21:00 min Clinical Manifestation and Screening of Liver Disease (Rudinsky In Class Feb 3rd) Flashcards
Notes Card
SBA Testing:
- 2 hr post-prandial SBA (PPSBA)
- Stimulates EHC
- Endogenous challenge test
- Food considerations
- protein and fat content (release CCK)
- < 10 lbs … > 2 tsp
- > 10 lbs … > 2 tbsp
- Liver-specific function test
- Portosystemic shunting
- Severe hepatocellular dysfunction
- Urea cycle abnormality
What test is this?
Blood Ammonia
The liver plays the single most important role in the detoxification/clearance of many different substances such as:
- Drugs
- Toxins
- Hormones
- Metabolites
Hepatic Drug Metabolism:
- Primary oxidation
- Enzymes of SER (microsomal)
- Usually inactivates drugs
- May convert active to active
- May convert pro-drug to active drug
- May bioactivate to toxic compound
Phase I
Hepatic Drug Metabolism:
- Primary conjugation
- Occurs in ER or cytosol
- Renders H2O soluble/less toxic/readily excreted
- Species differences
- Glutathione conjugation**
- Less susceptible (than Phase I) to the effects of disease and other drugs
Phase II
- Making things less toxic
(T/F) Hepatic dysfunction and effects of clearance can be predicted
False, unpredictable & complex
Characterize features:
- decreased albumin, decreased BUN, decreased cholesterol, decreased glucose
- increased SBA; coagulopathy not responsive to Vit K
Hepatocellular dysfunction (Metabolic dysfunction)
Characterize features:
- increased ALT/AST»_space;> ALP
Hepatocellular injury
Characterize features:
- Increased ALP»_space;> ALT
- Hyperbilirubinemia, bilirubinuria
- Increased cholesterol, Increased SBA, Vit K response coagulopathy
Cholestatic Disorder
Characterize features:
- Increased NH3; N to Increased FSBA/Increase PPSBA
Possible portosystemic shunting
** FILLER CARD **
Hepatobiliary Vascular Disorders and Hepatic Encephalopathy (Rudinsky - Feb 7th - In Class)
- These are the following cards after this
- Anorexia - Dull
- Lethargy - Difficulty training
- Disorientation - Behavioral changes
- Head-pressing* - Blindness
- Circling, pacing - Hypersalivation
- Ataxia - Seizures
- Weakness - Coma
Hepatic Encephalopathy
- metabolic encephalopathy = signs can wax and wane; may be normal at times
(T/F) Brain effects of substances normally metabolized by the liver
True
Hepatic Encephalopathy: Neurologic disorder
Portosystemic Shunts:
- Single shunting vessel
- Intrahepatic (large breed dogs)
- Extrahepatic (cats, small dogs)
Congenital
- young animal showing early signs
Portosystemic Shunts:
- Multiple (2 degree to portal hypertension)
- Much less common
Acquired shunts
List the Clinical findings for PSS:
- CNS signs
- Hepatic encephalopathy
- Hypersalivation (CATS)
- GI signs
- Intermittent vomiting/diarrhea
- Pica/repeated FB ingestion
- Urinary tract signs
- pU/pD
- Hematuria, dysuriaa, pollakiuria (urate stones)
- Other
- stunted growth, drug intolerance; prolonged anesthetic recovery
Hepatic Blood Flow (HBF)
- 20% of HBF
Arterial blood flow
Hepatic Blood Flow (HBF)
- 80% of HBF
Portal blood flow
- Vascular communication between the portal and systemic venous systems
- Portal blood bypasses the liver
Portosystemic Shunt
The portal blood drains from:
- Intestines
- Stomach
- Pancreas
- Spleen
If you see elevated bilirubin, is it useful to then go on and do Serum Bile acids testing?
No, because it’s the same saturable system
- Bilirubin is pulled out by hepatocytes from the blood & sent to excreted in the bile
- If bilirubin is increased, you will automatically have abnormal bile acids
** FILLER CARD **
Hepatobiliary Vascular Disorders and Hepatic Encephalopathy (Rudinsky - Feb 7th - In Class)
- Radiography **
- Ultrasonography (very dependent on the user, sensitivity is bad for this (inconclusive))
- Angiography
- Portogram
- Arteriogram
- Venogram - Portal scintigraphy (referral center)
- CT/MRI (referral center)
These are …
Imaging for Hepatobiliary disease
What are the treatments for Congenital PSS?
- Medical management of HE
- Protein-restricted diet
- Lactulose, antibiotics
- Correct precipitating events - Shunt attenuation (Surgery)
Congenital PSS
Definition:
- Is an inner ring of casein that is surrounded by a stainless steel sheath
- Slow closure –> gradual closure
Ameroid Constrictor
Complications:
- Portal Hypertension
- Seizure
- Hemorrhage
- Hypoglycemia
- Treatment Failure
** FOLLOWING CARDS **
***** Hepatobiliary Disease
Cholestatic Liver Dz, LECTURE 3 **
Cat with Yellow ear
What’s with the yellow?
Icterus or Jaundice
- Indicates that T bili > 2.5 mg/dl
- Bilirubinuria
- Rarely Acholic feces (complete bile duct obstruction)
- RBCs are broken down into three components and are repackaged and reutilized
- HEME has to be ______________
Metabolized
Definition:
- excess unconjugated bilirubin is produced faster than the liver is able to conjugate it for excretion
- anything that lyses RBCs
- Elevated unconjugated bilirubin in serum
Prehepatic (hemolytic) Jaundice
- IMHA
- Cats less common…
What can you do to determine where the bilirubin is coming from?
- PCV/TS **
- CBC
- Clin Path
Cats
- Anemia signs predominate
- Anemia is usually regenerative (4-6 day lag time)
- Infectious Ddx
- Noninfectious Ddx
This describes …
Pre-hepatic Cats
Definition:
- Hepatocytes can’t do their job, because something is blocking it
- Problem with liver
- Both conjugated and unconjugated bilirubin may be elevated in serum
Intrahepatic Jaundice (Hepatic)
Definition:
- Impaired excretion due to mechanical obstruction to bile flow
- Elevated conjugated bilirubin in serum
Extrahepatic Jaundice (Post-hepatic)
Variable appearance:
- Diffuse enlarged, hyperechogenicity
Hepatic lipidosis
Variable appearance:
- Hypi/Iso/Hyperecho
Cholangiohepatitis
Variable appearance:
- Nodules, diffuse hyper/ hypoechogenicity, mixed patterns
Neoplasia
List the top three most common Cholestatic Liver Diseases:
- Hepatic Lipidosis (30%)
- Idiopathic
- Secondary - Cholangitits (29%)
- Neoplasia (23%)
List the Diagnostics for Cholestatic Liver Disease:
- Blood work
- Imaging
- Aspirates
- Biopsy
- Empirical treatment
- Most common feline liver disease
- Obese cats, anorexia, wt loss
- Massive hepatic fat accumulation
- Intrahepatic cholestasis ***
- Hepatic failure
- Fatal without treatment, curable with food
Feline Hepatic Lipidosis
- Stressful Triggers (“Primary”)
- Diet change
- Boarding
- Social environment (new pets, people, or home)
- Nonhepatic catabolic illnesses (“Secondary”)
These are Clinical Associations for …
Feline Hepatic Lipidosis
- Middle-ag or older cats
- No breed or sex predisposition
- Prior obesity
- Prolonged anorexia (> 2 weeks)
- Weight loss (often >25%)
- Vomiting, lethargy, diarrhea or constipation, hepatic encephalopathy infrequent
- PE: icterus, hepatomegaly, dehydration, muscle wasting; ventroflexion of head/neck
These are Clinical Findings for …
Feline Hepatic Lipidosis
- Cholestatic pattern
- Increase ALP > Increase ALT
- But normal GGT
- Hyperbilirubinemia
- Bilirubinuria
- Increase serum bile acids
- Vit K responsive coagulopathy
- Increase ALP > Increase ALT
These are Lab Findings for …
Feline Hepatic Lipidosis
What is the “key” for hepatic lipidosis?
You feed them!
- once you put nutrients back into the system, it reverses it
- There are 3 types (rare disease)
- Neutrophilic - Most common primary disease
- Liver lobe involvement variable
- Confusing literature
- Different classification schemes
Feline Cholangitis
- Ascending biliary bacterial infection
- Gram neg
- anaerobes - Inflammation focused on bile ducts
- Necrosis of hepatocytes beyond limiting plates
This is describing …
Feline Cholangitis - Neutrophilic
- Pancreatitis
- IBD
- Cholecystitis
- Cholelithiasis
- Sludged bile
- Biliary obstruction
These are Associated Conditions for …
Neutrophilic Cholangitis
- Liver biopsy
- Bacterial culture** better
- Aerobic
- Anaerobic
- Liver or BILE
- Surgery
- If biliary obstruction
These are Diagnoses for …
Neutrophilic Cholangitis
- Chronic signs (tends to be less severe)
- Middle-aged/older
- Signs
- Vomiting, diarrhea, jaundice
- May be episodic
- Hepatomegaly
This is describing …
Cholangitis - Lymphocytic
List the indications for Liver Biopsy:
Methods
- ULS-guided (small samples)
- Laparoscopy
- Surgery
- Persistent increase in liver enzymes or SBA
- Abnormal hepatic parenchyma including liver mass(es)
- Acute versus chronic
- It is going to be better for Chronic disease evaluation - Obtain quantitative Cu
- Monitor therapy
Liver Biopsy
What are the Pre-biopsy Considerations (liver patients can bleed)?
- Hemostasis evaluation
- Method of biopsy
- Pre-biopsy treatment
- Vitamin K1
- Plasma transfusion
Liver Biopsy
What are your post-biopsy evaluations?
Monitor
- PCV
- TPP
- ULS
- Other
When doing a liver biopsy, what evaluations are you doing?
- Cytology
- Histopathology
- Culture
- Chemical analysis
- test for heavy metals
What is a nutrient class that is most effective at reducing lipid accumulation in neg energy balance?
Protein
What do fats and fat-soluble vitamins require for absorption?
Micelle formation
Vitamin K Deficiency: Liver Disease
Treatment:
What route of administration is essential to treat vitamin K deficiency due to biliary obstruction?
Parenteral (IV, IM, SC not PO)
Hepatoprotectants:
- Synthesized and found in almost every cell type
- Hepatocytes maintain particularly high levels
- Physiologic and metabolic functions
- Antioxidant
Glutathione
Hepatoprotectants:
- Provide glutathione (antioxidant)
- Enteric-coated
- Empty stomach
- Nontoxic
- May cause upset stomachs
S-Adenosylmethionine (SAMe)
Hepatoprotectants:
- Acts as a nutritional antioxidant
Vitamin E (alpha-Tocopherol)
Hepatoprotectants:
- Flavonoid mixture
- Derived from seeds of Silybum marianum
- Natural liver remedy for >2000 years (ancient Greece)
- Variable amounts in products
- Variable absorption
- Herbal supplement (Antioxidant)
- Antifibrotic
- Anti-inflammatory
- Decrease hepatic uptake of Amanita mushroom toxicity
Milk Thistle (Silybin)
Hepatoprotectants:
- Ursodeoxycholic acid
- 1-degree bile acid in Chinese Black Bear
- Hydrophilic bile acid
- Healing powers
- Now commercially synthesized
- Marketed for dissolution of cholesterol gallstones (man)
- Other effects on liver
Ursodiol (Actigall)
- Fav used in tOSU
Hepatoprotectants:
What do we get from Ursodiol (Actigall)?
- Anti-inflammatory
- Anti-fibrotic
- Immunomodulatory
- Choleresis
Mechanisms: - Replace hepatotoxic hydrophobic bile acids
“Dog” Extrahepatic Cholestasis EHBDO:
- Is an inappropriate accumulation of mucus or inspissated bile in the gallbladder lumen
Gallbladder Mucocele
- Kiwi appearance
“Dog” Extrahepatic Cholestasis EHBDO:
- Is a medical condition resulting from the formation of stones in the gallbladder
Cholelithiasis
“Dog” Extrahepatic Cholestasis EHBDO:
- Tumors, etc
Biliary Obstruction
List what to do to manage Biliary Obstruction:
- Vitamin K
- Parenteral
- 24-48 hrs
- Antibiotics
- Exploratory surgery
- Relive obstruction
- Bacterial culture
- Tissue biopsy
