Gastritis Induced by Hepatic Disorders in Canines

 Vandana^1*, Ankit Dahiya², Pooja Solanki³, Rajashekar Kamalla⁴ and Varun Kumar Sarkar⁵

^1,3,4,5PhD Scholar, Division of Medicine, ICAR-IVRI, Bareilly, Uttar Pradesh ²MVSc Scholar, Division of Medicine, ICAR-IVRI, Bareilly, Uttar Pradesh Email: vandanamudgil9@gmail.com

Introduction

 Dogs affected with liver diseases frequently display gastrointestinal (GIT) signs which may be elicited by ulceration. The liver has a vital role in inactivation of various forms of gastrin. Therefore, hypergastrinaemia has been implicated in the pathogenesis of gastrointestinal ulcerations related to liver dysfunction (Tovi et al., 2012).

Portal Hypertensive (PH) Gastropathy: Histologically, this gastropathy is defined by mucosal and submucosal vascular ectasia in the absence of inflammation. Similar lesions can be found in the small and large bowel. Various factors implicated in pathophysiology of PH gastropathy include: 1) Changes in splanchnic circulation 2) Humoral factors and 3) Dysregulation in tone of local vasculature. Among human beings, 50-98% of patients with PH gastropathy reveal gastric ulcers and mucosal lesions. PH gastropathy is also associated with greater risk of GIT bleeding in human beings which may be acute or chronic.

In veterinary medicine the characteristic histopathological lesions observed in PH gastropathy have not been reported till now, however hepatic disorders increase the likelihood of development of gastric ulcers in canines and felines. In huma patients with portal hypertension, gastric mucosal defense is impaired, caused by circulatory stasis in mesenteric vascular bed due to thrombosis, alterations in GIT motility, overgrowth of intestinal bacteria occurs due to absence of bile acids in GIT lumen, and mucosal edema caused by increased permeability of GIT mucosa. Increased production of vasocontrictors like endothelin-1, along with overproduction of free radicals, has been thought to be involved in pathophysiology of PH gastropathy (Buob et al., 2011).

Gastric mucosal lesions such as portal hypertensive (PHT) gastropathy are increasingly recognized at endoscopy as common features in patients with portal hypertension. Furthermore, they are recognized as a cause of anemia or even overt hemorrhage. Using endoscopy, severe PHT gastropathy is located in the fundus and the corpus. Severe PHT gastropathy is specific to cirrhosis (Payen et al., 1995).

Liver disease (unspecified chronic hepatitis, vascular disease, acute liver failure) can cause gastrointestinal ulceration in dogs. But gastrointestinal ulceration in dogs may result due to various other factors also which include extensive trauma, severe pancreatitis or septicemia, strenuous exercise, corticosteroids, gastroduodenal inflammation, gastroduodenal neoplasia, hypoadrenocorticism, gastric or duodenal foreign bodies, or extragastrointestinal neoplasia (gastrinoma and mast cell tumors) etc. (Daure et al., 2017).

The exact nature of the association between liver disease and gastroduodenal ulceration in small animals is unclear. Recent results also suggest that gastrointestinal (GIT) bleeding is a frequently occuring complication in dogs with acute liver failure. Association between gastrointestinal ulceration and chronic liver disease exists in humans, particularly those with portal hypertension (Daure et al., 2017).

Gastric mucosal lesions are common in portal hypertension. They may lead to significant blood loss, which may be slow and insidious causing anaemia, or sudden and severe, causing massive and occasionally fatal haemorrhage (Cormack et al., 1985).

Major causes of portal hypertension are increased vascular resistance, enhanced blood flow in portal circulation or both. (Buob et al., 2011).

Gastric Homeostasis

 Despite the harsh environment, the integrity of the stomach is preserved by an intricate system of homeostatic mechanisms. Several conditions can disrupt the mucosal barrier of gastrointestinal tract, leading to gastric mucosal damage (e.g., gastritis, gastric erosions, ulcers). Gastric injury occurs when noxious factors overwhelm the natural defenses, as seen when there is overproduction of gastric acid, and also when there is impairment of the gastric cytoprotective defense mechanisms.

The cytoprotective mechanisms in the stomach can be divided in six categories:

(1) pre-epithelial factors, including the mucous barrier and phospholipids; (2) the epithelial barrier, including the surface epithelial cells and tight junctions; (3) epithelial cell turnover; (4) trophic factors and prostaglandins; (5) high mucosal blood flow; and (6) sensory innervations (Daure et al., 2017). The fifth defense mechanism is the high rate of mucosal blood flow supplied by a dense network of submucosal capillaries. This mucosal blood flow, which is regulated largely by PGs, supplies oxygen and vital nutrients to the surface cells and is necessary to meet the high metabolic demand for production of gastric secretory products and cell renewal. Gastric mucosal blood flow is also vital in the disposal or buffering of back-diffusing hydrogen ions by carrying bicarbonate to the mucosal surface (Henderson and Webster, 2006). The chronic liver disease leads to ischemia in GI mucosa that causes portal hypertension and thrombus formation into the gastric vessels (Stanton and Bright, 1989).

Pathophysiology

 Gastric mucosal injury is common in veterinary patients because many regularly used drugs and common diseases can surpass the gastric mucosal defense mechanism. When the integrity of the mucosal barrier is compromised, a cascade of pathologic events follows, contributing to further damage of the mucosal layer. First, the rate of back diffusion of gastric acid and pepsin increases, leading to inflammation and hemorrhage. Various inflammatory (neutrophils, mast cells) and Endothelial cells get activated and release different pro-inflammatory factors like histamine, leukotrienes (LTs), platelet activating factor (PAF), proteases and oxygen free radicals. Histamine release causes further acid secretion, whereas other mediators promote vasodilation, venoconstriction, increased capillary permeability, edema, translocation of inflammatory cells, and capillary plugging. These events exacerbate the initial mucosal damage by reducing blood flow, leading to ischemia, impaired cell renewal, and reduced mucus and PG secretion (Henderson and Webster, 2006).

Hepatic disease, both acute and chronic, is frequently identified as a significant predisposing cause of gastric and duodenal ulceration. In a retrospective study conducted on 43 dogs with gastroduodenal ulceration, hepatic disease and NSAID use most common factors associated with ulceration (Stanton and Bright, 1989).

Satani et al. induced portal hypertension (PH) in dogs by whole liver compression and measured gastric blood flow, tissue oxygen levels and other biochemical indicators of oxygen availability in the gastric mucosa. This group concluded that portal hypertension reduced mucosal blood circulation and oxygen tension indicating that gastric mucosal hypoxia may lead to haemorrhagic gastritis.

The pathogenesis of ulceration associated with liver disorders is still uncertain; reduced mucosal blood flow due to portal hypertension and increased gastric acid secretion secondary to hypergastrinaemia have been suggested as potential mechanisms (Fraser et al., 1993).

Liver disease can also result in hypergastrinemia, although not usually to the degree seen with a gastrinoma. The impairment of normal hepatic function leads to accumulation of various metabolic byproducts and toxic substances that may cause direct injury to gastric mucosa and affect gastric function producing symptoms of gastritis. Increase in permeability of gastric mucosa, decreased mucosal blood flow leading to mucosal ischemia creates an even more acidic environment within gastric mucosa (Webb and Twedt, 2003).

In hepatic disease, the pathogenesis is multifactorial and somewhat speculative, including increased secretion of gastric acid and derangement in mucosal circulation. Increase in acid secretion in hepatic disease is partially due to decreased hepatic degradation of gastrin and histamine, resulting in increased blood levels of these secretogogues and thus increased acid secretion. Compounding this is an increase in serum bile acid concentration, which stimulates gastrin secretion and can induce apoptosis of gastric epithelial cells. Decreased GI mucosal blood flow occurs in chronic liver disorders as a result of portal hypertension (PH) and thrombosis of gastric vessels. In acute liver failure, reduced blood flow may also occur as a result of thrombosis secondary to DIC. Mucus production and epithelial cell turnover are secondarily diminished because of poor mucosal blood flow. (Henderson and Webster, 2006).

According to other study, the pathophysiology of gastric erosions or ulcers in dogs with hepatic pathology is unknown. A recent study showed that gastrin concentration in serum of dogs with hepatocellular diseases and porto-systemic shunts was normal, so hyperacidity due to poor gastrin clearance is likely not an important factor. Other possibilities for gastric damage in hepatic disease include impaired gastric secretion of bicarbonate ions and mucus, microvascular abnormalities, bile acid-induced epithelial cell apoptosis, impaired healing capacity of GIT mucosa, and portal hypertension (Daure et al., 2017).

Gastrointestinal signs, including vomiting, diarrhoea and anorexia, are common in dogs affected with hepatic disorders and may be elicited by gastrointestinal ulceration among other mechanisms (Webster, 2005).

Diagnosis of Portal Hypertension

 CBC: Microcytosis is commonly seen. Other findings include anemia, thrombocytopenia or both.

Liver Function Tests (LFTs): Abnormal LFT is a significant indicator of PH. Concentration of ammonia in blood or that of bile acids in serum may be increased due to multiple acquired portosystemic shunts (MAPSS). Other indicators of liver dysfunction in cats or dogs with portal hypertension include hyperbilirubinemia, decreased serum albumin, urea nitrogen (BUN) and cholesterol concentrations.

Coagulation Parameters: Prothrombin time (PT) and activated partial thromboplastin time (APTT) are reliable indicators of coagulation disorders in dogs and cats with portal hypertension and consequently indicate the degree of hepatic dysfunction. Decreased concentrations of antithrombin, fibrinogen and protein C in serum also indicate liver dysfunction associated with portal hypertension in cats and dogs.

Measurement of blood pressure (BP) in portal vein: Dog: >11 mmHg

Ultrasound: Ultrasonography (USG) is a very useful non-invasive tool to detect the gastric ulceration in dogs. Ultrasonographic findings associated with gastric ulcers include thickened gastric wall, loss of the 5-layered structure, defect in wall or accumulation of fluid in stomach and decreased gastric motility. The localized thickening of gastric wall varies from 0.9-1.6 cm. The crater is often localized centrally in thickened site and appears as a defect in mucosa along with persistent accumulation of tiny echoes, representing micro bubbles. However, there is no definitive differentiation between malignant and benign ulcers, and gas within the gastric lumen may interfere with imaging (Parrah et al., 2013).

Detection of MAPSS: It appear as a network of small, twisted splenic to renal blood vessels in left dorsal peri-renal area. There is decreased velocity of blood flow in portal vein along with decreased hepato-fugal flow in portal vein. Single congenital shunt can be differentiated from Multiple AV shunts, as the latter are greater in number (more than 2) and smaller in size (less than 4 mm). there may be hepatomegaly with hypoechoic liver with due to posthepatic PH or liver may be decreased in size due to chronic disease (Buob et al., 2011).

Treatment of gastropathy induced by hepatic disease

 Gastrointestinal (GIT) ulceration accompanied by hepatobiliary dysfunction can be treated with :

• Antacids: H2 receptor blockers or proton-pump inhibitors (PPIs)
• Mucosal protectants like sucralfate

H2 Blockers may cause a rare idiosyncratic reaction in human beings leading to hepatotoxicity but there are no such reports in veterinary medicine as of now (Buob et al., 2011).

Adjunctive therapy with antiemetics, fluid therapy and elimination of predisposing factors all contribute to successful ulcer management.

Surgical treatment (Resection of the ulcer with or without pyroplasty, Bilroth I or II, vagotomy) is indicated when uncontrolled haemorrhage, gastric outlet obstruction or acute perforation occurs (Stanton and Bright, 1989).

References: 

• Buob, , Johnston, A.N. and Webster, C.R.L. 2011. Portal hypertension: pathophysiology, diagnosis, and treatment. J Vet Int Med. 25(2): 169-186.
• Webb, and Twedt, D.C. 2003. Canine gastritis. Vet Clin Small Anim. 33(5): 969-985.
• Daure, , Ross, L. and Webster, C.R. 2017. Gastroduodenal ulceration in small animals: part
  1. Pathophysiology and epidemiology. J Am Anim Hosp Assoc. 53(1): 1-10.
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• Satani, , Yamana, H. and Kakegawa, T. 1986. Studies on hemorrhagic gastritis after extended gastric devascularization using portal hypertensive dogs. Nihon Geka Gakkai Zasshi. 87(10): 1284-1292.
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• McCormack, T., Sims, J., Eyre-Brook, I., Kennedy, H., Goepel, J., Johnson, A.G. and Triger,

D.R. 1985. Gastric lesions in portal hypertension: inflammatory gastritis or congestive gastropathy?. Gut. 26(11): 1226-1232.

• Webster, C. L. 2005. History, clinical signs, and physical findings in hepatobiliary disease. In Textbook of Veterinary Internal Medicine. 6th edn. Eds S. J. Ettinger, E. J. Feldman. Elsevier pp 1422–1435.

Traumatic Reticuloperitonitis[TRP] (Hardware disease, Traumatic gastritis)

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