= will produce a proportionate increase in 00, provided compliance is normal. Therefore, 00 can give information about S= /therefore 00 is reduced in patients who have suffered severe haemorrhage for example1. ' reduction in compliance will increase 00 for a given S=. This is significance in patients with atherosclerosis as a greater wor"load is placed on the left ventricle. ' similar situation arises in hypertensive is patients as compliance is reduced at higher pressures. What mechanisms are involved in the control of blood ressure? The main mechanisms comprise 3aroreceptors. 'utonomic nerve pathways.

Surgical Physiology &; =asomotor centre. *ardioinhibitory centre. Two additional intrinsic cardiac regulatory mechanisms influence the blood pressure The 'nrep effect- a response to acute increase in afterload, leads to initial reduction of stro"e volume. The 3owditch effect- a response to change in heart rate, the contractility increasing as the rate increases.

What factors control blood ressure? 3lood pressure controlling factors can be categorized into immediate, early and long term. %. %mmediate factors are6. The central nervous system response occurs if blood flow to the vasomotor centre falls below 4< mmDg, at which level the centre is excited and the blood pressure is raised by sympathetic control. 2. 3arorecptors in large arteries relay impulses to tractus solitarius, which as pressure increases, inhibits the vasomotor centre and excites the vagal centre, leading to the blood pressure falling. 3. *hemoreceptors of the aortic and carotid bodies are sensitive to decreased 0a@2 and increased 0a*@2, which excite the vasomotor centre and raise blood pressure. %%. .arly control mechanisms act within 3< minutes in response to changes in blood pressure, they consist of6. 7ennin angiotensin system, increases in renal perfusion pressures cause less angiotensin %% to be produced, causing a decrease in vascular resistance. 2. Stress relaxation occurs as high arterial pressures cause relaxation in blood storage areas. 3. *apillary fliud shift allows decreased capillary fliud loss with lower blood pressure allowing an increase in blood volume. &. 'drenaline8 #oradrenaline cause sympathetic vasoconstriction to raise blood pressure. ,. '9D secretion is increased with hypotension and has a direct vasoconstriction effect, and decreases fluid loss. %%%.Cong term control occurs through The renal control of body fluid. 's blood pressure increases, the "idney loses more fluid and #a(. in the long term, changes to the renal output curve develop. What are barorece tors and where are they found? 3aroreceptors are stretch receptors which respond to distension and are present in *arotid sinus. 'ortic arch. 'trium. =entrivle.

Surgical Physiology &> @ther centres intrinsic to barorecptor function =asomotor centre- a group of neurons in the ventrolateral medulla that maintain the tone of vascular smooth muscle. *ardioinhibitory centre /ventral medulla1- inhibits the vasomotor centre5 tone increased by baroreceptor discharge.

How do these rece tors res ond to a fall in blod ressure? These stretch receptors respond to a fall in pressure by reducing afferent signals carried via the %G and G cranial nerves to the cardiac and vasomotor centres in the medulla. This results in increased sympathetic activity via the autonomic system and reduced vagal tone. The conse:uence of this is vasoconstriction, increased heart rate and stro"e volume. This raises both peripheral resistance and *@, restoring blood pressure. How does transection of the cord at the level of 09 lead to )s inal cord)? Coss of sympathetic tone results in profound vasodilatation and a fall in total peripheral resistance. %n addition, unpaired vagal drive causes bradycardia and contributes to lowering the blood pressure. What hormonal mechanisms influence the long term control of blood ressure? Dormonal mechanisms involved in longer term blood pressure control 7ennin angiotensin system. 'ldosterone. =asopressin /'9D1. 'trail natriuretic peptide /'#01. Why is hy ertension relevant to surgical ractice ? Ancontrolled hypertension will result in cancellation of a surgical patient from theatre owing to the increased ris"s of cerebrovascular events and cardiac failure. Severe hypertension may rarely result in aortic dissection, particularly of the thoracic aorta, and this brings the patient to the attension of the cardio thoracic surgeons as it may need emergency surgical repair. !or the ma+ority of patients. Dypertension is controlled by oral mediation but the surgeon should recognize that a labile blood presuure pre operative may indicate widespread atherosclerosis. 9iuretic treatment often gives rise to fluid and electrolyte dis turbances, which should be assessed and corrected prior to embar"ing on surgery. Most antihypertensives are cardioprotective and should continue to be given pre operatively with a sip of water, even when patients are K nil by mouth K.

Surgical Physiology &?

What causes of hy ertension can be treated surgically ? ?< I of people with hypertension have no obvious cause5 this idiopathic or essential hypertension. The treatment of these cases lies with the physician and his plethora of medications. @nly 6< I of cases have a discernible cause, some of which are amenable to surgical correction and should be sought before the diagnosis of essential hypertension is accepted, particularly in young patients. 9ysfunction of the adrenal gland is a potent cause of hypertension .xcess cortisol from *ushingKs syndrome, driven by either a pituitary or adrenal tumour is amenable removal. 'ldosterone secreting tumour of the adrenal gland, *onnKs syndrome, may be surgically cured. 7enovascular hypertension causes, by means of a reduction in +uxta glomerular perfusion, a potent stimulus to the rennin angiotensin system, causing profound hypertension. This is readily to surgical treatment by excision of the stenosed segment with primary anastomosis or by radiological angioplasty techni:ues. 0haeochromocytoma also causes hypertension , which is usually paroxysmal, by release of huge :uantities of catecholamines, causing mar"ed vasoconstriction. Most are surgically removable . What com ensatory mechanisms are activated in severe haemorrhage ? !our interlin"ed mechanisms are activated following haemorrhage 6.!ollowing haemorrhage there is a fall in mean arterial pressure and this produces a baroreceptor response /stretch receptors in the aortic arch and carotid sinus send afferents to the brain stem1. 2.=agal /parasympathetic1 tone is decreased resulting in V Deart rate. 3.The V in sympathetic tone causes 0eripheral vasoconstriction leading to V systemic vascular resistance. V %notropic effect. V *hronotropic effect. V Stro"e volume and thus cardiac output. There is W blood flow to the s"in, s"eletal muscle and splanchnic circulation. &.The rennin angiotensin aldosterone axis is also activated due to the fall in renal perfusion and glomerular filtration rate. This leads to arteriolar vasoconstriction

Surgical Physiology ,< and sodium retension, which increases plasma osmolarity and stimulates thirst and '9D release from the posterior pituitary leading to water retension.

How does the body res ond to an acute fall in blood ressure due to a large gastrointestinal bleed* for e%am le ? The body responds in such a way as to try to normalize its internal environment and maintain tissue perfusion of essential organs at a normal level, and this varies with the degree of shoc". 0hysiological changes in response to haemorrhage Degree of Pro ortion of &es onse shoc$ blood volume lost *lass 6 L 6, percent Minimal signs and symptoms. /L ;,< ml1 There may be a slight tachycardia *lass %% 6, 3< percent Tachycardia increases. /;,< U 6,<<1 #arrowing of the pulse pressure due to catecholeamine induced peripheral vasoconstriction. 'nxiety may become manifest *lass %%% 3< &< percent Tachycardia. /6,<< U 2<<<1 Tachypnoea. ' fall in systolic blood pressure. Mental confusion. The s"in is cool and plate as blood is diverted to essential organs *lass =% X&< percent There is a mar"ed drop in systolic pressure. 9iastolic pressure is often unobtainable. Arine output negligible . %f X,< I blood volume is lost, unconsciousness ensues, and the pulse and blood pressure become unrecordable / X 2<<< 1.

Surgical Physiology ,6

"utoregulation
What is autoregulation and give an e%am le of it at wor$ ? 'utoregulation is the ability of an organ to maintain a constant blood flow over a widw range of mean arterial pressures within certain limits. %t is seen in the heart and "idney but is best demonstrated by examining cerebral blodd flow. *erebral perfusion pressure /*001 Q Mean arterial pressure / map1 Yintracranial pressure pressure/ *=01 Z

%*0

(*entral

venous

This curve shows that, up to a *00 of 4< mmDg / point'1, an increase of pressure will increase cerebral blood flow /*3!1. 3etween pressures of 4< and 64< mmDg /' to 31, any increase in *00 does not result in alteration of *3!. 3ut, with a *00 of over 64< mmDg, the blood flow increases with pressure again.

Surgical Physiology ,2

Draw the brain com liance curve and e% lain what it means in ractical terms 's volume increases, compensation occurs so that almost no rise in intracranial pressure / %*01 follows /' to 3 on the curve1. This wor"s up to a critical point /*1, after which even a small increase in volume causes a rapid rise in %*0 /* to 91.

How do you manage a atient with raised intracranial ressure after closed head in.ury ? The Munro )elly doctrine points out that the cranium is a fixed volume box, the contents of which brain, *S! and blood are not compressible. 7ises in volume cause a rapid rise in %*0 at that point on the compliance curve. The brain constitutes >, I of the intracranial volume but is the least amenable to manipulation of its volume. *S! represents 6< I.

Surgical Physiology ,3 3lood, the most accessible , I . The following measures all aim to reduce the volume of one or other of the three contents of the box, and thus protect ade:uate cerebral oxygen delivery6. 0osture- 6,[ of head up tilt will reduce venous congetion. The avoidance of venous obstruction also helps, such as "eeping the head central without tapes or lines around the nec". 2. =entilation- protection of the airway and maintainance of good oxygenation are essential. 'void hypercarbia as *@ 2 is a potent vasodilator, which at first seems li"e a good idea in order to maintain cerebral oxygen delivery, but the increased blood volume actually increases %*0 and is counterproductive. 'im for low normal *@2 levels. 3. Mannitol- an osmotic diuretics. %t increases colloid osmotic pressure, and draws water into the vascular space and is a potent free radical scavenger. %t causes a decrease in *S! production and causes a reduction in blood viscosity allowing increased *S!. Too much mannitol, however, may cause a rebound phenomenon, as the lea"y capillaries allow mannitol into the inter stitium reversing the colloid gradient. &. Steroids- are only useful when dealing with organized masses, such as tumours and the inflammatory reaction that accompanies them. They are not indicated in closed head in+ury. ,. *S! drainage- placement of an interventricular catheter not only allows accurate measurement of %*0, thus allowing calculation of cerebral perfusion pressure, but allows therapeutic drainaige. Bhilst these measures are aimed at ensuring ade:uate @2 delivery, the patient will also be helped by decreasing @2 demand. Thus a sedated well analged patient with ade:uate anti epileptic prophylaxis will have lower oxygen demands than an awa"e, anxious, fitting patient. Similarly, surface cooling will reduce the overall metabolic re:uirements.

Surgical Physiology ,&

2lood flow dynamics

What are the resistance vessels ? The arterioles are the main resistance vessels in the body. They offer the greatest resistence to the flow of the flow of the blood pumped by the heart. The main component of their walls is smooth muscle which is sensitive to a variety of factors, such as nitric oxide which reduces vascular tone and increases luminal diameter , and hence decreases resistance to flow. What is the im ortance of these resistance vessels ? These vessels provide a mewchanism for controlling the systemic vascular resistance /S=71 and therefore the blood pressure /301. /30 Q *ardiac @utput \ S=71 Thus, these vessels influence perfusion to all parts of the body. How are these resistance vessels regulated ? These resistance vessels are regulated by both neutral and metabolic factors6. #eutral regulation- is predominantly through the sympathetic vasoconstrictor fibres to the blood vessels. 2. Metabolic regulation- is achieved by vasodilator metabolites produced locally by the tissue when metabolically active or during anaerobic conditions. The metabolic factors producing vasodilatation include *@ 2 , D( ,)(, adenosine and nitric oxide. What rocesses are involved in controlling the movement of fluids across the ca illary bed? The movement of water and small solutes across the capillary endothelial wall occurs by three processes- diffusion, filtration and absorption. The relationship between filtration and absorption is dependent on StarlingKs forces. The principal force in capillary filtration is the capillary hydrostatic pressure. The main force that prevents fluid loss from the capillaries is the osmotic pressure of the plasma proteins otherwise "nown as the colloid osmotic or oncotic pressure.

Surgical Physiology ,, The capillary filtration pressure is the capillary hydrostatic pressure minus the interstitial hydrostatic pressure. The hydrostatic pressure within the capillaries is regulated by the arterial pressure, venous pressure and the resistance of the arterioles.

What influences the coronary artery blood flow ? *oronary artery blood flow is influenced by a combination of physical, metabolic and neutral factors. 6. 0hysical factors- the main ones are aortic pressure, myocardial rate and contractility. 'ortic pressure plays a primary role in determining myocardial perfusion . it itself is dependent on heart rate and stro"e volume. Thus, during early diastole coronary inflow is maximal, and minimal during early ventricular systole. 2. Metabolic factorsMyocardial metabolic activity closely parallels coronary blood flow /this relationship is preserved in the denervated heart1. %ncreased myocardial oxygen demand stimulated the release of vasodilator substances from the myocardium into the interstitial fluid causing relaxation of the coronary vessels and so increasing blood flow. 3. #eutral factorsThe direct neutral influence on coronary blood flow is through the sympathetic nervous /]6 receptors1. Dowever, Stimulation of the sympathetic nervous sytem itself causes release of circulating catecholamines thereby increasing heart rate and contractility /]2 receptors1 and so influences coronary blood flow indirectly. How is the cerebral circulation regulated ? The cerebral circulation is regulated by physical /main influence1, metabolic and neutral factors. 6. 0hysical factorsThe cranium should be considered a rigid, fixed box, so increases in the volume of the blood, extracellular fluid, cerebrospinal fluid or cerebral material /a tumour for example1 would increase the intracranial pressure. *erebral perfusion pressure /*001 Q mean arterial pressure /M'01 U %*0. *erebral blood flow itself is autoregulated between a certain range, thus blood flow is "ept relatively constant despite changes in the *00.

Surgical Physiology ,4 The changes in blood volume are influenced by changes in arteriolar diameter which are in turn affected by the 0a*@2 level. 2. Metabolic factors*erebral blood flow is autoregulated so that total cerebral blood flow is constant. Dowever, 7egional cortical blood flow is also related to local cortical activity. This is influenced by metabolic factors, especially carbon dioxide, potassium, adenosine and hydrogen ions. Digh levels of these metabolites cause vasodilatation and increased blood flow. 3. #eutral factors The cerebral vessels receive a sympathetic supply but their influence in regulating blood flow is minimal. How is the cerebral circulation affected by changes in ventilation? =entilation produces its main effect on the cerebral circulation through changes in arterial 0a*@2 levels causing cerebral vasoconstriction with a subse:uent lowering of %*0. This techni:ue is used to reduce the %*0 in patients with head in+ury, The lowered %*0 helps to maintain the *00 and reduce cerebral ischaemia.

Surgical Physiology ,;

Hydratic filter
What is the rinci le function of the arterial system ? To distribute blood to the capillary beds throughout the body ensuring tissue perfusion. What do you understand by the term )hydraulic filtering) in relation to the arterial system? Dydraulic filtering reduces the amount of wor" re:uired to perfuse tissues. What features of the arterial system roduce hydraulic filtering ? There are two features- the compliance of the great vessels and regulation of flow by high resistance arteiorles. Do you $now of any classic analogies to hydraulic filtering ? Dydraulic filtering has classically been compared to the Bind"essel of a steam engine which is a compressible air trap which converts the intermittent flow of water to a steady outflow.

Surgical Physiology ,>

2lood flow in a vessel

What is flow and can you distinguish the different ty es of flow ? !low is the amount of fluid moving per unit of time. !low may be Caminar- in which flow is smooth, without eddy currents. Molecules at the periphery move more slowly than those in the centre. Turbulent- when tube is unevently shaped /e.g. flow through a narrow orifice15 or during laminar flow when flow velocity exceeds critical velocity. &eynold1s number describes the relationship between tube and fluid characteristics and the velocity at which turbulent flow occurs 7eynoldKs number L 2<<< U flow li"ely to be laminar. 7eynoldKs number X 3<<< U flow li"ely to be turbulent.

How do you measure flow ? 2aseous flow- flow meters. Ci:uid flow 9ilution techni:ues. .lectromagnetic flow measurement. !ic" principle. How is flow related to the radius of a tube ?

Surgical Physiology ,? !low is proportional to 7& /radius to the power of &1. The Dagen Upoiseuille e:uation describes laminar flow !low Q /0 \ 7& \^1 8 / > \ _ \ l1 Bhere 0 Q pressure gradient across the tube. 7Q radius of the tube. _Q viscosity of the tube. C Q length of the tube.
0oiseuilleKs law - determines the flow of fluids through cylindrical tubes . %t is applicable to #ewtonain fluids with steady laminar flow .0oiseuilleKs law statics .

"re there any other laws relating to blood flow that can be a lied ? Ses, @hmKs law can be applied` 0 Q !low \ S=7. %f this law is applied to the systemic circulation then 30 Q *@ \ S=7 Where is the greatest vascular resistance in the systemic circulation ? The small arteries and arterioles. S=7 is regulated mainly by the arterioles. What is the significance of a arallel arrangement of ca illary beds? ' parallel arrangement of capillary beds allows for oxygenated blood to perfuse all beds and there can be independent of regulation of blood flow to each individual bed. 'lso, the total S=7 is determined by the collective the resistance in all capillary beds in the following way- 68S=7Q 6876 ( 6872 ( 6873 etc. /76,2,3, are the resistances in the respective capillary beds1 What is meant to be velocity and flow in a blood vessel? and how are these two ro erties related? =elocity refers the speed of individual components of blood /m8second1. whereas !low refers to the :uantity of blood pressure through the vesse perunit time. They are related in the following way- !low Q velocity \ cross sectional area. How does arterial stenosis affect blood flow and velocity ? Stenosis causes increased resistance to flow and produces a pressure drop across the stenosed area /pressure proximal to stenosis X pressure distal to stenosis1. 'ssuming that flow remains constant, velocity will increase through the area of stenosis. 's velocity increases there is a ris" that smooth lamina flow will change to turbulent flow 7eynoldKs number /#7 is used to estimate the li"ehood of turbulent flow /when #7 X 3<<< flow will be turbulent1. What is meant by critical stenosis and when does it occur ? 'rterial stenosis is said to be critical when the flow rate reduces through the area of stenosis. This point usually occurs when there is around ;<I stenosis. Can you name some circulating factors that can cause vasodilatation and some that cause vasoconstriction? =asodilatation- somatostatin, histamine and brady"inin. =asoconstriction- angiotensin %% and adrenalin.

Surgical Physiology 4< Can you do the same for endothelial+derived factors ? =asodilatation- nitric oxide5 prostaglandin %2 /02%21. =asoconstriction- endothelin and thromoxane.

Can you do the same foe neurotransmitters? =asodilatation- adenosine triphosphate /'T01, vasoactive intestinal peptide /=%01 and substance 0. =asoconstriction- noradrenaline.

Can you do the same foer metabolic factors ? =asodilatation- "( and *o2. =asoconstriction- *a 2(.

"re there any im ortant $ey elements in the control of vascular smooth muscle tone? There is an intimate relationship with the endothelial lining with a number of signals from the circulation being transmitted to =SM through an effect on the endothelium. The contractile elements in =SM are more disorganized than those instriated muscle and this may facilitate longer periods of contraction in =SM. There are a variety of voltage U and receptor operated channels /=@*Ks and 7@*Ks, respectively1 which allow an influx of *a 2( into =SM cells. Types of =@*Ks and 7@*Ks in different capillary beds will all different responses to the same stimulus.

Starling1s 3orces
How do Starling1s forces affect the ca illary level? StarlingKs forces- it is the !actors determining the movement of fluid across the capillary wall endothelium. Movement of water into the interstitium is produced by the hydrostatic pressure gradient and counteracted by the colloid osmotic gradient. How do these forces interact ? 0cQ *apillary hydrostatic pressure /varies from artery to vein1. 0if Q %nterstitial hydrostatic pressure. ap Q @ncotic pressure due to plasma proteins /2> mmlDg1. ^ifQ @ncotic pressure due to interstitial proteis /3 mmDg1. #et filtration Q /pc U pif 1 U /ap U ^if1.

Surgical Physiology 46

What factors can lead to the develo ment of oedema ? 9efinition- 2eneralised or local excess of extracellular fluid. '. %ncreased lea"iness of capillaries@ccurs in burns, sepsis or '79S. 3. %nceased hydrostatic pressure at the venous endThis leads to increased hydrostatic pressure throughout the capillary and more net movement of fluid into the interstitial space. @ccurs in 9=T. =enous hypertension /which often accompanies varicose veins and ulcers1. 0elvic venous compression /by tumours1. Civer cirrhosis. 7enal cell carcinoma infilteration and right sided heart failure. *. 9ecreased colloid oncotic pressure3asically any cause of hypoalbuminaemia. @ccurs in Civer failure /lac" of synthesis1. %ncreased loss, nephrotic syndrome, protein losing enteropathies, poor nutirtion. 9. !ailure of lymphatic system to drian Q lymphoedema 0rimary lymphoedema- un"nown aetiology. Secondary lymphoedema- damage of lymphatic system caused by surgery /especially breast1, radiotherapy or carcinoma.

Ca illary Dynamics
What is the ma.or determinant of blood flow in ca illaries ? 3lood flow is dependent on the contractile state of the arterioles. Which rocesses govern movement of substances across ca illaries ? 9iffusion. !iltration. 0inocytosis.

How is the hydrosratic ressure within the ca illary determined ?

Surgical Physiology 42 This depends on arterial pressure, post capillary venous pressure and the tone of pre and post capillary sphincters. %ncrease in arterial or venous pressure increases hydrostatic pressure. %ncrease in sphincter tone lowers hydrostatic pressure. Which is the ma.or force retaining fliud within the ca illary ? This colloid osmotic pressure exerted by the plasma proteins that are retained within the capillary. How does the inter lay between hydrostatic and oncotic resuure determine net fluid movement across the ca illary ? This can be represented by StarlingKs law!luid movement Q " Y/pc ( ai1 U / pi ( ^p1Z Bhere Q !iltration constant for capillary membrane. " 0c Q *apillary hydrostatic pressure. ^i Q %nterstitial fluid oncotic pressure. 0i Q %nterstitial fluid hydrostatic pressure. ^p Q 0lasma protein oncotic pressure. %f the net figure is positive filtration out of the capillary occurs, if negative absorption into the capillary ta"es place.

"rterial waveform
What are the im ortant features of the arterial waveform? Systolic pressure. 9iastolic pressure. 9icrotic notch. 0ulse pressure.

Surgical Physiology 43 Mean arterial pressure /the pressure at which the area above the mean e:uals the area below the mean1.

What information can be gained from studing the arterial waveform? 'rterial blood pressure. Stro"e volume and cardiac output- from the area under the systolic part of the waveform. Myocardial contractility- from the slope of the upstro"e /change in pressure8change in time1. @utflow resistance- from the slope of diastolic decayo ' slow fall suggests vasoconstriction. o ' rapid fall suggests vasodilatation. Dypovolamia- suggestedo ' low dicrotic notch. o ' large variation in pes" pressures in patients who are being ventilated. How does the arterial waveform changes in the resence of aortic valve? 'ortic stenoids U slow Urising waveform with a prolonged plateau. 'ortic incompetence U excessive pulse pressure, low diastolic pressure.

Surgical Physiology 4&

Central venous ressure

What are the indications for gaining central venous access? =ascular access. Measurement of central venous pressure /*=01. %nsertion of pulmonary artery wedge catheter. Transvenous pacing. 0arentral feeding /long term1.

What roblems can be associated with central venous access ? %nfection. 'rrhythmias. 'ir embolism. *ardiac8lung perforation. *entral vein thrombosis. #eurovascular damage.

What are the com onents of the venous waveform? o a wave- atrial contraction. o c wave- tricuspid valve bulges bac" into the atrium during ventricular isometric systolic phase. o x descent- atrial relaxation. o v wave- rise in atrial pressure before the tricuspid valve opens. o y descent- atrial emptying into the ventricle.

#otes #o a wave in atrial fibrillation.

Surgical Physiology 4, .nlarged a wave in tricuspid stenosis, pulmonary hypertension. .nlarged v wave in tricuspid regurgitation. *annon waves /not corresponding to a , v, or c waves1 in 6. *omplete heart bloc" /irregular1. 2. bunctional arrhythmias /regular1.

:ym hatics
What is the function of the lym hatic system ? The function of the lymphatic system is to return plasma, capillary filtrate and protein to the vascular system. The lymphatic system also !ilters the lymph nodes thereby removing foreign particles including bacteria. *arries nutrients absorbed from the gastrointestinal tract including chylomicrons /fats1 bac" to the circulation.

What is the difference between lym hatic and blood ca illaries ? Cymphatic capillaries are similar to blood capillaries in many ways, but have two important differences6. Tight +unctions are not present between capillary endothelial cells. 2. !ine filaments anchor lymph vessels to the surrounding connective tissue. What tissues in the body do not contain lym hatic vessels ? *artilage, bone, *#S tissue and epithelium do not contain lymphatic vessels. What factors affect lym hatic flow ? Cymphatic flow is influenced by any mechanism that enhances the rate of capillary filtration. Thus, increased capillary pressure or capillary permeability or decreased plasma osmotic pressure all have an effect. Cymph flow also varies in proportion to the degree of muscular activity and is almost nil in resting s"eletal muscle.

Surgical Physiology 44

4alsalva manoeuvre
What is malsalva manoeuvre ? Sustained expiratory effort against a closed glottis, i.e. a sustained increase intrathoracic pressure against a closed or occluded glottis. Can you give some e%am les ? =oluntary increased abdominal pressure against a closed glottis. *oughing. Mechanically induced by an anaethetist in a ventilated patient.

What ha ens to S2P as a result of a voluntarily induced vasalva manoeuvre? 't the initiation of the manoeuvre there is an initial increase, followed by a decrease bac" towards normal . 't the end of the manoeuvre there is another transient increase in S30. Can you e% lain these changes? %nitial rise in S30- due to compression of the abdominal aorta by voluntary staining. 7eduction in systolic bac" towards normal- sustained pressure on the inferior vena cava results in reduced venous return and, due to the fra" Starling relationship, there is a reduced *@. 's blood pressure Q cardiac output \ total peripheral resistance /30 Q *@ \ T071 there is a reduction in blood pressure. 7ise in systolic at the end of the manoeuvre release of pressure on the inferior vena cava increases venous return and, therefore, for the same reasons outlined above, an increase in *@ and S30.

What ha ens to the heart rate and systemic vascular resistance during the valsalva manoeuvre ? They both increase steadily.

Surgical Physiology 4;

Can you e% lain this? 7educed venous return due to pressure on the inferior vena cava results in a reduced *@ /!ran" Starling relationship1. This results in a reduction in 3aroreceptor stimulation and, therefore, an increase in sympathetic outflow to the heart and peripheral vasculature. What ha ens to your ca illaries when you stand u 8 erform valsalva manouever? 6. *@ Q S= D7. 2. 30 Q *@ S=7. 3. 9raw StarlingKs curve. ' valsalva manoeuver /forced expiration against a closed glottis1 causes increased intrathoracic pressure and hence a decrease in venous return as above. This leads to a decrease in S= and hence *@ /StarlingKs curve1. This leads to a decrease in 30. This drop in 30 is sensed by the baroreceptors and there is a reflex constriction of the capillaries and arterioles to maintain 30 as the *@ component of e:uation has dropped. There is also a reflex bradycardia and an increase in contractility caused by sympathetic activation of the heart.

&es iratory

Surgical Physiology 4>

Mechanics of res iration

What do you understand by the trem mechanical breathing ? %t is the movements of the thorax that enable ventilation of the lung tissue. There are two types of mechanical breathing Puiet breathing- which occurs at rest. !orced breathing- which occurs during exercise or when there is diseased lung tissue, re:uiring extraventilation to oxygenate the blood.

Can you describe the mechanical rocess of breathing? There are two phases of breathing%nspiration The thorax expands in three dimentions. 9uring inspiration, the thorax expands mainly in its vertical diameter, as a result of the contraction and flattening of the diaphragm /"nown as diaphragmatic breathing1 supplied by the phrenic nerve /*3, *&, *,1. Thoracic breathing involves movement of the upper 2 to ; ribs in a Kpump handleK action, which increases the anteroposterior diameter of the chest. The lower > to 62 ribs move in a Kbuc"et handleK manner, thereby increasing the lateral diameter of the chest. These movements of the ribs are brought about by the contraction of the external and internal obli:ue intercostals muscles. This causes the pressure in the pleural cavity to drop to & mmDg, causing air to flow into the lungs down the pressure gradient. The accessory muscles of respiration are used in forced and in deep inspiration /sternocleidomastoid, scalene muscles, pectoralis minor and ma+or and serratus anterior1.

.xpiration .lastic recoil of the lungs and chest wall rather than muscular contration is responsible for :uiet expiration. !orced expiration involves theo abdominal muscles and latissimus dorsi.

Surgical Physiology 4?

Control of res iration

What is the res iratory centre ? The respiratory centre is formed by two groups of neurons in the medulla near the floor of the %= ventricle. The dorsal group contains mostly inspiratory neurons. The ventral group, expiratory and inspiratory nuclei. Where are the res iratory centres? 7espiratory centres are located in the pons and the medulla . What are the main sensors controlling res iration ? The main sensors are the central and peripheral chemoreceptors. *entral chemoreceptors are situated on the ventral surface of the medulla and are sensitive to fluctuations in the 0D of the cerebrospinal fluid /*S!1. 0eripheral chemoreceptors are situated in the carotoid bodies and aortic arch and are primarily sensitive to fluctuations in 0a@2. There are also mechanical receptors in the lungs and in muscles which help regulate respiration. What factors control breathing ? #on chemical and chemical factors are thought to have an important influence on the control of breathing The cortex /impulses from higher centres may be important in increasing ventilation in voluntary exercise1. 0roprioceptive impulses from the muscles of repiration 3lood pco2 and pD. 7espiration is finely regulated by pa*o2 levels /central chemo receptors1 which when increases stimulates ventilation. ' fall in blood pD also stimulates ventilation. Dypoxia itself stimulates breathing indirectly via the aortic and carotid body receptors. %t does not have a direct effect on the chemoreceptors of the reticular formation.

How do fluctuations of CS3 H relate to res iration ? Anli"e D( ions, *@2 reasdily crosses the blood brain barrier. 's 0*@2 rises in the periphery it crosses into the *S! and results in an increase in D ( ion formation, thereby stimulating the central chemoreceptors. What is the most im ortant determination of re iratory control ?

Surgical Physiology ;< 0a*o2 is the most important factors in controlling respiration. %ncrease in pa*o2 leads to increase in respiration. What is the main control of re iration in longstanding lung disease ? %n longstanding lung disease, changes in *S! pD compensate for the rise in D ( and after a prolonged period the central chemoreceptors reset. Bhen this has happened the main drive for respiration is p a@2 detected by the peripheral chemoreceptors. Why is ure o%ygen contraindicated in atients with C6PD? %n *@09, the central chemoreceptors are chronically exposed tp high levels of *@2 as a result of poor gas exchange in the lungs. Dence, the set point for 0*@ 2 increases for the centeal chemoreceptors, and they no longer respond to small changes in 0*@2. These patients therefore purely rely on hypoxia to stimulate the peripheral chemoreceptors, which in turn stimulates the respiratory centers to increase the drive to breath. %f 6<<I oxygen is given, there is no hypoxia to stimulate the peripheral chemoreceptors and because the central chemoreceptors also no longer respond to a build up of *@2 /as D(1, the patient has no drive to breath. #ote that, in practice, however, it is more dangerous to leave the patients in life threating hypoxia than to adminster oxygen. What factors govern res iratory gas e%change in the lungs? 7espiratory gas exchange in the lungs depends on three factors ventilation, diffusion and pulmonary capillary blood flow =entilation- involves the volume and distribution of the inspired air which ventilates the alveoli. 9iffusion- involves the passage of gases between the alveoli and blood in the alveoalar capillaries. 0ulmonary capillary blood flow- involves the total volume of blood and its distribution to all the ventilated alveoli.

What effects does general anesthesia have on the res iratory system? 2eneral anaesthesia produces a rise in pa*@2 due to a direct depressant effect of anaesthetic agents on the brain. %n the post operative period, there may be partial collapse of the small airways, resulting in a reduced ventilation perfusion ratio, so leading to segmental collapse. 2eneral anaesthesia may also cause increased sputum production, impairment of the cough reflex and reduced ciliary action. 'spiration may occur during or after anaesthesia, so causing respiratory distress.

Surgical Physiology ;6

Pulmonary dynamics
What do you understand by the terms com liance and hysteresis ? They are both measures of the change in lung volume per unit change in pressure /`=8`01 during the breathing cycle. They are, therefore, measures of the degree of elasticity of the lungs. *ompliance is measure of lung elasticity as the lung inflates. Dysteresis is a measure of lung elasticity as the lung deflates. What is lung com liance and in what situations is it decreased ? *ompliance refers to the elasticity of the lungs. /9efined as change in lung volume per unit change in pressure1. 0oor lung compliance occurs ino Cung disease, eg in pulmonary fibrosis. o 9isease of the chest wall, eg in thoracic scoliosis. What are the values of com liance and hysteresis different in the same lung? This is direct result of the action of surfactant /a detergent li"e substance rich in lecithin1 which lowers alveolar surface tension and decreases the wor" of breathing. What are the im lications of this difference when ma$ing ressure+volume measurements in the lung? The volume of the lung at any given pressure will be greater if measured during expiration than if measured during inspiration. This results in the classic pressure volume loops. What is meant by the term ) wor$ of breathing )? To expand the lung the inspiratory muscles must overcome the elastic recoil of the lungs and the resistance of the airways to flow. !s there any way of measuring this wor$? Ses, by measuring intrapleural pressure.

Surgical Physiology ;2

Pulmonary gas e%change and blood gas trans ort

How is o%ygen trans orted? @xygen is carried in two ways6. 'ttached to haemoglobin. 2. 's dissolved oxygen in the blood. What barriers must o%ygen travers to ass from the air in the alveolus to attach to haemoglobin? 6. Surfactant. 2. 0lasmalemma of alveolar epithelium /outer surface of epithelium1. 3. *ytoplasm of alveolar epithelium &. 0lasmalemma of alveolar epithelium /inner surface of epithelium1. ,. 3asement membrane of epithelium. 4. %nterstitium. ;. 3asement membrane of endotheCium. >. 0lasmalemma of endothelium /outer surface of endothelium1. ?. *ytoplasm of endothelium. 6<. 0lasmalemma of endothelium /inner surface of endothelium1. 66. 0lasma. 62. 0lasmalemma of red erythrocyte. 63. *ytoplasm of erythrocyte. What do you understand by im airment of diffusion? %mpaired e:uilibrium between the alveolar gas and the capillary blood. What diseases can cause im aired diffusion of o%ygen?

Surgical Physiology ;3 'sbestosis, sarcoidosis and interstitial fibrosis.

6%ygen delivery
!n what ways can o%ygen be delivered to the atients ? The patient can breathe room air as normal with an inspired oxygen concentration of 26 I . %ncreased concentrations can be inspired using a mas" system attached to an oxygen supply, but this gives a very variable concentration of inspired oxygen /!i@21 owing to a dilutional effect of the oxygen escaping around the mas". Digh air flow oxygen entainrment /D'!@.1 uses the =enturi principle with a high flow low pressure system to suc" in oxygen to give a "nown !i@2. ' reservoir bag uses the oxygen in the bag effectively to $dilute$ the inhaled mixture, increasing !i@2. To deliver !i@2 greater than &< I reliably , endotracheal intubation and ventilation is re:uired. %t should be noted that prolonged exposure to !i@2 greater than >< I is in+urious to the lung. Dyperbaric oxygen therapy also occasionally impinges on surgical practice in cases such as necrotizing fasciitis, %t delivers 6<< I oxygen at greater than 6 atmosphere of pressure in specially constructed tan"s . What is CP"P and what are its indications ? %t stands for continuous airway pressure. 0atients with impeding respiratory failure may be helped by this techni:ue, which uses a one way valve in a very closely appllied facemas". 's the patient expires, gas is expelled through the valve until a certain pressure is reached, after which no further gas is allowed to escape. This has the effect of always

Surgical Physiology ;& maintaining a positive pressure in the airways as the name suggests preventing collapse of alveoli, and even recruiting previously collapsed ones. %t is the stage of respiratory management before intubation and ventilation, but many patients find it very uncomfortable and are unable to tolerate the mas". There are also problems with the mas" causing pressure necrosis of the face particulary over the nasal bridge. !f the atient re#uires ventilation* What modes of ventilation are you familiar with? Describe what arameters the ventilator can be set to? The patient can, of course, be allowed to ventilate spontaneously, but this is not common in the %TA setting. %ntermittent positive pressure ventilation /%00=1 %t is the commonest mode, also "nown as continuous mandatory ventilation /*M=1. %n this mode, there is no patient interaction and the gas mixture is forced into the lungs at regular intervals, which has important physiological conse:uences. %n normal breathing , there is a negative intrathoracic pressure in inspiration, whereas in %00= the reverse is true, as there is a positive pressure in both inspiration and expiration . This has the effect of compressing the great vessels and impeding venous return cardiac output. %n this setting, a patient with borderline right heart function may well be tipped into right ventricular failure5 conversely, it may help left ventricular failure by assisting the s:ueeze of blood into the aorta. The machine can be set to give a set number of breaths per minute and to deliver either a set volume of gas or to provide gas at a given pressure or a given flow rate, one can also set the ratio of inspiration to expiration and this can be varied according to the clinical need in '79S or asthma, for example. Synchronized intermittent mandatory ventilation /S%M=1 %t allows the patient to do some of the worse. The ventilator is set to the lowest acceptable parameters and, if the patient does not breathe. The machine will cut in and perform that breath instead5 it is used as a weaning tool. 0ressure support ventilation /0S=1 %t allows the patient to breathe on their own, without a set respiratory rate but, if the patientKs breath does not reach a pressure trigger point, then the ventilator will aid the breath another weaning tool. What is P''P and autoP''P? 0..0 stands for positive end expiratory pressure. 's air leaves the lungs in expiration, the alveoli will tend to collapse. %n normal lungs, surface tension "eeps the alveoli open and allows inflow of gas with the next breath. %n the situation of poor repiratory function, alveoli will tend to collapse at the end of a breath . 3y setting the ventilator to a certain 0..0 level , as the airway pressure falls, the closure of a valve in the circuit will not allow the pressure to fall bac" below that level or to a negative pressure as happens in physiological ventilation thus splinting the alveoli open. The stiffer the lungs, the higher the level of 0..0 needed to achieve this aim.

Surgical Physiology ;, %n actuely ill asthmatics, the pressures in the airway are so high that they are still exhaling when the next breath starts, thus splinting the airway open so called auto0..0.

6%ygen trans ort

Describe the relationshi that governs 6 5 trans ort in the blood and draw the o%ygen+haemoglobin dissociation curve . ??I percent of oxygen is carried bound to haemoglobin with only 6 I carried in solution in plasma in proption to the partial pressure. The relationship between partial pressure /oxygen tension1 and percentage saturation is given by a sigmoid shaped curve. 0oint '%t is "nown as the p,< point. %t is the oxygen pressure at which haemoglobin is ,< I saturated. %t is important for two reasons6. %t helps to draw the curve. 2. %t is often used to compare the effects of conditions that shift the curve to either the right or the left. 0oint 3%t is the normal mixed venous point. 0oint *%t is the normal arterial point.

Surgical Physiology ;4

& memorable points ?;I ;,I ,<I 6<I ><mmDg /6< "0a1-normal arterial. &<mmDg /,.3 "0a1 normal mixed venous. 2,mmDg /3.4 "0a1 0,<. 6< mmDg /6.3 "0a1.

There are three reference points on the curve 0,< Q 3.4 "pa 0;, Q,.3"pa 06<<Q63.3 "pa

%mportant points on the curve The normal oxygen saturation of arterial blood is ?>I when the 0a@2 is 6<< mmDg. The normal oxygen saturation of venous blood is ;,I when the 0a@2 is &< mmDg. 't a pa@2 of 24 mmDg under normal physiological conditions, the saturation of Db is ,< I.

Why is the curve sha ed li$e it is ? %t is a sigmoid curve because haemoglobin exhibits peculiar binding characteristics. 3inding of one oxygen molecule to one haem molecule ma"es it easier for further binding to occur, which is represented by the steep mid portion of the curve. %t demonstrates large increases in percentage saturation for minimal increases in partial pressure, i.e. oxygenation of haemoglobin is relatively easy. This facilitation occurs until three out of four binding sites are occupied after which it gets slightly harder again, reflected by the curve flattening out at the higher saturations. What is the hysiological advantage of a sigmoid sha ed curve ? ' sigmoid shaped curve maximizes the :uantity of oxygen ta"en up in the lungs at low alveolar oxygen tension but maximieses the :uantity released in the system capillaries at a relatively high partial pressure. What is the im ortance of the sigmoid sha ed curve ?

Surgical Physiology ;; ' fall in 0o2 is tolerated provided the saturation remains above ?<I /lie the flat part of the curve1. %ncreasing the 0o2 above normal has little effect unless hyperbaric oxygen is used, when the amount of oxygen in solution in the plasma becomes significant. @n the steep part of the curve, small decreases in 0o 2 lead to large falls in saturation /lie oxygen content1.

What factors affect the affinity of haemoglobin for o%ygen ? D(, 0*@2 , tempreture and 2,3 diphosphoglycate- a rise of any of these factors reduce the affinity of haemoglobin for oxygen and will result in a rightward shift of the oxygen haemoglobin dissociation curve. How do clinical conditions affect the sha e of the curve ? The curve is shifted to the right /i.e. decreased affinity for oxygen 1 by6. 'cidosis. 2. %ncreased 2,3 902. 3. %ncreased tempreture. &. Dypercapnia /3ohr effect1. The curve is shifted to the left / ie increased oxygen affinity1 by 6. !etal haemoglobin /Db!1. 2. 9ecreased 2,3 902. 3. 'l"alosis. &. Methaemoglobinamia. ,. *arbon mnonxide poisoning. 4. Dyperthermia. ;. Dypocapnia. What is the effect of a right shift in the o%ygen dissociation curve ? ' shift of the curve to the right decreases the affinity of oxygen for Db i.e. oxygen is released more readily from Db at a given p@ 2. Therefore, at a given pressure of oxygen, say 24 mmDg, the standard Db oxygen dissociation curve has a saturation of ,<I which is reduced to &<I with a small right shift. What are the 2ohr and Haldane effects? The 3ohr effect%t is the shift in the curve due to changing /D(1. /'s the 0D of blood decreases its affinity for oxygen descreases, this is related to deoxygenated haemoglobin having a greater affinity for D ( than oxyhaemoglobin1. %t is due to binding effects with the imidazole groups of histidine. The Daldane effect-

Surgical Physiology ;> %t describes the effect of the differing buffering capacities of *@ 2 for both oxyhaemoglobin and deoxyhaemoglobin. 't the cell, deoxyhaemoglobin has a high buffering capacity for *@ 2 and accepts it readily. @nce returned to the pulmonary circulation, the binding of oxygen converts it to oxyhaemoglobin, which has a low buffering capacity, and thus offloads *@2 readily. What do the curves for myoblobin* carbon mono%ide and fetal haemoglobin loo$ li$e?

The implications are as follows!or myoglobin, it is positioned such that it will release its single molecule of oxygen only at low oxygen tensions, thus is not useful as a transport mechanism. *arbon monoxide has an avid affinity for haemoglobin, some 2<< times that of oxygen- the molecule is saturated at even very low tensions of *@ and is very difficult to displace. !etal haemoblobin, which has J instead of ] globin moieties, has a left shifted curve, increasing its affinity for oxygen at the lower tensions found in the fetus. What ha ens to the o%ygen dissociation curve in anaemia? 'naemia reduces the overall oxygen carrying capacity of the blood but does not affect the percentage saturation of Db, therefore the curve is inchanged.

How is C65 carried in the blood? *@2 is transported in the blood by three means6. D*@3 buffer system- accounts for approximately 4<I of *@2 carriage. 2. *arbamino haemoglobin compounds- account for approximately 3<I of carriage of *@2. *@2 reacts with the amine groups in haemoglobin to form carbamino Db. This reaction is faster if the Db is deoxygenated, as in venous blood

Surgical Physiology ;? 3. 9issolved *@2. *@2 is 2< times more soluble in blood than oxygen. This represents approximately 6<I of the total *@2 carriage. What is the alveolar gas e#uation? The alveolar gas e:uation describes the relationship between alveolar ventilation and 0a*@2. %t is the 0a*@2 that is constantly KsensedK by the brain stem repiratory centre and used to regulate alveolar ventilation. The e:uation states that the product of alveolar ventilation and arterial 0 a*@2 is a constant at any given level of *@2 production. What affect does a raised C65 have on blood vessels? 7aised *@2 concentrations have a moderate vasodilatory effect in most tissues, but have a mar"ed dilatory effect on the cerebral and coronary vasculature. %f *@2 is considered as the waste product of cellular respiration, any accumulation in areas, such as ischemic muscle, will have the effect of increasing blood flow through the area to try and reduce the tissue concentrations. What affect does a raised metabolic PaC65 have on res iration? 7aised metabolic *@2 gives rise to a metabolic acidosis because of combination with water forming carbonic acid, as detailed above. %n order to attempt to correct this, the respiratory rate is increased to exhale more *@ 2 and thus correct blood biochemistry. This is called respiratory compensation. What ha ens to a atient with carbon mono%ide inhalation? The carbon monoxide combines with haemoglobin to form carboxyhaemoglobin, stopping normal oxygen transport. Symptoms include6. Mental impairment. 2. Deadache. 3. #ausea. &. =omiting. ,. *lassic pin" s"in /usually rosy chee"ed1 due to the carboxyhaemoglobin. 4. *oma. ;. 7espiratory distress. >. *ardiac arrhythmias develop, leading to death if untreated . Treatment6. 7emoval from the *@ source. 2. 'dministering high flow oxygen5 in some centre. 3. Dyperbaric oxygen therapy is also used to increase the amount of oxygen held in direct solution as a compensatory mechanism, whilst the *@ is removed from the system.

What are the effects of hy ercarbia? 9efinition - 0a*@2 X 4 )0a . *entral nervous system effects %ncreases cerebral blood flow /increased hydrogen ions1. Stimulates sympathetic nervous system.

Surgical Physiology >< *arbon dioxide narcosis at levels c 62 )pa. 7espiratory system effects *arbon dioxide stimulates respiration at levels d 63 )0a, above this level, it acts as aaa depressant. %ncreases peripheral vascular resistance.

*ardiovascular system effects Myocardial depressant /effect blunted due to sympathetic stimulation initially, but at higher levels cardiac output is severely affected1. 'rrhythmias. 7enal effects *onstriction of glomerular afferent arterioles, leading to reduced urine output with high levels of carbon dioxide. What are the clinical features of carbon dio%ide retention? 6. !lushed s"in. 2. *haracteristic coarse flap of the hands /asterixis1. 3. 3ounding pulse. &. Muscle twitching. ,. Dypertension. 4. =entricular ectopics. ;. *onvulsions. >. *oma.

Surgical Physiology >6

&es iratory assessment

Draw a res iratory trace to show the volumes and ca acities of the lung?

What is the difference between a volume and a ca acity? ' capacity represents the sum of two or mor volumes. What is the functional sifnificance of the functional residual ca acity ? The functional residual capacity /!7*1%t is a effectively the bodyKs reservoir. %t is that volume of gas remaining in the lung after a normal exhalation. %t is the volume in which gas exchange actually occurs and, as such, is of the utmost significance. %n patients with repiratory failure, attemps are made to increase the !7*, by using continuous positive airway pressure /*0'01 or positive end expiratory pressure /0..01, in order to recruit more alveoli for gas exchange. What is meant by tidal volume? The volume of air entering8leaving the lungs during normal inspiration8expiration. What is meant by forced vital ca acity ? The volume of air expelled by maximal expiration following full maximal inspiration. What is meant by e% iratory reserve volume? The volume of air left in the lumgs following maximal expiration. What is the 3'4;834C ratio and why is it useful? %t is the ratio of forced expiratory volume in one second over the total forced vital capacity. %n a normal sub+ect this ratio is <.>.

Surgical Physiology >2 %t provides a useful way of distinguishing restrictive lung disease /!.=68!=*X <.>1 from obstructive lung disease /!.=68!=*L <.>1. "t is the difference between anatomical and hysiological dead s ace ? 'natomical dead space %t is the portion the tidal volume that remains in the upper part of the respiratoyu tree that is not involved in gas exchange. /the volume of gas exhaled before the *@2 concentration rises to its alveolar plateau1. %t is not constant and is influenced by many factors, including Size of the sub+ect. 0osture. 0osition of the nec" and +aw. Dypoventilation. 9rugs. Dypothermia. 'ge and the lung volume at the end of inspiration. 0hysiological dead space %t includes all non exchanging parts of the repiratory tree, i.e. anatomical dead space and alveoli not ta"ing part in gaseous exchange. %t is defined as the sum of all parts of the tidal volume. %t varies according to age, sex, size, posture , duration of inspiration and breath holding. %t is well "nown that prolongation of inspiration reduces the deadspace, allowing gas mixing to ta"e place between deadspace and alveolar gas. 4italogra hy is generally a laboratory tool. What other sim le measurements may hel you assess res iratory function? ' good history %t will allow you to ma"e an assessment of respiratory function by gauging ability to perform everyday tas". .xamination .xamination of the chest may reveal clunbing, barred chest,wheeze, or the crac"les of fibrosis or failure. %nvestigations ' chest x ray will reveal much in the way of pulmonary pathology, such as emphysema, basal fibrosis and right heart enlargement. 'rterial blood gas analysis will give useful information regarding the state of gas exchange in the patient. ' non invasive measure of respiratory capacity can be provided by using a hand held flow meter to measure pea" expiratory flow rate /0..71. What would you e% ect your P''& to be << and that for an acute severe asthmatic? 'n average adult would have a 0..7 between &,< and 4,< C8min depending on sex, build and degree of fitness. %n acute severe asthma, the 0..7 falls to between 33 and ,< I of normal or best predicted for that patient. %f the 0..7 falls below 33 I of best predicted, then it is termed life threatening asthma and warrants careful consideration of %TA treatment.

Surgical Physiology >3

:ung function tests

What is the ea$ e% iratory flow rate ,P''&-? %t is maximal rate of air flow during a sudden forced expiration / litres8minute1 6. #ormal female 0..7- 3,< ,<< litres8minute. 2. #ormal male 0..7- &,< ;<< litres8minute. 3. 7educed in obstructive disease, eg asthma. Can you define the values obtained in s irometry? !.=- !orced expiratory volume5 volume of gas forcibly exhaled from full inspiration. !.=6- !orced expiratory volume ehhaled in 6 second /reduced in obstructive pulmonary disease1. !=*- !orced vital capacity5 largest volume if air forcibly expired after maximum inspiration /reduced in restrictive disease, if supine, elderly, muscle wea"ness, emphysema1. !.=68!=*- expressed as a percentage5 normal is X ;<I /reduced in obstructive disease5 increased8normal in restrictive disease1. What is lung com liance ? %t is volume change per unit of pressure change, ie a measure of distensibility. #ormal lung compliance is 6,< 2<< ml8cm D2@. *an be divided into Static compliance- i.e. alveolar distensibility /reduced in pulmonary fibrosis and pulmonary oedema1. 9ynamic compliance- related to aiway resistance /decreased in chronic bronchitis1. What is the effect of P"C65 and P"65 on minute volume and res iratory rate? 7epiratory rate 7epiratory rate

0'*@2 @n a minute to minute basis, the 0'*@2 is proportional to the repiratory rate. This is 0'@2 brought about by the centeal chemoreceptors. The 0'*@2 brings about an increase in repiratory rate and minute volume only at :uite low values, this being effected by the peripheral chemoreceptors.

Surgical Physiology >&

What are the investigations for aasessing re iratory function? #on invasive6. 0ea" flow- bedside measure of respiratory muscle function and airway resistance. 2. 0ulse oximetery- estimated arterial oxygen saturation. 3. *apnography- end tidal *@2 is measured as a mar"er of ventillatory function. &. Spriometry- a measure of lung volumes and forced expiratory capacity. ,. 2as transfer function- a measure of the diffusing capacity across the alveolus. 4. =8P scanning and *T pulmonary angiography if pulmonary emboli are suspected. ;. .chocardiography- assessment of 0' pressure and right heart function in pulmonary hypertension. @ther imaging modfalities- plain radioglo. *t and M7%. %nvasive6. '32s- gold standard measurment of arterial oxygenation and 0a*@2. 2. 'lso crucial formassessment of acid base balance. 3. 3ronchoscopy- for assessment of lesions and8or secretions, can be flexible or rigid. &. Cung biopsy- *T guided or open via thoracic procedure or open thoracotomy. 3low+volume loo s in obstructive = restrictive ulmonary disease? 0lotting the relationship between airflow and lung volume over the respiratory cycle gives an indication of the type of pulmonary disease. @bstructive disease, such as asthma, brochiectasis and *@09 show an increase in the total lung capacity and residual volume as a result of air trapping and hyperinflation. 7estrictive disease shows a reduction of all volumes because of 'n alteration inlung parenchyma /e.g. idiopathic pulmonary fibrosis, fibrosing alveolitis1. or 9isease of the pleura. *hest wall /e.g. "yphoscoliosis1. #euromuscular apparatus as seen

Surgical Physiology >,

Hy o%ia
How do you classify hy o%ia? 6. Dypoxaemic hypoxia- reduced 0a@2 due to hypoventilation, diffusion impairment, shunt, =8P mismatch. 2. Stagnant hypoxia- inade:uate blood supply to an organ5 0a@2 and haemoglobin may be normal. 3. *ytotoxic hypoxia- normal oxygen delivery but cells prevented from utilizing it /cytochrome poisoning1. &. 'naemic hypoxia- 0a@2 normal, haemoglobin low. Can you suggest methods of su lementary o%ygen delivery ? Q 3<I &<I. #asal cannula Q up to ,<I. !ace mas" Q up to 4<I. =enture mas" / fixed performance1 Q up to 6<<I. 7eservoir bag What are the roblems and ris$s associated with o%ygen thera y? 7educed hypoxic ventilator drive /be aware of this in *@091. 0ulmonary toxicity /increased free oxygen radicals5 decreased surfactant and compliance. 'telectasis. !ire ris".

Surgical Physiology >4

Physiological effects of altitude and diving

What are the main hysiological effects of altitude ? The physiological effects include Dypoxia hyperventilation low 0a*@2. 7ise in cerebral blood flow cerebral oedema.

Cow @2 pulmonaryvasoconstrictionpulmonary hypertensionpulmonary oedema 's one ascends to high altitude, the first effect is a fall in 0a@2. This hypoxia stimulates a number of compensatory mechanisms. Dyperventilation is caused by stimulation of the peripheral chemoreceptors /mainly the carotoid bodies1. This causes the 0a*@2 and Y D(Z to fall . What are the changers at altitude? ". !mmediate changes> 7epiratory M acid base 0eripheral chemoreceptors detects a drop in 0@ 2 which leads to a reflex tachypnoea and increase in depth of repiration. This results in 7epiratory al"alosis and its associated features /tingling, fingers, etc.1. Dypocapnia, which reduces the drive of the central chemoreceptos /nont suitable1. This is compensated for in the short team by removal of bicarbonate ions by the choroid plexus from the *S!. 'l"alosis has an adverse effect on oxygen delivery-

Surgical Physiology >; 3ecause al"alosis shifts the oxygen haemoglobin dissociation curve to the left, thus ma"ing it more difficult for the haemoglobin to give up oxygen at the tissues at a given 0@2. 7educed humidity can lead to a dry cough. *ardiovascular 7eflex tachycardia and cardiac output increase initially, via stimulation of the peripheral chemoreceptors by hypoxia, to increase oxygen delivery to the tissues. *erebral blood flow increases to increase delivery of oxygen to brain. 2. Slow changes> 7espiratory M acid base The al"alosis created by tachypnea is compenstaed for in the "idney by increased excretion of D*@3 ions, a slow metabolic compensation. %ncreased production of 2,3 diphosphoglycerate /9021 compensates for the left shift of the @2 haemoglobin dissociation curve and facilitates releaase of oxygen to the tissues. The chronic hypoxia leads to increased production of erythropoietin by the "idney, which causes increased haemoglobin synthesis. This improves oxygen carriage, and individuals chronically exposed to altitude become chronically polycythemic. There is a blunted response to hypoxia as the individual acclimatizes and the al"alosis improves over time. There may also be an increase in the alveolar size and a decrease in the thic"ness of the alveolar membranes, leading to more efficient gas transfer. *ardiovascular *hronic hypoxia leads to pulmonary vasoconstriction and hypertension, and this can lead to pulmonary oedema. 3lood viscosiy increases at altitude. C. 6ther medical roblems> Thrombosis. 7etinopathy. %mmunosuppression. What hysiological changes can be seen with acclimati/ation ? %nitially in the acclimatation process there is an increase in respiratory drive /hyperventilation1 Cater Daemoglobin concentration increases which has the effect of increasing the oxygen carrying capacity. 2,3 902 /diphosphoglycerate 1 concentration rises, which in turn decreases the affinity of Db for oxygen so causing a right shift of the @2 dissociation curve. What are the main hysiological effects of diving ? !or every 6< m of depth in sea water, the ambient pressure increases by 6 atmosphere. The lung volume halves at a depth of 6< m and the partial pressures of the gases

Surgical Physiology >> double. This may lead to nitrogen narcosis, oxygen toxicity, impairment of intellectual functions, tremors or drowsiness. What are the main dangers of a fast ascent ? 3arotrauma, air embolism and decompression sic"ness are the main dangers of fast ascent. #itrogen escapes from solution and bubbles in the tissues may cause severe pains /especially +oints1, neurological symptoms and in more severe cases the bubbles may obstruct the cerebral, pulmonary and coronary vessels.

?idney* "cid+base = 'lectrolytes

Surgical Physiology >?

0he $idney
What are the functions of the $idney? The important functions of the "idney include6. Maintaenance of body fluid osmolarity and volume, electrolyte and acid base balance. @smolarity is regulated by the excretion of water and #a*l. 'cid base balance is achieved through secretion of D ( and absorption of D*@3 .

2. .limination of water soluble waste products of metabolism and foreign substances Metabolic products include urea /from amino acids1 and creatinine /from muscle protein1. !oreign substances include brea"down products of drugs.

3. Dormone production and secretion. Dormones include 7ennin. 6,2, dihydroxycholecalciferol. .rythropoietin. 0rostaglandins and "inins /such as brady"inin1.

What are hormones are roduced by the $idney? 7ennin- released from the +uxtaglomerular cells. )alli"rein- produced in the distal nephron. Dydroxylase production- converts 2, hydroxycholecalciferol into 6,2, dihydroxycholecalciferol. .rythropoietin- produced in response to anemia. 0rostaglandins- produced in the cortex and medulla.

What are the main buffers in the maintenance of acid+base balance? 0roximal tubule- D*@3 8D2*@3 buffer system. 9istal tubule - D0@&2 8D20@& buffer system. The phosphate buffer is the most important in normal renal function. #D&( buffer system is the weast buffer but allows the excretion of acid without the loss of #a(.

Surgical Physiology ?< Where are the sites of water reabsorbtion ? 6. 0roximal tubule- passive transport along osmotic gradient/ ;,I of resorbtion1. 2. 9escending limb of loop of Denle - passive transport. 3. 9istal tubule - under the control of antidiuretic hormone /'9D1. &. *ollecting ducts - under the control of '9D. How is the osmolarity of urine controlled? The concentration of urine is under the control of '9D on the collecting duct. '9D increases permeability and results in increased water resorbtion . @smolarity varies between ,< and 62<< mosmol86.

How does the $idney maintain a constant e%tracellular fluid , 'C3- osmolarity? #a*l is the ma+or determent of .*! osmolarity. Carge variations of water and #a*l ingestion do not produce similar changes in .*! volume and osmolarity, as the "idney is able to compensate by excreting urine that is either hyperosmotic /concentrated1 or hypo osmotic /dilute1 with respect to *S!. %f .*! osmolarity increases The hypothalamus responds by increasing anti diuretic hormone /'9D1 release. '9D increases the permeability of the collecting ducts of the "idney to water. Bater is thus reabsorbed resulting in a small volume of concentrated urine %f the .*! osmolarity decreases '9D secrestion and the sensation of thirst are both supported. This results in reduced water reabsorption from the collecting ducts and production od a large volume of dilute urine. How is 'C3 volume regulated? The .*! volume is regulated by low and high pressure sensorsDigh pressure sensors6. 3aroreceptors /pressure sensors1 in the aortic arch, carotis sinus. 2. 'nd afferent arterioles of the "idneys send afferent impulses to the brain stem via the vagus and glossopharyngeal nerves about the .*! volume. !or example if .*! volume rises, there is decreased sympathetic activity and reduced '9D secretion. %n addition, pressure receptors in the afferent arterioles of the "idney suppress renin secretion through a negative feed bac" loop. The net result is system vasodilatation and decreased renal #a ( absorption. Cow pressure sensors /pulmonary vessels and atria1 have the opposite effect so that sympathetic activity, '9D secretion and the 7enin 'ngiotensin 'ldesterone axis are all stimulated. What is the glomewrular filtration rate ,(3&- ? 9efinition- =olume /in ml1 of plasma filtered by the "idneys per minute /normal is 62< ml8minute1.

Surgical Physiology ?6

How do you measure (3&? The 2!7 is measured by infusion of a substance that is freely and neither reabsorbed nor secreted by renal tubulesThe basic formula for clearance /*x1 of a substance x is 2!7 /*x1 Q /urine concentration of x /mg8dl1 x urine volume 8time1 8 plasma concentration of x %nulin can be used but is difficult to measure. 'n alternative is to use creatinine clearance /approximates to the 2!71, averaged over 2& hours /normal range is ?< 63< ml 8minute1.

What are the indications for dialysis haemofilteration? The indications are Symptoms of uraemia. *omplications of uraemia e.g pericarditis. Severe biochemical derangement in the absence of symptoms /e.g. rising trend in an oliguric patient1. Dyper"alemia not controlled by conservative measures. Severe acidosis. 7emoval of drugs causing acute renal failure /gentamicin, lithium, aspirin overdose1.

Surgical Physiology ?2

(lomerulus
Can you describe the glomeulus ? The glomerulus is formed by a group of capillaries, supplied by an afferent arteriole, invaginnating into the 3owmanKs capsule and drained by an efferent arteriole. What is the anatomy of the ne hron?

The blood is filtered at high pressure in the glomerulus, the large proteins and cells remain in the blood and water, and solutes pass into the bowmanKs capsule and the nephron5 6;< 6><C of plasma are filtred a day.

Surgical Physiology ?3 Several solutes are actively reabsorbed in the proximal tubules, including sodium, glucose, calcium, phosphate and chloride. Bater is also reabsorbed as are amino acids. The renal medulla contains a gradient of sodium, which is most concenterated at the center and more dilute at the periphery. More sodium is pumped out actively at the thic" ascending limb of the loop of henel to maintain the sodium gradient. What is the function of the glomerular membrane? The glomerular membrane allows passage of neutral substances up to &mm in diameter into the 3owmanKs capsule and excludes substances with a diameter of over > mm, though the charge of the substance affects its passage across the membrane. /The endothelium of the glomerulus is fenetrated and contains pores ;< ?< nm wide and the glomerular epithelium contains filtration slits 2,nm1. How is the glomerular filtration rate ,(3&- measured ? The 2!7 can be measured by measuring the extraction and plasma level of a substance that is freely filterd through the glomerular and is neither secreted nor reabsorbed by the renal tubules. The total amount of plasma filtred through the glomeruli is 6;< 6>< 68day. 2!7 is approximately 62,ml8minute. What substances can be used to measure (3&? %nulin can be used to measure 2!7 /inulin is a fructose polymer1. What are the factors that increase (3&? %ncreased renal blood flow. %ncreased capillary hydrostatic pressure. %ncreased afferent arteriolar pressure. 9ecreased efferent arteriolar pressure. %ncreased glomerular permeability. Dypoproteinemia.

What factors decrease (3&? The opposite of any of the factors listed in the :uestion above , and 9ecreased systemic blood pressure /L ?<mmDg1. Areteric obstruction. @edema of the "idney. 9ehydration. 9ecreased in effected filtration surface area.

Surgical Physiology ?&

:oo of Henle
What is the function of the loo Henle? 9escending limb- water , #a( and *l U are reabsorbed. 'scending limb- impermeable to water but #a( and *l are reabsorbed. !ormation of countercurrent multipliers.

What are the different ty es of loo of Henle? Cong /+uxtamedullry nephrons1 and short /cortical nephrons1 loops. %n man 6,I of nephrons have long loops. Which are im ortant in the formation of a countercurrent multi lier? The long loops, the longer the loop the greater the osmolarity at its tip. What is the advantage of this countercurrent multi lier ? ' high osmotic gradient is formed across the "idney with the cortex being isotonic and the medulla hypotonic. This allows a very dilute urine to be produced in the distal tubule.

Surgical Physiology ?, Countercurrent multi lier formation> The thin desecending limb of the loop of Denle is permeable to water and the thic" asecending limb is not. Sodium is pumped actively from the tubular fluid in the ascending limb of the loop of Denle to the interstitium /at the centre of the loop1. !luid moves from left to right through the loop. The se:uence of events is as follows6. 'll concentrations are e:ual. 2. Sodium is prepared out of the ascending limb . 3. The increased concentration of sodium in the interstitium e:uilibrates with the fluid in the descending limb. &. !luid moves around the loop of Denle. ,. 'gain , fluid is pumped from the thic" ascending limb into interstitium. 4. The fluid concentrations e:uilibrates as before. ;. The fluid moves once again. ' gradient has started to form. This is maintained by the sodium pumps and the constant delivery of the sodium to the loop of Denle. The fluid leaving the loop of Denle is very hypotonic because sodium has been pumped away from it. Bater is later reabsorbed through water channels in the collecting system. This sodium gradient, together with the coutercurrent multiplier arrangement of the loop of Denle and the blood supply, allows the urine to be concentrated, because water follows sodium, the main anion in the blood. 's the fluid filtered by the 3owmanKs capsule enters the loop of the Denle and progress through the permeable descending limb, water enters the more concentrated interstitium by osmosis. Sodium and chloride are reabsorbed here.

How do loo and thia/ide diuretics wor$? 's water follows sodium, bloc"ing of the sodium channels in the proximal tubule, loop of Denle or distal tubule causes a dieresis /sodium not reabsorbed, so excreted with water15 this is the basis of the action of different types of diuretic. %n the loop of Denle, bloc"ing of the sodium channels dissipates the sodium gradient and the "idney cannot concentrate urine /loop diuretics such as frusemide1. %n the proximal tubule, if sodium reabsorption is bloc"ed /thiazide diuretics such as bendrofluazide1 more water and sodium are excreted. D!S0": 0@2@:' %n the distal tubule, potassium is excreted under the control of aldosterone, in exchange for sodium.

Surgical Physiology ?4 %n the collecting duct, water is reabsorbed via water channels, the synthesis of which is mediated by '9D. Some urea is passively reabsorbed, but the main contents of the urine here are urea, sodium and water.

&enal failure
Classify renal failure and give e%am les each ty e ? %t can be easily classified into pre reanl, renal and post renal renal fai"lure. 0re renal failure%t is due to inade:uate renal perfusion due to reduced intravascular volume or lowerd effective arterial circulation *ommonest surgical causes include6. 2astrointestinal losses. 2. Daemorrahge. 3. Sepsis. &. Third space losses. May lead to acute tubular necrosis if untreated.

Surgical Physiology ?;

7enal 'cute tubular necrosis. 2lomerulonephritis. 9rugs. 0ost renal failure ocuurs due to 3loc"age of the passage of urine %t may be within the "idney, such as when myoglobin bloc"s the glomeruli. The bloc"age is extra renal by neoplasms, calculi, prostatic enlargement, strictures or catheter occusion. Aou are as$ed to see a catheteri/ed* male* osto erative surgical atient who hasn1t assed any urine for B hours. How are you going to assess the roblem? True anuria is generally only caused by a bloc"ed outflow tract commonly a bloc"ed catheter, and so this is li"ely to be oliguria rather than anuria, oliguria being defined as a urine output less than /<., ml8"g per hour1. %nitially, a history is ta"en and the patient examined. Specific evidence of previous renal insufficiency an enlarged bladder and the state of circulatory filling is sought. The catheter should be flushed to ensure it is not bloc"ed. .xamination of his fluid input8output charts would indicate, along with his pulse, blood pressure and pulse pressure, whether he was li"ely to be underfilled. 'll recent urea and electrolyte results should be examined and a new set re:uested. 'll information is interpreted in light of the patientKs operation and operative fliud losses. %n general, post renal causes should be excluded and any evidence to suggest intrinsic renal failure is sought.

What is the management of osto erative oliguria? %n the evident, the patient appeared fluid depleted increased intravenous fluid are prescribed, giving due regard to his cardiovascular status and the patientKs ability to accept fluid loading. %f fluid filling within the limits of clinical monitoring did not abate the oliguria, then more invasive monitoring in the form of a central venous pressure line is appropriate. Bith a *=0 line in situ, a fluid challenge is given to the patient to gain an indication of the state of filling. %f clinically and with *=0 readings the patients is well filled but still oliguric, then the use of diuretics may be appropriate, normally in the form of intravenous frusemide. KCow dose renalK dopamine has not convincingly been shown to help this type of oliguric patient beyond acting as an additional diuretic.

Surgical Physiology ?> %f the patient were well filled and remained oliguric after diuretics, and outflow obstruction from rare conditions, such as bilateral uretic obstruction was excluded, then the %TA should be contacted for assistance. %n the face of deteriorating reanl function, as witnessed by rising urea and potassium concentrations and fliud accumulation, then renal dialysis should be considered. %n patients with compressed renal function, #S'%9 should be avoided as should '*. inhibitors if possible. 2entamicin is nephrotoxic and should be changed to another antibiotic if possible.

What are the indications for renal re lacement thera y? 7enal replacement therapy /77T1 is indicated in 7enal failure of whatever aetiology. Ancontrollable rising serum potassium, sympathetic uraemia or its complications. Severe acidosis or pulmonary oedema from fluid overload. How can &&0 be achieved ? 'vailable methods are haemodialysis, peritoneal dialysis and haemofiltration. %n haemodialysisThe patientKs blood is pumped through an artificial "idney with a dialysis to KfilterK the blood by ultrafiltration. 3oth hydrostatic pressure from the pump and an osmotic pressure generated from the glucose present in the dialysis fluid are used to drive the ultrafiltration process. 0eritoneal dialysis%t allows a dialysis fluid to reside in the peritoneal cavity with exchange of metabolites by diffusion alone. DaemofiltrationThe patientKs blood is driven through a filter by the patientKs arterial pressure, and a dialysis added around the filter and diffusion of waste metabolites occurs into the dialysis. it is, in essence, a slow haemodialysis.

"cute renal failure

How do you define acute renal failure? 'cute renal failure in adults may be defined as a creatinine X 62, emol8l recoreded within the last &> hours and oliguria of L 63, ml in the last > hours. !n ractice what should the normal urinary out ut be above? <., ml8"g per hour. What does the icture of oliguria and high urine osmolarity indicate? This indicates that the "idneys are concentrating urine appropriately and indicates a pre renal cause for the oliguria. %f you have oliguria and a urine osmolarity similar to serum osmolarity, i.e.3<< emol8l, this suggests established renal failure.

Surgical Physiology ??

Can renal failure occur without oliguria ? Ses, particularly if diuretics are used to maintain urine flow. What are the common causes of acute renal failure in a surgical atient? The common causes of acute renal failure in surgical patients are sepsis and hypotension. Can you list any ris$ factors that redis ose a surgical atient to develo ing ost+o acute renal failure? The potential ris" factors are factors are 0re existing renal disease. 9iabetes mellitus. 0re existing cardiac failure. .vidence of reno vascular disease and hypertension. The older patient is also more prone to developing renal failure. 9iuretics, antibiotics such as amino glycosides /gentamicin1, non steroidal anti inflammatory agents, cyclosporine and contrast media will exacerbate renal failure. %n addition, +aundice or myoglobinaemia will have detrimental effects on the "idneys. How may e%amination of the urine be useful in the management of acute renal failure? The presence of white cells suggests infection or inflammation. Daematuria suggests stones or tumor. Bhole castsd suggests intrinsic disease /e.g. glomerulonephritis1. 0rotein suggests glomerular in+ury. Specific gravity X 6.<22 suggests intact concentrating ability. Spot urinary sodium concentration may help differentiate prerenal failure from acute tubular necrosis /fractional sodium excretion in prerenal failure is L6I fractional sodium excretion in acute tubular necrosis is X6I1. Arine culture for infection.

Can you outline the rinci les of management of acute renal failure ? The management of acute renal failure is not restricted to the "idney but the management of the patient as a whole. %t is important to treat any multiple organ dysfunction. The patient should be resuscitated. Dypoperfusion must be corrected, with the use of fluids, blood and inotropes as necessary. %nvasive cardiovascular monitoring may be of advantage depending on the patientKs condition. T reatment of any underlying sepsis should be commenced. 'ppropiate antibiotics must be given having ad+usted for reduced excretion rates due to renal failure. #utrtitional support should also be considered.

Surgical Physiology 6<<

"re diuretics of any use in the treatment of acute renal failure? 9iuretics may be useful in some patients to maintain urine volume. Dowever, if they are used inappropriately they may precipitate acute renal failure. !urosemide %t has theoretical benefit in that it may reduce medullary wor" thereby reducing tubular oxygen demand. %t acts on the loop of DenleK and reduces chloride and hence sodium re absorption. Some studies have shown that a continuous infusion of !uresemide rather than boluses is more beneficial, as blousing may induce further hypovolaemia. Mannitol %t has also been used and is often described as a renal protective agent due to its osmotic diuretic, free radical scavenger and renal vasodilatory effects. Dowever, protective trials have not demonstrated any clear benefit. %t is of great importance when considering using diuretics in patients with acute renal failure to ensure that cardiovascular resuscitation and fluid loading has been performed before instituting diuretic treatment.

&enin+"ngiotensin+"ldosterone system
What is rennin and what stimulates its release? 7ennin is a proteolytic enzyme /molecular weight &<.<<< 9a1. Synthesized and stored in the +uxtaglomerular apparatus. 7eleased in response to decreases in circulating volume 9ecreased afferent arteriolar pressure. 9ecreased sodium delivery at the macula densa.

Surgical Physiology 6<6 What are the actions of angiotensin !!? =asoconstriction- intrarenal and systemic. %ncreased proximal tubular sodium reabsorption. 'ldostrerone release from the adrenal cortex. %ncreased distal tubular sodium reabsorption. Stimulates thirst. 'ntidiuretic hormone release- leads to water retension.

What are the causes of hy eralsosteronism? 0rimary- adrenal cortical tumour /*ronnKs syndrome1. Secondary 0regnancy. Deart failure. *hronic diuretic therapy. 9ietary salt restriction. *irrhosis with ascitis. #ephrosis.

What is the body1s rimary mineralocorticoid? Describe its synthesis and control of its secretion? 'ldosterone is the ma+or mineralocorticoid. %t is synthesized in the zona glomerulosa of the adrenal cortex by 6> hydroxylation of a cholesterol s"eleton. %t is under the control of the rennin angiotensin system and not the hypothalamic pituitary axis. ' decrease in the glomerular filtration rate /2!71 stimulates release of rennin from the +uxtaglomerular apparatus which in turn cleaves angiotesinogen to angiotensin%. This is, in turn, acted upon by angiotensin converting enzyme /'*.1 to cleave the decapeptide into an octapeptide, angiotensin%% , one of the most potent vasoconstrictors yet isolated. The effect of angiotensin %% %ncrease peripheral resistance, particulary at the efferent renal arteriole. Stimulate synthesis of aldesterone. The primary role of aldesterone is regulation of sodium. %t increases sodium resorption in the "idney and water will follow by osmosis, thus increasing extracellular volume and hence correcting 2!7. %t should be noted that when sodium is resorbed under the control of aldesterone, it exchanges at the cell membrane with either potassium or hydrogen ion5 thus aldosterone excess can lead to hypo"alaemia. 'lternatively, if potassium is already low, the #a( will exchange for D(, which increases bicarbonate production leading to hypo"alemic al"alosis. 'ldosterone is metabolized by hepatic con+ugation and urinary excretion.

Surgical Physiology 6<2

What is Conn1s syndrome and how does it resent? *onnKs syndrome is primary hyperaldosteronism @ver half of the cases are due to a single benign adrenal cortex adenoma. 6< I are multiple adenomata. @ne third due to bilateral hyperplasia. Secretion from a carcinoma is extremely rare. .xcess plasma sodium, freed from normal negative feedbac" control, stimulates increased antidiuretic hormone /'9D1 secretion. '9D acts in response to increased extracellular fluid osmolarity by increasing distal tubular permeability and increasing the volume of resorbed water5 thus '9D excess leads to water retention and an expanded extracellular fluid volume. The clinical features of this are6. Dypervolaemic hypertension. 2. Dypo"alaemic al"alosis which may be so severe as to lead to tetany owing to the effect on calcium binding. 3. Muscle wea"ness and even paralysis due to the hypo"alaemia. &. %ncreased plasma bicarbonate, hypernatraemia and low urinary sodium contentration also occur. What are the causes of secondary hy eraldosteronism? Secondary hyperaldosteronism occurs when there is a low 2!7 in spite of normovolaemia. 2ood examples are 9amaged renal vessels from either hypertension or renal artery stenosis. 7educed colloid osmotic pressure, as in the nephritic syndrome or cardiac failure, causing poor renal perfusion. %n secondary hyperaldosteronism plasma rennin is elevated because of the mechanisms described overstimulating the +uxtaglomerular apparatus. %n the primary condition, aldosterone is elevated, which increases plasma volume and therefore, results in low levels of plasma rennin. 6utline your management of an adrenal lesion identified as an incidental finding on C0 scanning So called $incidentalomas$ are thought to arise with an incidence of up to 6< I. %. %nitial investigation is to determine whether the lesion is functional or not Serum aldosterone and cortisol. Arinary catecholamines and cortisol. Cow dose dexamethasone suppression test. #either biochemical mar"ers nor scanning will reliably distinguish benign from malignant tumors in most cases. %n most centres, management depends on the size of the lesion and age of the patient Cesions greater than & cm in size in patients under the age of ,< should be surgically removed. Smaller lesions should be monitored closely with serial scanning. The ris"s of malignancy increase with the size of the lesion and the relative ris"s for a given size of tumor are higher the younger the patientKs age.

Surgical Physiology 6<3

"cid+2ase 2alance
!nter ret the arterial blood gas readings shown? 3lood gas value

Surgical Physiology 6<& 0D 0@2 0*@2 ;.24> 2&.3 )0a ,.<, )0a 'cid base status c 3ase /.cf1c U >.? mmol8C c D*@3 /p,st1 c 6;.6 mmol8C .lectrolyte values c)( ,.< mmol8C ( c#a 63; mmol8C c*a(2 6.64 mmol8C c*l 66,mmol8C c)( ,.< mmol8C Metabolite values c2lu ?.<mmol8C c Cac <.? mmoll8C @ximetry values ctDb ,.3g8dl !@2Db ?;.4I !MetDb <.;I ! DDb <.,I Dct 64.>I !*@Db 6.2I 0D is log6< 68/D(1 and is a measure of hydrogen ion concentration, i.e. acidity or al"alinity. #ormal blood 0D is ;.3, ;.&, p@28p*@2 measure the partial pressures of oxygen and carbon dioxide in the blood. They are affected by changes in respiratory function, and the p*@2 is particularly affected by acidity, since D( ions will combine with *@2 to form bicarbonate and water. #ormal ranges are p@2 6< 63.3 "0a and p*@f &.> 4.6 "0a. Standard bicarbonate is the amount of D*@3 in the sample when e:uilibrated at 3;<*, p@2 63.3 "0a and p*@2 ,.3 "0a. #ormal values are 22 3< mmol8C. lower values imply a metabolic acidosis. 3ase excess the amount of acid or al"ali that needs to be added to the sample at 3;o* to achieve a 0D of ;.& with p@2 63.3 "0a, and p*@2 ,.3 )0a. 0ositive base excess is an al"alosis and negative base excess is acidosis. #ormal value are 2 to (2. Tissues metabolizing glucose with an inade:uate oxygen tension produce lactate. Cactate rises with decreased tissue perfusion or with tissue ischaemia. #ormal values are less than 6.< mmol8C. The patient has a profound acute metabolic acidosis. The 0D is low with a low bicarbonate and a significant base deficit. The p@2 is high /this patient is receiving oxygen therapy1 and the p*@2 is in the normal range. *ommon potential causes of this picture are shoc", renal failure and tissue ischaemia, such as ischaemic bowel. What is the normal PH range in the blood? The normal 0D range is ;.3, ;.&,. Why is the PH maintained within such a narrow range?

Surgical Physiology 6<, The purpose of regulating the 0D within this narrow range is to maintain the shape and structure of enzyme which control numerous metabolic reactions in the body. !ailure of regulation leads to cellular damage. How is this PH maintained ? 'ny 0D changes are buffered to minimize any immediate effects. The "idney and lungs are then involved in further modification through the excretion of $acid$. What is the main buffer system in the e%tracellular fluid? The *@28D*@3 buffer is the most important system in the body. *@2 ( D2@ g D2*@3gD( ( D*@3 *arbonic anhydrous /*'1 catalyses the first /rate limiting1 step. The second step is instantaneous. What is an acid* a base and a buffer? 'n acid is a proton donor. ' base is a proton acceptor. ' buffer is a combination of a wea" acid and its con+ugate base. %t wor"s best at a 0D e:ual to its 0)a, i.e. when it is maximally dissociated. What is acidosis* al$alosis = base e%cess? 'cidosis /or acidaemia1 is an excess of D( ions in the blood. 'l"alosis /or al"alaemia1 is a deficiency of D( in blood. 3ase excess /normal value <1- measures how far removed bicarbonate is from its normal value. 'cidosis %f 0*@2 X ,.3 "0a Q repiratory acidosis. %f D*@3 L 2& mmol8C Q metabolic acidosis. 'l"alosis %f 0*@2 L &.> "0a Q repiratory al"alosis. %f D*@3 X 2> Q metabolic al"alosis. What is acidosis and how is it classified? 'cidosis occurs when the 0D of the arterial blood is less than ;.3, %t may be classified into metabolic and non metabolic causes. This distinction is made via the anion gap which is defined as the sum of the ma+or cations /i.e. sodium and potassium1 minus the sum of the ma+or anions /bicarbonate and chloride1. The normal range for the anion gap is between 62 mmol8C and 2< mmol8C. 'n acidosis with a normal anion gap results from the replacement of bicarbonate by chloride, causes by6. 2astrointestinal losses diarrhoea, pancreatic fistula, ileostomy 2. 7enal renal tubular acidosis types%%% and %=. 'n acidosis with an increased anion gap signifies that there has been addition of exogenous or endogenous fixed acids, as in6. Cactic acidosis. 2. 9iabetic "etoacidosis.

Surgical Physiology 6<4

How is acid roduced in normal metabolism? Two forms of $acid$ are produced in normal metabolism. Metabolism of carbohydrates and fats produce *@2 which is called a $ volatile acid$ because it can be excreted from the lungs. The metabolism of many foods, particularly those that have a high protein content produce $non volatile acids$ such as sulphuric, hydrochloric and phosphoric acid. What do you understand by the term metabolic acidosis? Metabolic acidosis is the condition where the plasma 0D falls below ;.3, following a decrease in the plasma D*@2 . What are the common causes of metabolic acidosis? 6. 'naerobic metabolism secondary to poor oxygen delivery to the tissue /The commonest cause161 Metabolic shoc" /post M%1. 21 Dypovolaemia /trauma, septic shoc"1. 31 %n situation of increased oxygen demand /sepsis, trauma1. 2. 9iabetic "etoacidosis. 3. 3ody canKt get rid of acid- renal failure. &. 0oisoning with acid /e.g. aspirin1. ,. Coss of bicarbonate /e.g. diarrhea1. What are the causes of res iratory acidosis? 'ny cause of hypoventillation cardiac arrest, *@09, pneumonia, asthma. What are the harmful effects of acidosis? 6. Suboptimal enzyme action. 2. 9ecreased myocardial contractility8arrhythmia. 3. 9ecreased oxygen carrying ability of haemoglobin. &. 9ecreased response to vasopressor agents. ,. Dyper"alemia and impaired potassium secretion. 4. Dyperventillation and exhausion. How would you inter ret these arterial blood gases? PH C.DE* HC6D ;F mmol8:* C65 DEmmHg. The 0D is X ;.3, so this represents an acidosis. To determine whether this is a metabolic or respiratory acidosis we must loo" at the 0*@2 and D*@3. the 0*@2 here is low, so a respiratory acidosis may be excluded. Therefore, the only other condition that this could be is a metabolic acidosis. This is also suggested by the fact that the D*@3, the lungs compensate by increasing the excretion of *@2 /thus 0*@2 falls1. What are the causes of res iratory al$alosis? %ncreased respiration /e.g. hyperventillation, 0.1. What are the causes of metabolic al$alosis? Coss of D( /e.g. vomiting1. What is an anion ga ?

Surgical Physiology 6<; %s a calculation used to detect an unmeasured concentration of anion /acid1 in the blood. %t helps in differential diagnosis of causes of metabolic acidosis. The number of anions and cations in the blood should be e:ual. The main anions M cations /#a(, )(, D*@3 , *l 1 are measured when calculating the anion gap, soN/#a(1 ( /)(1O U N/*l 1 ( /D*@3 1O Q /unmeasued anions1 U /unmeasured cations1 #ormal range is 6< 6> mmol8C because there are more unmeasures anions than cations. %f the anion gap is increased, an unmeasured anion is present in the blood in increased :uantities. *auses of metabolic acidosis with increased anion gap include lactic acidosis, "etoacidosis and salicylate poisoning. *auses of metabolic acidosis with normal anion gap include diarrhea and 7T'. What are the ma.or buffering system in the human body? 6. The bicarbonate system is the ma+or buffer in the blood 2. @thers include the phosphate and the ammonia systems. 3. The proteins in the body also buffer changes in 0D /eg. 2lobin chains in the blood and cytoplasmic proteins intracellularly1. These factors ma"e up the immediate buffers. 'cutely, the respiratory system can assist in 0D homeostasis by reducing the concentration of volatile acid /by blowing off carbon dioxide1. %n chronic states, buffering occurs in the "idney, where filtered bicarbonate and phosphate are replaced with regenerated bicarbonate, and new bicarbonate is formed from glutamine. 3one also buffers protons in exchange with anions from its mineral matrix and the liver can secrete new bicarbonate and ammonia, again from glutamine. How does the $idney handle bicarbonate ion? 3icarbonate is freely filtered at the glomerulus and is reabsorbed by the renal tubular cells but these cells are actually impermeable to bicarbonate. The mechanism of bicarbonate resorption is as follows *ellular hydrogen ion is exchanged through an ion transport mechanism with sodium in the filtrate. The D( combines with D*@3 forming D2*@3, which then dissociates into *@2 and water. *@2 freely diffuses into the renal tubular cell where upon it reforms D2*@3, catalysed by carbonic anhydrase and the se:uence starts again. This wor"s in a steady state but, if the "idney is presented with acid to excrete, then it must generate more bicarbonate.

'% lain the role of hos hate and ammonium as urinary buffers? These come into play when the "idney has to excrete a hydrogen load.

Surgical Physiology 6<> The hydrogen ion transported out of cell in exchange for sodium combines with the phosphate ion which is excreted in the urine. The conversion of cellular water and carbon dioxide, again catalysed by carbonic anhydrous, provides the stream of hydrogen ions for excretion and generates one molecule of bicarbonate each time. %n the case of ammonium buffering, glutamine in the renal tubular cells splits into glutamate into ammonium ion, which further dissociates into ammonia and D(. this hydrogen ion is incorporated into 2 oxyglutarate formed from the continued deamination of glutamine to form glucose and the mmonia couples with the free D( ion to be excreted as ammonium chloride.

Discuss renal tubular acidosis? 7enal tubular acidosis /7T'1 may be ac:uired or inherited and both types are rate in adults. There are four types described. 6. 7T' type %- is a distal tubular defect and is often referred to as classical 7T'. The luminal cells are abnormally permeable to D( and cannot establish an ion gradient across which the normal cellular mechanisms can excrete hydrogen ion. 2. 7T' type %%- is a proximal tubular abnormality in which sodium bicarbonate cannot be resorbed proximally. This loss of bicarbonate leads to systemic acidosis and excretion of bicarbonate in the urine. 3. 7T' type %%%- is a combination of % and %% and is very rare indeed. &. 7T' type %=- is the condition of hyporeninaemic hypoaldosteronism and is commonly caused by non steroidal anti inflammatory drugs.

Potassium

Surgical Physiology 6<? How is otassium distributed in the body? Most potassium is intracellular. The normal serum potassium concentration is 3., ,.< mmol8C. How is otassium homoestasis maintained? .xtracellular potassium concentration is controlled primarily by the "idney. !iltered potassium is almost completely reabsorbed in the proximal tubules. What are the ma.or mechanisms involved in maintaining ?G homeostasis? )( homeostasis is primarily maintained by the "idney. The 2% tract plays a smaller role. %n the "idney !iltered )( is almost completely reabsorbed in the proximal tubule. Arinary )( excretion is mainly a passive process. Dowever, fine ad+ustments to )( balance are made through active secretion in the distal convoluted tubule. This regulation is under the aldesterone control. 'ldosterone stimulates the renal tubular cells to secrete )( /and absorb #a( concurrently1 causing reduction in plasma)(. The amount of )( lost in the urine depends on several factors 6. The amount sodium available for reasorption in the distal convoluted tubule. 2. The availability of hydrogen and )( ions in the cells of the distal convoluted tubule. 3. The renal tubular fluid flow rate /a decreased flow rate results in a decreased secretion of )( and an increase in plasma )(1. @ther endogenous substances have an effect on )( levels in the body and they include %nsulin and adrenaline which cause )( to pass from the extracellular fluid into the cells resulting in a reduction in plasma )(, through its action on the #a8)( 'T0ase pump. '9D also has an effect on )( levels. How does acid+base balance affect the distribution of ?G ions? %n metabolic acidosis, hydrogen ions are secreted in preference to )(, thus there is a tendency for )( levels to rise. %n contrast, in al"alosis, fewer hydrogen ions are available for excretion, therefore more )( is excreted. 'cid base disturbances due to respiratory disorders have a negligible effect on )( homoestosis.

" atient of yours has a otassium of 9.H mmol8:. in general* what are the causes of hy er$alaemia and which are commonest in surgical atients?

Surgical Physiology 66< 6. 'rtefactual is the commonest cause of hyper"alaemia, caused by a haemolysed sample. 0otassium is predominantly an intracellular ion and, if a sample is mishandled, cell lysis release large amounts of potassium. 2. %ncrease of total body potassium caused by overenthusiastic potassium therapy or failure to stop potassium treatment. 3. 7edistributive cause. Severe in+ury /7habdomyolyis, 3urns1 particularly crush in+uries release huge amounts of potassium after reperfusion, again due to cell in+ury. This could be classed as a. &. ' rare condition "nown as hyper"alaemic familial periodic paralysis is also in this category. ,. @liguric renal failure. 4. Sodium depletion and the causes thereof will tend to cause hyper"alaemia, as potassium excretion is dependent on the amount of sodium available to exchange with. ;. 'ny form of glomerular dysfunction can be responsible as can any mineralocorticoid deficiency such as addisonKs disease or congenital adrenal hyperplasia, where 26 hydroxylase deficiency ensures no aldesterone is synthesized. >. '*. inhibitor by reduction in aldosterone secretion, owing to interference in the rennin angiotensin pathway. ?. 3oth acidosis and hypoxia impair the #a(8)( pump and cause a net gain of .*! potassium. 6<. %nsulin normally enhances the passage of potassium from the .*! into the cell, but in situations of deranged glucose metabolism, such as diabetic "etoacidosis, potassium remains in the *S! space, resulting in the hyper"alaemia. %f glomerular function is intact, however, urinary potassium loss continues but at an insufficient rate to correct the hyper"alaemia. There is a decrease in total body potassium but a rise in serum potassium. What are the 'C( changes of hy er$alaemia? Dyper"alaemia increases the ris" of cardiac arrhythmia. %nitially, there are Digh pea"ed T waves. Bidened P7S complex. ST depression ensues followed by disappearance of the T waves. *ardiac arrest may supervene. How would you treat hy er$alaemia? .xogenous potassium therapy should be halted immediately. *alcium will temporarily antagonize the depressive effect of potassium on the myocarcardium, so where the potassium is grossly raised, the emergency measure of priority is the administration of 6< ml of 6< I calcium gluconate as a cardioprotective agent. 2lucose and insulin /,<g glucose and 2< units human actrapid %=1 will reduce potassium levels by driving the )( bac" into the cells. ' total of &< ml >.& I sodium bicarbonate will also reduce hyper"alaemia. ' , mg salbutamol nebulizer can be tried as salbutamol activities the #a(8)( 'T0ase, again moving extracellular potassium into the cells. The underlying cause should be sought.

Surgical Physiology 666 %f it is a chronic condition, then calcium resonium orally will bind gut potassium and reduce absorption. %f these measures fail and potassium continues to rise, then consideration should be given to haemodialysis.

What are the causes of hy o$alaemia? 9iuretics. 9iarrhea and vomiting. 0yloric adenoma of the rectum. =illous adenoma of the rectum. %ntestinal fistulae. *ushingKs syndrome. *onnKs syndrome. 0urgative abuse. How do you treat hy o$alaemia? %f the serum potassium is L 2.,mmol8l, it needs urgent treatment, with cautious intravenous potassium with continuous electrocardigraphy /.*21 monitoring. %f the serum potassium is mild X2.,mmol8l, potassium may be given orally.

Surgical Physiology 662

Distribution of body water

What are the different fluid com artments of the body? Total body water accounts for ,< ;<I of body weight. %t is distributed into%. %ntracellular fluid /3 &<I of body weight1. %%. .xtracellular fluid /2<I of body weight1 %nterstitial fluid /6,I of body weight1. %ntravascular fluid /,I of body wight1. How do you determine the si/e of the fluid com artments? Total body water comprises approximately two thirds of body weight. @f this%. Two thirds is intracellular. %%. @ne third is extracellular Two thirds is interstitial. @ne third is intravascular. Dowever, there is a higher percentage of water in the young, thin and men, and a lower percentage in the elderly, obese and women. What is meant by osmolarity and osmolality ? @smolarity is a measure of concentration per litre of solution. @smolality is a measure of concentration per "ilogram of solvent. @smolality of plasma is maintained at 2>< 3<, mosmol8"g. it may be estimated by mosmol8"g Q glucose ( urea ( /2 x sodium1 /mmol8l1 How do you intravenous fluids distribute when infused into the body? #ormal saline %t rapidly distributes across the entire extravascular compartment, which is & times as large as the intravascular compartment. So of 6<<< ml of normal saline, only 2,< ml would remain in intravascular compartment. , I dextrose %t distributes across both intracellular and extracellular compartments. The intravascular compartment represents only ,8&< this of the fluid compartments as a whole. So only >I or >< ml of ,I dextrose would remain in the intravascular compartment. What are the common causes of water e%cess? The infusion of ,I dextrose. Transurethral bladder irrigation with 6.,I glycin solution. .xcess antidiuretic hormone /'9D1 secretion. %nappropriate /lung cancer, central nervous system /*#S1 disorders and pulmonary sepsis1. 'ppropriate /following surgery1.

Surgical Physiology 663

Sodium
Definition- plasma sodium L 63, mmol8l. What is the distribution of sodium in the body? The adult body contains approximately 3<<< mmol of sodium ;<I of which is free. 3<I is complexed in bone. The ma+ority of free sodium is extracellular. The normal extracellular sodium concentration is 63& 6&, mmol8l. The normal intracellular sodium concentration is & 6< mmol8l. How is sodium homoeostasis maintained ? The volume of the .*! is directly proportional to the total body sodium content. .*! volume is controlled by *arotid sinus baroreceptors The +uxtaglomerular apparatus 'trial natriuretic peptide What are you actually measuring when you measure the serum sodium? The ration of extracellular sodium /mmol1 to extracellular water/61. How do you asses fluid status? .xamine the patient, paying particular attention to 3lood pressure /especially postural drop1. bugular venous pressure /b=01. 3asal crac"les /interstitial compartment1. 0eripheral perfusion and oedema /interstitial compartment1. .xamine the charts for serial weights and fluid balance /input8output1. 'dditional tools that may be useful include *hest radiograph /signs of pulmonary oedema1. *entral venous pressure /*=01 line /used dynamically1. 'nd8 or a swan 2anz catheter.

Surgical Physiology 66&

Hy onatraemia
What are the causes of hy onatraemia? Dyponatraemia may be due to water excess or sodium deficit. Salt deficient may be caused by Carge sodium losses from the gut 9iarrhea. =omiting. !istula. Small bowel obstruction. 7enal salt loss in 9iuretic overuse. @smotic diuresis in hyperglycemia. Tubulo intersitial renal disease. =olume overload %t is uncommon in a person with normal "idneys, but postoperative overtransfusion of crystalloid is a common cause. %t commonly presents in Deart failure. Depatic cirrhosis. #ephritic syndrome. The syndrome of inappropriate anti diuretic hormone secretion /S%'9D1 occurs in con+unction with many other conditions, particularly pulmonary and central nervous system diseases. '9D secretion may also be ectopic from malignant tumors and presents with hyponataemia with normal fluid volume. What are the sym toms of hy onatraemia? Sym toms Deadache. #auses. *onfusion. *oma. *onvulsions /symptoms depend on the rate as well as the magnitude of the fall in plasma sodium1. What investigations might hel you? %nvestigations should include both a plasma and urinary sample for sodium analysis. This allow an assessment of whether the body is concentrating sodium or not. %n volume overload- there is little sodium in the urine. whereas %n sodium overload- There are usually normal to high amounts. How would you treat hy onatraemia? Treat underlying cause. *orrection should be gradual /otherwise, problems that may arise include subdural haemorrhge, pontine lesions, cardiac failure15 correct at a rate of , 6< mmol8day /faster if plasma sodium L 62< mmol8l1.

Surgical Physiology 66, Salt deficient hyponatraemia should be treated by @ral $ slow sodium$ or in patients who are vomiting by %= saline. =olume excess hyponatraemia should be treated by 7estriction of fluid inta"e and review of diuretic therapy. The clinical picture of continuing, uncorrected salt deficient hyponatraemia, symptoms are neurological as water moves into the brain cells due to falling extracellular osmolarity. Symptoms are *onfusion and restlessness. !ollowed by drowsiness, myoclonic +er"s convulsions and coma. What are the com lications of correcting low lasma sodium levels? !luid overload, secondary to excessive sodium administration which increases .*! volume and central pontine myelinosis. What are the causes of hy ernatraemia ? True sodium excess in very rare and is usually iatrogenic. Dypernatraemia can be due to6. Bater loss in excess of sodium 9iarrhea. =omiting. 3urns. 2. %ncorrect i.v. fluid replacement. 3. 9iabetes insipidus /this may follow head in+ury1 osmotic diuresis. How do you treat hy ernatraemia? 6. Treat the cause. 2. 2ive water orally if possible. 3. @therwise ,I dextrose or normal saline /which is hypotonic in hypernatraemic patients to achieve normal sodium levels in &> hours.1.

Surgical Physiology 664

Calcium
What is the normal lasma concentration of calcium? The normal range of calcium in plasma is 2.2 2.4 mmol8l /corrected for albumin concentration, as calcium is bound to albumin in blood1. What is the a ro%imate distribution of CaGG ions in the body? ??I bone. <.?I intracellular. <.6I extracellular. 'pproximately &<I of serum *a(( is protein bound. What are the functions of calcium in the body? Structural- bone and teeth. #euromuscular- control of excitability, release of neurotransmitters, initiation of muscle contraction. .nzymes- a co enzyme for coagulation factors. Signaling- an intracellular second messengers. What hormones are res onsible for calcium homeostasis and can you briefly describe their actions? 0arathyroid hormone increases serum calcium Stimulates osteclastic activity, leading to bone resorption. %ncreases renal phosphate secretion and decreases calcium excretion. Stimulates 6 F hydroxylase activity in the "idney /enhances vitamin 9 formation1. =itamin 93 cholecalciferol increase serum calcium and calcification of bone matrix To increase calcium and phosphate resorption from the gut. To increase calcium and phosphate resorption in the "idney. To enhance bone turnover. %nhibit 0TD release. *alcitonin decreases serum calcium %nhibits bone resorption through inhibition of osteoclast activity. Stimulates excretion of calcium, phosphate, sodium and chloride in the "idney. How is serum calcium affected by PH? %n al"alosis, hydrogen ions dissociate from albumin and calcium binding to albumin increases. There is also an increase in calcium complex formation. So, the concentration of ionized calcium falls. This is why hyperventilation causes tetany. %n acidosis the opposite happens. How is serum calcium affected by albumin?

Surgical Physiology 66; The plasma total calcium concentration must be corrected for changes in albumin concentration!or NalbuminOL &<, corrected calciumQ NcalciumO ( <.<2 x /&< NalbuminO1mmol8l !or NalbuminOL &,, corrected calciumQ NcalciumO <.<2 x /NalbuminO &,1 mmol8l How does CaGG influence the action otential? *a(2 influences the relationship between the membrane potential and #a( influx. ' higher extracellular *a(( concentration stabilizes the membrane by decreasing excitability. ' lower *a(( concentration increases the exitability of nerve and muscle cells by decreasing the amount of depolarization necessary to initiate the changes in #a( and )( flux that produce the action potential. Thus muscle cramps and tetany are seen. How do you correct the serum calcium measurement and why? 's &, I of serum calcium is albumin bound, the albumin concentration directly affects the total calcium concentration measured in plasma and variations in albumin concentration and therefore total plasma calcium may not accurately reflect the concentration of ionized calcium. %t is variations in the plasma calcium ion content that give rise to symptoms, but unfortunately it is difficult to measure free calcium concentrations, so a standard correction is made to the total calcium concentration to account for variations in plasma protein. !or each gram per litre the albumin concentration is below &<, the calcium concentration is increased by <.<2 mmol8C. an identical negative ad+ustment is made for albumin concentrations above &< g8C. 6utline the clinical resentation of hy ercalcemia? 7aised serum calcium may be the result of wide range of underlying pathologies. 6. Malignancy is the commonest cause. 2. Dyperparathyroidism /primary M tertiary1. and these two causes are responsiple for more than ?< percent of all cases. 3. Thyrotoxicosis. &. 'ddisonKs disease. ,. Sarcoidosis. 4. Mil" al"ali syndrome. ;. !amilial hypocalcuric hypercaalcemia. Malignant neoplasms may elevated the calcium levels by direct osteolysis from secondary deposits or a primary tumor. Myeloma, for example, may mobilize s"eletal calcium or may be a focus of ectopic 0TD secretion, in common with other tumors, such as small cell lung cancer. The clinical presentation is the classical student rhyme of $ bones$ stones, abdominal groans and psychic moanKs. 3ones changes range from !lorid prepperpot s"ull. Subperisosteal erosions of the phalanges. and commonly present with pain.

Surgical Physiology 66>

The urinary tract Susceptible to recurrent stone formation and the patient may display 0olyuria. Daematuria. Dypertension from nephrocalcinosis. 7enal failure 2astrointestinal symptoms 'bdominal pain #auasea =omiting Digher incidence of peptic ulceration owing to the gastrin stimulating action of calcium. 0atients become prone to constipation and gallstone. 0sychic moanKs 0sychiatric disoreders /lethargy and depression1. How might hy ercalcaemia resent to the surgeon? %ncidental findings. #on specific musculos"eletal symptoms. @steoporosis. Areteric colic. 0eptic ulcer. .pigastric pain. 'cute pancreatitis. What is the treatment of hy ercalcaemia? Treatment of hyprecalcaemia is an emergency, because it can cause arrthymias. %t is treated in short term by vigrous fluid resuscitation and adminstration of pamidronate, which lowers the calcium levels. The cause should be sought and treated where possible.

Surgical Physiology 66?

What are the features of hy ocalcaemia? 0araesthesia around the mouth and of the fingers. Seizures. Tenaty. TrousseauKs sign /twitching of facial muscles on tapping facial nerve1. *hvoste"Ks sign /*arpopedal spasms1. Malaise. Dyperreflexia. Dypotension, bradycarias, dysrhythmias and congestive cardiac failure. 0rolonged PT interval. What are the causes of hy ocalcaemia? Dypoparathyroidism /primary, secondary or most commonly post surgical1. 7enal failure. =itamin 9 deficiency. 0seudohypoparathyoidism. Severe magnesium deficiency. 'cute complexing or se:uestration of calcium. 'cute pancreatitis. 7habdomylysis. How would you mange ost+ arathyroidectomy hy ocalcamia? 0ost parathyroidectomy, mild hypocalcemia normally results. This re:uires observation only, in the absence of symptoms. ' nadir occurs at day , post operatively. Dowever, in patients who have parathyroid bone disease, a profound hypocalcaemia may occur shortly after the parathyroids are removed. This may cause a profound and severe hypocalcaemia which re:uires several daysK treatment %f symptomatic administer 6< ml of 6<I calcium gluconate. Cong term therapy is with oral calcium and activated vitamin 9 /alfacacidol1. The serum calcium should not exceed 2.3< mmol8l because of an increased ris" of nephrolithiasis. How would you treat acute severe hy ercalcemia? Dypercalcaemia has an enormous range of conse:uences, including renal tubular damage, peptic ulceration, hypertension, cardiac arrythmias and bone pain. 's an acute severe event-

Surgical Physiology 62< =olume repletion is the mainstay of therapy, as patients are usually mar"edly dehydrated. !rusemide will help to increase renal clearance. 3iphosphonate infusion binds hydroxyapatite in bone and decreases bone turnover. 'fter which attention must be turned to identifying the cause of the hypercalceamia.

How is vitamin D formed and what are its metabolites? There are two sources of vitamin 9 0roduced in the s"in by A= light /vitamin931. %ngested in the diet /vitamin 921. 3oth 92 and 93 have identical biological actions and so both forms are "nown as vitamin 9. The active metabolites of vitamin 9 are produced by the 2, hydroxylation step in the liver /forming 2, hydroxy cholecalciferol1 and 6F hydroxylation in the "idney /forming 6,2, 9D** or 6,2, dihydroxycholecalciferol1. The 6,2, 9D** is the most active metabolite of vitamin 9 and is almost entirely responsible for the actions of vitamin 9. What is the role of vitamin D? =itamin 9 acts on The intestine to increase *a(( and phosphate absorption and s"eletal mineralization. 3one, stimulating osteoclastic resorption. )idney increases calcium and phosphate resorption. Dence, vitamin 9 deficiency results in the formation of unmineralised osteoid. %n children, this will affect the bony growth plates resulting in bowing of the extremities and collapse of the chest wall /ric"ets1. %n adults, bone pain, vertebral collapse and stress fractures will ensue /osteomalacia1. What are the ossible causes of vitamin D deficiency? %nsufficient sunlight exposure to the s"in of individuals who have a diet poor in vitamin 9. Civer disease / affects the 2, hydroxylation step1 7enal failure /affects the 6 F hydroxylation step and hence production of the most active metabolite 6,2, 9D**1. Classify hy er arathyroidism? Dyperparathyroidism represents an increase in the concentration of circulating parathyroid hormone, and it may be calssified as primary, secondary or tertiary. 0rimary hyperparathyroidism%t occurs with excess 0TD production, so 0TD and serum calcium are both elevated. 6. >< I of cases are due to a single adenomatous gland. 2. 6, I of cases are due to generalized parathyroid hyperplasia. 3. , I. of cases are due to multiple adenomata.

Surgical Physiology 626 &. 0arathyroid carcinoma may also the cause of primarily elevated 0TD but with an incidence of loss than 6 in 6<< cases. Secondary hyperparathyroidism%t occurs when there is excess calcium loss, usually in renal failure. *alcium is normal or low, but 0TD is raised in an attempt to increase calcium mobilization. Tertiary hyperparathyroidism%t occurs in patients who have had their cause of secondary hyperparathyroidism treated, typically individuals whose renal failure was treated by transplantation. 'lthough the stimulus has been removed, the parathyroids remain hyperplastic and secrete excess 0TD, i.e. autonomously5 both 0TD and calcium are elevated. Dyperparathyroidism may occur as part of the multiple endocrine neoplasia syndromes and as such may be familial with an autosomal dominant inheritance. 3oth parathyroid hyperplasia and adenoma are included in the disease, which is common to M.# types % and %%.

Surgical Physiology 622

Magnesium
What is the distribution of magnesium in the body? The adult body contains approximately 6<<< mmol8l Dalf of which is in bone. @ne :uarter in muscle. @ne :uarter in other soft tissues. @nly 6, 2? mmol is found in the .*!. The plasma concentration is <.> 6.2 mmol8l What are the hysiological roles of magnesium? 6. Magnesium acts an essential cofactor for some 3<< enzymes, involved in protein synthesis, glycolysis and transmembrane ion transport. 2. ' magnesium adenosine triphosphate /'T01 complex is the substrate for many enzymes re:uiring 'T0. 3. Magnesium is important in the maintenance of the structures of ribosomes, nucleic acids and some proteins. &. Magnesium, by its interactios with calcium, affects the permeability of excitable membranes and their electrical properties. When might you measure serum magnesium? Severe or intractable diarrhea and8or malabsorption /e.g. short bowel syndrome and inflammatory bowel disease1. Cife threatening alcohol withdrawal. 7efractory cardiac dysrhthmias /especially ventricular1. Dypocalcaemia and tetany unresponsive to calcium. 7efractory hypo"alamia . #euromuscular symptoms after cisplatin or mannitol. 7enal failure. 9uring parentral nutrition. What are the causes of hy ermagnesaemia? Dypermagnesaemia is uncommon. 't concentration of 2., ,.< mmol8l- *ardiac conduction is affected. =ery high concentration /X ;., mmol8l1 cause respiratory paralysis and cardiac arrest. Dypermaneseamia may be ssen in renal failure.

Surgical Physiology 623 What are the causes of hy omagnesaemia? 6. Malabsorption, malnutrition and fistulae. 3. 9iuretic therapy /especially loop diuretics1. ,. 7enal tubular disorders.

2. &. 4.

'lcoholism. *irrhosis. *hronic mineralocorticoid excess.

How do you treat hy omagnesaemia ? Mild magnesium deficiency is treated with oral supplementation. %n severe deficiency and with malabsorption, magnesium may be given by slow intravenous infusion. How do you treat hy ermagnesaemia ? %ntravenous calcium may give short term protection against hypermagnesaemia. %n renal failure, dialysis may be necessary.

'ndocrine Physiology

Surgical Physiology 62&

0hyroid gland
2riefly describe the synthesis of tri+iodothyronine ,0D- and thyro%ine ,0B-. %odide in the blood is ta"en up by the iodide pump present in thyroid follicular epithelial cells. The iodide is oxidized by thyroidal peroxidase and is transported within the cell. Dere, the newly formed iodine is lin"ed to tyrosine residues in the protein thyroglobulin. %t is then secreted into the colloid at the centre of each follicle /a thyroid follicle is colloid surrounded by thyroid follicular cells1. 't the +unction of the follicular cells and the lumen further action by peroxidase converts the tyrosine residues to mono iodotyrosine /M%T1 and di iodotyrosine /9%T1. M%T then couples with 9%T to form T3 and 9%T coupled to 9%T to form T&. Thyroglobulin is stored within the colloid until the gland is stimulated to secrete thyroid hormone. The stores typically last for 2 months. Bhen thyroid hormones are re:uired, thyroglobulin is redirected into the follicular cell by pinocytosis. 0roteases act on thyrpglobulin to produce T3 and T&, which are then released into the circulation. Thyroid stimulating hormone /TSD1 stimulates each step in the synthesis of T3 and T&. the remaining M%T and 9%T is deiodinated by thyroid deiodinase. The % 2 released is recycled to synthesis more thyroid hormones. How are 0D and 0B trans orted in the blood stream? %n the bloodstream T3 and T& are bound predominately to thyroxine binding globulin /T321 but also to albumin and thyroid binding prealbumin. More T& is produced than T3 and in the peripheral tissue T& converted to T3 by , iodinase. Which is more biologically active* 0D or 0B? T3 is at least & times as potent as T&. however, T3 has a much shorter half approximately 6 day compared with 6 wee" for T&. How is thyroid hormone secretion controlled?

Surgical Physiology 62, TSD has a direct positive effect on thyroid hormone production. TSD is secreted from the anterior pituitary and is itself regulated by thyroid releasing hormonr /T7D1 secreted by the hypothalamus. T7D is produced in response to low circulating thyroid hormone concentration and a fall in external temperature. The hypothalamus pituitary thyroid axis wor"s by negative feedbac", i.e. thyroid hormone production inhibits T7D secretion from the hypothalamus and TSD secretion from the anterior pituitary. The thyroid gland itself shows some ability to autoregulate depending on the iodine supply. Digh iodine circulating levels are inhibitory to thyroid hormone production. 9eficiency states in endemic regions are associated with goiter as the glands infrastructure swells in an attempt to produce thyroid hormone.

What are the effect of thyroid hormones in the body ? Thyroid hormones are steroid hormones and wor" by increasing 9#' transcription in cells with a resultant increase in new m7#'. The new m7#' is translated into the production of new specific proteins that have physiological actions. These effects are widespread in the human body and can be summarized as follows5 *entral nervous system /*#S1 maturation This is totally dependent on thyroid hormone production in the perinatal period. Cac" of hormone or deficiency can result in mental retardation and cretinism and as result hypothyroidism is screened for in the neonatal period. 2rowth and s"eletal maturation Thyroid and growth hormones act synergistically to promote bone formation and maturation. 7egulation of basal metabolic rate /3M71 and temperature regulation Thyroid hormones cause increased oxygen consumption by mitochondria with a subse:uent increase in /'T01 formation in most organs of the production indirectly and therefore explains why thyrotoxic patients complain of heat intolerance. Thyroid hormones influence /3M71 directly i.e. patients with hypothyroidism have a low 3M7 and vice versa. Metabolic effect There is a net increase in protein brea"down and hence thyroid hormones are catabolic. There is an increase in fat mobilization and degradation. 2lucose absorption is promoted from the gastrointestinal tract and there is an increase in glycogenolysis and gluconeogenesis. Sympathomimetic Many effects of thyroid hormone are analogous to 3 adrenegenic stimulation. This explains how thyrotoxic patients can get some symptomatic relief with 3 bloc"ers. @ther effects-

Surgical Physiology 624 Thyroid hormones cause an increase in stro"e volume and heart rate. Since these two parameters have an effect on cardiac output, this too increases. This is combination with increased ventilation, another effect of thyroid hormones, promotes increased oxygen delivery to tissues. Thyroid hormones also play a role in regulation of gut motility and s"in8 hair development. What is the atho hysiology of (raves1 disease? 2ravesK disease is an autoimmune condition in which high circulating levels of thyroid stimulating immunoglobulins or long acting thyroid stimulators /C'TS1 are present. These antibodies are directed at the TSD receptors and are stimulatory. 's a result thyroid hormone levels in these patients are raised. They present with generalized hyperthyroid syndrome, symptoms specific to 2ravesK /exopthalmos, acropachy and pretibial myxoedema1 or a combination of both. TSD levels are low due to the negative feedbac" mechanism.

Parathyroid gland
What actions does arathyroid hormone ,P0H- have? 0TD is secreted in response to a reduced sereum calcium. %t promotes resorption of bone. reasorption of calcium in the distal convoluted tubule of the "idney. increases production of 6,2, dihydroxy holecalciferol. 'll these processes act to increase the serum calcium. %ncreased 6,2, dihydroxycholecalciferol production in the "idney has a direct effect on increasing intestinal absorption of calcium. The bone resorption effect promotes an increase in both phosphate and calcium in the extracellular fluid. #ormally &<I of calcium is bound to plasma proteins. 4<I is filtered by the "idney. The filtered load is either bound to anions or is free ionized calcium. 0TD helps to increase free uncomplexed calcium, which is the biologically active form. What are the causes of rimary hy er arathyroidism? 0arathyroid adenoma />,I1. 0arathyroid hyperplasia /6&I1. 0arathyroid carcinoma /6I1. What is the net biochemical changes in rimary hy er arathyroidism? 6ry hyperparathyroidism leads to a raised serum calcium, 0TD level and a decreased serum phosphate. What are the signs and sym toms of ;ry hy er arathyroidism? 'lthough some patients may be asymptomatic, many will show the effects of hypercalcaemia-

Surgical Physiology 62; Bea"ness, fatigue, nausea and vomiting. 0olyuria, polydepsia and dehydration. 7enal calculi. 'bdominal pain, peptic ulcer disease, pancreatitis M constipation. *ardiac dysrrhythmias. 7enal impairment. *orneal M vascular deposits. 0sychiatric illness /depression1. 3ony conditions- s"eletal pain, fractures, subperosteal erosions especially of phalanges and cystic fibrosis.

How can ;ry hy er arathyroidism be treated? Treatment can involve surgical exploration with removal of the offending gland in cases of adenoma or carcinoma. Bith hyperplastic glands, 3., out of & are removed in order for symptomatic control. %n asymptomatic disease the debate still continues whether surgery be underta"en as long term se:uelae are still possible. How does renal failure cause 5ry hy er arathyroidism and what serum biochemival will enuse? %n renal failure glomerular filteration is reduced and phosphate excretion is hampered. 's a result more phosphate is available to bing to calcium M thus the free or ionized calcium pool is reduced M patients tend to become hypocalcaemic. There is active vitmain 9 formation which also prevents intestinal absorption of calcium confounding the problem. The bodyKs response to this is to try M incease serum calcium. %t achieves this by increasing parathyroid hormone and eventually this leads to secondary hyperparathyroidism /i.e. an increase in 0TD in response to low serum calcium1. The increased bone resorption in combination with reduced intestinal absorption eventually leads to osteomalacia and produces the apt named renal osteodystrophy seen in these patients. The biochemical will include a raised parathyroid hormone level and phosphate level with a decreased serum calcium level. What are the causes of hy o arathyoidism and what biochemical changes would occur in rimary disease? #ec" surgery /e.g. thyroid surgery1. *ongenital conditions /e.g. 'lbrights hereditary osteodystrophy1. 0rimary hypoparathyroidism causes a low 0TD, with a low serum calcium and a raised serum phosphate.

Surgical Physiology 62>

Pitriotary gland
Describe the functional anatomy of the ituitary gland? 'lthough named as one gland, functionally and embryologically it is two. 6. The anterior pituitary /'denohypophysis1 %t is derived from 7ath"eKs pouch, an outgrowth of pharyngeal epithelium. %t is connected to the hypothalamus via the pituitary portal system of blood vessels though which the hypothalamic releasing and inhibitory factors arrive at the anterior pituitary. 2. The posterior pituitary /#eurohypophysis1 %t is a downward pro+ection of the hypothalamus. %t is in direct neural connection with the hypothalamus above5 indeed, the cell bodies of the neural cells of the neurohypothysis reside in the hypothalamus ans the hormones are transported to the posterior pituitary down the axons. What hormones are secreted from the ituitary? The anterior gland secrets6. 2rowth hormone /2D1. 2. 'drenocorticotrophic hormone /'*TD1. 3. Thyroid stimulating hormone /TSD1. &. 0rolactin. ,. !ollicle stimulating hormone /!SD1. 4. Ceutinizing hormone /CD1. The posterior pituitary secrets6. 'ntidiuretic hormone. 2. @xytocine. What is ortal circulation?

Surgical Physiology 62? %t is a circulation that connects 2 capillary beds but doesn,t receive a direct arterial supply nor drain into a venous system. The 2 of significance are the hypothalamic hypophyseal M hepatic portal systems. What is an acido hil adenoma and what are the endocrine conse#uences? *ells of the anterior pituitary are often classified according to their staining characteristics6. 'cidophil- s the cells that secret growth hormone and prolactine. 2. 3asophils- the cells secreting TSD, !SD, CD M '*TD. 3. *hromophobes- The cells with neutral sstaining characteristic. 'n acidophil adenoma is therefore, a tumour of the acidophil cells. The excess of 2D and sometimes prolcactin which will give rise too 2igantism, if present before epiphuseal fusion, or o 'cromegaly after fusion. Ancontrolled growth of an acidophil adenoma will also compress the rest of the gland and thus the patient may also suffer from hyposecretion of the basophil hormones.

What roblems may result from an enlarging non+secretory ituitary tumour? 'n enlarging tumour can compress normal functioning glandular tisssue causing hyposecretion and a large non secretory tumour may give rise to panhypopituitarism with a complete absence of all anterior pituitary hormones. @wing to its anatomical location in sella tursica, enlargement by tumour can cause pressure on the optic chiasm above leading to visual defects, such as a bitemporal hemianopia and ultimately blindness. Cateral extension can cause compression syndrome on those cranial nerves running through the cavernous sinuses. Tumours that have grown to enormous proportion may obstruct the 3 rd ventricle or produce through the sphenoid sinuses as a pseudo nasal polyp. What are the clinical manifestation of rolactinoma? The clinical manifestations typically depends on whether the tumour is a micro /L 6<mm in diameter1 or macro adenoma /X 6< mm in diameter1. The clinical manifestations of a micro prolactinoma are those of hyperprolactinaemia 2alactorrhea. Menstrual irregularities in females8 %nfertility in females. %mpotence in males. ' macroadenoma usually presents with a mass effect, as it is usually non secreting. %t would therefore cause Deadache. 0aralysis of the extra ocular muscles. =isual field abnormalities /bitemporal hemianopia1. 'nterior pituitary failure /secondary to compression1. What is the medical treatment for hy e rolcatinaemia?

Surgical Physiology 63< %n the normal individual, dopamine is secreted from the hypothalamus and inhibit prolactin secretion from the anterior pituitary. 3romocriptine, a dopamine agonist can therefore be used to inhibit prolactin secretion from the anterior pituitary. 3romocriptine is also used to reduce the size of macroadenoma prior to surgery. What is Sheehan1s syndrome* and how does it resent? SheehanKs syndrome is pituitary infarction following a postpartum haemorrhage. Symptoms are Those of panhypopiruitarism. Coss of libido. 'menorrahea. 2alactorrhea. Secondary hypothyrpodsim M adrenal suppression lead to tiredness, mental slowing M mild hypotension. The classic hypopituitary patient will be pale and hairless U the $alabaster s"in$ appearance.

Hormone 2rowth hormone

Site of action Civer. 0eripheral tissue

TSD

Thyroid gland 3reast 'drenal cortex

07C '*TD

!SD M CD

2onads

Controlling influence Dyperglycaemia. 2D7D is Secretion of %2! 6 excitatory. which stimulates Somatostatin is growth of unfused inhibitory. bone. Several anabolic, metabolic functions. 0romotes secretion T7D. of T& M T3 and T3 M T& feed increases their bac" Uve on the synthesis. pituitary. 0romotes breast 9opamine has development M mil" an inhibitory production. effect 0romotes secretion *7D of cortisol. /corticotrophin releasing hormone1. ve feedbac" by cortisol. 0romotes secretion 2n7D. of estrogen M *omplex progesterone in feedbac" female, in a cyclical mechanisms by fashion /menstrual their target

"nterior ituitary "ction

athologies 'cromegally /epiphyses fused1 2igantism. 9warfism. Dyper and hypothyroidism. 0rolactinoma. *ushingKs disease, 'ddisonKs sisease.

Surgical Physiology 636 cycle1 and hormones. testosterone in the male. Hormone =asopressin /'9D1 Site of acion *ontrolling Bater retension duct of the nephron Controlling athology influence %ts release is S%'9D, 9.%. increased by increased tonicity of blood. Aterus %nitiation of Aterus *ollecting parturition8stretch #eural inputs duct of the receptors in uterine from suc"ing nephron. contraction child /breast1 Smooth Mil" secretion. Mil" e+ection muscle cells Bater retension. reflex. in breast Posterior ituitary "ction

@xytoxin

"drenal (land = "ddison disease

What im rtant hormones are secreted from the different layers of the adrenal gland? The adrenal cortex- has 3 distinct zones6. Eona glomerulosa- secrets aldosterone. 2. Eona fasculata- secrets glucocorticoids /e.g. cortisol1. 3. Eona reticularis- secrets sex hormones /e.g. testosterone M oestrogen1. The adrenal medulla secrets catecholamines such as adrenaline and noreadrenaline. What are the actions of costisol? *ortisol is a catabolic hormone and is essential in the bodyKs response to stress. %ts actions are as follows%. 'nti inflammatory%t induces synthesis of lipocortin which acts on the arachidoonic metabolite pathway inhibiting the enzyme phospholipase '2. This enzymes liberates arachidonic acid from free phospholipids and goes on to produce the mediators of pain and inflammation /leucotrienes, prostagglandins M thromboxanes1. %n addition, it inhibits proliferation of T lymphocytes, prevents the production of interleu"in 2 and prevents mast cells and platelets causing histamine and serotonine sensitivity. %%. 0romotes protein catabolism M lipolysisThis ma"es more amino acids and gltcerol are avaialabe in the liver for gluconeogenesis. %%%. 7eduction in insulin sensitivity. %=. .nhances the effect of catecholamines on the peripheral vasculature#oreadrenaline causes vasoconstriction in the peripheral vasculature and this effect is potentiated by cortisol.

Surgical Physiology 632 %n addisonKs disease, where there is a distinct lac" of cortisol, the peripheral effect of noreadrenaline is diminished and patients therefore tend to develop postural hypotension. How is glucocorticoid secretion regulated? *ortisol level vary during a normal day, being highest in the morning. *ortisol secretion is dependent on stimulation of the adrenal cortex by '*TD. '*TD is secreted from the anterior pituitary in response to corticotrophin releasing hormone which is secreted from the hypothalamus. The system l"e other hypothalamo pituitary end organ axis is governed by negative feedbac" such that raised cortisol levels will cause a suppression the amount of *T7D M '*TD released from the hypothalamus and anterior pituitary repectively. What are the actions of aldosterone? o %ncreases #a( reabsorption in the distal convoluted tubule and collecting system of the "idney. o %ncreases )( secretion in the distal convoluted tubules and collecting system of the "idney. o 0romotes secretion of D( ions /acid1 from the "idney. How does aldosterone contribute to the homeostasis of the e%tracellular fluid com artment in the hy ovolaemic states? ' reduction in tissue perfusion of the "idneys secondary to a reduction in blood volume stimulates the renin angiotensin system. 's a result a surge in renin production occurs which causes angiotensinogen to be converted to angiotensin %. This is then converted to angiotensin %% by the action of angiotensin cenzyme. 'ngiotensin %% is a potent vasoconstrictor /helping to maintain mean arterial pressure1 and also acts on the zona glomerulosa of the adrenal cortex to stimulate secretion of aldosterone. 'ldosterone promotes #a( reabsorption in the "idney. 'long with this shift comes a shift in water thereby restoring the .*! volume towards normal. What is addison1s disease? 'ddisonKs disease or primary adrenocortical insuffieciency is usually due to bilateral destruction of the adrenal cortex. *auses 'utoimmune disease, which is the commenst. Tuberculosis. 'drenal adenoma8carcinoma. Sudden withdrawal of steroids. Daemochromatosis. 'myloidosis. Sarcoidosis. !ungal- balstomycosis. %atrogenic- surgical removal in the treatment of *ushingKs syndrome. Baterhouse !redreichson syndrome- meningococcal septicaemia can cause adrenocortical infarction.

Surgical Physiology 633 's a result the adrenal gland is unable to produce the mineralocorticoid, aldosterone, glucocorticoids such as cortisol or sex hormones. Treatment is with mineralocorticoid and glucocorticoid replacement. 9espite this patients tend to develop adrenal crises when the body undergoes furtheer stresses such as surgery, infection M immunosuppression. What are the clinical features of "ddison1s disease? o 2eneral- nausea, vomiting, weight loss, anorexia, malaise M wea"ness. o '*TD related- in producing high circulating level of '*TD, melanocyte stimulating hormone /MSD1 levels are also increased leading to hyperpigmentation which tends to manifest in the peripheral region. o 'ldosterone related- postural hypotension /Secondary to a reduction in .*! volume1, hyper"alemia, metabolic acidosis /aldosterone promotes acid secretion and therfore conversely leads to acidosis in aldosterone deficient states1. o Dyponatraemia. o *ortisol related- hypoglycemia, losss of cortisol induced peripheral vasoconstrictor effect with noreadrenaline /contribting to postural hypotension1. o Sex hormone related- reduced pubic M axillary hair in women. Describe an addisonian crisis and its treatment? 'n acute presentation may be precipitated by 'ny intercurrent infection. Situation re:uiring the body to mount a stress response. 'cute withdrawal of the patientKs normal corticoid supplements will also precipitate a crisis. The primary features are Massive hypovolaemia. Shoc". Deadache. #ausea M vomiting. Bea"ness. 'bdominal pain. *onfusion M coma. There is usually mar"ed hypotension. 3iochemical analysis demonstrates ' profound hponataremia which may be as low as 66, mmol8C, hyper"alemia M hypoglycaemia. There is often hyperglycaemia in addition. TreatmentThe resultant depletion of the intracellular and extracellular compartment may re:uire enormous volumes of fluid. The ma+or deficiencies of salt, steroid M glucose are addressed. 0rovided there is no cardiovascular disease, 6C of saline is given over 3< 4< minutes. %f hypoglycaemia, dextrose is infused concurrently. Subse:uent fluid re:uiremrents may be high M a central line should be considered for monitoring. Dydrocortisone 6<< mg %.=. is given 4 hourly until the patient is stable. !ludrocortisone isnKt needed in the acute setting. How is the diagnosis confirmed and what is the long+term treatment?

Surgical Physiology 63& The biochemical abnormalities should strongly suggest the diagnosis and further investigation used to confirm this. ' short synacthen test should prove the clinical suspension. ' standard dose of synacthen is given parenterally and plasma cortisol measured at adminstration and between 3< M 4< minutes later. ' normal sub+ect will demonstrate a rise in plasma cortisol, which is absent in the addisonian patient. %t is important to prohibit hydrocortisone adminstration for > hours prior to the test, as this leads to erroneous results. Cong term mangmento The cause should be treated, if possible, such as tuberculosis or blastomycosis. o Treatment is by replacement therapy, typically fludrocortisone and hydrocortisone. o The dose of glucocorticoid is +udged on patient well being and cortisol levels. o Mineralocorticoid dose is assessed by blood pressure response to standing i.e. it shouldnKt fall and suppression of plasma renin to normal activity. 0atients should be educated to increase their hydrocortisone when ill to mimic a $stres response$.

What is secondary hy oadrenalism? This is adrenal hypofunction due to non adrenal causes. %t occurs in Dypothalamic pituitary disease. Cong term steroid use when hypothalamic pituitary adrenal suppression occurs. %t is rested for by long synacthen test with a higher dose of synacthen, and blood test at <,6,2,3,&,,,> M 2& hours.

Surgical Physiology 63,

Cushing1s disease = Cushing1s syndrome

What is the difference between Cushing1s disease and Cushing1s syndrome? *ushingKs syndrome- is any clinical condition resulting from excessive inapproprtiate exposure to glucorticoid. *ushingKs disease- is where excess glucocorticoid results from a pituitary tumour. What are the causes of Cushing1s syndrome? 6. %atrogenic /the commenst1 U patients on long term exogenous steroids for immune suppression or treatment of diseases such as brittle asthma. 2. %ncreased autonomous secretion of '*TD from a pituitary microadenoma drives the adrenals into bilateral hyperplasia and hypercortisim with increased androgen secretion as well U this is cushingKs disease. 3. ' variety of extra adrenal tumours produce '*TD li"e substances, such as bronchogenic tumours and small carcinoid neoplasms5 this gives the ectopic '*TD syndrome. &. ' primary adrenal tumour either adenomatous or carcinomatous, may produce excess cortisol directly with normal or usually low '*TD. What are the ty ical manifestations and causes of hy ercorticism? The clinical picture of hypercortisolism, commonly referred as *ushingKs syndrome, is one of the most stri"ing of all the endocrine diseases. o 2lucocorticoid action stimulates appetite and gluconeogensis resulting in obesity and fat deposition in particular sites, creating buffalo hump, moon face and central obesity.

Surgical Physiology 634 o %n association with muscle wasting owing to toxic effect of cortisol on muscle, the classical appearance of $a lemon on toothpic"$ occurs. o 9ecrease in collagen synthesis give rise to thin s"in, which bruises easily, heals poorly M stretches causing striase. o 9iabetes melliteus enuses owing to the glucocorticoid action. o The mineralocorticoid effect of cortisol causes mar"ed salt M water retention giving rise to hypertension. o %ncreased adrenal androgen secretion, if there is increased '*TD, accounts for the acne and hirtism often seen. o %f there is often mar"ed osteoporesis and pathological fractures.

How would you diagnose Cushing1s syndrome? Ta"ing history and examination, bearing in mind that none of the above clinical findings are diagnostic of *ushingKs syndrome. ' methodical approach to the diagnosis is needed and initially confirm the diagnosis of hypercortisolism before attemping identification of the cause. %. 't first- serial plasma cortisol estimation loo"ing for 0ersistently raised levels. and Coss of diurnal variation as cortisol levels are highest at about ? am and lowest around midnight. %%. Then- an overnight dexamethasone suppression test by adminstering 6 mg dexamethasone at midnight and measuring the morning cortisol level. !ailure to suppress cortisol levels to less than ,<I of basal values points towards a diagnosis of *ushingKs syndrome. %%%. ' high dose dexamethasone suppression test /2mg 4 hourly for &> hours1 2 mg of dexamethasone is given 4 hourly for &> hours. 0lasma corisol is measured at <?-<< on the morning following the last dose. %t will suppress '*TD secretion in pituitary *uchingKs, resulting in a decrease of at least ,<I in plasma cortisol or urinary 6; hdroxy sterids. %f this test proves positive then arrange a cranial M7% to examine the pituitary fossa.

Surgical Physiology 63; %f the test was negative, suggests ectopic '*TDproduction or an adrenal tumour. Then assay plasma '*TD level. =ery high levels are consistent with ectopic '*TD secreting tumours. Cow plasma '*TD points to a primary cortisol secreting adrenal tumours. Daving differentiated between the two, *T or M7% scanning should be underta"en to image the lesion responsible.

What is nelson1s syndrome and e% lain its athogenesis? %t is the combination of hyperpigmentation following bilateral adrenalectomy. %n pituitary dependent hypercortisolism treated by bilateral adrenalectomy, up to 3<I of patients develop unrestrained growth of the pituitary tumomurs with enlargement of the sella tursica and very high levels of plasma '*TD. 7esidues 6 63 of the '*TD precursor molecules correspond exactly to F melanocyte stimulating hormone /F MSD1 and account for the s"in pigmentation that is the stri"ing feature of #elsonKs syndrome. The syndrome may develop acutely but is more commonly a chronic event with the meantime from adrenalectomy to onset being 3 years. 3ilateral adrenalectomy is less commonly performed these days, but anyone who has been treated in this way should be followed up regularly with cranial *T or M7% to loo" for an expanding sella tursica lesion.

Pheochromocytoma
Describe the synthesis and metabolism of catecholamine? *atecholamines are synthesized by chromaffin cells of the adrenal medulla and sympathetic nervous tissue5 both are derived from embryonic neural crest. 'drenaline is predominantly produced in the adrenal medulla and noreadrenaline in the sympathetic tissue. The pathway begins by hydroxylation of tyrosine to dihyroxyphenylalanine /9@0'1 follwed by decarboxylation to dopamine. This is further hydroxylated to noreadrenaline and t+en methylated to adrenaline. They are metabolized in the liver by further methylation and then deamination into vanilyl mandelic acid /=M'1, which is excreted in the urine. Arinary =M' M metanephrines may be measured. How might an e%cess of catecholamines resent clinically? *atecholamines excess, as in pheochromocytoma, presents with hypertension as the commenst symptom, which in ,<I of patients. @ther symptoms include Sweating M flushing. Dyperglycemia. 0heochromocytoma is "nown as 6<I tumour because 6<I of all tumours are extra adrenal. 6<I are bilateral.

Surgical Physiology 63> 6<I are malignant. 6<I are familial. 6<I occur in children.

How is the diagnosis confirmatory? The presence of excess circulating catecholamines is confirmed by 7aised urinary =M' M metanephrines /adrenaline, noradrenaline M dopamine1 in a 2& hour urine collection. 'fter the diagnosis is establishedThe tumour must be localized by M7% scanning better than *T bacause !unctioning M non functioning adrenal tumours have different characteristics on M7%, unli"e *T. The need for contrst which may trigger a hypertensive crisis is avoided in M7% scanning. %f the tumour isnKt localized by M7%, then M%32 /623% metaiodobenzyllguanidine1 scanning is both sensitive M spicific. What consideration need to be ta$en into account before embar$ing on surgery in these instances? @perating for phaeochromocytoma isnKt for the occasional surgeon or faint hearted anaesthetist. %nadverent handling of the tumour can stimulate an enormous outpouring of catecholamines5 even induction of anaesthesia in the unprepared patient can have the same effect. The patient must be fully F M ] bloc"ed before surgery. The long acting F bloc"er phenoxybenzamine is used along with a ] bloc"er such as propranolol. The timing of ] bloc"ade isnKt critical, but the F bloc"ade re:uires careful optimization. The patient is started on phenoxybenzamine ; 6< days before surgery, and the dose increased until hypertension is controlled and the patient develops orthostatic hypotension. The surgery iteself is now routinely performed laparoscopically for tumours less than 4 cm. The approach is most commonly transabdominal but smaller tumours can be removed endoscopically by a posterior retroperitoneal approach. 'fter removal of the tumour, the patienKt venous tone may disappear altogether, causing a massive relative hypovolaemia. Thus the anaesthetic should be warned when removal of the tumour is imminent in order to maximize the circulating volume. Might it be associated with other conditions? 6<I are familial, associated with M.# syndrome type %% /SippleKs syndrome1The other components of M.# %% are Dyperparathyroidism which may eb due to either parathyroid adenoma or hyperplasia. Thyroid medullary carcinoma. The condition is autosomal dominant with the genetic defect located on chromosome 6<. 'further variant M.# %%b encompasses-

Surgical Physiology 63? Same abnormalities, ( Mucosal neuromatosis. Marfanoid habitu. Musclos"eletal abnormalities. What is the rognosis for atients with malignant heochromocytoma? @verall 6<I of pheochromocytoma are malignant, but ,< I of all extra adrenal pheochromocytoma are malignant. M%32 scanning is useful to assess metastatic spread. Surgery is the mainstay of treatment as the tumours are unresponsive to chemotherapy, rediotherapy to bony metastases will provide local palliation. The , year survival is around &<I.

Pancrease
How much ancreatic fluid is secreted each day? 0ancreatic fluid is secreted 6,<< ml8day. What do ancreatic secretions contain? Bater, electrolytes /cations- #a(, )(, *a2( M Mg2(. 'nions D*@3 , *l ,S@&2 . 0D around >1 and enzymes. What is the e%ocrine function of ancrease? %t is to produce digestivenzymes, fluids M electrolytes to modify M optimise the 0D environment. What en/ymes does the ancrease synthesi/e? %t synthesizes 3 main groups of enzymes ' proteolytic group which includes trypsinogen, procarboxypeptidases and proelastase. The starch and polysaccharide enzymes /amylase1. ' lipolytic enzyme group consisting of lipase and phospholipase. What are their function? The proteolytic enzymes of which trypsinigen is the most important, activate other proteolytic enzyme precursors though an autocatalytic process.

Surgical Physiology 6&< 0ancreatic amylase hydrolyses starch, glycogen and other carbohydrates. 0ancreatice lipases-it is regulated by 2 mechanisms neural and hormonal. 6. #eural control%t occurs during the cephalic phase and gastric phases of digestion. The pancrease is stimulated by impulses along the vagus nerve to pancreatic enzymes. %t causes release of pancreatic secretions high in enzyme content. 2. Dormonal regulation%t is the most important mechanism. %t is mediated by hormones released from the mucosa when chyme enters the duodenum Secretin%t is produced by endocrine cells in the duodenum and +e+unum. %t is released when acid enters the duodenum. This causes the pancreatic ducts to secrete large amounts of fluid with a high bicarbonate content /M low enzyme content1. The bicarbonate neutralises the acid and creates the necessary luminal 0D for activity of pancreatic enzymes. *holecysto"inin%t is produced by endocrine cells in the duodenum M +e+unum. %t is released when food, particularly fatty acids, enters the duodenum. %t stimulates secretion of pancreatic +uice /high in enzyme content1. 'cetylcholine- acts on acinar cells. Somatostatin%t is released from pancreatic islet 9 cells. %t inhibits pancreatic secretions. What are the endocrine functions of the ancrease? The following hormones are secreted by the islets of Cangerhans%nsulin %t is produced by the ] cells. %t facilitates glucose upta"e to muscle, glyogen and fat synthesis in the liver. %t also inhibits glycogen brea"down. 2lucagon %t is produced by the F cells. %t stimulates glycogenolysis and glyconeogenesis in the liver. Somatostatin %t is released from pancreatic islet 9 cells. %t inhibits insulin and glucagon release. %t also inhibit pancreatic M gastric secretions. 0ancreatic polypeptide %t has a role in gastrointestinal function. What would the effects of subtotal ancreatectomy be? 7emoval of all or almost all of the pancreas will lead to a varying degree of malabsorption of fat. This will result ino !ailure to absorb fat soluble vitamins such as ', 9, . M ) and if not supplemented, may result in deficiency.

Surgical Physiology 6&6 o 0rotein malnutrition may enuse and without proper glucose control pateints may develop gleucose intolerance and diabetes.

"cute ancreatitis
What is ancreatitis ? 'cute pancreatitis - acute inflammation of the pancreas is a common cause of acute abdominal pain with considereable associated morbidity and mortality. %t can be divided into mild, moderate and severe, depending on presentation. What are the ossible causes of ancreatitis ? ' mnemonic to remember the causes of pancreatitis is 2.TSM'SD.9 2- gallstones /probably the most common cause, impacted at the ampulla of =ater and causig bac"wash of activated pancreatic enzymatic +uice into the parenchyma of the pancreas, leading to pancreatic autolysis and haemorrhage1. .- ethanol /alcohol is a very common cause of pancreatitis and people with alcohol problems often develop chronic pancreatitis after number of bouts acutely1. T - trauma. S -steroids. M- mumps /paramyxoviruses1. '- autoimmune / panartetitis nodosa or 0'#, systemic lupus erythematosus or SC.1. S- scorpion sting 8sna"e bite.

Surgical Physiology 6&2 D- hypercalcaemia, hyperlipidaemia8 hypertriglyceridaemia and hypothermia. .- .7*0 /endoscopic retrograde cholangiopancreatography1. 9- drugs /e.g. sulphonamides, furesemide, azathioprine, #S'%9s1. Cess common causes *arcinoma of the head of the pancreas. 0ancreas divisum. Cong common bile duct. !at necrosis. 0regnancy. 0ancreatic ischaemia as a result of bypass surgery. What are the clinical features of ancreatitis ? 'cute severe abdominal pain, usually constant, epigastric and radiating into the bac", and relieved by sitting forwards. =omiting is early and profuse. 0atient usually shoc"ed with rapid pulse, cyanosis. 'bnormal temperature- either subnormal or pyrexial. .xamination of the abdomen reveals generalized tenderness and usually garding with or without rebound tenderness. 3< I of cases have mild +aundice as a result of oedema of the pancreatic head obstructing the common bile duct. 'fter a severe attac", patient may develop a bluish discoloration in the loins from extravasation of blood stained pancreatic +uice into the retroperitoneum /2rey TuurnerKs1. 3luish discoloration and bruishing may occur in the periumbilical region /*ullenKs sign1.

What are the investigations? Tests confirm the diagnosis and utilize the creticria below to determine the severity. %n addition to arterial blood gases and venous sampling for amylase, liver function tests /C!Ts1, full blood count /!3*1 and urea and eletrolytrs / A(.s1 6. .*2- flattened T waves or arrhythmias may cause confusion with cardiac ischaemia 2. 'bdominal radiograph %t isnot usually helpful inacute pancreatitis but can show pancreatic calcification in cases of acute on chronic pancreatitis. %n some cases a K sentinel loop K of proximal +e+unum may be seen to be dialted.

Surgical Physiology 6&3 3. .rect chest radiograph to exclude a perforation , which can present in a similar manner. &. Altrasonography%t may show gallstones and8or dilated common bile duct and pancreatic duct. @ften gives poor views of the pancreas. 2ood for loo"ing for collecting in the acute setting U can also be used to loo" for pleural effeusions. ,. 'bdominal computed tomography /*T1 is the investigation of choice. 3ut is not usually performed before &> hours of onset of the episode. 9iagnostically , fat strea"ing is seen around the pancreas or fluid may be seen in the lesser sac, and this may be confirmatory in cases where the serum amylase is normal . !urther, later imaging may reveal necrosis in the pancreas is normal. !urther, later imaging may reveal necrosis in the pancreas or the formation of a pancreatic pseudocyst. 4. Serum calcium- may well be lowered as a result of fat saponification, and may lead to tetany and cardiac arrhythmias in severe cases. "SS'SSM'N0 63 P"NC&'"0!0!S S'4'&!0A o %t is essential to perform arterial blood gas sampling in all patient with pancreatitis to assess their acid base status and to "eep a regular chec" on their arterial 0o2. o Serum amylase is used as a diagnostic criterion but, in 6<I cases, it is normal, particulary in acute on chronic pancreatitis, where there is a loss of acinar cell mass, or in severe pancreatitis with pancreatic necrosis. o Scoring system- two very well "nown and used methods are the 7anson and the 2lasgow cretiria.

2lasgow criteria for severe pancreatitis The following criteria are assessed over the first &> hours. 3or more indicate severe pancreatits with a high mortality 'ge X ,, years.

Surgical Physiology 6&& Dyperglycaemia /glucose X6< mmol8C in the absence of a history of diabetes1. Ceu"ocytosis / 6, x 6< ? 8C1. Area X 64 mmol 8C after ade:uate rehydration. ho2 L > "0a on arterial blood gases. *alcium X 2.< mmol 8C. 'lbumin L 32 8C. Cactate dehydrogegenase /C9D1 X 4<< %A8C. 7aised aspirate tranaminase /'ST1X 6<< %A8C.

7ansonKs criteria for pancreatitis 7ansonKs criteria on admission 'ge X ,, years. Bhite blood cell count / B** 1 X 64 <<< eC. 2lucose X 66 mmol 8C / X 2<< mg8dC1. Serum C9D X &<< %A8C.

Serum 'ST X 2,< %A8C. 7ansonKs criteria after &> hours of admission !all in haematocrit by more than 6< I. !luid se:uestration of X 4 C. Dypocalcaemia /serum calcium L 6.< mmol8C / >.< mg 8dC11. Dypoxaemia / 0@2 L >< mmDg1. %ncrease in urea to X 6.?> mmol 8C /X , mg 8dC1 after intravenous fluid hydration. Dypoalbuminaemia /albumin L 3.2 g8dC1 in the firast &> hours of admission. 3ase deficit of X &.

The prognostic implications of 7ansonKs criteria are as follows Score < 2 Q 2 I mortality rate. Score 3 & Q 6, I mortality rate. Score , 4 Q &< I mortality rate. Score ; > Q 6<< I mortality rate. Patho hysiology of mar$ers of severity>

Surgical Physiology 6&, Dypoxia - a result of /'79S1 and pleural effusions. Dypocalcaemia - calcium is chelated after the saponification of omental fat by pancreatic lipases. 'cidosis - anaerobic respiration of tissues as a result of poor perfusion leads to a lactic acidosis. Digh urea- reflects dehydration. Digh B**- acute inflammatory response and probable pancreatic necrosis i superventing bacterial infection.

0reatmwnt> This is largly conservative and non surgical but aggressive, consisting of !luid resuscitation and replacement with either colloid or blood transfusion to treat profound shoc" that can result from acute pancreatitis. .lectrolyte replacement is often re:uired, with particular attension to potassium and calcium if necessary. 'll patients should be catheterized and a urometer should be used to produce a strict record of hourly urine output. !luid se:uestration can be very svere in acute pancreatitis, re:uiring many litres of fluid replacement to "eep up. %t is not uncommon for initial rescuscitation volumes of an individual with acute pancreatitis to be of the order of 6< 6, C over several hours . 'nalgesia - pain relief with pethidine commonly. Morphine is said to produce sphincter of @ddi spasm but there is little evidence to support this theory.patient controlled analgesia /0*'1 can be useful in this contex.

Surgical Physiology 6&4

2%T

Surgical Physiology 6&;

Swallowing and oeso hageal hysiology

What is the se#uence of events in swallowing? @ral phase !ood is chewed and a bolus is formed, which is pushed to the posterior pharynx by the tongue. Dere, afferent impulses in cranial nerves %G and G are transmitted to the swallowing centre / medulla1, which refluxly triggers swallowing via efferent impulses in cranial nerves %G and G.

7espiration is also refluxly inhibited. 0haryngeal phase The soft palate is pulled upward and palatopharyngeus helps to close the nasopharynx and prevent reflux. The true vocal folds are apposed and larynx elevates . The bolus pushes against the epiglottis to close the entrance to the respiratory tract and prevent aspiration. Apper oesophageal sphincter /cricopharyngeus muscle 1 relaexes.

The constrictor muscles /superior, middle, inferior1 se:uentially contract and force the bolus down into the oesophagus. @esophageal phase 3olus is propelled along the oesophagus by a primary peristaltic wave behind the bolus. Ta"es ? 6< seconds to transverse the oesophagus. Secondary waves can occur if the bolus is not cleared. Tertiary contractions are non propulsive and their presence is pathological.

What s hincteric mechanisms are there in the lower oeso hagus and how is reflu% normally revented ? Cower oesophageal sphincterThis is a physiological sphincter /there is no anatomical sphincter here1, located at the lower 2 cm of the oesophagus . %t is an area of high pressure. %ts finction is to prevent reflux of acid into the oesophagus. The factors preventing reflux are as follows 'cute angle of entry to the stomach acts li"e a valve. 7ight crus of diaphragm acts as sling around the lower oesophagus. %ntra abdominal pressure acts on segment of oesophagus below the diaphragm. Mucosal folds act as valve.

Surgical Physiology 6&> Cower oesophagus is normally contracted. ' degree of reflux occurs through this sphincter in normal individuals. Dowever, several factors can lead to disruption of this sphincter, and hence reflux Te upper stomach can herniated through the diaphragm /hiatus hernia1. %ncreased intra abdominal pressure in pregnancy or after a large meal can cause reflux. Some individuals have an incompetent lower sphincter

0he stomach
What volume of gastric secretions are roduced each day by a healthy adult? 'pproximately 2,<< ml. What are the contents of gastric secretions? Dydrpchloric acid. 0epsin. 2astric liYase. %ntrinsic factor. Mucus. Bater. %ons /e.g. #a(, )(, Mg2(, D0@&2(, S@&2(1. What is the function of hydrochloric acid? 6. 'ctivate pepsinogen to pepsin. 2. *onvert ferric acid to ferrous form. 3. 'cid environment aids the absorption of calcium. &. )illing of ingested bacteria. Which cells secret e sinI The chief cells secrete it as an inactive precursor pepsinogen. What is the function of e sin? 3rea"s down food proteins to peptides and polypeptides. Which cells secrte intrinsic factor? The parietal cells. What is the function of intrinsic factor? 3inds to vitamin 362 so that it can be absorbed by the ileal mucosal epithelial cells. How is acid secretion regulated? There 3 phases to acid secretion'. *ephalic phase- initiated by the site, smell, taste or thought of food. =agally mediated, acetylcholine directly stimualates the production of acid and indirectly causes acid secretion by stimulating secretion of gastrin /from 2 cells1 and histamine /enterochromaphin li"e cells1.

Surgical Physiology 6&? 3. 2atric phase- the mechanical effect of food in the stomach, distension of the body, antrum and pyloric are leads to the release of gastrin and also causes vagal stimuation leading to stimulation of pareital cells. 0rotein digestion products, calcium ions, caffeine, alcohol and amino acids in the antrum stimulate gastric secretion. *. %ntestinal phase- duodenal distension, presence of peptides and amino acids stimulate gastric secretion mainly by 2 cells in the duodenum. 'cid in the duodenum leads to the release of secretin, fatty acids in the duodenum causes the release of cholecycto"inin /**)1 and gastric inhibitory peptide all of which inhibit gastric secretion. What ha ens to gastric acid secretion when large arts of small intestine are removed ? 2astric acid secretion is increased and the amount is roughly proportional to the mount of intestine removed. Do you $now of any other factors that may influence acid and e sin secretion? Dypoglycemia can stimulate acid and pepsin secretion via cerebral and vagal influences. %n addition, stimulants such as alcohol and coffee can act directly on the gastric mucosa. What are the functions of the stomach ? 6. 7eservoir for food, mixing of food with gastric secretions to form chime. 2. .ndocrine function- secretion of gastrin. 3. .xocrine functionso 0roduction of acid- digestion of food and immune function. o .nzyme production / pepsin1 for protein digestion, intrinsic factor and mucous. 6. 7eservoir M mixing functions %ts volume can increase to 6., C without an increase in pressure. %t performs mixing and rudimentary digestion of proteins and carbohydrates. %t is able to deliver smaller, more manageable :uantities of material to the duodenum as re:uired and re+ect potentially harmful subsrances before absorption. %t renders the ingested contents relatively free of bacterial contamination by way of the bactericidal action of hydrochloric acid. 2. .ndocrine functionThe stomach produces a hormone called gastrin / 2 cells of the antral mucosa1. This hormone is released in response to the cephalic phase controlling acid secretion in the stomach. 2astrin acts to increase the secretion of acid by partial cells in the stomach. %t also causes histamine release, which potentiates the release of acid. D2 receptors such as ranitidine and cimetidine reduce gastric acidity by bloc"ing this mechanism. 3. .xocrine functions-

Surgical Physiology 6,< '. 'cid secretion. 3. %ntrinsic factor.

2ased on your $nowledge of the functions of the stomach * what are the effects of a total gastrectomy ? .arly dumping syndrome - food of high osmolarity, not mixed in the stomach, causes rapid fluid shift and oligaemia. This causes fainting and sweating from hypovolaemia Cate dumping syndrome- caused by rebound hypoglycaemia, or high insulin levels experienced after a high carbohydrate load is presented and absorbed by the duodenum. Similar symptoms to above. 0ernicious anaemia and iron deficiency anaemia. .arly satiety- loss of reservoir function. 3ilious vomiting- loss of pyloric sphincter. Dypocalcaemia and iron deficiency. 2astric stump carcinoma - cancers occur at the gastro+e+nal anastomosis 2< years or so after surgery. This may be a result of chronic irritation of gastric mucosa by duodenal secretions 2allstones- caused by increased gallbladder motility post vagotomy Which tumor can lead to the develo ment of multi le sever e tic ulcers? 2astrinoma 9ue to gastrin secreting adenomas in the pancreas, duodenum, stomach, or elsewhere /eg. *ystadenoma of the ovary1 or simple islet cell hyperplasia. ,<I 4<I of tumors are malignant of ,<I are multiple. 3<I of cases are associated with autosomal dominant disorder of multiple endocrine neoplasia /M.# 61 @verproduction of gastrin leads to Eollinger .lison syndrome, with widespread peptic ulceration and diarrhea. What is ernicious anaemia? The parietal cells of the stomach that secret D*C also secrete a glycoprotein "nown as intrinsic factor, which is essential for vitamin 362 absorption. %ntrinsic factor binds to 3626. 0rotects it from acid digestion in the stomach. 2. 'ids its absorption by pinocytosis at the intestinal brush border of the terminal ileum.

Surgical Physiology 6,6 9eficiency of intrinsic factor either as a result of chronic atrophic gastritis or the generation of autoantibodies to the parietal cell, gives rise to a megaloblastic anaemia "nown as pernicious anaemia. ' similar event occur after gastric resection. %t is easily treated by 3 monthly vitamin 362 in+ections. There is a lag period of several years between abolition of intrinsic factor function from whatever cause and the development of pernicious anaemia as the bodyKs reserves of vitamin 362 are considerable.

What factors increase the ris$ of develo ing gastric carcinoma? *ertain factors are recognized as ris" factors for the development of gastric cancer not least of which is a geographical distribution of the disease with a high prevalence in the +apenease. Bhether this is diet related or not is unclear. The other notable ris" factors are 0ernicious anaemia *hronic atrophic gastritis 2astric polyps !amily history- a small group of patients have a defect of . cadherin gene, which predisposes them to gastric carcinoma at a young age. The postgastrectomy8 gastrotomy stomach %ntestinal metaplasia *igarette smo"ing 3lood group ' 2astric ulceration. Where in the stomach do most cancers occur? Two thirds occur in the pyloric region, one :uarter in the body, with only 4 percent occurring in the cardia. ' further 3 percent will be the diffuse infilterating carcinoma "nown as linitis plastica involving the whole stomach. Dowever, these figures are contiously changing, since the distribution of gastric cancers has been changing over the last decade with a gradual decrease in distal cancers and an increase in proximal cancers. What are the biochemical abnormalities that commonly occur in a case of yloric stenosis? '% lain them? The typical biochemical upset is a hypo"alaemic al"alosis associated with hypovolaemia and haemoconcentration. The urine is acidic . The gastric parietal cells generate D( and D*@3 via the carbonic anhydrase reaction. D( enters the gastric lumen, with chloride ions as hydrochloric acid and the D*@3 enters the extracellular fluid /.*!1 to be subse:uently secreted into the duodenum in bicarbonate rich biliary and pancreatic +uice. Thus, when vomiting occurs with free connection between stomach and duodenum, the body loses volume, D(*C , D*@3 , #a( and )(.

Surgical Physiology 6,2 The clinical problem is one of volume deficit and electrolyte disturbance rather than D8D*@3 dise:uilibrium. #ow consider the setting of pyloric stenosis in which free connection between stomach and duodenum does not occur5 vomiting will loss volumes and D(*C only causing a relative gain of D*@3 . The loss of D( drives the carbonic anhydrase reaction to produce more D(8D*@3 5 thus, the bicarbonate gain increases and as renal compensation is slight metabolic al"alosis ensues. The "idney is a sodium preserving organ and in the proximal tubules as there is less chloride for sodium to be absorbed with, owing to decreased chloride from vomiting, #a( exchanges for D( giving rise to acidic urine and worsening al"alosis. 's D( becomes scarter, #a( then exchange with )(, giving rise to potassium rich urine and hypo"alameia.

What is the e idemiology of this condition in the aediatric setting? %t is classically a condition affecting the male infant, usually the first borne and with an increased incidence in children of affected parents. The incidence in caucasions is about & per 6<<<. %t presents at between & and 4 wee"s with pro+ectile vomiting, continuing hunger even after feeds, poor stools and weight loss. 9ehydration and wasting is now only seen in extreme cases of delayed presentation. Describe the diagnosis and management of a child with congenital hy ertro hic yloric stenosis? The history is usually higher suggestive of the diagnosis. Bitnessing a test feed is usually enough evidence, as the baby feeds hungrily and a pro+ectile vomit follows. The hypertrophic pylorus can often be palpated in the epigastrium as a firm olive sized swelling. Altrasound confirms the diagnosis. Treatment3y correction of biochemical abberations and scheduling the child for urgent surgery. 7amstedKs pyloromyotomy ' transverse or even periumbilical incision. The pylorus is identified and the hypertrophic muscle fibers divided until the intestinal mucosa is seen to pout through the incision. The abdomen is then closed.

Surgical Physiology 6,3

Small bowel
What substances are absorbed or digested by the small intestines? Bater and electrolytes. *arbohydrates. 0rotein. !at. %ron. !olate. *alcium. =itamin 362. What are the functions of the duodenum? *ontrol of gastric contents. Stimulation of gastric acid. 7eduction in gastric acid output. 0ancreatic secretion stimulation. Stimuates bile formation. Stimualtion of gall bladder contraction. 'bsorption of carbohydrates, amino acids, fatt acids, calcium and some vitamin. How is gastric acid out ut affected by the duodenum? 2astrin released by the duodenal 2 cells stimulates gastric acid secretion. Secretin and gatric inhibitory peptides secreted by duodenal S and M cells respectively reduce the secretion of gastrin in the stomach and therefore reduce gastric acid secretion. How does the duodenum control gastric acid? The mucosa of the duodenum is more resistant to the gastric acid. The duodenum is where neutralization of gastric acid occurs.

Surgical Physiology 6,&

How does neutrali/ation of gastric acid occur? 0ancreatic secretion containing D*@3 are stimualted by secretin and **) released from duodenum. **) also stimulates gall bladder contraction and bile formation. D*@3 is also secreted from the glands of 3runner in the submucosa. What are the effects of duodenectomy? 'cid contents reaching the +e+unum can causeulceration. %ncomplete neutralization leading to decreased absorption of iron, calcium and phophate. Coss of control of gastric emptying can lead dumpting syndrome. Coss of pancreatic and biliary stimulation leads decreased fat absorption.

What is dum ing syndrome? %t can be caused by excessive volumes of food entering the small intestine to fast. This leads to large volumes of extrscellular fluid into the lumen of the intestine and uncontrolled carbohydrate absorption leading to rapid changes in serum glucose. Symptoms include faintness, sweating, abdominal pain and tachycardia. What is the function of .e.unum? %t has , broad functions namely6. Transport of chyme between duodenum and ileum. 2. Mixing of this digextive fluid. 3. 'bsorption of various nutrients and electrolytes and water. &. Secretion both exocrine M endocrine. ,. Cymphoid function. 6. Transport function%t is obvious as the +e+unum provides the continuuity of the gastrointestinal tract 2. Mixing function's the repetitive chuming is accompained by contraction of the villi to help pump nutrient rich lymph away from the brush border. %nterspersed with this action are propulsive contraction of the +e+unum to propel the bolus of chyme down the gut. 3. The 'bsorption @f carbohydrate, protein, iron and folic acid as well as most of the water and electrolytes. !at and fat soluble vitamins are absorbed mainly in the +e+unum. Einc and copper have been shown to be absorbed mainly in the upper gastrointestinl tract 7esorption is driven by the osmotic forces generated by nutrient absorption. Carge proportion of electrolytes /#a(, *l , D*@3 1 are resorbed, in part by simple diffusion, in part by active transport mechanism and partly due to the osmotic pull of nutrient absorption an effect "nown as solvent drag. &. Secretion both exocrine M endocrine-

Surgical Physiology 6,, Such as somatostatin, secretin and motilin which is implicated in the intrinsic rhythmicity of the various gut segments. ,. Cymphoid functionThe entire gut performs an important immune function and is endowed with its own system of lymphoid tissue collectively "nown as mucosa associated lymphoid tissue /M'CT1. %t occurs in concentereated areas suchas the peyerKs patches as well as diffuse distribution of intraepithelial lymphocytes and mucosal mast cells which help protect the gut from the constant exposure to antigens within the gut lumen. How would you differentiate .e.unum from ileum in a athology s ecimen? The gut wall of +e+unum is thinner, but with thic"er more vascular mucosa than ileum. The +e+unum has a larger circumference. Ander microscope, the villi are taller and more numerous in the upper gut. The arterial arcades supplying the +e+unum are more obviously arborizes /tree li"e1 and plentful. There is much more fatty infilteration of the ileal mesentery than in the +e+unum, where the mesentery is often transparent. Describe the functions s ecific to the terminal ileum and the conse#uences of resection? .ffective absorption of bile salts and vitmain 3 62 onl occurs in the terminal ileum, since they ac:uire specific transport channels that areonly situated there. The bile salts are normally returned to the liver and recycled this is "nown as the enterohepatic circulation. 7esection of the terminal ileum prevents this pathway from functioning and an excessive loss of bile salts occurs. This in turn leads to malabsorption of fats and steatorrhea owing to the diminshed bile salt pool. =itamin 362 isnot absorbed when the terminal ileum has been resected and patients who have undergone resection should have regular blood cheec"s, and receive parenteral 362 regularly if needed. What are the causes of malabsor tion? 6. 'bnormal digestion in the intestinal lumen. 2. 0yloroplasty- dumping syndrome /inade:uate mixing of food with pancreatic secretion and bile1. 3. Small bowel resection- reduced absorptive area. &. *hronic pancreatitis. ,. *ystic fibrosis. 4. 3loc"age of bile duct /stone M carcinoma1. ;. .xcess gastric secretion- leading to inade:uate lipolysis. >. 3lind loop syndrome- causes bacterial overgrowth decreasing con+ugated bile salts. ?. *eliac disease. 6<. 9isaccharide deficiency. 66. 'bnormal fat transport in the lymphatics. What are the conse#uences of small bowel resection?

Surgical Physiology 6,4 'fter loss of most of +e+unum fat, protein and carbohydrate absorption is reduced due to loss of absorptive area. This leads to diarrrhoea with loss of water and electrolytes. The ileum over several wee"s ad+usts ta"ing over most of the functions of the +e+unum after resection. Bhen over 6 m of terminal ileum is resected bile salts and vitamin 362 absorption is reduced and the +e+unum is not able to compensate. Stores of vitamin 362 last over 3 years, the bile slat pool however declines, this leads to increased gallstone formation, steatorrhoea and decreased absorption of fat soluble vitamin /', 9, . M )1.

What are the causes and features of )short bowel syndrome)? Short bowel syndrome occurs when there is insufficient bowel remaining to support the absorptive function re:uired for normal growth and life. The minial amount of small bowel needed for normal absorption is approximately 6<<cm, although as little as ,< cm may be ade:uate, if a complete functioning colon is in situ. The symtpoms are due to the intestinal decompensation from both reduction in absorptive area and a greately reduced transit time. 'bsorption of fats and proteins are most severly affected followed by carbohydrates. The patient is malnourished and underweight, with diarrhoea or steatorrhoea. There are deficiencies of most vitamins and trace elements. Bith time, the bowel adapts with increased numbers of enterocytes and heightened villi in the remaining bowwel, and compensation to some degree can occur. The principal reason for short bowel syndrome is extensive small bowel resection5 indications include *rohnKs disease. Mesenteric infarction. 7adiation enteritis. Mid gut volvulus. Small bowel tumours. Coss of bowel length from congenital atresias and loss of functional length due to multiple fistulae may also be responsible.

Surgical Physiology 6,;

!ron absor tion and trans ort

What is the role of iron in the body? %ron is an absolute re:uirement for the synthesis of haemoglobin, so its deficiency leads to hypochromic microcytic anaemia. What is the usual daily re#uirment of iron? 'pproximately 2, mg of iron is re:uired daily for haemopoiesis. The ma+ority of iron in the body is recycled and only 6 mg of iron is absorbed per day. The normal diet contains between 6< and 2, mg a day. How does iron deficiency occur? %t generally results from increased losses. @nly in very rare instances does it occur as a result of failure of absorption or dietary deficiency. Where is iron absorbed? %t occurs in the upper small intestine. How is it absorbed? %t ossurs when iron is in the reduced ferrous form /!e 2(1. Daem iron is also relatively well absorbed /2<I1. %n the epithelial cell, iron is split from haem by the enzyme haemoxidase. @nce !e2( enters the epithelial cell, it is bound to a cytosolic protein called mobilferrin at the basolateral membrane of epithelial cells. Transferrin receptors mediate the transfer of the !e2( from mobilferrin to transferrin, and this !e2( transferrin complex is released into the extracellular fluid which then diffuses into the blood. Where is iron absorbed? %ron is stored in the liver, bone marrow and spleen, where it is stored as ferritin and haemosiderin.

Surgical Physiology 6,>

4itamin 2;5
What is the function of vitamin 2;5? %t is involved in the maturation of red blood cells and deficiency leads to 0ernicious anaemia. Subacute combined degeneration of the cord. %rritation. 9epression. Memory loss. Where is vitamin 2;5 stored? %t is manly stored in the liver, with small amount present in the bile. How long will the body store of vitamin 2;5 last if absor tion totally ceases? The bosyKs store of vitamin 362 is very large and will last 3 4 hours. Where is vitamin 2;5 absorbed? %t absorbed in the distal ileum. Can you describe the mechanism by which vitamin 2;5 is absorbed? !ollowing ingestion of food 0epsin in the stomach releases free vitamin 362 from proteins. This free vitamin 362 rapidly binds to a number of glcoproteins called 7 proteins. 9uring the intestinal phase of digestion 0ancreatic proteases start to degrade the complexes between the 7 proteins and vitamin 362. The free vitamin 362 then rapidly binds to intrinsic factor /which has been secreted by the parietal cells1, @nce bound to this complex is ta"en up by the ileal cells and is slowly transported into the circulation. 'bsorption of vitamin 362 normally occur in the presence of intrinsic factor. Dowever 6 2I occurs via instrinsic facot independent mechanisms. What other substances are absorbed in the distal ileum? !at soluble vitamins ', 9, . M ) and bile salts. What factors reduce absor tion of intrinsic factors? Cac" of instrinsic factors /pernicious anaemia and gastric resection1. Coss of terminal ileum /resection and crohnKs disease1. 3lind loop syndrome.

Surgical Physiology 6,?

:arge intestine
What are the main functions of the large bowel? 6. 'bsorption. 2. Secretion. 3. Motility. &. Storage. What does the large bowel absorb? Bater- 6 2 C enter the colon a day and only 6<< 2<< ml are excreted. .lectrolytes- #a( is actively absorbed. 'mino acids. !atty acids. =itamin ) and 3 complex vitamins. What is secreted from large bowel? .lectrolytes- )( and D*@3 are secreted. Mucus- secreted by the goblet cells. What is stored in the colon? !aeced are stored mainly in the transverse colon until defecation occurs. 2as mainly consisting of nitrogen, it also contains oxygen, carbon dioxide, methane /only 6I of the population1 and hydrogen sulphide. What are the conse#uences of diarrhoea? %n the acute situation absorption of #a( and water is reduced. Secretion of )( M D*@3 is reduced. This leads to dehydration and merabolic acidosis. %n chronic diarrhea'ldosterone leads to increase )( loss from the "idenys and large bowel causing hypo"alemia and a metabolic al"alosis. What are the causes of diarrhoea? 7educed absorptive capacity /bowel resection and colitis1. Malabsorption. .xcess bile. %ncreased peristalisis. %nfection. Tumours /carcinoid1. 9rugs /laxatives and antibiotics1.

Surgical Physiology 64<

:iver and he atic failure

What are the function of the liver? 6. 0roduction of bile 2. 0rotein , fat and carbohydrate metabolism 3. Storage of glycogen and vitamins / ',9,.,),3621 &. 9etoxification of drugs , hormones and toxins ,. 7eticulonoendothelial and haematopoietic / fetus 1 functions. 4. )upffer cells /macrophage function1. ;. 3lood reservoir and production of heat. ;. Production of bile. 5. Metabolism> Protein metabolism Muscle is bro"en down in starvation to amino acids and transported to the liver for glucuneogenesis. 0rotein is bro"en down in the liver to form nitrogegous waste products such as urea via the urea cycle. The liver is responsible for the synthesis of all non essential amino acids. %t is also responsible for the synthesis of protein, such as albumin, clotting factors and complement proteins

3at metabolism> The liver is responsible for synthesis of transport proteins for fatty acids , and in starvation it synthesizes "etone bodies. !atty acids are cleaved to produce acetyl *o' for the production of 'T0. %n starvation, the brain re:uires glucose to function but can also metabolize "etone bodies for energy. The liver can produce "etone bodies from fatty acids /which cannot be used to produce glucose1.

Carbohydrate metabolism> This occur during gluconeogenesis. %n Ktimes of plentyK, glucose is converted into glycogen, for storage /glycogenesis1. The brea"down of glycogen to glucose ta"es place in the liver in early starvation /fasting1, and is called glyconeogenolysis. D. Storage> The liver stores glycogen, vitamins ', 9, ., ) and 362, iron and copper.

Surgical Physiology 646 B. Deto%ification> 0eptide hormones /e.g. insulin1 and steroid hormones /e.g. testosterone1 are degraded in the liver. The cytochrome 0&,< system is involved in their metabolism, which includes increasing water solubility. 9rugs that increase or decrease the activity of the cytochrome 0&,< system may have an effect on other drugs being administered concomitantly.

What is the role of the liver in starvation ? o .arly starvation- glycogenolysis and gluconeogenesis /muscle brea"down to form amino acids1. o Cate starvation- brea"down of fatty acids. !ormation of "etone bodies, for use by the brain. )etosis occurs when the liverKs glycogen reserves are used up and the liver metabolizes fat to produce "etones. These are used as an energy source by respiring tissue, sparing glucose for the brain, which relies on a proportion of glucose for metabolism but can also use "etone bodies. What lasma roteins are synthesi/ed by the liver? 'cute phase proteins. 'lbumin. 0roteins that transport steroids. 0roteins that transport hormones. *lotting factors =, =%%, %G M G.

How are substances inactivated and e%creted by the liver? The liver reduces the toxicity and biological activity of substances and increases their water solubility. The cytochrome 0&,< system is involved in increasing water solubility. The formation of glucoronides of a vareity of substances including bilirubin, steroids and some drugs is catalyzed by the glucuronyl transferase system. What substances affect the cytochrome PBJE system? %ncrease activity is caused by- barbituates, phenytoin M rifampicin. 9ecrease activity is caused by- erythromycin, "etoconazole and cimetidine. What drugs interact with warfarin and how ? .rythromycin inhibits the cytochrome 0&,< system and phenytoin increases it, so warfarin, which is metabolized via this system, would have its effects potentiated if administered together with erythromycin, and reduced if admintered with phenytoin. What cells carry out the reticuloendothelial function in the liver? )upffer cells remove bacteria, toxins and abnormal erythrocytes.

Surgical Physiology 642 What com lications of liver disease are relevant in the erio erative eroid? 6. 3leeding 0rolonged prothrombin time /0T1. Thrombocytopenia. @esophageal and gastric varices. 2. .ncephalopathy. 3. Dypoglycaemia. &. 'scitis due to portal hypertension, sodium and water retention and low albumin. ,. 9epressed immune function. 4. 7enal failure. What is child1s classification? %t is a system of classifying the ris" of mortality for surgery and anaesthesia in hepatic failure, based on6. 3ilirubin. 2. 'lbumin. 3. 0rothrombin time. &. 'scitis. ,. .ncephalopathy. 4. #utrition.

Surgical Physiology 643

2ile
How much bile is roduced a day? %t is produced ,<< 6,<< ml8day and is stored in the gall bladder between meals. What is the function of bile? 3ile salts are re:uired for lipid digestion. D*@3 aids neutralization of gastric acid as it enters the duodenum. .xcretory route for bile pigment, cholesterol, steroids and fat soluble drugs. How do bile salts function? Depatocytes form primary bile salts /steroid molecules1 from cholesterol. 0rimary bile salts are dehydroxylated by intestinal bacteria to secondary bile salts. 3ile salts are detergents /containing a fat and a water soluble end1, in a:ueous solution bile salts form micelles /hydrophobic ends in the centre and the hydrophilic ends on the surface1 this enables them to solubalise and assist the absorption of lipids. Where are bile salts absorbed? >< I of bile salts are absorbed actively in the distal ileum and pass bac" to the liver via the portal circulation. The remaining bile salts enter the colon where they are converted to secondary bile salts /deoxycholate soluble and lithocholate insoluble1 and the soluble deoxycholate is absorbed. The bile salts are not absorbed /mainly lithocholate1 are excreted in the faeces. 3ile salts are recycled up to > times a day. What are bile igments and how they e%creted? 9egradation of the haem group of haemoglobin leads to the formation of biliverdin. This is then reduced to uncon+ugated bilirubin and is ta"en to liver attached to albumin. Ancon+ugated bilirubin is con+ugated with glucuronic in the liver. This is now water soluble and is excreted in bile. %ntestinal bacteria reduce the con+ugated bilirubin to urobilinogen /absorbed abd returns to the liver and is excreted into the bile1 and stercobilinogen /excreted in faeces1.

Surgical Physiology 64&

What is a )straberry gall bladder)? Bhen cholesterol precipitates from bile on the gall bladder wall, it forms yellow submucous collection of cholesterol with an appearance similar to a trawberry s"in. These are usually associated with cholesterol stones.

What different ty es of gallstones do you $nw and what are they made from? There three common varieteies of stones6. Mixed /;,I1 Most common type, often mutliple, pale Mfaceted. Ma+or component is cholesterol. *ut surface is laminated with alternate dar" M light zones of pigment and cholesterol respectively. 2. *olesterol /2<I1 @ften large solitary stones. *ut surface shows crystal radiating from the centre of the stone. Surface is yellow and greasy to touch. 3. 0igment /,I1 Small, blac", irregular and multiple, associated with haemolytic anaemia. *omposed of calcium bilirubinate and calcium carbonate. What roblems may gall stones cause? The ma+ority of gallstones are asymptommatic. Those that do cause problems they may do so withihn the gallbladder itself, within biliary tree or outside of the biliary system altogether. The site of the stones determines the further manahement of the patient. 0redisposing factor for carcinoma of the gallbladder. Bithin the gallbladder3iliary colic- obstruction of the gallbladder nec" by a gallstone gives rise to a sever colic"y pain, which may in contrast to most colics last for several hours. *holecystitis- the stones cause inflammation of the gallbladder wall. 0resents as right upper :uadrant pain, fever, leucocytosis and systemic upset. Mucocele- impaction of a stone in DartmannKs pouch can completely occlude the cystic duct. The gallbladder fills with mucus. .mpyema- infection of an obstructed gallbladder5 it turns into a bag of pus. Bithin the biliary tree@bstructive +aundice- bacause of occlusion of the common bile duct by a stone. %t tends to be painless as there is no muscle in the common duct wall to produce colic.

Surgical Physiology 64, 'scending cholangitis- is produced by infection in the stagnant bile of an obstructed system. The duct fills with pus and the patient is mar"edly unwell and septic. 0ancreatitis- due to impaction of a stone at the ampulla. @utside the gallbladder2allstone ileus- erosion of the stone through into the duodenum and passage through the small bowel may present wwith small bowel obstruction owing to the bloc"age of the ileocaecal valve by the gall stone. G rays reveal the stone in the right lower :uadrant and gas in the biliary tree, which is pathognomonic of this condition. Bhen is a T tube used and for how longR ' T tube is a rubber used to drain the common bile duct after surgical exploration. %t gives the bile a safe route to the surface, and forms a tract. The tube can be used to perform cholangiogram, and can be removed after 6< 6& days by which time a trac" will have formed. %n the event of bile duct stones remaining, they can sometimes be removed by the use of mechanical graspers down the tract under radiological control.

Surgical Physiology 644

!nflammatory bowel disease

Describe the ty ical athological features of Crohn1s disease? %t is a segmental discontinous full thic"ness inflammation of the bowel affecting the whole gastrointestinal tract from mouth to anus, which may have associated extraintestinal manifestations. Terminal ileitis is the commenst gastrointestinal lesion. The mucosa is reddened with small apthous ulcers that develop into superficial spreading ulcers with submucosal oedema and an increase in lymphoid tissue. This process may progress to deep narrow transmural ulcers and may result in fistulation U a common features of *rohnKs disease. .xtensive fissuring may leave islands of raised mucosa U cobblestonning. %n advanced disease, the bowel wall becomes fibrotic, giving rise to small bowel stricture or even longer $hosepipe$ segements. 'lthough *rohnKs is recognized as a chronic granulomatous condition, granulomata are only found in about ;<I of speciemen. What is a granuloma? %t is a collection of activated macrophages. What surgical interventions are common in Crohn1s disease? 's *rohnKs is a disease of the whole gastrointestinal tract, no resectional procedure is li"ely to be reliably curative as compared to ulcerative colitis. Surgical intervention should, therefore, be "ept to a minimum and the maximum legnth of bowel preserved. Dowever, it should be noted that recurrence rates are independent of resection extent and not increased if there microscopic, but not macroscopic, *rohnKs disease at the resection margrins. 0atients should be considered for surgery before advanced disease occurs, because mortality and morbidity are reduced and more conservative resection are possible with early surgical intervention. o Cocalized terminal ileal disease may be treated by a limited ileocaecal resection, which in many cases turns out to be the only surgical intervention necessary. o Small bowel strictures should ideally be treated by strictureplasty5 as opposed to resection and anastomosis, as this will preserve intestinal length.

Surgical Physiology 64; o 0erianal sepsis with fistulation is a particular problem associated with *rohnKs disease and surgical intervention should be weighed against the ris" of perianal recurrence. %t should be treated by clinicians with specialist interest in the condition. ' presentation of multiple8recurrent fistula should always raise the :uestion of *rohnKs disease involvement.

What are the ty ical clinical features of ulcerative colitis? The commest presentation is with diarrrhea with mar"ed faecal urgency. There is often blood present with the diarrhoea. This may be associated with abdominal pain although pain is more often a feature of *rohnKs disease. There is associated malaise, anorexia and weight loss. There are several well recognized extraintestinal manifestations of the disease, some of which are related disease activity such as0yoderma gangrenosum. .rythema nodosum. Musouc apthous ulcers. %ritis. Carge +oint arthritis. Those not related to disease activity includeSacroileitis8an"ylosing spondylitis. *hronic active hepatitis. *irrhosis. Sclerosing cholangitis. 0rimary biliary cirrhosis. *lubbing. How common is ulcerative colitis ,@C-? The incidence of A* approximately 6-6<,<<< population in the A). !s there any familiar tendency? Ses, there is evidnece of increased ris" in families of affected individuals. The ris" is between 6< 2<I for individuals who have a first degree relative with A*. What is the relationshi between smo$ing and @C? Smo"ing is protective against A*, stopping smo"ing increases the ris" of developing the disease and causes exacerbations in those patients in remission. How would you define an acute sever attac$ of @C? 'cute sever attac" nay be defines clinically by the presence of 4 or more bloody diarrhoeal stools per day. 0yrexia. Tachycardia. 'naemia. Beight loss. 'bdominal pain8tenderness.

Surgical Physiology 64> What blood tests would you re#uest to assess the activity of @C? Daemoglobin. 0latelet count. .S7. * reactive protein. Serum albumin. What other tests can be used to assess e%tent and activity of @C? 6. 0lain abdominal G ray loo"ing for colonic dilatation M thumb printing. 2. .rect chest G ray or lateral decubitus abdominal film if you suspet perforation. 3. 7adio labelled whhite cell scan /??Tc DM0'@1. &. 7igid or flexible sigmoidoscopy without excessive air insufflation. What is the initial su ortive treatment for acute active @C? %ntravenous fluid replacement i blood transfusion. #utritional support /enteral or parenteral depending on the clinical state1. 9=T prophylaxis /A* patients are at high ris" of developing thromboembolism1. 'voidance of drugs such as #S'%9s, anti diarrhoeal /loperamide, codeine phosphate1, opoid analgesic, anti spasmodics and anti cholinergic agents as they may provo"e colonic dilatation. What is the s ecific medical treatment of acute sever @C? 6. %ntravenous corticosteroids form the cornerstone of treatment. Dydrocortisone or methylprednisolone may be used. They are used to induce remissionn, which is then maintained by , aminosalicylic acid /, 'S'1 derivatives, such as mesalazine. 2. *yclosporin and heparin are still undergoing evaluation. 3. @ral azathioprine and 4 mercaptopurine wor" too slowly to be effective in the acute episodes. Cocalized proctitis may be treated by foam enemata of either steroids or , 'S'. 3ut widespread disease re:uies oral or %.=. therapy. Treatment including oral budesonide and azathioprine have been used to reduce the impact of standard steroid therapy. What are the indications for surgery in @C? %n the emergency situation 0erforation. 3leeding. Toxic dilatation. !ailure of aggressive medical treatment. %n the elective situation Malignant transformation. Steroid dependence. 7ecurrent acute exacerbations. 2rowth retardation in children.

Surgical Physiology 64? 0rophylaxis- A* increases the ris" of colonic adenocarcinoma5 the ris" is calculated at 6I per year after 6< years of disease.

What surgical o tions are available for elective management of @C? @peration 0roctocolectomy M ileostomy *olectomy M ileorectal anastomosis /if rectal sparing1 0roctocolectomy M pouch reconstruction 'dvantages Single operation. #o surveillance needed. Single procedure. #o stoma. Asually continent. 'll disease removed. 9isadvantages 0ermanent end stoma. 'll disease removed. 7esidual rectum with recurrent disease M cancer ris" needing surveillance. @ften X 6 operation. *omplications are common /3<I1.

Hiatus hernia
What is a hiatus hernia? Which ty es are you aware of? ' hiatus hernia is an ac:uired form of diaphragmatic hernia. There are two types Sliding- the gastro esophageal +unction slides through the esophageal opening diaphragm, predisposing to reflux and 3arrettKs oseophagitis. 7olling or paraoseophageal- +unction remains in position, but an area of stomach and peritoneum slides up alongside the esophagus into the thorax. What are the rinci les of management of gastro+eso hageal reflu%? *linical history is aided by the following basic investigastions Apper gastrointestinal endoscopy with biopsy to detect oesophagitis and 3arrettKs osophagus. 2& hour lower oesophageal pD recording. Ancomplicated reflux can be managed by the following lifestyle changes Beight loss. 'voidance of alcohol and smo"ing. 'voidance large meals at night. .levating the head of the bed. Medical treatment is successful in most patients, and includes the following 'ntacids. D2 antagonist. 0roton pump inhibitor /00%s1. The indications for surgery are as follows 0ersistent regurgitation. Sever reflux symptoms despite the compliance with medical advice. 0atient choice. What surgery can be erformed? #issenKs fundopolication is performed in over ?,I of patients.

Surgical Physiology 6;< @ther operations include 3elsy Mar" %= /fundopolication through a thoracotomy1. Dill gastropexy /securing the cardia to pre aortic fascia1. Describe the rinci les of Nissen1s fundo lication? This can be performed either laparoscopically or via an upper midline incision. The pateintKs consent is obtained and preoperative investigations are confirmed. The patient is placed in a supine position, given a general anaesthetic, and the head end of the table is elevated.