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==Introduction==
==Introduction==
Uraemia describes the clinical systemic syndrome that occurs in animals suffering from [[Kidney Renal Failure - Pathology|renal failure]]. Traditionally, uraemia was thought to be caused by [[Azotaemia|azotaemia]], an increase in the blood concentrations of urea and creatinine, but it is now apparent that multiple '''uraemic toxins''' cause derangements in many metabolic processes. Azotaemia is important in the diagnosis of uraemia but it is an insensitive indicator of renal failure, only becoming detectable when more than approximately two thirds of the nephrons are no longer functional.
Uraemia describes the clinical systemic syndrome that occurs in animals suffering from [[:Category:Renal Failure|renal failure]]. Traditionally, uraemia was thought to be caused by [[Azotaemia|azotaemia]], an increase in the blood concentrations of urea and creatinine, but it is now apparent that multiple '''uraemic toxins''' cause derangements in many metabolic processes. Azotaemia is important in the diagnosis of uraemia but it is an insensitive indicator of renal failure, only becoming detectable when more than approximately two thirds of the nephrons are no longer functional.
===Pathophysiology===
===Pathophysiology===
===Gastro-intestinal Disease===
===Gastro-intestinal Disease===
*'''Oral ulceration''' - This occurs especially at the [[Oral Cavity Overview - Anatomy & Physiology|fauces of the mouth ]]and on the margins of the [[Tongue - Anatomy & Physiology|tongue]]. Halitosis is often a feature of this syndrome as the lesions become secondarily infected with oral bacteria such as ''[[Fusobacterium necrophorum]]''. In severe cases, there may be extensive subepithelial necrosis and sloughing of the tip of the tongue. The lesions are often very painful and contribute to the anorexia often observed in animals with chronic kidney disease. Excessive dental calculus may be evident in animals with chronic kidney disease on oral examination.
*'''Oral ulceration or uraemic [[stomatitis]]''' - This occurs especially at the [[Oral Cavity Overview - Anatomy & Physiology|fauces of the mouth ]]and on the margins of the [[Tongue - Anatomy & Physiology|tongue]]. Uraemic vasculitis and thrombosis lead to necrosis and sloughing of the mucosa. There is irritation of the tissues from the ammonia produced by the bacterial degradation of urea. Halitosis is often a feature of this syndrome as the lesions become secondarily infected with oral bacteria such as ''[[Fusobacterium necrophorum]]''. In severe cases, there may be extensive subepithelial necrosis and sloughing of the tip of the tongue. The lesions are often very painful and contribute to the anorexia often observed in animals with chronic kidney disease. Excessive dental calculus may be evident in animals with chronic kidney disease on oral examination.
*'''[[Gastric Ulceration - all species|Gastric ulceration]]''' - This occurs for three main reasons. First, urea crosses lipid membranes freely and enters the gastro-intestinal lumen of azotaemic animals. The urea is degraded to ammonia by bacterial urease and the ammonia irritates the intestinal mucosa. This is compounded by damage to the blood vessels of the gastric submucosa by the fibrinoid necrosis that is a common feature of uraemia. Elevated serum concentrations of gastrin (which is normally metabolised in the kidney) also lead to excessive production of gastric acid from parietal cells in the stomach. Animals with gastro-duodenal ulceration may show '''anorexia''', '''vomiting''', '''haematemesis''' and [[Peritonitis - Cats and Dogs|'''peritonitis''']] and '''haemorrhage''' if the ulcers perforate. Hypergastrinaemia may also cause incompetence of the pyloric sphincter of the stomach, permitting reflux of irritant bile into the stomach. Similar processes result in the development of '''uraemic colitis'''.
*'''[[Gastric Ulceration - all species|Gastric ulceration]]''' - This occurs for three main reasons. First, urea crosses lipid membranes freely and enters the gastro-intestinal lumen of azotaemic animals. The urea is degraded to ammonia by bacterial urease and the ammonia irritates the intestinal mucosa. This is compounded by damage to the blood vessels of the gastric submucosa by the fibrinoid necrosis that is a common feature of uraemia. Elevated serum concentrations of gastrin (which is normally metabolised in the kidney) also lead to excessive production of gastric acid from parietal cells in the stomach. Animals with gastro-duodenal ulceration may show '''anorexia''', '''[[vomiting]]''', '''haematemesis''' and [[Peritonitis - Cats and Dogs|'''peritonitis''']] and '''haemorrhage''' if the ulcers perforate. Hypergastrinaemia may also cause incompetence of the pyloric sphincter of the stomach, permitting reflux of irritant bile into the stomach. Similar processes result in the development of '''uraemic colitis'''.
*'''[[Peritonitis - Cats and Dogs|Uraemic peritonitis]]''' - This is a form of chemical peritonitis that results from inflammation of the small mesothelial blood vessels.
*'''[[Peritonitis - Cats and Dogs|Uraemic peritonitis]]''' - This is a form of chemical peritonitis that results from inflammation of the small mesothelial blood vessels.
===Respiratory Disease===
===Respiratory Disease===
*'''[[Pulmonary Oedema|Pulmonary oedema]]''' - Damage to the small vessels of the pulmonary vasculature may result in the development of vasogenic pulmonary oedema and pleural effusion with dyspnoea, tachypnoea and coughing.
*'''[[Pulmonary Oedema|Pulmonary oedema]]''' - Damage to the small vessels of the pulmonary vasculature may result in the development of vasogenic pulmonary oedema and pleural effusion with dyspnoea, tachypnoea and coughing.
*'''Uraemic pneumonitis''' - This disease occurs due to movement of leucocytes into the alveoli and alveolar septa.
*'''Uraemic pneumonitis''' - This disease occurs due to movement of leucocytes into the alveoli and alveolar septa leading to oedema.
*Can have patchy or diffuse deposition of calcium on the alveolar walls.
===Electrolyte and Acid/Base Imbalances===
===Electrolyte and Acid/Base Imbalances===
*'''Electrolyte imbalances''' - The failure to excrete phosphate through the damaged kidneys results in hyperphosphataemia. This electrolyte complexes with calcium and also prevents the activation of vitamin D (dihydroxycholecalciferol), resulting in hypocalcaemia. This hypocalcaemia directly stimulates the production of parathyroid hormone (PTH) to try to maintain normal blood calcium levels and, in ~10% dogs with renal failure, hypercalaemia may develop due to an alteration in the set-point at which PTH is secreted. In the remaining 90%, calcium is mobilised from bone causing '''secondary renal hyperparathyroidism''' with resorption of bone, pathological fractures and fibrous osteodystrophy of the bones of skull ('rubber jaw').
*'''Electrolyte imbalances''' - The failure to excrete phosphate through the damaged kidneys results in hyperphosphataemia. This electrolyte complexes with calcium and also prevents the activation of vitamin D (dihydroxycholecalciferol), resulting in hypocalcaemia. This hypocalcaemia directly stimulates the production of parathyroid hormone (PTH) to try to maintain normal blood calcium levels and, in ~10% dogs with renal failure, hypercalaemia may develop due to an alteration in the set-point at which PTH is secreted. In the remaining 90%, calcium is mobilised from bone causing '''secondary renal hyperparathyroidism''' with resorption of bone, pathological fractures and fibrous osteodystrophy of the bones of skull [[Hyperparathyroidism|('rubber jaw')]].
*'''Metastatic mineralisation''' - The presence of excessive blood concentrations of phosphate leads to metastatic calcification in multiple tissues, particularly the rugae of the gastric mucosa, the pulmonary parenchyma and the heart.
*'''Metastatic mineralisation''' - The presence of excessive blood concentrations of phosphate leads to metastatic calcification in multiple tissues, particularly the rugae of the gastric mucosa, the pulmonary parenchyma and the heart.
*'''Metabolic acidosis''' - The kidney plays a vital role in the regulation of the normal acid/base balance.
*'''Metabolic acidosis''' - The kidney plays a vital role in the regulation of the normal acid/base balance.
*Parathyroid hyperplasia
===Cardiovascular Disease===
===Cardiovascular Disease===
*'''Atrial rupture''' - Mineralisation of the atria reduces their normal compliance and renders them susceptible to rupture. The resultant haemopericardium is often fatal as it causes acute cardiac tamponade.
*'''Atrial rupture''' - Mineralisation of the atria reduces their normal compliance and renders them susceptible to rupture. The resultant haemopericardium is often fatal as it causes acute cardiac tamponade.
*'''[[Arrhythmias Overview|Arrhthymias]]'''
*'''[[Arrhythmias Overview|Arrhthymias]]'''
*'''Necrotic endocarditis''' - necrosis of the endocardium in the left atrium. Lesions may also occur in the pulmonary artery and aorta with erosions being associated with thrombus formation.
*'''Cardiac hypertrophy''', especially left-sided, as a result of hypertension following release of renin from chronically damaged kidneys.
===Haematological Disease===
===Haematological Disease===
*'''[[Thrombocytopathia]]''' - The reduction in platelet function occur due to multiple alterations in normal [[Thrombocytes|thrombocyte]] metabolism.
*'''[[Thrombocytopathia]]''' - The reduction in platelet function occur due to multiple alterations in normal [[Thrombocytes|thrombocyte]] metabolism.
*'''[[Anaemia - Introduction|Anaemia]]''' - This occurs because the diseased kidneys produce less erythropoietin than normal and the uraemic toxins (especially PTH) decrease the lifespan of existing red blood cells. Erythrocytes may also be damaged as they pass along inflamed vessel walls, a form of microangiopathic haemolysis. Chronic gastro-intestinal haemorrhage may also result in iron deficiency.
*'''[[Regenerative and Non-Regenerative Anaemias|Anaemia]]''' - This occurs because the diseased kidneys produce less erythropoietin than normal and the uraemic toxins (especially PTH) decrease the lifespan of existing red blood cells. Erythrocytes may also be damaged as they pass along inflamed vessel walls, a form of microangiopathic haemolysis. Chronic gastro-intestinal haemorrhage may also result in iron deficiency.
===Neuromuscular Disease===
===Neuromuscular Disease===
The underlying cause of the renal failure should be treated. To alleviate the clinical signs of uraemia, it is particularly important to restrict phosphate by feeding a '''low phosphate diet''' and using '''phosphate-binding drugs''' such as aluminium hydroxide or chitosan. Deficient electroylytes should be supplemented but calcium should only be administered after hyperphosphataemia has been corrected to prevent further mineralisation of soft tissues.
The underlying cause of the renal failure should be treated. To alleviate the clinical signs of uraemia, it is particularly important to restrict phosphate by feeding a '''low phosphate diet''' and using '''phosphate-binding drugs''' such as aluminium hydroxide or chitosan. Deficient electroylytes should be supplemented but calcium should only be administered after hyperphosphataemia has been corrected to prevent further mineralisation of soft tissues.
Various [[Gastroprotective Drugs|gastro-protectant drugs]] can be prescribed to manage the gastro-intestinal signs of uraemia, including sucralfate and the acid secretory inhibitors ranitidine, cimetidine and omeprazole. Appetite stimulants such as mirtazapine can also be administered to anorexic animals to encourage voluntary food intake.
Various [[Gastroprotective Drugs|gastro-protectant drugs]] can be prescribed to manage the gastro-intestinal signs of uraemia, including sucralfate and the acid secretory inhibitors ranitidine, cimetidine and omeprazole. Appetite stimulants such as mirtazapine can also be administered to anorexic animals to encourage voluntary food intake. Oral pain can be controlled by topical application of lidocaine gel or sucralfate paste.
A major advance in the management of uraemia has been the introduction of '''recombinant erythropoietin''' which can be administered to anaemic animals as a series of subcutaneous injections. Some animals may become resistant to its effects over time due to the development of an immune response to the recombinant protein.
A major advance in the management of uraemia has been the introduction of '''recombinant erythropoietin''' which can be administered to anaemic animals as a series of subcutaneous injections. Some animals may become resistant to its effects over time due to the development of an immune response to the recombinant protein.
Renal failure that is sufficiently severe to cause uraemia is very severe and carries a poor prognosis for recovery. Lost renal function cannot be recovered and the best that can be hoped for is to manage the clinical syndrome as long as the patient maintains an acceptable quality of life.
Renal failure that is sufficiently severe to cause uraemia is very severe and carries a poor prognosis for recovery. Lost renal function cannot be recovered and the best that can be hoped for is to manage the clinical syndrome as long as the patient maintains an acceptable quality of life.
==Literature Search==
{{Learning
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|Vetstream = [https://www.vetstream.com/canis/search?s=uraemia Uraemia]
|flashcards = [[Veterinary Dentistry Q&A 17]]
|literature search = [http://www.cabdirect.org/search.html?it=any&q2=uremia&q1=uraemia&calendarInput=yyyy-mm-dd&occuring1=title&show=all&rowId=1&rowId=2&rowId=3&options1=AND&options2=OR&options3=AND&occuring3=freetext&occuring2=title&publishedend=yyyy&la=any&publishedstart=yyyy&fq=sc%3A%22ve%22&y=8&x=70 Uraemia publications]
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==References==
Ettinger, S.J, Feldman, E.C. (2005) '''Textbook of Veterinary Internal Medicine (6th edition, volume 2)''' ''Elsevier Saunders''
{{review}}
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[[Category:Oral Cavity - Metabolic Pathology]]
[[Category:Oral Cavity - Metabolic Pathology]]
[[Category:Respiratory_System_-_Pathology]][[Category:Cardiovascular_System_-_Metabolic_Pathology]]
[[Category:Lungs_-_Pathology]][[Category:Cardiovascular_System_-_Metabolic_Pathology]][[Category:Renal Failure]]
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