In fog fever nO' consistent abnormalities have been detected on routine hemato- logical and biochemical estimatiO'ns (Sel- man et al. 19'74). More recent experi ...
Acute Respiratory Distress Syndrome (ARDS) in Lambs Hematology by Martha J. Ulvund and Hallstein
Gr~nst~l
From the State Veterinary Research Station for Small Ruminants, Sandnes, Norway.
Acute Respiratory Distress Syndrome (ARDS)
In
Lambs
Hematology by Martha J. Ulvund and Hallstein
Gr~nst~l
Lambs suffering from Acute Respiratory Distress Syndrome (ARDS) shortly after they were moved from mountain pastures onto lush aftermath grazings were examined hematologically. Acute Respiratory Distress Syndrome (ARDS) may occur in lambs 18-72 hours after they have been moved from mountain pastures onto lush aftermath in September. So far, the condition has only been found in lambs of the Old Norwegian short tailed breed (Spael) and crosses with the Dala breed. Symptoms include heavy dysphne, frothing at the mouth, ruminal atony, and elevated temperature (40_42 C), though sometimes a tranquil transient phase is seen initially (Ulvund & Gr~nst~l 1984). The lambs seem to be in a hyperergic immunological sta,te as compared with healthy controls, and give a positive skin reaction to various fungi isolated from pasture plants (Ulvund et al. 1984). This paper comprises hematological examinations of lambs with ARDS as well as healthy lambs from one of the affected flocks during disease outbreak. To be able to evaluate what happens when lambs of different breeds are moved from mountain pastures onto lush aftermath, lambs from one flock without any previous disease history (Dala and Rygja breeds) and lambs from an earlier affected flock (Spael and Spael crosses) we're examined hematologically after return from mountain pastures. 0
Nord. Vet.-Med. 1984, 36, 170-178.
Materials and methods Blood samples from six affected lambs (5 Spael, 1 Dala cross) belonging to two different flocks were examined 1-5 hours afte'r onset of symptoms, and later mainly afte·r 24 and 72 hours, and 6 and 8 days (Ulvund & Gr~nst~l1984). Hematological variables comprised packed red cell volume (PCV), hemoglobin values (Hb), number of red and white blood cells (RBC, WBC) , total serum protein (TSP) , serum values for calcium, magnesium, inorganic phosphorous, iron, copper, zinc, indole and 3methylindole (3MI). Plasma potassium, sodium and glucose values were also de-, termined. The examinations were made by standard laboratory methods as recorded by Overas (1969, 1974) and Walby Norheim & Rygge (1978) using gas estimated by the gluco-rapid test (Med Kjemi, Hjiln, Norway). Plasma indole and 3-methyl indole (3MI) were examined by Norheim & Rygge (1978) using gas, chroma.tography and a nitrogen-phosphorous selective detector. Blood samples were also taken from 24 healthy lambs in one of the affected flocks (Flock 1, Spael and Spael crosses) from where 5 of the diseased lambs (Nos. 1-5) originated. The blood sampling
Respiratory Distress in Lambs
171
were examined for indole and 3MI, calcium and magnesium. The sheep flock of this Research Station, with no previous disease history, and consisting of about 220 ewes and hoggets and 230 lambs of the Dala and Rygja breeds, was transported from mountain pastures in lorries for about 3 hours in mid September. Before they were put onto lush grazings, blood samples from 30 lambs and 5 adult sheep,
was done two days after the symptoms had appeared in these lambs, i.e. 3 days after change to lush pasture. The following year 25 lambs from this flock were sampled on the day of arrival from mountain pastures. After blood sampling, the animals were put directly onto lush aftermath. Blood samples from the same lambs were then collected 1 and 4 days laler. Thai year, however, none of the lambs developed ARDS. All these samples
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Figure 1. Packed cell volume (peV) in six lambs suffering from ARDS, individual values (0) of 24 healthy lambs in Flock 1, about three days after disease outbreak, and mean value from the same lambs. Mean value from 278 healthy Dala and Rygja lambs belonging to this laboratory, grazing cultivated lowland pastures, and sampled in September during a 3-year"period, is included. The figures refer to lamb No.
Martha J. Ulvund and Hallstein
172
all of the Rygja breed, were collected. The following day blood samples were taken from 20 of the same lambs. The samples were examined for indole and 3MI. Results Estimated values in whole blood in diseased and healthy lambs are recorded in Figs. 1-3 and Table I. PCV, RBC and Hb values were elevated during or shortly after outbreak of symptoms (mean values of Hb being 14 g/100 ml, RBC: 13 mill/!!.!) and declined thereafter during the following 5 days as recorded for PCV
Gr~nst~l
(Fig. 1). A leucocytosis due to a distinct neutrophiHa was seen during the first 24 hours of disease, during the following 2 days the number was reduced, followed in two lambs (Nos. 2 & 4) by a second rise in WBC-count, 4-6 days after onset of symptoms (Fig. 2). During the period of neutrophilia, the nuclei of the neutrophilic cells were strongly lobulated, each nucleus consisting of 5-10 fragments connected by fine threads. One to three days after, the majority of the nuclei was rod-formed. During the outbreak of symptoms there was a tendency tow,a.rds lymphopenia. Eosinophilic cells were reduc,ed in number (scarcely found).
Table 1. Serum inorganic phosphorous, iron,and plasma potassium in six lambs with ARDS, and mean figures from 278 healthy lambs belonging to this laboratory and s,ampled in September over a 3year period. The control lambs were grazing heavily fertilized cultivated pastures «(ijveras et al. 1977). - : Not examined. Arrival: 1-5 hours after outbreak of symptoms. Lamb No.
3 1
2
4
6
8 278 control lambs
Time after arrival
0 4 24 0 24 6 8 0 24 6 8 13 0 2.4 6 8 0 4 4 6 0 5
hI'S.
" hI'S. days
" hrs. days
" " hrs. days
" hrs. days
" days
Inorg. P p.g/lOO ml
Fe p.g/100 ml
8.0 10.1 12.7 5.2 7.3 7.0 8.2 7.3 10.6 10.1 10.3
170 230 66 182
K
mEq/1
2.7
7.3 14.1 13.0 11.0 8.0
209 190 341 8'6 224 211 112 144 190 298 274 149
8.1 8.8 10.0 11.3
199 218 67 226
2.9 5.1 4.7 3.9 4.4 2.8 4.9 4.8 4.0 4.1 3.5 4.7 4.4 3.7 3.3 4.3 4.3 3.7 4.3 4.3
6.3
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173
Respiratory Distress in Lambs 14
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Figure 2. Number (103/(J.I) of neutrophilic leucocytes and lymphocytes in six Iambs with ARDS, during the acute phase of disease (arrival at the laboratory: 1-5 hours after onset of symptoms), and at various intervals thereafter. The figures refer to lamb No.
Martha J. Uluund and Hal/stein Gr¢nst¢l
174
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Figure 3. Serum calcium (mg/100 ml) in 6 lambs with ARDS, mean and S.E.M.values in 24 healthy lambs in FIGck 1, three days after outbreak of the disease, and mean and S.E.M.-values in 25 lambs in Flock 1 the year after, Gn the day Gf return frGm mGuntain pasltures, one and fGur days after. Mean value frGm 278 contrGI lambs sampled in September during a 3-year-period, is included. The figures refer to' lamb NO'.
Serum calcium was extremely IGW during the acute phase of the disease, and returned to' normal values within 3-6 days after outbreak Gm symptGms. Total serum prGtein was slightly lowered at arrival (mean value 6.59 g/1 00 ml), but rose to' 7.12 g/100 ml after 24 hGurs. In most lambs the CGntent in inGrganic phGsphGrGus increased during the first
24 hours, and stayed elevated during the test periGd (Table 1). Serum irGn was low in most lambs at arrival or 24 hGurs after. The potassium CGntent was IGW during the acute phase of disease, but returned to' normal level within a day or mGre thereafter (Table I). Plasma glucose values were largely within nGrmal limits at
Respiratory Distress in Lambs arrival, but decreas.ed to a subnOirmal level OIne day after (mean value 49.5 mg/ 100 ml). Three days later, 5 of the 6 lambs had again nQrmal values, except lamb NO'. 3 which had 38 mg/100 ml. Serum magnesium, copper and zinc, and plasma sodium contents were within normal ranges, in the affected lambs. The plasma indQle and 3MI values in the diseased lambs were not detectable or between 0.005 and 0.033 Itg/100 ml. As can be seen from Fig. 1, PCV values of the 24 healthy lambs in Flock 1, two days after disease outbreak in the flock, were also elevated and above the mean for the control lambs. That year, these lambs also had low serum calcium values, however, all we·re above those of the diseased Iambs (Fig. 3). Mean value of serum iron in these healthy lambs two days after the dise,ase outbreak, was 188 ltg/tOO ml. The year after disease outbreak, calcium levels were within normal limits (Fig. 3). Plasma indole and 3MI values in the healthy Iambs in Flock 1 the year of the outbreak of disease and the year thereafter, and in lambs and she'ep beIO'nging to this Research Station were not detectable or be,tween 0.005 and 0.033 ltg/tOO mI. Discussion Lambs suffering from ARDS showed elevated PCV, neutrophilia, a tendency towards lymphopenia, eosinopenia, hyperphO'sphatemia, hYPO'glycemia, and extremely low serum Ca values during the first one to two daws after outbreak of symptoms. Normal values were regained after two to five days. During the very acute phase, plasma potassium values were mostly IO'wered. Healthy lambs in Qne of the affected flocks (Flock 1) showed slightly elevated PCV and mean serum calcium level beIQW the mean value for the control lambs, two days afte'r outbreak Qf symptoms in
175
the flock. These results indicate general strain or affection Qf the whQle flock this year, hQwever, not mounting to' clinical outbreak in more than 6 lambs out OIf tQtally 47.0 (Ulvund & Gr~nst~l1984). In fog fever nO' consistent abnormalities have been detected on routine hematological and biochemical estimatiO'ns (Selman et al. 19'74). More recent experimental work indicates that fQg fever is caused by sudden ingestion of L-tryptophan in lush grass and its ruminal conversion to 3MI by lactobacilli (Dickinson et al. 19'67, Carlson et al. 1975, Breete & Carlson 19'82, Logan et al. 19'82). Elevated bloQd concentrations Qf 3MI have also been found in connection with clinical disease (Hammond et al. 19'79, Carlson & Dickinson 1978, Breeze & Carlson 1982). Because of the not detectable Qr very low plasma values of indole and 3MI, similar mechanisms operating in this disease can probably be ruled out. During an outbreak of atypical interstWal pneumonia in sheep in Australia, no blood parameters were recorded (Pascoe & McGavin 1969). Clinical and pathO'anatomical similarities between the two diseases are also few (Ulvund & Gr~nst~l 1984). Experiments on allergy/anaphylaxis are often of short duration ,and difficult to cQmpare with clinical material. Dependent on when the farmer OIb'erved the symptoms, and how soon the animals were transported to our laboratory, the ve'ry early hematological changes may have been missed in our material. Changes like se·vere neutropenia observed in calves during the first 10 minutes after antigenic challenge (Wells et al. 1973), may thus have been missed. Calves follQwed for 72 hours, however, have shO'wn a sharp rise in the number of neutrophils after between 6 and 12 hours (Wells et al. 1973). During experimental prO'duction of allergic pneumonitis in calves, neutrophilia, lymphopenia and
176
Martha J. Ulvllnd and Hallstein Gr(Jl1st¢i
eosinopenia were found to occur (Dllngworth 1965). Also during naturally occurring and experimental milk allergy in cows, a significant eosinopenia and neutropenia were found, together with hyperphosphatemia (Campbell 1970). In sheep, experiments on histamine and chemical releasers of histamine have shown increased PCV by 10 to 20 per cent within 5 minutes after the injections, returning to pre-treatment values within ten to forty minutes (Alexander et ai. 1967,1970). Matchette et al. (19'67) found a linear relationship between the histamine dose administered and each of the following dependent variables: PCV, plasma calcium and plasma potassium concentrations. PCV was found to increase, and the plasma levels of calcium and potassium decreased. The decrease in the plasma level of calcium, however, was not of a great magnitude as compared with that of our material. Greater hypocalcemic effects have been found in connection with multiple injections or continous administration of his,tamine in horses (Akerblom & Sj¢berg 1938). The same authors also found increased number of white blood cells for 4 days, mostly due to an increase in neutrophils. The number of eosinophils declined during the same period, the same did the small lymphocytes. Inorganic phosporous values were elevated. Thus, it seems that histamine may be involved in ARDS in lambs, either through an atopic reaction or because of acute ruminal acidosis and sudden histamine formation and absorption (Uivllnd & Gr¢nst¢i 1984, Ulvllnd et al. 1984). Hypocalcaemia has earlier been found to occur in sheep shortly after dietary change from hay to crushed oats or pelleted concentrate (Lllthman & Persson 1977), and also in cattle rapidly adapted to feedlot conditions (Bide et al. 1975) or on sudden consumption of fodder-beel (Worden et al. 1954).
Histaminemia is also known to occur in certain forms of acute endotoxemia, togethe,r with hemoconcentration, acidemia, hypoglycemia and polymorphonuclear leucocyte aggregation in the pulmonary capillaries (Liehr & Griln 1979, Dllngworth 1982, Brigham et al. 1979). Experiments with acute endotoxemia in various animals have resulted in acute pulmonary distress and also colic (Moore et al. 1981, Smith et al. 1981, Demling 1982). Experiments on the role an d effect of histamine, and endotoxemia, will be included in future work with ARDS. References Alexander, F., P. Eyre & K. W. Head: Effects of histamine and 5-hydroxytryptamine on sheep. J. Compo Path. 1967, 77, 1-12. Alexander, F., P. Eyre & K. W. Head: Effects of chemical histamine liberators in sheep. J. Compo Path. 1970, 80,19-30. Bide, R. W., W. J. Dorward & M. E. Tllmbleson: Clinical chemistry of grainfed cattle. I. A preliminary study of a basic biomedical profile. Can. J. Anim. Sci. 19'73, 53, 697-707. Breeze, R. G. & J. R. Carlson: Chemicalinduced lung injury in domestic animals. In: Cornelius, C. E. & C. F. Simpson (Eds.) : The respiratory system. Advances in veterinary science and comparative medicine, Academic Press, New York and London, 1982, 344 pp. Brigham, K. L., R. E. Bowers & J. Hayes: Increased sheep lung vascular permeability caused by Escherichia-coli endotoxin. Circ. Res. 19'79, 45, 292297. Campbell, S. G.: Clinical allergies in cattle. Cornell Vet. 1970, 60, 240-253. Carlson, J. R., E. O. Dickinson, M. T. Yokoyama & B. Bradley: Pulmonary edema and emphysema in cattle after intraruminal and intravenous administration of 3-Methylindole. Amer. J. Vet. Res. 1975,36,1341-1347. Carlson, J. R. & E. O. Dickinson: Tryptophan-induced edema and emphysema in ruminants. In: Keele'r, R. F., K. R. Van Kampen & L. F. James: Ef-
Respiratory Distress in Lambs fects of poisonous plants on livestock. AcademIc Press, New York, San Francisco and London, 19'78, 26-1-272. Demling, R. H.: Role of pros,taglandins in acute pUlmonary microvascular injury. New York Acad. Sci. 19'82, 384, 517-534. Dickinson, E. 0., G. R. Spencer & J. R. Gorham: Experimental induction of an acute respiratory syndrome in cattle resembling bovine pulmonary emphysema. Vet. Rec. 1967, 80, 487489. Dungworth, D. L.: The pulmonary respons,e of sensitized cattle to aerosol admini.s,tration of antigen. Proc. Symp. Acute Pulmonary Emphysema. N. 1, Laramie, Wyoming 19'65, NI-N15. Dungworth, D. L.: Interstitial uulmonary disease. In: Cornelius, C. E. & C. F. Simpson (Eds.) : The respiratory system. Advances in veterinary science and comparative medicine, Academic Press, New York and London, 1982, 344 pp. Hammnod, A. C., B. J. Bradley, M. T. Yokoyama, J. R. Carlson & E. o. Dickinson: 3-Methylindole and naturally occurring acute bovine pulmonary edema and emphys,ema. Amer. J. Vet. Res. 1979, 40, 139'8-14.01. Liehr, H. & M. Gran: Endotoxins in live,r disease. In: Popper, H. & F. Schaffner (Eds.): Progress in liver diseases. Vol. VI. Grune & Stratton, New York, San Francisco, London, 19'79, 313326. Logan, A., I. E. Selman, A. Wiseman, E. M. Allan & H. M. Pirie: Experimental production of diffuse pulmonary fibrosisand alveolitis in cattle: the efeffects of repeated dosage with 3methyl indole. Res. vet. Sci. 1982, 34, 97-108. Luthman, J. & J. Persson: Feeding-induced hypocalcemia. Nord. Vet.-Med. 1977, 29, 90~95. Matchetie, P. C., R. W. Hughes & H. J. Bozinch: Effect of intravenous administration of histamine on packed cell volume and plasma levels of calcium anrl potaSSIUm in sheep. Amer. J. vet. Res. 1967,28, 1897-1903. Moore, J. N., H. E. Garner, J. E. Shapland & R. G. Schaub: Equine endotoxemia: An insight into cause and treatment. J. Amer. Vet. Med. Ass. 1981, 179, 473 477.
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Norheim, G. & J. Rygge: Gas chromatographic determination of indole and 3-methylindole in ovine plasma and rumen fluid using a nitrogen-phosphorous selective detector. Journal of Chromatography 1978, 154, 29'1-294. Pascoe, R. R. & M. D. McGavin: Atypical interstitial pneumonia. Vet. Rec. 1969, 85, 376-377. Selman, I E., A. Wiseman, H. M. Pirie & R. G. Breeze: Fog fever in cattle: Clinical and epidemiological features. Vet. Rec. 19,74, 95, 139-146. Smith, M., R. Gunther, C. Zaiss, J. Flynn & R. Demling: Pulmonary microvascular injury from lipoxygenase infusion: Comparison with endotoxemia. Circ. Shock, 19'81, 8, 647-656. Ulvund, M. J. & H. Gr~nst~l: Acute Respiratory Distress Syndrome (ARDS) in lambs. Clinical ~nd pathoanatomical examinations. Nord. Vet.-Med. 1984, 36, 88-9,7. Ulvund, M. J., J. Drew Smith & H. Gr~n st~l: Acute Respiratory Distress Syndrome (ARDS) in lambs. Mycology and Hypersensitivity. Nord. Vet.-Merl. 19'84, 36, 9'8-102. Waldeland, H.: Toxoplasmosis in sheep. Haematological, serological and parasitological studies. Acta vet. scand. 1977, 18, 248-256. Wells, P. W., P. Eyre & J. H. Lumsden: Haematological and pathological changes in acute systemic anaphylacsis in calves: Effects of pharmacological agents. Can. J. Compo Merl. 1973, 37, 119-129. Worden, A. N., J. Bunyan & J. PickUp: A fatal hypocalcaemia-like syndrome in dairy cows following the excess consumption of fodderbeet. Vet. Rec. 19M, 66, 133. ~veras, J.: Studies on Eperythrozoon ovis-infection in sheep. Acta vet. scand. 19'69, Suppl. 28. ~veras, J.: A comparison between hay fed and grass silage fed sheep, with special reference to serum iron, total iron binding capacity and transferrin saturation. Nord. Vet.-Merl. 1974, 26, 545-555. ~veras, J., M. Pestalozzi, O. Helle, J. J. Nedkvitne & T. Matre: Mixed grazing research in Norway. The 28th Annual Meeting of the European Association for Animal Production. Brussels, August 22th-25th, 19'77.
178
Martha J. Ulvund and Hallstein Gr{fJnstpl
Akerblom, E. & K. Sjpberg: Das Blutbild
beim Pferde nach langdauernder Histaminapplikation. (The blood picture in horses after continuous dosing of histamine). In: Krehl, L & W. Straub: Archiv fUr Exper. Path. und Pharmakologie, Vol. 189, Verlag von F. C. W. Vogel, Berlin, 1938, 53-63. Summary Lambs suffering from Acute Respiratory Distress Syndrome (ARDS) showed elevated PCV, neutrophilia, a tendency towards lymphopenia, eosinopenia, hyperphosphatemia, hypoglycemia and extremely low serum Ca values during the firs:t couple of days afte,r the outbreak of symptoms. During the very early phase, plasma potassium values were mostly lowered (Figs. 1-3, Table I). The possibl¢ involvement of histamine is shortly
discussed: either 1) through an atopic reaction, 2) because of acute ruminal acidosis and sudden histamine formation, or 3) involvement of endotoxins. Sammendr,ag AkuH Respiratorisk Distress Syndrom (ARDS) hos lam. Hematologi.
Lam med ARDS ("pustesjuke") hadde forhpyet blodvolum'prosent, njiSytrofili, tendens til lymfopem, eosinopeni, hyperfosfaiemi, hypoglycemi og svrert lave serum kalsium verdier de fjiSrste par dagene etter at de ble sjuke. Plasma kalium var som regel noe lavt i den akuUe fasen (Fig. 1-3, Tabell I). Mulighetene for at his,tJamin er involvert, enten via 1) en s.traksaIiergi, 2) akutt vomacidose og histamindannelse i vomma eller 3) innvirkning av endotoksin, blir kort omtalt.
Descriptors: Lambs, respiratory distress, pasture-change, hematology, histamine, endotoxins. Modtaget af redaktionen 1984.01. 29. Authors' addresses: Martha J. Ulvund, S.V.F., Postboks 248, 4301 Sandnes, Norway. Hallstein Grpnstpl, S.V.L., Postboks 40, 5032 Minde, Norway.
