Metabolism And Excretion Lecture 6- Why Is It Yellow And Headpressing?

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signs of liver dysfunction/failure usually only manifest if:

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bile outflow is obstructed
livers large reserve function and regenerative capacity are depleted

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jaundice

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icterus
yellow discoloration of tissue and body fluids due to an excess of bilirubin in blood (hyperbilirubinaemia)

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cholestasis

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reduced flow of bile
may be intrahepatic and/or extrahepatic
common cause of jaundice but not all cases of jaundice are caused by this

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haemolysis

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PRE HEPATIC JAUNDICE
excessive breakdown of erythrocytes may overhwlem the capacity of hepatocytes to take up and conjugate unconjugated bilirubin

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haemolysis examples

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intravascular haemolytic anaemias
extravascular haemolytic anaemias
occassionaly see mild jaundice after severe haemmorage into internal body cavity with lysis of the extrvasated erythrocytes

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hepatocellular disease

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jaundice results from decreased uptake and conjugation of bilirubin by hepatocytes and especially from decreased secretion of objugated bilirubin

secretion of conjugated bilirubin into bile canaliculi is energy dependent and is the rate limiting step in bilirubin metabolism in most speices

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intrahepatic cholestasis

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common and commences in periacinar zones (zone 3) where bile flow comences

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intrahepatic cholestasis steps

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as bile accumulates, cannliculi becomes distended and plugged by bile and there is bilirubin discoluration of the cytoplasm of the hepatocytes

hepatocyte necrosis or canaliculi/cholangiolar rupture---> local release of bile-->inflammation +/- necrosis ( called bile infarcts); bile pogments may then be taken up by nearby kupffer cells

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toxins and intrahepatic cholestasis

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damaging smooth ER of hepatocytes in which bile conjugation and intracellular bile satl transport occurs or by damaging the contracile actin and myosin filaments in the periacanalicular cytoplasm of heptocytes

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anorexia and intrahepatic cholesatsis

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can develop in anorexia especially in horses

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bacteraemia/speticeaemia and intrahepatic cholestasis

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can develop due to bacteraemia/speticeaemia (jaundice of sepsis) although mechanisms not completely understood

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extrahepatic obstruction of bile flow (post-hepatic jaundice)

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obstruction of bile ducts by luminal parasites, choleliths (gall stones), inflammation, fibrosis or neoplasia
see initial distention of extrahepatic ducts immediatly proximal to obstruction
in liver first becomes obvious in portal areas
may cause extensive fibrosis around bile ducts

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jaundice may be detectable in mucous memebranes of small animals when the total serum bilirubin concentration exceeds

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35 micromol/L

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photosensitisation

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develops in herbivores with intra or extra hepatic cholestasis of several days duration if eating green feed and if exposed to sunlight

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photosensitisation steps

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phylloeythrin (photodynamic agen produced by action of herbivores GI bacteria on chlorophyll) --> transported to the liver in portal venous blood--> excreted by hepatocytes via the same mechanisms as bilirubin

in choleostasis phylloerythrin leaks from hepatocytes into the general circulation and is deposited in tissue

in the skin it is activated by absorption of UV light (290-400 nm wavelength) to produce reactive oxygen species (free radicals) that damage nuclei, cell membranes and organelles in adjacent cells

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photosensitisation signs

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lesions usually restricted to hairless or sprsley haired, non or lightly pigments skin exposed to sunlight

skin hyperaemia (reddening due to increased perfusion with aterial blood), oedema, intense prutitus ( ithciness), self-excoriation (self traumatic damage), exudation and necrosis , desiccation and sloughing

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photosensitisation cause example

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example: facial eczema caused by mycotoxin, sporidesmin

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hepatic encephalopathy seen in

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common in ruminants and horses with hepatic failure and in dogs with portosystemic shunting and chronic hepatitis

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hepatic encephalopathy clinical signs

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anorexia, depression, dullness, lethargy, compulsive or aimless movment, subtle behavioral changes, mania, siezures, circling, headpressing, central blindness, tremors, ataxia, fever, nausea, hypersalivation, and/or intermittent vomiting and diarrhoea

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hepatic encephalopathy definition

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complex, mutifacotiral autointoxication due to failure of hepatic detoxification function or circulatory bypass of the liver

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hepatic encephalopathy- encephalotixins implicated

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ammonia
mercaptans
shor chain fatty acids
skatoles
indoles
aromatic aa
octopamine
tryptophan
seratonin
gamma aminobutyric acid

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hepatic encephalopathy pathogenisis

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ammonia is responsible for most of the structural lesions in the brain--> accumulation by astrocytes-->cytotoxic oedema--> altered gene expression and neurotransmission and cerebral oedema

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hypoalbuminaemia

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due to long half life it develops only late in hepatic disease when at least 78-80% of functional mass is lost

chronic heptaic dysfunction, protein losing nephropathy, protein losing enteropathy, chronic protein malnutirtion are likley to cause severe hypoalbuminaemia (<20 g/L)

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ascites

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accumulation of non inflammatory oedema fluid in the abdominal cavity associated with hepatorenal pathology develops most commonly in cats and dogs, occasionaly in sheep and rarley in cattle and horse.

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pre hepatic mechanims for ascites

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any condition that leads to portal hypertension e.g external compression of the protal vein by a space occupying mass in the abdmonial cavity

portal hypertension venous blood pools in veins, venules and capiliary beds of the stomach, intestine, spleen, pancreas and mesentaries = passive congestion
increased blood volume trapped in microcirculation-->increased plasma hydrostatic pressure-->transudation of low protein fluid from capilliaries into bowel lumen and from other cappiliairies into abdominal cavity

typically a transudate

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acites due to increased hydrostatic pressure in the perisinusoidal space

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most common mechanism
leads to increase lymph formation
post hepatic mechanisms

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acites due to increased hydrostatic pressure in the perisinusoidal space
post hepatic mechanisms

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right sided heart failure
pericardial disease
obstruction of the thoracic caudal vena cava or heaptic veins
any process that causes increase to resistance to blood flow through heptaic sinusoids (hepatic parnchymal inflammation, neoplasia etc)

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acholic feaces

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bile flow must be completely interrupted to result in acholic feaces

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steatorreah

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due to abscence of bile acids required for fat digestion and interruption of enterohepatic cycling of dietary chlorophyll pigments in herbivores may contribute to faecal pallor

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hepatorenal synfrome

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acute renal failure may develop in animals with cirrhosis and ascites

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bilurubinuric nephrosis

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so called due to being origionally ascribed to putative toxic effect of conjugated bilirubin on renal renal tubular epithilial cells

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ammonium biurate crystalluria

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dogs with portosystemic shunts or heaptic failure develop hyperammonaemia and hence hyperammonuria

suppersatuartion of urine with ammonium ions may promote formation of ammonium biurate crystals, espcially in alakline urine

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drug intolerance in liver

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impaired hepatic biotransformation of administered drugs due to liver failure

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foetor hepaticus

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a musty or sweet and sour odor due to retention in cirulation of mercaptans due to liver failure

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impaired hepatic uptake, conjugation and excretion of steroid hormones

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can lead to hyperoesterognism in males with testicular atrophy/degeneration, and other abnormal secondary sex characteristics due to liver failure

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hepatocutaneous syndrome

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abnormal skin keratinisation--> hypekeratosis and crushing +/- erosion of especially high friction areas due to altered plasma amino acid concentrations due to liver failture

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absence or atresia or extrahepatic bile ducts

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can be of clinical significance and can cause jaundice and deficiency of fat soluble vitamins, affected animals may develop vitamin D deficiency rickets or vitamin K insufficiency , hemmorage

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impaired hepatic uptake, conjugation and excretion of steroid hormones

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can lead to hyperoesterognism in males with testicular atrophy/degeneration, and other abnormal secondary sex characteristics due to liver failure

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hepatocutaneous syndrome

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abnormal skin keratinisation--> hypekeratosis and crushing +/- erosion of especially high friction areas due to altered plasma amino acid concentrations due to liver failture

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absence or atresia or extrahepatic bile ducts

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can be of clinical significance and can cause jaundice and deficiency of fat soluble vitamins, affected animals may develop vitamin D deficiency rickets or vitamin K insufficiency , hemmorage

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congenital portosystemic shunts
cats and small dog breeds

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usually a single extrahepatic shunt between the portal vein and the caudal vena cava or the azygous vein

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congenital portosystemic shunts
large breed dogs

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usually a single large intrahepatic shunt
usually due to presistance of the foetal ductus venosus in the left part of the liver but ocassionaly due to an anomalous vessel elsewhere within the liver

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congenital portosystemic shunts

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an anomalous blood vessel allows a proportion of the portal venous blood returning from the abdominal viscera to be shunted away from the liver into the systemic circulation

bypassed liver typically small in size due to deperivation of hepatrophic factors

cannot rely on biopsy to confirm shunt

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congenital and biliary cysts

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occur in all species
may be dervied from intrahepatic bile duct system or from the hepatic capsule
may be single or mutiple, large or small
cyst content is usually clear and watery and the cyst cavity is lined by epithilium

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displacement of liver

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usually caudal displacment with hepatomegaly or space occupying masses in the thorax
cranial displacment is common in diaphragmatic hernias
lobes strangled by hernial ring undergo congestion and oedema and eventually venous infraction

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liver lobe torsion

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espeically left lateral hepatic lobe in sows and dogs
the lobe undergoes venous infarction

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hepatic rupture

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blunt abdominal trauma
energetic resuscitation in small animals
diffuse hepatomegaly with tension on capsule
rupture of hepatic parynchma may lead to fatal haemoperitenum
parencymal fissure racture responsible for haemmorage may be quite subtale at necropsy