0.5 TRANSP0RT 0F RESPIRAT0RY GASES (AHLJ

-

Growth hortnone is another polypeptidehormone produced in the anterior pituitary.One of its main targets is receptors in liver cells.The binding of growth horurone stinttlatesthe release of insulin-like growth factor whichcirculates in thc blood and stim.ulates bone andcartilage growth. Growth horrnone has a numberof additional affects, otte of whicl'r is iucrease inr-r'ruscle mass. For this reasou, it has been tlsed as

a performance euhancing drr.rg. Tl-re availabilityof growth hortnoue has increased due to thedevelopmetrt of genetically modified organismsthat can prodltce it ir-r large quantities.

Because there is a correlation between urusclesize and strength, conpetitors in sports thatrequire short bursts of explosive strength wouldbeneflt. While it is clear that it leads to greaterrnuscle mass, the data is not clear that it leads togreater strength. Another clairn is that it allowstired nuscles to recover lllore quickly allowingan individual to train harder and more often.The scientiflc research on the topic suggeststhat the benefìts provided in tern'ì.s of enhancedperfornance are smaÌl or nott-existent comparedto the risks of injecting tlte horurorte. For thisreasor-r, use of the clrug is banned by rnostinternational sporting federations.

0.6 Transport of respiratorg gases

Understandingà Oxggen dissociation curves show the aftinitg of

hemoglobin for oxggen.

t Carbon dioxide is carried in solution and boundto hemoglobin in the blood.

Ð Carbon dioxide is transformed in red blood cellsinto h gdrogencarbonate ions.

; The Bohr shift explains the increased release ofoxggen bg hemoglobin in respiringtissues.

à Chemoreceptors are sensitive to changes ¡nblood pH.

; The rate of ventilation is controlled bg therespiratorU control centre in the medullaoblongata.

Ð During exercise the rate of ventilation changesin response to the amount of C0, in the blood.

Ð Fetal hemoglobin is different from adulthemoglobin allowing the transfer of oxggen inthe placenta onto the fetal haemoglobin.

fAHL)

Consequences of high altitude for gas exchange.

pH of blood is regulated to staU within thenarrow range of 7.35 to 7.45.

Causes and treatments of emphUsema.

@ srillsà Analgsis of dissociation curves for hemoglobin

and mgoglobin.à ldentification of pneumocutes, capillarg

endothelium cells and blood cells in lightmicrographs and electron micrographs oflung tissue.

ftþ ruatLlre 0f sc¡encË+ Scientists have a role in informing the public:

scientific research has led to a change in publicperception of smoking.

699

HUMAN PHYSIOLOGY

normal p iol ogical rangeal pressuresof oxggen

5101sPartial pressure of oxggen/kPa

r Figure 1 Oxggen dissociation of hemoglobin

0xggen dissociation curvesOxggen dissociation curves show the affinitu ofhemoglobin for oxggen.Hemoglobin is an oxygen transpoft protein in the blood. Thedegree to which oxygen binds to hemoglobin is determined bythe partial pressure of oxygen (pOr) in the blood. The oxygendissociation curve shown in figure I describes the saturationof hemoglobin by oxygen at different partial pressures ofoxygen.

Note the significant change in saturation over a narrow rangeof oxygen partial pressure. This narrow range typifies oxygenpressures surrounding cells under normal metabolism. At lowpOr, such as might occur in the muscles, O, will dissociate fromhemoglobin. At high pO, such as might occur in the lungs, thehemoglobin will become saturated.

the hemoglobin becomes saturated atverg high p02, as all the heme groupsbecome bound

100C9, qnj-"Xof80ì.E ?oo-úP60EofsooC,? qog=Ë30oüzocoË10o-

0

at higher p02,more hemegroups are boundto oxUgen,making it easierfor more oxggento be picked up

Carbon dioxide transport in the bloodCarbon dioxide is carried in solution and bound tohemoglobin in the blood.Carbon dioxide is carried in three forms in blood plasma:o dissolved as carbon dioxide;o reversibly converted to bicarbonate (hydrogencarbonate) ions

(HCO;) that are dissolved in rhe plasma;o bound to plasma proteins.

Table I shows the amounts of each form in arterial blood and in venousblood at rest and during exercise.

groups are boundto oxggen, sohemoglobin

at few h

does not camuch n

Form oftransportArterial

mmol-l blood

Venous

mmol-l blood

Rest Exercise

dissolved C0. 0.68 0.78 1,.32

bicarbonate ion 13.52 t4.sr 14.66

C0, bound to protein 0.3 0.3 0.24

total c0, in plasma 14.50 15.59 16.22

pH of blood 7.4 7.37 7.1.4

Ä Table 1 C0, transport in blood plasma at rest and during exercise

0.6 TRANSP0RT 0F RESPIRAT0RY GASES fAHL)

[2]

Conversion of carbon dioxide into hgdrogencarbonate ionsCarbon dioxide is transformed in red blood cells intohgd rogencarbonate ions.The majority of carbon dioxide produced by the body during cellularrespiration is converted to the more soluble and less toxic bicarbonate(hydrogencarbonate) ion. The reaction occurs inside red blood cells andis catalysed by the enzyme carbonic anhydrase'

Co2 + Il2o =H2COr = H+ * HCOtThe two-sided arrows indicate that the reaction is reversible. In the tissueswhere carbon dioxide is generated, the reaction proceeds to the right; thatis, more bicarbonate ion is generated as are H* ions. This lowers the pH ofthe blood. In the lungs, when carbon dioxide leaves the blood, the reactionis driven to the left and bicarbonate ion is converted to carbon dioxide.

The Bohr sh¡ftThe Bohr sh¡ft exple¡ns the increased release of oxggenbg hemoglobin in respiring t¡ssues.Increased metabolism results in greater release of CO, into the blood,which lowers the pH of the blood. This increased acidity shifts theoxygen dissociation curve to the right, which results in a decreasedafflnity of the hemoglobin for oxygen; that is, a gleatel release of oxygenfrom hemoglobin at the same partial pressure of oxygen (see figure 2).

This is known as the Bohr shift. This ensures that respiring tissues haveenough oxygen when their need for oxygen is greatest. Also, in thelungs, pCO, is lower, so saturation of hemoglobin can occur at lowerpartial pressures of oxygen.

Efrect of COz on ventilation rateDuring exerc¡se the rate of ventilation changes ¡nresponse to the amount of COz in the blood.Exercise increases metabolism and leads to an increase in the productionof CO, as a waste product of cellular respiration. Increased CO, causesblood pU to decrease because CO, dissolves in water to form carbonic acid

Activitg1 Using the data in table 1, calculate the

percentage ofC0. found as bicarbonate ionsin the plasma of venous blood at rest.

2 Compare the changes in total C0. in the threeforms between venous blood at rest and venousblood during exercise.

3 Deduce, with reasons, which forms of carbondioxide are used to transport carbon dioxidefrom respiring tissues to the lungs.

4 Discuss which form of carbon dioxide is mostimportant for transport:aJ at restbJ during exercise.

Pco2 :3kpa

t2l

fzl l2lt2l

100

75

50

25

CoootXor.Y

=C.oG

=oØoo¡ocoIoÈ

Pco2: 6 ¡0,

s1015Partial pressure of oxggen/kPa

À Figure 2 The Bohr shift

t, Figure 3 Hgperventilation occurs followingvigorous exercise as a mechanism to maintainblood pH bg riddingthe bodg of carbon dioxide

0

HUMAN PHYSIOLOGY

(HrCOr) which further dissociates into H* and HCO;. Recall that high H*concentration means low pH. chemoreceptors in the medulla, the aortaand the carotid artery are able to detect a change in blood carbon dioxide.High levels of carbon dioxide in the blood trigger an increase in theventilation rate in order to rid the body of the carbon dioxide build-up.carbon dioxide diffuses into alveoli and ventilation expers the carbondioxide from the body. This explains the hyperventilation that occurs inresponse to exercise.

Regulation of the vent¡lation rateThe rate of ventilation is controlled bg the respiratorgcontrol centre in the medulla oblongata.The rate of ventilation is regulated by the respiratory centre inthe meduÌla oblongata of the brainstem. TWo sets of nerves travelto the lungs from this centre: the intercostal nerves stimulate theintercostal muscles of the thorax and the phrenic nerves stimulatethe diaphragm.When the lungs expand due to stimulation from the nerves, stretchreceptors in the walls of the chest and Ìungs send signals to therespiratory centre which triggers a cessation of the signals leading toinspiration until the animal exhales. Then a new signal is sent.

Chemoreceptors and blood pHChemoreceptors are sens¡tive to changes in blood pH.If an increase in blood carbon dioxide or a drop in blood pH is detected,the chemoreceptors in the carotid artery and the aorta send a message tothe breathing centre in the medulla oblongata. Nerve impulses are sentfrom the medulla to the diaphragm and the intercostal muscles causingthem to increase the ventilation rate. This leads to an increased rate ofgas exchange. There are also chemoreceptors in the medulla oblongatathat can detect in an increase in blood carbon dioxide.

@ n.gulation of blood pHpH of blood is regulated to stag within the narrow range of 2.35 to 2.45ff the blood pH falls below 7.35, ttrenchemoreceptors signal to the respiratory centre toincrease the rate of ventilation. Hyperventilationwithdraws carbon dioxide from the blood drivingthe carbonic acid reaction to the left. This withdrawshydrogen ions from the blood raising the pH.

co2 + Hro = H2CO1 = H+ * HCOtIn the kidney, H* ions can be secreted into theurine bound to buffers to raise the pH. Greater

amounts of bicarbonate will be reabsorbed fromthe tubules to neutralize the acid.

If the blood becomes too basic, then bicarbonateions can be secreted into the distal convolutedtubule of the kidney.

Chemical buffers exist within the extracellularfluid and these can't remove the acids or bases,but they can minimize their effect.

0.6 TRANSp0RT 0F RESPTRAT0RY GASES fAHL)

@ m.lgsis of dissociation curvesAnalgsis of dissociation curves forhemoglobin and mgoglobin.Myoglobin is a specialized oxygen transportprotein in muscles. It has a much higher affinityfor oxygen and will only release its oxygenwhen the pO, is quite low, for example in themuscles during heavy exercise. The shapes ofthe two curves in figure 4 are different becausehemoglobin has four chains with four hemegroups, whereas myoglobin has one. Therelease of each O, from hemoglobin triggersa conformational change, which causes thehemoglobin to more rapidly release subsequentO, molecules.

m goglobin

<-r-+I Partial pressure of oxggen/kPaI

p02 in muscle capillaries:mgoglobin is saturated with oxggen;hemoglobin is giving up oxggen

p02 in muscle cells: mgoglobinrs grvrng uP oxggen

A Figure 4 A comparison of the 0, dissociationcurves of hemoglobin and mgoglobin

100coo0ÐxoE:!_ìc.oe50foØoo¡)ocoooo-

Difrerences in oxggen aftinitg between fetaland adult hemoglobinFetal hemoglobin is different from adult hemoglobinallowing the transfer of oxggen in the placenta onto thefetal haemoglobin.Figure 5 compares the oxygen dissociation curves of adult and fetalhemoglobin. Note that fetal hemoglobin has a higher affinity for O, at allpartial pressures. This ensures that O, is transferred to the fetus from thematernal blood across the placenta.

@ C"r exchange at high altitudeConsequences of high alt¡tude for gas exchatìge"At high altitude there is a low pO, in the air. Hemoglobin may notbecome fully saturated and as a consequence, the tissues may not beadequately supplied with oxygen. To some degree, human physiologycan adapt to high altitude. Red blood cell production can increase, whichincreases the total amount of circulating hemoglobin. Ventilation rateincreases to increase gas exchange. Muscles produce more myoglobin toensure delivery of oxygen to the tissues. Populations living permanentlyat high altitude have greater mean lung surface area and larger vitalcapacities than people living at sea level. Their oxygen dissociation curveshifts to the right, encouraging release of oxygen into the tissue.

HbA

0246810Partial pressure of oxggen/kPa

a Figure 5 A comparison of the 0, dissociationcurves of fetal and adult hemoglobin

10

05

Cod)XoE

=Coo=ooo0oCoooù

H

703

HUMAN PHYSIOLOGY

@ Cf,.nging attitudes to smokingScientists have a role in informing the public: scientif ic research has ledto a change in public perception of smoking.Figure 6 is a surprising picture which shows anathlete with a cigarette.

^r Figure 6 British hurdler Shirleg Strong

In the early part of the 20th century, there wasa belief that tobacco smoking could improveventilation. Doctors even prescribed smoking ofmedicine for such conditions as asthma.

In the 1930s and 1940s, smoking was commonin both men and women. Even a majority ofmedical doctors smoked. At the same time, therewas rising public concern about the health risksof smoking cigarettes. One response of tobaccocompanies was to devise advertising that featuredimages of physicians and scientists, to assure theconsumer that their respective brands were safe.

As epidemiological evidence mounted, the USSurgeon General published a report in 1964calling upon evidence from more than 7,000scientiflc journal articles to link smoking tochronic bronchitis and several tlpes of cancer.

The number of smokers is in steady decline indeveloped nations with nearly half of all livingadults who have ever smoked having quit. This isa credit to public health departments pushing forpolicy measures informed by convincing scientificevidence.

@ erphgsemaCauses and treatments of emphgsema.Emphysema is a lung condition in which the wallsbetween individual alveoli break down leading toan increase in their size and therefore a reductionin the surface area for gas exchange whichrestricts oxygen uptake into the blood.

Figure 7 shows a computer tomography scanof the lungs with one of the characteristicindications of emphysema: large areas of trappedair that show up as transparent areas in images.This can cause the lungs to become trapped in"inspiration" position in the ventilation cycle.This is known informally as "barrel chest".

The main cause of emphysema is long-termexposure to airborne irritants, most commonlylobacco smoke, but possibly also air pollution, coaland silica dust. r Figure 7

0.6 TRANSP0RT 0F RESPIRAT0RY GASES fAHL)

The damage to lung tissue by smoke is due tothree factors:o Oxidation reactions produced by high

concentrations of chemicals known asfree radicals in tobacco smoke.

¡ Inflammation due to the body respondingto the irritating particulates within smoke,

o Free radicals and other components oftobacco smoke impair the activity of the

r. Figure I

@ lnterpret¡ng micrographs of lung tissueldentification of pneumocgtes, capillargendothelium cells and blood cellsin light micrographs and electronmicrographs of lung tissue.The wall of the alveolus is composed of twotypes of cells. 90% of the surface of the alveolusis composed of cells referred to as type Ipneumocytes. They are extremely thin. Theirprimary purpose is gas exchange. The second typeof cell forming the wall is the type 2 pneumocyte.These cells are covered in microvilli, are thickerand function to secrete surfactant, a substancethat reduces surface tension, preventing thealveolus from collapsing.

enzyme alpha- I -antitrypsin which wouldnormally block the activity of proteasesthat degrade the proteins that maintain theelasticity of the lung.

A rare genetic cause of emphysema is a deficiencyin the enzyme alpha- I -antitrypsin.

Emphysema can't be cured, but the symptomscan be alleviated and the spread of the diseasecan be checked by treatment. Figure 8 shows aman sitting in a chair at home, breathing oxygenthrough a tube to the nose. Beside him is oxygenadministering equipment. Oxygen therapysupplies oxygen-enriched air to emphysemapatients.

Patients are trained in breathing techniques thatreduce breathlessness and improve the abilityof the patient to exercise. Quitting smoking isessential so sometimes prescription medicationscan facilitate this process. Surgery is sometimesundertaken to reduce the volume of the lungs byremoving damaged lung tissue. Lung transplantsare also sometimes performed on patientssuffering from emphysema.

tgpe 1 pneumocgte

endothelium cell

"--íoot'"

l. Figure 9

capillargtgpe 2 pneumocgte

705

HUMAN PHYSIOLOGY

0uestionsI A number of chemicals have been shown to

cause tissue damage due to the productionof free radicals. Free radicals are chemicals,such as superoxides and peroxides, which canreact to damage DNA and lipids. Antioxidanrsproduced by our body, such as reducedglutathione, combine with free radicals anddecrease tissue damage. Reduced glutathionereacts with free radicals and in the process isconverted to oxidized glutathione.Recently dietary antioxidants such as ligninshave also been shown to protect againsttissue damage. Flaxseed is known to containlignins but its antioxidant effects have yetto be evaluated. Research was done to see ifflaxseed could help prevent damage to theliver by tetrachloromethane. Metabolism oftetrachloromethane by the liver leads to theformation of free radicals. Rats were pretreatedby oral injection with flaxseed extract (+) orcorn oil (-) (control) for three days and theninjected with buffered saline solurion (control)or tetrachloromethane. The glutathione levelswere then measured.

! reduced glutathione

! oxidized glutathione

€ +> .€* <.ê'

control tetrachloromethanepre-treatment with fl axseed extract

Source: Endoh, et ol J Vet Medicol Science, IZ0OZ),64, page 261

a) (i) State the reduced glutathionecontent of liver tissue injected withtetrachloromethane with no flaxseedpretreatment. tll

(ii) Calculate the total glutathione conrent(oxidized * reduced) in liver rissuetreated with flaxseed extract but notinjected with tetrachloromethane. ttl

b) Describe the effect of tetrachloromethaneinjection on total glutathione and reducedglutathione content in liver tissue withoutflaxseed pretreatment. 12)

c) Predict, using the data, the effect of usingflaxseed extract in protecting liver tissuefrom damage due to tetrachloromethane. [3]

2 Blind mole rats (Spalax ehrenbergi) are adaptedto live in underground bu¡rows with very lowoxygen conditions. Scientists compared blindmole rats and white rats in order to determinewhether these adaptations are due to changesin their ventilation system.

Both types of rat were placed on a treadmilland the amount of oxygen consumed wasmeasured at different speeds. This study wasdone under normal oxygen conditions andunder low oxygen conditions. The results areshown in the scatter graph below.

Blind mole rats1.6II r.qIf r.zhoc tflo ''-.FaE 0.8=ø5 o.eoc3o 0.4Ðxo

o.2

1.6I

-9 r.¿IA t.?too _'"'FcE 0.8fØ

ã o.sC3o O.¿)Xo

o.2

oo

6

'-5Eõe4€E-ØoØ^y.F53go=^c)o-=o3Iõo

0

Ooo

ô Q normal oxggeno low oxggen

0.0 0.? 0,4 0.6 0.8treadmillspeed/ms-1

1.0 r.2

+ +White rats

o

0.0 0.2 0.4 0.6 0.8 1.0

treadmill speed/ms-1

Source: Hans R. W¡dmer et o/., "Working underground: respiratorgadaptations in the blind mole rat", PNAS

[4 March 1992 I , vol. 94, issue 4, pp.2062-2067, Fig. I,O 2003 National Academg of Sciences, USA

r.2

0uEsil0Ns

a) Compare the oxygen consumption of blindmole rats and white rats when the treadmillis not moving. tll

b) Compare the effect of increasing thetreadmill speed on the oxygen consumptionin both types of rats under normal oxygenconditions. t3l

c) Evaluate the effect of reducing the amountof oxygen available on both types of rat. [2]

The lungs of both types of rats were studiedand the features important to oxygen uptakewere compared. The results are shown in thebar chart below.

160

t40r20

E white rats

I blind mole rats

lung volume alveolar area capillarg area

features important 1o oxggen uptake

Source: Hans R. Widmer et ol., "Working underground:respiratorg adaptations in the blind mole rat", PNAS

[4 March 1997], vol.94, issue 4,pp.2062'2O67, Fig. 1,

O 2003 National Academg ofSciences, USA

d) Using your knowledge of gaseous exchangein lungs, explain how these adaptationswould help the blind mole rats to survivein underground burrows. t3l

e) Suggest how natural selection played animportant paft in the adaptations of blindmole rats. t3l

In the production of saliva, the acinar cellsactively transport ions from the blood plasmainto the ducts of the salivary gland resultingin water being drawn into the ducts. As thissaliva moves down the duct, some ions arere-absorbed but the amount that can be re-absorbed depends on the rate of flow of saliva.

Graph A below shows how the compositionof saliva varies depending on the rate of flowof saliva. Graph B shows the composition ofblood plasma.

Graph A Graph B

Na+160

140

L t.o

ct-HC03-

¡1+co¡-

K+

160

140

120

100

80

60

40

20

0

IJoEEco.FocoocoI

100

80

60

40

20

0

c-

È<) roo=9Boo860o'40

20

0

Na+

1.0 2.0 3.0 4.0rate of flow of saliva/ml min-1

Source: Jørn Hess Thagsen and Niels A. Thorn, Excretionof Urea, Sodium, Potassium and Chloride in Human Tears,

Americon Journol of Phgsiologg,178 L60-I64, 1954.American Phgsiological Societg.

a) Using the data provided compare theconcentration of ions in saliva producedaL 4.0 ml min-t with the concentration ofthose ions in the blood plasma. Í21

b) Outline the relationship between theconcentration of Na+ in saliva and the rateof flow of saliva. l2l

c) As the saliva moves down the ducts, Na+ isre-absorbed into the blood plasma. Deduce,with a reason, the type of transport used tobring Na+ back into the blood plasma. tll

d) Suggest why the concentration of Na*varies with rate of flow Í21

t