Download Integrated Teaching Area (ITA) Scenarios for Semester One

Integrated Teaching Area (ITA) Scenarios for Semester One
Weeks 5 and 6
Introduction:
Four new clinical scenarios relating to chest pain are given below. These will form
the basis for the ITA sessions at Ninewells in week 6.
To help you prepare the background for these ITA sessions you should:
1. Prepare answers to the structured tutorial questions on page 3. Take your
answers to the meeting with your tutor in week 5. At these tutorials there will
be a group discussion about the questions.
2. Meet in your small groups to discuss the topics and listed under “Small Group
Work” on page 4. You should plan how the group will research the topics and
feedback the results of that research to the rest of the group.
At the ITA sessions in week 6, further questions will be set, and additional material
will be available to help you better understand how the basic principles you are
studying in semester one relate to the patient scenarios.
Scenario 1:
Arthur Jones is a 44 year old office worker. For the past 2 years he has developed
central chest pain on exercise. Initially this was only when walking up steep hills,
although now he gets chest pain walking up a single flight of stairs. The chest pain
resolves when he takes his GTN spray. He lives on the 4th floor of a tower block in
Lochee, with his wife and 20 year old son, John.
After a consultation about a sore throat, Mr Jones mentions that he is worried by his
family history of heart disease. His brother George died at the age of 45 following a
myocardial infarction and his sister Amelia has angina at the age of 33. He has two
other sisters, Mary (age 50) and Louise (age 37) who are both well. Mr Jones tells you
that both his mother and father died from “heart problems”, his mother at age 71 and
his father at 38.
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On examination in the clinic, Mr Jones is overweight, weighing 107kg with a height
of 173cm. He smells strongly of cigarette smoke. There are no other findings on
cardiovascular examination. His blood pressure is 120/80.
Scenario 2:
Marie is a 22year old Nigerian working as a nursing assistant in the UK for the last 2
years. She has had numerous episodes of bone pain over the years, mainly affecting
her knees and shoulders, and knows that she has Sickle Cell Disease. She usually
manages to control these painful “crises” by using paracetemol at home together with
plenty of oral fluids. However, on three occasions she has required hospital
admission and treatment with diamorphine analgesia.
Three days ago she developed a further episode of right shoulder pain, associated with
general malaise. This pain was not controlled with simple analgesia, and she
developed a high temperature, sharp pain in her right chest on intake of breath, and
felt short of breath on exertion. She was admitted to the haematology ward, had a
chest X-ray which showed opacification in the lower right lung, and was found to be
hypoxic (oxygen saturation of the blood 89%). She was treated with intravenous
fluids, oxygen by face mask, a diamorphine infusion, and intravenous antibiotics.
With no improvement after 24 hours she underwent an exchange transfusion of red
cells, after which the proportion of sickle haemoglobin (HbS) in her blood had fallen
from 95% to 40%. She was well enough to go home 7 days later.
Scenario 3
Ian Smith (age 22) develops a severe cough and right sided chest pain. He deteriorates
rapidly and is admitted to intensive care, requiring mechanical ventilation.
John was diagnosed as being affected with cystic fibrosis at the age of 3 because of
his slow growth and malabsorption of food. You meet his mother Mary, father John
and sister Claire in hospital where he is being treated.
John’s sister, Claire, is 12 weeks pregnant when she comes to the clinic.
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Scenario 4
Fred White (age 45) was having breakfast one morning, when he developed sudden
onset pain in the centre of his chest. On admission to hospital a diagnosis of aortic
dissection was made. He makes a good recovery following urgent surgery and you see
him 5 days post operatively on the ward.
On examination you note that he has long fingers, and long arms and legs in relation
to his body. He also has marked cutaneous striae. You make a diagnosis of Marfan
syndrome.
Following discharge from hospital, Mr White comes to the genetics clinic with his
two sons, James age 16 and John age 18. Mr White has a sister, Jane,who has severe
curvature of the spine, and a brother Arthur who is in good health.
Structured Tutorial Questions Week 5
(Linked to ITA Week 6: Chest Pain 2 Scenarios)
What is the normal human chromosome complement: how do chromosomes divide at
(a) meiosis and (b) mitosis?
How can two genes on the same chromosome segregate independently (as described
by Mendel’s first law)?
Why are people different – how does the genome of one person vary from that of
another person?
What is a gene made of, and what are its component parts? – How does the cellular
machinery recognise these?
What are the different stages in the manufacture of a protein from a gene?
What are the different ways in which changes in a gene can affect the protein
product?
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Small Group Work before the ITA Session: Week 5
(Linked to ITA Week 6: Chest Pain 2 Scenarios)
In your small groups the aim is for you to identify the learning issues that are
important when considering the genetic basis of disease. The formal teaching sessions
are one source of information about these issues. You are likely to get more from
these teaching sessions if you approach them with prior knowledge and a spirit of
enquiry. Some examples are given below, but you will need to add to these.
What are the different ways in which a genetic disease can be inherited?
How does one person’s genetic material differ from another?
How can changes in a gene cause disease?
How might inheriting a change in a gene be beneficial?
What are the risks and benefits of having a genetic test?
Are genetic tests different when compared to other sorts of blood test?
What other areas do you think are important to consider?
General Questions for all cases
a. How is the condition inherited?
b. What are the other clinical features that you might expect in this disorder?
c. What is the best diagnostic test for the condition?
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Structured Tutorial Questions Week 5
(Linked to ITA Week 6: Chest Pain 2 Scenarios)
Tutors’ Briefing Notes
What is the normal human chromosome complement, how do these divide at
(a) meiosis and (b) mitosis?
46 XX (female) or 46 XY (male) i.e. 22 pairs or autosomes and the sex
chromosomes. Chromosomes are recognised by their size and banding pattern.
Mitosis is the production of two diploid daughter cells from one diploid parent cell.
The genetic complement is identical (give or take a few somatic mutations). At
meiosis, four haploid daughter cells are formed from one diploid parent cell. Don’t
forget to discuss formation of chiasmata and crossing over.
How can two genes on the same chromosome segregate independently (as
described by Mendel’s first law)?
Crossing over at meiosis. Two loci close together on one chromosome may
segregate together as crossing over is less likely to happen between them (they are
said to be in linkage disequilibrium).
Why are people different – how does the genome of one person vary from that
of another person?
Single base changes in genes that may or may not affect gene function. Some are
completely neutral, some will affect gene function, either by altering the amino
sequence or altering the regulatory elements.
What is a gene made of, and what are its component parts? – How does the
cellular machinery recognise these?
Promotor, start codon, introns, exons, stop codon and polyadenylation signal.
Consensus sequences, e.g. g/gtaag and ag/ marking start and finish of intron.
What are the different stages in the manufacture of a protein from a gene?
Transcription, splicing (nuclear), translation (ribosome) and post-translational
modification (eg. glycosylation and folding) and transport to final resting place.
Interaction with other proteins. Don’t forget the genetic code and 3 base pairs = 1
amino acid.
What are the different ways in which changes in a gene can affect the protein
product?
Neutral polymorphism, change in amino acid sequence, premature stop, abolition of
splice site, deletion or insertion in frame or out of frame, trinucleotide repeat (intronic
– not transcribed or exonic causing polyglutamine tract in protein).
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