Pathogenesis (disease development)
The cause of chronic peripheral arterial occlusive disease (pAVD) (of the lower extremities) is atherosclerosis (arteriosclerosis, hardening of the arteries) in approximately 95% of cases. In rare cases, there is an inflammatory cause. Atherosclerosis is probably initially caused by fatty streaks. In this process, lipoproteins accumulate in the intima (“inner wall layer”). In addition, leukocytes/white blood cells (lymphocytes and monocytes) are activated to spread in the intima. The monocytes give rise to foam cells, which produce increased amounts of cytokines (proteins that promote the growth and differentiation of cells) and growth factors, leading to cell necrosis (death of a cell due to damage to the cell structure). At the same time, there is a destruction of the structure of the vascular segment, where there is then connective tissue proliferation and deposition of further lipids.Due to a simultaneously occurring increase in permeability with subsequent endothelial damage, there is a further accumulation of cellular debris deposited at structurally disturbed vascular sites, independent of the pathway listed above. The result of these remodeling processes is the restriction of arterial diameter. The pathogenesis of atherosclerosis is comprehensively described under the topic of the same name. Claudication intermittens is now due to exercise-induced hypoxia (insufficient oxygen supply to the tissues) of the leg muscles.
Etiology (causes) of peripheral arterial disease (pAVD)
Biographic Causes
- Age – increasing age: highest incidence (frequency of new cases) in the sixth and seventh decades of life.
Behavioral causes
- Nutrition
- Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
- Consumption of stimulants
- Tobacco (smoking) – relative risk of smokers for pAVD was more than twice their risk for coronary heart disease (CHD) and apoplexy (stroke); for pAVD risk, it took about 30 years to return to normal; for CHD risk, after twenty smoke-free years and apoplexy risk normalized within five to twenty years.
- Psycho-social situation
- Negative workplace stress increased risk of severe major pAVD in a manner similar to apoplexy (stroke) and myocardial infarction (heart attack)
Disease-related causes
- Diabetes mellitus (88% increased risk of pAVD).
- Hyperfibrinogenemia – increased levels of fibrinogen in the blood.
- Hypertension (high blood pressure)
- Renal insufficiency (kidney weakness)
Laboratory diagnoses – laboratory parameters that are considered independent risk factors.
- C-reactive protein (CRP)
- Glomerular filtration rate (GFR) ↓
- Hypercholesterolemia – elevated cholesterol blood lipid levels.
- Hyperhomocysteinemia – increased concentration of the amino acid homocysteine in the blood.
Etiology (causes) of intermittent claudication
Causes of stenosing (“narrowing”) and/or occlusive (“closing”) arterial lesions in the lower extremities that can lead to intermittent claudication:
- Atherosclerosis (arteriosclerosis, hardening of the arteries).
- Aortic isthmic stenosis (ISTA; synonym: coarctation of the aorta: coarctatio aortae) – constriction of the aorta (main body artery) in the region of the aortic arch.
- Claudication spinalis – pain syndrome when the spinal canal is too narrow in the lumbar spine.
- Fibromuscular dysplasia – structural changes in the wall of the arteries that lead to narrowing of the diameter of the vessels.
- Congenital (congenital) or acquired vascular malformations.
- Compression syndromes, e.g.: Entrapment syndrome (synonym: popliteal compression syndrome; English : popliteal artery entrapment syndrome, PAES) – circulatory disorder of the lower leg, which is based on damage to the popliteal artery (popliteal artery).
- Vascular tumor
- Peripheral arterial occlusive disease (pAVK)
- Peripheral embolism (can also lead to acute ischemia/decreased blood flow).
- Popliteal cyst (outpouching of the joint capsule into the popliteal fossa and lower leg).
- Popliteal aneurysm (pathological dilatation of the popliteal artery).
- Pseudoxanthoma elasticum (PXE, synonym: Grönblad-Strandberg syndrome) – autosomal dominant or recessive inherited disorder in which the elastic fibers of the connective tissue are altered by mineral (calcium) deposition.
- Primary vascular tumors
- Thrombangiitis obliterans (synonyms: endarteritis obliterans, Winiwarter-Buerger disease, Von Winiwarter-Buerger disease, thrombangitis obliterans) – vasculitis (vascular disease) associated with recurrent (recurring) arterial and venous thrombosis (blood clot (thrombus) in a blood vessel); symptoms: Exercise-induced pain, acrocyanosis (blue discoloration of the body appendages), and trophic disturbances (necrosis/tissue damage resulting from the death of cells and gangrene of the fingers and toes in advanced stages).
- Takayasu arteritis (granulomatous vasculitis of the aortic arch and outgoing great vessels; almost exclusively in young women)
- Vasculitis ( inflammatory rheumatic diseases leading to inflammation of the vessels).
- Cystic adventitia degeneration – rare vascular disease that can lead to stenosis (narrowing) or obstruction (occlusion) due to cystic formations in the adventitia, especially in the popliteal artery
- Trauma or radiation damage
Medication
- Aceclofenac, similar to diclofenac and the selective COX-2 inhibitors, is associated with an increased risk of arterial thrombotic events.
