Introduction

Pathogenesis

Pathophysiology

Primary congenital lymphedema

• A congenital defect in the normal development of lymphatics and lymph nodes such that extracellular protein-rich tissue fluid cannot be drained away from the affected tissue site, resulting in local edema.
• An autosomal dominant mode of inheritance has been proposed for this defect.

Acquired lymphedema

• Might develop secondary to the effects of a variety of lesions resulting in extra-lymphatic or intra-nodal blockade of the drainage of lymphatic fluid from a tissue site.
• These lesions are most commonly neoplastic, but chronic inflammatory disease, trauma, chemical damage or surgical damage to lymphatic vessels might produce a similar effect.
• The blockage must be relatively severe and involve several major lymphatic channels or a chain of lymph nodes in order to produce clinical signs.
• Minor lymphatic blockage will not → clinical disease as the lymphatic flow would be diverted to collateral vessels, or lymph may be re-routed through lymphatic-venous anastomoses or via dermal lymphatics or even tissue spaces.
• Compromise of both lymphatic and venous drainage would therefore → more severe and rapid onset tissue swelling.

Intestinal lymphangiectasia

• May rarely be a primary congenital defect in lymphatic vessels draining the gut, or be acquired in adults due to blockage to the outflow of lacteal vessels.
• Although obstructive neoplastic or inflammatory lesions, eg of mesenteric lymph nodes, are often incriminated in this respect, the presence of such lesions is not always confirmed by histopathological examination of gut biopsies.
• Alternatively, the failure of lymphatic outflow might reflect the presence of venous hypertension, ie in congestive heart failure, thoracic venous thrombosis.
• Obstruction of lymph flow through the thoracic duct has been suggested as another underlying causation. Blockage of lacteal outflow → the accumulation of lymphatic fluid within the lacteals, which undergo very prominent dilation causing expansion and blunting of the intestinal villi.
• There is edema of the villous lamina propria and dilation of lymphatics in submucosa, muscularis, serosa and mesentery. These changes → subsequent loss of the lymphatic fluid across the enterocyte barrier into the intestinal lumen. The loss of this protein-, lipid- and lymphocyte-rich fluid results in hypoproteinemia Hypoproteinemia , hypocholesterolemia, hypocalcemia and lymphopenia.
• The hypoproteinemia may lead to the development of systemic edema including hydrothorax and ascites. This protein losing enteropathy Protein-losing enteropathy is associated with diarrhea, anorexia, lethargy, vomiting, abdominal pain and weight loss.
• The pathogenesis of the diarrhea involves malabsorption of lipid and loss of plasma protein and lymphatic fluid into the gut lumen.
• Hypocalcemia occurs due to loss of calcium associated with plasma albumin and malabsorption of both calcium and vitamin D.
• Hypocholesterolemia similarly reflects lipid malabsorption and plasma loss.
• Local loss of lymph fluid → accumulations of macrophages, which are the basis for the characteristic lipogranulomas that form associated with lymphatic vessels.
• Lipogranulomas are more likely to be a sequel to local leakage of lymph rather than the primary cause of the lymphatic blockage. Experimental occlusion of mesenteric lymphatic vessels → lymphangiectasia and hypoproteinemia, but not diarrhea and weight loss suggesting that the clinical syndrome might have a more complex pathogenesis than just simply involving lymphatic blockage.

Timecourse

Primarycongenital lymphedema

• May show clinical signs at birth or during the perinatal period.

Acquired lymphangiectasia

• Disease states will generally have a relatively chronic course.

Intestinal lymphangiectasia

• Insidious onset with slow progression of clinical signs over several months before the features of the protein losing enteropathy Protein-losing enteropathy become clinically apparent.

Diagnosis

Treatment

Outcomes