Week 4 - GI Flashcards
1
Q
What are some CS for liver dz?
A
anorexia
vomiting
weight loss
weakness
ascites
polyuria
icterus
seizures
melena
polydipsia
grey feces
lethargy
fever
dark urine
obtundation
2
Q
Why would you get ascites with liver dz?
A
- hypoalbuminemia, decreased colloidal oncotic pressure
- portal hypertension
3
Q
Why would you get seizures with liver dz?
A
hepatic encephalopathy
4
Q
What are the 5 liver parameters that assess function?
A
- Albumin
-made exclusively by hepatocytes
-decreased - BUN
-decreased, since the formation of urea is related to the hepatic metabolism of ammonia (liver takes ammonia and makes BUN)
-would be increased with GI bleeding - Glucose
-decreased, reflecting impaired gluconeogenesis - Bilirubin
-might be normal or increased due to cholestasis - Cholesterol
-synthesized by liver, so severe liver dysfunction is
associated with decreased cholesterol synthesis (hypocholesterolemia)
-but with cholestatic dz – would see an increase
5
Q
Increased liver enzymes tell NOTHING about liver function. What are the liver enzymes?
A
ALT
AST
ALP
GGT
6
Q
What’s ALT?
A
-Alanine aminotransferase (ALT)
-cytosolic
-leakage enzyme – leaks from hepatocytes when cell membrane permeability increases and when the cell undergoes necrosis
-SPECIFIC to liver (small amt in heart, kidneys, muscle)
-t1/2 for dogs: 2.5days (60 hours), so a 50% decrease over 2 to 3 days is a good prognostic sign
-t/12 for cats: 6 hours, MUCH faster, should decrease faster
-anticonvulsants and corticosteroids can cause induction of ALT
-ALT elevation indicates a hepatic abnormality in both species, it provides little information regarding diagnosis, prognosis or appropriate therapy
7
Q
What’s AST?
A
-Aspartate aminotransferase (AST)
-not as specific to liver, present in: liver, skeletal muscle, heart, kidneys, brain, plasma
-Serum AST is derived from liver, skeletal muscle, and cardiac muscle sources
-leakage enzyme
-cytosolic and mitochondrial liver isoenzymes
–cytosolic enzyme: released with reversible or irreversible damage to hepatocyte plasma membranes and usually parallels increases in ALT
–mitochondrial liver enzyme: released only with irreversible hepatocyte injury (necrosis)
-t/12 for dogs: 12 hours
-t/12 for cats: 77 minutes
–so AST should return to normal faster than ALT
-if serum AST is much higher than serum ALT, a muscle source of the enzymes should be explored
–usually and increase in AST + CK would mean skeletal muscle damage is playing a bigger factor
8
Q
What’s ALP?
A
-Alkaline phosphatase (ALP/AP)
-produced by bile duct epithelium (PRODUCTION enzyme)
-found in liver, bone, intestinal mucosa, kidney, and placenta
–usually never released by other organs, so increased ALP can be specific, particularly in cats (nearly all cats with increased ALP will have liver dz)
–ALP bone isoenzyme increases due to osteoblast activity
-Glucocorticoid-induced isoform in DOGS (not cats)
-Mild increases in feline SAP are significant because cats have only one third the concentration of AP per gram of liver than dogs + shorter t1/2
-t/12 of dogs: 66-72hours
-t/12 of cats: 6hours
-ALP bone isoenzyme can increase with osteoblast activity
9
Q
What’s GGT?
A
-Serum gamma-glutamyl transferase (GGT)
-increases due to obstructed bile flow
–most marked elevations in GGT result from diseases of the biliary epithelium, such as
bile-duct obstruction, cholangitis, and cholecystitis
-more sensitive/less specific when compared to ALP for necroinflammatory bile disease
-increases both after administration of glucocorticoids
-GGT»_space; ALP in inflammatory disorders of portal triad and bile ducts
-Both ALP and GGT should always be evaluated concurrently
-in CATS, GGT is more sensitive than ALP for bile dz
**Hepatic Lipidosis: increased ALP, normal-mild increase GGT
**Cholangitis: increased ALP, moderate-marked increased GGT
10
Q
Why is bilirubinemia ALWAYS ABNORMAL in a cat?
A
- Higher renal threshold vs. dog - cat is a 9x threshold, so if bilirubin is high, it is truly high
- Cats cannot conjugate bilirubin in PCRT
11
Q
Why is Increased ALP activity is ALWAYS ABNORMAL in cats?
A
- No corticosteroid-induced isoenzyme
- Short half-life of ALP (6 hours)
- Less ALP in hepatocytes vs. dogs
12
Q
Is triaditis more common in dogs or cats?
A
CATS
liver, pancreas, bowels
13
Q
Common causes of secondary (reactive) hepatopathies
A
- Diabetes mellitus
- Hypoxemia
- Hyperlipidemia
- Hyperthyroidism
- GI disease (e.g., IBD)
- Pancreatitis
- Drug-induced
- Right-sided congestive heart failure
14
Q
What is the Diagnostic Utility of Serum Bile Acids Test?
A
- Relatively sensitive for diagnosing PSS – 88.9% in dogs
*value of function, so don’t need to run serum BA test if you know liver is already trash
- Improves the diagnostic performance of routine
tests for hepatic disease when used adjunctively - One should perform pre- and post-prandial bile
acid measurements
-BAs under enterohepatic circulation
-BA concentrations provide no information regarding the type or severity of the disease, nor does it differentiate primary from secondary liver disorders
-Serum BA test is not usually indicated w icterus unless you cannot differentiate between pre, hepatic, post
–serum BA test usually more indicated when normal
–NORMAL BAs - prehepatic
–HIGH BAs - hepatic or post
15
Q
What is the Diagnostic Utility of Blood Ammonia Test?
A
-marker for liver disease in dogs, particularly
identification of those with HEPATIC ENCEPHALOPATHY due to portal vein vascular anomalies
-ammonia is produced in the GIT, due to microbial degradation of nitrogenous matter in the colon
-ammonia is removed by liver/hepatocytes and converted into BUN
–could be impaired in liver disease or when portal blood does not flow through liver normally
-Blood ammonia in cats is less useful than in dogs, since increases may occur in any disease that produces anorexia
-not routinely done
16
Q
What are common liver dz in cats?
A
- Hepatic lipidosis (idiopathic vs. secondary – 26-50%)
- Cholangitis (inflammation of biliary system)/Inflammatory liver dz – 25%
- Neoplasia – 20%
-Hepatic cyst adenomas
-Lymphoma
-Carcinoma
-Mast cell tumor - Secondary reactive hepatopathies – 16%
- Vascular – 6%
- Toxic – 5%
- FIP - < 2%
17
Q
What is Hepatic Lipidosis?
A
-accumulation of excess triglycerides in hepatocytes with resulting cholestasis and hepatic
dysfunction
->80% of hepatocytes would be vacuolated
18
Q
What is the pathogenesis to Hepatic Lipidosis?
A
-not well understood
-takes up to 6 weeks to see CS
*protein deficiency
* Excessive fatty acid uptake
* Inability to oxidize fatty acids
* Excessive lipogenesis
* Inhibition of synthesis/secretion of very-low-density lipoproteins (VLDLs)
19
Q
What is the prognosis for Hepatic Lipidosis?
A
good, improved over years. good outmode with long term enteral feedingprognosis for IHL is influenced to a large
prognosis affected by the ability of the clinician or owner to aggressively meet the cat’s caloric requirements via enteral feeding
poorer prognosis with pancreatitis
20
Q
What are pre-disposing factors for Hepatic Lipidosis?
A
obesity
stress
anorexia
21
Q
Should you restrict protein from a cat with Hepatic Lipidosis?
A
NO – you should NOT restrict protein from a cat with liver dz (ONLY if it has encephalopathy)
protein is needed for VLDL synthesis, which is already decreased during Hepatic Lipidosis, so help a cat out
22
Q
How do you DIAGNOSE hepatic lipidosis?
A
- Signalment and history
- Moderate-marked increase in ALT and ALP
- Moderate increase in serum bilirubin
- Normal to mildly increased GGT
- Enlarged/hyperechoic liver on ultrasound - LIVER BIG AND BRIGHT
- Vacuolar hepatopathy on cytology and histology
-Most affected cats are clinically jaundiced; hence they will have concurrent hyperbilirubinemia.
23
Q
How do you TREAT Hepatic Lipidosis?
A
- Food aversion plays important role in anorexia
- Do not force feed the cat!
- Appetite stimulants (benzodiazepines) have limited benefits and may exacerbate the hepatopathy
–benzos can be hepatotoxic - oxepezam, diazepam
–Elura, Mirtazapine, Cyproheptadine - Treat the underlying disease!
- Proactive nutritional and fluid support
- Nasoesophageal feeding tube - temp support of critically ill patient
1. small size, so only liquid diet
2. used in patients that can’t go under GA for other feeding tubes
*Esophagostomy or gastostomy feeding tube - need GA for placement - Avoid feeding orally for first 10-14 days following
tube placement - nothing by mouth
–after 10-14 days, try a novel food and see if cat wants to orally eat, if not, wait another 10-14 days and try again with a diff novel food - Do not restrict dietary fat or protein in cats with HL
- Diets containing 25-40% fat (DM) are well tolerated
24
Q
Why is ensuring daily energy intake very important in a cat with Hepatic Lipidosis?
A
-Provision of adequate daily energy intake is the cornerstone of successful medical management
adequate supply of energy is needed to:
1) prevent catabolism of amino acids for energy
2) inhibit peripheral lipolysis
3) avoid excessive energy consumption which will promote hepatic triglyceride accumulation
commercial diets with:
-25-40% fat
-30-45% protein
25
What is one electrolyte that should be particularly assessed in cats with hepatic lipidosis?
POTASSIUM
-cats can be hypokalemic
-may develop due to inadequate potassium intake, vomiting, magnesium depletion, and concurrent
renal failure.
-Hypokalemia was significantly related to nonsurvival
-may prolong anorexia and exacerbate hepatic encephalopathy
-diet should have potassium/the cats should be supplemented with potassium
26
Why would CARNITINE be given to a cat with hepatic lipidosis?
-Carnitine transports long chain fatty acids across the inner mitochondrial membrane into the mitochondrial matrix for β oxidation
-removes potentially toxic acyl groups from cells and equilibrates ratios of free CoA/acetyl-CoA between the mitochondria and cytoplasm
-diets supplemented with L-carnitine can safely facilitate rapid weight loss in privately owned obese cats
27
How do you calculate the RER/resting energy requirements?
* RER = [BW (kg) x 30] + 70 (kCal/day)
-linear formula only good for 2-40kg
* RER = 70 x BW 0.75 (kCal/day)
-logarithmic
-any weight in kg
must feed slow 3-4x a day, 20 min at a time
feed in 20-25% of RER increments
28
What is cholangitis?
-Inflammation centered on the biliary tree/inflammatory disorder of the hepatobiliary system
-often concurrently associated with duodenitis, pancreatitis, cholecystitis, and/or cholelithiasis
29
What are the 3 forms of cholangitis?
1.Neutrophilic (acute and chronic phases) – 80%
-bacterial infections
2. Lymphocytic – 20%
-immune mediated or viral
3. Chronic cholangitis due to liver flukes
30
What are the CS for cholangitis?
non-specific
* Anorexia
* Weight loss
* Lethargy
* Icterus
* Vomiting
* Diarrhea
* Fever (neutorophilic bc infections)
31
What would cholangitis look like on US?
can be associated with:
-gall bladder
-common bile duct distension
-tortuosity
-cholelithiasis
-cholecystitis
-bile sludging
32
What is Neutrophilic Cholangitis?
-infiltration of large numbers of neutrophils into portal areas of the liver and into bile ducts
-Can begin as ascending bacterial infection from the GIT
-Secondary to pancreatitis, IBD, cholelithiasis?
-Predispositions: Congenital or acquired abnormalities of the biliary system, including anatomic abnormalities of the gall bladder or common bile duct and gall stones
33
What bacteria is associated with Neutrophilic Cholangitis?
E. coli
Clostridia
Bacterioides
Actinomyces
alpha-hemolytic Strep
34
You can have acute and chronic Neutrophilic Cholangitis. What's the difference?
difference is histologically is based on:
-presence of increased plasma cells, acute
-lymphocytes ± macrophages with the chronic phase
-Cats with acute cholangitis tend to be younger than chronic cholangitis and HL
-Male cats are more frequently affected with acute neutrophilic cholangitis
35
What is Lymphocytic Cholangitis?
-later stage of neutrophilic cholangitis, or may represent a separate disease entity
-Small lymphocytes mainly restricted to portal areas, variable portal fibrosis, and biliary proliferation
-PORTAL TRIAD LESION
-associated diseases: inflammatory bowel disease
and pancreatitis
36
What is Chronic Cholangitis secondary to fluke infestations?
-happens in Florida, areas like that
-severe ectasia of the bile ducts
-mild to severe hyperplasia of the biliary epithelium
-severe concentric periductal fibrosis
-occasional presence of adult flukes and/or operculate eggs within bile duct lumina
36
What is Chronic Cholangitis secondary to fluke infestations?
-happens in Florida, areas like that
-severe ectasia of the bile ducts
-mild to severe hyperplasia of the biliary epithelium
-severe concentric periductal fibrosis
-occasional presence of adult flukes and/or operculate eggs within bile duct lumina
37
When is Surgical Management of Feline Cholangitis indicated?
Only if discrete choleliths or complete biliary
obstruction observed
Cholecystoduodenostomy or cholecystojejunostomy
38
How do you DIAGNOSE Cholangitis?
-Hematologic and biochemical testing are essential to establish a diagnosis of liver disease
-need BIOPSY to differentiate between cholangitis - liver cytology or histopathology is essential to establish a definitive diagnosis
-BW and imaging can help figure things out, but BIOPSY is needed for a definitive diagnosis
39
Which test is the test that is most consistently abnormal in all types of inflammatory liver diseases and hepatic lipidosis?
Serums Bile Acids / Serum BAs
40
Lab findings of acute cholangitis?
-mild neutrophilia and left shift
-normal to slight increase in serum bilirubin
-normal/slight increase in serum alkaline phosphatase (SAP/ALP)
-substantial increase in alanine aminotransferase (ALT)
This profile tends to differentiate acute cholangitis from chronic cholangitis, hepatic lipidosis, and hepatic neoplasia
41
______ cats frequently have elevations in serum ALT and SAP, although the
magnitude of the elevation tends to be less than that of inflammatory hepatopathies
Hyperthyroid cats
42
Culture of _____ is superior to culture of liver
parenchyma for the isolation of bacteria
BILE
done via US-guided FNAs
43
How do you TREAT cholangitis?
-Treat underlying disease!
-Fluid and electrolyte replacement therapy
-nutritional support
-antibiotics
-immunosuppressives (chlorambucil, prednisolone)
-Ursodeoxycholic acid (Actigall)
-antioxidants (Denamarin which contains SAMe and Silybin)
44
Why is nutritional support important when treating cholangitis?
-many cats undergo esophagostomy tube placement to facilitate enteral nutritional support
45
Why is antibiotics support important when treating cholangitis?
-major specific therapy for acute cholangitis is antibiotics
-abx should be excreted in the bile in active form, and should be active against aerobic and anaerobic intestinal coliforms
-Tetracycline, ampicillin, amoxicillin, erythromycin, chloramphenicol, and metronidazole can be used
--AMPICILLIN OR AMOXICILLIN COMBINED WITH CLAVULANIC ACID AND ENROFLOXACIN are frequently used
-tx 4-6weeks
46
Why would you give immunosuppressives to a cat with cholangitis?
Lymphocytic cholangitis
prednisolone and chlorambucil
47
Why is Ursodeoxycholic acid (Actigall) support important when treating cholangitis?
-neutrophilic or lymphocytic cholangitis
1. anti-inflammatory, immunomodulatory,
and antifibrotic properties
2. Choleretic action: changes composition of bile -- makes it more hydrophilic > enhances bile flow
48
Why are antioxidants (Denamarin) support important when treating cholangitis?
-S-Adenosylmethionine (SAMe) + Silybin
-S-adenosylmethionine increases
hepatic glutathione levels in dogs and cats. Glutathione is a potent antioxidant that protects
hepatocytes from toxins and death.
49
What's the prognosis of Cholangitis?
-Prognosis is extremely variable based on the
underlying cause (neutrophilic vs. lymphocytic)
and the stage of disease
-Survival of cats with the neutrophilic form of cholangitis is fairly good with appropriate antibiotic tx
-Persistent increases in ALT activity and serum total bilirubin concentration and/or increasing SAP activity suggest that treatment has been inadequate
50
What are Hepatic Dz in dogs?
1. “Reactive” Hepatopathy
2. Copper Hepatopathy
-Primary
-Secondary
3. Chronic Hepatitis
4. Portosystemic shunts
-Microvascular dysplasia (Portal Venous Hypoplasia)
5. Hepatic neoplasia
6. Superficial Necrolytic Dermatitis
51
What is Copper Hepatopathy?
-abnormal accumulation of copper within hepatic lysosomes
-Bedlington Terrier, West Highland White
Terrier, Skye Terrier, and Doberman Pinscher
-copper accumulation typically occurs in the centrilobular hepatocytes
-Up to 10,000 ppm (n = < 400 ppm)
-Absorption of copper is enhanced by amino acids and high dietary protein
-absorption of cooper is reduced by zinc, ascorbate, and fiber
52
What are the causes of Copper Hepatopathy in dogs?
-predominantly due to increased dietary Cu and change from CuO to more bioavailable CuSO4
-genetics - Bedlington Terrier
--Autosomal recessive inherited disease
--Deletion of COMMD1 gene – inability to excrete Cu in bile canaliculi
--abnormal expression of the copper binding protein metallothionein.
53
Cholestasis can cause Cu accumulation. What's the difference between cholestasis and Abnormal Cu Metabolism?
* Primary copper metabolic disorders - copper accumulates around the central vein (zone 3 of the liver lobule) = CENTRILOBULAR AREA
* Cholestasis can cause the accumulation of copper primarily localized in the portal tracts (zone 1 of the liver lobules) = PERIPORTAL AREA
-Doberman pinschers (often middle-aged female Dobermans) usually develop hepatic copper accumulation in periportal hepatocytes
look at slide 39 of liver lectures
54
How do you DIAGNOSE Cu-associated Hepatopathy in dogs?
-liver biopsies of multiple liver lobes
because the copper accumulation can be variable from lobe to lobe
* Blood chemistry profile abnormalities
-Increased ALT
-Increased ALP
-increased bilirubin
* Hepatic histochemical staining
* Quantitation of hepatic copper
-Atomic absorption spectroscopy
-Digital image analysis of rhodanine stained sections
55
How do you TREAT Cu-associated Hepatopathy in dogs?
1. Dietary copper restriction (Commercial vs. Home-cooked
-Vitamin E may help protect against copper-induced lipid peroxidation
-affects future Cu levels/absorption
2. Zinc to decrease copper absorption by inducing synthesis of metallothionein (protein)
-Zinc gluconate - 5 mg/kg TID separate from meals
-metallothionein binds copper tightly, rendering it
unabsorbable from the intestine and possibly detoxifying it in the liver
-affects FUTURE Cu absorption, doesn't do anything about current Cu levels
3. Copper chelating agents
-used when Cu levels are higher
-->600ppm w liver changes
-->1000ppm with little liver changes
-should ideally not be administered concurrently with zinc to avoid zinc chelation (so give zinc AFTER chelation)
-D-penicillamine - can be GI toxic
-Trientine (Syprine)
--15 – 30 mg/kg BID prior to meals
--Removes about 1000 ppm Cu/year
4. Anti-oxidants (Denamarin)
5. Ursodeoxycholic acid
56
What 2 liver dz can be diagnosed without a biopsy?
1. PSS
2. SND
57
What is Chronic Hepatitis?
dz can have multiple triggers
* Idiopathic inflammatory condition (genetics of dog + trigger)
-Copper-toxicity
-Infectious diseases (Leptospirosis)
-Drugs (tetracycline, etc)
-Idiopathic causes - most of the time
* Immune mediated disease secondary to hepatocyte injury and release of hepatic antigens
-injury caused by infectious agent, toxin, drug -- causes release of hepatic antigens
58
What breeds are more likely to get Chronic Hepatitis?
-dobermans - females
* Labrador retriever, WHWT, Skye terrier, Dalmatian (Cu-associated)
* Cocker spaniel, standard poodle, Scottish terrier (non-Cu-associated)
59
What is Chronic ACTIVE Hepatitis suggest?
there is a neutrophilic component to the pathology
neutrophils on biopsy
60
What typical age of dogs get Chronic Hepatitis?
-Middle-aged dogs
-Marked predisposition in Dobermans
--> 95% females
61
What are some CS with Chronic Hepatitis?
Weight loss, anorexia, lethargy, PU/PD, icterus, ascites, seizures, bleeding
Presentation is variable:
* Short fulminant course and death
-acute presentation of CS
* Progressive signs of liver disease
--Waxing and waning of signs
* Asymptomatic at presentation
--most animals are asymptomatic
--diagnosing under elective surgeries -- realizing BW looks weird pre-op
62
Lab features of Chronic Hepatitis
* Increased serum activity of ALT and ALP first
* Increased serum bilirubin (75%)
* Hypoalbuminemia (50%)
* Abnormal bile acids
63
Histological features of Chronic Hepatitis
* Early PERIPORTAL infiltrates of lymphocytes and plasma cells
-Neutrophils (active form) and macrophages
-what cells you see depends on stage of disease
* Bile duct hyperplasia
* Bile stasis
* Fibrosis
* Necrosis
64
How do you TREAT Chronic Active Hepatitis?
IMMUNE MEDIATED UNTIL PROVEN OTHERWISE
1. Manage excess Copper if present
2. Arrest inflammation
* Cyclosporine - added benefit of not altering ALT and ALP activity
* Prednisolone
* Azathioprine?
* Ursodeoxycholic acid
3. Resolve fibrosis
* Colchicine? - prevent future deposition of fibrosis, not routinely used
4. Zinc, esp with Cu tox
5. Antioxidants (Denamarin)
6. Ursodeoxycholic acid
7. Treat hepatic encephalopathy if present
65
What are Portosystemic Vascular Shunts?
-anomalies reflect the abnormal presence of one or more vascular channels that divert
portal blood from its normal route through the hepatic sinusoids
-vascular anomalies that connect the portal circulation to the systemic circulation (portal circulation drains gut, spleen, pancreas -- bypasses the liver -- straight into systemic circulation = shunt)
66
What 3 questions do you need to ask in terms of shunts?
1. congenital vs acquired?
-congenital more common
2. intrahepatic vs extra hepatic?
3. single vs multiple?
67
What breeds get shunts? What kind of shunts?
Toy breeds: Yorkers, min. schnauzers, cairin terriers
-congenital, extra hepatic, single
Large/giant breeds: irish wolfhound, golden, labs, old english sheepdog
-congenital, intrahepatic, single
68
What kind of shunts do cats get?
congenital, extra hepatic, single
69
Why do acquired multiple shunts happen?
due to portal hypertension (ex. could be from cirrhosis) -- multiple shunts would be to try to offset the hypertension
acquired multiple shunts are NOT indicated for surgery
70
How do you DIAGNOSE Portosystemic Shunts?
-signalment
-minimum database: CBC, Chem, Urinalysis
CBC
-microcytosis
CHEM
-low albumin, glucose, and BUN may be present
-Liver enzyme activities are often normal
* Hypoalbuminemia
* Decreased BUN
* Hypocholesterolemia
* Hypoglycemia
* Increased ALT
URINALYSIS
-Ammonium biurate Crystals
-portal venography
-Serum bile acids
-Abdominal radiographs
--Mild-moderate microhepatica
-Abdominal ultrasound
* Microhepatica
* Locate shunt vessel(s)
* Look for bladder stones
-Hepatic scintigraphy - GOLD STANDARD
-Exploratory laparotomy
71
What about Serum Bile Acids test is important for shunts?
-lack specificity
-BUT, if preprandial BAs or normal/slightly elevated, and then postprandial are markedly elevated, then you can be confident there is a shunt
-if postprandial levels are normal, then portosystemic shunt is unlikely
72
How would you MEDICALLY TREAT Hepatic Encephalopathy?
* Avoid metronidazole! - neurotoxic and can intervene between differentiating between neuro CS of HE
--Can cause cerebellar or vestibular ataxia and
signs that mimic encephalopathy
--Can cause lethargy, weakness, and anorexia
* Ampicillin or Neomycin
-ampicillin has less bioavailability than amoxicillin, so want it to stay in GIT to work on bacteria there
73
What is Hepatic Encephalopathy?
Hepatic encephalopathy (HE) is a complex metabolic disorder characterized by abnormal mental status resulting from severe hepatic insufficiency
74
Why give abx to medically manage Hepatic Encephalopathy + PSS?
1. decrease the urease-producing bacterial population
2. prevent hyperammonemia
75
Why give Lactulose to medically manage Hepatic Encephalopathy + PSS?
-synthetic disaccharide that is hydrolysed by colonic bacteria
1. Lowering colonic pH with subsequent trapping of ammonium ions
2. inhibiting ammonia generation by colonic bacteria through a process known as catabolite repression
3. decreasing intestinal transit time due to its cathartic properties
4. suppressing bacterial and intestinal ammonia generation by providing a carbohydrate source
--
1. shortens time of urease bacteria to make ammonia by decreasing intestinal transit time
2. acidify colon - makes Nh3 to Nh4 (ammonia to ammonium)
76
What's important with Dietary Protein and
Portosystemic Shunts?
-do NOT restrict protein unless HE
-Dietary protein should not be restricted in patients with portosystemic shunts that are not showing any signs of hepatic encephalopathy
-Dairy proteins (especially cottage cheese) are better tolerated than proteins from mixed
sources, and vegetable proteins are better tolerated than meat proteins
--decreased heme
--decreased RNA nitrogen
--increased dietary fiber in vegetable protein > decreases intestinal transit time, reduces colonic
intraluminal pH, and increases fecal ammonia excretion
77
When is surgery indicated for a portosystemic shunt?
The treatment of choice for dogs and cats with a congenital PSS is surgical attenuation of the
anomalous vessel.
78
What is Surgical Attenuation of Shunting Vessel?
can use a Ameroid Ring Constrictor (ARC)
79
What is PVH?
PORTAL VENOUS HYPOPLASIA (MICROVASCULAR DYSPLASIA)
-hypoplastic small intrahepatic portal
veins > congenital hepatobiliary disorder
-Increased arterial blood flow to maintain
hepatic sinusoidal blood flow resulting in
sinusoidal hypertension > Acquired shunting develops to transport blood to central vein and reduce pressure
80
Clinical hallmark of PVH?
increased serum bile acids
81
What breeds get PVH?
Cairn terriers, Yorkshire terriers, toy-breeds
82
How do you diagnose PVH?
-BIOPSY + all other tests will be negative (Abdominal ultrasound, Colorectal scintigraphy, Portal venography)
-Increased serum bile acids but NO demonstrable
macroscopic vascular shunt
83
What's special about a biopsy from PVH vs PSS?
-histologic lesions are similar to those observed in dogs with portovascular shunts
* Atrophy of hepatocytes
* Portal triads appear closer together
* Prominent hepatic arterioles
* Prominent smooth muscle of hepatic venules
84
Prognosis for a dog with PVH?
excellent
85
What is hyperbilirubinemia?
elevated serum/plasma bilirubin
can be hyperbilirubinemic WITHOUT jaundice
86
What is jaundice/icterus?
subsequent yellowing of plasma/tissues
87
What is bilirubinuria?
bilirubin in urine
-can be physiologic in dogs
-NEVER normal in cats
--this is bc they have a higher renal threshold for bilirubin AND have a greater ability to resorb bilirubin
88
What is Cholestasis?
decrease in bile flow (intra or extra-hepatic)
89
What does an Icteric animal HISTORY usually consist of?
-weight loss
-v/d
-inappetence
-acute or chronic CS
-Collapse if severe anemia (PREHEPATIC)
-PU/PD if liver dysfunction? (HEPATIC)
-Abdominal pain (POSTHEPATIC)
-Uncommonly grey (acholic) feces (POSTHEPATIC)
--if complete biliary obstruction, no bilirubin pigment giving brown
-People w/ icterus describe pruritus
--bilirubin is irritating and uncomfortable (esp with bile peritonitis)
90
INTRAVASCULAR hemolysis causes __________
EXTRAVASCULAR hemolysis causes __________
intravascular hemolysis = hemoglobinuria
extravascular hemolysis = bilirubinuria
extravascular hemolysis occurs in the hepatic and splenic macrophages
91
What's a typical PE for icteric animals?
* Typically quiet, often dehydrated
* Pale mm. if anemic
* Icterus most noticeable in sclera, 3rd eyelid, pinnae, mucous membranes (gingiva, soft palate, genitalia), non-haired skin
* +/- abdominal pain, effusion, or hepatomegaly
* Bleeding/bruising if liver failure
* Icterus detectable in tissues if serum bilirubin ≥ ~2 mg/dL
92
What is the bilirubin metabolism pathway?
1. you start with a RBC
-RBC can die two different ways
a. senescence, norma/natural death
b. pathology/dz - hemolysis
-RBCs in dogs last 3ish months (90-100days)
-RBCs in cats last 2ish months (60-80days)
SPLEEN
2. once a RBC dies, it is broken down into Heme and global. HEME is taken up by spleen/spleen macrophages.
3. it is then converted into biliverdin
4. then converted to unconjugated bilirubin
-lipid soluble
-hemolytic anemia has uncojugated bilirubin
UNCONJUGATED BILIRUBIN LEAVES SPLEEN, GOES INTO BLOODSTREAM
5. uncojugated bilirubin bound by albumin
UNCOJUGATED BILIRUBIN w/ ALBUMIN GOES TO LIVER
6. uncojugated bilirubin becomes conjugated bilirubin
-water soluble -- excreted well in bile (which is composed a lot of water)
-conjugation happens in the liver!
Stored in GALLBLADDER, then goes out the common bill duct in to the DUODENUM/INTESTINES
7. conjugated bilirubin is then deconjugated and converted to Urobilinogen
-yellow appearance to stool
8. Some of Urobilinogen is converted to Stercobilin
-brow appearance to stool
Other part of Urobilinogen is REABSORBED from ileum -- enters Enterohepatic Circulation (EHC)
-some goes back to liver
-some goes back to kidney - yellow pee!
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Where does bilirubin conjugation happen in body?
LIVER
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Hemolytic anemia means you'll have ________ bilirubin
Liver disease means you'll have _______ bilirubin
If you have a post-hepatic cause to disease, you'll have ________ bilirubin
Uncojugated bilirubin
Unconjugated OR conjugated bilirubin (usually conjugated
Conjugated bilirubin
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Conjugated and Uncojugated bilirubin isn't ideally clinically helpful. T/F
True
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What is Pre-hepatic Icterus?
-hemolytic jaundice
-hemolytic anemia
-mainly unconjugated bilirubin
-pathologic hemolyis (liver dz or severe hemolysis > (as opposed to low-grade physiologic hemolysis of senescent RBCs)
97
What is Hepatic Icterus?
-hepatic jaundice
-from defective bilirubin handling in hepatocytes due to liver dysfunction
-or from intrahepatic cholestasis
-conjugated >>> unconjugated bilirubin
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What is Post-Hepatic Icterus?
-obstructive jaundice
-extra-hepatic bile duct obstruction (EHBDO)
-or rupture (bile peritonitis)
-mainly conjugated bilirubin
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What are some differentials for Pre-Hepatic Icterus?
Remember, if you're icteric, you're hyperbilirubinemic
* Immune-mediated (IMHA): 1° or 2°; intravascular (hemoglobinuria) or extravascular (bilirubinuria) hemolysis
* Heinz body anemia (oxidative damage)
-eg, zinc, onion, acetaminophen toxicity
-pennies have zinc!
* Infectious (eg, Mycoplasma, Babesia, etc)
* Transfusion reaction
* Microangiopathic (eg, DIC, HSA, HW dz)
-shearing of red blood cells
-heartworm, splenic mass
-result is shistocytes
* Severe hypophosphatemia (low ATP)
* Envenomation
* Congenital enzyme deficiency
--eg, PK, PFK
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What are some differentials for Hepatic Icterus?
* Hepatic lipidosis - cats
* Cholangitis - cats
* FIP - cats
* Neoplasia (eg, lymphoma) - both
* Acute or chronic toxin - both
* Bacteremia - both (“cholestasis of sepsis”)
* Cholangiohepatitis - d>c
*cholangitis - c>d
-inflammation or infection of biliary epithelium of biliary tracts
* Chronic hepatitis - dogs
* Copper-associated hepatitis - dogs
* Cirrhosis - dogs, not really a cat thing
--typically end-stage of another process
--any of these, if chronic enough, can lead to cirrhosis
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What are some differentials for Post-Hepatic Icterus?
-liver is technically fine, but something is affecting liver
* Obstruction (EHBDO)
-severe pancreatitis
--pancreas lives right next to CBD
-hepatic ducts (CBD)
-gallbladder mucocele - hepatobiliary system
-cholecystitis - inflammation of gallbladder
-neoplasia (CBD, pancreas, duodenum)
-cholelith (“gallstone”) - uncommonly obstructive
--gallstone in gall bladder
-choledocolith (bile duct stone)
--gallstone in bile duct
-stricture (of CBD or major duod. papilla)
* Rupture of GB or bile duct(s)
-hit by car, severe cholecystitis that ruptures
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What is the composition of bilirubin?
water, bile acids, bile salts, bilirubin, cholesterol, FAs, lecithin, electrolytes, bicarbonate
remember bilirubin and cholesterol are liver function parameters, so a biliary obx would have HIGH bilirubin and cholesterol
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Where is bile produced and stored?
Bile continually produced; stored & concentrated in GALLBLADDER
released by the hormone CCK (as are pancreatic enzymes)
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What are bile acids?
steroid acids made by liver (from cholesterol)
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What are bile salts?
salts of these bile acids (Na+/K+)
-acids that come together with sodium or potassium
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What are main functions of bile?
1. fat emulsification and digestion (bile salts/acids)
including absorption of fat-soluble vitamins
2. excretion of waste products (eg, bilirubin, cholesterol, drugs, toxins)
3. bactericidal, alters GI pH
107
What does a CBC look like for Pre-hepatic Icterus/Hemolysis?
-regenerative anemia (takes 3-5 days)
-normal total solids
-RBC morphology: spherocytes or auto-agglutination if IMHA, Heinz bodies if oxidative damage, schistocytes with HSA or DIC, hemoparasites, etc
-severe thrombocytopenia if Evan’s syndrome
-icteric (+/- hemolyzed) plasma
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What does a CBC look like for Hepatic/Post Hepatic Icterus?
-poss. mild NNN anemia of inflammatory disease or microcytosis
-possible leukogram abnormalities
-icteric (+/- hemolyzed) plasma
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What will Chem panels look like for icteric patients?
-all will have HYPERBILIRUBINEMIA
PREHEPATIC
-minimal other changes; possible mild ↑ALT/AST due to anemic hypoxia (reactive hepatopathy)
HEPATIC
-elevated liver enzymes (ALP/GGT > ALT/AST)
-may see liver dysfunction (↓alb, ↓BUN, ↓chol, ↓gluc)
POST HEPATIC
-often ↑↑↑cholesterol and ↑ LEs (ALP/GGT > ALT/AST)
110
What does a Urinalysis look like for an icteric patient?
* Isosthenuria if liver dysfunction (and low BUN)
* Elevated USG if dehydrated (and normal liver function)
* Bilirubinuria
--always pathologic in cats!! - higher renal threshold for bili (~9x dogs)
--can be physiologic in dogs
--if noted in ill dog, evaluate serum bilirubin
* Ammonium biurate crystals if PSS or severe dysfunction (and breed-related) - dalmatians, bulldogs
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What would US look like for an icteric patient?
* Most important diagnostic to differentiate hepatic vs. post-hepatic
* Hepatomegaly: often acute liver disease and neoplasia
* Microhepatica: often chronic liver disease, espec. dogs
* +/- evidence of pancreatitis, mucocele,
masses, chole(docho)liths, stricture
* EHBDO: distention of GB and biliary ducts
* +/- evidence of bile peritonitis
also abdominocentesis for fluid analysis
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Other diagnostics for icteric patients?
* Ammonia levels to assess for hepatic encephalopathy
* Coagulation profile to “stage” and further assess liver function
* Consider liver FNA or biopsy if hepatic icterus
* Thoracic radiographs if neoplasia a differential
* CT scan to further assess cause of EHBDO or acquired PSS, or for sx planning (note that congenital PSS usually have normal bilirubin)
* Serum bile acids generally not necessary w/ icterus (as you already know there’s dysfunction or biliary obstruction)
--BAs more indicated when bilirubin normal
--so serum BAs if you can't tell pre/hepatic/post
--HIGH BAs - hepatic or post
--NORMAL BAs - prehepatic
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How to treat icteric patients?
* Pre-hepatic: treat underlying cause of hemolysis +/- pRBC transfusion
* Hepatic: treat the underlying hepatopathy
* Post-hepatic
-often surgical (eg, mature GB mucocele, severe cholecystitis, mass, traumatic rupture, severe pancreatitis)
-sometimes medical (eg, pancreatitis, mild cholecystitis)
