Describe the mechanism by which pyrrolizidine alkaloids (PA) cause chronic megalocytic hepatopathy in the horse, including the role of Zone III microsomal enzymes in the biotransformation process. Identify the pathognomonic cellular change that results from this toxicity and explain why the onset of clinical signs of hepatic failure is often significantly delayed after the ingestion of PA-containing plants.
Mechanism: Ingested PA are carried via portal circulation to the liver. They are metabolized primarily by the cytochrome P-450 microsomal enzymes found in Zone III of the hepatic acinus. This biotransformation converts the PA into highly reactive toxic pyrrole derivatives. Cellular Effect: The pyrroles alkylate nucleic acids and protein, thereby inhibiting cellular replication and protein synthesis. This results in the cells enlarging instead of dividing, forming megalocytes. athognomonic Change: The characteristic finding is megalocytosis, often accompanied by portal fibrosis and bile duct hyperplasia.
Delayed Onset: The effects are cumulative. Clinical signs of hepatic failure (HE, photosensitization) are usually delayed 4 weeks to 12 months after consumption. This delay occurs because significant fibrosis (and failure) only ensues when the megalocytes die, and clinical signs do not become apparent until greater than 80% of the hepatic mass is lost
The clinical syndrome of Hepatic Encephalopathy (HE) is highly correlated with the accumulation of ammonia, which is toxic to neuronal tissue by altering CNS energy production and neurotransmission. Detail the mechanism by which the liver normally eliminates free ammonia. In a horse exhibiting signs of HE, identify two pharmaceutical classes administered orally that are intended to reduce the production or absorption of enteric-derived neurotoxins, citing their proposed mechanism of action.
Normal Ammonia Elimination: The liver has sole responsibility for converting free ammonia or glutamine into urea. This occurs via the Krebs-Henseleit cycle (urea cycle) in the hepatocyte mitochondria. Urea is then released into the blood and transported to the kidney for excretion as BUN. Ammonia Toxicity: Failure of this process leads to hyperammonemia, causing astrocyte swelling, cerebral edema, and disruption of CNS energy metabolism and neurotransmission.
Oral Pharmaceuticals to Reduce Neurotoxins: The goal is to reduce the production or absorption of toxic protein metabolites generated by enteric bacteria.
1. Antimicrobials (e.g., Neomycin, Metronidazole): Mechanism: They alter the gastrointestinal flora, thereby reducing the production of ammonia and other neurotoxins by enteric bacteria.
2. Lactulose (Disaccharide): Mechanism: Metabolized by colonic bacteria to organic acids, which reduces the luminal pH. The lower pH converts unionized ammonia (NH
3) into the ionized, less diffusible form (NH
4+), thereby trapping the ammonia in the bowel lumen and preventing its absorption
Theiler’s disease (serum-associated hepatitis) has historically been linked to the administration of equine-origin biologic antisera. Identify the most recently discovered DNA virus that has been shown on experimental inoculation to cause liver disease in horses, and explain the immunological finding that suggests why Nonprimate Hepacivirus (NPHV) infection may cause mild disease documented by elevations in liver enzymes.
Newly Discovered DNA Virus: The most recently discovered virus associated with Theiler’s disease, which has been proven on experimental inoculation to cause liver disease in horses, is an equine DNA virus called equine parvovirus. This virus has been found in consecutive cases associated with tetanus antitoxin administration.
NPHV Immunological Finding: Nonprimate Hepacivirus (NPHV) infection in horses generally results in mild disease documented by elevated liver enzymes. This is suggested to be linked to the immune response: the enzyme elevations appear shortly after the development of measurable antibodies. This suggests that antibody-mediated activity related to the virus could cause some disease. Support for this theory comes from experimentally infected SCID foals that produced no antibody and showed no increase in GGT. Needs more study to see if this is important for chronic hepatitis?
iscuss the major cellular and acellular components of the equine hepatic microarchitecture found adjacent to the sinusoids, specifically detailing the specialized functions and locations of Kupffer cells and Ito cells (hepatic stellate cells). Furthermore, explain the steps by which Ito cells contribute to the pathogenesis of hepatic fibrosis in response to chronic liver injury
inusoid Lining and Content: Hepatic sinusoids are larger than capillaries. They are lined with endothelial cells and Kupffer cells. Kupffer cells are tissue-fixed macrophages. A cleft, called the space of Disse, lies between the hepatocytes and the cells lining the sinusoids.
* Blood Flow Path: The blood supply to the liver comes 70% from the hepatic portal vein (deoxygenated blood) and 30% from the hepatic artery (oxygenated blood). This arterial and portal venous blood mixes together in the hepatic sinusoids. The sinusoidal blood then flows along the plates of hepatocytes toward the central vein.
* Portal Vein Sources: The hepatic portal vein receives blood from the stomach, spleen, pancreas, small intestines, cecum, and large colon.Role in Detoxification: Kupffer cells are part of the mononuclear phagocyte system. They are located strategically along the hepatic sinusoids where the portal blood can be cleansed, for example, of bacterial endotoxin, before the toxins are exposed to the hepatocytes and the systemic circulation.
* Other Functions: Kupffer cells function mainly in phagocytosis. They also recycle iron from senescent or injured red blood cells and, as a result, they accumulate hemosiderin, which can be pronounced even in disease-free horsesIto cells, or hepatic stellate cells, are located in the space of Disse. In their quiescent (normal) state, they store fat or fat-soluble vitamins (e.g., vitamin A).
* Fibrosis Pathogenesis: Hepatic fibrosis is promoted predominantly by these hepatic stellate cells in response to chronic injury. When the liver is damaged, nearby Kupffer cells produce tumor necrosis factor–α (TNF-α). This cytokine production causes the stellate cells to activate, decrease their vitamin A stores, and secrete collagen (thus causing fibrosis). This mechanism is crucial because fibrosis occurs when the rate of ongoing necrosis exceeds the rate of regeneration
Define the three major clinical classifications of hyperbilirubinemia in the horse: Prehepatic (Hemolytic) icterus, Hepatic (Retention) icterus, and Regurgitation (Cholestatic) icterus. For each classification, state the predominant fraction of bilirubin (conjugated vs. unconjugated) that increases in the blood, and provide a specific, recognized cause of that condition in horses, drawing from anemia, anorexia, or intestinal disease.
- Bilirubin Metabolism and Excretion Pathway
Your description of bilirubin synthesis, transport, conjugation, and excretion is accurate according to the physiology of the horse.
* Synthesis (Heme Breakdown): Bilirubin is the breakdown product of tetrapyrroles, primarily formed from hemoglobin and myoglobin. Nonheme pigments, such as the cytochromes, also contribute.
* Macrophage Processing: Macrophages in the spleen, bone marrow, and liver (Kupffer cells) engulf the pigments, convert them to biliverdin, and then convert biliverdin to free, insoluble bilirubin.
* Transport (Unconjugated/Indirect): This free, insoluble bilirubin is also referred to as indirect-reacting or unconjugated bilirubin. It is bound with albumin in the plasma to decrease its hydrophobicity and is delivered to the liver.
* Hepatic Uptake and Conjugation: At the hepatocyte surface, unconjugated bilirubin is transferred from albumin to ligandin, an intrahepatic transport and storage protein. Within the hepatocyte’s endoplasmic reticulum, the bilirubin is conjugated with glucuronide.
* Excretion (Conjugated/Direct): Conjugated bilirubin, also called direct-reacting bilirubin, is water soluble and is excreted into the bile canaliculi. Under normal circumstances, little conjugated bilirubin escapes into the general circulation.
* Intestinal Processing: Microflora in the intestinal tract reduce conjugated bilirubin to urobilinogen and stercobilin. Urobilinogen is absorbed by the intestinal mucosa and transported back to the liver via the enterohepatic circulation. A small amount spills over into the urine. Also, a small amount of conjugated bilirubin in the intestinal lumen is hydrolyzed back to unconjugated bilirubin and subsequently is reabsorbed.
Prehepatic: ause: Increased production of bilirubin occurs with hemolysis (intravascular and extravascular) and after reabsorption of erythrocytes following massive intracorporeal hemorrhage.
* Bilirubin Fraction: This form, called hemolytic or prehepatic icterus, results in an increased concentration of unconjugated bilirubin in the blood, as the rate of production temporarily exceeds the liver’s ability to conjugate and excrete it.
* Spillover: Occasionally, the concentration of conjugated bilirubin also mildly increases in the blood due to “hepatic spillover” when the liver processes the excessive bilirubin.
* Specific Cause: Hemolysis is a primary cause* Cause: This form results from impaired uptake and conjugation of bilirubin. It is the most common form in horses with liver disease, usually resulting from acute hepatocellular disease.
* Bilirubin Fraction: This results in increased blood levels of unconjugated bilirubin.
* Specific Causes in Horses:
◦ Anorexia: Anorexia in horses causes variable degrees of hyperbilirubinemia. Starvation reduces the store of ligandin (the intrahepatic protein responsible for extracting unconjugated bilirubin from albumin), thereby impeding bilirubin uptake.
◦ Hepatocellular Disease: Acute hepatocellular disease.
◦ Drugs: Administration of certain drugs (e.g., steroids or heparin) can impede bilirubin uptake and conjugation.
◦ Congenital Deficiencies: Persistent hyperbilirubinemia without anorexia, hemolysis, or acquired liver disease that closely resembles Gilbert’s syndrome (an inherited deficiency in conjugating enzymes) has been reported in Thoroughbreds.
C. Posthepatic (Regurgitation/Cholestatic) Icterus
- Cause: If the excretion of conjugated bilirubin into the biliary tract is impeded, regurgitation icterus occurs. This is caused by blockage of bile flow.
- Bilirubin Fraction: Because conjugated bilirubin is water soluble, the elevated fraction is conjugated bilirubin.
- Key Diagnostic Ratio: If the conjugated bilirubin concentration is greater than 30% of the total value, cholestasis should be suspected. Increases in the conjugated fraction of less than 25% of the total are usually indicative of predominant hepatocellular disease.
- Specific Causes in Horses: Blockage can accompany:
◦ Cholangitis/Hepatitis/Cholelithiasis: Inflammation of the biliary tract, obstructive cholelithiasis (CL), or cholangiohepatitis (CH).
◦ Intestinal Obstruction: Physical obstruction of the biliary tract associated with colon displacements or duodenal ulcers.
Clarification on Posthepatic Bilirubin Fraction: It is important to note that while posthepatic (regurgitation/cholestatic) icterus is caused by the impeded excretion of conjugated bilirubin, leading to its accumulation and subsequent “regurgitation” into the bloodstream, the majority of the increase in total bilirubin in hepatocellular disease (hepatic icterus) is typically from unconjugated bilirubin. In cholestasis, the diagnostic feature is the proportionate increase in the conjugated fraction (greater than 30% of total).
Describe the typical presentation, age range, and causative agent of Tyzzer’s Disease in foals. What is the definitive antemortem diagnostic challenge, and what laboratory findings, specific to carbohydrate metabolism, are common?
Causative Agent: Clostridium piliforme (a motile, spore-forming, obligate intracytoplasmic bacterium) causes acute necrotizing hepatitis.
Presentation/Age: Limited to foals between 7 and 42 days of age (average age 20 days). Clinical signs are often nonspecific (loss of suckle, depression, fever, icterus, shock) or foals are found dead without premonitory signs.
Transmission: Foals are infected by ingesting feces of their dams or contaminated soil. The bacteria replicate in the intestinal epithelium and reach the liver via the lymphatics and blood.
Diagnostic Challenge: Antemortem diagnosis is difficult due to the peracute onset and nonspecific signs. Definitive diagnosis often requires demonstration of the organism on silver stains or by PCR analysis at necropsy.
Carbohydrate Metabolism Findings: Foals typically exhibit profound hypoglycemia (glucose less than 60 mg/dL; 3.33 mmol/L)
What increases the risk of Tyzzers disease
- young mares (<6y)
- mares new to the premises
- antimicrobial (TMPS)
- corticosteroid
- high protein diet
Describe the pathogenesis of dependent abdominal edema and ascites in chronic liver failure, including the role of albumin. Also, define Hepatorenal Syndrome (HRS) and list a key speculative cause of HRS in hyperlipemic ponies.
Hypoalbuminemia: Edema can occur with chronic liver failure due to hypoalbuminemia (decreased albumin synthesis by the liver) and subsequent water retention. Because albumin has a long half-life (19 to 20 days), hypoalbuminemia is a rare clinical sign, appearing only after massive hepatic loss for prolonged periods.
Ascites/Portal Hypertension: Liver disease may cause portal hypertension, which leads to increased hydrostatic and oncotic pressure in the intestinal mucosa, resulting in water and protein loss into the peritoneal cavity (ascites).
Hepatorenal Syndrome (HRS): HRS is characterized by acute azotemia and anuria.
Speculative Cause in Hyperlipemia: HRS may occur in ponies with hyperlipemia and hepatic lipidosis. Speculative causes include reduced effective circulating volume, decreased hepatic inactivation of renin, and endotoxemia.
Compare Bromsulphthalein (BSP) and Indocyanine Green (ICG) clearance tests to Serum Bile Acids (SBA) concentration. Explain the primary limitation of BSP clearance related to bilirubin levels, and provide the typical clearance half-life for BSP in horses.
Comparison: SBA is the current standard functional test, having essentially replaced foreign dye clearance tests (BSP/ICG). Both BSP and ICG are exogenous substances removed by the liver, conjugated, and excreted into bile. BSP clearance half-life is prolonged when greater than 50% of hepatic function is lost.
BSP Half-Life: The normal half-life of BSP in horses is 2.8±0.5 minutes.
Limitation of BSP: If the blood concentration of bilirubin is greatly increased, the bilirubin will compete with the BSP for binding sites and conjugating enzymes in the liver. This competition causes the apparent half-life of BSP to be prolonged, hindering accurate interpretation of true hepatic function. Prolongation seen with decreased blood flow and decreased half time seen wiht decreased protein
Explain why hemorrhagic diathesis frequently accompanies hepatic insufficiency. Specify which vitamin K–dependent coagulation factor has the shortest half-life and detail how cholestasis exacerbates coagulopathy.
Mechanism of Hemorrhagic Diathesis: The liver is responsible for the synthesis of numerous factors involved in coagulation and fibrinolysis. Hepatic insufficiency leads to decreased synthesis of these factors, resulting in abnormal hemostasis and clinical signs such as petechial hemorrhages or spontaneous bleeding. Additionally, failure of Kupffer cells to remove activated coagulation factors and FDPs (fibrin degradation products) from the circulation also interferes with platelet function and fibrin clot formation.
Shortest Half-life Factor: The vitamin K–dependent factors (II, VII, IX, X, and protein C) are especially sensitive to hepatic disease. Factor VII has the shortest half-life, only 4 to 5 hours, making abnormalities frequently first observed in the prothrombin time (PT).
Cholestasis Exacerbation: Vitamin K is fat soluble and requires bile acids for proper absorption from the intestinal tract. During hepatic insufficiency, when bile excretion is decreased (cholestasis), malabsorption of Vitamin K occurs, directly impairing the synthesis of Vitamin K–dependent factors and worsening coagulopathy.
In a horse presenting with Cholangiohepatitis (CH) or Cholelithiasis (CL), discuss the expected pattern of liver enzymes and bilirubin, noting the significance of the conjugated bilirubin fraction being greater than 30% of the total. Describe two specific ultrasonographic findings supportive of CH/CL. Finally, explain the unique histopathological finding of concentric fibrosis and its importance.
Enzyme and Bilirubin Pattern: Hepatocellular enzymes (SDH/GLDH) may be increased 2–4 times normal, but the GGT and ALP are often markedly elevated (GGT commonly 7–20 times normal). Bilirubin Significance: If the conjugated bilirubin concentration is greater than 30% of the total value, cholestasis should be suspected.
Ultrasonographic Findings: 1. Dilated bile ducts: Visible as enlarged channels running parallel to the portal veins; normally undetectable. 2. Hyperechoic choleliths: Stones (calculi) casting an acoustic shadow (seen in 50%–75% of CL cases).
Concentric Fibrosis: Histologically, this finding involves circumferential biliary hyperplasia and fibrosis around a bile duct. This is characteristic of an obstruction of the common bile duct, and its presence on biopsy can be extremely helpful when an obstructing stone cannot be seen on ultrasound.
Detail the two main phases of hepatic biotransformation (detoxification), explaining the purpose of each. Identify the key enzyme system responsible for Phase 1 reactions, stating the acinar zone where this activity is highest. Finally, explain how therapeutic agents referred to as inducers or inhibitors alter biotransformation rates
Overall Purpose: To alter the physical properties of substances (usually water-insoluble) to render them more susceptible to renal or biliary excretion.
Phase 1: Purpose: Polar groups are added to the compound or existing polar groups are exposed via oxidation, hydroxylation, deamination, or reduction. Key Enzyme System: Primarily occurs on the enzyme-bound systems of the endoplasmic reticulum, known as microsomes. The key enzymes are the P-450 system (mixed function oxidases), which have the highest activity in Zone III of the hepatic acinus.
Phase 2: Purpose: The product of Phase 1 is conjugated, usually with glucuronate or sulfate.
Drug Interactions:
Inducers (e.g., Barbiturates, Phenylbutazone): Saturate the enzymes, causing hypertrophy of the endoplasmic reticulum and accelerating removal rates of both themselves and other substances.
Inhibitors (e.g., Chloramphenicol, Cimetidine): Inhibit microsomal enzymes, thus prolonging the effect of other substrates
Describe the pathogenesis of equine hyperlipemia in susceptible equids (ponies, Miniature Horses, donkeys), focusing on the hormonal and metabolic triggers. Explain why the overproduction of Very Low-Density Lipoprotein (VLDL) by the liver is the primary mechanism responsible for the clinically high blood triglyceride levels.
usceptible Equids: Ponies, Miniature Horses, and donkeys are most susceptible. Triggers: Stressful events or negative energy balance (e.g., late gestation, lactation, anorexia, underlying disease) trigger the release of catecholamines and glucocorticoids. Adipose Mobilization: These hormones stimulate hormone-sensitive lipase in adipose tissue, causing lipolysis and the release of free fatty acids (FFA) into the blood.
Hepatic Role: The liver takes up the FFA. If the supply of FFA exceeds oxidation capacity, the FFAs are esterified into triglycerides. These triglycerides are packaged with protein, carbohydrate, and cholesterol in the hepatocyte into VLDLs.
Primary Mechanism: Hyperlipemia results from the efficient and excessive hepatic synthesis of triglycerides, with subsequent secretion of triglyceride-laden VLDL into the blood. Crucially, the activity of the rate-limiting enzyme responsible for VLDL removal, lipoprotein lipase, is not impaired and may even be increased in affected ponies; thus, overproduction is the primary problem, not impaired removal.
Beyond the accumulation of ammonia, describe two other distinct mechanisms or hypotheses proposed for the pathogenesis of Hepatic Encephalopathy (HE) in horses with liver failure. Address the mechanism involving false neurotransmitters derived from aromatic amino acids (AAAs), and contrast this with the hypothesis involving augmented activity of inhibitory neurotransmitter systems (GABA-benzodiazepine).
- False Neurotransmitter Accumulation (AAA Hypothesis): Hepatic failure leads to decreased metabolism of Aromatic Amino Acids (AAAs) (phenylalanine, tyrosine, tryptophan) by the liver, resulting in increased serum concentrations and a decreased BCAA-to-AAA ratio. This promotes the influx of AAAs into the brain. In the CNS, phenylalanine and tyrosine are converted to false neurotransmitters, such as octopamine and phenylethanolamine. These false neurotransmitters replace true neurotransmitters (like dopamine and norepinephrine), causing a net effect of reduced neuronal excitation and increased neural inhibition.
- Augmented Inhibitory Neurotransmitter Activity (GABA Hypothesis): The pathophysiology of HE involves augmented activity of the GABA-benzodiazepine inhibitory neurotransmitter system. Hyperammonemia itself has been shown to increase GABAergic tone. The hypothesis posits that endogenous diazepam-like substances (natural benzodiazepines) accumulate in the brain during liver failure. These substances bind to the benzodiazepine binding site on the GABA receptor complex, potentiating GABA-induced sedation, hyperpolarization, and neuronal inhibition
In a horse suspected of having chronic megalocytic hepatopathy (Pyrrolizidine Alkaloid toxicity), describe the characteristic gross and microscopic findings expected in the liver parenchyma at necropsy, including the specific name for the histopathological finding of enlarged, inhibited hepatocytes. Explain the expected pattern of serum enzyme elevations (SDH/GGT) in chronic PA toxicosis when clinical signs are present, and state the concentration of Serum Bile Acids (SBA) that is associated with a grave prognosis in these cases.
Gross Findings: The liver typically appears smaller than normal and develops a firm texture due to extensive fibrosis.
Microscopic Findings: The characteristic histopathologic finding is periportal megalocytosis (enlarged hepatocytes that cannot divide due to inhibited replication), often accompanied by portal fibrosis and biliary hyperplasia. Megalocytes may not be seen until 30 days or more after exposure.
Enzyme Pattern (Chronic): By the time clinical signs of failure develop, hepatocellular enzymes like SDH and AST are often normal or only mildly increased. Because fibrosis occurs periportally, biliary enzymes such as GGT and ALP are persistently increased.
Grave Prognosis SBA: Concentrations of serum bile acids greater than 50 μmol/L in horses with pyrrolizidine toxicosis are associated with a grave prognosis.
Unlike most mammals, the horse lacks a gallbladder. Describe the anatomical location where the common bile duct and the pancreatic duct empty into the equine duodenum, and explain the physiologic consequence of lacking a gallbladder and a sphincter at this site for the concentration and flow pattern of bile. Additionally, identify the specific layer of bile ducts that facilitates water and electrolyte exchange.
Duct Entry Point: Both the common bile duct and the pancreatic duct empty into the duodenum at the major duodenal papilla.
Physiologic Consequence (Lack of Gallbladder/Sphincter): Because the horse does not have a gallbladder or a sphincter at the site of entry of the hepatic duct into the intestine, the bile is unconcentrated and flows almost continuously.
Water/Electrolyte Exchange: Water and electrolyte exchange takes place between the bile and the bile duct epithelium; however, isotonicity is maintained
Define Theiler’s disease (serum-associated hepatitis), citing its typical temporal association with equine-origin biologic administration. Detail the expected laboratory findings (enzymes and bilirubin) that suggest this acute disease, and identify the DNA virus now most closely associated with the syndrome. What factors warrant a poor to grave prognosis?
Definition/Association: Theiler’s disease is one of the most commonly described causes of acute diffuse hepatic necrosis in adult horses. It frequently occurs 4 to 10 weeks after the horse has received an equine-origin biologic antiserum (e.g., tetanus antitoxin, plasma). Laboratory Findings (Acute): Hepatocellular enzymes like SDH, GLDH, and AST are typically increased several fold. GGT is increased but not to the magnitude of the hepatocellular enzymes. Both unconjugated and conjugated bilirubin levels are increased, but the conjugated portion generally remains less than 25% of the total. Associated Virus: The most recently discovered virus shown on experimental inoculation to cause liver disease is an equine parvovirus (an equine DNA virus). Prognosis: The prognosis is poor to grave in horses with severe HE, hemorrhage, or hemolysis. A prolonged PT or APTT also suggests poor prognosis.
Differential diagnosis of acute hepatic disease
- Viral:
°theilers disease
°non-primate hepatitis (subclinical)
°EHV-1
°EIA (acute necrotic hepatitis)
°EVA (rare) - Bacterial:
°Tyzzers disease
°primary (rare)
° Septicemia
° Ascending cholangiohepatitis
° Clostridium novyi type B (black disease -> SHEEP) - Toxic
°Drugs
°Plants (Pyrrolizidine!)
°mycotoxins (fumonisine B1, aflatoxines)
°Iron - Hyperlipemia/lipidosis
Chronic liver disease ddx
- pyrrolizidine intoxication
- clover intoxication
- chronic active hepatitis
-cholelithiais/cholangitis/cholangiohepatitis - gastroduodenual ulceration
- abces
- neoplasia
°cholangiocarinoma (!)
°hepatocellular carinoma
°hepatoblastoma
°lymphoma (metastatic) - amyloidosis
- hypoxemia
Choleliths are predominantly composed of calcium bilirubinate. Detail the precise role of ascending enteric bacterial infection in the formation of these stones.
Bacterial Role in Cholelith Formation: Ascending retrograde bacterial infection from the small intestine (as bile is normally sterile) is probable. Enteric organisms (e.g., Clostridium spp., E. coli) produce bacterial β-glucuronidase. This enzyme deconjugates the water-soluble bilirubin (bilirubin diglucuronide), leading to the precipitation of calcium bilirubinate which forms the calculi.
Congenital extrahepatic Portosystemic Shunts (PSS) and Biliary Atresia are rare causes of hepatic failure in foals. Contrast the most consistent nitrogen metabolism abnormality found in PSS versus the most consistent bilirubin abnormality found in biliary atresia. Provide two highly sensitive diagnostic techniques used to confirm a PSS.
Nitrogen Metabolism in PSS: Consistent findings include decreased BUN (due to reduced urea synthesis) and increased blood ammonia concentration. Bilirubin in Biliary Atresia: Laboratory evaluation is consistent with biliary obstruction, specifically markedly increased GGT and conjugated bilirubin. Highly Sensitive Diagnostic Techniques for PSS: 1. Transrectal Hepatic Scintigraphy: Technetium pertechnetate is detected in the heart almost immediately, as it bypasses the liver. 2. Bubble Gram (Agitated Saline Echocardiography): Agitated saline injected transsplenically is immediately detected in the right side of the heart, confirming shunting.
What are 3 fecal occult blood tests?
- Guiaiac based test –> needs 1-2L of blood loss before positive result
- ELISA (caronic anhydrase I): can detect 50µg hemoglobin
- Lateral flow immunoassay (SUCCEED)
–> all have variable results –> not really sensitive/specific enough yet
