Lymphedema is an accumulation of protein-rich lymph fluid in body tissues due to lymphatic insufficiency or obstruction, leading to swelling, discomfort, and impaired movement. It can be classified into primary, related to congenital issues, and secondary, often due to illnesses or treatments, with cancer-related cases being common. The clinical manifestations include variable swelling, changes in skin texture, discomfort, and restricted motion, particularly in limbs affected by prior surgeries or radiation.

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School of Medicine and Pharmacy
DOC I
GROUP V
CARDIOVASCULAR SYSTEM MODULE
Topic: Pathophysiology and clinical manifestation of
lymphedema
November 21, 2016

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Reg. number Names Surnames
214002211 BIZIMANA Arlette
215023224 GACUTI Benissa
215002409 GIRIMPUHWE Rodrigue
215006227 HATANGIMANA Patrick
215001051 HATEGEKIMANA Vincent
215004257 HATEGEKIMANA Vincent
215005303 IRADUKUNDA Robert
215011253 ISANGANO Samuel
215003362 ISHIMWE Pascal
215002765 ISHIMWE Belyse
215009404 ISHIMWE Celine
216351480 ITUZE Ange Marie
215019414 IYAMUREMYE Protogene
215007216 KANKINDI Alice
215007804 KWIZERA JEAN Raymond
215001058 MBABAZI Prince
215003549 MUGABIRE Prudence
215003736 MUSONI Venuste
216351146 MWIZERO Aria Genaelle
215002734 NDAYISHIMA Patrick
215004113 NGIZWENAYO William
215005137 NISHIMWE Raymond
215001845 NSENGIMANA Sosthene
216352126 NTADOHOKA Ariella
215007309 NTAMBARA Sabiniane
215005290 NTEZIYAREMYE BALINDA Vicky Oni
215004445 NTIBASHIRAKANDI Pilote
215003134 NTIRENGANYA Yves Parfait
215003295 NYIRABAHIZI Clarisse
215004658 RAFIKI Etienne
215008534 RWANDARWACU VICTOR Pacifique
215019725 SHYAKA Wilson
215001849 SIMBI SANGWA Leandre
215012932 SINABUBARAGA Vincent
215013483 TUYISHIME Yannick
215003122 TUYISHIMIRE Brigitte
215004762 UWAMAHORO Angelique
215005003 UWAMBAYINGABIRE Angelique
215019331 UWIZEYIMANA Anastase

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1. DEFINITION
Lymphedema is build up of excess protein-rich lymph fluid in body tissues due to
lymphatic insufficiency or obstruction of lymphatic drainage back into the blood
stream. The affected area can become swollen and distorted in shape. This can
result in pain, heaviness, discomfort, impairment of movement and it impact on
daily activities.
They are classified into two classes: primary and secondary lymphedema
 Primary lymphedema is related to congenital malformation of the
lymphatic channels.
 Secondary lymphedema results from illness or treatments that obstruct
lymphatic drainage. Cancer related lymphedema can occur due to the
physical location of a tumor, or as a result of investigations or treatment e.g.:
lymph node excision or radiation.
2. PATHOPHYSIOLOGY OF LYMPOEDEMA
a. Normal physiology
The normal function of the lymphatics is to return proteins, lipids, and water from
the interstitium to the intravascular space; 40-50% of serum proteins are
transported by this route each day. High hydrostatic pressures in arterial capillaries
force proteinaceous fluid into the interstitium, resulting in increased interstitial
oncotic pressure that draws in additional water. Interstitial fluid normally
contributes to the nourishment of tissues.
About 90% of the fluid returns to the circulation via entry into venous capillaries.
The remaining 10% is composed of high-molecular-weight proteins and their
oncotically associated water, which are too large to readily pass through venous
capillary walls. This leads to flow into the lymphatic capillaries, where pressures
are typically subatmospheric and can accommodate the large size of the proteins
and their accompanying water. The proteins then travel as lymph through
numerous filtering lymph nodes on their way to join the venous circulation.

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b. Disease-related changes in lymphatic flow and their effects
In a diseased state, the lymphatic transport capacity is reduced. Consequently, the
normal volume interstitial fluid formation exceeds the rate of lymphatic return,
resulting in the stagnation of high-molecular-weight proteins in the interstitium.
This usually occurs after flow has been reduced by 80% or more. The result, as
compared with forms of edema that have much lower concentrations of protein, is
high-protein edema, or lymphedema, with protein concentrations of 1.0-5.5 g/mL.
This high oncotic pressure in the interstitium favors the accumulation of additional
water. Accumulation of interstitial fluid leads to massive dilatation of the
remaining outflow tracts and valvular incompetence that causes reversal of flow
from subcutaneous tissues into the dermal plexus. The lymphatic walls undergo
fibrosis, and fibrinoid thrombi accumulate within the lumen, obliterating much of
the remaining lymph channels. Spontaneous lymphovenous shunts may form.
Lymph nodes harden and shrink, losing their normal architecture. In the
interstitium, protein and fluid accumulation initiates a marked inflammatory
reaction. Macrophage activity is increased, resulting in destruction of aelastic
fibers and production of fibrosclerotic tissue. Fibroblasts migrate into the
interstitium and deposit collagen. The result of this inflammatory reaction is a
change from the initial pitting edema to the brawny nonpitting edema characteristic
of lymphedema. Consequently, local immunologic surveillance is suppressed, and
chronic infections, as well as malignant degeneration to lymphangiosarcoma, may
occur.
The overlying skin becomes thickened and displays the typical peau d'orange
(orange skin) appearance of congested dermal lymphatic. Chronic lymphedema
causes fissuring and impairment of the epidermis, allowing bacteria to enter and
grow, and leading to lymphorrhea, the leakage of lymph onto the surface of the
skin. With chronic lymphedema, the development of verrucous, cobblestone
plaques, a condition known as elephantiasis nostra verrucosa (ENV), can occur.
Protein composition in lymphedema a theory has also been proposed that chronic
lymphedema changes the protein composition of lymph in affected areas. A
decrease in alpha-2 globulin levels and an increase in the albumin-to-globulin ratio

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have been reported. This change in proteins and the resultant slowing of transport
to the lymphoid tissue have been suggested to play a role in diminishing the
effectiveness of immune surveillance and to prevent early detection of tumor-
specific antigens. Additionally, repeat episodes of chronic ulceration and healing
may stimulate the proliferation of keratinocytes, which may contribute to
neoplastic transformation.
3. CLINICAL MANIFESTATIONS OF LYMPHOEDEMA
 Onset of the onset of lymphedema is usually insidious. Affected patients may
initially experience aching pain at the affected area and a sense of heaviness or
fullness of the limb. Over time, the skin becomes dry and firm with less pitting
and is fibrous to palpation.
 Laterality Two-thirds of cases of lymphedema are unilateral, although the
laterality depends on the precipitating event. For example, an axillary node
dissection will increase the risk of lymphedema in the ipsilateral arm while a
pelvic node dissection increases the risk of bilateral lower extremity edema.

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 Swelling At onset, swelling in the affected limb is typically characterized as
“soft” and “pitting”. Pitting is variable in patients with lymphedema and reflects
movement of the excess interstitial water in response to pressure. It is generally
absent with progressive lymphedema, reflecting the evolution of fibrosis and
adipose tissue deposition.
 For patients who had previously undergone a lymph node
dissection and/or radiation, lymphedema is typically characterized by slowly
progressive ipsilateral swelling of an arm following axillary node dissection or
a leg following inguinal node dissection. The swelling may first be apparent
only in the proximal portion of the limb, or it can affect only a portion of the
distal limb including the digits.
Among patients with breast cancer, there may also be swelling over the
ipsilateral breast and/or upper chest wall. Other manifestations include a feeling
of heaviness, tightness, aching or discomfort in the limb, and restricted range of
motion.
 Skin changes with worsening lymphedema, dermal thickening becomes
clinically apparent, which is manifested by cutaneous fibrosis. The overlying
skin of the affected limb also becomes hyperkeratotic, which can lead to
verrucous and vesicular skin lesions.
 Discomfort which is a feeling of heaviness, tightness, aching or discomfort in
the affected limb commonly accompanies swelling.
 Restricted range of motion with later stages of lymphedema, patients may
develop restricted range of motion in the affected limb as a result of the
increased weight, which may limit their ability to perform activities of daily
living (ADLs).

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REFERENCE
 www.uptodate.com
 www.ncbi.nlm.nih.gov