Vascular and Haematology Flashcards
(227 cards)
1
Q
What is an aneurysm?
A
a localised dilatation of an artery with a permanent diameter that is >1.5x its usual size
can be true or false
2
Q
True aneurysms
A
where the wall of the artery forms the aneurysm
Can be fusiform or saccular
3
Q
False aneurysms
A
aka pseudoaneurysm
where other surrounding tissues form the wall of the aneurysm
A small hole in the blood vessel wall allows blood to leak out and pool around the vessel.
4
Q
Fusiform aneurysm
A
where artery wall balloons out symmetrically
5
Q
Saccular aneurysm
A
where artery wall only balloons out on one side of the artery
6
Q
The pathophysiology of aneurysms
A
- weakening of the blood vessel wall => vessel struggles to contain the pressure of the blood pushing against its walls causing it to dilate.
- This leads to dilatation of blood vessel wall= ANEURYSM.
- When the diameter of the vessel lumen increases, the pressure flowing through it increases
- This leads to a positive feedback loop, of continuous bulging of arterial wall (which means aneurysm gets bigger)
7
Q
Where do aneurysms most commonly occur?
A
Most commonly in the aorta
~60% occur in abdominal aorta (AAA).
~40% occur in thoracic aorta.
8
Q
Where do AAAs most commonly occur?
A
95% of AAA occur below the point where the renal arteries branch out of the abdominal aorta
9
Q
What is the most common peripheral aneurysm?
A
popliteal artery aneurysm
~50% of people with these also have AAAs.
10
Q
Risk factors for aortic aneurysm
A
Similar to those for atherosclerosis:
- Hypertension
- History of smoking (ex- and current)
- Male and >60 years
- Diabetes
- High LDL levels
Other risk factors include:
- Genetic disorders (anything affecting connective tissue)
- Coarctation of aorta
- Pregnancy
- Coronary, cerebrovascular or peripheral arterial disease.
- COPD
- European family origin
- FH of AAA
11
Q
How does Marfan’s Syndrome impact blood vessels?
A
fibrillin and other elastic properties are impaired therefore causing weak blood vessel walls
12
Q
How does Ehler’s Danlos syndrome impact blood vessels?
A
ability to form collagen properties are disrupted
13
Q
Complications of an aneurysm
A
If intact - may have effects from an aneurysm compressing nearby structures (such as IVC).
Main concern is rupture
=> subarachnoid haemorrhage
=> aortic insufficiency
=> Blood flow into retroperitoneal space
14
Q
How can a thoracic aortic aneurysm cause aortic insufficiency?
A
if near the aortic valve, prevents the valve from shutting properly => backflow of blood into the left ventricle during diastole
15
Q
Clinical presentation of stable aneurysm
A
usually no S+S, found incidentally
16
Q
Clinical presentation of unstable/ruptured aneurysm
A
Severe pain (usually epigastric, radiating to back/groin) Hypotension Collapse, syncope Tachycardia Anaemia Shock Vomiting Expansile mass in abdomen
17
Q
Aneurysm - investigations
A
Abdominal Ultrasound scan – location and staging
CT Angiography – to create highly detailed image of aneurysm and surrounding structures
18
Q
Management of ruptured aneurysm
A
A-E assessment
Bloods - FBC, U&E, coagulation, G&S, XM
Fluids
Activate major haemorrhage protocol
Vascular Team
Imaging
Surgery as soon as stabilised
19
Q
Management of AAA
When is surgery indicated?
A
AAAs <5.5cm
=> regular imaging
=> modification of risk factors
=> Will probably eventually require surgery
Surgery if:
=> AAA >6cm (risk of rupture greatly increases at 6cm)
=> AAA expanding at <1cm/year
=> Symptomatic aneurysm
20
Q
Aneurysm surveillance
A
All men >66 years are screened for AAA.
=> involves having an abdominal USS done to measure size of the artery and check if there is any aneurysm
Anyone with increased risk also requires surveillance.
21
Q
Aortic dissection
A
The inner layer (intima) of the aorta tears due to a weakening of the wall.
This causes blood to surge through, causing the intima and media layers to separate.
This separation creates a new ‘false’ lumen, which can lead to rupture.
MEDICAL EMERGENCY
22
Q
What can a weakening in the aortic wall cause?
A
- aneurysm
2. dissection
23
Q
DeBakey Classification of aortic dissection
A
I. Intimal tear in the ascending aorta and descending aorta is also involved.
II. Only ascending aorta is involved.
III. Only descending aorta is involved.
24
Q
Standford Classification of aortic dissection
Which type is more common?
A
A. Ascending aorta is involved (same as DeBakey I & II)
B. Descending aorta is involved (same as DeBakey III)
Type A is more common than type B.
25
Complications of aortic dissection
1. Pericardial tamponade = FATAL.
2. External rupture and massive haemorrhage = FATAL.
3. compression of nearby vasculature such as subclavian or renal artery leading to hypoxia of upper limbs or kidneys respectively.
26
Risk factors for aortic dissection
```
Hypertension – main risk factor
Smoking
Hyperlipidaemia
Thoracic Aortic Aneurysm
Aortic Valve abnormalities
Family History of aortic dissection
Previous cardiac surgery
Trauma
Cocaine/Amphetamine Use
```
Connective Tissue Disease – e.g. Ehlers-Danlos or Marfan’s
27
Aortic Dissection - clinical features
Severe, very sudden onset chest pains.
=> Radiation to back/arm (can mimic MI)
=> Described as “tearing”
Weak pulses in downstream arteries
Difference in BP between right and left arm.
Hypotension
Shock – significant blood loss if rupture.
28
Aortic Dissection - Imaging
1. CXR – would show a widened mediastinum due to widened aorta
2. Transoesophageal Echo (TOE) – more sensitive for detecting false lumen.
3. CT Angio – will give a more detailed picture of the blood vessels and tear in the vessels
29
Stage 1 HTN
Clinic > 140/90 + Ambulatory BP average > 135/85
30
Stage 2 HTN
Clinic > 160/100 + Ambulatory BP average > 150/95
31
Severe HTN
> 180/110
32
Primary vs secondary HTN
1. Primary (essential)
=> no known cause, multifactorial
=> accounts for 85-95% of HTN cases in adults
2. Secondary hypertension
=> caused by an identifiable underlying condition
=> accounts for 5-15% of HTN cases in adults
33
Modifiable risk factors for essential HTN
```
Obesity
?excess salt
Lack of exercise
Stress
Smoking
Excess of Alcohol
Diabetes
```
34
Non-modifiable risk factors for essential HTN
```
Older age
FHx
Ethnicity
Male (if <65)
Female (if >65)
```
35
What are some causes of secondary HTN?
```
Pregnancy
Renal disease
Endocrine
Pharmacology
Coarctation of aorta
Obstructive sleep apnoea
```
36
What endocrine conditions can cause HTN?
```
Phaeochromocytoma
Conn's
Cushing's
Thyroid dysfunction
Acromegaly
Hyperparathyroidism
```
37
What drugs can cause HTN?
Alcohol, cocaine
COCP
anti-depressants
herbal remedies
38
Benign hypertension
= gradual elevation of blood pressure over years.
Leads to gradual hypertrophy of the muscular media in artery walls, reducing their capacity to expand and increasing their fragility
39
Malignant hypertension
= severe HTN, which develops over a short period of time
Leads to intimal proliferation, reducing luminal size and leading to cessation of blood flow through small vessels
=> signs of end organ damage
40
How can malignant HTN present?
May present with headache, confusion, visual disturbances, seizures (hypertensive encephalopathy)
41
Hypertensive Encephalopathy
= general brain dysfunction due to significantly high blood pressure
Sudden onset
Symptoms may include headache, vomiting, trouble with balance, and confusion
When it occurs in pregnancy it is known as eclampsia.
42
Management of malignant HTN
Need to reduce the BP
This needs to be done gradually to reduce the chance of stroke occuring
43
End organ damage due to HTN - cardiovascular
```
Left ventricular hypertrophy
=>
diastolic dysfunction
=>
congestive heart failure.
```
44
End organ damage due to HTN - renal
CKD, Renal failure and other renal problems.
45
End organ damage due to HTN - retinal
Hypertensive retinopathy (4 grades)
I Tortuous arteries with shiny walls (copper/silver wiring)
II A-V nipping – narrowing as arterioles cross veins
III Flame haemorrhages and cotton wool spots
IV Papilloedema
46
End organ damage due to HTN - cerebrovascular
Higher risk of infarction and haemorrhage.
| Can lead to vascular dementia, stroke, encephalopathy.
47
How can you assess for a secondary cause of HTN?
* 24-hour urinary metanephrines
* Cortisol
* Renin:aldosterone ratio
* Calcium
* Imaging of renal arteries
48
How can you assess for end organ damage in HTN?
* Urine dipstick (protein and blood)
* Renal function
* Renal ultrasound
* 12 lead ECG (LVH)
* Echo
* Fundoscopy
49
What are the two main superficial veins in the lower limb?
What is their course?
Great saphenous vein – ascends up medial side of leg and eventually drains into Femoral vein.
Small Saphenous vein – ascends at posterior aspect of leg and drains into Popliteal vein
50
What are the deep veins in the lower limb?
Anterior Tibial vein – formed from the dorsal venous arch (which drains the foot).
Posterior Tibial
Fibular vein
Popliteal vein – Anterior & posterior tibial and fibular vein unite to form this.
Femoral vein – when the popliteal vein enters the thigh.
51
What are varicose veins?
tortuous, dilated veins which occur due to incompetent venous valves causing further reflux of blood into superficial veins, causing them to become tortuous.
52
Risk factors for varicose veins?
* Increased age
* F>M
* Obesity
* Sedentary lifestyle
* Pregnancy
* Smoking
can also occur secondary to deep venous incompetence, due to:
- Previous DVT
- Raised systemic venous pressure – compression, arterio-venous fistula or severe tricuspid incompetence.
53
Varicose veins - clinical features
Enlarged, tortuous veins in leg
Pruritis of leg
Oedema – starts at ankle and may move up to calf.
Tiredness and aching/throbbing of the legs.
Yellow or red-brown skin pigmentation – RBC breakdown causing haemosiderin release.
54
Characteristics of venous ulcers
* Shallow
* Sloping, gradual outline.
* Generally minimal pain
* Often fairly large.
* Very wet, lots of exudate.
* Usually present at medial malleolus.
55
Complications of varicose veins
```
Venous ulcers
Thrombophlebitis
Excessive bleeding from minor trauma
Venous eczema
Lipodermatosclerosis
```
56
Lipodermatosclerosis
Localised, chronic inflammation and fibrosis of skin and subcutaneous tissues of the lower leg
57
Thombophlebitis
Inflammation and thrombosis of a superficial vein.
Painful and red veins
58
Varicose veins - investigations
Usually diagnosis is made on clinical history and examination.
Can do Duplex USS:
=> Look at structure of vein and valves
=> Look at blood flow through veins to check for retrograde flow
59
Varicose veins - management
Conservative - compression stockings
Surgical - Vein ablation or Complete removal of the vein
60
Use of compression stockings
may improve venous return
MUST rule out arterial disease first, otherwise these can block blood flow
61
Lymphoedema
a chronic swelling resulting from failure of lymphatic drainage.
i.e. when capillary filtration exceeds lymphatic drainage
62
What are the two types of lymphoedema?
1. Primary – occurs due to intrinsic genetic abnormality of lymphatic system.
2. Secondary – occurs when there is damage to otherwise normally functioning lymphatic system
63
Causes of secondary lymphoedema
* Cancer treatment, infection, trauma
* Venous oedema
* Oedema associated with immobility
* Obesity
* Heart Failure
* Oedema of advanced cancer or other advanced condition (e.g. liver disease)
64
Pathophysiology of VTE
Thrombi do not form through atheroma (as in arteries) but usually at the site of valves
Valves within veins protrude into the lumen and often become a site of turbulent flow leading to thrombus formation.
Once formed, a thrombus in a vein grows by successive adherence of platelets and fibrin
65
How can valves in veins be damaged?
trauma, stasis and occlusion.
66
What are the potential outcomes of thrombus formation in a vein
1. Lysis and resolution – if small, the thrombus resolves (fibrinolytic action e.g. plasmin)
2. Organisation – scar tissue obliterates lumen and blood flows through collateral vessels
3. Recanalisation – leads to scar formation and residual thrombus in lumen
4. Embolism – fragmentation of thrombus leads causes embolus to travel through the vessel.
67
what is the main cause of PE?
| How does this occur?
thrombosis in leg veins
thromboemboli travel up the IVC through the right atrium through the right ventricle and into the pulmonary artery
68
Virchow's triad for risk of thrombosis
1. Hypercoagulable state
2. Vessel wall injury
3. Stasis
69
What can contribute to a hypercoagulable state?
```
Oestrogen therapy (HRT, COCP)
Pregnancy and puerperium
Sepsis (and severe infections)
Malignancy
Nephrotic syndrome
Myeloproliferative disorders
Congestive heart disease
Inherited thrombophilia
Acquired thrombophilia
```
70
What can contribute to Vessel Wall Injury?
Trauma or surgery (particularly to lower limbs)
Indwelling venous catheters
Chemical irritation (e.g. chemotherapy)
71
What can contribute to stasis in vessels?
```
Age
Venous insufficiency
Varicose veins
Obesity (BMI >30)
Immobility (>3 days bed rest)
Long travel (>3-4h)
Hospitalisation
```
72
Risk factors for VTE:
Virchow’s Triad
Previous history of VTE
Family history of VTE
73
What are the MOST SIGNIFICANT risk factors for VTE?
```
Trauma to lower legs or pelvis
Major trauma
Hip or knee arthroplasty
Major general surgery
Spinal cord injury
```
74
VTE prophylaxis
VTE = recognised preventable complication of hospital treatment
A low-dose anticoagulant may be given to the patient during their hospital stay (commonly enoxaparin)
Compression stockings can be worn and early mobilisation of the patient encouraged
75
Diagnosing VTE - Hx
PC, HPC
PMHx - any prior VTE? Inflammatory disease/malignancy/thrombophilia?
PSHx - any recent surgeries? recent hospital admissions?
DHx - anything with oestrogen, any prior need for anticoagulation
Obstetric Hx - Pregnancy, Termination, Birth in past 6 weeks
FHx and SHx
Travel Hx - recent travel >3 hours
76
How does a DVT typically present?
Unilateral localised pain (usually throbbing) in one leg.
=> Uncommonly occurs in arm or bilateral legs.
Oedema of leg.
Calf swelling/tenderness
Redness and warmth of calf.
Distension of superficial veins
77
Well's score for ?DVT
= a diagnostic aid for determining the probability of a patient having DVT, which can then influence clinical decision making.
it is NOT a replacement for clinical reasoning
78
D-dimer test - sensitivity and speciticity
D-dimer assay measures a degradation product released by the lysis of a cross-linked fibrin clot.
=> elevated levels have a 99.5% sensitivity for the diagnosis.
=> there is VERY POOR SPECIFICITY and can be elevated in many clinical scenarios: older patients, sepsis, recent surgery, pregnancy, chronic inflammatory disease, malignancy, Covid-19.
79
When should a D-dimer test be done in ?VTE ?
D-Dimer is typically elevated in VTE
A negative D-dimer can exclude patients with a LOW probability of PE, but it is not useful in confirming diagnosis in high-risk patients.
D-dimer SHOULD NOT be done I those with a high clinical probability of VTE (as it will not change management).
80
What is an unprovoked DVT?
DVT when there are no major risk factors in the patient’s history.
81
May-Thurner Syndrome
also "Iliac vein compression Syndrome"
Compression of the left common iliac vein by the right common iliac artery.
This causes stasis in the vein and a DVT can form.
82
When would a doppler USS be requested in ?VTE
Request to Radiology in patients with:
- Wells score ≥2,
- High clinical suspicion
- A low Wells score but positive D-dimer
83
Saddle embolism
= a large embolus that straddles the bifurcation of the pulmonary trunk, extending into both the right and left pulmonary arteries
This commonly causes near-immediate death.
84
Minor PE
small peripheral vessels are blocked, and patients may be asymptomatic
85
Major PE
middle-sized pulmonary arteries are blocked, leading to breathlessness, pleuritic chest pain and haemoptysis
86
Massive PE
>60% of the pulmonary circulation is blocked (large or extensive thrombus; saddle PE; bilateral PE), leading to rapid cardiovascular collapse
87
Premonitory Embolus
= a massive PE following a minor PE
88
Clinical features of PE
```
Dyspnoea (may present as tachypnoea)
Pleuritic chest pain
Signs of DVT
Cough
Substernal chest pain
Fever
Haemoptysis
Syncope
Unilateral leg pain
```
```
Tachypnoea
Tachycardia
Reduced consciousness (GCS or AVPU)
Hypoxia
Hypotension
```
89
What 3 symptoms are patients with PE most likely to present with >1 of?
Dyspnoea (may present as tachypnoea)
Pleuritic chest pain
Signs of DVT
90
What day post-surgery is PE most likely?
~10 days post surgery
91
Diagnosis of PE
Well's score of PE
=> If score is low (0-4) and D-dimer is negative, then PE is unlikely.
=> If score is low (0-4), and D-dimer is positive, then CTPA.
=> If Score >4, PE is likely and CTPA is needed
92
Investigations for PE
```
FBC, U&E, clotting, D-dimer
ABG – type 1 RF
CXR – can be normal, or show dilated pulmonary arteries.
ECG – tachycardia, RBBB, RV strain
Echo – can confirm right heart strain.
```
CTPA – gold-standard
=> V/Q scan if unavailable to do CTPA, but less accurate if there is pre-existing lung disease
93
When would a patient not be able to have a CTPA?
if they cannot receive contrast - e.g. in (renal failure or anaphylactic contrast allergy
94
V/Q scan
Ventilation (V): shows how well air reaches the lung parenchyma.
Perfusion (Q): shows how well blood circulates in the lung parenchyma
V/Q mismatch = pulmonary emboli
95
ECG changes in PE
ECG changes are not specific or sensitive enough to diagnose PE - The ECG may be completely normal.
- Sinus tachycardia is the most common finding in PE.
Other changes:
- Dominant R wave in lead V1.
- T wave inversion in leads V1-V4 (right heart strain) or RBBB
- “Classical” ECG findings of SI QIII TIII indicates cor pumonale (rare finding).
96
What is the SI QIII TIII ECG sign?
| What does it indicate?
slurred S wave in lead I, with a Q wave and T wave inversion in III
indicates cor pumonale
97
Management of PE
1. Anticoagulation (oral or parenteral) in low-risk cases.
2. Thrombolysis (in patients with haemodynamic compromise) by IV infusion => high risk of bleeding.
3. Interventional radiology or endovascular techniques (often where thrombolysis fails or is contraindicated) – e.g. catheter assisted thrombolysis or thrombectomy.
98
What is important to remember in the management of PE?
patients with a PE can deteriorate – low risk can become sub-massive or massive.
Deterioration to massive could lead to heart failure and pulmonary hypertension
99
Peripheral Arterial Disease
narrowing or occlusion of peripheral arteries, affecting the blood supply to lower limbs.
100
How can chronic limb ischaemia present?
1. Intermittent claudication
2. Critical limb ischaemia
3. Chronic limb-threatening ischaemia
101
Intermittent claudication
= diminished circulation leads to pain in the lower limb on walking or exercise that is relieved by rest
(can also be caused by Cauda equine syndrome)
102
Critical limb ischaemia
= where circulation is so severely impaired that there is an imminent risk of limb loss
103
Chronic limb-threatening ischaemia
= represents end stage peripheral arterial disease where there is threatened limb viability relayed to several factors.
104
Acute Limb Ischaemia
a SUDDEN decrease in arterial limb perfusion, due to thrombotic or embolic causes
105
Where does atherosclerosis tend to occur?
where the vessels branch, curve or are irregular and where blood undergoes sudden changes in velocity and in direction of flow
Most commonly:
1. Circle of Willis
2. Carotid arteries
3. Popliteal arteries
4. Coronary arteries
5. Abdominal aorta
106
What is the resulting pathology of atherosclerosis?
Weakening of vessel wall – arterial aneurysm or dissection
Demand-supply mismatch – coronary heart disease, peripheral arterial disease, vascular dementia
Thrombosis – acute coronary syndromes, acute ischaemic stroke, acute limb ischaemia
Renovascular hypertension
107
Risk factors for atherosclerosis
```
Obesity
Physical inactivity
Hypertension
Smoking
Hypercholesterolaemia
Diabetes mellitus
Older age
```
108
Clinical features of atherosclerosis
Mostly asymptomatic until complications occur.
```
Signs may include:
• Xanthelasma
• Bruits (carotid or abdominal)
• Aortic aneurysm on palpation
• Poor peripheral pulses
```
109
Risk factors for chronic peripheral arterial disease
The same as for atherosclerosis:
- Obesity
- Physical inactivity
- HTN
- Smoking (one of the strongest risk factors for PAD)
- Hypercholesterolaemia
- Diabetes mellitus
- Particularly if poorly controlled.
- Older age
The more risk factors you have, the increased chance of getting peripheral vascular disease.
110
Causes of chronic PAD?
Atherosclerosis = most common cause
=> Narrowing of affected arteries limits blood flow to affected limb.
Vasculitis
=> Inflammation of artery causes stenosis and limits blood supply.
Fibromuscular dysplasia
=> Non-inflammatory artery wall thickening.
111
Why is intermittent Claudication only pain on exercise?
At rest, perfusion is adequate to meet O2 demands of the tissue.
During exercise, perfusion is not adequate enough to meet increased O2 demands of the tissue.
112
Classical features of intermittent Claudication
* Gripping, cramp-like pain (typically, in the calves)
* Induced by exercise
* Typically relieved by rest
* Usually predominates in one leg
* Reproducible
113
Where is the lesion causing calf claudication
typically a lesion causing narrowing of arteries in the thighs
114
Where is the lesion causing buttock claudication
a narrowing in the internal iliac arteries (or higher up)
If bilateral, both iliac arteries are compromised.
115
Leriche's Syndrome
absent femoral pulses;
intermittent claudication of the buttocks;
pale, cold legs;
impotence.
116
Cauda Equina Syndrome
= compression of the cauda equina in the spinal canal by central disc protrusion or canal stenosis.
117
How to differentiate Cauda Equina syndrome from arterial insufficiency
CAUDA EQUINA
Variable claudication distance
Pain often better when walking uphill, but worse downhill.
Pain disappears after 15-30 mins typically
LMN findings such as reduced reflexes but pulses present as normal
ARTERIAL INSUFFICIENCY
Fixed claudication distance
Pain exacerbated by walking uphill, but better downhill.
Pain disappears after 1-2 mins of rest typically
Absent peripheral pulses and reduced ABPI but no evidence of neurological findings.
118
Progression of Symptoms of PAD
1. At first, generally symptoms of exercise-induced claudication.
2. Claudication distance reduces (e.g. from 10 metres to 2 metres).
3. Ischaemic rest pain
4. Limb ischaemia – gangrene
119
What are the clinical features of ischaemic rest pain?
Generally worse at night due to reduced cardiac output and loss of gravity.
Improvement of symptoms if hang legs out of bed or sleep in a chair.
120
Clinical Signs of PAD
```
Pale, cold and hairless legs
Reduced Capillary refill
Arterial ulceration
Arterial bruits
Weak/absent pulses
```
121
Arterial Ulcers
* Deep
* Punched out
* Painful
* Small
* Present over toe joints, heel and lateral aspect of leg (malleolus commonly)
122
What are the two main symptoms of critical Limb Ischaemia?
1. Rest pain due to insufficient blood supply to the limbs.
| 2. Tissue loss – development of necrotic tissue which if infected becomes gangrene
123
PAD - Investigations
BEDSIDE TESTS:
Observations
ECG
BLOODS:
FBC, ESR, lipid levels, blood glucose.
Thrombophilia screen
IMAGING:
ABPI
Duplex USS
MRI/CT angiography (gold-standard)
124
What two things seen on an FBC can aggravate PAD?
anaemia
| polycythaemia
125
Ankle Brachial Pressure Index (ABPI)
= a method of quantifying severity of arterial disease in the legs
* Uses a doppler to measure the blood pressure in the brachial artery and the two arteries in the foot
* As arterial disease progresses in the legs, we get reduced flow through the arteries and hence the blood pressure falls
* This is commonly measured in patients with ulcers to help differentiate the type of ulcer.
126
Management of PAD
ABPI >0.6 - conservative management
ABPI <0.6 or highly symptomatic - invasive measures
127
What are the causes of acute limb ischaemia?
Thrombotic – Blood clot forms around a ruptured atherosclerotic plaque (most common)
Embolic – Dislodged blood clot, usually cardiac in origin.
Trauma
128
Embolic vs thrombotic acute limb ischaemia
Embolic is more sudden
Embolic often more severe due to lack of collateral circulation
129
What is the prognosis for acute limb ischaemia?
Mortality rate = 15-20%
Limb prognosis is linked to severity of arterial disease, acute onset and how rapidly reperfusion is achieved
130
6P's of acute limb ischaemia
Pain — constantly present and persistent.
Pulseless — ankle pulses are always absent.
Pallor (or cyanosis or mottling).
Power loss/paralysis due to nerve ischaemia
Paraesthesia or reduced sensation or numbness.
Perishingly cold.
131
Which symptoms suggest a threatened acute ischaemic limb?
Paralysis and paraesthesia
also pain on passive movement or squeezing the calf.
132
Irreversible limb ischaemia
appears as mottled, non-blanching appearance with hard woody muscles and skin blistering
requires urgent amputation or taking a palliative approach.
133
DDx for acute limb ischaemia
Chronic peripheral neuropathy
=> pulses should be present and Temp normal
Compartment syndrome
=> muscles will be tense
DVT
=> red, hot, swollen calf
134
Acute limb ischaemia - management
SURGICAL EMERGENCY
Urgent admission
Heparinisation
Surgical management depends on cause
135
Reperfusion injury
Inflammation and oxidative damage when blood flow is restored to a tissue after long period of anoxia.
Products of cell death are released can result in rhabdomyolysis, cardiac dysrhythmia, AKI, multiorgan failure and DIC.
Can lead to oedema and compartment syndrome due to increased compartmental pressure.
136
What are the main vasospastic disorders?
Raynaud’s syndrome
Acrocyanosis
Livedo reticularis.
137
What is the colour change involved in Raynaud's disease/phenomenon?
1. Pale (ischaemia)
2. Blue (cyanosis)
3. Red (reactive hyperaemia)
As the fingers return to normal there may be numbness, burning sensation or severe pain
138
What is Raynaud's disease/phenomenon?
paroxysmal vasospastic and subsequent vasodilatory chain of events affecting small peripheral arterioles
attacks usually <45mins but can last for hours
139
What can cause Raynaud's?
More common in women
Precipitated by the cold and emotion/stress
Sometimes other triggers – beta-blockers, injuries/trauma, extended use of digits, smoking.
Usually affects hands (but usually the thumb is spared) and feet.
140
Primary vs secondary Raynaud's
Primary is more likely to present as a younger patient, female with a genetic component with no features of underlying disease.
Secondary is more likely to present as an older patient, with more severe symptoms (digital scars, ulceration or gangrene and nail changes)
141
What is anaemia?
Anaemia = decreased haemoglobin in the blood, such that there is inadequate oxygen delivery to tissues
Typically Hb <135 g/L in men; Hb <115 g/L in women.
142
Symptoms of Anaemia
* Tired
* Short of breath – (normal oxygen saturations)
* Lightheaded/feeling faint
* Pounding heart/palpitations
* Pounding in ears
* Pale
143
RBC lifecycle
Erythropoiesis (production of red blood cells) occurs in the bone marrow.
=> Stimulated by erythropoietin (EPO) produced by the kidneys
Average RBC lifespan is 120 days.
=> The ageing RBC are removed from the circulation.
This process normally occurs at the same rate of production by erythropoiesis, balancing the total circulating red blood cell count hence patients have a stable Hb
144
When can patients become anaemic?
1. Not making enough RBCs
=> Reduced erythropoiesis (or haematopoiesis)
2. Losing or breaking down RBCs too quickly.
=> Bleeding
=> Haemolysis
145
What are some causes of reduced erythropoeisis?
```
Haematinic deficiency
Bone marrow disorders
Myelosuppressive drugs
CKD
Chronic disease/inflammation
Endocrine dysfunction
```
146
What does the MCV and MCH represent?
MCV - the size of each RBC
| MCH - the amount of haemoglobin in each RBC
147
what is microcytic anaemia and what are some causes?
= low Hb and MCV
Iron Deficiency
Thalassaemia
Anaemia of chronic disease
Lead poisoning
148
what is normocytic anaemia and what are some causes?
= low Hb and normal MCV
```
Acute blood loss
Anaemia of chronic disease
Haemolysis
Combined deficiency (e.g. iron and B12 deficient)
Bone marrow disorders
```
149
what is macrocytic anaemia and what are some causes?
= low Hb and high MCV
```
B12 deficiency
Folate deficiency
Myelodysplasia
Alcohol excess
Haemolysis
Other defects of DNA synthesis (e.g. chemotherapy)
Severe hypothyroidism
```
150
Investigations for anaemia
* B12, folate, ferritin, transferrin saturation
* Blood film
* Reticulocyte count
* LDH (raised in haemolysis), haptoglobin (low), bilirubin (high)
* Immunoglobulins, serum free light chains
* Review medication chart
151
Iron storage
Iron is absorbed in the duodenum - promoted by gastric HCl.
Ionized iron is toxic so nearly all iron in the body is bound to protein - E.g. Hb, myoglobin, transferrin, ferritin, haemosiderin
Iron is stored in 2 forms – ferritin and haemosiderin
=> Ferritin is soluble, haemosiderin insoluble.
Iron continuously circulates in plasma bound to transferrin
152
Causes of iron deficiency
Inadequate intake.
Increased requirements – e.g. pregnancy.
Malabsorption – e.g. coeliac, gastrectomy.
Chronic haemorrhage – e.g. hookworm, menorrhagia, GI tract bleed.
153
Diagnosing IDA
1. MCV low
2. Blood film - hypochromic, microcytic, pencil cells
3. A gold-standard would be iron stain on bone marrow
4. Serum ferritin – roughly correlates with the amount of iron stored in the tissues.
=> Ferritin levels increase in inflammatory conditions (e.g. acute/chronic infection, malignancy) Therefore, can be iron deficient with normal or high ferritin levels.
5. Transferrin saturation (%)
=> If iron levels are low, less transferrin has iron bound to it.
=> Transferrin saturation is a marker of iron status.
154
Hx to identify cause of iron deficiency anaemia
diet
recent blood loss - e.g. menorrhagia
Systems review – any PV/PR bleeding, weight loss, bowels.
155
Management of IDA
Address the underlying cause as appropriate.
Oral ferrous sulphate 200mg
Advise dietary increase in dark green vegetables, fortified bread/cereals, lean red meat and prunes/raisins.
If ferrous sulphate not tolerated, consider switch to ferrous gluconate.
Monitor for improvement in symptoms and blood parameters after one month.
=> Should be a 20 g/L increase in Hb (if bleeding has stopped)
Treatment should be continued for 3 months after blood parameters return to normal, to replenish stores.
156
Side effects of iron supplementation
GI-related – cramping, bloating, nausea, vomiting, constipation, black stools
157
B12 Absorption
* B12 in food is mainly bound to protein – pepsin in the stomach releases B12 from protein.
* B12 binds to intrinsic factor, produced by gastric parietal cells in the stomach.
• Intrinsic factor transports B12 into the epithelial cells of the distal half of small intestine.
=> B12 absorbed in the ileum.
• The body generally has stores of B12 for 2+ years
158
what foods generally contain vitamin B12?
Generally animal sources – meat, fish, eggs, milk
159
What neurological symptoms can B12 deficiency cause?
peripheral neuropathy,
| subacute combined degeneration of the cord
160
Causes of B12 deficiency
• Inadequate intake
• Inadequate secretion of intrinsic factor
=> Pernicious anaemia
=> Gastrectomy
* Malabsorption - Crohns, ileal resection
* B12 levels will measure low if patient is taking OCP or HRT, even if there are normal levels.
161
What is pernicious anaemia?
Antibodies against intrinsic factor and/or gastric parietal cells
162
How does B12/folate deficiency cause macrocytic anaemia?
B12 deficiency causes macrocytic anaemia, as B12 acts as a co-enzyme for the conversion of folate (B9) to activated folate.
Activated folate is required for DNA synthesis – so B12/folate deficiencies lead to DNA synthesis malfunctions.
DNA fails to “stop” erythrocyte development, leading to very large cells.
Large cells are eventually trapped and destroyed in the reticulo-endothelial system.
163
diagnosis - B12 deficiency anaemia
* Raised MCV
* Blood film – oval macrocytes, hypersegmented neutrophils, tear drop cells
* Low B12
* Test for anti-parietal cell or anti-IF antibodies.
* Schilling Test – distinguishes between pernicious anaemia and small bowel disease
164
Folate deficiency
Folate is absorbed in the duodenum and jejunum. The body generally has folate stores for ~5-6 months
- Inadequate intake
=> Poor diet, alcohol excess (impairs utilisation), anorexia.
- Increased requirements
=> Pregnancy, haemolytic anaemia, lactation, prematurity, malignancy.
- Malabsorption
=> Coeliac disease, jejunal resection
- Anti-folate drugs
=> Trimethoprim, methotrexate, anti-convulsants.
165
diagnosis - folate deficiency anaemia
* Raised MCV
* Blood film – macrocytes, hypersegmented neutrophils (i.e. same picture as B12 deficiency).
• Reduced folate – can measure serum or red cell
=> Serum folate levels are readily affected by a short period of negative folate balance
=> Red cell folate often a more reliable assessment of folate stores
166
Management of folate deficiency
Folic acid 5mg daily – at least 3 months
Treat underlying cause
Borderline/slightly low B12 and/or folate doesn't cause significant anaemia
167
What type of antibody do people have against ABO antigens?
IgM antibodies against whichever antigen they do not express on their RBCs.
168
What type of antibody do people have against rhesus D antigens?
If a rhesus negative individual is exposed to rhesus positive blood, they can develop IgG antibodies directed against the rhesus D antigen
If exposed to rhesus positive blood products again, there will be haemolysis
169
What is a mismatched transfusion?
= when a patient receives a transfusion from an incompatible blood group
170
What occurs in cross-matching for transfusion?
* The patient’s pre-transfusion blood sample is tested to determine the ABO and RhD groups
* The patient’s plasma is screened for the presence of antibodies against other non-ABO red cell antigens which could still be capable of causing a haemolytic transfusion reaction.
* Antibody screening is performed using a panel of red cells that contains examples of the clinically important blood group antigens.
* Once the blood group and screen has been performed, compatible blood units can be selected
171
Transfusion Reactions
Anti-A and/or anti-B in the recipient’s plasma binds to the transfused cells and activates the complement pathway.
This leads to destruction of the transfused red cells (intravascular haemolysis) and the release of inflammatory cytokines that can cause:
* Shock
* Renal failure
* Disseminated intravascular coagulation (DIC).
* Death
172
what is the role of WBCs?
protection against invading microorganisms/immune attack
173
differentiation of blood cells
Blood cells are all derived from a self-renewing pluripotent stem cell.
Differentiation into committed MYELOID or LYMPHOID progenitors which then mature into all the mature blood cells
174
What is the purpose of neutrophils?
Respond chemotactically to various stimuli
=> complement, lymphokines and bacterial membrane components
Perform phagocytosis of foreign particles and microbes
175
What can cause neutrophilia?
```
Infection/inflammation (bacterial or fungal)
Neoplasia
Bleeding
Infarction (including MI)
Smoking
Burns
Drugs (glucocorticoids)
```
176
What can cause neutropenia?
```
Viral or malaria infection
Drugs (e.g. carbimazole, chemotherapy)
B12/folate deficiency
Autoimmune
Cyclical neutropenia
Haematological malignancy
Hereditary
```
177
What is important to know in neutropenia?
```
Is the patient unwell?
Any previous normal counts?
Ethnicity?
Any other cytopenia?
Is the patient on chemotherapy?
Other DHx?
```
178
Severity of neutropenia?
Normal = 2.0 - 8.0
* Mild (1.0-1.7), functionally normal
* Moderate (0.5-1.0)
* Severe (<0.5) – RISK OF INFECTION
179
Neutropenic sepsis
fever >38*C and neutrophils <1.0
a medical emergency requiring urgent hospital admission and IV broad spectrum antibiotics within 1 hour.
180
What are the major cell types of lymphocyte?
1. T lymphocytes – 80% (derived from thymus, circulate in blood)
2. B lymphocytes – 20% (mainly in the lymph nodes, few in blood)
3. Natural Killer cells (large, granular lymphocytes)
181
T-lymphocytes
Involved in cell-mediated immunity and regulating go B-lymphocytes
182
B-lymphocytes
Production and secretion of antibodies
Participation in “immunological memory”
183
Primary causes of lymphocytosis
Lymphoid malignancies
- Chronic lymphocytic leukaemia
- Lymphomas
- Monoclinal B lymphocytosis
184
Reactive causes of lymphocytosis
Viral (EBV, CMV, HSV, VZV)
Whooping cough
TB
Stress – septic shock, trauma, MI, drug-induced
185
Chronic causes of lymphocytosis
```
Cigarette smoking
Autoimmune disorder
Chronic inflammation
Sarcoid
Raised BMI/metabolic syndrome.
```
186
What do monocytes do?
Phagocytosis – ingest and destroy fungi, bacteria and damaged or degenerated cell
Stimulate the immune response by presenting the products of phagocytosis to lymphocytes
Attract neutrophils to the damaged site by secreting chemical attractants.
Aid in maintenance of blood vessels
187
Causes of monocytosis
Atypical Infections – e.g. TB
Inflammation
Autoimmune diseases
Haematological malignancies – e.g. chronic myelomonocytic leukaemia (CMML)
188
Causes of eosinophilia
* Parasitic infections
* Allergy
* Asthma
* Drugs
* Skin disorders – e.g. eczema
* Haematological malignancies – e.g. Hodgkin’s disease, CML
189
Causes of basophilia
very rare - usually only seen in chronic myeloid leukaemia
190
What do basophils do?
Secretes substances during an allergic reaction
Secretes large amounts of heparin (anticoagulant)
Secretes histamine, which participates in constriction of the blood vessels, bronchioles and intestines
191
What is leukaemia and what is its incidence?
= Cancer of the WBCs
Most common of childhood cancers but seen most commonly in age >50
Increasing incidence (aging population)
192
what is the most common leukaemia in children?
Acute lymphoblastic leukaemia (ALL)
193
Acute leukaemias
= no differentiation, primitive “blast” cells
Acute myeloid leukaemia (AML)
Acute lymphoblastic leukaemia (ALL)
Acute bi-phenotypic leukaemia
194
Chronic leukaemias
= normal differentiation into mature white cells
Chronic myeloid leukaemia (CML)
Chronic lymphoblastic leukaemia (CLL)
195
Symptoms of leukaemia
symptoms resulting from:
1. bone marrow failure
2. organ infiltration with leukaemic cells
3. both.
The time course is variable
=> Some patients, particularly younger ones, present with acute symptoms over a few days to 1-2 weeks.
=> Others have a longer course, with fatigue or other symptoms lasting from weeks to months.
196
What symptoms indicate bone marrow failure?
anaemia (tiredness / lethargy/ SOB),
neutropenia (infection),
thrombocytopenia (bruising and petechiae).
197
Signs of leukaemia
* Anaemia
* Low OR High white cell count
* Thrombocytopenia
* Pancytopenia
* May be circulating ‘blast’ cells seen on blood film
198
What is Westermark sign?
on CXR
=> enlarged pulmonary artery
=> distally to this there are fewer lung markings
199
“Tennis ball sign” in aorta
indicates tear in the intima
= aortic dissection
200
What is haemostasis?
= the process by which the body stops bleeding if there is injury to a blood vessel
201
What is the role of primary haemostasis?
Begins immediately after endothelial disruption
vascular contraction, platelet adhesion and aggregation, and formation of a soft haemostatic plug
202
What is the role of secondary haemostasis?
the process of stabilisation of the soft haemostatic plug through a complex interaction between platelet membrane, enzymes and coagulation factors
203
Process of primary haemostasis
* Injury causes vasoconstriction (slows blood flow, enhancing platelet adhesion and activation) and exposure of collagen (trigger for platelet activation)
* Von Willebrand factor attaches to the sub-endothelium. Glycoproteins on the platelet surface adhere to vWF.
* Platelets collect across injured surface. Platelets are activated by contact with collagen.
* Collagen-activated platelet membranes expose receptors which bind circulating fibrinogen.
* Aggregation of platelets and fibrinogen build up to form a soft haemostatic plug
204
What are some important molecules involved in primary haemostasis?
```
Thromboxane A2
Arachidonic acid
ADP
vWF
GPIb, GPIIb/IIIa
```
205
What are the clinical features of impaired primary haemostasis?
```
1. Mucocutaneous bleeding
• Bruising
• Epistaxis
• Gum bleeding
• Menorrhagia
```
2. Intra-op or immediate post-op bleeding
206
What are the causes of impaired primary haemostasis?
Reduced platelet number (i.e. thrombocytopenia)
Impaired platelet function - congenital or acquired
Reduced amount/impaired function of vWF (i.e. von Willebrand disease)
207
What is coagulation factor I?
Fibrinogen
208
What is coagulation factor II?
Prothrombin
209
What is coagulation factor IIa?
thrombin
210
Vitamin K deficiency - causes and consequence
can be caused by:
- Malabsorptive conditions (K = fat soluble vitamin)
- Cholestatic jaundice (no bile salts)
- Antibiotics (gut flora disturbances)
leads to a reduction in activated factors, which will lead to an increased PT and haemorrhage
211
Which factors are dependent on vitamin K?
II, VII, IX, X
212
What are the causes of thrombocytopenia?
```
INCREASED PLATELET DESTRUCTION
Sepsis/inflammation
DIC
Thrombotic thrombocytopenic purpura
Autoimmune, Alloimmune
Drug-induced
```
```
DECREASED PLATELET PRODUCTION
Alcohol
Cytotoxic drugs
Bone marrow failure
Infections
```
OTHER
Hypersplenism
Haemodilution
213
Which drugs can cause increased platelet destruction?
heparin, antibiotics, antimalarials, NSAIDs
214
What are anti platelet drugs?
Aspirin
Clopidogrel
Ticagrelor
Abciximab or Eptifibatide
215
Coagulation factors
Mostly produced in the liver.
Factors circulate in an inactive form until the coagulation cascade is initiated
When active, these factors mainly act as serine proteases to activate other factors
216
What are the pathways to activate the coagulation cascade?
1. intrinsic pathway (damaged endothelial surface)
| 2. extrinsic pathway (trauma)
217
What does the coagulation cascade ultimately result in?
The conversion of fibrinogen to fibrin
218
What are the physiological inhibitors of the coagulation cascade?
Anti-thrombin III – serine protease inhibitor
Activated protein C – activated by thrombin and acts with the co-factor protein S
=> destroys factor V and VIII, reducing further thrombin generation and inhibits stabilisation of the fibrin clot
219
What are the clinical features of impaired secondary haemostasis?
Haemarthrosis
Muscular/soft tissue bleeding
Extensive bruising
Delayed post-op bleeding and poor wound healing (rather than immediate effects)
220
Causes of impaired secondary haemostasis
Reduced coagulation factors
=> congenital (haemophilia A or B)
=> acquired - anticoagulation, liver dysfunction, DIC, acquired haemophilia
221
Coagulation tests - primary haemostasis
FBC and Blood Film – platelet number and morphology
Platelet function tests and complex platelet test by specialist
Von Willebrand factor assays
222
Coagulation tests - secondary haemostasis
Clotting Screen
- Prothrombin time (PT) = “extrinsic”
- Activated partial thromboplastin time (APTT) = “intrinsic”
Mixing studies – patient plasma mixed with normal fresh frozen plasma.
=> If this fully corrects then factor deficiency
=> If not then there is presence of inhibitor
Clauss fibrinogen test
Clotting factor assays – measure individual factor level
223
Process of PT/APTT
1. Citrated blood sample (i.e. blue bottle) Citrate removes Calcium.
2. Samples is centrifuged to remove platelets (creating Platelet Poor Plasma)
3. Platelet poor plasma is mixed with an activator and calcium
=> PT (extrinsic) = add Tissue Factor and Calcium
=> APTT (intrinsic) = add Kaolin, Phospholipids and Calcium
4. The time to clot formation is calculated.
224
What is DIC?
= systemic activation of coagulation pathways leading to extensive intravascular coagulation and fibrin clot development
Thrombotic occlusion of the arterial microvasculature
Simultaneous depletion of clotting factors and consumption of platelets leads to haemorrhage.
Eventually organ failure develops.
225
Haemophilia A vs. B
```
A = factor VIII
B = factor IX
```
A is more common than B, as the factor VIII gene is larger
226
How does haemophilia affect more severely?
Both X-linked recessive disorders
Affects males more severely, women can be affected severely but tend to be carriers and only mildly affected.
227
Severity of haemophilia
Based on the amount of the factor present, compared to normal
Severe <1%
Moderate 1-5%
Mild >5%
Severe => spontaneous bleeding
Mild => just excessive bleeding if injured
