Severe azotemia in a young breeding ram following to acute urethral obstruction by throughout  intra-luminal blood clots


 Urethral obstruction is a very important problem in small ruminants` flocks, as it affects breeding rams and so invaluable genetic reserves of the population. A three-years-old breeding ram referred to the teaching hospital with the owner`s compliant of lack of urination in previous two days. The ram was the only one in the flock which it had unlimited access to fat-tailed ewes. The other signs consisted of anorexia, reluctance to walking and final lateral recumbency. Severe depression, anuria, dribbling of blood drops from the glans and firmness of the enlarged penis in palpation were detected in the clinical examination. But noticeably there was no local subcutaneous edema and even swelling outside of the penis as it could be usually observed in urolithiasis. It was noticeable that the animal had remarkable bleeding tendency. An obvious splashing sound was heard using stethoscope auscultation on the right flank along. Abdominal paracentesis demonstrated a blood-tinged peritoneal fluid. Ultrasonography showed a completely distended urinary bladder. The animal died because of severe obstructive azotemia. The distended urinary bladder was opened and large amounts of blood-tinged urine flashed out. The urethra was incised but no urinary stones were detected in the lumen. Otherwise, an intra-luminal blood clotting at full length was detected following to the proximal internal hemorrhage. Obviously, this complex case may be confused with urolithiasis and should be exactly differentiated. There is no available reported data concerning the entity in literature. This case report is discussing the matter.


Introduction
Urethral obstruction including urolithiasis is a very important problem in small ruminants` ocks, as it affects breeding rams and so invaluable genetic reserves of the population. Urolithiasis is the most common cause of urethral obstruction in ruminants (Videla, and Van Amstel, 2016). Feedlots of castrated male lambs and kids suffer frequently from such a problem as well as genetically-registered rams and bucks, that the problem may cause greatest economic losses to ock owners in tropical and subtropical countries (Constable, et al., 2017;Riedi, et al., 2018aRiedi, et al., , 2018b. Long urethra, narrowed diameter lumen, the sigmoid exure of urethra and urethral process in male small ruminants make them much vulnerable to any kinds of urethral blockade by urinary calculi, traumas and/or blood clots (Byers, 2020;Constable et al., 2017). The urethral process in small ruminants is a location that should be routinely examined in suspected urinary obstruction in animals (Kümper, 1994). Urinary bladder distention and rupture, uroperitoneum and increased concentrations of urea and creatinine (azotemia) in body uids are consequences of urethral obstruction (Byers, 2020;George et al., 2003). Iatrogenic trauma during castrations may result in tissue damage to urethra and its secondary stricture (Lakamy et al., 2017). On the other hand, urethral intra-luminal hemorrhage syndrome can lead to widespread formation of blood clots and a secondary obstruction that may be confused with urolithiasis. However, there is no available data concerning the entity in literature. This case report is discussing the matter.

Case Description
A three-years-old ram with 60 kilograms weight referred to the teaching hospital with the owner`s compliant for lack of urination in previous two days. This ram was the only one in the ock which it had unlimited 24-hours a day access to the ewes, and therefore frequent attempts of mounting. The other signs included inappetence, reluctance to walking and nal lateral recumbency. Additionally, severe depression, anuria, dribbling of blood drops from the glans, and rmness of the enlarged penis in palpation were detected in the clinical examination ( Fig. 1). But noticeably there was no detectable local subcutaneous edema and swelling outside of the penis, which it can be observed in ordinary urolithiasis. The ram showed teeth grinding, paddling movements of limbs and vocalizing during palpation of the painful penis. The conjunctival and oral cavity mucosal membranes were hyperemic. It was noticeable that the animal had remarkable bleeding tendency as normal clotting did not occur following to the blood sampling from jugular vein for submitting to the laboratory. The rectal temperature was 39.7 centigrade degrees and heart rates as 80/min and respiratory rates 100/min. The accompanying signs were dyspnea and expiratory grunting. An obvious splashing sound was heard using stethoscope auscultation on the right ank along with concurrent abdominal ballottement. Abdominal paracentesis of right umbilical region demonstrated a blood-tinged peritoneal uid which submitted to the laboratory (Fig. 2). Ultrasonographic imaging accomplished by using a convex transducer and frequency of 3.5 MHZ that it showed a completely distended urinary bladder (Fig. 3). Finally, the comatose ram died before any medical intervention because of severe obstructive azotemia.

Results
Multiple subcutaneous petechial and ecchymotic hemorrhages were evident in various parts of the breeding ram`s cadaver. Signi cant bilateral renal enlargement and hydronephrosis was observed in necropsy of the ram ( Fig. 4 and Fig. 5). Abdominal cavity had an accumulation of blood-tinged peritoneal uids and distended urinary bladder which its external wall was reddish and congestive ( g.6). The distended urinary bladder was opened and large amounts of blood-tinged urine ashed out (video: ). Signi cant enlargement of penis without any rupture and exuding urine into the peripheral tissues was observed in the necropsy. The urethra was incised by a scalpel blade and no urinary stones were detected in the lumen. Otherwise, an intra-luminal blood clotting at full length was detected following to the proximal internal hemorrhage in the urethral lumen (Fig. 7). The laboratory ndings of blood and peritoneal uid samples taken from the ram showed decreased hemoglobin concentration and red blood cell count, apparently normal hematocrit, hyperglycemia, hypocalcemia, hypophosphatemia, signi cant increased concentrations of urea (~9 times of the average value) and creatinine (~7 times of the average value) in the blood and peritoneal uid (table 1,2).

Discussion
As the ram in the present article a rapid clinical course, particularly in the absence of urinary bladder rupture, and occurring uroperitoneum prior to death has been reported in male small ruminants involved in acute urethral obstructions (Byers, 2020;Kümper, 1994).
A notable thrombocytopenia was occurred in the ram which it may be resulted in the multiple foci of hemorrhages observed in its cadaver (Table1). Though, association between uremia and coagulopathies has reported since more than 200 years ago (Morgagni, 1764) and increasing data about the complex effects of uremia have been gathered in this period including induced bleeding tendency, metabolic acidosis, dysfunction of platelets and prostaglandins (Berns, 2020;Noris, 1999;1957;Tsai, 2019;Warnock, 1988 ).
However, severe uremia may be the principal reason for the observed bleeding tendency, urinary bladder`s wall hemorrhage, subcutaneous petechial and ecchymotic hemorrhages, blood-tinged urine and peritoneal uid, and subsequent anemia in the ram ( Fig. 1 and Fig. 6). It seems signi cant red blood loss due to widespread hemorrhagic foci in the ram may be prevented appearance of hemoconcentration and subsequent hematocrit increase. (Table2). Oppositely, hemoconcentration was a nding concerning 270 small ruminants with obstructive urolithiasis (Ried et al. 2018a).
Signi cant hyperglycemia in the ram may be due stress-related endogenous corticosteroids which can increase blood glucose concentration by catabolism of glucogenic amino acids and appearance of insulin resistance (Table2). Increased sympathetic tone in response to the painful urethral obstruction may have a role in the increased blood glucose in the ram.
Hypophosphatemia in the ram was in accordance with the data in the urethral obstruction in sheep (George, 2003), but in contrary to hyperphosphatemia observed in bovine urolithiasis, as uroperitoneum will always result in cattle hyperphosphatemia in direct proportion with the volume of urine in cattle`s abdomen (Constable et al., 2017). On the other hand, the con rmed cases of urolithiasis in weaner lambs showed slightly higher phosphorus in serum (VinodhKumar et al., 2010). This paradoxical metabolic impacts of uremia on the phosphate`s concentration in various species of ruminants is controversial and it emphasizes necessity of further comprehensive researches in this regard.
Remarkable leukocytosis in the azotemic ram encounters stress neutrophilia and also secondary bacterial invasions to the injured mucosal membranes of urogenital and digestive tracts (Table1). Consequently, it is rational that toxemia following to bacterial proliferation and invasion to in amed mucosal membranes can be occurring due to azotemia and thus potentiating the severity of the clinical syndrome.
Urethral examination including catheterization in male small ruminants has many di culties because of above-mentioned anatomical limitations and even could cause further damage to the ram`s urethra. Although, as the present article, non-invasive techniques such as ultrasonography in cases of distended urinary bladder and urinary bladder rupture can help greatly in reaching to de nitive diagnosis of acute urethral obstruction of any kinds including urolithiasis, external traumas, internal traumas due to calculi, and intra-luminal blood clotting (Fig. 3).
It is evident that a widespread intra-luminal blood clotting was occurred in the ram`s urethra (Fig. 6). However, it may be appeared an important question! Why the ram wall or the adjacent skin of the ram. Secondary hemorrhage following intra-luminal irritation by urinary calculi may be source of the throughout blood clotting. But, the ram s urethra in necropsy. However, in our opinion, it is more probable that frequent attempting to mount on the fat-tailed ewes by the single breeding young ram may be leaded to severe internal hemorrhage in the enriched urethral vasculature, which in turn could produce completely obstruction of the lumen by formation of intra-luminal blood clots at its full length and the subsequent life-threatening azotemia.
In conclusion this case report discussed a new entity in small ruminants` medicine that may be a cause for creation of urethral obstruction and the involved animal should be thorough clinically and paraclinically examined to differentiate from other cause of urethral obstruction particularly urolithiasis.

Declarations
Statement of Animal right: The research was performed in accordance with the ethical standard laid down in the 1996 declaration of Helsinki and its later amendments.
Lakamy, S., Martina, C., Giovanni, A., Tiberiu, A.N., Giuseppe, S., Riccardo, Z., Agnes, E., 2018. Dysuria in a saradinian ram with glans penis traumatic injury.   Page 5/5 Lateral recumbency, severe enlargement of the penis and bleeding tendency in the young breeding ram Signi cant enlargement of kidneys in the young breeding ram Figure 5 Bilateral hydronephrosis in the young breeding ram Figure 6 Severe hemorrhage of wall in the distended urinary bladder in the ram Figure 7 Severe enlargement of the penis and throughout blood clots in urethral lumen of the young breeding ram

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download. Splashingoutofdistentedurinarybladder.mp4