small animal med-hepatobiliary diseases part 1 (pages 1-14)

how many lobes does the liver have?

6 lobes

-left is the largest, divided into lateral and medial (2)

-right is divided into lateral and medial (2)

-quadrate located between left and right medial lobes

-caudate location on the visceral surface of the liver

where is the gallbladder located?

between the right medial and quadrate lobes

where does the liver attach to in the body?

attached to the diaphragm on convex/rostral surface

the peritoneum forms ligaments that attach the liver to the body wall and organs

concave/caudal surface: touches stomach, pancreas, right kidney, duodenum

which type of anemias may be seen with some liver diseases?

1. non-regenerative (normocytic, normochromic) due to chronic disease

2. microcytic anemia (seen in animals with PSVA or cirrhosis)

3. iron deficiency anemia (due to chronic bleeding into the GIT from portal hypertension)

what other possible RBC morphology changes occur with liver disease in cats and dogs?

poikilocytes secondary to RBC membrane fragility- common in cats

target cells secondary to cell membrane abnormalities or iron deficiency

are alterations in liver enzymes sensitive and specific to liver disease?

highly sensitive, but have low specificity for liver dz:

-can still be abnormal when dz is not of hepatic origin

-also not specific for certain dz's, prediction of hepatic function, or determining return to function

-enzyme elevation will not determine severity of damage

what is the lack of predictability of hepatic enzyme alteration due to?

due to the immense regenerative capacity of the liver

why are liver enzymes not increased in endstage liver disease?

the functional mass of liver cells is so reduced that fewer enzymes are produced

what is ALT?

leakage enzyme that suggests increased membrane permeability- is leaked into circulation

half life in dogs is 2.5 days, unknown in cats

what are increases of ALT associated with?

increases may be seen with hepatic inflammation, necrosis, shunting, neoplasia, certain drugs, and benign processes like nodular regeneration

severe muscle inflammation or necrosis may also affect ALT

how can ALT be used as a prognostic indicator with acute liver disease?

a drop in ALT at or above 50% over 48 hours is considered a good prognostic indicator of acute liver disease

what is AST?

a leakage enzyme; more sensitive but less specific than ALT because large amounts of AST are found in the muscle

what do increases in AST indicate?

1. if the degree of AST elevation more significant than ALT (and ALT is increased) then muscle origin should be suspected

2. AST increases for the same conditions as ALT in hepatobiliary disorders (hepatic inflammation, necrosis, shunting, neoplasia, etc.)

what is the half-life of AST?

dogs: 5-12 hours

cats: 77 minutes

because half-life of AST is much shorter than ALT, AST will decrease faster with recovery in acute liver disease

what is ALP?

intracellular and membrane bound forms:

-extracellular membrane bound portion is greatest where it acts as a glycoprotein involved in many metabolic functions (this is inducible by drugs)

-serum ALP has many forms, so poorly specific

in general, what can cause increases in ALP?

ALP can increase due to synthesis or release from membrane

generally with diseases with a cholestatic component

what causes ALP increases in dogs?

hepatic neoplasia, hepatobiliary dz, corticosteroids, anticonvulsants, chronic illness, and nodular regeneration

what causes ALP increases in cats?

hepatobiliary dz

ALP increases in cats is not as dramatic due to shorter half-life and lower hepatic stores of this enzyme

cats also dont have corticosteroid ALP, so ALP wont change with gluccocorticoid administration

what is GGT?

primarily from the liver, membrane bound enzyme

associated with diseases involving a cholestatic component

what causes GGT alterations in dogs?

can be induced by certain drugs like phenobarbital and gluccocorticoids

what causes GGT alterations in cats?

cholangitis, cirrhosis, biliary obstruction (will see a GGT increase more significant than ALP in cats)

in cats, does hepatic lipidosis cause a more markedly elevated ALP or GGT?

ALP

how are bile acids formed?

by cholesterol in the liver

-in the liver, conjugated to glycine or taurine and excreted into the bile

what stimulates release of bile?

dietary fat and protein in the duodenum stimulate cholecystokinin which causes contraction of the gall bladder and therefore transport of bile into the duodenum

what are causes of increased bile acids?

decreased extraction by the liver from portal blood (shunting, hepatocellular failure)

cholestasis (reflux into bloodstream)

what are causes of decreased bile acids?

artificially by decreased/inadequate fat or protein

severe ileal disease (cant absorb from GI tract)

variations in gastric emptying

variations in intestinal transit time

variations in cholecystokinin release

what proteins are synthesized in the liver?

albumin, non-immunoglobulins, and coagulation factors

what are hepatic-originating causes of hypoalbuminemia?

severe liver disease such as synthetic failure

portal hypertension, sodium retention, and water retention can cause increased leakage or mild dilutional effects

what coagulation factors are synthesized by the liver?

all factors except factor 8

what anticoagulants are produced by the liver?

protein C, antithrombin 3, antiplasmin

what is protein C?

vitamin dependent proenzyme that is activated when thrombin binds thrombomodulin on endothelial cells

protein C is an anticoagulant that cleaves factors Va and VIIIa to down regulate thrombin production

what happens to PT and aPTT in severe liver disease?

these may be prolonged

why may animals with severe cholestasis have clotting issues?

inhibition of bile flow may lead to impaired uptake of fat soluble vitamins like vitamin K

w/o vit.K, activation of factors 2, 7, 9 and 10 may not occur

what hepatobiliary diseases is hypoglycemia seen in?

severe acute liver failure, chronic liver failure, or in breeds with vascular anomalies

also seen in paraneoplastic syndromes of some liver tumors (hepatoma, hepatocellular carcinoma)

glycogen storage dz's will be hypoglycemic due to interference with glucose production

which organ is responsible for maintenance of euglycemia during fasting?

liver

how is BUN formed?

liver turns ammonia into urea to detoxify blood in the form of BUN

how does BUN increase?

due to dehydration, increased protein intake, and/or GI hemorrhage

what causes decreases in BUN?

secondary to liver failure (not producing much)

by medullary washout from fluid diuresis or increase in glomerular filtration rate

is BUN a reliable indicator of liver disease?

not really, BUN supports but does not indicate liver disease

how is ammonia cleared in the liver?

via metabolism thru the hepatic urea cycle

urea can be consumed when producing glutamine in liver, kidneys, muscle, brain and intestines

what are causes of increased circulating ammonia levels (hyperammonemia)?

caused by a detoxification failure:

-PSS

-severe hepatitis and hepatic necrosis

-diffuse hepatic neoplasia

-cirrhosis

what lab test can be performed to test successful extrahepatic shunt ligation?

fasted ammonia test

what causes icterus?

bilirubin retention that is prehepatic, hepatic, or posthepatic

can bilirubin be a normal finding in dog urine?

yes, kidneys of dogs can conjugate and excrete bilirubin normally

what does bilirubin in cat urine suggest?

suggests hemolytic or hepatic disease

which type of crystals are sometimes detected in the urine with liver disease?

ammonium biurate crystals

-uric acid is a by product of purine metabolism in the liver

-in disease, deficiency of hepatic urate oxidase causes hyperuricemia

-increased blood urate and ammonia are excreted into urine and crystals may form

t or f: crystals and stones secondary to liver disease are common with portosystemic shunts

true

however, presence of crystals does not always mean there will be stones

is liver cytology accurate for assessing hepatic fibrosis or inflammation?

no

when is liver cytology most useful for identifying neoplasia?

most beneficial in correctly identifying cancers that exfoliate well, such as lymphoma, histiocytic sarcoma, and carcinoma

also those that are poorly differentiated

what are some metabolic changes that occur in the liver?

vacuolation (may be indistinct or more distinct lipid vacuolation)

what are causes of indistinct (rarefaction) vacuolation in the liver?

as a result of water or glycogen:

-glycogen: increased endogenous/exogenous steroid hormones

-water: accumulation is a nonspecific response to cellular injury

how does lipid vacuolation in the liver occur?

occurs in conditions with increased mobilization and/or metabolism of lipids

ex: diabetes mellitus and hepatic lipidosis

what infections can liver cytology be useful in identifying?

bacteria, fungi, algae, trematodes, and protozoa can be ID'd in some cases

why is it important to avoid/be careful when aspirating the liver for cytology if amyloidosis is suspected?

aspirates can result in severe hemorrhage in some cases

important to know which breeds may be affected/predisposed

how much liver is needed for a biopsy to diagnose inflammatory/fibrotic liver disease?

need a sample of about 15 portal triads--> will need a large cup(t?)/wedge biopsy

can liver aspirates be collected for biopsy to diagnose inflammatory/fibrotic liver disease?

no, liver aspirates will only provide cells aspirated thru a needle and no anatomic structure is preserved

should animals be anesthetized for liver biopsies?

cats: require GA for all biopsies (except FNAs)

dogs: US-guided tru-cut biopsies can be taken with heavy sedation, but GA is recommended

why should blood coagulation be run before liver biopsies?

due to possibilities of:

-inadequate clotting factor (severe hepatic dysfunction)

-decreased vitamin K reabsorption from GIT (cholestasis)

-DIC

what is a contraindication to performing liver biopsies?

if PTT is over 2x normal

treat coagulopathy prior to biopsy

what can occur if the bile duct is punctured during tru-cut needle biopsies?

vagal response occurs causing hyoptension and shock

where should liver biopsies be taken from?

from periphery and center of lesion

what are advantages of surgical and laparoscopic liver biopsies?

-visualization of the liver

-increased sample size

-ability to sample a particular area of interest

-ability to evaluate rest of the abdomen

what can be evaluated in liver biopsies?

type of disease

severity/extent

cellular infiltrate

chronicity/fibrosis

do liver biopsies always provide the exact cause of liver disease?

no- it is common for biopsies to fail to ID exact cause of liver dz, but they may reveal clues to disease processes that could cause the lesions

how are radiographs used to observe the liver?

-estimate size of liver (shouldn't extend beyond last rib)

-evaluate for abdominal fluid

-gastric axis should be parallel to ribs (if vertical: normal or microhepatica)

what are focal causes of hepatic enlargement seen on radiographs?

common causes: neoplasia, cysts, regenerative nodule

rare: granuloma, abscess, aterioportal fistulas

what are generalized causes of hepatic enlargement seen on radiographs?

common: neoplasia, lipidosis, glycogen accum., extra-medullary hematopoiesis, acute hepatitis, reticuloendothelial system cell hyperplasia

rare: storage diseases, amyloidosis

what are types of mineralizations seen in the liver on radiographs?

-choleliths

-choledocholithiasis

-chronic gallbladder infection/inflammation

-neoplasia of gall bladder

-granulomas

-abscesses

-resolving hematomas

-regenerative nodules

what are causes of gas opacities in the liver/biliary tree seen on radiographs?

hepatic abscesses

emphysematous cholecystitis

biliary obstruction

what are causes of a generalized hyper-echoic liver seen on ultrasound?

glycogen

hepatic lipidosis

amyloid

fibrosis

cholangiocarcinoma (rare)

what are causes of a generalized hypo-echoic liver seen on ultrasound?

suppurative hepatitis

passive congestion

lymphoma

are hepatic cysts and hematomas hyperechoic, hypoechoic, or anechoic?

cysts: anechoic

hematomas: start out hyperechoic--> hypoechoic--> anechoic

why may CT be a better imaging modality than ultrasound for the liver? what does ultrasound have high SN/SP for?

US has low sensitivity for detecting lobe masses- CT is better for this

ultrasound does have a high sensitivity and specificity for detecting congenital PSS (CPSS)

what is CT best for when investigating liver disease?

dual and triple phase CT has been successful in ID'ing CPSS and acquired shunts in dogs

may be more sensitive for detecting liver masses

when is gallbladder aspiration indicated?

in cases of suspected infectious biliary disease

however, if the gallbladder wall is diseased, rupture and bile peritonitis may occur

when is gallbladder aspiration contraindicated?

should not perform when distended biliary ducts suggest obstruction

how are gallbladder aspirates performed?

aspirate thru parenchyma (less risk of leakage), the liver itself will put pressure on gall bladder wall

aerobic and anaerobic culture should be used

why may cholecentesis and gall bladder emptying be indicated for intoxications that undergo enterohepatic circulation?

can decrease persistent toxic damage

what is the flow of blood from the liver to the aorta?

hepatic portal vein (from GI and spleen)--> liver--> hepatic veins--> caudal vena cava--> RA-> RV-> pulmonary arteries-> lungs-> pulmonary veins-> LA-> LV-> aorta

what is portal hypertension?

hypertension in pre-hepatic, hepatic, and post-hepatic disease

do collateral veins form with portal hypertension? are they functional?

collateral veins can be formed only in prehepatic and hepatic disease

collaterals will only be functional if portal pressure is greater than systemic pressure

why are collateral veins not commonly seen in post-hepatic disease?

bc portal vein and vena cava will equilibrate

in acute post-hepatic disease, why do effusions have low protein?

due to tight endothelial junctions

why do effusions in hepatic disease result in higher protein levels?

due to fenestrated hepatic sinusoids

what are sequelae to increases in portal pressure?

increased portal pressure--> ischemic necrosis of intestines/ulceration with hemorrhage--> makes hepatic encephalopathy worse

what are causes of pre-hepatic hypertension?

-portal vein obstruction (thrombus, invasive neoplasia, fibrosis/stricture)

-congenital atresia/stenosis

-A-V fistula

-post PSS ligation

-extraluminal neoplasia

-cysts

-abscess

what are causes of hepatic hypertension?

1. pre-sinusoidal:

-primary hypoplasia of portal vein (NPH, IHF, HPF)

-congenital hepatic fibrosis

-carolis's dz

-flukes

2. sinusoidal: chronic hepatitis, cirrhosis

3. post-sinusoidal: veno-occlusive dz

what are causes if post-hepatic hypertension?

right-sided failure

pericardial disease

pulmonary hypertension

budd-chiari (thrombus, intra/extra vascular tumor)

because direct venous line of the portal vein is not commonly performed, presence of what other dz processes make portal hypertension suspected?

portal hypertension suspected in patients with:

-ascites

-hepatic encephalopathy

-gastric ulceration

-visible collaterals on imaing

-low velocity portal vein flow and portal vein:aorta ratio >0.65 with no CPSS

what is presence of ascites a negative prognostic factor for?

cirrhosis and chronic hepatitis

is presence of ascites a negative prognostic factor for non-cirrhotic portal hypertension, primary hypoplasia of the portal vein, and portal vein atresia?

no

what is hepatic encephalopathy?

the liver cannot metabolize toxins that are made as a result of protein digestion in GI tract

ammonia is the most important toxin (also benzos, aromatic amino acids, glutamine, gamma-aminobutryic acid, tryptophan, Mn, opioids and serotonin)

what are clinical signs of hepatic encephalopathy?

lethargy

aggression

vocalization

head pressing

stupor

coma

seizures

death

what is the pathogenesis of clinical signs caused by hepatic encephalopathy?

normal function of GABA, glutamate, benzos, and serotonin receptors in the CNS/PNS are messed up

ammonia can cause cerebral swelling

with shunts, toxins cross the BBB which cause dysfunction in neurotransmitters

why do cats get hepatic encephalopathy if they stop eating?

bc arginine is required for the hepatic urea cycle and ammonia detoxification

what are the 3 types of hepatic encephalopathy?

type 1: congenital PSS with no intrinsic liver disease

type 2: congenital/acquired chronic hepatic disease, PH and acquired disease

type 3: fulminant acute hepatic failure

what can make hepatic encephalopathy worse?

1. infection (blood, respiratory, urinary)

2. hypoglycemia

3. protein catabolism

4. dehydration

5. alkalosis (increase production of and uptake of ammonia in CNS)

6. hypokalemia

7. ascites

8. GI bleeds

how can hypokalemia worsen hepatic encephalopathy?

due to decreased intake, GI losses, diuretics, hyperaldosteronism:

shifts intracellular K out of cell and Na and H into the cell--> NH3 and H+ formed --> ionized to NH4 (ammonium) which cannot exit cell

hypokalemia increases renal ammoniagenesis

how can ascites worsen hepatic encephalopathy?

loss of fluid into the abdomen stimulates RAAS system, causing Na and H2O retention and increased potassium secretion (in which hypokalemia also worsens HE)

how can GI bleeds worsen hepatic encephalopathy?

bc blood is the most ammoniagenic protein