CHAPTER 37 The Liver, Biliary Tract, and Exocrine Pancreas
Development of the Hepatobiliary System and Pancreas
Development of the Hepatic Circulation
Metabolic Functions
Liver enzyme activity
Age-appropriate reference intervals for serum liver enzyme activity are essential for interpreting laboratory data in neonatal puppies and kittens. Differences in serum enzyme activities between neonates and adults reflect physiologic adaptations during the transition from fetal and neonatal life stages, trauma associated with birthing, colostrum ingestion, maturation of metabolic pathways, growth effects, differences in volume of distribution and body composition, and nutrition. Activity of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) usually increase greatly during the first 24 hours of life. In kittens, ALP, CK, and LDH activity exceeds adult values through 8 weeks of age, whereas AST increases only transiently after birth. The early increases in AST, CK, and LDH likely reflect muscle trauma associated with birthing, whereas ALP activity reflects bone isoenzyme associated with bone growth. Enteric absorption of colostral macromolecules during the first day of life causes a substantial increase in ALP in puppies and kittens, and of gamma-glutamyltransferase (GGT) in puppies (Figure 37-1, A and B). This phenomenon is not unique to dogs and cats as it has also been documented in neonatal calves, lambs, pigs, foals, and human infants. Studies also have confirmed significant differences in ALP activities develop between colostrum-deprived and suckling pups and kittens within 24 hours of birth, with a similar change in GGT also observed in puppies. These differences are short lived, resolving within the first 2 weeks, but can be used as a surrogate marker of effective colostrum ingestion. Studies have confirmed that colostrum contains substantially higher GGT and ALP activity than that resident in the serum of the respective dam or queen. For example, colostral or milk GGT in bitches is 100-fold and ALP is tenfold greater than sera until day 10. However, by day 30, GGT and ALP activity in milk is significantly lower than before suckling had commenced. Although a marked influence of colostrum on serum ALP activity in neonatal kittens also occurs, the effect on GGT is modest compared with that in neonatal puppies. Sustained increases (first 6 to 12 months of life) in serum ALP activity in puppies and kittens (maximally threefold more than high normal adult reference values) reflect the bone ALP isoenzyme derived from osteoblast activity.
Hepatic mineral storage
Age-related variations in hepatic concentrations of iron, copper, zinc, and selenium (per gram of dry liver weight) have been reported for Beagle dogs from 8 to 193 days of age (Table 37-2). A decrease in hepatic iron concentrations during the first 20 days after birth likely reflects mobilization of iron for hemoglobin synthesis in bone marrow, the relative iron deficiency of a milk diet, and decrease in hepatic extramedullary hematopoiesis. In many species, hepatic copper concentrations are higher in pediatric individuals relative to adults. In dogs, hepatic copper concentrations change little with advancing age unless challenged with a copper-rich diet. In dogs with copper-associated hepatopathy (primary metabolic or copper transport disorder, dietary copper loading, cholestatic liver injury), hepatic copper concentrations significantly increase over time (see later discussion on Copper Storage Hepatopathy).
TABLE 37-2 Hepatic mineral concentrations in Beagles (mean ± standard deviation; µg/g dry weight)
Mineral content | 8 to 40 days of age (n = 10) | >40 days of age (n = 20) |
---|---|---|
Iron | 1025 ± 882 | 585 ± 258 |
Copper | 285 ± 75 | 304 ± 90 |
Zinc | 225 ± 88 | 143 ± 30 |
Selenium | 2.5 ± 0.4 | 1.9 ± 0.4 |
Summarized from Keen CL, Lonnerdal B, Fisher GL: Age-related variations in hepatic iron, copper, zinc, and selenium concentrations in beagles, Am J Vet Res 42:1884, 1981.
Hepatobiliary Disorders of the Young Dog and Cat
TABLE 37-3 Hepatobiliary disorders in puppies and kittens less than 4 months of age: gross and histopathologic tissue evaluations
Disorder | Puppies (n = 312) | Kittens (n = 132) |
---|---|---|
Infectious hepatopathies | 68 | 18 |
Parvovirus | 30 | 0 |
Herpesvirus | 7 | 0 |
Canine distemper | 11 | — |
Infectious canine hepatitis | 4 | — |
Feline infectious peritonitis | — | 17 |
Parasite migration | 4 | 0 |
Hepatic abscessation | 12 | 1 |
Severe hepatic necrosis | 54 | 41 |
Hepatic congestion | 63 | 25 |
Hepatic lipidosis | 36 | 16 |
Extramedullary hematopoiesis | 39 | 10 |
Cholangitis | 9 | 10 |
Trauma (hematoma, laceration) | 10 | 6 |
Nonspecific hepatitis | 14 | 3 |
Portosystemic vascular anomaly | 1 | 11 |
Hepatic atrophy | 3 | 2 |
Vasculitis | 1 | 0 |
Lymphosarcoma | 1 | 0 |
Diaphragmatic hernia (liver involvement) | 1 | 0 |
Congenital Anatomic Malformations
Cystic hepatobiliary lesions
Cats with cystic liver lesions should be DNA tested for the renal polycystic gene mutation if they are intended for breeding. It remains unclarified if there are variants of this disorder associated with primary liver involvement. DNA testing is done using a cheek swab kit (available from felinegenome@ucdavis.edu). Treatment is usually not indicated for congenital cystic liver lesions unless a large cyst causes abdominal discomfort or fluid accumulation causes pressure effects on adjacent organs or tissues. Periodic aspiration of large problematic cysts has been used to manage some patients. Other alternatives include partial cyst wall resection, entire cyst excision, or removal of an involved liver lobe. In some Persian cats, the polycystic renal or hepatic involvement is recognized during the first few months of life. In some of these, polycystic kidney disease is rapidly lethal. In others, the disorder is mild, does not cause overt signs, and is recognized incidentally later in life.