Liver and Kidney Overview

Liver and Kidney Anatomy, Physiology, and Function in Cats and Dogs #

Introduction #

The liver and kidneys are vital organs in cats and dogs, serving essential roles in metabolism, detoxification, and homeostasis. While sharing many anatomical and physiological similarities, these organs exhibit species-specific differences that influence their function, particularly in drug metabolism and response to physiological mediators such as dopamine.

Liver Anatomy #

In both cats and dogs, the liver is the largest internal organ, positioned in the cranial abdomen behind the diaphragm. The canine liver typically comprises six lobes: left lateral and medial lobes, right lateral and medial lobes, the quadrate lobe, and the caudate lobe. The feline liver follows a similar pattern but with some structural variations. The liver receives blood from two sources: oxygenated blood via the hepatic artery (25-30%) and nutrient-rich blood via the portal vein (70-75%)[1].

The basic histological unit of the liver is the hepatic lobule, consisting of hepatocytes arranged in plates radiating from a central vein. Portal triads, containing branches of the hepatic artery, portal vein, and bile duct, are located at the periphery of each lobule. Hepatocytes perform most liver functions, while Kupffer cells serve as resident macrophages[2].

Notable anatomical differences between species include liver size relative to body weight: approximately 3-4% in dogs versus 2-3% in cats. Additionally, the feline liver has a relatively smaller caudate lobe and less distinct lobulation compared to dogs[3].

Liver Physiology and Function #

The liver performs over 500 functions, including:

1. Metabolism of carbohydrates, proteins, and lipids
2. Synthesis of plasma proteins, coagulation factors, and bile
3. Storage of vitamins, minerals, and glycogen
4. Detoxification of endogenous and exogenous compounds
5. Biotransformation of drugs and toxins

Blood entering the liver through the portal system delivers nutrients absorbed from the gastrointestinal tract for processing. The liver regulates blood glucose through glycogenesis, glycogenolysis, and gluconeogenesis, maintains ammonia homeostasis through the urea cycle, and synthesizes cholesterol and lipoproteins[4].

Species Differences in Hepatic Drug Metabolism #

A significant species difference between cats and dogs lies in their hepatic drug metabolism capacity, particularly regarding glucuronidation. Glucuronidation is a phase II biotransformation pathway that conjugates drugs with glucuronic acid, increasing water solubility and facilitating excretion.

Cats exhibit decreased glucuronidation capacity compared to dogs due to deficiencies in several UDP-glucuronosyltransferase (UGT) enzymes, particularly UGT1A6, which is expressed as a pseudogene in felines. This deficiency explains cats’ sensitivity to drugs like acetaminophen, carprofen, and certain NSAIDs that rely heavily on glucuronidation for elimination[5,6].

Dogs possess a more robust glucuronidation system, though still less efficient than humans. They can tolerate higher doses of drugs requiring glucuronidation, though individual and breed variations exist. Cats compensate for their glucuronidation deficiency through alternative pathways such as sulfation, acetylation, and glutathione conjugation, though these pathways may become saturated with high drug doses[7].

Kidney Anatomy #

Canine and feline kidneys are paired, bean-shaped organs located in the retroperitoneal space of the abdomen. Each kidney consists of an outer cortex and inner medulla, surrounded by a fibrous capsule. The renal pelvis collects urine, which then passes through the ureter to the bladder.

The functional unit of the kidney is the nephron, comprising the glomerulus, proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct. Dogs possess approximately 400,000-500,000 nephrons per kidney, while cats have 190,000-200,000[8].

Anatomical differences include:

• Kidney shape: Canine kidneys are more elliptical, while feline kidneys are more rounded
• Dogs have multilobular kidneys with multiple medullary pyramids, while cats have unilobular kidneys with a single pyramid
• Relative to body weight, feline kidneys are larger (0.4-0.6%) than canine kidneys (0.3-0.5%)
• Cats typically have shorter renal papillae than dogs[9]

Kidney Physiology and Function #

The kidneys perform several critical functions:

1. Filtration of blood and excretion of waste products
2. Regulation of fluid, electrolyte, and acid-base balance
3. Production of hormones (erythropoietin, renin, calcitriol)
4. Regulation of systemic blood pressure
5. Concentration and dilution of urine

Blood enters the kidney through the renal artery, which branches into progressively smaller vessels culminating in the glomerular capillaries. The glomerular filtration rate (GFR) in healthy dogs ranges from 2-4 ml/min/kg, while in cats it ranges from 1.6-2.8 ml/min/kg[10].

Dopamine Effects on DA1 Receptors #

Dopamine receptors are classified into D1-like (DA1, D5) and D2-like (D2, D3, D4) families. DA1 receptors are present in both the renal vasculature and tubular epithelium of cats and dogs. Activation of DA1 receptors produces vasodilation in the renal, mesenteric, coronary, and cerebral vascular beds and increases natriuresis through inhibition of sodium reabsorption[11].

In dogs, DA1 receptor stimulation causes:

• Renal vasodilation, increasing renal blood flow
• Increased GFR
• Inhibition of sodium reabsorption in proximal tubules
• Natriuresis and diuresis

Cats show similar responses but with reduced sensitivity. Feline renal vasculature contains fewer DA1 receptors, resulting in attenuated renal vasodilatory responses to dopamine compared to dogs. This difference explains why therapeutic doses of dopamine (1-3 μg/kg/min) reliably increase urine output in dogs but have variable effects in cats[12,13].

This species difference has important clinical implications for managing acute kidney injury. Low-dose dopamine therapy may be beneficial in dogs but less effective in cats, necessitating alternative approaches for feline patients[14].

Clinical Implications #

Understanding species differences in liver and kidney function is crucial for veterinary medicine:

1. Drug dosing must account for feline glucuronidation deficiencies, with appropriate dose adjustments or alternative medications
2. Interpretation of liver and kidney function tests must consider species-specific reference ranges
3. Therapeutic approaches for renal perfusion enhancement must account for differential dopamine responsiveness
4. Nutritional management of hepatic and renal disease should address species-specific metabolic needs

References #

1. König HE, Liebich HG. Veterinary Anatomy of Domestic Mammals: Textbook and Colour Atlas. 7th ed. Thieme; 2020.
2. Eulitz CM, Scheuermann DW. Comparative morphology of the liver of dog and cat. Anat Histol Embryol. 2019;48(6):519-536.
3. Dyce KM, Sack WO, Wensing CJG. Textbook of Veterinary Anatomy. 5th ed. Saunders; 2018.
4. Center SA. Liver function in health and disease. In: Ettinger SJ, Feldman EC, Côté E, eds. Textbook of Veterinary Internal Medicine. 8th ed. Elsevier; 2017:1588-1671.
5. Court MH. Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms. Vet Clin North Am Small Anim Pract. 2023;53(1):37-51.
6. Shrestha B, Reed JM, Starks PT, et al. Evolution of a major drug metabolizing enzyme defect in the domestic cat and other Felidae: phylogenetic timing and the role of hypercarnivory. PLoS One. 2011;6(3):e18046.
7. Court MH, Greenblatt DJ. Molecular basis for deficient acetaminophen glucuronidation in cats. Biochem Pharmacol. 2000;60(2):181-186.
8. Verlander JW. Renal physiology. In: Klein BG, ed. Cunningham’s Textbook of Veterinary Physiology. 6th ed. Elsevier; 2020:460-494.
9. DiBartola SP, Westropp JL. Urinary tract disorders. In: Nelson RW, Couto CG, eds. Small Animal Internal Medicine. 6th ed. Elsevier; 2020:663-669.
10. Von Hendy-Willson VE, Pressler BM. An overview of glomerular filtration rate testing in dogs and cats. Vet J. 2011;188(2):156-165.
11. Hussain T, Lokhandwala MF. Renal dopamine receptors and hypertension. Exp Biol Med. 2003;228(2):134-142.
12. Wohl JS, Schwartz DD, Flournoy WS, et al. Renal hemodynamic and diuretic effects of low-dosage dopamine in anesthetized cats. J Vet Pharmacol Ther. 2007;30(6):479-485.
13. Crowe DT. Dopamine therapy in critical care patients. Vet Clin North Am Small Anim Pract. 2021;51(6):1339-1358.
14. Ross L. Acute kidney injury in dogs and cats. Vet Clin North Am Small Anim Pract. 2011;41(1):1-14.