Acute Limb Ischemia
Comfortable after 5mg morphine (relatively small
This occurs when there is blockage of a peripheral
artery, either from a thromboembolism, or
sometimes from an embolic plaque:
Thrombus in situ - 40%
Emboli 38%
Angioplasty occlusion 15%
Trauma
Compartment syndrome - rare
Signs and Symptoms
Classically, the SIX Ps
Pulseless
Parasthaesia
Pain muscles also become tender to palpation
after about 6-8hours Aneurysm and AAA
Paralysis
Pallor
Perishing cold
Fixed mottling of the skin implies irreversibility
BEWARE hot red leg may sometimes be
present, which can result in misdiagnosis
of gout or cellulitis
Diagnosis
You can roughly localise the blockage by locating
the bifurcation distal to the last palpable pulse.
Diagnosis is clinical
Treatment
It is an EMERGENCY!
22% of cases are fatal
16% of cases result in amputation
Thrombolytic agent e.g. tissue plasminogen
activator (tPA) most effective when given
via local arterial catheter (Fogarty
Catheter), particularly for occlusions <2
weeks. Therapy is usually given via the
catheter for 8-24hr
Open surgery / angioplasty DON'T BE
AFRAID TO DO THESE! equally, dont
be afraid to do angiography in cases of an
unsure diagnosis.
The decision to opt for thrombolysis over surgery
depends on risk assessment on an
individual patient basis (i.e. risks of
surgery vs risks of thrombolysis)
You should use heparin anticoagulation after both
surgery and thrombolysis!
After initial treatment
Look for a source of emboli e.g. ultrasounds of
aorta, popliteal and femoral arteries for
signs of aneurysm
Watch out for reperfusion injury which can lead
to compartment syndrome
Case Example
92 year old nursing home patient
Painful left leg, sudden onset
Deaf and dementia
dose)
BP 110/40 probably slightly low
HR 80 irregular
RR 16
Heart sounds normal
Apyrexic
Whole left leg is white and cold
Some mottling from foot to just above knee
Calf is very tender
Can barely move right leg, but can wiggle toes.
Cannot move left leg at all.
Pulses on the right are normal.
No palpable aortic aneurysm
No obvious swelling of the leg.
An aneurysm is an artery that has a localised
dilation, with a permanent diameter of >1.5x that
expected of the particular artery.
True Aneurysm the wall of the artery forms the
wall of the aneurysm
The most frequently involved arteries are; in
decreasing incidence: abdominal aorta,
iliac, popliteal, femoral and thoracic aorta
False aneurysm aka pseudoaneurysm - other
surrounding tissues form the wall of the aneurysm
These most commonly occur in the femoral artery
following femoral artery puncture. If there
is inadequate pressure to the entry site of
the puncture, then blood can spill out and
form a haematoma. Eventually the
surrounding soft tissue will form the wall
of the aneurysm.
I think the difference between this and a true
haematoma is that in a pseudoaneurysm
there is still communication between the
lumen and the fluid collection, but in a
haematoma, there is either no connection,
or just a one way 'leakage' of fluid..
Aneurysms can either be fusiform or sac-like.
Fusiform describes a shape that is tapered at both
ends (a bit like a raindrop with a pointy bit
at both ends), whilst sac-like describes a
more rounded characteristic.
When inspecting an aneurysm you should feel for
them being expansile. This means they expand and
contract. Swellings that are pulsatile are different
these do not expand and contract but just transmit the
pulse e.g. nodes overlying arteries.
Etiology
Despite the different pathology between aneurysmal
and atheromatous disease, the risk factors for both
are similar, and include:
Hypertension
Smoking
Age
 Diabetes
Obesity
High LDL levels
Sedentary lifestyle
Genetic factors are more important in
aneurysmal disease than in atherosclerotic
disease, although they have a role in both.
10% of cases have a first-order relative
also with the condition
Specific aetiological factors for aneurysm include:
Co-arctation of the aorta
Marfans syndrome, and other connective tissue
disorders
Previous aortic surgery
Pregnancy (particularly 3rd trimester)
Trauma
Incidence increases with age 5% of men over 60
have one
Occur 3-5x more often in men than women
Complications
Aneurysms in themselves do not often constitute a
primary problem. They may cause a local
obstruction (e.g. of IVC), and they can also cause
impaired bloodflow to the lower limbs. They are also
a risk factor for thrombosis and embolism. However,
the main risk comes from the tendency of aneurysms
to dissect and rupture most commonly an aortic
aneurysm will rupture into the retroperitoneal space.
Elective repair of aneurysms before rupture is
comparatively safe
Repair after rupture has very high mortality
40% of AAA patients also have iliac artery
aneurysms, and 15% have popliteal aneurysms.
General features of Aortic Aneurysm
Often symptomless, and discovered incidentally
(examination, AXR, ultrasound, CT)
Mean age of presentation 65
Often discovered on AXR about 65% of cases
are sufficiently calcified to show up on
radiograph
Ultrasound is usually used to stage the
aneurysm. It is accurate at assessing the
site of the aneurysm, and easy to follow up
cases to asses development. CT is more
accurate, and particularly useful at looking
at the surround structures (e.g. to see if
there is any compression) but more
expensive, thus is usually used only for
pre-op assessment.
Risk of dissection (bursting). Risk increases with the
diameter of the aneurysmA source of thrombus
formation, which can embolise to the lower limbs
Rarely, may be completely occluded by thrombus
Management of Aortic aneurysm
The nice guidelines state that an aortic aneurysm of
greater than 5.5cm in diameter should be treated.
Below this size, the risk of dissection is outweighed
by the risk of surgery.
At 5.5cm the annual risk of rupture is 25%
At 6.5cm it is 35%
At >7cm it is 75%
In some cases, symptomatic aneurysms of smaller
size may be operated on.
Pain is thought to be a risk factor for rupture
Thrombo-embolus is also an indication for
surgery and can prevent limb-loss.
Sugery is the treatment of choice. There are two
options:Open Laparotomy - the affected segment
of aorta may be clamped and replaced by a prosthetic
segment, (most common a Dacron graft). Graft
failure is rare. In a variation of the treatment, the
affected artery segment is bypassed.
Complications are generally rare. There may be
kidney problems, and sometimes
paraplegia or ischaemic colitis. fistula
formation with the small bowel can also
occur but is rare. Infection is also rare.
Mortality
- See 5-8% in elective asymptomatic AAA
10-20% for symptomatic emergency AAA
50% for ruptured AAA
Long-term survival for most patients is almost
identical to the general population
Endoluminal surgery EVAR - Endovascular
aneurysm repair - an aortic graft is inserted through
the femoral artery, and up into the abdominal aorta.
This method is generally preferred (lower mortality
1.2%) but many patients are not suitable. There must
be at least 2.5cm normal aorta between the aneurysm
and the renal arteries to securely fix the graft in
place.
complications with the actual graft are more
common with the endoluminal technique
than with open surgery. the graft can fail,
or it may be moved, allowing blood to
refill the aneurysm. Although, the risks of
the procedure itself are far less than open
surgery.
Generally, rupture cannot be treated by the
endoluminal method, although there are
ongoing trials.
Back to top
Dissection and Rupture of AA
Death rates from this rises with age:
Age 55-59 death rate is 12.5 per 100 000
Age 80+ - death rate is 273 per 100 000
>75% with a ruptured AAA die usually before
getting to hospital.Of those that do reach hospital,
surgery has a 50% mortality rate. Thus only around
10% of those with a ruptured AAA will survive.

Rupture is essentially where the wall of the aorta
completely fails, and blood escapes freely into a
body cavity (e.g. abdominal cavity).
This is different from dissection! However,
dissection often leads to rupture.
Dissection is where blood escapes through the
innermost layer of the wall of the artery,
and prises apart the media, creating a new
lumen. Sometimes, this lumen is absorbed
back into the main lumen, creating a
double-barrelled aorta. This may be
stable, but may rupture. If it is close to the
aortic valve (thoracic aortic aneurysm) it
may compromise valve function.
The dissection is sometimes able to track back all
the way to the pericardium, and can cause
haemopericardium.
Dissection is a medical emergency and has to be
treated asap. If the blood manages to escape through
all the layers of the wall of the aorta, then rupture is
the result.
Classification of Dissecting AA
- See Type A 2/3 of cases. These involve the
ascending aorta, and may also include the
descending aorta
Type B affect the descending aorta only
Symptoms
Pain
Sudden onset, severe pain. Often described as
tearing and usually radiates to the back.
Pain usually follows the line of the dissection
Ascending aorta pain will be in the chest
Descending aorta pain often in the back
Collapse (due to hypotension)Expansile (not
pulsatile) mass in the
abdomenShockHypotensionTachycardiaPr
ofound anaemiaSudden deathOther signs may Most probably pathology
include:
Testicular pain
Symptoms similar to renal colic
Symptoms similar to diverticulitis
Non-specific back pain this results from gradual
erosion of the vertebral bodies in patients
with long-standing aneurysm.
If in doubt about the diagnosis; assume ruptured
AA!
Investigation
Diagnosis is usually clinical, and needs to be made
quickly!
Mortality in dissection is about 1% per hour
This is much higher if it progresses to rupture!
Treatment
Type A require Emergency surgery usually by
open surgery (Dacron Graft). for further
details see above : Management of aortic
aneurysm
Type B often not quite as urgent as type A
depending on the individual case.
Possibility to treat endoluminally, although
open surgery is often still the treatment of
choice.
Abdominal Aortic Aneurysm
Usually in the infrarenal segment of the aorta
(80%)These most commonly occur below the
level of the renal arteryFeatures of pain:
Rapid expansion or rupture will cause epigastric
pain radiating to the back. Pain may also
be present in the groin, iliac fossae and
testicles.
Can be a constant or intermittent pain
Be careful not to dismiss it as renal colic!
Thoracic Aortic Aneurysm
Asymmetrical brachial/radial/carotid pulses if the
dissection involves the aortic arch. Variable pattern
depending on where the dissection is.
BP may be different in each arm under similar
circumstances to the above.
Pathology of Aneurysm
An aneurysm is a permanent dilation of the vessel
wall. The fact that it is permanent implies that the
vessel wall itself is altered in some way.
Atheromatous degeneration is the most common
cause of true aneurysm. Thus the risk factors are the
same as for CHD:
Smoking
Family history
Diabetes
Hypertension
Age
Hyperlipidaemia
There is ischaemia of the aortic media where
there is an atherosclerotic plaque. This is
as a result of release of macrophage
enzymes (released when macrophages
become activatived) that break down the
elastic fibres (collagen and elastin)
There is evidence that various genetic variants of
collagen are more susceptible, and this
probably accounts for the familial aspect
of aneurysms.
Where this ischaemia occurs there is loss of the
normal elastic nature of the media,
allowing it to expand.
Marfans syndrome
A connective tissue disorder, and is sometimes (but
not always) inherited in an autosomal dominant
manner. It is caused by mutations of the fibrinin
gene on chromosome 15. It is very common, and is
thought to affect about 1 in 5000 individuals, 25% of
which will be the result of a new mutation.
Males and females are equally affected.
Fibrillin-1 gene mutations can be seen in 80% of
cases, and aid diagnosis. Testing for this can also be
used to screen other family members in known cases.
The most common clinical features are in the
musculoskeletal system:
Arachnodactyly abnormally long and thin
fingers in comparison to the palm. Fingers
may also be bent backwards at the MCP to
180 in some cases.
Joint hypermobility
Scoliosis lateral curvature of the spine
Chest deformity
High arched palate
Dislocation of lens in the eye
Patients are usually tall and thin, with long limbs
These are generally mild, features, but the disease
can also have serious complications, including:
Heart valve defectsPre-disposes to aneurysms
There is weakening of the media layer of the
aorta, leading to dilation. In these cases,
the dilatation typically occurs in the
ascending aorta. There may also be valve
defects (e.g. aortic regurg) which
complicate the issue.
In Marfans Syndrome, the root of the aorta is
typically affected
Lung disorders
Dura disorders
It is thought that as well as the fibrin defects, there
are also problems in TGF- (transforming-growth-
factor-). This is thought to accumulate in heart
valve and blood vessels, and alter their underlying
structure, leading to the complications mentioned
above.
Treatment of Marfans
-blocker therapy has been proven to reduce the
rate/risk of dilatation of the aortaMonitoring of
aortic dilatation via X-Ray, Echo, MRI or CT can
be useful in patients with known Marfans. Usually
patients are followed up with yearly echo to assess
the size of the aorta. In some cases, elective
replacement of the ascending aorta may be
recommended, to prevent dissection but has a
mortality of 5-10%.Avoidance of endurance sports
/ activitiesIn pregnancy as both pregnancy and
Marfans are risk factors for AA, then during
pregnancy, the aorta is closely monitored by 6
weekly echos.
If the aortic root >4cm, ceasarian section should
be considered
blocker therapy is safe to continue during
pregnancy
Atherosclerosis
Epidemiology
Cardiovascular disorders are the leading cause of
death in western society
In England and Wales, they account for 40% of
all deaths:
Ischaemic heart disease is 27%
Cerebral vascular disorders 13%
Atherosclerosis is by far the most important cause
In the developed world the incidence has
increased massively
In the US and some European countries,
incidence has actually peaked and in
declining
In the rest of Europe, and in the middle and far
east, incidence is rising rapidly
Pathology
Atherosclerosis can have 3 main types of
manifestation:
Coronary heart disease angina, MI, sudden
death
Cerebrovascular disease stroke, TIA
Peripheral vascular disease claudication, critical
limb disorder
These situations often co-exist, and the pathology is
very similar. For example, patients presenting with
stroke or claudication will very likely have coronary
artery disease and this co-existing disease is an
important cause of mortality.
Normal artery structure:
There are 3 layers of arterial tissue:
Tunica Intima this is the innermost layer, and
has a single layer of endothelium, with a
sparse supportive tissue. This layer is very
very thin!
Tunica Media this is separated from the intima
by the internal elastic lamina. The media is
made up of smooth muscle and elastic
tissue. In the heart, the elastic tissue is
most predominant, but in most arteries,
this layer is mostly made up of smooth
muscle.
Tunica Adventitia this is a fibrous connective
tissue. The external elastic lamina
separates this from the media. Very small
blood vessels can be found in this layer
called vasa vasorum and these filter down
to supply the media.
The intima and innermost media receive
their nutrients from the arterial
lumen via diffusion.
Normal age-related changes
These will usually be inconsequential by age 40, and
very common by age 70. They are often termed
arteriosclerosis. the changes affect all blood vessels,
right down to the arterioles. They include:
Progressive fibrous thickening of the intima
Fibrosis and scarring of the muscular and elastic
media
Accumulation of mucopolyysaccharide ground
substance
Fragmentation of the elastic laminae

Ultimately these changes reduce the strength and
elasticity of the vascular wall. Clinically, this will
mean there is dilation of the aorta and coronary
arteries and this finding is common.
In the aorta this can lead to stretching of the aortic
ring resulting in valve incompetence
Dilation of the aortic arch and thoracic aorta can
also lead to unfolding of the aorta
which can be seen in chest x-rays as a loss
of the aortic notch, and a widened
appearance of the central vascular column
in the x-ray.
To compensate for these changes, there is often
smooth muscle hypertrophy and production of extra
layers of collagen in the internal elastic laminae.
Atherosclerosis
This is a disease of the medium and large sized
arteries only. It is very uncommon in arteries of less
than 2mm diameter. It is caused by 3 types of lesion:
Fatty streaks
Fibrolipid plaques
Complicated lesions
The major risk factors are:
Age
Male gender pre-menopausal women in
particular seem to be a very low risk
being pre-menopausal is a preventative
factor. After the menopause, gender
differences disappear rapidly. HRT also Pathology
has no role in reducing the risk infact
oestrogen therapy appears to increase the
risk.
Hypertension anti-hypertensive therapy reduces
coronary mortality, stroke and heart
failure.
Smoking this link is also dose related
Diabetes
High levels of LDL
Low levels of HDL
Obesity
Sedentary lifestyle
Increased levels of blood coagulation factor VII
Low birth weight this is thought to be
particularly important. Those with a low
birth / infant weight are at higher risk of
adult obesity. Those with a low birth
weight and a subsequent level of obesity in
adulthood are 2-3x more likely to die from
heart disease than those with a high infant
weight. A low infant weight is often (in the
past at least) associated with low socio-
economic status.
Low socio-economic status
Genetic factors often things like hypertension,
hyperlipiedaemia and diabetes run in
families, and are multi-genetic.
HOWEVER it is also important to
remember than families often share the
same environment and environmental
factors may be involved in the apparent
family history link.
Clinically we say a significant family
history is present when first
degree relatives have had acute
events at <50 years for men and
<55 years for women.
However it is important to note that there are wide
variations in the severity of the disease, even within
similar populations. These variations are possibly
due to genetic factors. For example;
There is an inherited genetic abnormality
whereby an individual has a lack of LDL
receptors familial hyperlipidaemia? -
about 1 in 500 caucasians are heterozygous
for this abnormality to cope with their
reduced number of receptors, they produce
increased amount of LDLs. These people
develop coronary heart disease in their
40s or 50s.
Some patients may even be
homozygous for this gene in
this case these patients will often
die from coronary heart disease
in their infancy or teens.
The effect of risk factors is multiplicative, rather
than additive. Also remember the difference between
relative and absolute risk. For example a man in his
30s with high cholesterol who smokes, is far more
likely to have an acute event in the next 10 years
than someone of his age who doesnt smoke with a
normal cholesterol BUT his absolute risk is still
very low.
In atherosclerosis, there is inflammation of the
arterial wall, characterised by lipid-rich deposits of
atheroma. These deposits do not cause a problem
until they become large enough to occlude the artery,
or until they ulcerate, or until they become disrupted
and a thrombosis forms on their surface.
Signs of atherosclerosis appear early in life, for
instance fatty streaks in the arteries of children
have been noted as young as the age of 7. However,
these are asymptomatic.
The disease is basically characterised by:
Fibrosis
Lipid deposition
Chronic inflammation
In the early stages of the disease, there may be many
separate streaks and deposits, but in late disease,
these all may be confluent.
Progression
Early atherosclerosis
Fatty streaks:
These will occur at areas of turbulent flow, such
as bifurcations, and they are associated
with abnormal endothelial function.
They themselves are of no clinical significance,
and occur in all populations
They are basically a yellow linear elevation of the
intimal lining.
Pathogensis

Endothelial cells will begin to show unusual

adhesion molecules (e.g. ICAM-1 and E-
selectin). These may be similar to those
seen in acute inflammation.
This attracts monocytes (macrophages) to the site
and these can be seen both entering and
leaving the endothelium.
At the same time, high levels of LDL in the blood
will begin to accumulate in the arterial
wall. It may be that these lipid deposition
sets off an inflammatory reaction, and the
macrophages are attracted like they would
be to any type of inflammation.
The macrophages entering the arterial wall will
come into contact with these lipid cores,
and will take up the oxidized LDL,
becoming foam cells. The macrophages
will also be activated by the inflammatory
products released by the arterial wall.
The foam cells can die, and they release their
products, causing the formation of a pool
of lipid. This pool is called a lipid core.
The activated macrophages will release lots of
their own products. These include
cytokines and growth factors, particularly
PDGF. These growth factors lead to
proliferation of the smooth muscle layer. It
will proliferate towards the lipid pool, and
in an attempt to repair and stabilise the
lesion, it may form a layer around the pool.
The smooth muscle cells change their
phenotype from contractile, to repair
they now permanently become repair type
cells.
If this process of repair is successful, Advanced atherosclerosis
the plaque will be a stable If inflammation dominates over the repair
atherosclerotic plaque and will mechanisms of the smooth muscle, then the plaque
remain asymptomatic, unless it may become active or unstable, and this could
grows big enough to occlude an lead to ulceration and thrombosis.
artery. Many more products are released by the
At some point, T lymphocytes will also invade the macrophages, including, IL-1, TNF-,
plaque. interferon gamma, PDGF and
matrix metalloproteinases.
These can cause the smooth muscle cells
overlying the plaque to thin, and thus the
protective fibrous cap covering the
plaque can become weak.
The macrophages themselves can also digest
collagen struts that are holding the cap in
place.
These changes in themselves dont completely
destroy the cap, but make it more
vulnerable to external shearing forces
When the contents of the plaque become exposed
to the lumen, this can trigger thrombus
formation. This may cause complete
occlusion at the site of the plaque, but the
thrombus may also break off, and cause a
blockage somewhere else.

As the disease progresses, there are:

More plaques
A greater number of macrophages and t-
lymphocytes within the plaques
Release of more cytokines and growth factors
 (including IL-1 and IL-6 that are
chemotactic for macrophages
Elevated levels of antibodies to pathogens, such
as Chlamydia pneumoniae. Some people
aregue that such organisms (also including
cytomegalo virus, herpes and helicobacter)
have a causatory role (to initially start the
inflammation) although the evidence for
this is limited.
In coronary artery disease elevated levels of
inflammatory markers; such as CRP this
is an indicator of future acute events.
In transplanted hearts patients with transplanted
hearts may have a particularly quickly
progressing form of the disease in the
transplanted heart. The pathology of this
disease is also slightly different from that
of normal atheroma. This further supports
the theory that the disease is a result of an
immune problem. To minimize the risk all
heart transplant patients are given lipid
lowering drugs.
Monoclonal cells some people have likened the
plaques to small benign tumours because the
smooth muscle proliferation that is part of plaque
formation occurs from the proliferation of one cell;
the cell clones itself many times. In this way, the
growth factors can be thought of as mutagens,
although efforts to localise and identify a single
mutagen have been unsuccessful.
Disease Progresssion
Individual plaques even within the same patient will
progress at different rates. This rate is strongly
linked to mechanical stress the greater the stress,
the greater the proliferation.
Vulnerable plaques are those in a place of high
mechanical stress, with a lipid-rich core and a thin
fibrous cap.
Stable plaques have a thick fibrous cap, possibly
with calcification, and they have a small lipid pool,
and many collagenous cross-struts.
It is thought that lipid lowering therapy helps to
stabilise vulnerable plaques.
Thrombus formation on plaques
There are two different mechanisms. Either the
fibrous cap of the plaque itself gets a superficial
injury, and a thrombus forms on it, or, in more
advanced, unstable plaques, the fibrous cap
completely ruptures, and not only can some of the
contents escape, but blood can also enter the plaques,
forming a thrombus within the remaining cap of the
plaque.
The platelets then release serotonin and thromboxane
A2 and this causes vasoconstriction in the area
resulting in reduced bloodflow to the myocardium,
and ischaemic injury.
A bit about lipids
Lipoproteins
These are the form in which most lipids are
transported in the blood. They contain large
insoluble glycerides as well as cholesterol. They
have a superficial coating of phospholipids and
protein, which make the lipoproteins soluble. The
proteins coating these molecules will often bind to
specific cell membrane receptors, signalling the
uptake of that particular phospholipid.
There are four main types of lipoprotein:
Chylomicrons these consist of 95% triglyceride.
These carry absorbed lipids from the gut to
the liver.
VLDLs very low density lipoproteins these
carry triglycerides manufactured by the
liver, as well as small amounts of
phospholipid and cholesterol. The primary
function of these is to transport
triglycerides to peripheral tissues. These
are the largest of the -DLs.
LDLs low density lipoproteins these contain
very few triglycerides, a few more
lipoproteins, and lots and lots of
cholesterol! These are the bad
cholesterol. Their primary role is to
deliver cholesterol to peripheral tissue.
HDLs high density lipoproteins these are the
smallest of the -DLs. They have roughly
equal amounts of lipid and protein. The
lipids are mainly phospholipid and
cholesterol. These will transport excess
cholesterol back from peripheral tissue to
the liver to excretion in the bile! They are
good cholesterol.
Lifecycle
The liver will synthesise VLDLs. These will then be
released into the blood to deliver triglycerides to the
peripheral tissues. Lipoprotein Lipase will remove
lots of triglycerides from these lipoproteins, creating
intermediate density lipoproteins. These will then go
back to the liver, where they will have more of their
triglycerides removed, and lots of cholesterol added
to them. They will then be released as LDLs to
deliver cholesterol to peripheral tissue.
LDLs are absorbed by receptor mediated
endocytosis into peripheral cells. The amino acids
and cholesterol will be released into the cytoplasm.
Cholesterol not used by the cell will diffuse back out
of it. It will diffuse back into the blood, where it will
be taken up by HDLs and then taken back to the
liver. They will have their cholesterol removed for
excretion, and the HDLs will then continue in the
blood stream to pick up more cholesterol.
Prevention
Primary prevention aims to prevent the disease in the
first place, and involves:
Cessation of smoking
Control of BP
Weight reduction
Regular exercise
Dietary modifications
Diets that are low in saturated fat are
particularly associated with a
reduced risk of disease
Fatty acids found in fish also have
cardio-protective effects thus it
is recommended you eat at least
 2 portions of oily fish per week.
Secondary prevention aims to reduce the risk of
acute events in the presence of atheroma. It basically
involves the use of drugs, but you should remember
these drugs are intended for long term use after an
MI and are not involved in the acute treatment of a
recent MI.
Generally patients should be offered a combination
of the following 4 drugs:
ACE inhibitor
Aspirin
-blocker
Statin
COBRA-A mnemonic for Secondary Prevention in
ACS
C Clopidogrel anti-platelet agent
O Omacar Omega 3
B Bisoprolol -blocker
R Ramipril ACE-i
A Aspirin
A Atorvastatin very potent statin!
Delirium
Delirium is defined as an acute and fluctuating
disturbance in level of consciousness, attention and
global cognition.
Prompt treatment is required to avoid potential
brain damage.
The underlying mechanism is poorly understood,
but believed to involve neurotransmitter
abnormalities and inflammation.
Epidemiology
Delirium occurs most commonly in the elderly and
very young.
It is predicted that 10% of patients over 65 show
signs of delirium on admission to hospital.
Affects 15% of in-patients.
Signs and Symptoms
Reduced level of consciousness;
Psychiatric symptoms:
Disorientation (time/place/person);
Inattention;
Illusions/hallucinations;
Altered personality;
Mood disorders;
Speech disorders (slurred
speech/aphasic error/chaotic
pattern).
Lacking insight.
These symptoms fluctuate over the course of the
day and tend to be worse at night. Patients
may show signs of hyperactivity (typically
in withdrawal states) or lethargy (common
in hepatic encephalopathy).
Causes
CNS
Stroke, abscess, tumour, subdural haematoma
Drugs (or withdrawal)
Anticholinergics, antiemetics, antipsychotics,
corticosteroids, digoxin, levodopa, TCAs, opioids,
alcohol
Endocrine
Hyperparathyroidism, hyper/hypothyroidism
Infection/injury
Encephalitis, meningitis, pneumonia, sepsis, UTI,
burns, hypothermia
Metabolic
Acid-base disturbance, hepatic encephalopathy,
uraemia, hypo/hyperglycaemia, electrolyte
abnormalities, thiamine/vitamin B12 deficiency
Other
Post-operative states, other mental disorders, sleep
depravation
Diagnosis
A collateral history is needed to determine if the
changes in mental status are recent and the
patients normal level of functioning.
This would be different in a patient with
dementia, where the memory problems are
more likely to be chronic with a gradual
onset. Patients with dementia are also less
likely to have inattention or impaired level
of consciousness until the later stages of
disease.
Delirium Vs. dementia
Delirium
Sudden onset and fluctuating course over days -
weeks
Variation in level of consciousness
Impaired attention
Psychomotor changes
Dementia
Gradual onset, slowly progressive over months
years
Consciousness unimpaired
Attention preserved
Often Normal
It is also important to take a drug history (consider
any with CNS effects or new additions as a potential
cause) and alcohol history.A mini-mental state
examination is likely to show deficits in attention
(e.g. immediate repetition of 3 objects).Diagnostic
tools such as the Confusion Assessment Method
(CAM) states that the following features are
diagnostic:
Acute change in cognition which fluctuates
during the day;
Inattention;
Disturbance of consciousness;
Disorganised thinking.
The patient should be examined to look for potential Short term memory is more readily
sites of infection or any focal neurological signs affected, and confusion may
(suggesting a structural CNS disorder. often result. For example,
patients may buy many identical
items of food on separate
Treatment occasions, and then wonder why
their cupboards are full of these
items.
Treating the underlying cause or removing
Visuo-spatial problems patients may be easily
aggravating drugs is the principle treatment.
disorientated by unfamiliar surroundings
Environmental management: nurse patients in a quiet
Emotional disturbance
and well-lit room.
Loss of normal social behaviour
Minimise sensory deficits (check hearing
Language problems - Problems both
aids/glasses etc.)
understanding what is being said, and
Agitation can be managed with haloperidol (0.5-
naming objects
1.0mg PO) or lorazepam (0.5-1.0mg PO), however,
Concentration issues
they should be avoided as they may worsen or
Short attention span - Also unable to plan,
prolong delirium.
organise, or sequence activities
Behavioural changes - Delusions (persecutory),
Dementia
agitiation, aggression, wandering
Variable mood
Dementia is a progressive global decline cognitive
Poor sleep
function, without impairment of consciousness.
Restlessness
There are many causes of dementia, but the two most
Hallucinations
common are:
Apathy
Alzheimers disease (~40-50%)
Depression / euphoria - Severe depression is rare,
Diffuse vascular disease (aka multi-infarct
due to loss of insight
dementia) ~25%
In practice it is often difficult to differentiate the
In later stages of the disease, there may also be:
type of dementia present
Self-neglect
Change in personality which generally involves
Epidemiology
loss of inhibition
Very rare <55 years 5-10% prevalence in >65s 20%
Motor and sensory abnormalities
in >80 years 80% in >100 years
Seizures
Etiology
In very late stage disease there may be:
Alzheimers disease
The patient may become mute
Genetic predisposition
They may take little interest in anything
About 15% of cases are familial. These
Parkinsonianism
fall into to two categories:
Wasting
An early on-set autosomal dominant
Seizures
disease
Incontinence
A later onset type of disease, whose
These can be particularly distressing for relatives.
inheritance is variable
The most common gene mutation is
In Alzheimers disease the progression of the
apoE4 although mutation of this
symptoms is always gradual, but in diffuse vascular
gene does not necessarily mean
disease, the symptoms are more likely to occur
you will develop Alzheimers.
acutely. There is often a step-wise progression, as
Insulin resistance may be a predisposing factor
more small infarcts cause damage.
Female:Male ratio = 2:1
The majority of cases are sporadic
In cases of vascular dementia you may also find
No environmental factors have yet been proven
other vascular sings, for example:
Cholesterol, atherosclerosis and
Raised BP
inflammation are thought to be
Past strokes
implicated
Sudden onset / stepwise increase of symptoms
Symptoms
Diagnosis
General symptoms of Alzheimers and Vascular
dementia
The main symptom is usually confusion. Diagnosis
Memory loss this is usually the first symptom to
is usually clinical, and made with the help of the
appear
MMSE (Mini-Mental State Exam). Sometimes, IQ
The damage to brain tissue is not
tests (Wechsler Adult Intelligence Scale, may also be
universal, and thus some areas of
used). However, as confusion is often apparent, you
memory, notably
may have to perform many other tests to rule out
autobiographical and political
other differentials. The later on in life the
memory is stored in areas that
presentation, the less likely it is to be investigated.
are less often affected.
Always assume confusion is due to an acute illness The damage is variable, and can occur at different
until proven otherwise. This might mean, depending rates in different parts of the brain. Most
on the history, that you are going to have to do a lot likely to be affected are the Amygdala,
of blood tests: temporal cortex, and a few selected
Vitamin deficiencies - folate, B12, thiamine brainstem nuclei.
these could be primary deficiencies, or There is no change in the number of muscarinic
may be alcohol related. receptors, but the number of nicotinic
TFTs thyroid problems receptors is reduced.
FBC anaemia In very late stage disease there can be variable
U+Es renal failure / dehydration depletion of other neurotransmitters
LFTs carcinoma, cirrhosis, encephalopathy There may be the excess deposition of beta-
Glucose diabetes amyloid in the brain leading to the
CRP/ESR acute infection formation of beta-amyloid plaques.
Imaging of the brain CT/MRI this may be Vascular Dementia
used to exclude treatable space occupying This is the result of many small infarcts.
lesions, such as: Cerebrovascular disease has to be pretty advanced
Hydrocephalus for vascular dementia to become apparent, as large
Tumour parts of the cortex have to have been affected.
Subdural haematoma The disease will have a step-wise progression, so for
HOWEVER the most common instance, there will be no apparent change in the
abnormality seen on brain scan is condition, perhaps for many months, and then there
general atrophy. is a sudden drop in function. Infarcts are particularly
History likely to affect function if they damage the white
This is very important. Dementia is slowly matter.
progressive, and the symptoms may have started
years ago. It is highly likely you will need to speak As well as dementia, eventually there may be:
to relatives as well as to the patient themselves Pseudobulbar palsy
Shuffling gait with small steps marche a petits
Differentials for Confusion pas sometimes called atherosclerotic
Alcohol abuse Parkinsons disease.
Substance misuse There is often also a history if TIAs
Diabetes
Dementia Differentiating types of dementia
Delusion
Infection (UTI is particularly common) In the past, as long as B12 and TSH levels were
Dehydration normal, this was not necessary, however, these days,
Constipation there are specific treatments for Alzheimers. The
Acute confusional state types of dementia can be differentiated by a
Renal failure combination of; history, CT/MRI and
Tumours (meningioma) neuropsychological testing.
Subdural Haematoma
Parkinsons Making a will
Syphilis If the disease is discovered early enough, then it is
possible to make a will, and/or an advanced directive
Pathogenesis before the patient becomes to ill for one of these to
be accepted by law. The patient must be able to:
Alzheimers dse Understand and retain the information involved
Believe the information is true
The mean survival is 7 years. Most will survive Demonstrate they are able to weigh up the pros
between 2-7. and cons of an argument and come to a
Death usually results from bronchopneumonia decision based on these
There is a general atrophy of brain tissue, and the
weight of the brain is usually reduced. The
frontal and temporal lobes are particularly Management
affected. In all types of the disease, the management is only
There is often compensatory dilatation of the able to reduce the rate of progression of the disease.
ventricles, resulting in hydrocephalus. There is no cure.
The cerebellum and spinal cord are normal
There is a build up of amyloid plaques in the Alzheimers
brain. These are the breakdown products of Anticholinesterase drugs e.g. donepezil,
amyloid factors. galantamine, rivastigmine
There is also atrophy of cholinergic fibres that run Mechanism these drugs work by inhibiting
from the hippocampus to the cerebral cholesterases, and thus increasing
cortex. Initially there is a reduction on cholinergic transmission within the brain.
cholinergic transmission, and later a Unwanted effects anorexia, nausea, vomiting,
reduction in the synthesis of acetylcholine, diarrhoea, abdo pain, insomnia, confusion,
particularly in the cerebral cortex itself. agitation, headache
 Note that some of these effects are
similar to the clinical symptoms
of Alzheimers!
Clinical use will delay the decline of cognitive
impairment in 40% of patients probably
only by about 3-6 months.Probably more
effective in those without the gene apoE4.
Important to assess efficacy, and to stop
treatment in those who do not
respond.
Rapid decline is seen when the drug is
stopped in previously responsive
individuals
Have functional benefits that may
improve QOL.
NMDA receptor antagonists memantine
Mechanism an inhibitor of glutamate NMDA
receptors. It binds selectively, depending
on the voltage, and thus prevents
excitotoxicity, without altering gluatamtes
role in normal memory and learning.
It can be given WITH anticholinesterases
Unwanted effects:
Diarrhoea, insomnia, dizziness,
headache, hallucinations
Again, note that some of these are
similar to symptoms of
dementia!
Clinical use
Usually more well tolerated than
anticholinesterases, but probably
not as effective
May provide some benefit in cognitive
function, and may slow cognitive
decline
Not widely used
### Drug treatment should only be initiated in those
with a MMSE of >12! ###
This is mild to moderate dementiaNICE
guidelines state:
Treatment to be reviewed every 6 months
Dont treat if MMSE <12, as side effects of drug
likely to outweigh benefits
Treatment only to be administered and monitored
by specialist centres
Dont rely on MMSE as your only tool for aiding
prescribing, e.g. get collateral histories,
assess function and behaviour
Drug therapy is controversial
Drugs are expensive
Some trials have shown no benefit of the drugs
over placebos
In many cases it is thought that they at least allow
a few more months in a home care
environment
Vascular Dementia
Prevention
Reduction of vascular risk factors:
Aspirin or warfarin therapy aspirin often quoted
anecdotally, but there is actually now
evidence that the sort of low dose therapy
that many individuals take provides any
benefit against vascular dementia. Some at
risk patients may be put on warfarin
therapy.
Controlling BP use normal system (A-C-D
(+B)) for initiating bloop pressure
maintenance therapy
Anticholinesterases and memantine may have
some benefit in vascular dementia.
The burden of care
The course of the disease is often distressing for both
families and patient. Supportive care is necessary to
ensure the patient stays in a familiar home
environment as long as possible. Often the burden of
care falls to relatives.
Some recent evidence suggests that engaging in
cognitively taxing activities late on in life
can protect against dementia!
Vitamin E has shown in some instances to
protect against dementia
Other types of dementia
Lewy-body dementia (~15-25% of all cases of
dementia)
This is characterised by the presence of Lewy bodies
in the brainstem and neocortex. It can be
differentiated from other types of dementia by:
Symptoms fluctuate
Permanent memory dysfunction is not apparent in
the early stages
Associated with Parkinsonianism
Associated with depression and sleep disturbance
Causes visual hallucinations often frightening
and persecutory
There may be transient LOC
The drug rivastigmine may help to improve
symptoms
Fronto-temporal dementia
In this condition there is atrophy of the fronto-
temporal region, without the histology seen in
Alzheimers. it may be difficult to differentiate from
Alzheimers, but behavioural/personality change are
more likely to occur early on, and things like
memory and spatial awareness may be preserved for
longer. There is often massive disinhibition.
Rare causes
Whipples disease
Parkinsons disease
Alcohol/drug abuse
Huntingtons disease
CJD
HIV
Picks disease
Differentials for Dementia
Pseudodementia seen in mood disorders(e.g.
depression). Symptoms mimic depression
e.g. a decline in cognitive function, but
will resolve when the mood disorder is
treated. There is also often a history of
depression or other mental illness
Delerium
Mild/moderate learning difficulties