16 – Liver Flashcards
1
Q
What are some roles of the liver?
A
- Synthesizes many different proteins
- Detoxifies many substances
- Synthesizes lipoproteins, cholesterol, TGs
- Participates in fat metabolism
- Secretes bile and digestive substances
- Formation of lymph
- Storage of substances
- Participates in endocrine, immune system, BP and some blood storage
2
Q
What are some causes of hepatocellular damage/injury?
A
- Toxins
- Inflammation
- Neoplasia
- Ischemia/hypoxia
- Metabolic
- Traumatic
- Intralesional hemorrhage
3
Q
Portal triad
A
- Hepatic artery branch: bring nutrients from the body
- Portal vein: drains caudal half of body and metabolites, brings in nutrients from GI tract
o Goes towards the central vein to caudal vena cava to heart - Bile duct
o Goes in opposite direction and collects in bile duct
o If hepatocytes swell=block the bile duct
4
Q
What does hepatocellular damage look like on a small animal chem panel?
A
- ALT (alanine aminotransferase): Muscle injury can also contribute, but it is usually minimal
- GLDH (glutamate dehydrogenase): from mitochondria
- SDH (iditol dehydrogenase): ‘whiny’ (so use it but not anymore, except horses)
5
Q
What does hepatocellular damage look like on a large animal chem panel?
A
- AST (aspartate aminotransferase): in the cytoplasm, not specific for the liver, muscle damage can also contribute
o Also look at CK values to determine if muscle injury - GLDH can be used
- SDH=valuable in HORSES
6
Q
What is structural cholestasis?
A
- Obstruction of flow/excretion of bile
- Intrahepatic and extrahepatic
7
Q
Intrahepatic cholestasis
A
- Hepatic injury with cell swelling=compress upon adjacent biliary canaliculi
- Inflammation of bile ducts (cholangitis) or periportal inflammation
- Ex. hepatic lipidosis, hepatic neoplasia
8
Q
Extrahepatic cholestasis
A
- Obstruction outside of liver (gall bladder, common bile duct obstruction) =extrahepatic biliary system
- Physical obstruction
- Ex. cholelithiasis (gallbladder stones), neoplasia, pancreatitis, cholecystitis
9
Q
Biliary tree: cat
A
- Common bile duct empties into intestines and at a common place in the pancreas (common bile duct)
o If cat has pancreatitis can get scarring=can get a retrograde cholestasis (doesn’t happen in a DOG as often) - The cystic duct ‘fills’ the gall bladder
10
Q
What is functional cholestasis?
A
- NO physical obstruction present
- Excretion of conjugated bilirubin from hepatocyte to canaliculi is impaired
- *defects/downregulation in bile transporter (sepsis)
- Ex. altered cytokine environment or a patient with sepsis (impaired transport of bile)
11
Q
What do you see on a chem panel for cholestasis?
A
- ALP (alkaline phosphatase): membrane bound, different isoforms
o *SHORT half life in cats=any elevation even if mild is significant! - GGT (gamma-glutamyl transferase): membrane bound
- Elevated bilirubin
- Elevated cholesterol
- Can cause elevated bile acids
- (defects in Vit K-dependent factors)
12
Q
ALP in cholestasis
A
- Isoforms
o Bone (ex. bone remodelling)
o Liver (ex. cholestasis)
o ONLY canids: steroid-induced (ex. chronic stress, Cushing’s, GC therapy) - Can be hard to determine what is contributing
o Take other factors into consideration
13
Q
GGT increased
A
- Cholestasis
- Could also suggest biliary hyperplasia
14
Q
What are different causes of elevated cholesterol?
A
- Cholestasis
- Non-fasted sample
- Endocrinopathies: hypothyroidism, DM, Cushing’s
- Pancreatitis
- Nephrotic syndrome
15
Q
What is a pre-hepatic cause of hyperbilirubinemia?
A
- Hemolysis=MAIN CONTRIBUTOR
o Albumin ‘carries’ the unconjugated bilirubin to the liver
o Amount of bilirubin generated overwhelms liver’s capacity to uptake and bilirubin continues to circulate while ‘waiting in line’ - ‘NOT the liver’s fault’
16
Q
Fasting/anorexia hyperbilirubinemia
A
- Can occur in horses, sometimes bovine and cats
- Enhanced lipolysis for energy leads to increased FFAs in serum/plasma
o FFA can compete with hepatocyte receptors for bilirubin=results in bilirubin accumulating in serum
17
Q
Hepatic and post-hepatic hyperbilirubinemia: causes
A
- The same things that cause intrahepatic and post-hepatic cholestasis
18
Q
What are some bilirubin fractions that can be measured?
A
- Direct bilirubin: conjugated bilirubin
- Indirect bilirubin: unconjugated bilirubin
- *used as a guide, understanding the pathophysiology is much more IMPORTANT
19
Q
Example: IMHA with marked yet comparable elevations in both direct and indirect bilirubin
A
- Pre-hepatic hyperbilirubinemia COUPLED WITH hypoxic hepatopathy LEADING TO hepatic hyperbilirubinemia (hepatocyte damage=blockage=elevated conjugated bilirubin too)
20
Q
Hepatocellular injury vs. function
A
- Liver can have injury, but retain adequate function
- Injury can occur independent of cholestasis (but often are found together)
- *use chem panel findings
21
Q
How do you evaluate for a hepatopathy?
A
- Chem panel
- Imaging
- FNA +/- biopsy
o Look for changes to hepatocytes; architecture or evidence of disease
22
Q
*What are 4 things to look for on a chem panel when there is hepatic insufficiency?
A
- Low urea value
- Hypoalbuminemia
- Hypocholesterolemia
- Hypoglycemia
- *if 2 or more decreased=increase your suspicion of liver problems/failure
23
Q
How do you confirm hepatic insufficiency?
A
- Imaging: small liver size, evidence of extrahepatic shunt
- Bile acid challenge test (false positives and negatives can occur)
- Ammonia clearance test
o Do NOT perform if patient is seizuring or has other neurological signs) - Ammonia measurement in patients with low urea values (per rectum or per os)
- Biopsy to check micro-architecture: intrahepatic shunt (check hemostasis parameters first!
24
Q
What are the steps for the bile acid test?
A
- Collect fasted serum sample
- Feed small amount of food (ex. high fat meal=stimulates gall bladder contraction)
- Collect serum sample 2 hours later (if above threshold=not doing its job and ‘absorbing’ the bile acids)
25
Q
What are some causes of elevated (post-feeding) bile acids?
A
- Decreased hepatic function (liver failure)
- Altered enterohepatic circulation (portosystemic shunt)
- **cholestasis
o Do NOT perform bile acids test if patients with clinical icterus or overt hepatic or post-hepatic cholestasis (increased direct/conjugated bilirubin) - ‘normal’ Maltese dogs have higher serum bile acids than other breeds
26
Q
Why might there be random (not pre/post) elevated bile acid concentrations in horses?
A
- No gallbladder
27
Q
What might be contributing if fasting bile acids is GREATER THAN post-prandial bile acids?
A
- Premature gallbladder contraction
28
Q
What might lower bile acid concentrations?
A
- Prolonged fasting
- Intestinal malabsorption
- Altered GIT transit time
29
Q
What are two things that can contribute to increased blood ammonia levels?
A
- Liver failure
- Portosystemic shunts (PSS)
30
Q
How can you test ammonia levels?
A
- Fasting ammonia levels can be measured, but difficult
o Very TIME sensitive so not practical in most clinics (within 60min) - “Tolerance” test: collect second sample after giving oral ammonium chloride
o Ammonia is highly toxic=neurological symptoms
o Rarely performed as risk of causing hepatic encephalopathy
31
Q
What are some hemostatic disorders an animal with liver disease might exhibit?
A
- *decreased hepatic production of coagulation factors
- *decreased activation of Vit K-dependent enzymes (2, 7, 9, 10) in cholestatic liver disease
o Vitamin K is fat soluble=needs bile secretion for absorption - Production of abnormal factors: dysfibrinogenemia
- Initiation of DIC
- Defects in platelet number and function
32
Q
What can be done for as a minimum bleeding risk assessment?
A
- Platelet count
- PT
- PTT
- *prophylactic Vit K therapy, may or may not need treatment
- *blood products available if going to biopsy
33
Q
Portosystemic shunts
A
- Abnormal single or multiple blood vessels which directly connect the blood supply from the intestines to the systemic circulation
- Congenital and acquired
- *congential portal vein hypoplasia with microvascular dysplasia: ‘microscopic’ intrahepatic shunts (affects many of the same breeds as congenital extrahepatic PSS)
34
Q
Congenital portosystemic shunt
A
- Intrahepatic: medium-large breed dogs (Ex. Irish Wolfhounds)
- Extrahepatic: small breed dogs (Yorkies, Maltese, ShihTzus and cats)
35
Q
Acquired portosystemic shunt
A
- Extrahepatic: multiple reasons, end stage liver disease (cirrhosis) and portal hypertension
36
Q
Congenital PSS signs
A
- Poor weight gain, stunted growth, poor recovery from anesthetic
- May see neurological abnormalities or GI signs
- May develop urate calculi
37
Q
Congenital PSS: common lab abnormalities
A
- Microcytic anemia (non-regenerative)
- Decreased BUN, albumin, cholesterol
- Increased liver enzymes (may be mild)
- Ascites with protein-poor transudate
- Increased bile acids (fasting and post-prandial) and plasma ammonia levels
- Ammonium urate crystalluria
38
Q
Congenital PSS Dx
A
- Imaging +/- portogram
- Exploratory
- Liver biopsy with histopathology
39
Q
Congenital PSS treatment
A
- Medical management (low protein diet, lactulose) +/- surgical closure
40
Q
Congenital portal vein hypoplasia
A
- Many asymptomatic or have very mild signs
- Common lab abnormalities
o CBC/chem/UA often normal
o Often have normal fasting, but increased post-prandial bile acids
o Liver histopath: similar changes as congenital PSS - Dx: vascular imaging studies + liver biopsy
- Good prognosis (may affect up to 50% of yorkies)
- Rarely: dogs are more severly affected=may go on to develop multiple acquired shunts
41
Q
Is hemoglobinemia in an adult dog significant?
A
- Not considered clinically significant
o Monitor, especially if patient is dehydrated and you’ll be giving fluids
42
Q
What is acute liver failure in dogs? What can cause it?
A
- *sudden loss of 70% or more of liver function due to massive hepatic necrosisi
- Toxins
o Blue-green algae
o Amanita mushrooms
o Aflatoxins in pet food - Drugs
o Carprofen
o Acetaminophen - Infectious agents
o Leptospirosis
o Canine adenovirus-1
43
Q
Mushroom toxicity In dogs
A
- Amanita phalloides
- Amatoxin: GI crypt, hepatocytes, renal tubular cells
- 4 phase of clinical disease
o Latency period
o GI signs
o False recovery
o Fulminant hepatic, renal and multiorgan failure - Dx: history of ingestion, ID of specimen, urine tox screen
44
Q
Xylitol toxicosis in dogs
A
- Dose-related insulin release (6x greater than glucose)=may lead to SEVERE hypoglycemia
o Onset of signs: rapid or delayed
o Vomiting, weakness, ataxia - *lab findings
o Hypoglycemia
o Mild to moderate hypokalemia: transcellular shifting (K into cells)
o Liver enzyme elevations - Good prognosis if uncomplicated hypoglycemia +/- mild liver enzyme elevations (guarded if sever liver enzyme increases, ~60% fatal)
45
Q
Hepatic lipidosis in cats
A
- Excessive accumulation of fat (TGs) in liver leading to liver failure
- Secondary to marked decrease in appetite, especially in obese cats
o Underlying process: change in diet, stressful event, concurrent metabolic or digestive disease - Clinical signs: rapid weight loss, jaundice, v/d, lethargy, enlarged liver, muscle weakness
- Dx: can be confirmed with FNA of liver (cytology)
- *high ALP with low to normal GGT = not specific for hepatic lipidosis so follow-up with imaging/cytology for confirmation
