Hepatobiliary System

Liver - Atrophy

Narrative
Comment:
Hepatic atrophy is seen with severe caloric deficits as well as when animals are exposed to high doses of xenobiotics. The size of the hepatocytes and their nuclei is reduced, with nuclei appearing more closely spaced. There is typically no evidence of glycogen accumulation, and pigmentation (most likely lipofuscin) representative of cellular breakdown may be present in Kupffer cells and hepatocytes (Figure 2). Figure 3 and Figure 4 represent a normal liver.
Recommendations:
Except in dramatic examples, as in this case, diagnosis of hepatic atrophy is a difficult morphologic determination and may be better assessed by organ weight. Grading of hepatic atrophy is likewise difficult. If it becomes necessary to accurately document subtle atrophic changes, a blind evaluation of the slides comparing the relevant dose groups with controls is recommended.
References:

Eustis SL, Boorman GA, Harada T, Popp JA. 1990. Liver. In: Pathology of the Fischer Rat (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 71-94.

Greaves P. 2007. Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, 3rd ed. Elsevier, Amsterdam.

Abstract: http://www.sciencedirect.com/science/book/9780444527714

Harada T, Enomoto A, Boorman GA, Maronpot RR. 1999. Liver and gallbladder. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA, Gaul BW, eds). Cache River Press, Vienna, IL, 119-183.

Abstract: http://www.cacheriverpress.com/books/pathmouse.htm

National Toxicology Program. 1994. NTP TOX-38. Toxicity Studies of Sodium Selenate and Sodium Selenite (CAS. No. 13410-01-0 and 10102-18-8) Administered in Drinking Water to F344/N Rats and B6C3F1 Mice. NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/tox38abs

Thoolen B, Maronpot RR, Harada T, Nyska A, Rousseaux C, Nolte T, Malarkey D, Kaufmann W, Kutter K, Deschl U, Nakae D, Gregson R, Winlove M, Brix A, Singl B, Belpoggi F, Ward JM. 2010. Hepatobiliary lesion nomenclature and diagnostic criteria for lesions in rats and mice (INHAND). Toxicol Pathol 38:5S-81S.

Full Text: http://tpx.sagepub.com/content/38/7_suppl/5S.full
  • Image of atrophy in the liver from a female F344/N rat in a subchronic study

    Atrophy in a female F344/N rat from a subchronic study.

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Atrophy in a female F344/N rat from a subchronic study.
Atrophy in a female F344/N rat from a subchronic study.
Atrophy in a female F344/N rat from a subchronic study.
Atrophy in a female F344/N rat from a subchronic study.
Normal liver in a control female F344/N rat from a subchronic study.
Normal liver in a control female F344/N rat from a subchronic study.
Normal liver in a control female F344/N rat from a subchronic study. Higher magnification of Figure 3.
Normal liver in a control female F344/N rat from a subchronic study. Higher magnification of Figure 3.

Author

Robert R. Maronpot, DVM, MS, MPH, DACVP, DABT, FIATP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

John Cullen, VMD, PhD, DACVP, FIATP
Anatomic Pathology, Professor
North Carolina State University College of Veterinary Medicine
Raleigh, NC

David E. Malarkey DVM, PhD, DACVP, FIATP
Head, National Toxicology Program Pathology Group
Cellular and Molecular Pathology Branch
Division of the National Toxicology Program
National Institute of Environmental Health Sciences
Research Triangle Park, NC