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<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>:<strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong><strong>ANSWER</strong> QUESTIONS INGENERAL & SYSTEMICPHYSIOLOGY


QUESTIONS1.6 An organelle is a discrete structure of a cellhaving specialised functions. There are manytypes of organelles, particularly in the eukaryoticcells of higher organisms. What is the organellethat regenerates and replicates spontaneously?A Golgi apparatusB MitochondrionC Smooth endoplasmic reticulumD Rough endoplasmic reticulum E Vacuolegeneral1.7 Atractyloside is an inhibitor of the electrontransport chain. It would be expected to havelittle or no effect on the functioning of which ofthe following cell types?A Cardiac muscle cellsB Parietal cells of the stomachC Parotid duct cellsD Proximal convoluted tubule cells E Red blood cells1.8 Action potentials can be created by many types ofcells, but are used most extensively by the nervoussystem for communication between neurones andto transmit information from neurones to otherbody tissues such as muscles and glands. Duringthe activation of a nerve cell membrane:A Chloride ions flow outwardB Potassium ions flow inwardC Potassium ions flow outwardD Sodium ions flow inward E Sodium ions flow outward5


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGYgeneral1.9 Skeletal muscle fibres can be divided into twobasic types, type I (slow-twitch fibres) and type II(fast-twitch fibres). Fast muscle fibres:A Use anaerobic metabolismB Have lots of myoglobinC Are shorter for great strength of contractionD Have relatively high endurance E Have numerous mitochondria1.10 A patient developed a stitch granuloma followingsurgery. Which leukocyte in the peripheral bloodwill become an activated macrophage in thisgranuloma?A BasophilB EosinophilC LymphocyteD Monocyte E Neutrophil1.11 A 36-year-old man with end-stage renal diseasewho is undergoing haemodialysis has normocyticnormochromic anaemia. Which of the following isthe most appropriate therapy? C Folate D Vitamin B 6 E Vitamin B 12A ErythropoietinB Ferrous sulphate6


QUESTIONS1.18 A 45-year-old man on warfarin for a mechanicalmitral valve was admitted in the Accident andEmergency Department with persistent bleedingfollowing dental extraction. He was told that hiscoagulation was deranged. Which of the followingstatements about blood coagulation is CORRECT?A Absence of Ca 2+ promotes blood coagulationB Disseminated intravascular coagulation (DIC) results indepletion of fibrin split productsC Patients with haemophilia A usually have a normalbleeding timeD von Willebrand factor suppresses platelet adhesion E von Willebrand factor suppresses blood coagulationgeneral1.19 Nerve gas (organophosphate) is a weapon ofchemical warfare that kills by causing respiratoryand cardiovascular failure. The expected effect oforganophosphate poisoning on the heart wouldbe:A Decrease the force of myocardial contractions bypotentiating the vagal tone to the ventricular muscleB Decrease the rate of rhythmicity of the sinoatrial (SA)node by inducing hyperpolarisationC Depolarise cells of the SA node by closing potassiumchannels under the control of the muscarinicacetylcholine receptorD Increase the rate of rhythmicity of the SA node byincreasing the upward drift in membrane potentialcaused by sodium leakage E Increase conductivity at the atrioventricular (AV)junction by inducing depolarisation9


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGYgeneral1.20 The resting membrane potential of a neuronal cellbody is –60 mV. Opening chloride channels in theneuronal membrane will most likely cause:A Depolarisation to about –30 mVB Depolarisation to about +30 mVC Hyperpolarisation to about –70 mVD Initiation of an action potential E No change in membrane potential1.21 Chloride ions are associated with changes inneuronal membrane potential. Which of thefollowing statements most accurately describesthe response of a neurone to a decrease in theconductance of the cell membrane to chlorideions?A The cell will depolarise if its membrane potential ispositive with respect to the equilibrium potential forchloride ionsB The cell will hyperpolarise if its membrane potential ispositive with respect to the equilibrium potential forchloride ionsC The cell will hyperpolarise if the external chlorideconcentration is greater than the internal chlorideconcentrationD The cell will hyperpolarise if the external chlorideconcentration is less than the internal chlorideconcentration E No change in membrane potential will occur if theexternal and internal chloride ion concentrations areequal10


SECTION 1:GENERAL PHYSIOLOGY –<strong>ANSWER</strong>S1.1Answer: CGap junctionsgeneralA gap junction is a junction between certain animal cell typesthat allows different molecules and ions to pass freely betweencells. The junction connects the cytoplasm of cells. One gapjunction is composed of two connexons (or hemichannels), whichconnect across the intercellular space. They are analogous to theplasmodesmata that join plant cells. In vertebrates, gap-junctionhemichannels are primarily homo- or hetero-hexamers of connexinproteins. Invertebrate gap junctions comprise proteins from thehypothetical innexin family. However, the recently characterisedpannexin family, functionally similar but genetically distinct fromconnexins and expressed in both vertebrates and invertebrates,probably encompasses the innexins. Gap junctions formed fromtwo identical hemichannels are called homotypic, while those withdiffering hemichannels are heterotypic. In turn, hemichannels ofuniform connexin composition are called homomeric, while thosewith differing connexins are heteromeric. Channel composition isthought to influence the function of gap-junction channels but it isnot yet known how.Gap junctions:• allow for direct electrical transmission between cells• allow for chemical transmission between cells, throughthe transmission of small second messengers, such asIP 3and Ca 2+• allow any molecule smaller than 1 kDa to pass through.201


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGY1.2Answer: DLysosomesgeneralLysosomes are organelles that contain digestive enzymes (acidhydrolases) to digest macromolecules. They are found in both animaland plant cells but they are rare in plant cells. They are built in theGolgi apparatus. The name comes from the Greek words ‘lysis’, whichmeans dissolution or destruction and ‘soma’, which means body.They are frequently nicknamed ‘suicide-bags’ by cell biologists dueto their role in autolysis. Lysosomes were discovered by the Belgiancytologist Christian de Duve in the 1949. The lysosomes are used forthe digestion of macromolecules from phagocytosis (ingestion ofcells), from the cell’s own recycling process (where old componentssuch as worn out mitochondria are continuously destroyed andreplaced by new ones and receptor proteins are recycled) and forautophagic cell death, a form of programmed self-destruction orautolysis, of the cell, which means that the cell is digesting itself.Other functions include digesting foreign bacteria that invade a celland helping repair damage to the plasma membrane by serving as amembrane patch, sealing the wound. Lysosomes also do much of thecellular digestion required to digest tails of tadpoles and to removethe web from the fingers of a 3–6-month-old fetus. This process ofprogrammed cell death is called apoptosis.1.3Answer: BSynthesis of proteinsThe rough endoplasmic reticulum (ER) contains proteinmanufacturingribosomes (the ribosomes on its surface areresponsible for its being named ‘rough’) and transports proteinsdestined for membranes and secretion. Rough ER is connected tothe nuclear envelope as well as linked to the cis cisternae of the Golgicomplex by vesicles that shuttle between the two compartments.The rough ER works in concert with the Golgi apparatus to targetnew proteins to their proper destinations.202


<strong>ANSWER</strong>S1.4Answer: A Acts like haemoglobin and binds with O 2Myoglobin is a single-chain globular protein of 153 amino acids,containing a haem (iron-containing porphyrin) prosthetic groupin the centre around which the remaining apoprotein folds. Witha molecular weight of 16 kDa, it is the primary oxygen-carryingpigment of muscle tissues. Unlike the blood-borne haemoglobin,to which it is structurally related, this protein does not exhibitco-operative binding of oxygen, since positive co-operativity is aproperty reserved for multimeric proteins. Instead, the binding ofoxygen by myoglobin is unaffected by the oxygen pressure in thesurrounding tissue. Myoglobin is often cited as having an ‘instantbinding tenacity’ to oxygen given its hyperbolic oxygen dissociationcurve. In 1958, John Kendrew and associates successfully determinedthe structure of myoglobin by high-resolution X-ray crystallography.For this discovery, John Kendrew shared the 1962 Nobel Prize inchemistry with Max Perutz.general1.5Answer: AIt is monosynapticA stretch reflex is a muscle contraction in response to stretchingwithin that muscle. It is a monosynaptic reflex that provides automaticregulation of skeletal muscle length. Muscle spindles are sense organssensitive to stretch of the muscle in which they lie. The patellar (kneejerk)reflex is an example. Another example is the group 1a fibresin the calf muscle, which synapse with motor neurones supplyingmuscle fibres in the same muscle. A sudden stretch, such as tappingthe Achilles’ tendon, causes a reflex contraction in the muscle as thespindles sense the stretch and send an action potential to the motorneurones, which then cause the muscle to contract; this particularreflex causes a contraction in the soleus–gastrocnemius group ofmuscles. This reflex can be enhanced by the Jendrassik manoeuvre.Jendrassik’s manoeuvre (Erno Jendrassik, Hungarian physician, 1858–1921) is a medical manoeuvre wherein the patient flexes both setsof fingers into a hook-like form and interlocks those sets of fingerstogether. The tendon below the patient’s knee is then hit with areflex hammer. The elicited response is compared with the reflex203


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGYgeneralresult of the same action when the manoeuvre is not in use. Often alarger reflex response will be observed when the patient is occupiedwith the manoeuvre, as the manoeuvre may prevent the patientfrom consciously inhibiting or influencing his or her response to thehammer. This manoeuvre is particularly useful in that, even if thepatient is aware that the interlocking of fingers is just a distractionto elicit a larger reflex response, it still functions properly.1.6Answer: BMitochondrionA mitochondrion (plural mitochondria) is a membrane-enclosedorganelle, found in most eukaryotic cells. Mitochondria aresometimes described as ‘cellular power plants’, because they convertfood molecules into energy in the form of ATP via the process ofoxidative phosphorylation. A typical eukaryotic cell contains about2000 mitochondria, which occupy roughly one-fifth of its totalvolume. Mitochondria contain DNA that is independent of the DNAlocated in the cell nucleus. They have the ability to regenerate andreplicate spontaneously.1.7Answer: ERed blood cellsAn electron transport chain (also called electron transport system orelectron transfer chain) is a series of membrane-associated electroncarriers mediating biochemical reactions that produce ATP, which isthe energy currency of life. Only two sources of energy are availableto living organisms: oxidation–reduction (redox) reactions andsunlight (photosynthesis). Organisms that use redox reactions toproduce ATP are called chemotrophs. Organisms that use sunlightare called phototrophs. Both chemotrophs and phototrophs utiliseelectron transport chains to convert energy into ATP. The overallpurpose of the electron transport chain is to create ATP using energycontained in high-energy electrons.204


<strong>ANSWER</strong>SThis is achieved through a three-step process:• Gradually sap energy from a high-energy electron in aseries of individual steps.• Use that energy to forcibly unbalance the protonconcentration across the membrane.• Use the proton concentration’s drive to rebalanceitself as a means of producing ATP.Electron transport chains are present in the mitochondria. Energysources such as glucose are initially metabolised in the cytoplasm. Theproducts are imported into mitochondria. Mitochondria continuethe process of catabolism using metabolic pathways including theKrebs cycle, fatty acid oxidation and amino acid oxidation.generalThe end-result of these pathways is the production of two energyrichelectron donors, NADH and FADH 2. Electrons from these donorsare passed through an electron transport chain to oxygen, whichis reduced to water. This is a multi-step redox process that occurson the mitochondrial inner membrane. The enzymes that catalysethese reactions have the remarkable ability to simultaneouslycreate a proton gradient across the membrane, producing athermodynamically unlikely high-energy state with the potential todo work. Although electron transport occurs with great efficiency,a small percentage of electrons are prematurely leaked to oxygen,resulting in the formation of the toxic free radical, superoxide.Four membrane-bound complexes have been identified inmitochondria. Each is an extremely complex transmembranestructure that is embedded in the inner membrane. Three of themare proton pumps. The structures are electrically connected bylipid-soluble electron carriers and water-soluble electron carriers.The overall electron transport chain is:NADH → Complex I → Q → Complex III → Cytochrome c →Complex IV → O 2↑Complex II205


<strong>ANSWER</strong>S1.9Answer: AUse anaerobic metabolismSkeletal muscle fibres can be divided into two basic types, type I(slow-twitch fibres) and type II (fast-twitch fibres). Type I musclefibres (slow-oxidative fibres) use primarily cellular respiration and,as a result, have relatively high endurance. To support their highoxidativemetabolism, these muscle fibres typically have lots ofmitochondria and myoglobin and so appear red or what is typicallytermed ‘dark’ meat in poultry. Type I muscle fibres are typically foundin muscles of animals that require endurance, such as chicken legmuscles or the wing muscles of migrating birds (eg, geese). Type IImuscle fibres use primarily anaerobic metabolism and have relativelylow endurance. These muscle fibres are typically used during tasksrequiring short bursts of strength, such as sprints or weightlifting.Type II muscle fibres cannot sustain contractions for significantlengths of time and are typically found in the ‘white’ meat (eg, thebreast) of chicken.generalThere are two subclasses of type II muscle fibres, type IIa (fastoxidative)and IIb (fast-glycolytic). The Type IIa fast-oxidative fibresactually also appear red, due to their high content of myoglobin andmitochondria. Type IIb (fast-glycolytic) tire the fastest and are theprevalent type in sedentary individuals. These fibres appear whitehistologically, due to their low oxidative demand, manifested by thelack of myoglobulin and mitochondria (relative to the type I and typeIIa fibres). Some research suggests that these subtypes can switchwith training to some degree. The biochemical difference betweenthe three types of muscle fibres is in their myosin heavy chains.1.10Answer: DMonocyteA monocyte is a leukocyte, part of the human body’s immune systemthat protects against blood-borne pathogens and moves quickly(approx. 8–12 hours) to sites of infection in the tissues. Monocytesare usually identified in stained smears by their large bilobednucleus. They are produced by the bone marrow from haemopoieticstem cell precursors called monoblasts. Monocytes circulate in thebloodstream for about one to three days and then typically move207


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGYgeneralinto tissues throughout the body. They consist of between 3 and 8%of the leukocytes in the blood. In the tissues, monocytes mature intodifferent types of macrophages at different anatomical locations.Monocytes are responsible for phagocytosis (ingestion) of foreignsubstances in the body. Monocytes can perform phagocytosisusing intermediary (opsonising) proteins such as antibodies orcomplement that coat the pathogen, as well as by binding to themicrobe directly via pattern-recognition receptors that recognisepathogens. Monocytes are also capable of killing infected hostcells via antibody, termed antibody-mediated cellular cytotoxicity.Vacuolisation may be present in a cell that has phagocytosed foreignmatter.Monocytes that migrate from the bloodstream to other tissues arecalled macrophages. Macrophages are responsible for protectingtissues from foreign substances, but are also suspected to be thepredominant cells involved in triggering atherosclerosis. They arecells that possess a large smooth nucleus, a large area of cytoplasmand many internal vesicles for processing foreign material.A monocyte count is part of a complete blood count and is expressedeither as a ratio of monocytes to the total number of white blood cellscounted or by absolute numbers. Both may be useful in determiningor refuting a possible diagnosis. Monocytosis is the state of excessmonocytes in the peripheral blood. It may be indicative of variousdisease states. Examples of processes that can increase a monocytecount include:• chronic inflammation• stress response• hyperadrenocorticism• immune-mediated disease• pyogranulomatous disease• necrosis• red cell regeneration.208


<strong>ANSWER</strong>S1.11Answer: AErythropoietinErythropoietin, or EPO, is a glycoprotein hormone that is a cytokinefor erythrocyte (red blood cells) precursors in the bone marrow.Also called haematopoietin or haemopoietin, it is produced by thekidney and is the hormone regulating red blood cell production.Erythropoietin is available as a therapeutic agent produced byrecombinant DNA technology in mammalian cell culture. It is used intreating anaemia resulting from chronic renal failure or from cancerchemotherapy. Its use is also believed to be common as a dopingagent in endurance sports such as bicycle racing, triathlons andmarathon running.general1.12Answer: DIgGIgG is a monomeric immunoglobulin, built of two heavy chains γ andtwo light chains. Each molecule has two antigen-binding sites. Thisis the most abundant immunoglobulin and is approximately equallydistributed in blood and in tissue liquids, constituting 75% of serumimmunoglobulins in humans. This is the only isotype that can passthrough the placenta, thereby providing protection to the newbornin its first weeks of life before its own immune system has developed.It can bind to many kinds of pathogens, for example viruses, bacteriaand fungi, and protects the body against them by complementactivation (classic pathway), opsonisation or phagocytosis andneutralisation of their toxins. There are four subclasses: IgG1 (66%),IgG2 (23%), IgG3 (7%) and IgG4 (4%):• IgG1, IgG3 and IgG4 cross the placenta easily• IgG3 is the most effective complement activator,followed by IgG1 and then IgG2• IgG4 does not activate complement• IgG1 and IgG3 bind with high affinity to Fc receptorson phagocytic cells• IgG4 has intermediate affinity and IgG2 affinity isextremely low.209


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGY1.13Answer: AA positiveAccording to the ABO blood typing system there are four differentkinds of blood types: A, B, AB or O.general• Blood group A - If you belong to the blood group A,you have A antigens on the surface of your red bloodcells and B antibodies in your blood plasma.• Blood group B - If you belong to the blood group B,you have B antigens on the surface of your red bloodcells and A antibodies in your blood plasma.• Blood group AB - If you belong to the blood group AB,you have both A and B antigens on the surface of yourred blood cells and no A or B antibodies at all in yourblood plasma.• Blood group O - If you belong to the blood groupO, you have neither A nor B antigens on the surfaceof your red blood cells but you have both A and Bantibodies in your blood plasma.Many people also have a so-called Rh factor on the red blood cell’ssurface. This is also an antigen and those who have it are calledRh+. Those who have not are called Rh–. A person with Rh– blooddoes not have Rh antibodies naturally in the blood plasma (as onecan have A or B antibodies, for instance) but they can develop Rhantibodies in the blood plasma if they receive blood from a personwith Rh+ blood, whose Rh antigens can trigger the production ofRh antibodies. A person with Rh+ blood can receive blood from aperson with Rh– blood without any problems. So, in this vignettethe patient’s blood group is A positive as he has antigen A, antibodyB and Rh antigens.210


<strong>ANSWER</strong>S1.14Answer: CIt is the largest immunoglobin moleculeIgM forms polymers where multiple immunoglobulins are covalentlylinked together with disulphide bonds, normally as a pentameror occasionally as a hexamer. It has a large molecular mass ofapproximately 900 kDa (in its pentamer form). The J chain is attachedto most pentamers, while hexamers do not possess the J chain dueto space constraints in the complex. Because each monomer hastwo antigen binding sites, an IgM has 10 of them; however, it cannotbind 10 antigens at the same time because they hinder each other.Because it is a large molecule, it cannot diffuse well and is found inthe interstitium only in very low quantities. IgM is primarily foundin serum; however, because of the J chain, it is also important as asecretory immunoglobulin.generalDue to its polymeric nature, IgM possesses high avidity and isparticularly effective at complement activation. It is sometimescalled a ‘natural antibody’, but it is likely that the antibodies arisedue to sensitisation in the very young to antigens that are naturallyoccurring in nature. For example anti-A and anti-B IgM antibodiescan be formed in early life as a result of exposure to anti-A- andanti-B-like substances that are present on bacteria or perhaps alsoon plant materials. In germ-line cells, the gene segment encodingthe µ constant region of the heavy chain is positioned first amongother constant-region gene segments. For this reason, IgM is thefirst immunoglobulin expressed by mature B cells.IgM is also by far the physically largest antibody in the circulation. IgMantibodies are mainly responsible for the clumping (agglutination)of red blood cells if the recipient of a blood transfusion receivesblood that is not compatible with his/her blood type. IgM antibodiesappear early in the course of an infection and usually do not reappearafter further exposure. IgM antibodies do not pass across the humanplacenta. These two biological properties of IgM make it useful inthe diagnosis of infectious diseases. Demonstrating IgM antibodiesin a patient’s serum indicates recent infection or, in serum from aneonate, indicates intrauterine infection such as congenital rubella.211


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGY1.15Answer: EVascular endotheliumgeneralFactor VIII (FVIII) is an essential clotting factor. The lack of normalFVIII causes haemophilia A, an inherited bleeding disorder. The genefor Factor VIII is located on the X chromosome (Xq28). FVIII is aglycoprotein pro-cofactor. Factor VIII is synthesised predominantly inthe vascular endothelium and is not affected by liver disease. In fact,levels usually are elevated in such instances. It is also synthesised andreleased into the bloodstream by the liver. In the circulating blood, itis mainly bound to von Willebrand factor (vWF, also known as factorVIII-related antigen) to form a stable complex. Upon activation bythrombin or factor Xa, it dissociates from the complex to interactwith factor IXa in the coagulation cascade. It is a co-factor to factorIXa in the activation of factor X, which, in turn, with its co-factorfactor Va, activates more thrombin. Thrombin cleaves fibrinogeninto fibrin, which polymerises and crosslinks (using factor XIII)into a blood clot. No longer protected by vWF, activated FVIII isproteolytically inactivated in the process (most prominently byactivated protein C and factor IXa) and quickly cleared from thebloodstream. FVIII concentrated from donated blood plasma oralternatively recombinant FVIII can be given to haemophiliacs torestore haemostasis. So, FVIII is also known as antihaemophilicfactor. The transfer of a plasma by-product into the bloodstreamof a patient with haemophilia often led to the transmission ofdiseases such as HIV and hepatitis before purification methods wereimproved. In the early 1990s, pharmaceutical companies began toproduce recombinant synthesised factor products, which nowprevent nearly all forms of disease transmission during replacementtherapy.1.16Answer: AAutosomal dominantvon Willebrand’s disease (vWD) is the most common hereditarycoagulation abnormality described in humans, although it can alsobe acquired as a result of other medical conditions. It arises froma qualitative or quantitative deficiency of von Willebrand factor(vWF), a multimeric protein that is required for platelet adhesion. It212


<strong>ANSWER</strong>Sis known to affect humans and, in veterinary medicine, dogs. Thereare three types of hereditary vWD, but other factors such as ABOblood group may also play a part in the cause of the condition. Thevarious types of vWD present with varying degrees of bleedingtendency. Severe internal or joint bleeding is rare (only in type 3vWD); bruising, nosebleeds, heavy menstrual periods (in women)and blood loss during childbirth (rare) may occur. Death may occurThe vWF gene is located on chromosome 12 (12p13.2). It has 52 exonsspanning 178 kbp. Types 1 and 2 are inherited as autosomal dominanttraits and type 3 is inherited as autosomal recessive. Occasionallytype 2 also inherits recessively. In humans, the incidence of vWD isroughly about 1 in 100 individuals. Because most forms are rathermild, they are detected more often in women, whose bleedingtendency shows during menstruation. The actual abnormality(which does not necessarily lead to disease) occurs in 0.9–3% of thepopulation. It may be more severe or apparent in people with bloodgroup O. Acquired vWD can occur in patients with autoantibodies.In this case the function of vWF is not inhibited but the vWF–antibody complex is rapidly cleared from the circulation. A formof vWD occurs in patients with aortic valve stenosis, leading togastrointestinal bleeding (Heyde’s syndrome). This form of acquiredvWD may be more prevalent than is presently thought. Acquired vWFhas also been described in the following disorders: Wilms’ tumour,hypothyroidism and mesenchymal dysplasias.generalPatients with vWD normally require no regular treatment, althoughthey are always at increased risk for bleeding. Prophylactic treatmentis sometimes given for patients with vWD who are scheduledfor surgery. They can be treated with human-derived mediumpurity factor VIII concentrates. Mild cases of vWD can be trialledon desmopressin (1-desamino-8-D-arginine vasopressin, DDAVP)(antihaemophilic factor, more commonly known as humate-P),which works by raising the patient’s own plasma levels of vWF byinducing release of vWF stored in the Weibel–Palade bodies in theendothelial cells.213


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGY1.17Answer: CIron is more efficiently absorbed in the ferrous state(Fe 4 ) than in the ferric state (Fe 3+ )generalThe absorption of non-haem iron in any food is strongly affected bythe composition of the meals. Iron is more efficiently absorbed in theferrous state (Fe 2+ ) than in the ferric state (Fe 3+ ) and commercial ironpreparations often contain vitamin C to prevent oxidation of Fe 2+ toFe 3+ . Still, only 3–6% of the ingested daily iron is actually absorbed inthe upper gastrointestinal tract. Seventy per cent of the total bodyiron is used for haemoglobin and myoglobin; the remainder is storedas readily exchangeable ferritin and some is stored in less easilymobilised haemosiderin. When old red blood cells are destroyedby the tissue macrophage system, haem is separated from globinand degraded to biliverdin. Iron in the plasma is bound to the irontransportingprotein transferrin. Transferrin level (total iron-bindingcapacity) and saturation are clinically important indicators of irondeficiencyanaemia.1.18Answer: CPatients with haemophilia A usually have a normalbleeding timeProlonged bleeding time is characteristic of platelet disorders,eg, thrombocytopaenia. Patients with haemophilia A or B (ieabsence of factor VIII or IX, respectively) have a prolonged partialthromboplastin time (PTT), but do not have a prolonged bleedingtime. Ca 2+ is a necessary co-factor for blood coagulation, andchelation of Ca 2+ ions by citrate inhibits coagulation. Von Willebrandfactor is part of the factor VIII complex and also promotes plateletadherence to the vascular subendothelium. Patients who lack thisfactor (von Willebrand’s disease) have both a prolonged PTT and aprolonged bleeding time. Disseminated intravascular coagulationresults in depletion of coagulation factors and accumulation offibrin split products.214


<strong>ANSWER</strong>S1.19Answer: BDecrease the rate of rhythmicity of the sinoatrial (SA)node by inducing hyperpolarisationThe toxic effects of nerve gas derive from its ability to inhibit theenzyme cholinesterase. The inhibition of this naturally occurringdegradative enzyme engenders a massive accumulation ofacetylcholine evoking an overstimulation of the acetylcholinereceptors throughout the body. In the heart, specifically,acetylcholine released by the vagal nerve stimulates muscarinicreceptors in the cells of the sinoatrial (SA) node. This results in theopening of potassium channels and hyperpolarisation of the SAnode. It therefore takes longer for sodium leakage to cause themembrane potentials of these cells to reach the threshold requiredfor an action potential. The rate of rhythmicity is so decreased. Asimilar hyperpolarisation of the fibres at the atrioventricular (AV)junction decreases conduction velocity of atrial impulses to theventricle. The force of ventricular contractions is not affected bythe vagus nerve.general1.20Answer: CHyperpolarisation to about -70mVIncreasing the membrane’s conductance to chloride will result inchloride influx and the membrane potential approaching the valuedictated by the chloride equilibrium potential (calculated from theNernst equation), which is about –70 mV for neurones. A value of–30 mV is near the Nernst potential for Cl − ions in smooth musclecells, but not in neurones; +30 mV is near the Nernst potential for Na +ions. The membrane potential would remain unchanged only if thecell resting membrane potential is already at the Nernst potential ofthe ion channels that were opened. Action potentials occur if thecell membrane is depolarised above threshold.215


<strong>ACCESS</strong> <strong>TO</strong> <strong>SURGERY</strong>: <strong>500</strong> <strong>SINGLE</strong> <strong>BEST</strong> <strong>ANSWER</strong> QUESTIONS IN GENERAL AND SYSTEMIC PHYSIOLOGY1.21Answer: AThe cell will depolarise if its membrane potential ispositive with respect to the equilibrium potential forchloride ionsgeneralAlthough electrogenic pumps may contribute to the membranepotential of certain cells, the major determinants of membranepotential are the external and internal concentrations of permeantions and their relative permeabilities in the membrane. Decreasingthe conductance causes the membrane potential to move awayfrom the equilibrium potential for that ion. So, a decrease in theconductance of a membrane to chloride ions causes the cells todepolarise – that is, become more positive – if the membranepotential is positive with respect to the chloride equilibriumpotential. Conversely, increasing the conductance for an ion causesthe membrane potential to approach the equilibrium potentialfor that ion. External and internal ion chloride concentrations areneeded to calculate the Nernst potential for this ion, but a simplecomparison of these two values does not allow predictions aboutthe change in membrane potential.1.22Answer: EReflex inhibition of motor neuronesThe stimulation of receptors in the Golgi tendon organs leads to theinverse stretch reflex. This reflex is responsible for the relaxationthat is observed when a muscle is subjected to a strong stretch.Impulses from the organs travel in type Ib fibres to the spinal cord,where they activate inhibitory interneurones. These in turn suppressthe activity of motor neurones and therefore lead to relaxation ofthe extrafusal muscle fibres attached to the tendons. The state ofcontraction of intrafusal fibres, the gamma-efferent discharge rateand the activity in group II afferent fibres control the stretch reflex,which, distinct from the inverse stretch reflex, is mediated by theGolgi tendon organs.216

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