liver is the Gate keeper of the systemic circulation-- blood from all digestive organs goes to it for it to scrutinize. Works as a metabolic filter, and removes translocated bacteria/toxins/drugs.
pic recapping liver anatomy and the flow of portal blood
in what direction does bile flow?
OPPOSITE THE BLOOD FLOW! bc bile ducts are with the portal veins.
what is the portal zone?
what is the lobular zone? why do we care about it?
we care because damage in different zones (portal vs lobular)
zone 3 damage might indicate..
hypoxia, Copper tox
zone 1 damage might indicate..
non-specific reactive, CHOLESTASIS (remember bile flows in opposite direction, so if bile duct backs up this is the first place it affects) and toxicity (bc portal vein brings toxic stuff which needs to be metabolized here first)
what will a FNA of the liver look like with cholestasis. histology?
explain how the portal tract/triad will be affected with cholestasis?
more bile ducts appear, vacuolated hepatocytes/damaged limiting plate of hepatocytes, inflammatory cells, edema..
easy way to recognize cholestasis in pts?
Pre-hepatic reason for icterus
hepatic reason for icterus
post-hepatic reason for icterus
bile duct obstruction
what is icterus/what causes this?
elevated serum bilirubin
what are the 3 measurements/types of bilirubin, explain how they are related?
obv you can measure total bilirubin. So then there is conjugated vs unconjugated. The LIVER is what conjugates the bilirubin. So before it gets to the liver it is unconjugated, and isn't water soluble, so it is bound to albumin. When it is processed by the liver, it becomes conjugated ( ester with glucuronic acid is what conjugation is) and after it is conjugated it is secreted into bile. Bile goes to poop--> bacteria degrade it into stercobilin (why poop is brown). OR enterohepatic recirculation & urinary excretion causes it to be urobilinogen.
how might you be able to tell that the icterus is pre-hepatic?
pre-hepatic is hemolysis, so you would also see them being pale and yellow
how would you be able to tell if icterus is due to hepatic causes? (ex's of what would cause this)
ALT > ALP elevation, you would also see Hepatocytic: hepatitis/cirrhosis, lipidosis, FIP, lymphoma.
ALP vs ALT with icterus-- which means what?
IF ALT IS HIGHER... HEPATIC PROB. IF ALP IS HIGHER...BILIARY OBSTRUCTION (post hepatic)
how would you be able to tell if a icterus is due to extra/post-hepatic causes? (ex's of what would cause this)
alp elevated (alt variable), Pancreatitis, cholangitis,foreign body, neoplasia, sepsis…
what is the million things Hepatocytes do?
Bile production, Glycogen storage, Urea synthesis, Metabolize fat, Synthesize plasma proteins( Including clotting and anti clotting factors), Detoxify drugs and toxins, Activates hormones, Extramedullary hematopoiesis
what do kupffer cells do?
Specialized macrophages, part of RES (mononuclear phagocyte system (MPS) also known as the reticuloendothelial system(RES) )
what do stellate cells do? (aka?)
aka Ito cells. dormant until activated, live in the space of disse, involved in fibrosis
how does ammonia come about in the body? (2 types of sources) and how does the liver deal with ammonia?
There are Endogenous and dietary sources- bacterial, intestinal, high protein meals/GI blood, Lean body mass breakdown (ammonia is made of nitrogen, nitrogen comes from protein) So Ammonia arrives at liver through portal vein, and it is converted into urea and then released into the systemic circulation (for kidney to pick it up later)
what are ammonia and urea levels like with a PSS?
since portal vein is shunting around the liver, the ammonia doesn't reach the liver to be converted into urea, so high systemic ammonia and low urea
what are ammonia and urea levels like in hepatic lipidosis?
since the liver is kinda crapped out, even though the blood is going to the liver, it can only convert a LITTLE bit of the ammonia into urea, so there is still high systemic ammonia and low urea.
fasting cats are esp at risk of hepatic lipidosis-- aside from very low urea levels, what other parameter is off?
(1) an excess of ammonia leading to the ammonia-glutamate pathway (more in other card) (2) high ammonia coming from the GI (diet/bact) (3) diseased liver (has high capacity, can still remove some of the ammonia) (4) cats with hepatic lipidosis
what are the CSs of HE like in CATS? what are the causes in cats?
Less specific symptoms than in dogs: apathy, salivation, stupor. ***IN CATS, HE ISNT RESTRICTED TO PSS--- OFTEN ASSOCiATED WITH HEPATIC LIPIDOSIS
poster child for HE in dogs?
explain why AMMONIA causes CNS depression
excess ammonia (NH3) crosses BBB and the NH3 inhibits glutaminase from converting glutamine into glutamate. Which means now there is a lot of glutamine. The high levels of glutamine efflux out of the brain in exchange for an Influx of aromatic Aminoacids, esp tryptophane and tyrosine, and tryptophane is converted into serotonin and tyrosine to dopamine. and serotonin and dopamine have sedative and hypotensive effects
what will CBC look like with HE?
microcytes, and target cells (bc cholestasis---her notes: chlosterol ↑in Intrahepatic cholestasis...put more in cell membrane? wiki says: In patients with obstructive liver disease, lecithin cholesterol acetyltransferase activity is depressed, which increases the cholesterol-to-phospholipid ratio and produces an absolute increase in the surface area of the red cell membrane. In contrast, membrane excess is only relative in patients with iron-deficiency anemia and thalassemia because of the reduced quantity of intracellular hemoglobin)
what is UA like with with HE?
Dilute USG, Ammonium biurate crystals, Bilirubinuria, Urobilinogen (hemolysis-- probably because of crappy RBC membranes bc the cholesterol synth is messed up, idk)
how are cholesterol levels different between PSS, fibrosis, and intrahepatic cholestasis?
in PSS/FIBROSIS, the cholesterol decreases. In cholestasis, the cholesterol increases (lecithin cholesterol acetyltransferase activity is depressed)
DIAGNOSTIC TEST: LIVER FXN VS LIVER DAMAGE
FUNCTION: (CBAG) Cholesterol, BUN, Albumin, Glucose.....and then also bilirubin (conjugated), coagulation factors, and bile acids. DAMAGE: you see inc levels of liver ENZYMES with DAMAGE bc cell damage releases the enzyme inside of them. ALT, AST, ALP, GGT inc
what are the 4 liver enzymes?
ALT, AST, ALP, GGT
which enzyme is actually a good indicator of specifically hepatocyte injury?
what is AST? what does an inc in it mean?
aka Aspartate Aminotransferase, this is a Mitochondrial enzyme which is a Marker for cellular damage. IT IS NOT SPECIFIC TO THE LIVER. It is suggestive of LIVER OR kidney, myocardial, or muscle damage. **CHECKING FOR AST IS NOT A FXN TEST. Generally a sec inc is 2-3x normal (not true in cats tho)
what is ALT? what does an inc in it mean?
aka Alanine Aminotransferase. it is a Cytoplasmic enzyme and is a **** Accurate indicator of hepatocyte injury. MAx at 48 hrs post-injury. Remember that its NOT A FXN TEST.
when is ALT at a max after injury? what is half life like? what kinda incs are used to indicate how bad the damage is?
Max at 48 hours post acute injury. Half life in dogs is like 3 DAYS but only like 6 HOURS in cats. IN DOGS a mild injury is like 1-2x, moderate 3-5x, >5-10x is severe. ***only for dogs, not true in cats (bc peak at 48 hrs but cats halflife is only like 6hrs lol )
which enzyme= cholestasis?
ALP (can be intra or extrahepatic) ....GGT too (leaks out of bile duct, so only extrahepatic)
what is ALP? what does an inc in it mean?
aka Alkaline Phosphatase, it is MEMBRANE BOUND (such as in the bile canaliculi). NOT a function test! However, there are many ISOENZYMES of ALP-- liver, steroids (in dog- endogenous AND exogenous which can be differentiated), Phenobarbital, bone, preg, skeletal growth.
in _________ any elevation of ALP is a concern
what is GGT? what does an inc in it mean?
Membrane bound, bile duct epithelium. It is parallel to ALP and is less affected by steroids in dogs.
concurrent eval of ALP and GGT is probably beneficial in cats... what can it tell us?
They think if ALP > GGT might mean hepatic lipidosis
Isolated enzyme elevation: What would you do it the pt was.... asymptomatic? exceptions?
recheck in 4-6 weeks-- UNLESS IT IS A DOMBERMAN then you should immediately follow up with a bile acids test bc they tend to get liver dz without clinical signs
Isolated enzyme elevation-- if still elevated after waiting 4-6 weeks, or there is symptoms, what do you do next? what are the two possible results from this?
DO A BILE ACIDS TEST! If the BAs are normal, wait another 4-6 weeks. If they are abnormal, time for more follow up tests
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