Pathology leading to amputation

Introduction

Worldwide prevalence estimates of amputation are difficult to obtain, mainly because amputation receives very little attention and resources in countries where survival is low[1]. Limb loss can be the result of trauma, malignancy, disease, or congenital anomaly. Peripheral Vascular Disease is the most common cause of limb loss overall[2], with the rate of dysvascular amputation being nearly 8 times greater than the rate of trauma related amputations, the second leading cause of limb loss[3].

Peripheral Vascular Disease

Peripheral Vascular Disease is also known or referred to as Peripheral Artery Disease or lower extremity occlusive disease. It affects the peripheral vascular system, mostly the arteries, and is a manifestation of systemic atherosclerosis and atherothrombotic conditions which may include stenotic, occlusive and aneurysmal disease[4].

The peripheral vascular system consists of the veins and arteries beyond or distal to the chest and abdomen supplying the arms, hands, legs and feet.
 
The peripheral vascular system consists of the veins and arteries beyond or distal to the chest and abdomen supplying the arms, hands, legs and feet.

Atherosclerosis, which is the process of Peripheral Arterial Disease (PAD), affects several arterial beds including the coronary and peripheral circulation[5]. Peripheral vascular disease is thus considered as a form of cardiovascular disease. Its onset is gradual but progressive. It is often asymptomatic but causes serious effects. Atherosclerosis is commonly seen with an increase in age in adults and elderly. In peripheralarterialdisease there is build up of fatty deposits in the walls of the arterial system. These fatty deposits, also known as atheromas, cause a reduction in the lumen of the arteries. The reduction in the lumen causes stenosis and restricts the blood flow and supply to the particular area affected.

The illustration shows how P.A.D. can affect arteries in the legs. Figure A shows a normal artery with normal blood flow. The inset image shows a cross-section of the normal artery. Figure B shows an artery with plaque buildup that's partially blocking blood flow. The inset image shows a cross-section of the narrowed artery.

The illustration shows how P.A.D. can affect arteries in the legs. Figure A shows a normal artery with normal blood flow. The inset image shows a cross-section of the normal artery. Figure B shows an artery with plaque buildup that's partially blocking blood flow. The inset image shows a cross-section of the narrowed artery.

An increase in age brings about related vascular changes also known as arteriosclerosis. It may be referred to as hardening of the arteries wherethereisgeneraliseddegenerationof the elastic tissue and muscles composing the arterial system. This tissue is replaced by fibrous tissue and the elastic vessels become harder with stretching of collagen and calcium depositing in the walls of the arteries causing them to become hard and tortuous.

https://youtu.be/BmsQri-XmCs

Diabetes Mellitus and Diabetic Ulcers

Diabetes is also another condition that has an effect on the pathology that may lead to lower limb amputation. The risk of amputation is higher where peripheral vascular disease and diabetes coexist. 

Diabetes Mellitus (Type 2)  Diabetes mellitus is also present in almost half of all cases, and people with diabetes mellitus have a 10 times higher risk of amputation[6]. It is characterised by chronic compensatory hyperglycaemia that results from progressive insulin resistance especially in muscle tissue together with insufficient pancreatic secretion of insulin to aid glucose uptake in tissues [7]. Diabetes Mellitus usually has an insidious onset and presentsaspersistenthyperglycaemia. This is defined by the American Diabetes Association as a fasting plasma glucose level ≥126mg/dL.

Symptoms may include:

  • fatigue
  • dry or itchy skin
  • lower extremity pain or paraesthesia
  • numerous infections
  • delayed wound healing and
  • hypoglycaemiaafterexercise.

Potential complications of DM include diabetic retinopathy, nephropathy, hypertension, neuropathy, coronary artery disease, diabetic foot ulcers and peripheral arterial disease[8].

Patients who suffer from Diabetes Mellitus are at a high risk of developing ulcers and associated complications.[9] Studies indicate that diabetic patients have up to a 25% lifetime risk of developing a foot ulcer[10]. Peripheral neuropathy and ischaemia from Peripheral vascular disease are two contributing factors to the development of foot ulcers. Once a foot ulcer develops there is a high risk of wound progression that may lead to complications and amputation. On analysing causal pathways for diabetic lower-limb amputation foot ulcers preceded around 84% of amputations[11]. Foot ulcers are considered to be reasonably common and they not only affectthepatient'sfuntionalstatusandwell being but can also identify individuals who may be at a higher risk of amputation. Ulcers result fromneuropathyandischaemia.Indiabeticindividuals the hyperglycaemic-induced metabolic abnormalities cause a conversion of intracellular glucose to sorbitol and fructose. The accumulation ofthesesugarscause a reduction in the synthesis of products required for normal nerve conduction and function. The chemical conversion of glucose will also increase the oxidative stress on nerve cells and leadtofurtherischaemiaandthuscausing further nerve cell injury and death.

Neuropathy in diabetic individuals affects the motor, sensory and autonomic componentsofthethenervoussystem. Sensation and proprioception input are decreased. The innervation of the intrinsic muscles of the foot is affected and damage leads to an imbalance between the flexors and extensors of the affected foot and therefore causing anatomic deformities. Such deformities include the toes being pulled up into a hammer toe or claw foot flexion deformity. These will cause abnormal bony prominences and pressure points, such as on the tops of the toes or under the metatarsal heads, which may eventually lead to skin breakdown and ulceration.

Further damage may be caused through the affected autonomic nervous system. Autonomic neuropathy causes the reduction in sweat and oil gland function with the foot loosingitsnaturalability to moisturisetheoverlyingskin. The skin becomes dry and susceptible to tears or breaks with subsequent development of infection. Minor trauma is also a contributing factor to ulcers that may eventually lead to amputation. Individuals suffering from peripheral vascular disease and diabetic peripheral neuropathy experience a loss of sensation that may exacerbate the development of ulcers. Many times diabetic individuals are unable to detect trauma to an affected area such as the foot. This may result in injury with wounds either going unnoticed or progressively worsen when the affected area is exposed to repetitive pressure or forces such as shear forces during ambulation[12][11]. Poor healing of such wounds, due to compromised circulation, will eventually lead to amputation of the involved limb. 

Diabetic foot ulcer (DFU) and diabetic foot infection (DFI) pathophysiology. DFU results from a complex interaction of a number of risk factors. Neuropathy (with alterations in motor, sensation, and autonomic functions) plays the central role and causes ulcerations due to trauma or excessive pressure in a deformed foot without protective sensibility. Once the protective layer of skin is broken, deep tissues are exposed to bacterial colonization. Infection is facilitated by DM-related immunological deficits, especially in terms of neutrophils, and rapidly progresses to the deep tissues.

Diabetic foot ulcer (DFU) and diabetic foot infection (DFI) pathophysiology. DFU results from a complex interaction of a number of risk factors. Neuropathy (with alterations in motor, sensation, and autonomic functions) plays the central role and causes ulcerations due to trauma or excessive pressure in a deformed foot without protective sensibility. Once the protective layer of skin is broken, deep tissues are exposed to bacterial colonization. Infection is facilitated by DM-related immunological deficits, especially in terms of neutrophils, and rapidly progresses to the deep tissues.

Intermittent Claudication

In the case of peripheral circulation where the the arteries of the lower limbs are affected, pain and tissue damage develop which may eventually lead to amputation in some cases. Patients suffering from peripheral arterial disease present with pain referred to as Intermittent Claudication. It is defined as reproducible ischaemic muscle pain. This type of pain presents after physical activity such as walking. In individuals suffering from PAD the blood flow in the lower limbs is reduced due to processes causing stenosis. Blood circulation is usually sufficient when one is at rest, however when one starts walking and the demands are greater the blood supply is not sufficient to the lower limb muscles causing cramps and pain. Thus such pain gets worse with greater demands example: when walking uphill and improves or is relieved after a short rest[13].

Vascular Investigations and Surgical Techniques for the Ischaemic Limb

Peripheral arterial disease is one contributing factor to ischaemia involving the lower limbs. The latter is one of the causal factors when amputation of the affected lower limb may be considered. Common vascular investigations used to determine ischaemia or peripheral arterial disease include:

  • Pulse Examination
  • Ankle-Brachial Index (ABI) tool (Calculated as the ratio of systolic blood pressure at the ankle to that in the arm where the normal range is 0.9-1.1 whilst a ratio of
  • Angiography - a criteria standard for imaging of the arterial system, especially when diagnosing PAD
  • Ultrasonic Imaging - this is used to determine or investigate lower limb vascular disease. This includes Duplex Scanners and Colour Doppler scanners. 'Ultrasonic scanning is now established as a valuable non-invasive method for investigating lower-limb vascular disease. It is the first method of choice for arterial stenosis and occlusion, and for venous incompetence[14]. Ultrasonic imaging is non-invasive and can provide clinical information about the site and severity of narrowing of arterial vessels or of any blockages of main vessels. Where multiple stenoses are present such imaging can determine which stenosis is causing more restriction to blood flow[14].

The Common Femoral Arterty (CFA) divides into the Superficial Femoral Artery (SFA) and the Profunda Femoris Artery (PFA).  Arterial Blood flow is from left to right. The skin surface is located at the top of the image whilst markers on the right indicate depth in cms.

The Common Femoral Arterty (CFA) divides into the Superficial Femoral Artery (SFA) and the Profunda Femoris Artery (PFA). Arterial Blood flow is from left to right. The skin surface is located at the top of the image whilst markers on the right indicate depth in cms.

Surgical interventions for the ischaemic limb include:

  • Angioplasty: stent placing where a balloon catheter is inserted in the artery and inflated where there are areas of narrowing or blockage
  • Graft Bypass surgery :a graft is surgically inserted to bypass a diseased area of the vessel

Smoking

Tissue viability is affected not only by internal factors such as PAD or Diabetes Melllitus but also by external stimuli such as smoking. Smoking is considered to be another or an added risk factor for lower limb amputation due to its effect on the circulation and potential for healing. It has a detrimental effect on wound healing due to the local and systemic processes that nicotine has[15]. Nicotine being a vasconstrictor reduces the blood flow to the skin and thus causes tissue ischaemia together with an impairment in the healing process. Nicotine also promotes an increase in the level of platelet adhesiveness which in result raises the risk of thrombotic microvascular occlusion leading to further tissue ischaemia[15].

Trauma

Amputation of a limb can occur due to trauma. The amputation can take place at the site of the accident i.e. a direct limb transection or may be due to severe open fractures or severe neurovascular injuries . Examples of traumatic injuries include: compound fractures, blood vessel rupture, severe burns, blast injuries, stab or gunshot wound, compression injuries and cold trauma[16]. In cases of traumatic injury amputation of the limb is considered either as a life saving procedure or where the limb is so severely injured that reconstruction will be less functional than amputation. In the case of trauma limb amputation can also take place months or years after the actual trauma when reconstructive procedures or healing hava failed.

Infections

Lower limb amputation can also occur due to systemic infections such as bacterial infections. Previously healthy individuals when affected by such infections are at a risk of amputation of limbs not only as a treatment of choice but also as a life saving measure. Infections include: Meningococcal Meningitis, Staphylococcus and MRSA infections and Necrotizing Fascitis.

Tumours

"Bone- and cartilage-forming tumours (osteosarcomas and chondrosarcomas) are rare malignant neoplasms. These tumours are clinically aggressive and often need extensive local and/or systemic treatment. Whereas no other treatment but surgery is currently available for chondrosarcomas, osteosarcomas show an approximately 50–80% response rate to adjuvant chemotherapy. Surgical removal of these tumours is currently mostly performed with limb salvage, but amputation may be required in some cases. In addition, the tumours have a risk of local recurrences adversely affecting the prognosis compared to the primary tumour".[17].

Congenital Limb Deficiency

A child can be born with complete or partial absence of a limb. In order to facilitate scientific communication the International Organization for Standardization (ISO) developed a system of accurate classification. The mentioned classification is constructed on an anatomical bases due to a failure of formation. Congenital Limb Deficiencies are described as either transverse or longitudinal. Transverse Deficiencies resemble an amputation residual limb, where the limb has developed normally to a particular level beyond which no skeletal elements are present. Longitudinal deficiencies include a reduction or absence of an element within the long axis of the limb[18]  

References

  1. Aleccia J. 2010. Limb loss a grim, growing global crisis. Retrieved March 17 2015, from http://haitiamputees.nbcnews.com/_news/2010/03/19/4040341-limb-loss-a-grim-growing-global-crisis
  2. Stewart and Jain. Cause of death of lower limb amputees. Prosthetics and Orthotics International, 1992,16,129-132
  3. Amputee Coalition of America. 2010. ACA's Limb Loss Task Force warns of increasing limb loss in the U.S. O&P Business News, 19(7):50
  4. Dressendorfer, R., Palmer, E. (2014). Peripheral Artery Disease: Clinical Review. Cinahl Information Systems.
  5. Welten GM, Schouten O, Chonchol M, Hoeks SE, Bax JJ, Van Domburg RT, Poldermans D., 2009, Prognosis of patients with peripheral arterial disease, J Cardiovasc Surg (Torino). 2009 Feb;50(1):109-21.
  6. Carmona GA, Hoffmeyer P, Herrmann FR, Vaucher J, Tschopp O, Lacraz A, Vischer UM. 2005, Major lower limb amputations in the elderly observed over ten years: the role of diabetes and peripheral arterial disease. Diabetes Metab. 2005 Nov;31(5):449-54.
  7. Palmer E. (2013). Clinical Review – Diabetes Mellitus, Type 2, and Exercise. Cinahl Information Systems
  8. Masharani, U.(2013). Diabetes mellitus and hypoglycaemia. In Papadakis, M.A. McPhee, S.J., eds. Lange 2013 Current Medical Diagnosis and Treatment. 52nd ed. New York, NY: McGraw Hill Medical: 1192-1244.
  9. http://jdfc.org/spotlight/diabetic-foot-infections-current-diagnosis-and-treatment/
  10. http://total-contact-casting.com/diabetic_foot_disorders/diabetic-foot-disorders.html
  11. 11.0 11.1 Reiber, G. E., Vileikyte, L., Boyko, E.J., del Aguila, M., Smith, D.G. Lavery, L.A., Boulton, A.J. (1999). Causal Pathways for incident lower extremity ulcers in patients with diabetes from two settings. Diabetes Care 22: 157-162
  12. Clayton,W. and Elasy, T.A. (2009). A Review of Pathophysiology, Classification, and Treatment of Foot Ulcers in Diabetic Patients. Clinical Diabetes, Vol 27, no 2, pp 52-58.
  13. Circulation Foundation. Intermittent Claudication.http://www.circulationfoundation.org.uk/help-advice/peripheral-arterial-disease/intermittent-claudication/ (accessed online 5 March 2015)
  14. 14.0 14.1 Lunt, MJ. Review of duplex and colour Doppler imaging of lower-limb arteries and veins. In http://www.worldwidewounds.com/2000/sept/Michael-Lunt/Doppler-Imaging.html (accessed 5 March 2015)
  15. 15.0 15.1 Hampton, S. and Collins, F. (2004). Tissue Viability. Whurr Publishers Ltd, UK.
  16. Barbara Engstrom and Catherine Van de Ven, 1999, Therapy for Amputees, 3rd Edition, Churchill Livingston ISBN: 978-0-443-05975-9
  17. Pathology of primary malignant bone and cartilage tumours, L.B: Rozeman, A. M Cleton-(2006), http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172744/
  18. Day, H.G.B . The ISO/ISPO Classification of Congenital Limb Deficiency in Atlas of Limb Prosthetics: Surgical, Prosthetic and Rehabilitation Principles. http://www.oandplibrary.org/ (accessed 5 March 2015)