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HL Paper 2

Hypoxia is a condition in which tissues of the body are deprived of an adequate oxygen supply. A study was carried out in rats to examine the effects of continuing hypoxia on the structure of the diaphragm, and to determine whether nitric oxide is implicated in adaptation of the diaphragm to hypoxia. The diaphragm helps to supply oxygen to tissues and organs in the body by ventilating the lungs.

A group of 36 adult male rats were kept for 6 weeks in low oxygen while 36 adult male rats were kept in normal oxygen levels.

[Source: Reproduced with permission of the © ERS 2011. European Respiratory Journal June 2011, 37 (6) 1474–1481; DOI: 10.1183/09031936.00079810]

The graph shows the effect of hypoxia on the endurance of rats’ diaphragm muscle after 6 weeks. Endurance is the change in force measured as a percentage of the initial force.

[Source: Reproduced with permission of the © ERS 2011. European Respiratory Journal June 2011, 37 (6) 1474–1481; DOI: 10.1183/09031936.00079810]

The sodium–potassium pump plays a role in muscle activity. Nitric oxide may have a role in the recovery of hypoxic muscles. The production of nitric oxide can be blocked with an inhibitor of the enzyme nitric oxide synthase. The graph shows the concentration of sodium–potassium pumps in the diaphragm of control and hypoxic rats without and with nitric oxide synthase inhibitor.

[Source: Reproduced with permission of the © ERS 2011. European Respiratory Journal June 2011, 37 (6) 1474–1481; DOI: 10.1183/09031936.00079810]

Skeletal muscle contractions can take two different forms: if they are stimulated by a single action potential they take the form of a twitch and if they are stimulated by a series of action potentials the contraction is longer lasting (tetanic). The table shows the effects of hypoxia on the force of twitch and peak tetanic contraction in the diaphragm.

[Source: Reproduced with permission of the © ERS 2011. European Respiratory Journal June 2011, 37 (6) 1474–1481; DOI: 10.1183/09031936.00079810]

Outline the effect of hypoxia on body mass and erythrocyte percentage.

[1]
a.

Using the data in the graph, deduce whether hypoxia increases or decreases the endurance of the rats’ diaphragm muscle.

[2]
b.

Using the data presented in this question, explain the effect of hypoxia on the body.

[2]
c.

Analyse the graph to obtain two conclusions about the concentration of sodium–potassium pumps.

 

 

[2]
d.i.

Muscle fibres are stimulated to contract by the binding of acetylcholine to receptors in their membranes and the subsequent depolarization.

Suggest a reason for increasing the concentration of sodium–potassium pumps in the membranes of diaphragm muscle fibres.

[1]
d.ii.

Outline the effect of hypoxia on the force of contraction of the diaphragm.

[1]
e.i.

Hypoxia caused a 13 % increase in the surface area to volume ratio of the diaphragm. Suggest a reason for this change.

[1]
e.ii.

Using all relevant data in the question, evaluate the effectiveness of the rats’ adaptation to hypoxia.

[3]
f.

Discuss the advantages and disadvantages of using rats as models in this investigation.

[2]
g.

Markscheme

Erythrocyte percentage increased AND body mass reduced/smaller increase in mass

a.

a. increases endurance «in relation to the control»

b. higher force/endurance at every testing time/throughout

    OR

    smaller decreases in force «over time»

c. the magnitude of the difference is similar throughout the five minutes experiment/testing

d. differences are «statistically» significant

e. endurance of control is «approximately» 35 % versus endurance of hypoxia «approximately» 55 % «after 5 minutes»

Accept ±5 % for both percentages

[Max 2 Marks]

 

 

 

b.

a. diaphragm more endurance/stronger/generates more force for more ventilation/inspiration

b. right ventricle mass increases to pump more blood

c. erythrocyte percentage increases to transport oxygen

d. less growth/body mass which reduces oxygen demand

Reject “loss of body mass”

The physiological reason is required for each mark

[Max 2 Marks]

c.

a. hypoxia increases the concentration of sodium–potassium pumps

b. nitric oxide needed for/stimulates «production of» sodium-potassium pumps

c. nitric oxide synthase inhibitor reduces the concentration of pumps
   OR
   concentration of pumps reduced by inhibiting nitric oxide production

Award up to [1] for a conclusion on lines labelled 1 and up to [1] for a conclusion on the lines labelled 2

[Max 2 Marks]

d.i.

a. resting potential restored faster

b. increases the «maximum» frequency/rate of contractions

    OR

    can contract again sooner

Accept shorter refractory period for mpa

Do not accept faster contraction/depolarization/ repolarization

[Max 1 Mark]

d.ii.

reduces «force of» twitch AND peak tetanic contraction

e.i.

a. decrease in volume/atrophy/loss of cells/less muscle fibres/less tissue in the diaphragm

b. SA to volume ratio increased to make oxygen uptake into muscle/cells faster

Do not accept reduction in area of diaphragm

[Max 1 Mark]

 

e.ii.

a. not effective because body mass lost

b. effective because body mass still increases/rats still grow

c. not effective because contractions/force exerted by diaphragm decreases

d. effective because more sodium-potassium pumps so more/faster rate of diaphragm/muscle contractions

e. effective because endurance of diaphragm increases

f. effective because mass of right ventricle increases

g. effective because erythrocyte percentage increases

For each marking point the candidate must make it clear whether they are arguing for adaptation being effective or not. This can be done by giving the physiological benefit of a change, for example greater mass of right ventricle so more blood pumped.

[Max 3 Marks]

f.

Advantages:

a. small size

   OR

    easy to look after in research labs

b. short lifespan

    OR

    study can extend over several generations

c. can be killed «to get experimental results» if benefits of research justify it

d. «mammalian» so similarities with humans

e. fewer ethical objections than if humans are used/not ethical to subject humans to hypoxia/does not cause harm to humans

Accept any one of the advantages

Disadvantages:

f. ethical objections

   OR

   wrong to cause suffering to animals/rats

g. rat physiology/anatomy not same as human

Accept any one of the disadvantages

[Max 2 Marks]

g.

Examiners report

[N/A]
a.
[N/A]
b.
[N/A]
c.
[N/A]
d.i.
[N/A]
d.ii.
[N/A]
e.i.
[N/A]
e.ii.
[N/A]
f.
[N/A]
g.



Cholinergic synapses use acetylcholine as their neurotransmitter. They are widespread in the body, passing on signals to muscle cells. These synapses are affected by neonicotinoid pesticides.

The diagrams, which are not drawn to scale, show the synapse between two neurons and a detail of the synaptic cleft.

On the diagrams, label with a letter H the hydrophilic end of a phospholipid.

[1]
a.i.

On the diagrams, label with a letter E a vesicle involved in exocytosis.

[1]
a.ii.

On the diagrams, label with a letter P a location where a neonicotinoid pesticide could bind.

[1]
a.iii.

Outline how depolarization of the membrane of an axon occurs.

[2]
b.

Explain how acetylcholine initiates an action potential in a postsynaptic membrane.

[2]
c.

State the action of the enzyme acetylcholinesterase.

[1]
d.i.

Explain what happens to an enzyme if there is a change of pH.

[3]
d.ii.

Markscheme

hydrophilic end of phospholipid shown ✔

For 2a, i, ii and iii, accept letters written on the structure even if a line is not drawn.

Award the mark if the full word is used to label the structure. Labels must be unambiguous.

a.i.

an exocytic vesicle shown ✔

For 2 a, i, ii and iii, accept letters written on the structure even if a line is not drawn.

Award the mark if the full word is used to label the structure. Labels must be unambiguous.

Accept any of the three intact circles or the exocytosis shown within the box.

a.ii.

any receptor protein on post synaptic membrane marked ✔

For 2 a, i, ii and iii, accept letters written on the structure even if a line is not drawn.

Award the mark if the full word is used to label the structure. 

Must unambiguously be pointed to a receptor on the synapse side. Accept labels of acetylcholinesterase.

a.iii.

a. (local depolarization) causes ion / sodium / voltage gated channels to open ✔

b. altering membrane permeability to sodium ions/Na+/positive ions / Na+ diffuses into the cytoplasm ✔

c. membrane potential (of the axon) changes from negative to positive ✔

d. a threshold potential is reached and an action potential is generated ✔

Do not accept sodium pumps.

Mp b requires evidence that the student recognizes sodium is an ion.

Numerical values indicating change from −70 to +30/+40/+55 can be accepted.

b.

a. acetylcholine binds to the receptor protein ✔

b. (causing a) change in tertiary structure / conformation of protein ✔

c. diffusion/entry of ions / Na+ through the receptor/channel protein allowed ✔

c.

breaks down acetylcholine (to acetyl and choline) ✔

d.i.

a. change in pH can cause a change in the tertiary structure of the enzyme
OR
enzyme denatured ✔

b. causing a change in the active site / substrate not able to bind ✔

c. the enzyme will not work as efficiently / decreased rate of reaction ✔

d. (may no longer be) the optimum/optimal pH for enzyme activity ✔

Allow answer in the form of a graph.

d.ii.

Examiners report

There were numerous examples of ambiguous labels, for example, an H without an arrow placed beside the membrane making it unclear whether the student was indicating the hydrophobic or hydrophilic part of the membrane.

a.i.
[N/A]
a.ii.

Both receptor proteins and acetylcholinesterase were accepted as proteins to which acetylcholine can bind. The markscheme did not accept locations other than on the synaptic side.

a.iii.

In many exams, candidates seemed to confuse the voltage gated ion channels with sodium-potassium pumps.

b.
[N/A]
c.
[N/A]
d.i.
[N/A]
d.ii.



In winter when temperatures drop, brown bears (Ursus arctos) enter a cave and hibernate. The graph shows the mean values for the body temperature, heart rate and activity of 14 brown bears throughout the year. The grey shaded areas indicate the periods when the bears are in transition between hibernation and normal activity.

[Source: Adapted from Evans, A.L., Singh, N.J., Friebe, A., Arnemo, J.M., Laske, T.G., Fröbert, O., Swenson, J.E. and Blanc,
S., 2016. Drivers of hibernation in the brown bear. Frontiers in Zoology, 13(7). This article is distributed under the terms of the
Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).]

It was observed that during hibernation bears are not susceptible to osteoporosis, a condition characterized by a decrease in the density of bone, resulting in porous and fragile bones. This condition may develop in humans during long periods of inactivity and with increasing age. The graph shows the porosity of the tibia bones of black bears (Ursus americanus) and humans at different ages. Age is expressed as the proportion of normal life span.

[Source: Adapted from Journal of Biomechanics, 39(8), Donahue, S.W., McGee, M.E., Harvey, K.B.,
Vaughan, M.R. and Robbins, T., Hibernating bears as a model for preventing disuse osteoporosis,
pp. 1480–1488. Copyright (2006), with permission from Elsevier.]

Healthy bone is constantly being broken down (bone resorption) and at the same time being rebuilt (bone formation). Bone mass should therefore not normally change, nor bone diseases occur. To test whether these processes occurred during hibernation in black bears, blood serum was tested for the markers ICTP (indicating bone resorption) and PICP (indicating bone formation).

[Source: Republished with permission of Company of Biologists Ltd, from Parathyroid hormone may maintain bone formation
in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis. Donahue, Seth W; Galley, Sarah A; Vaughan,
Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L; McGee, Meghan E, Journal of experimental
biology, 01 May 2006, Vol. 209, Issue Pt 9, pages 1630–1638; permission conveyed through Copyright Clearance Center, Inc.]

Osteocalcin is a peptide hormone that causes calcium to bind in the bones, so is involved in bone formation and regeneration. Research shows that changes in the mean concentration of osteocalcin in blood serum occur before and after hibernation in bears. In this research, concentration of both osteocalcin and parathyroid hormone were measured in the blood serum of bears. Results are shown in the bar chart and graph.

[Source: Republished with permission of Company of Biologists Ltd, from Parathyroid hormone may maintain bone formation
in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis. Donahue, Seth W; Galley, Sarah A; Vaughan,
Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L;McGee, Meghan E, Journal of experimental
biology, 01 May 2006, Vol. 209, Issue Pt 9, pages 1630–1638; permission conveyed through Copyright Clearance Center, Inc.]

Estimate the difference between the highest and lowest mean body temperatures.

[1]
a.

Compare and contrast the changes in mean ambient and body temperatures during 2012.

[2]
b.

Explain the change in heart rate during the period of hibernation.

[2]
c.

Distinguish between the changes in porosity of the bones in humans and bears as age increases.

[1]
d.

The life expectancy of a human at the time of the study was 80 years. Estimate the porosity of the bones of the individual who was approximately 32 years old.

[1]
e.

The researchers assessed age as a proportion of normal life span, rather than in years. Suggest one reason for this.

[1]
f.

Describe what is happening to the bone during hibernation.

[2]
g.

Suggest how the graph would differ for a human during a long period of inactivity.

[1]
h.

Calculate the percentage increase in the mean concentration of osteocalcin from pre-hibernation to hibernation.

[1]
i.

A hypothesis has been proposed that an increase in parathyroid hormone concentration causes an increase in osteocalcin in bears. Evaluate the evidence for this hypothesis provided by the data.

[2]
j.

Discuss how helpful these studies of bears can be in developing an understanding of osteoporosis in humans.

[2]
k.

Markscheme

5 °C;

Units required. Accept answers in the range 4.5 to 5.5 °C.

a.

  Accept one similarity:

  1. both rise and then fall / both fall with hibernation and rise with activity
  2. both reach minimum during hibernation and maximum during activity;
  3. both lowest in January/February / both rise from January/February;

    Accept one difference
    :

  4. one peak of ambient temp but body temp has two peaks / OWTTE;
  5. body temp remains maximal for longer/plateaus whereas ambient peaks;
  6. body temperature is always higher than ambient temperature;
  7. ambient range is greater than body temperature range / OWTTE;
b.
  1. decreased/slower heart rate because bears less active/use less energy;
  2. less (cell) respiration / lower (rate of) metabolism;
  3. less oxygen/glucose required / less CO2 produced/needing to be removed;
  4. less muscle contraction/muscles require less blood;
  5. conserves energy;
c.

porosity increased in humans and decreased in bears;

Both needed.

d.

6 %;

Accept answers in the range 6.0 to 6.5 %.
Percentage sign required.

e.
  1. to allow comparison of bears and humans;
  2. bears have a different life span to humans / bears do not live to 80 years;
  3. because they age at different rates;
f.
  1. resorption/breaking down occurs and formation/rebuilding occurs;
  2. at similar rates / more resorption at most times;
  3. no/little (overall) change (in bone mass);
  4. lag between bone resorption rising and formation rising / OWTTE;
  5. bone resorption rising towards end as formation dropping / OWTTE;
g.
  1. more resorption than formation;
  2. PICP/bone formation (always) lower (than in bears);
  3. ICTP/bone resorption (always) higher (than in bears);
  4. ICTP above PICP by a greater amount in humans (than in bears);
h.

250 % (Allow 240 to 260 %)

i.
  1. (hypothesis supported by)
    positive/direct correlation/direct relationship (between parathyroid hormone and osteocalcin)
    OR
    osteocalcin rises as parathyroid hormone rises/vice versa;
  2. no evidence for causal link / causal link cannot be assumed / correlation does not prove causation;
    OR
    no evidence that parathyroid hormone causes change in osteocalcin;
    OR
    other factors may cause change in osteocalcin;
j.

  Accept one reason for the studies being helpful:

  1. (helps us understand how)) bears avoid osteoporosis;
  2. bone structure of bears and humans is similar / both are mammals;
  3. suggests that hormones/osteocalcin/parathyroid hormone might be a (preventative) treatment;

    Accept one reason for the studies not being helpful
    :
  4. humans do not hibernate / are not inactive for long periods;
  5. humans live for much longer;
k.

Examiners report

70 % of candidates were able to read two temperatures from the graph and subtract the higher from the lower correctly.

a.

Many candidates realized that they were expected to give similarities and differences between the curves, but most struggled to do this clearly. Rather than make eclectic statements about the data that may be correct but are not significant, the aim with a question such as this is to make comments that would allow someone who has not been shown the curves to sketch them. Some students confused maxima or minima with increases and decreases, so for example stating that ambient body temperature increased in July, when it reached a maximum in July and stopped increasing.

b.

Many candidates mentioned lack of activity as a reason for lower heart rate and some went on to mention reduced respiration rates or other aspects of physiology. Other candidates failed to offer an explanation and instead just described the data. A few claimed wrongly that bone porosity was directly proportional to age, in which case all those of a certain age would have the same degree of osteoporosis, which is plainly not the case.

c.

Well answered with most candidates referring to the positive and negative correlations.

d.

This question was very unusual in that the discrimination index was negative — stronger candidates were slightly less likely to answer correctly than weaker candidates, for reasons that are not obvious! Only a minority gave the expected answer of 6 %. A very common answer was 7 %, which is reached by calculating the age proportion correctly as 0.4 but using the trend line rather than the data point for the individual who was 32 years old. Careful reading of the question was needed to avoid this mistake.

e.

Most candidates were successful here, using the argument that humans and bears have different life spans.

f.

In this question candidates were expected to deduce the changes to bone from the concentrations of the markers. Given that neither of them reaches zero, we can assume that bone formation and resorption both continue throughout the hibernation period. Few candidates made this point clearly. The other 'best' answer was to comment on relative overall amounts of formation and resorption, either by stating that they are approximately equal or that there is slightly more resorption.

g.

Candidates were expected to suggest a difference between the bears and humans in the concentration of one or both of the markers, that would result in loss of bone mass. A common fault was to predict changes in the markers during a period of inactivity in humans, but changes over time were not the issue — it was differences between humans and bears that were relevant to the question.

h.

A very small proportion of candidates correctly calculated the percentage difference. There were many different incorrect answers, with 350 % being the most popular, which is the amount of osteocalcin during hibernation as a percentage of the amount pre-hibernation.

i.

This type of question is increasingly well answered with more candidates understanding that two variables being positively correlated does not prove a causation. The situation would have been different if an experiment had been done with the levels of parathyroid hormone as the independent variable controlled by the researchers.

j.

Answers here were very varied. The best included the idea that an understanding of how bears maintain bone mass despite inactivity during hibernation might lead to preventative treatments for humans. Because this was a discuss question, some counterargument was expected, based on differences between bears and humans.

k.