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What is the most common cause of sudden cardiac death in young healthy people?
Hypertrophic cardiomyopathy
What are the three things that we see in hypertrophic cardiomyopathy (at a micro level)?
Myocyte hypertrophy
Myocyte disarray
Interstitial fibrosis
What are the two categories of sudden cardiac death? And which of these will have abnormal post-mortem?
Structural causes - will have an abnormal post mortem

Arrhythmogenic causes - won't have an abnormal post-mortem -> we can't figure out what killed them
What is the normal thickness of the septum of the heart?
What can it get to in hypertrophic cardiomyopathy?
Normally 10mm (approx)
Can get to 30mm in HCM
Have we been able to identify genes associated with hypertrophic cardiomyopathy?
YES!
the genes are almost all associated with sarcomeres
What part of the muscle fibre is most stuffed up in hypertrophic cardiomyopathy? Ie we call it disease of the what?
SARCOMERE
What percentage of sudden death in the young can not be explained by post-mortem? What group of diseases are responsible for this?
31% is unexplained
These are the 'arrhythmogenic causes'
What part of the heart muscle is stuffed in long QT syndrome?
The ion channels
What most commonly causes long QT syndrome?
It's usually acquired eg due to medications
Have we been able to identify genes involved in long QT syndrome?
Yes
If someone died of long QT syndrome, would we be able to find anything in the post mortem?
No because it's an arrythmogenic cause of disease
But now we know some of the genes involved, we can take a blood sample and test for these genes!
By how much does depression (independent of other risk factors) increase your risk of CV disease?
It doubles your risk
What is the age expectancy gap between people with mental health disorders and the normal population?
10-12 years
Does depression predict poor outcome after an MI ?
YES
If you have a heart attack, what is your chance of dying if you're a) normal, b) depressed?
Normal mortality is about 10%
Depression - 20%
Is the link between depression and CVD stronger in men or women?
WOMEN
what is the biological explanation of the association between CVD and depression? (3 things)
- their platelets are more reactive -> more likely to clot
- there is greater variability in their HR
- they're more likely to have metabolic syndromes
What is the difference in compliance to meds between normal person and depressed person?
Depressed -> 3 times more likely not to comply
What does 'diagnostic overshadowing' refer to in the context of depressed people and acute cardiac events?
Drs / nurses are more likely to attribute a depressed person's symptoms on their mental illness rather than their underlying medical condition
-> increased 'time to needle' in the ER
What is the difference in mortality rates in hospital between a normal and a depressed person?
Depressed -> double mortality
If we treat a depressed person's depression, will it improve their mortality from their CVD?
No. not if it's just the mainstream / simple treatment
But if we use more complex and LT treatment, maybe
What is cachexia?
Significant loss of weight and muscle mass in someone who is not actively trying to lose weight (ie severe illness)
Do we lose muscle mass as we age?
Yes
What are the four anatomical factors that determine a muscle's force?
- Number and size of muscle fibres
- Arrangement of the fibres
- Fibre type and myosin isoenzymes
- Insertion of tendons / lever ratios etc
What is a motor unit?
A motor neuron and the muscle fibres it innervates
What are the functional factors that determine a muscle's force?
- Number of motor units activated
- Rate of firing of APs in the motor nerve
- How much overlap we have (ie joint position)
If we stimulated someone's peripheral nerve and the force generated by their muscle was greater than their maximal voluntary contraction, where is the problem occurring?
In the central NS
If we stimulated someone's muscle directly and the force generated by their muscle was greater than their maximal voluntary contraction, where is the problem occurring?
In the neuromuscular junction, peripheral nerve itself of CNS
What is muscle fatigue?
It's the REVERSIBLE decrease in force generating by muscles with intense activity
Due to metabolites acting on functional components in the muscle
Which fibres (fast or slow) fatigue easily?
The fast fibres work by anaerobic glycolysis -> they fatigue easily
Which fibres (fast or slow) are fairly fatigue resistant?
The sow ones. They have lots of mitochondria, use aerobic metabolism -> they can produce ATP at the same rate as they consume it
What sorts of things can make muscles fatigue more rapidly than normally? (think of more systemic things)
- Inadequate blood flow (atherosclerosis, diabetes, heart failure)
- Inadequate O2 supply (resp disease, anaemia)
- Any process that's caused an increase in fast fibres (eg inactivity)
- Abnormal muscle metabolism
- Muscle wasting
What are the three things we need for hypertrophy?
Exercise, diet and hormones (both local and general)
Are the pathways involved in atrophy of muscles just the reverse of those involved in hypertrophy?
No. not just the opposite!
What is MYOSTATIN?
A negative regulator of hypertrophy ie it promotes atrophy
What happens if we inactivate the protein myostatin?
The protein normally promotes atrophy -> if we inhibit it, will get increased muscle development
What do we tag proteins with to signal them for degradation?
Ubiquitin
What protein degradation pathway is upregulated in cachexia?
The ubiquitin-proteasome pathway
In expts where we compare biceps force in controls and people with chronic fatigue, what difference do we see in force production?
THERE IS NO SIGNT DIFFERENCE IN FORCE PRODUCTION
In expts where we compare fatigue and recovery after fatigue between controls and chronic fatigue people, what difference do we see?
There is no difference in their fatiguability
But there does appear to be a statistically significant difference in their recovery time
What percentage of all presentations to GP are for tiredness?
5-10%
Of the people presenting to their GP with tiredness, what percentage have a psychosocial cause?
50-80%
What physical things can cause tiredness?
- Lots of medical conditions -> need to look at associated symptoms etc
- Lots of meds
- Infections
When do we consider chronic fatigue syndrome as a possibility in our patients?
When they've had fatigue lasting more than 6 months + other possible underlying diseases have been ruled out
Is chronic fatigue syndrome a physical or psychological illness?
This is still hotly debated
Most people believe it's a combo of the two
During latency, are viruses transcribing any genes?
Their gene expression is significantly lower than normal but they transcribe a few viral genes during latency
Do hep C and HIV become latent?
No
What can be consequences of chronic viral infections?
- reactivation -> acute illness
- can lead to 'non-communicable' diseases eg malignancies (Burkitt's lymphoma with EBV and cervical cancer with HPV) or degenerative CNS syndromes
- produce long term damage to their target organ
Is it illegal for doctors to treat their family and friends?
No but it's not recommended
What are the 7 big main reasons why people go to see a doctor?
Symptoms/signs that threaten their quality/duration of life
symptom or sign that's not currently a problem but may be in the future
no evidence of disease, but they have reason to fear they might dvelop it
want to stay in good health with screening and general health advice
they cope with life by using illness as a shelter
they don't perceive they're ill, been sent by fam or friends
overwhelmed by anxiety or angst
What are some of the problems associated with treating your friends and family ?
They mightn't accept your authority when you give them advice
Language you use with friends/fam isn't 'language of medicine' - could easily be distorted / mis-interpreted
Hard to offer probabilistic advice (might offer false hope)
Also hard to break bad news
What is the most common cause of fainting?
Vasovagal syndrome
What is the definition of syncope?
Disturbance or loss of consciousness as a result of abrupt reduction of blood flow to the brain. Typically of short duration (secs to mins)
(there's usually autoregulation of flow to the brain so even if arterial BP drops a bit, brain still gets enough blood. But large fall in BP -> autoregulatory mechanism is overwhelmed)
What are the four main factors that can cause abrupt and large decreases in BP leading to syncope?
Obstruction to circulation
Transient arrhythmias
Neurological disorders
Vasovagal syndrome
What is vasovagal syndrome?
"vaso" - peripheral vasodilation (most impt contributor)
"vagal" - vagally mediated cardiac slowing (bradycardia)
-> Both CO and TPR are reduced --> BP falls significantly
In vasovagal syndrome, if we block the vagal contribution with atropine, will we still have the syncope?
YES
shows that the vasodilation is the most important
What do we call people with vasovagal who faint in the absence of obvious stimuli?
Malignant vasovagal
What causes the vasodilation in vasovagal syncope?
Inihbition of symp vasoconstrictor nerve activity
Is baroR reflex acting normally in vasovagal syndrome?
No. It appears to be suppressed because it would otherwise act to increase symp innervation of BVs -> vasoconstriction
What are the four main expectations of the sick role according to Parsons?
They're exempt from normal social responsibilities eg work
They're not held accountable for their illness
They have a duty to experience illness as undesirable
They have a duty to seek out expert assistance and to cooperate with recommendations in order to get better
What are the three criticisms of Parson's 'sick role'?
- More appropriate for acute disorders - chronic disorder -> might be encouraged to continue normal social role responsibilities
- Removes patient's responsibilities for behavioural choices
- culture and class problems
What does the brain rely on as its substrate for energy?
glucose
At rest, what percentage of total CO goes to the brain?
15-20%
Do we have many collateral blood vessels in the brain?
Yes.
Reduces risk of occlusion in one artery causing serious ischaemia in that region
But there are some regions that are only supplied by one artery (no collaterals)
Over what range of mean arterial pressures does cerebral blood flow stay constant?
60-150mmHg
What happens to cerebral blood vessels if there's a decrease in arterial pressure?
Decreased resistance ie vasodilation
In a hypertensive person, what happens to the range of arterial pressures over which they're able to maintain cerebral blood flow? What's the effect of this?
It gets shifted up. Normal max is 150 but in HTs, this increases. So then does the min (above 60) -> decrease in arterial P to say 65 can result in ischaemia in HTs (this P wouldn't cause ischaemia in a normotensive persoN)
Are cerebral blood vessels innervated by the ANS? What is the effect of this?
Yes, by symp NS - doesn't change the calibre of the vessels, rather chages the autoregulatory range (symp innervation increases the range)
What is the main factor reuglating the resistance of cerebral arterioles?
Local metabolic activity (namely H+ (also dependent on CO2) and adenosine. Believed that NO might be involved too)
What can hyperventilation do to cerebral arteriolar patency?
Hyperventilation -> decreased CO2 in the cerebral arterioles -> vasoconstriction -> decreased cerebral blood flow -> unconsciousness
What is the role of glial cells (astrocytes) in the coupling between neuronal activity and cerebral blood flow?
When NTs are released, there's a change in intracellular Ca2+ conc of the nearby astrocytes -> they release vasodilating substances --> increased blood flow to match the increased activity
What is battery?
Intentional touching of another person without consent of that person and without lawful excuse
Is informed consent the same as valid consent
No.
Informed consent is only one part of valid consent
Do you need to get valid consent in an emergency?
No. the courts have presumed that an unconscious person in life threatening situation would have consented to treatment
If a patient says that they don't want to know about what's going to happen and that they don't want to make the decision themselves, that they want the doctor to make the decision for them, what should the doctor do?
The doctor should not make the decision for the patient. This is waiving teh important fundamental right to autonomy
Instead, they should get a third party to make the decision for the patient
Medical practioner can not assume the right to make decisions on the part of the patient, except in an emergency