The largest physiological system is often overlooked when considering domestic animal physiology. In passing, we might consider agricultural products, for example, leather and wool derived from skin, but we often fail to appreciate their physiological relevance. The skin and its derivates (sweat and oil glands), hair (wool, fur), and nails (claws, hoofs) comprise a complex mix of tissues that together create the integumentary system. Regardless, this organ system is critical to the health and well‐being of our animals. It is easy to appreciate that its primary function is protection. But it is more than a simple physical protective covering. Without the skin, our animals would quickly fall prey to environmental pathogens and rapidly die from dehydration and heat loss. Our purpose is to outline some of the physiological attributes of the integumentary system that are essential for homeostasis. The following list illustrates the critical functions of the integumentary system.

• Physical protection: a barrier against the outside
  
• Prevention from dehydration
  
• Body temperature regulation
  
• Sensory information via cutaneous receptors
  
• Metabolic actions
  
• Excretion of wastes

The skin covers the entire exposed surface of the body and is continuous with the mucous membranes lining openings onto the body surface, the digestive, respiratory, and urogenital systems. We begin by considering the structure of the skin.

Overview of Skin Structure

It is apparent that the thickness of the skin varies from region to region of the body. Consider our own bodies and the toughness of the skin on the plantar (sole) surface of our feet compared with the skin of our faces. Now imagine how tough the skin of a horse, cow, or elephant must be to withstand the environmental and physical demands. This is reflected in the durability of leather‐covered furniture. However, no matter the location or thickness, skin is composed of two distinct tissue regions—epidermis and dermis. The epidermis, the outer layer, is composed of multiple layers of epithelial cells and a mix of specialized cells. The underlying dermis is largely composed of connective tissue and provides for the passage of blood vessels and nerves. The epidermis is also avascular. This means that nutrients must diffuse from capillaries located within the dermis to supply the epidermal cells. The tissue that lies just under the dermis is the hypodermis, often referred to as subcutaneous tissue. This subcutaneous tissue is not strictly part of the skin, but it contains areolar connective tissue and adipose tissue. It acts to cushion and protect both the skin and underlying muscle and organs. A combined needle and syringe are often called a hypo or hypodermic syringe. Penetrating the skin and releasing medicine into the space just below the dermis constitutes a hypodermic injection, hence the name.

Epidermis

The epithelium of the epidermis is a keratinized stratified squamous epithelium. It consists of four cell types and four to five distinct layers (depending on location). The most common epidermal cell is the keratinocyte. As the name suggests, a major function of these cells is to produce keratin, a fibrous protective protein. Keratin acts to waterproof the skin and, along with secretions produced by accessory glands, protects the underlying tissues from heat, microbes, abrasion, and chemicals. Keratinocytes are closely connected by desmosomes, which anchor the cells together, creating a stronger protective barrier. The keratinocytes first appear in the cell layer closest to the underlying dermis called the stratum basale. As the cells age, they are progressively pushed into layers closer to the surface of the body. By the time the cells reach the outermost layers, they have accumulated large amounts of keratin. The turnover of epidermal cells is rapid. The entire epidermis can be replaced every 25–50 days. In areas subjected to abrasion, cell proliferation and replacement are even faster.

Essentially, new cells are formed in the stratum basale (or stratum germinativum). This is the deepest of the epidermal layers. It is composed of a single row of cuboidal to columnar‐shaped epithelial cells that divide rapidly to produce new keratinocytes. In addition, approximately 20% of the cells are melanocytes. As new cells push older cells outward, these older cells become the stratum spinosum, typically 8–10 cells thick. These cells contain thick bundles of intermediate filaments (tonofilaments). In histological preparations, these cells often shrink. This causes the cells to have a prickly or spiked appearance. This explains the name of this layer, that is, spinosum (little spine). Because the stratum germinativum and stratum spinosum are immediately adjacent to the dermis, these are the only epidermal cells that receive adequate sustenance via diffusion of nutrients from the capillaries of the underlying dermis. With further degeneration and increased keratin accumulation, the cells appear in the stratum granulosum. In this layer, the keratinization process begins in earnest, and the cells begin to die. This layer is called granulosum because the accumulation of keratin granules becomes more evident in dead cells. In areas of thick skin, a layer called the stratum lucidum can be distinguished. Here, a thin layer of cells (typically 2–3 cells in thickness) becomes translucent. With time, the dead cells, accumulated keratin, and lipids combine to create the outermost layer of skin, the stratum corneum. The relative thickness of these layers varies from region to region. Figure 5.1 provides a diagram of these tissue layers, and Figure 5.2 and Figure 5.3 provide histological examples.

There is interest in the antimicrobial properties of molecules produced in the epidermis. For example, Schroder and Harder (1999) described an inducible, transcriptionally regulated antibiotic peptide produced by human skin. The peptide (human beta‐defensin‐2; HBD2) was effective in killing Gram‐negative bacteria. In the intervening years, it has become clear that antimicrobial peptides, such as β‐defensin, are an important part of the innate immune system. Such findings are likely to find application in multiple areas of animal agriculture, especially considering major efforts to minimize the use of antibiotics because of overuse and attendant creation of antibiotic‐resistant bacteria.

For example, the opening of the teat end of cows, a continuation of skin, is lined by stratified squamous epithelium, which continues into the teat opening as the streak canal. It is well known that keratin and other molecules serve as a barricade to seal the streak canal of the teat and protect the mammary gland from mastitis. Protection involves the physical closure of the teat opening between milking episodes, but there is substantial evidence that specific components within the keratin layer have antimicrobial properties. Many such substances are analogous to HBD2, but others may be derived from mammary secretions that become trapped within the epithelium of the streak canal. Effects might involve the direct killing of microorganisms or the prevention of colony formation.

During machine milking, there are dramatic physical effects on the teat, the teat end, and the streak canal. Given the rate of milk flow, it is reasonable to expect that resulting shear forces might remove the protective keratin. It is also probable that milk constituents become absorbed into the keratin during the time of milking or from milk droplets remaining after milking. If milking removes some of the keratin or if renewal is delayed, the effectiveness of the streak canal as a barrier is reduced. In fact, experimental removal of streak canal keratin markedly increases the rate of intramammary infections. In Holsteins, keratin weight before milking was 1.6 times greater than after milking (3.1 vs. 1.9 mg/teat). Jerseys, by contrast, showed negligible effects of milking (3.5 vs. 3.1 mg/teat). There is a negative correlation between keratin loss at milking (r = 0.53, wet weight basis) or (r = 0.65, dry weight basis) and milk production. Total lipid in the keratin is similar before and after milking. In addition, although the major aspects of the fatty acid profiles are also similar before and after milking, keratin after milking has more short‐chain fatty acids. This is consistent with the addition of milk‐derived lipids to the keratin by contamination of milk droplets remaining in the streak canal. In the case of the Holsteins, a greater proportion of the keratin contained these lipids after milking (Bitman et al., 1991). Initially thought to regenerate, that is, only slowly, 2–4 weeks, detailed quantitative studies show that following an initial collection, the keratin regenerates at a rate of 1.5 mg (wet weight) or 0.6 mg (dry weight) per day per teat. This suggests complete restoration of the keratin occurs within 1–2.5 days (Capuco et al., 1990). Just as in human medicine, there is considerable research interest in the identification of epidermal‐keratin components that might act to protect the udder from infection.

Clearly, techniques to enhance the protective function of the integumentary system are applicable to animal production. As outlined by Kumar et al. (2020), most antimicrobial peptides, or host defense peptides (HDPs), occur after the cleavage of cellular proteins in response to activated proteases. These agents are highly conserved across many species and are important in providing nonspecific innate immunity and, depending on the specific peptide, can be active against Gram‐positive and Gram‐negative bacteria, as well as fungi and viruses.

Daneshi et al. (2023) have reviewed current knowledge of β‐defensins related to mastitis and factors which control their production in the bovine mammary gland. Their focus is on the creation of novel, natural, antibacterial treatments for dairy cows with reduced dependence on antibiotics. Dijk et al. (2023) have outlined the evolutionary diversification of defensins and cathelicidins (another family of HDPs) in birds and primates. These results emphasize the importance of these localized agents, their significance in the innate immune system, as well as the complexity of their production and actions (Chen et al., 2024).

While keratinocytes are most plentiful, other cells also play important roles. For example, Merkel cells function as sensory receptors (touch). They orient with elements from the nervous system to create a disc‐shaped sensory nerve ending called a Merkel disc. Other nerve endings and specialized receptor cells also occur in the skin, but these are located within the dermis.

A very specialized immune system cell type, Langerhans cells, develops in the bone marrow but migrates to the epidermis, where they assume residence. Also called epidermal dendritic cells, they are modified macrophages. Their name reflects their morphology. Usually located within the stratum spinosum, they nestle between keratinocytes and send multiple projections between the cells to create an extensive network. In this way, the cells function as monitors to detect the presence of foreign debris, microorganisms, and other materials. When simulated, they actively process these materials and function as antigen‐presenting cells to induce the activity of T and B‐lymphocytes. We have all experienced the results of immunological response in the skin after exposure to irritants, that is, itch and rash. The skin gets exposed to an incredible variety of antigenic stimuli. Consequently, a wide array of immune responses occurs in part because of mediators secreted by keratinocytes, dendritic cells, and mast cells in the skin.

Melanocytes are the final cell type of the epidermis. They reside in the lowest layer, the stratum basale, where they function to produce the pigment melanin. Synthesized melanin accumulates in secretory vesicles, melanosomes, which sequester in elongated cellular processes. The presence of these peripheral vesicles causes the cells to have a spider‐like appearance. Released melanin absorbed by surrounding keratinocytes becomes oriented in the region of the cell facing the exterior. This pigment shields and protects the nucleus of the cell from ultraviolet radiation.

Dermis

The second major subdivision of the skin, the dermis, accounts for about 80% of the total mass. Like most connective tissues, there are a variety of cell types present, but as you might expect, fibroblasts are common, along with their products, that is, collagen, elastin, and reticular fibers that provide essential strength and flexibility. Unlike most other connective tissues, there is also seemingly a dizzying array of specialized structures. Most are related to the sensory side of the nervous system. Since the integumentary is intimately associated with the external environment, various receptors provide the central nervous system information necessary to maintain homeostasis: external temperature, pressure and touch, and the presence of noxious or damaging agents. There are also other specialized epithelial structures that assist the maintenance of homeostasis: sweat and sebaceous glands and hair.

The dermis consists of two layers, the papillary layer and the reticular layer. The papillary layer is the outer region closest to the epidermis. In this area, there are fingerlike projections called dermal papillae (these also give the layer its name), which penetrate the epidermis. In select areas, for example, the palms of the hands or fingertips in humans and apes, or the pads of a cat’s foot, the papillae are arranged on the top of larger structures called dermal ridges. This acts to increase friction and allow for a stronger grip. The pattern of ridges is unique to each individual and is the basis for fingerprints in humans or other primates. These projections contain capillaries and a variety of nerve endings and receptors. Three broad groupings of receptors include (1) exteroceptors, (2) interoceptors (sometimes called visceroceptors), and (3) proprioceptors. Exteroceptors are concerned with stimuli that arise from the outside. Most exteroceptors are located on or near the body surface. These are the focus of our study of the integumentary system. Interoceptors react to stimuli from within the body, for example, chemical signals, temperature, or gut motility. Proprioceptors also reflect internal responses but are specifically involved in the relay of information concerned with muscle, tendon, or ligament movement or stretch. In other words, they monitor the musculoskeletal organs. The latter two classes of receptors are discussed in subsequent sections. Our focus now is on exteroceptors of the skin.

These receptors are also classified based on their structural complexity. Free nerve endings, for example, are structurally simple, especially when compared with receptors associated with the special senses (vision, hearing, olfaction, or taste). Even the simple receptors of the integumentary can be divided into unencapsulated (free nerve endings) and encapsulated groupings. Specialized Meissner’s or Pacinian corpuscles are examples of encapsulated receptors. Pacinian corpuscles have a structure like the layers of an onion; pressure induces ion changes that are translated into graded potentials in the associated nerve fibers (Fig. 5.5). These impulses are interpreted as touch or pressure by neurons in the cerebral cortex. Table 5.1 summarizes the types and classes of sensory receptors within the skin.

The reticular layer is the thicker and deeper layer of the dermis. It is composed of dense irregular connective tissue and contains thick bundles of interlacing collagen fibers and coarse elastic fibers. However, elastin fibers are typically only visible after special staining. These fibers run in several directions, which increases strength, but most are oriented parallel to the skin exterior. The fibers provide much of the strength and resistance to stretching in the skin and the long‐wearing attributes of leather. The reticular layer is also abundantly supplied with blood vessels and nerves. These elements of the dermis are illustrated in Figure 5.3. Figure 5.4 and Figure 5.5 show histological examples of other structures that occur within the dermis.

Specialized Structures

Sweat Glands

The dermis contains a variety of glandular structures. Sweat glands in primates are plentiful and widely distributed. The most common type is the eccrine gland. These simple coiled glands open onto the surface in pores. They produce a hypotonic, watery secretion derived from interstitial fluids. It is mostly water and dissolved salts, lactic acid, and traces of other waste products. The rate of secretion is controlled by the activity of the sympathetic nervous system. In humans, a typical response occurs with overheating. Sweating induced in this way begins on the forehead and progresses downward. Emotionally induced sweating—fright, embarrassment, or nervousness—begins on the palms, soles, and armpits and spreads to other areas. Of course, the primary function of sweat is to cool the body via evaporation. A second type of sweat gland, apocrine glands, makes up a small proportion of the total. These glands are larger than eccrine glands, and their ducts open onto hair follicles. They are primarily confined to the axillary and anogenital areas of the primate body. The secretions, in addition to watery sweat, also contain fatty acids and proteins. These glands are affected by sex steroids; that is, activity begins with the onset of puberty. For this reason, apocrine glands are believed to be analogous to the scent glands of other animals. Eccrine sweat glands are sparse among domestic animals. For example, dogs and cats are located only on the footpad. This limited distribution means that these glands have no effect on heat loss, but they do act to moisten the surface and improve traction. We have all noticed the panting dog on a sweltering day or after exercise. Panting is an effective cooling mechanism because it moves greater amounts of air over moist surfaces. This extra water‐saturated air is exhaled, and in the process, body temperature decreases.

Although eccrine sweat glands are lacking, horses, cattle, sheep, swine, dogs, and cats have abundant apocrine glands. In the dog, for example, the proteinaceous, whitish secretions from the apocrine glands mix with the oily secretions of the sebaceous glands to form an emulsion‐like coating on the skin. The characteristic dog, horse, or cow odor is primarily a result of bacterial action on these accumulated secretions. These secretions also impact heat loss, but this is most effective in horses, followed by cattle, sheep, dogs, cats, and swine. Regardless of the evaporative effect of heat lost from sweat, the skin of these animals is nonetheless important in temperature regulation. This is because simply changing the rate of blood flow through capillaries in the skin alters the volume of warm blood near the surface of the body, thereby affecting thermoregulation (Mota‐Rojas et al., 2021).