AbaxisUniversity

EvaluatingforLiverDamageandDysfunction

AndrewJRosenfeld,DVMABVP

SectionI:PreCaseandCaseWorksheet

AbaxisUniversityCaseWorkSheet

EvaluatingforLiverDamageandDysfunction

A. Rosenfeld,DVMABVP

2009

Instructions: Prior to taking the online course, please review the course notes andevaluatethehospitalcase.Pleasetakesometimeandfillouttheprecourse section of the case to the best of your ability. Once in lecture, the case will be discussed and new diagnostic testing and treatment options will become available. As the class progresses, each team member will outline diagnostic testing and treatment concerns to help identify the primary and secondary concerns of the patient, understand treatment options and be able to discuss theseconcernswiththeclient.Goodluck. PrecourseSectionPleasefilloutpriortoattendingtheonlineclassroom Signalment:Pewter,20kgMaleNeutered 5yearoldEnglishbulldog CC:Lethargic,depressed,anorexicandhavingsoft stoolfor7days. InitialTriageExamination Temp:101.2degreesFahrenheit Pulse:160 Resp:5060breaths/min CRT:2secs MM:LightPink Hydration:8%dehydrated Mentation:Depressed Abdomen:Soreandpainfultotouch

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HistoryPleaselistquestionsthatyouwouldliketoaskduringyourmedical history. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. WhatClinicalDiagnosticsshouldbecompletedatthistime? 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

2| E v a l u a t i n g f o r L i v e r D a m a g e a n d D y s f u n c t i o n

InitialDatabaseAvailable: Tubes: PurpleTop RedTop PackedCellVolume PCV: 24%(l) (2545%)

TotalProtein6.2 (5.07.5mg/dl)

CompleteBloodCount: Test WBC Lymphocytes Monocytes Neutrophils Eosinophils Basophils RBC HCT Hemoglobin Platelet Findings 7500 1250(l) 1000 4500 750 0 6000 32%(l) 11(l) 328000 Normal 5,50019,500 15007000 0850 250012500 01500 0100 55008500 3555% 9.515 200000500000

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Chemistry: Test Albumin AlkPhos ALT Amylase TBilirubin BUN Calcium Phosphorus Creatinine Glucose Na K TP Globulin Findings 2.3(l) 143 112 752 0.5 4(l) 9.2 5.6 1.4 115(h) 149 2.8(l) 6.2 3.9 Normal 2.54.4g/dl 20150IU/L 10118IU/L 2001200IU/L 0.10.6mg/dl 725mg/dl 8.611.8mg/dl 2.96.6mg/dl 0.31.4mg/dl 60110mg/dl 138160mEq/l 3.75.8mEq/l 5.48.2g/dl 2.35.2g/dl

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BasedonPhysicalExamandClinicalDiagnosticsthusfar,pleaseidentifya problemlistforthepatient: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Pleaselistotherdiagnosticsthatneedtobecompleted: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

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Giventheconcernsofthepatient,whataresecondaryconcernsthatmedical teammustmonitorfor? 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. STOPTherestofthecasewillprogressduringtheonlineclass.

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OnLineClassPortion:Pleaserevieweachdiagnostictestordered,copydown theabnormalandlistconcernsbasedonthesefindings: ClinicalDiagnostic#1: ProblemList:

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ClinicalDiagnostic#2: ProblemList:

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ClinicalDiagnostic#3: ProblemList:

9| E v a l u a t i n g f o r L i v e r D a m a g e a n d D y s f u n c t i o n

ClinicalDiagnostic#4: ProblemList:

10| E v a l u a t i n g f o r L i v e r D a m a g e a n d D y s f u n c t i o n

ClinicalDiagnostic#5: ProblemList:

11| E v a l u a t i n g f o r L i v e r D a m a g e a n d D y s f u n c t i o n

Pleaselistacompletedproblemlistbasedonthecaseincludinghistory,physical exam,andclinicaldiagnostics: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. As we treat this patient, what are some monitoring diagnostics that will be necessarytoevaluatetheeffectivenessofourtreatmentoptionsandconcerns ofsecondarydiseaseconditions? 1. 2. 3. 4. 5. 6. 7. 8.

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SectionII:LectureNotes

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Evaluating for Liver Damage and Dysfunction

Andrew J Rosenfeld, DVM ABVP 2009

Material Courtesy of Clinical Pathology for the Veterinary Team, Rosenfeld, A and Dial, S. Wiley Blackwell, Ames Io, 2010

Case I : Pewter
Signalment: 20 kg Male Neutered 5 year old English Bull Dog CC: Lethargic, depressed, anorexic and having soft stool for 7 days.

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Initial Triage Exam

Temp: 101.2 degrees Fahrenheit Pulse: 160 Resp: 50-60 breaths / min CRT: CRT 2 secs MM: Light Pink Hydration: 8% dehydrated Mentation: Depressed

Abdomen: Sore and painful to touch

History What should we ask?

1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
Now What?

What should be in our clinical database?

1. 2. 3. 4. 5. 6. 7. 8.

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Initial Database
Tubes:
Purple Top Red Top p

Packed Cell Volume

PCV : 34 % (L) Total Protein: 6.0 (35-55%) (5.0-7.5 mg/dl)

Complete Blood Count

Test WBC Lymphocytes Monocytes Neutrophils eut op s Eosinophils Basophils RBC HCT Hemoglobin Platelet Findings 7500 1250 (l) 1000 4500 500 750 0 6000 32% (l) 11 (l) 328000 Normal 5,500-19,500 1500-7000 0-850 2500-12500 500 500 0-1500 0-100 5500-8500 35-55% 9.5-15 200000-500000

Chemistry
Test Albumin Alk Phos ALT Amylase T Bilirubin BUN Calcium Phosphorus Creatinine Glucose Na K TP Globulin Findings 2.3 (l) 143 112 752 0.5 4 (l) 9.2 5.6 1.4 115 (h) 149 2.8 (l) 6.2 3.9 Normal 2.5-4.4 g /dl 20-150 IU/L 10-118 IU/L 200-1200 IU/L 0.1-0.6 mg/dl 7-25 mg/dl 8.6-11.8 mg/dl 2.9-6.6 mg/dl 0.3-1.4 mg/dl 60-110 mg/dl 138-160 mEq/l 3.7-5.8 mEq/l 5.4-8.2 g/dl 2.3-5.2 g/dl

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Problem List
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

What other diagnostics are needed to be completed?

1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

What are secondary concerns that medical team must monitor for?
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

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Introduction
As opposed to clinical diagnostic evaluation of renal disease and kidney function, the ability to evaluate liver damage vs. hepatic function is much more complex. The goal of this chapter is to understand that patients with liver trauma have changes in liver enzymes. However, this does not y always mean the liver is non-functional. The other concern is that a patient with have severe debilitating liver disease with poor function, can have blood work parameters within normal limits. Team members must be able to understand the importance and the limitation of hepatic clinical diagnostics when approaching a patient with potential liver disease.

Liver Physiology
The liver has many functions in the body; the most important is detoxification of toxins. The small intestine absorbs all food stuffs, microbes and toxins into a large venous system called the Portal Venous System System. The large portal vein carries all of these substances into the liver where intracellular chemicals (enzymes) detoxify toxins into inert waste products.

Liver Detoxification
For the liver to be able to detoxify blood, the internal architecture of the liver must be adapted to filter blood, harvesting necessary nutrients and removing toxins. To do this the liver architecture is divided into i di id d i t sinusoids where oneid h cell thick layers of hepatocytes filter blood flowing from the portal vein to the hepatic central vein The function of these cells is to absorb all toxins, bacteria, and nutrients that are in the portal blood supply.

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Liver Detoxification
The nutrients are absorbed, altered into other proteins, energy and fats needed by the body and then released back into the blood venous flow for general circulation. The toxins and bacteria are deactivated and then released into channels, called Canniculi, running between layers of hepatocytes. These canniculi lead to the bile ductules, which then move all deactivated sludge and debris into the gall bladder.

Liver Detoxification
If the body is unable to detoxify these compounds, the active toxins can build up into the blood stream and tissues. This can produce anorexia, weakness, weight loss, vomiting and diarrhea. Further specific toxins can penetrate the central nervous system producing neurologic symptoms such as Seizures Acute blindness Circling Head pressing Abnormal behavior

Neurologic symptoms produced secondary to decrease hepatic function is called Hepatic encephalopathy. Since this process is stimulated by the absorption of nutrients and improper detoxification of toxins, neurologic signs can be closely associated with feeding.

Liver Production
The liver produces many of the bodys building blocks necessary for normal maintenance, growth and production. Of these factors, the liver produces
Glycogen Red Blood Cells Precursors Clotting Factors Body Proteins (Albumin)

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Risks of patients with reduced hepatic function

Issues with Detoxification:
Hepatic Encephalopathy: Development of neurologic symptoms secondary to improper detoxification of microbes and toxins which remain in the body affecting the central nervous system. Physical Symptoms due to build of toxins and bilirubin: Increased toxins can produce nausea, anorexia, depression, vomiting, diarrhea, weakness and weight loss.

Risks of patients with reduced hepatic function

Alteration in Protein Production
The liver also produces a protein molecule called albumin. Albumins function is to carry other molecules and hormones around the blood stream in a deactivated form until the body requires the chemical. In order to move albumin through the blood stream, large amounts of fluid must be ll d from th ti b pulled f the tissue. This physiological draw of fluid that albumin exerts on the tissue is called Oncotic Pressure. Loss of albumin production secondary to liver dysfunction can decrease oncotic pressure, increasing the amount of fluid returning to the tissue. If severe, large amounts of fluid accumulation can occur within the abdomen (ascites). Further medical team members must be extremely cautious with hospitalize patients on intravenous fluids with low albumin levels since these patients have increased risk of pushing larger amounts of fluids into the tissue. This increases risks of moving fluid into lung tissue producing pulmonary edema and developing fluid overload.

Risks of patients with reduced hepatic function

Decreased Production: Anemia:
Due to lack of Red Blood Cell precursors. Animals with chronic hepatic disease may develop chronic anemia and may have decreased ability to clot blood.

Increased Clotting Time:

The liver produces clotting factors that finalize clot formation. With this concern, no jugular blood collection should ever be attempted with patients suffering from potential hepatic disease or dysfunction.

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Liver Function

Concern of Dysfunction

Hepatic Encephalopathy: Development of neurologic symptoms secondary to improper detoxification of microbes and toxins which remain in the body affecting the central

Detoxification

nervous system. Physical Symptoms due to build of toxins and bilirubin: Increased toxins can

produce nausea, anorexia, depression, vomiting, diarrhea, weakness and weight loss.

Formation of Building Blocks

Anemia: Lack of Red Blood Cell precursors Increased Clotting Time: The liver produces clotting factors that finalize clot formation. Hypoalbunemia: Due to lack of blood albumin, the body can shift fluid from the vascular supply to the tissue, increasing fluid accumulation in the body producing ascites, edema and pulmonary edema (with patients on IV fluids).

Glucose Storage

Hypoglycemia (rare)

Causes of Liver Disease

Infectious Liver Disease: Viral, bacterial, fungal and parasites pathogens can infect and invade normal liver tissue producing acute or chronic disease and debilitation

Inflammatory Disease: Hepatitis is the activation of the immune system by some foreign antigen within the liver. This antigenic stimulation produces an influx of white blood cells through healthy liver causing damage and irritation. Inflammatory disease can be acute, chronic or end stage (Cirrhosis).

Cancer (Neoplasia): The liver is both the site of primary cancer and a common site of secondary metastatic disease. Some

common cancers that primarily affect the liver are Hepatic Adenocarcinoma, Hepatic Cholangioadenocarcinoma, Lymphoma, and Mast Cell tumor.

Causes of Liver Disease

Metabolic Disease: This form of liver disease occurs as inert compound build-ups within the liver, destroying the normal architecture and liver function. Common metabolic diseases of the liver include: Hepatic Lipidosis: This disease syndrome occurs commonly in the cat and horse (pony) when these animals have a diseases entity that produces a profound anorexia. The animals shunt large amounts of fat into the liver to transform it into sugar. The movement of fat into the liver is so severe that normal liver architecture and liver function can be affected. Protein: Amyloidosis is an accumulation of an inert protein in the liver which can chronically destroy normal liver tissue. This build up of this abnormal protein is most commonly seen in the Shar-pei breed. In this breed, amyloidosis can be associated with kidney and liver disease and inflammatory changes in joint capsule.

Toxin Disease: Since the liver is the major detoxifying organ in the body; toxins can damage normal liver tissue affecting function. Porto-caval Shunts: In some patients, a small blood vessel, called a shunt, can occur from the portal vein to the caudal vena cava producing a by-pass of blood flow around the liver.

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Identifying Liver Damage vs. Hepatic Dysfunction

Within the liver cells are enzymes that function to change or produce specific body building blocks or detoxify toxic chemicals in the body. Clinically we evaluate the following intracellular enzymes: Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Gamma-Glutamyltransferase (GGT) Alkaline Phosphatase (Alk Phos) ( )

Unlike evaluating kidney disease by monitoring azotemia, these clinical diagnostics do not represent a build up toxin, but rather normal enzymes produced within the hepatocytes. Normally, a specific level of each enzyme leaks from the hepatocyte into the blood stream. Acute trauma to hepatocytes can produce sharp elevations of liver enzymes. Increases in these liver enzymes support liver trauma, but do not always suggest liver dysfunction. However, with chronic to end stage disease, there may enough hepatic enzymes within the blood stream to produce normal blood levels in clinical testing, but the liver may not be functional.

Liver Damage Enzymes

ALT (Alanine aminotransferase): Alanine aminotransferase (ALT) is responsible for the conversion of 2oxoglutarate to pyruvate and glutamate in the liver cells (hepatocytes). The following patterns in the ALT level can be observed: Low ALT activity is not generally associated with disease conditions. Increased activity of the enzyme in the blood occur when there are alterations in the lipid membrane of the hepatocytes, secondary to injury, inflammations or infection within the liver. The increase blood levels do not indicate the severity of the damage to the hepatocytes or degree of reversibility of the disease process. Further ALT activity can also be increased secondary to: Chronic use of anticonvulsants, steroids and other drugs Physical trauma Cardiac Disease

Liver Damage Enzymes

Aspartate aminotransferase (AST or SGOT): Aspartate aminotransferase (AST) is an intracellular enzyme in all cells, but has higher levels of activity in muscle and liver cell damage. The following patterns in the AST level can be observed: Decreased AST activity: disease conditions. Low ALT activity is not generally associated with

Increased AST activity: As with ALT, AST blood levels in the blood occur when there are alterations in the lipid membrane of the hepatocytes secondary to injury hepatocytes, injury, inflammations or infection within the liver. The increase blood levels do not indicate the severity of the damage to the hepatocytes or degree of reversibility of the disease process. Further AST activity can also be increased secondary to: Disease, which affect the muscular skeletal system (e.g. trauma or seizure) Disease, which produce red blood cell destruction (e.g. Immune Mediated Hemolytic Anemia), since there is significant levels of AST in red blood cells.

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Liver Damage Enzymes

Gamma-glutamyltransferase (GGT): Gamma-glutamyltransferase is more an indicator of gall bladder obstruction or lack of bile flow. GGT is an intracellular enzyme responsible for cleaving C-terminal glutamyl groups from one substrate or molecule to another, and is thought to be involved in pathways used to protect cells from oxidative injury. GGT is present in all cells except it has higher concentration in renal epithelial, bile duct and hepatic cells. The following patterns of GGT levels can be observed: Decreased GGT activity: Low GGT activity is not generally associated with disease conditions. Elevations in GGT: Increased GGT activity can be associated with decreased bile flow (cholestasis) Unlike AST and ALT, GGT does not leak from hepatocytes; its activity is increased due to increased production (induction) of the enzyme in response to disease.

Liver Damage Enzymes

Alkaline Phosphatase (SALP or ALP): Alkaline Phosphatase is present within the liver, intestine, bone, kidneys and placenta. On most chemistry panels, Alkaline Phosphatase activity represents the combined activity all combined tissue alkaline phosphatase levels. The following patterns of ALP can be observed: Decreased ALP activity: Low ALP activity is not generally associated with disease conditions. Increased Alkaline Phosphatase activity: High ALP can originate from diseases and non-diseased conditions. Similar to GGT, ALPs activity increases because of increased production of the enzyme (induction) in response to disease. Some conditions that increase Alkaline Phosphatase activity are: Hyperadrenocorticism Liver and Gall Bladder Disease Long Term Medication Bone growth

Liver Dysfunction Enzymes

Bilirubin:

Bilirubin is a toxic metabolite produced from the red blood cell destruction in the spleen and the breakdown of hemoglobin. A red bl d cells age, th As d blood ll they are removed from circulation in the spleen, lysed, and the iron molecule removed from the hemoglobin molecule to be used again. The remaining chemical is bilirubin, which is moved to the liver to be detoxified and excreted through the gall bladder.

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Liver Dysfunction Enzymes

Bilirubin: The buildup of bilirubin in the serum and body in association with liver disease indicates liver dysfunction. However, it should be noted that although patients that are icteric secondary to liver disease have liver dysfunction; however not all patients with liver dysfunction are icteric. Further, increase levels of Bilirubin also can be associated with increase intravascular red blood cell destruction (e.g. Immune-mediated Hemolytic Anemias) or gall bladder obstruction.

Liver Dysfunction Enzymes

Blood urea nitrogen (BUN): A low BUN level can be associated with the livers inability to produce take ammonia molecules and produce BUN. When observed on clinical diagnostics, it may suggest a liver dysfunction. A low BUN by itself does not always indicate liver dysfunction. Low protein diets can also result in a low BUN.

Albumin: Albumin is a small carrier protein that binds to hormones and other components in the blood stream to maintain and move necessary elements throughout the body. Decreases in blood albumin concentration can occur generally with a number of disease syndromes that effect production or loss of the protein molecule. A decrease in functioning hepatocytes will compromise the livers ability to produce albumin. As a general rule, at least 75% of normal liver function must be lost before albumin concentration is decreased. When attributable to liver disease, hypoalbuminemia can be an indicator of altered liver function. However, low body albumin can also be associated with Kidney disease, bleeding and intestinal disease.

Liver Dysfunction Enzymes

Bile Acids
Hepatocytes also produce chemicals called bile acids that help to emulsify fat within the small intestine. Bile acids are stimulated when the patient eats. Bile acids then empty through the g bladder and into the common bile py g gall duct. After fat is emulsified, bile acids are then rapidly reabsorbed by the small intestine. In liver disease, bile acids are not properly reabsorbed and represent a true liver dysfunction. To evaluate bile acids, the patient is fasted for 12 hours and a baseline level of bile acids are drawn. Then the animal is fed a high energy food, and two hours later another bile acid level is collected. In an animal with liver dysfunction, pre-feeding (pre-parandial) bile acids are high and post feedings post-parandial bile acids are even higher.

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Hepatic Clinical Diagnostics

Since liver disease, trauma and dysfunction can be difficult to evaluate based on blood work alone, the medical team must also evaluate the history, physical examination and other diagnostic aids. There are many potential forms of liver disease, blood work can appear normal and there can still be significant liver dysfunction. Further, clinical diagnostics and imaging alone are often not sufficient to diagnose the cause of the liver disease present. If the medical team determines that hepatic dysfunction is occurring, a liver biopsy (fine needle, tissue biopsy, or core biopsy) may be recommended to obtain a final diagnosis and help outline treatment protocols.

Hepatic Clinical Diagnostics

Complete Blood Count: Components of the complete blood count can vary dependent on the form of liver disease; however general trends should be monitored for: Red Blood Cells: With chronic waning disease, chronic anemia may be present secondary to the lack of precursors for cellular components. Also chronic liver disease can affect the patients ability to clot blood. With significant anemia, platelet number, clotting times and a blood film should be evaluated to determine if the patient has a non-regenerative anemia vs. chronic bleeding concerns. non regenerative

White Blood Cells: With concerns of infectious disease, changes in white blood cells should be evaluated. With certain forms of cancer (i.e. hepatic lymphoma), white blood cell elevations can be severe with extremely abnormal cytology and high white blood cell.

Platelets: With concerns of decreased clotting factors and an inability to finalize the clotting process (coagulopathy), platelets counts should also be closely monitored. Animal should be carefully assessed for bruising, and jugular sticks should not be attempted if there is concern of a coagulopathy.

Hepatic Clinical Diagnostics

Blood Film:
Changes in Red Blood Cell Morphology
Acanthocytes / Echinocytes Burr Cells Hepatic Lipidosis Schistocytes

White Blood Cell : Lymphoma Abnormal Lymphocytes / White cells Low Platelet Number

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Hepatic Clinical Diagnostics

Chemistry:
Liver Damage Enzymes:
ALT AST GGT Alk Phos

Liver Dysfunction Enzymes:

Elevated Total Bilirubin Paired Bile Acids Hypoalbunemia (Suggestive) Low Blood Urea Nitrogen (Suggestive) Hypoglycemia (Rare)

Urinalysis
A urinalysis should always accompany all blood work evaluations to help determine and indicate multiple organ issues. Key concepts to monitor are: Urine Specific Gravity: Determine Renal Azotemia vs. Pre-renal Azotemia Bilirubinuria: Dog urine can have trace to 1+ bilirubin with no underlying disease. Although bilirubinuria can be found in normal dog urine, it should not be completely discounted. Bilirubinuria will be seen before hyperbilirubinemia in dogs with early hepatic disease. In cats, the presence of bilirubin in feline urine is always significant. The diseases that cause of bilirubinuria are the same as those that result in hyperbilirubinemia; liver disease, hemolysis, bile duct obstruction and sepsis.

Urine Sediment: Ammonium Biurate Crystals can be seen in neutral to high urinary pH and are associated with liver disease and portocaval shunts. However this can be a normal finding in Dalmatians. Bilirubin crystals are seen in any urinary pH and are associated with liver disease and immune-mediated hemolytic anemia

Hepatic Clinical Diagnostics

Coagulation Screen: Evaluating clotting times (Activated Clotting Time (ACT), Partial Thromboplastin Time (PT), Activated Partial Thromboplastin Time (APTT)) can help detect early trends of the patients ability to clot blood. Blood Gas: As discussed in Renal Course of Abaxis University, a metabolic acidosis can be produced by disease which decrease glomerular filtration, increase toxins and toxic metabolites and increase the loss of bicarbonate rich fluids. Since liver disease can produce all these components, a metabolic acidosis can be noted. noted The following parameters are observed with metabolic acidosis: Blood pH < 7.35 A normal to low pCO2 A low base excess (BE) A low Sodium Bicarbonate Level (NaHCO3) A normal to high Anion Gap (AG)

In most cases, treating the underlying liver disease will resolve the metabolic acidosis. However, monitoring blood gas helps the medical team understand the response to treatment and allows for a more accurate prognosis to be made.

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Hepatic Clinical Diagnostics

Abdominal Radiography: Abdominal radiographs can help assess for changes in hepatic size and shape, evidence of gall bladder for stones (Cholelithe), and any other changes in the abdomen that can suggest serious disease. Abdominal Ultrasound: Abdominal ultrasound can assess the internal architecture of the abdominal organs g for changes suggestive of focal or diffuse hepatic disease, changes in the gall bladder wall suggestive of infection or obstruction, and identification of abnormal blood vessels that could suggest a Porto-caval shunt. It is important to note that changes in hepatic architecture can only suggest focal or diffuse disease and rarely helps the medical team confirm diagnosis. Cellular or tissue biopsy is possible through ultrasound guided biopsy techniques.

Exploratory Surgery: In some cases, when ultrasonic biopsy or fine needle aspirate is non-diagnostic, exploratory or laparoscopic surgery and wedge or core biopsy of the liver may need to be completed.

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SectionIII:Appendix

AbaxisUniversityAppendix

EvaluatingforLiverDamageandDysfunction
A. Rosenfeld,DVMABVP TableI:SecondaryConcernsofLiverDysfunction LiverFunction

2009

ConcernofDysfunction
Hepatic Encephalopathy: Development of neurologic symptoms secondary to improperdetoxificationofmicrobesandtoxinswhichremaininthebodyaffecting

Detoxification

thecentralnervoussystem. Physical Symptoms due to build of toxins and bilirubin: Increased toxins can produce nausea, anorexia, depression, vomiting, diarrhea, weakness and weight loss. Anemia:LackofRedBloodCellprecursors Increased Clotting Time: The liver produces clotting factors that finalize clot formation. Hypoalbunemia: Due to lack of blood albumin, the body can shift fluid from the vascular supply to the tissue, increasing fluid accumulation in the body producing

FormationofBuildingBlocks

ascites,edemaandpulmonaryedema(withpatientsonIVfluids).

GlucoseStorage

Hypoglycemia(rare)

TableII:EnzymeswhichevaluateLiverDamage
Alanine aminotransferase (ALT) is responsible for the conversion of 2oxoglutarate to pyruvate and glutamateinthelivercells(hepatocytes). NormalLevel: Alanine aminotransferase (ALTorSGPT) Canine:670IU/L Feline:2876IU/L

ThefollowingpatternsintheALTlevelcanbeobserved: LowALTactivity Notassociatedwithdiseaseconditions Increasedactivityoftheenzymeoccurswith: ACUTELIVERDAMAGE ChronicDrugTherapy(Anticonvulsants,Steroids) PhysicalTrauma CardiacDisease

Aspartate aminotransferase (ASTorSGOT)

Aspartateaminotransferase(AST)isanintracellularenzymeinallcells,buthashigherlevelsofactivity inmuscleandlivercelldamage. NormalLevel: Canine:1043IU/L

Feline:1240IU/L

ThefollowingpatternsintheALTlevelcanbeobserved: LowASTactivity Notassociatedwithdiseaseconditions Increasedactivityoftheenzymeoccurswith: ACUTELIVERDAMAGE Disease,whichaffectthemuscularskeletalsystem(e.g.traumaorseizure) Disease,whichproduceredbloodcelldestruction(e.g.ImmuneMediatedHemolytic Anemia),sincethereissignificantlevelsofASTinredbloodcells.

Gammaglutamyltransferase (GGT): Gammaglutamyltransferase is more an indicator of gall bladder obstruction or lack of bile flow. GGT is an intracellular enzyme responsible for cleaving Cterminal glutamyl groups from one substrate or molecule to another, and is thought to be involved in pathways usedtoprotectcellsfromoxidativeinjury.GGTispresentinallcellsexceptithashigherconcentrationin renalepithelial,bileductandhepaticcells. NormalLevel: Canine:08IU/L Feline:01IU/L

Gamma glutamyltransferase (GGT):

ThefollowingpatternsintheALTlevelcanbeobserved: LowGGTactivity Notassociatedwithdiseaseconditions Increasedactivityoftheenzymeoccurswith: ACUTELIVERDAMAGE IncreasedGGTactivitycanbeassociatedwithdecreasedbileflow(cholestasis) UnlikeASTandALT,GGTdoesnotleakfromhepatocytes;itsactivityisincreaseddueto increasedproduction(induction)oftheenzymeinresponsetodisease.

AlkalinePhosphatase(SALPorALP):AlkalinePhosphataseispresentwithintheliver,intestine,bone, kidneysandplacenta.Onmostchemistrypanels,AlkalinePhosphataseactivityrepresentsthe combinedactivityallcombinedtissuealkalinephosphataselevels. NormalLevel: Canine:876IU/L Feline:862IU/L

AlkalinePhosphatase (SALPorALP):

ThefollowingpatternsintheALTlevelcanbeobserved: LowAlkPhosactivity Notassociatedwithdiseaseconditions I IncreasedAlkalinePhosphataseactivity:HighALPcanoriginatefromdiseasesandnondiseased conditions.SimilartoGGT,ALPsactivityincreasesbecauseofincreasedproductionofthe enzyme(induction)inresponsetodisease.SomeconditionsthatincreaseAlkalinePhosphatase activityare: Hyperadrenocorticism LiverandGallBladderDisease LongTermMedication Bonegrowth

TableIII:EnzymeswhichevaluateLiverDysfunction
Bilirubinisatoxicmetaboliteproducedfromtheredbloodcelldestructioninthespleenandthe breakdownofhemoglobin. NormalLevel: Bilirubin (TotalBilirubinorT. Bili) Canine:00.6mg/dl Feline:00.4mg/dl

ThefollowingpatternsintheALTlevelcanbeobserved: LowBilirubinactivity Notassociatedwithdiseaseconditions Increasedactivityoftheenzymeoccurswith: The buildup of bilirubin in the serum and body in association with liver disease indicatesliverdysfunction. However, it should be noted that although patients that are icteric secondary to liverdiseasehaveliverdysfunction;howevernotallpatientswithliverdysfunction areicteric. Further,increaselevelsofBilirubinalsocanbeassociatedwithincreaseintravascular redbloodcelldestruction(e.g.ImmunemediatedHemolyticAnemias)orgallbladder obstruction.

Albumin

Albumin is a small carrier protein that binds to hormones and other components in the blood streamtomaintainandmovenecessaryelementsthroughoutthebody. NormalLevel: Canine:3.14.5g/dl Feline:2.44.1g/dl

LowAlbuminlevelsmayindicate: Decreases in blood albumin concentration can occur generally with a number of disease

syndromesthat effectproductionorlossoftheproteinmolecule. A decrease in functioning hepatocytes will compromise the livers ability to produce albumin.Asageneralrule,atleast75%ofnormalliverfunctionmustbelostbeforealbumin concentrationisdecreased. Whenattributabletoliverdisease,hypoalbuminemiacanbeasuggestionofalteredliver function. However, low body albumin can also be associated with Kidney disease, bleeding and intestinaldisease.

Bloodureanitrogen (BUN)

AlowBUNlevelcanbeassociatedwiththeliversinabilitytoproducetakeammoniamoleculesand produceBUN.Whenobservedonclinicaldiagnostics,itmaysuggestaliverdysfunction. AlowBUNbyitselfdoesnotalwaysindicateliverdysfunction.Lowproteindietscanalsoresultina lowBUN. Hepatocytesalsoproducechemicalscalledbileacidsthathelptoemulsifyfatwithinthesmallintestine. Bileacidsarestimulatedwhenthepatienteats.Bileacidsthenemptythroughthegallbladderandinto thecommonbileduct.Afterfatisemulsified,bileacidsarethenrapidlyreabsorbedbythesmallintestine.

BileAcids

NormalLevel: Canine:Preparandial:05.0mol/lPostParandial:3.912.7mol/l Feline:Preparandial:05.0mol/lPostParandial:5.010.0mol/l

AlterationsinBileAcidscanindicateatrueliverdysfunction.

TableIV:SuggestedOverviewofClinicalDiagnosticsofLiverDz
Redbloodcellcount:ElevationsofHCT/PCVDehydration,ConcernsofChronicAnemia WhiteBloodCellCount:Bacterial,fungal,parasiticorprotozoalcausesofinfectioushepaticdisease, leukocytosis Completebloodcount Platelets:LowPlateletcountcansupportchronicbleedingsecondarytodecreasedclottingfactors, thrombocytopenia. BloodSmear:NonregenerativeAnemiaduetosecondarytolackoferythropoietin,possibledecreased plateletnumber,andredbloodcellabnormalities(Acanthocytes/Echinocytes,BurrCellsHepatic Lipidosis,Schistocytes) AST ALT ALKPHOS GGT TotalBilirubin(HepaticDisease) Bloodchemistry LiverDysfunction (SeeTableII) LowAlbumin(HepaticDisease) LowBUN +/BloodGlucose ElevationsinPostParandialBileAcids UrineSpecificGravity(USG):tohelpdifferentiaterenalfromprerenalazotemia Urinalysis UrineStick:Bilirubinuria:>+1(Canine)/>Trace(Feline) UrineSediment:AmmoniumBiurateCrystals&Bilirubincrystals

Bloodchemistry LiverDamage (SeeTableII)

Elevationsin: CoagulationProfile ActivatedClottingTime(ACT) PartialThromboplastinTime(PT) ActivatedPartialThromboplastinTime(APTT))

MetabolicAcidosis Thefollowingparametersareobservedwithmetabolicacidosis: BloodGas AnormaltohighAnionGap(AG) BloodpH<7.35 AnormaltolowpCO2 Alowbaseexcess(BE) AlowSodiumBicarbonateLevel(NaHCO3)

Inmostcases,treatingtheunderlyingliverdiseasewillresolvethemetabolicacidosis.However, monitoringbloodgashelpsthemedicalteamunderstandtheresponsetotreatmentandallowsfora moreaccurateprognosistobemade.

AbdominalRadiography:Abdominalradiographscanhelpassessforchangesinhepaticsizeand shape,evidenceofgallbladderforstones(Cholelithe),andanyotherchangesintheabdomen thatcansuggestseriousdisease.

AbdominalUltrasound: Abdominalultrasoundcanassesstheinternalarchitectureoftheabdominalorgansfor changessuggestiveoffocalordiffusehepaticdisease,changesinthegallbladderwall suggestiveofinfectionorobstruction,andidentificationofabnormalbloodvesselsthat couldsuggestaPortocavalshunt. Itisimportanttonotethatchangesinhepaticarchitecturecanonlysuggestfocalor diffusediseaseandrarelyhelpsthemedicalteamconfirmdiagnosis. Cellularortissuebiopsyispossiblethroughultrasoundguidedbiopsytechniques.

OtherPossible DiagnosticExams

ExploratorySurgery:Insomecases,whenultrasonicbiopsyorfineneedleaspirateisnon diagnostic,exploratoryorlaparoscopicsurgeryandwedgeorcorebiopsyofthelivermayneed tobecompleted.