Lots of UNCONJUGATED/indirect bilirubin means the prob is where?
liver dz (liver too sick to convert it so pre-conversion part is high)
***where and how blood gets broken down: so start with old RBC or lysed RBC or something.... how do we get to conjugated bili?
MACROPHAGES break down Hgb/myoglobin to biliverdin, which in blood binds to albumin which makes it UNCONJUGATED/INDIRECT bilirubin.--> goes to liver, liver conjugates it to be bilirubin CONJUGATED/DIRECT (conjugated onto glycoproteins and glucose)--> once conjugated goes out with the bile, through the bile duct, to the GIT
if you have high CONJUGATED/DIRECT biliruben, where is the problem then?
bile duct obstruction (technically unconj and conj would be dammed up, depending on chronicity)
why might neonates not have color in their feces if there is shunting, but an adult will still have feces color?
chloroform will donate color to the feces...but bbs still only on milk
what does HSL (hormone sensitive lipase) do?
stimulates FAT BREAK DOWN and the release of NEFA (non-esterified fatty acids) and FFA (free fatty acids)/ TG (triglycerides) into the blood which travel to the liver. (HSL affects insulin sensitivity (dec it) bc insulin is a storage enzyme and HSL is an unpacking enzyme)
what is the thing that comes out of the liver once the liver has too much fat in it?
explain how more insulin vs more glucagon affects the liver and fat metabolism
lots of glucagon= inc fat break down (bc wants to make glucose available to the cells) and release of VLDL from liver. lots of insulin= less fat break down and no release of VLDL from liver
what ratio contols HSL?
which hormone tells the liver to release VLDL?
liver beta-oxidizes fatty acids which results in _________ which has implications for...
acetyl CoA, which plays a big role in the krebs cycle (make energy!)
what are propionate and acetate? why do we care about them?
These are VFAs (volatile fatty acids) which are the main energy sources for ruminants!
which VFA can keep krebs cycle running?
2 things rumis have to keep krebs cycle running?
glucose or propionate
If you dont have glucose or propionate donating to the krebs cycle, what happens? (explain path to ketones)
you end up stopping the TCA (krebs/citric acid) cycle....which means you have to mobilize fat, that fat goes into beta-oxidization (under the influence of HSL) which releases acetyl CoA, but can't go into citric acid/krebs cycle without the glucose or propionate, so it has to find somewhere else to go, so it makes ketones. And rumis are reallly good at making ketones
when is a very common time to see problems with ketones in rumis?
they just gave birth, want to make colostrum for baby, so all the glucose and propionate goes to make lactose. which means TCA cycle cant run. So acetyl CoA dams up and fills up the liver. So then you get fatty liver.
which tissues struggle to use ketones as an energy source?
brain can use some ketones but also has to use glucose. Most tissues can use ketones. The liver MAKES ketones, but cant really use them for its own energy
what are the 3 ketones again?
acetoacetate, acetone, hydroxybutyrate
so the liver can make ketones or pump out VLDLs. what are VLDLs composed of? what is the part Rumis dont have much of, what implications does this have?
triglyceride+ cholesterol+Apolipoprotein A or B. BUT rumis dont have a lot of the apolipoproteins. This means they dont get to export a lot of VLDLs to blood....which means they are really good at making fatty livers.
icterus (improper disposal of RBC waste, damming back of bili, not common in rumi's but can happen), edema (liver makes proteins for oncotic pressure bc makes albumin..but liver is pretty trashed before this happens. more commonly, liver lymphatics have high protein content, and there is portal hypertension, so when that lymphatic stuff leaks out to make ascites, it leaks out a lot of protein, which leaks into abdomen, and draws even more fluid), coagulopathy (makes clotting factors-- liver has to be pretty bad to see this- factors 2,7,9,10 are affected bc liver stores vitamin K), **CHRONIC WEIGHT LOSS(*FIRST THING YOU SEE USUALLY.)(liver is important for metabolism, and "metabolism engine" is kinda destroyed--> probs with weight gain), sunburn/photosensitization (chlorophyll-->phyloerythrin), hepatic encephalopathy, tenesmus-->rectal prolapse (they dont know why), diarrhea (portal hypertension damming blood back into GI-->intestinal wall edema--> fluid in intestinal tract), ascites/pendulous abdomen with fluid wave
what is the main thing that causes hepatic encephalopathy?
AMMONIA (bc liver not working well enough to covert ammonia to urea so it builds up)....we also feed them ammoniated feeds, but need to feed at constant rate. if irreg, or stop and then start,the microflora arent primed for it.
why might rumi be hypoglycemic with liver prob?
(not super common bc rumis dont really run off glucose, but more common in prerumis) liver metabolises glucose
why is serum BUN lower in liver failure?
liver is what turns ammonia into urea. (microbes use urea to make proteins) so can be confusing bc if have starved animal and not making proteins, microbes can suck up urea from blood and use that to make proteins for themselves...so might see low BUN in an animal that has been starved that doesnt have liver dz
why do you see hypoalbuminemia in liver dz?
liver makes albumin-- T1/2 for albumin is about 14-16 d and liver has to be pretty damaged to stop making albumin
how is bilirubin affected with liver dz?
inc total bili: cholestatic dz, moderate inc of direct bili more common with hemolysis in rumis (what she basically is saying is high bili-- think hlysis before liver dz)
which clotting factors are affected by liver dz
major ones are 2,7,9,10. but 1 and 11 are also affected
liver fxn things?
CBAG= cholesterol, BUN, albumin, glucose
what is the most sensitive enzyme for hepatocyte damage?
IDH (formally known as SDH)-- but super sensitive. even bumping the liver can elevate this.
SDH (AKA IDH. SAME THING. NOW IDH)-- what does this tell you?
this is the MOST SENSITIVE enzyme for liver damage. (almost too sensitive)
what is GLDH? what does it tell you?
aka glutamate dehydrogenase. good to tell you about ACUTE (not chronic) liver dz, but not commonly run at labs so not always helpful
what does GGT (gamma glutamyl transpeptidases) tell you?
present in ANY duct system, useful for telling you about bile duct problems, useful for liver dz in rumis. Tell you about biliary dz first, but if liver dz can lead to damage to bile ducts, GGT will come up (common in rumis. even in sthing like h.lipidosis which usually doesnt damage bile ducts, you can see GGT coming up). Slide says: tells you about biliary dz in animals, but tells you about HEPATOBILIARY dz in rumis.
most important liver enzyme for ruminants- and why?
GGT (gamma glutamyl transpeptidases)-- its a DUCT enzyme, but in rumis even liver problems which normally dont inc GGT can inc it
when is GGT inc considered sig?
what is AST? what does it tell you? (how is it useful, how is it not useful)
aspartate aminotransferase. It is useful in that it has a longer half life than SDH/IDH (past 2-3x normal is sig). Not useful bc ALSO originates in mm and RBCs
what does ALP tell you?
hard to interpret bc there are wide fluctuations of normal and can come from different place in the body. Can indicate cholestasis, hepatocyte damage, or bone activity (growing youngstock)
Trematodes: fasciola hepatica, fasciola magna (fasciola gigantica in the tropics)
what kinda lifecycle do liver flukes have?
indirect- usually some asshole sail involved. IH is snail. either can eat snail or vegetation snail was on (snail= galba/lymmnya sp)
where do you find diff stages of liver fluke?
Adult F. hepatica in bile ducts. Adult F. Magna in liver parenchyma (stuck bc cattle aberrant host)...immature for both burrow through parenchyma.
which stages of the fluke are pathogenic?
short answer: larval stages. long answer: larvae burrow in the liver, irritate that, then move to bile ducts, irritate that, start growing into adults in bile ducts, chronic inflammation leads to bile duct calcification
what kinda environment do we find liver fluke probs in?
pasture with ponds/dams/streams (esp stagnant water)
when is the transmission period of flukes (when do cattle/ small rumis get infected)?
WARM WEATHER- depends on where you are in the world when that is. Where there is a mild winter and a brutal summer, transmission occurs in late winter and through spring. Where there is a harsh winter and a mild summer, transmission occurs in late spring and through summer and fall
how do we dx liver flukes in cattle?
fecal sedimentation, serum or milk Ab levels (ELISA)
how many liver flukes make a sig. economical impact?
MILD impact: 10-40 worms. SEVERE economic impact: 40-200 worms.
how many eggs of liver flukes would be considered a significant economic impact? when would you do the fecal sedimentation
do 2-4mo after transmission time (immature larva arent gonna sen out eggs, gotta wait for maturity). (3eggs/2g=possible impact). 10 eggs/2g= SIG impact
what are the 3 drugs we can use to tx fascioliasis, which is good for treating younger flukes? juveniles? mature?
(1) Triclabendazole can treat less than 2 week old matures but resistance is common. (2) albendazole treats mature flukes (at least 20wk) in bile ducts. (3) clorsulon treats mature and 6 week old juveniles
so which drug is able to kill flukes at their youngest-- and how old is that?
clorsulon at 6w juvenile stage
WHEN should you treat for liver flukes?
Basically needs to be between >12wk old (so old enough to tx-- earliest kill with clorsulon at 6w) but less than 6mo bc at that point they have already done damage and drugs are less effective (albendazole for matures)
3 most sig. consequences of liver fluke infection in cattle?
(1) poor production. (2) blacks disease (clostridium novyi type B) (3) Bacillary hemoglobinuria (clostridium novyi type D)
What is the fancy name for red water dz? Toxins? What causes it? CS? dx?
Bacillary hemoglobinuria, caused by clostridium novyi type D (aka C. hemolytica). Has beta toxin, which hepatic necrosis, hemolysis (duh), and capillary endothelial damage. It can lead to sudden death andd big irreg infarcts in the liver. Dx: IFA on liver, PCR on blood. (vs have short lived efficacy)
What causes black dz? what toxins? CSs?
caused by clostridium novyi type b (b for blacks) has alpha (entry) AND beta toxins (necrotizing) (so tripple B-- Black type B with Beta (and alpha bc triple bonus) ) toxins enter blood and cause damage to tissues (neurons, vascular endothelium), can be congestion of skin sudden death. NO red urine, but fast autolysis. (vx short lived :()
epistaxis, haemoptsis, also tachycardia, tachypena, pyrexia. Cool extremities and dull. sounds like what dZ?
Caudal vena cava syndrome
explain pathogenesis of caudal vena cava syndrome
Ruminal acidosis--> rumen wall damage--> ruminal bact colonize in rumen wall--> bake abscesses there, translocate via blood to liver--> overwhelm kupfer cells, start making abscesses in liver--> also moves to heart and lungs via ca vena cava from liver as septic thrombi. Hemoptysis/epistaxis caused by erosion of BVs
most common valve affected by valvular endocarditis, why?
(often associated with ca vena cava syndrome) tricuspid valve is first valve encountered by septic thrombi from liver
most common bact involved in ca vena cava syndrome? (explain it a bit)
Fusobacterium necrophorum: Gram negative anaerobe that likes to ferment starches and uses up lactate (hence it flourishes in ruminal acidosis), has endotoxins (allow it colonize ruminal wall). (also other possible bact include: Trueperella, Bacteroides spp, Clostridium, soliforms(aka coliforms), pastureslla, peptostreptococcus Povetella, staph, strep)
if you encounter a Ca vena cava syndrome case, how do you tx?
Antimicrobials: **penicillin, **tylosin(good for anaerobes), chlortetracycline, oxytetracycline
in terms of herd management, how can you help prevent ca Vena Cava syndome?
balance diet better- avoid grain overload, SARA
possible routes of infection for the liver?
(1) septic emboli via hepatic artery (2) umbilical vein in neonate (remember its the neonate vein-- think about portal vein, this is bbs portal vein in mom) (3) bile duct system with GI obstruction/ diarrhea (4) direct extension (TRP)
what is the toxic principal in senico? how does it cause liver damage?
contains Pyrrolizidine Alkaloids, bioactivated in the liver, it alkylates/cross-links DNA--> inhibits mitosis, leading to megalocytosis. Eventually megalocytes replaced by fibrosis
what are CSs associated with pyrrolizidine alkaloid tox? (what plants again?)
cows much more sensitive than sheeps and goats. (horses also very sensitive)
where are the lesions from pyrrolizidine alkaloids most commonly seen? which biochem thing is most likely to be elevated (most sig)
seen around CENTRAL region the most (aka zone 3--- where things are coming in and getting bioactivated and PAs are bioactivated to active compounds. she said zone 1 in class buttttt im gonna go with tox on this one, if the toxin isnt bioactivated and is just toxic in and of itself, then it would be zone one.)-- GGT will be most activated
what is a ddx for phylloerythrin (photosensitivity)
could be facial excema caused by fungus making sporidesmin which grows on pasture
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