SWELLING DISEASE (Swelsiekte)-The Capillary Leak
By Dr Mackie Hobson BSc(Agric),BVSc

1. Field Studies
2. Disease Syndromes

Where is all the protein going?

Swelling disease, ‘swelsiekte’ in Angora goats is the acute onset of severe subcutaneous oedema (fluid) of the lower body parts ventral neck, chest and abdomen, front and hind legs. The swelling is cold, pits on pressure and is painless.

The first cases of swelling disease in South African Angora goats have been reported during the early 1970’s.  However, no conclusive evidence had been found to establish the cause of the disease.

See: https://www.angoras.co.za/article/swelsiekte-theories-tested-and-trials-conducted#189

It has been well documented in a number of studies that the main clinical findings in Swelling disease have been:

1. Low oncotic pressure (low TSP and Albumin)

https://www.angoras.co.za/article/swelsiekte-the-role-of-blood-proteins

2. Elevated Wbc count.

https://www.angoras.co.za/article/swelsiekte-possible-role-of-the-inflammatory-process

Albumin is largely responsible for maintaining intravascular oncotic (colloid osmotic) pressure, contributing up to 80%.  Reduced oncotic pressure is clearly related to the occurrence of ‘Swelsiekte’.

The question has been, where has the Albumin been going?

In 2015 the South African Mohair Growers Association (SAMGA) Veterinarian M. Hobson sampled 3 outbreaks of ‘Swelsiekte’ on different flocks under different conditions which confirmed the low plasma protein levels. 

• Young ewes grazing on the veld,
• Old ewes kraaled during cold weather and

• Young ewes grazing on Lucerne lands.

 10 goats with Swelling and 10 without were sampled from each group (60 in total).

 A battery of tests was carried out by Idexx laboratories.

Where is the Albumin going?

Collating data from:

• Blood samples were taken from normal and swelling Angora goats at Grootfontein( (M.Snyman/A.Snyman) &  swelling Angora goats (Mitchel, Hattingh, Ganhoa 1983) and blood samples from normal and swelling Angora goats ( SAMGA vet M.Hobson 2015/2016).
• Oedema fluid analysis from swelling goats (Grootfontein M.Snyman, A.Snyman) and (Mitchel, Hattingh, Ganhoa 1983).
• Interstitial fluid from normal Angora goats (SAMGA Vet M.Hobson 2017). 

Under normal circumstances in various species documented the A: G ratio of interstitial fluid is not largely different from that of plasma. (Y. Zurovsky, G.Mitchell and J.Hatting 1994).

This is reflected in the figures from Rabbits (Y.Zurovsky, G.Mitchell and J.Hatting 1994), Rats (Coetzee et al 1982), Boer goats (G.Mitchell, J.Hattingh, M.F. Ganhao 1983) and Angora goats (this study).

What causes the Albumin: Globulin ratio to be so different in SWELLING disease?

From the results in Table 1 (above), it can be seen that in swelling disease:

Blood Plasma:

• A:G ratio DECREASES by 0.22 (0.66 to 0.44) (33.3%)

This is due to albumin concentration reducing to a greater extent than globulin in the plasma compartment so the A: G ratio decreases

• Albumin decreases by 13.3g/l (45.5%)
• Globulin concentration decreases 10.35g/l (23.8%)

Interstitial fluid:

• A:G ratio INCREASESby 0.51 (0.69 to 1.2) (74%)

This is due to the albumin concentration reducing to a lesser extent than globulin in the interstitial fluid after dilution so the A: G ratio increases.

• Albumin decreases by 9.5g/l (59.4%)
• Globulin concentration decreases 18.72 g/l (81.4%)

A low oncotic pressure (reduced albumin) in the plasma of swelling goats would cause fluid to filter into the interstitial space through the capillary walls and lower the concentration of interstitial proteins (albumin and globulin) to a similar extent.

If there had been no leakage of albumin through the capillary wall then the A: G ratio in the interstitial fluid of swelling goats (1.2)  would have been similar (diluted ) or lower than that of the interstitial fluid of normal goats (0.69). (See Table 1)

The A: G ratio of interstitial fluid in swelling Angora goats is 1.2 This is 74% higher than a normal goat.

Therefore the albumin as well as fluid leaks through the capillary wall in swelling disease.

Globulins have a higher molecular weight than albumins and are larger than Albumin so cannot pass as easily.

This reflects findings by Mitchel, Hattingh, and Ganhoa (1983) using Boer goat interstitial fluid as a comparison suggesting that oedema was primarily due to hypoproteinaemia as well as a higher capillary permeability.

Capillary membranes are of three basic forms continuous, fenestrated, and discontinuous or sinusoidal and are found in different regions of the body.

• Continuous capillaries have a continuous endothelial lining. They have tight junctions between their endothelial cells along with intercellular clefts through which small molecules can pass. These are generally found in the nervous system (also lungs and testicles where no swelling is seen in Angora goats)

)

• Fenestrated capillaries have small openings in their endothelium known as fenestra. Fenestra has a non-membraneous, permeable membrane, which is diaphragm-like and spanned with fibrils. This arrangement allows quick movement of macromolecules in and out of the capillary. The basement membrane of the epithelial cells in the lining remains unbroken by the fenestra.

These are found in tissues where a large amount of molecular exchange occurs, such as the kidneys, endocrine glands, and small intestine.

• Sinusoidal capillaries sometimes referred to as sinusoids, or discontinuous capillaries, have endothelial linings with multiple fenestrations (openings). These have no diaphragm and either a discontinuous or non-existent basal lamina. This allows blood cells and serum proteins to pass through the capillary wall.

Sinusoidal capillaries are mainly found in the liver, between epithelial cells and hepatocytes. Sinusoidal capillaries can also be found in the lymph nodes, bone marrow and some of the glands of the endocrine system.

• The Blood-Testis and Blood-Epididymis have tight junctions and that is why we do not see swollen testicles/scrotums in swelling disease.

• Lung epithelium also have tight junctions and again the reason we do not get lung oedema in swelling disease in Angora goats although severe ascites and a large amount of pleural will occur along with ventral oedema of the body.

CONCLUSION:

The loss of Albumin leading to a lowered oncotic pressure causing Swelling disease is due to a CAPPILARY LEAK SYNDROME.

Although some of the predisposing factors reported may contribute to a lower oncotic pressure (brown stomach worm, coccidiosis, LPE as examples); it is the increased capillary permeability that is the primary disease mechanism causing the hypoproteinaemia and significant reduction in plasma oncotic pressure.

What causes the capillary leak?

The role of the inflammatory response, as well as an abnormal immune response in Angora goats, must be considered in swelling disease.

 See Website https://www.angoras.co.za/article/swelsiekte-possible-role-of-the-inflammatory-process

References

• COMPOSITION AND VISCOSITY OF INTERSTITIAL FLUID OF RABBITS

ZUROVSKY*, G. MITCHELL AND J. HATTINGH Department of Physiology and -Department of General Physiology, University of the Witwatersrand, Johannesburg,

• Mitchell, G.; Hattingh, J.; Ganhao, M.F The composition of plasma and interstitial fluid of goats with swelling disease. Journal of the South African Veterinary Association (1983) 54 No.3, 181-183 (En). MRC/University Circulation Research.Unit, Department of Physiology, University of the Witwatersrand, 2001 Johannesburg, Republic of South Africa.
• GUYTON, A. C. (1963). A concept of negative interstitial fluid pressure based on pressures in implanted perforated capsules. Circulation Research 12, 399-414.
• Swelling disease  - GF Bath & SO Vermeulen  1985- Grootfontein Agricultural Development Institute
• Snyman MA, Snyman AE   2005 - The possible role of Ostertagia circumcincta, coccidiosis and dietary protein level in the development of swelling disease in Angora goat kids            J. S. Afr. Vet. Ass. 76(2) : 63-68
• Snyman MA, Herselman MJ   2004       Investigation into the probable cause, predisposing factors and effective treatment of swelling disease in Angora goats      The Angora Goat and Mohair Journal, 46(1) :
• Vermeulen SO      1986       Die etiologiese rol van bruinmaagwurm (Ostertagia circumcincta) ten opsigte van swelsiekte by Angorabokke               Karoo Agric, Vol 3, No 7, 1986, 45-50
• The Blood-Testis and Blood-Epididymis Barriers Are More than Just Their Tight Junctions, Payal Mital, Barry T. Hinton, and Jannette M. Dufour.