Overview of disorders of blood vessels:
Arteries:
Artherosclerosis normally effect elastic and muscular arteries. Hypertension normally affect resistant (small) arteries. Tunica intima. Tunica media (smooth muscle). Tunica adventitia (nerves and vasa vasorum). Elastic arteries, elastic fibers in media (aorta and major branches – subclavian, carotids, iliac). Muscular, smooth muscle in media. Most inflammation cause WBC exudation at the post-capillary venule because it doesn’t have loose CT.
Vascular anomalies
Arteriovenous fistula – direct connection between arteries and veins, bypassing the capillaries. Put extra strain on the heart because larger volume needs to be pumped.
Fibromuscular dysplasia – focal irregular thickening of medium and large arteries, can occur at any age. Angioplasty show string of beads appearance.
Endothelium
Activation by cytokines, bacteria toxins, advanced glycation end-products, hypoxia, results in vasoconstriction and vasodilation. Relaxing factor NO and contraction factor endothelin. Endothelium dysfunction – change in endothelial phenotype.
All injuries result in tunica intimal thickening by proliferation of smooth muscle, which are special muscle cells that are mobile and have biosynthetic capability.
Hypertension
Essential hypertension 95% idiopathic. Reduced sodium excretion – however at higher pressure, a new steady state is achieved by pressure natriuresis.
Secondary hypertension from renal or adrenal disease. Most common hyperaldosteronism. Renovascular hypertension pathogenesis – renal artery stenosis reduce the volume and pressure of afferent arteriole. This activate renin angiotensin system causing rise in angiotensin II (systemic vasoconstriction) and aldosterone (increase H2O and Na+ retention). Gene mutation of enzyme that break down aldosterone, and Liddle syndrome where there is gain of function of Na+ channel.
Malignant hypertension 200/120 mmHg.
Two vascular pathology of muscular artery. Hyaline arteriolosclerosis – caused by protein exudation (hyalinized) and smooth muscle cells proliferation. Nephrosclerosis impair renal supply. Hyperplastic arteriolosclerosis – concentric laminated thickening of the walls (like onion skin) with luminal narrowing, due to multiplication of basement membrane.
Veins:
Varicose Vein – dilation and tortuous vessels. Stasis dermatitis occur because of extravasated red cells. Esophageal varices – due to embolism of portal vein and dilatation of the portosystemic shunts. Hemorrhoids occur in pregnancy due to dilatation of anorectal junction.
Thrombophlebitis – can occur in varies organs – the dural sinuses, portal vein and pelvic venous plexus. Tumors produce procoagulant factors which cause migratory thrombophlebitis, where it appear in one sit then disappear to another. Deep vein thrombosis – pain, swelling, redness and engorged veins. Immobilization => stasis and thrombus formation. Often associate with PE so any clot above knee needs to be put on anticoagulation medication.
Superior vena cava and inferior vena cava syndrome are due to obstruction. Often by neoplasm that grow in within veins such as hepatocellular and renal cell carcinoma.
Lymph:
Lymphangitis acute inflammation most commonly by bacteria. Red painful subcutaneous streak and enlargement of draining lymph node (lymphadenitis). Primary congenital blockage. Secondary – tumor, radiation. Chronic lead to persistent edema and deposition of interstitial CT that lead to orange peel appearance of skin. Rupture cause accumulations of lymphs leading to chylous ascities, chylothorax and chylopericardium.
Overview of Ulcers:
Venous ulcers – due to increase venous pressure and exudation of fibrinogen. Perivascular fibrin deposition and reduce O2 supply. Commonly found above ankles. Lipodermatosclerosis – induration, redbrown pigmentation (hemosiderin) and inflammation. Can be painful. Manage: high compression bandaging and leg elevation. Doppler to exclude arterial diseases. Skin graft prevent recurrence. Most heal within 6 months.
Arterial – higher up the legs, associated with claudication and PVD. Keep the ulcer clean and vascular reconstruction.
Neuropathic – Pressure area such as metatarsal head due to repeated trauma.
Pressure – immobile patients.
Skin:
BCC – pearly, telangiectasia. Nodular, superficial, ulcerated, basosquamous, sclerosing and pigmented.
SCC – ulcerated with indurated and keratotic skin due to squamous cells hyperplasia.
Melanoma – ABCDE, asymmetry, boarder, colour, diameter above 5cm, elevation.
Raynaud phenomenon:
Red (reactive capillary dilation), white (ischemia) and blue (cyanosis) appearance. Benign uncommon to cause gangrene. Primary – hyper reaction to cold or emotion. Secondary – autoimmune diseases, asymmetrical and progressively worsen, it maybe the first manifestation for underlying immune-mediated vasculitis.
Pulmonary Embolism – etiology, pathophysiology, clinical features and complications
- etiology ® risk factors include; certain medications, immobilization for a long period of time, fractures, severe trauma, surgery, congestive heart failure, oral contraceptive pill with high estrogen content, primary disorders of hypercoagulability.
- Pathophysiology ® PE occurs when a blood clot gets wedged into an artery in your lungs. These blood clots most commonly come from the deep veins in your legs (deep vein thrombosis). In the lungs it decreases blood flow, causing a decrease in oxygenated blood thus you get symptoms of shortness of breath.
- Clinical features ® pulmonary hypertension, chest pain, SOB, acute right-sided heart failure
- Complications ® cardiac arrest and sudden death, shock, abnormal heart rhythms, death of part of the lung (pulmonary infarction), pleural effusion, paradoxical embolism, pulmonary hypertension.
- Varicose veins – pathology and clinical features
- Varicose veins are the most common cause of venous ulcers (wet, oozing, dermatitis, gaiter region)
- Dilated, tortuous superficial veins due to reversal of venous flow
- Can be congenital or acquired (more common)
- Veins become dilated due to increased pressure (venous HTN) and weak walls (note: superficial veins have no muscle/fascia to support them and therefore dilate when overloaded)
- Normally: skeletal muscle pump helps guide venous blood back to the heart and the valves stop backflow of blood
- therefore if the skeletal muscle pump is not being engaged (long periods of immobility – travel/depression/hospitalization) the venous blood can pool increasing pressure in the superficial veins of the lower limbs
- also: congenital valve defects can lead to inadequate forward venous flow to the heart à blood falls back into the superficial vessels
- complications: dermatitis, skin ulcers, superficial thrombophlebitis (painful!)
- Important: rare for varicose veins to cause DVT because of flow reversal (unlikely for thrombus to go backwards from superficial veins to deep veins)
- Risk factors: obesity (increased intra-abdo pressure = decreased venous return) , job that requires long periods of standing (gravity – venous pooling)
- Clinical features:
- Large tortuous veins
- Mild swelling of ankles/feet
- Painful/achy or heavy legs
- Pain worse after standing/sitting for a long time
- If complications: may see ulcers, venous stasis dermatitis (itching) and patient may have sore/red/swollen/hot area of skin over veins affected by superficial thrombophlebitis
- Revision: skin malignancies – SCC, BCC and melanoma à gross and microscopic features
Gross features
Microscopy
SCC
arise from pre-existing solar keratoses
indurated nodules with keratotic surface
highly variable appearance
no telangiectasia, no peary edge
often a crusted surface, rolled edge and ulceration
note: squamous cell carcinoma in any tissue looks similar
keratin pearl aggregate formations – concentric layers of abnormal squamous cells
appear pink
BCC
arise in normal skin
telangiectasia
pearly appearance
different types:
- Nodular
- Superficial
- Ulcerative
- Morphoeic
- Pigmented
- recurrent
abnormal proliferation of basal skin cells
Melanoma
ABCDE -
asymmetric – in pigment, shape
border is irregular
colour usually pigmented (note: amelanotic can occur)
diameter greater than 6mm
can occur in areas not exposed to sun
evolve over time (depends on type)
EFG – nodular melanoma
E – elevated above the skin surface
F – firm to touch
G – growing
different types:
- Superficial spreading
- Lentigo maligna melanoma
- Acral lentiginous/sub-ungual melanoma
- Amelanotic
- Desmoplastic melanoma
- Nodular melanoma (most dangerous)
excess proliferation of large bluish cells producing pigment = melanocyte cells
Vasculitis – Overview of Different Types:
Vasculitis – Overview of Different Types:
Buerger’s:
- Characterised by segmental, thrombosing, acute and chronic inflammation of the medium-sized and small arteries
- Principally the tibial and radial arteries with occasional secondary extension into the veins and nerves of the extremities.
- Often leads to vascular insufficiency, especially of extremities
- Almost exclusively occurs in smokers, before age 35
- Pathogenesis
- Tobacco à idiosyncratic endothelial cell toxicity OR immune response to components of tobacco smoke that modify host vascular wall proteins
- Smoking abstinence in early stages can often ameliorate further attacks but once established vascular lesions typically do not respond to smoking abstience
- Clinical features
- Raynaud phenomenon
- Intermittent claudication
- Instep claudication
- Venous inflammation
- Severe pain
- Ulcerations à gangrene
Giant Cell:
- Chronic inflammatory disorder of large to small-sized arteries that principally affects arteries in the head
- Especially temporal arteries but also vertebral and ophthalmic
- Medical emergency
- Pathogenesis
- T cell mediated immune response against one of handful of vessel wall antigens à proinflammatory cytokine production (TNF in particular) à granulomatous response (Responds to steroids)
- Predilection for a single vascular site unknown
- Microbiology – Anti-endothelial cell and anti-smooth muscle cell antibodies can also be demonstrated in roughly 2/3 of patients
Polyarteritis:
- Systemic vasculitis of small or medium sized muscular arteries, typically involving renal and visceral vessels but sparing the pulmonary circulation
- 30% have chronic Hep B and deposits containing HBsAg-HBsAb complexes in affected vessels, indicate an immune complex- mediated etiology
- Unknown cause
- Clinical features
- Typically young adults, but can occur in older and pediatric
- Ischemia à clinical manifestations
- Remitting and episodic – long term symptom free intervals
- Classic – rapidly accelerating hypertension due to renal artery involvement, abdominal pain and bloody stools caused by vascular GIT lesions; diffuse myalgia’s, peripheral neuritis (predominantly motor nerves)
- Treated with immunosuppression
- Typically fatal untreated
Arteriosclerosis vs Arteroelosclerosis:
- Atherosclerosis → a hardening of an artery specifically due to an atheromatous plaque
- Arteriosclerosis → a general term describing a hardening of medium or large arteries
- Arteriolosclerosis → a hardening of arterioles
Varicosities—Why do they form and where? —Pathophysiology of varicose vein formation.
Varicose veins are abnormally dilated, tortuous veins produced by prolonged, increased intraluminal pressure leading to vessel dilation and incompetence of the venous valves.
In healthy veins, the flow of blood is generally through the superficial system into the deep system and then towards the right atrium. One way valves are found in both the deep and superficial systems and incompetence in any of the valves can cause bi-directional flow (in the opposite direction) of blood and lead to venous hypertension.
Once venous hypertension is present, the venous dysfunction continues to worsen through a vicious cycle. Pooled blood and venous hypertension leads to dilated veins which then worsen valvular incompetency. This is more likely to occur in the superficial veins rather than the deep veins. Deep veins can withstand higher levels of pressures.
- Outline the clinical features of peripheral vascular disease—Arterial and Venous
Disease.
- Staging of PVD
- Fontaine Stages
- Asymptomatic
- Mild claudication
- Moderate-severe claudication
- Ischaemic rest pain
- Ulceration or gangrene
- Rutherford grades and categories – basically the same thing
- Fontaine Stages
Arterial
Venous
Dry, dark, painful
Wet, oedematous, oozing
Clear border, with no bleeding
Irregular and shallow
Painful
Painless
Dorsum of foot and distal areas e.g. toes
Gaiter region
Shiny skin, loss of hair, atrophy surrounding area
Stasis dermatitis surrounding area
Due to atherosclerosis
Due to varicose veins and lack of venous outflow
Do not use compression bandage
Use compression bandage
2. Describe the risk factors for DVT –especially travel – think Virchow’s Triad.
- Pregnancy and post-partum period Ú hypercoagulability
- Recent sepsis
- Malignancy Ú hypercoagulability
- Prior VTE
- Central venous access
- Hormonal contraceptives or hormonal replacement therapy
- Other drugs such as antipsychotics, tamoxifen
- Prolonged travel – flights 6-8 hours long or any travel longer than 4 hours
- Thrombophilia
- Family history of VTE
- CV risk factors incl. obesity
- Prolonged sitting
- Invasive procedures
- Q Thrombosis risk calculator predicts risk of VTE in primary care patients
- Based on:
- Age
- Gender
- BMI
- Smoking status
- Medical history
- Current medication
- Based on:
3. Outline the symptoms and signs of DVT.
- Unilateral pitting oedema
- Leg swelling, especially if circumference is more than 3cm compared to asymptomatic leg
- Calf tenderness, especially upon compression of calf muscles
- Be careful not to palpate too hard bc risk of dislodging clot into systemic circulation and causing PE
- Prominent superficial veins (superficial vein distension)
- Note: Homans’ sign is not particularly useful (pain during dorsiflexion of foot)
Wells criteria for PE
4. Wells criteria for PE
- Wells Score System is used for DVT probability
- One point each for the below clinical findings
- Negative 2 if alternative diagnosis as likely or more likely than DVT
- Note: not good for:
- Elderly patients
- Patients with comorbidities
- Recurrent DVT
- Pulmonary embolism
- Clinical findings (BPTSOCCCA):
- Bedridden – recently for more than 3 days or major surgery within past 4 weeks
- Paralysis, paresis or recent orthopaedic casting of lower extremity
- Tenderness – localised in deep vein system
- Swelling – entire leg
- Oedema – pitting in the symptomatic leg
- Calf swelling – 3cm greater than asymptomatic leg
- Cancer – active or cancer treated within 6 months
- Collateral non-varicose superficial veins
- Alternative diagnosis – more likely than DVT e.g. Baker’s cyst, cellulitis, muscle damage, superficial vein thrombosis, inguinal lymphadenopathy, external venous compression etc.
- NOTE this is -2 points!
What are the risk factors for ischemia?
- Smoking
- Diabetes
- Overweight or obesity
- Sedentary lifestyle
- High cholesterol
- High blood pressure
- Family history of vascular disease
Symptoms and signs of ischemic lower limb, including critical ischemia?
- rest pain in legs
- non-healing wounds
- tissue necrosis (gangrene)
- burning pain in feet and toes that is worse at night
- pain is exacerbated by the recumbent position
- edema of the feet and ankles
Value of D dimer and first line investigations for suspected DVT and thrombo-embolism
D dimer is used as a biological marker for early DVT after TKA, sensitivity is 68%, specificity is 55%, accuracy is 60%. So it cant be relied on as a sole diagnosis.
First line investigations ® ultrasound, a D-dimer test, venography.
Leg ulcers—differential diagnoses—including skin cancers (Benign, BCC, SCC, melanoma, Mossman ulcer ‐mycobacterium)
- Venous ulcer
- Arterial ulcer
- Neuropathic ulcer
- Diabetic ulcer
- Pressure ulcer
- Hypertensive ulcer
- Skin cancer (BCC, SCC, melanoma)
- Pyoderma gangrenosum
- Small vessel vasculitis
- Medium vessel vasculitis (polyarteritis nodosa), granulomatosis polyangiitis)
- Rheumatoid ulceration
- Necrobiosis lipoidica
- Systemic sclerosis
- Livedoid vasculopathy
- Warfarin-induced skin necrosis
- Heparin-induced necrosis
- Cholesterol embolism
- Septic emboli
Colonisers and Pathogens and interpretation of ulcer swabs
· All open skin wounds are colonised by bacteria, however, this does not mean that all wounds are infected
· The result of an ulcer swab will only provide information about the organisms present and their antibiotic susceptibilities. The results will not tell you if infection is present in the ulcer as this is a clinical diagnosis
· All ulcers are colonised by bacteria, which may progress to a level of so-called ‘critical colonisation’. Above this, healing is delayed and significant infection occurs. No simple test can differentiate colonisation from infection; early colonisation of venous leg ulcers is not considered adverse to healing
o Group A -haemolytic streptococci can be associated with significant infection and delayed healing. When diagnosed, these infections justify early, aggressive, systemic antimicrobial therapy
o Other streptococci, Staphylococcus aureus and anaerobes may be associated with clinical infection. Most other bacterial colonisation of wounds is not considered to adversely affect healing
· Treatment to be based on signs of infection, as inclusion of antibiotic susceptibilities on the report does not mean that an organism is significant or that it requires antibiotics
Clinical features of Venous, Arterial, diabetic/neuropathic ulcers
Venous Ulcers
Arterial Ulcers
Diabetic/Neuropathic Ulcers
- Predisposing factors include varicose veins, a history of DVT and obesity
- First symptom is often heaviness of the legs, followed by oedema
- Haemosiderin pigmentation, pallor and firmness of surrounding skin and sometimes venous/gravitational eczema develops (this progresses to lipodermatosclerosis – firm induration due to fibrosis of the dermis and subcutis)
- Ulceration is often precipitated by trauma or infection
- Relatively painless, moist ulcers
- Typically occur on the medial lower leg
- Deep, painful, punched-out ulcers on the lower leg, especially the shin and foot
- Likely to be due to arterial disease (risk factors include smoking, hypertension, diabetes and hyperlipidaemia)
- Foot is cold and dusky and the skin atrophic and hairless
- Peripheral pulses absent or reduced
- Most common cause of neuropathic ulcers are diabetes and Hansen’s disease (leprosy)
- Ulcers occur over weight-bearing areas, such as the heel
- In response to pressure, the skin increases in thickness (callus)
Spread of MRSA; Vancomycin resistance; infection control
- Spread of MRSA; Vancomycin resistance; infection control
a. Spread of MRSA:
Anyone can get MRSA (methicillin-resistant Staphylococcus aureus) on their body from contact with an infected wound or by sharing personal items, such as towels or razors, that have touched infected skin. MRSA infection risk can be increased when a person is in activities or places that involve crowding, skin-to-skin contact, and shared equipment or supplies. People including athletes, day-care and school students, military personnel in barracks, and those who recently received inpatient medical care are at higher risk.
b. Vancomycin resistance:
Vancomycin is a glycopepetide antibiotic used for the treatment of Gram-positive bacterial infections. Clinical isolates of MRSA strains with decreased susceptibility to vancomycin and more recently with high-level vancomycin resistance (vancomycin-resistant S. aureus – VRSA) have been described. The rare VRSA strains carry transposon Tn1546, acquired from vancomycin-resistant Enterococcus faecalis, which is known to alter cell wall structure and metabolism.
c. Infection control:
· Standard precautions:
o Hand hygiene
o Gloving
o Mouth, nose, eye protection
o Gowning
o Appropriate device handling of patient care equipment and instruments/devices
o Appropriate handling of laundry
· Contact precautions:
o Patient placement – assign priority of single-patient rooms to patients with known or suspected MRSA colonisation or infection; if single rooms are not available, cohort patients with the same MRSA in the same room
o Gloving
o Gowning
o Patient transport – in hospitals, limit transport and movement of patients outside of the room; when patients are transported, ensure that infected or colonised areas of the patient’s body are contained and covered
o Patient-care equipment and instrument/devices – use disposable noncritical patient-care equipment or implement patient-dedicated use of such equipment
o Environmental measures – patient rooms should be prioritised for frequent cleaning and disinfection (e.g. at least daily)
- Why do patients get confused with Warfarin prescribing?
- Because the dose is not necessarily ‘fixed’ à dosing likely to change over time
- Requires regular blood tests to determine INR and alter dose accordingly so that the therapeutic targets are being met (monthly check ups)
- INR- international normalised ratio, standardised measure of PT- extrinsic clotting pathway
- How does warfarin /aspirin prevent clots?
Warfarin
Aspirin
- Competitive antagonist for Vitamin K reductase à decreases amount of reduced vitamin K à decreases factor II, VII, IX, X, protein C and S (all vitamin K dependent clotting factors)
- Less activation of coagulation cascade from deficiency of these factors
- Good for low pressure vessels- veins
- Antiplatelet drug: irreversible inhibition of COX1 function à prevents TXA2 production from AA metabolism à reduces platelet aggregation and vasoconstriction
- Thus prevents platelet plug formation
- Good for high pressure vessels- eg arteries
- Managing patients with comorbidities
- Always be careful of drug-drug interactions, toxicities etc
- Regular GP consults to touch base with patient and ensure no adverse effects arise from multiple drugs being used
- Simplifying administration of medications if multiple- eg Webster packs
- Lifestyle changes are key for sustainable management, cannot rely solely on medications as this will not ‘fix’ the cause
- Difficulty of warfarin prescribing- monitoring and prescribing issues
- INR needs to be monitored once a month
- If too low- procoagulant state
- If too high- increased bleeding risk
- Can have many interactions with alcohol/foods: eg those high in vitamin K are likely to reduce INR (procoagulants)
NOTE: INR REFERENCE RANGES
Normal INR (healthy individuals)
0.9-1.1
Optimal range from Warfarin therapy
2-3
High risk groups (previous thromboembolism or antiphospholipid syndrome)
2-3
DVT of leg, PE
2-3
