Transcript All of medicine in 12 hours…

iBSc: Question 7
By Alan McLeod
Getting the best marks
Read the whole question – a latter
section may give you a clue about
an earlier one.
To see how many points you need
look at the marks allocated – for
example a 3 point question is
generally looking for 3 salient
points
If giving a list answer put the best
answers first – examiners will not
usually mark answers too far
down a list
Always write something – it may
get you part of a mark and is
anonymised so no one will think
you are stupid!
If you genuinely have no clue then
re-write the question to see if this
sparks some ideas.
If not then move on and come
back at the end. And remember –
always write something.
Good luck!
Question 7
Dennis, a 17 year old Q7.1
• List 3 differentials (3)
boy presents with
weight loss and
constant tiredness. Q7.2
• List the three most
important blood tests
(3)
Question 7
Dennis is diagnosed
with Type 1 diabetes
mellitus.
Q7.3
• List differences
between diabetes
mellitus Types 1 and
2 (3)
Question 7
In this disease less
insulin is produced
Q7.4
• List three functions of
insulin (3)
Q7.5
• Where is insulin
produced? (2)
Question 7
In this disease less
insulin is produced
Q7.6
• Describe the structure
of the active insulin
molecule (3)
Q7.7
• List the stages by
which insulin is
produced (6)
Question 7
• One class of drug
used to treat diabetes
are sulphonyureas –
their mechanism is
well understood.
Q7.8
• Explain the
mechanism of action
of sulphonylureas (4)
Q7.9
• List another drug that
can be used to control
diabetes and its mode
of action (3)
Question 7
Dennis’ attitude
towards his illness
leads to handicap.
Q7.10
• Describe the
differences between a
disability and a
handicap (3)
The Answers
View these on ‘note view’ rather
than on full screen – additional
notes are provided for some slides
Generating Differentials:
I’D GET VINO…
I
D
G
E
T
V
I
N
O
Infectious / inflammatory
Degenerative
Genetic / Idiopathic
Endocrine
Trauma
Vascular
Iatrogenic / ingested
Neoplastic
Organs
Diabetes
• Pancreatic Islets
• 60% beta cells
– Secrete insulin
• 25% alpha cells
– Secrete glucagon
• Reciprocal action of
hormones
– Not usually present
together
• Secretions enter
pancreatic vein into
portal system
Diabetes
Type 1
• Childhood
• Often thin
• Failure insulin prod.
• Insulin dependent
Type 2
• Traditionally older
• Often overweight
• Insulin resistance
• Lifestyle/drugs/insulin
Functions of Insulin
Anabolic
• Promotes glucose
uptake
• Promotes use of
glucose as a fuel
•
•
•
•
•
• Promotes K+ uptake
• Decreased proteolysis
• Decreased lipolysis
• Decr. gluconeogenesis
– Used to treat
hyperkalaemia
Protein synthesis
Blood proteins
Muscle tissue
TAG synthesis
Glycogen synthesis
Insulin
Peptide hormone
• Alpha chain
– Species specific
• Beta chain
– Biologic activity
• C-peptoid joins chains
Packaging and Release
Insulin production
• Increased by glucose
– Transcription
– Translation
• Pre-proinsulin
– Signal peptide cleaved
• Packaged in Golgi into
secretory granules
– Insulin
– C-peptide
• Insulin forms hexamers
• Proinsulin
– Disulphide links
– Excision of C-peptide
• Insulin
• Secreted via exocytosis
Insulin
‘C’ Peptide
‘B’ Chain
‘A’ Chain
S
S
S
S
S
S
Insulin
‘C’ Peptide
‘B’ Chain
‘A’ Chain
S
S
S
S
S
S
Insulin
‘B’ Chain
‘A’ Chain
S
S
S
S
S
S
Release of Insulin
• GLUT-2 admits glucose
– Keeps intracellular conc
same as interstitial fluid
•
•
•
•
•
ATP prod stimulated
ATP:ADP ratio changes
ATP binds to K+ channel
Channel closes
Cell depolarisation
• Depolarisation
– Opening of voltage
gated Ca++ channels
– Increased [Ca++]
• Exocytosis
– Release of insulin
Sulphonylureas
Insulin
Vesicle
Beta
Cell
K+
SUR1
K+
SUR1
Insulin Vesicle
Sulphonylurea Molecules
K+
SUR1
K+
SUR1
Insulin Vesicle
Sulphonylurea Molecules
Rising K+
SUR1
SUR1
Insulin Vesicle
Sulphonylurea Molecules
Ca++
Ca++
Ca++
Ca++
Ca++
Ca++
Depolarisation
Ca++
Ca++
SUR1
Ca++
SUR1
Ca++
Ca++
Insulin Vesicle
Sulphonylurea Molecules
Ca++
Ca++
Ca++
Insulin
Ca++
Ca++
SUR1
Ca++
Ca++
Ca++
SUR1
Ca++
Ca++
Other Drugs
Metformin
• Unknown mechanism
•  Gluconeogenesis
•  Insulin sensitivity
• No weight gain
• Epigastric discomfort
• Diarrhoea
• Anorexia
Glitazones
• Alpha ketoglutarase
inhibitor
•  carbohydrate
breakdown in gut
• Abdominal discomfort
• Diarrhoea
• Flatulence
The End
The slides here should allow you to mark
your own work – remember 1 mark per
answer up to the maximum for the
question. Multiply by 3 to get percentage
points. I assume a 60% pass mark. Sorry
but I am unable to give further advice on
answers due to time constraints.