SWELLING DISEASE (Swelsiekte)-Is this the Answer?
By Dr Mackie Hobson BSc(Agric),BVSc

1. Diseases
2. Field Studies
3. Disease Syndromes

SWELLING DISEASE ‘SWELSIEKTE’

Farmers and researchers have reported a number of possible scenarios and predisposing factors that may lead to swelling disease. But the question has always been as to how these factors could possibly be connected and able to cause Swelling disease (Swelsiekte).

A number of theories and trials have been conducted to determine the cause of the swelling in the past: See: https://www.angoras.co.za/article/swelsiekte-theories-tested-and-trials-conducted

What do the predisposing factors have in common that could lead to Swelling?

All the predisposing factors that have been considered to be a possible underlying cause all have something in common:

• They lead to an increased white blood cell count (leucogram).

Graph below: scatter graph of Wbc pattern in relation to Albumin levels

• ORANGE Dots (Non-Swelling goats),
• BLUE Dots (Swelling Goats)

Light green box (normal reference range wbc x10^{9 g/l} IDEXX)

Dark green box (normal reference range Albumin g/i)

Stress or inflammation?

Both stress and inflammation can manifest with similar leukogram patterns, a mature neutrophilia (no left shift or toxic change), monocytosis and lymphopenia and eosinopenia (although all changes may not be present in every animal).

Swelling disease surveys and history have often suggested a component of stress such as after shearing or housing during cold weather. Perhaps intense stressors over-activate the immune system? Young weaned Angora goats under 18 months are known to have an over reactive immune response (Lymphocytic-Plasmacytic-Enteritis).

Other trials where swelling occurred after a stressor was observed after shearing (M.Snyman, A. Snyman Grootfontein). The goats were shorn during Week 10 of the experiment. In week 12 of the study 19, of the goats developed some subcutaneous oedema. Just prior to the swelling a hot day was followed by cold rainy conditions. The number of goats that developed oedema was fairly evenly distributed among the various treatment groups.

Large bodies of evidence indicate that stress can activate an inflammatory response in humans (and rats). Recent researchers have also proved that Cortisol can also have a pro-inflammatory impact on the immune system (Pérez-Nievas et al., 2007).

Acute stressors seem to enhance immune function, whereas chronic stressors are suppressive. Intense stressors over-activate the immune system, leading to the imbalance of inflammation and anti-inflammation. (Miller et al., 2009).

In common, an over-activated immune system, increased activity through sympathetic nerve pathways and reduced Cortisol responsiveness may work together in the activation of inflammatory responses during stress.

For more info on the Role of inflammation see the website:

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

Why is there no obvious rise in the cortisol level if stress is involved?

Blue dots (Swelling goats), Orange dots non-swelling goats

The expectations that a sick animal, as well as a stressed goat, should show a stress leucogram and increase in cortisol level? This does not appear the case when you look at the table.

The explanation for this may be the fact that the cortisol levels measured by the labs reflect both free and bound cortisol. (>90% of cortisol is protein-bound). Therefore a reduction in TSP/Albumin would reflect in a low Cortisol level even though the free Cortisol levels may in fact be much higher.

What has post mortems told us about the relationship between swelling and inflammation?

The splenic changes may indicate that a systemic inflammatory response took place, but a cause cannot be determined from the findings and may also be parasite related or due to terminal septicaemia/endotoxaemia.  DR E C DU PLESSIS-( Idexx Pathologist).

How does this inflammatory response lead to Swelling?

The Capillary leak

We have always known that swelling goats have a lower Total Serum Protein (TSP) but we have been uncertain as to where all the protein/Albumin has been going?

The graph below compares the Albumin and TSP levels of goats with swelling disease compared to goats without swelling in the same flocks (n=60)

BLUE Dots: Goats with swelling

ORANGE Dots: Goats without swelling

It is quite clear from the graph that swelling goats have a lower TSP and Albumin levels.

For more info on the Role of the blood proteins see the website:

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

We have been able to prove that the Albumin is being lost through the capillary wall (leak) although certain conditions such as LPE, roundworms and coccidiosis will contribute to a lower protein level.

By doing field studies we were able to determine the interstitial (fluid between cells of tissues) levels of Albumin and Globulin in normal non-swelling goats. From this study and using previously collected data, we could prove by comparing the Albumin: Globulin ratios of swelling fluid and normal interstitial fluid that the Albumin was being lost through the capillary walls.

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).

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).  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.

For more info on the role of the Capillary leak see the website:

https://www.angoras.co.za/article/swelsiekte-swelling-disease-in-angora-goats

Farmers/Vets would have also noticed that with swollen goats that goats seldom die of lung oedema or swelling of the brain despite general oedema, ascite and a fluid-filled chest cavity. They would also have noticed that although the underside of the goat has swollen the testis don’t swell to the same extent.

The reason this occurs is that there are 3 types of junctions in the capillary blood vessel walls.  Continuous capillaries have a continuous endothelial lining. They have tight junctions between their endothelial cells.) The brain, lungs and epididymis of the testis have tight junctions and leaking is less likely. Leaking will occur more in Fenestrated capillaries that have small openings in their endothelium (such as the kidneys and small intestine). Sinusoidal capillaries, or discontinuous capillaries, have endothelial linings with multiple fenestrations (openings). They are mainly found in the liver, lymph nodes, bone marrow and endocrine glands.

CONCLUSION

Capillary leak syndrome” occurs in systemic inflammatory response syndrome (SIRS). Due to damage to the capillary endothelium, there is increased loss of medium to high molecular weight compounds, particularly albumin, into the extravascular space. The more permeable the capillary barrier is to proteins, the higher the interstitial oncotic pressure and increased swelling of the goat.

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 the 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.
• Bath (1983),Vermeulen (1984) ,Bath & Vermeulen (1988) and De Wet & Bath (1994)
• Mitchel, Hattingh,Ganhoa (1983),
• Dr Johan Van Rooyen (Grootfontein)
• com, Cornell University
• Rohleder, 2014; Calcia et al., 2016). Inflammation: The Common Pathway of Stress-Related Diseases.Yun-Zi Liu, Yun-Xia Wang, and Chun-Lei Jiang 2017
• Corticosterone as a marker of susceptibility to oxidative/nitrosative cerebral damage after stress exposure in rats.BG Pérez-Nievas, B García-Bueno, JR Caso 2007
• Transient responses of inflammatory cytokines in acute stress. Author links open overlay panelKaoriYamakawaaMasahiroMatsunagabcTokikoIsowadKentaKimuraeKunioKasugaicMasashiYonedacHiroshiKanekobHidekiOhiraa