13
Cardiovascular System

The cardiovascular system (cardio = heart; vascular = blood vessels) includes three components: blood, the heart, and blood vessels. Blood is essential for transporting nutrients and wastes, thermoregulation, immunity, and acid–base balance. The heart and blood vessels help deliver the blood throughout the body.

Functions and Composition of Blood

Functions of Blood

Hematology is the study of blood, blood‐forming tissues, and blood disorders. Because of simple physics, animals composed of organs with multiple layers of cells, unlike single celled organisms, cannot rely on simple diffusion to deliver nutrients and remove waste. Instead, the blood, lymph, and interstitial fluids are necessary for these functions. Blood is a connective tissue consisting of materials suspended in a nonliving liquid matrix called plasma. Blood has three main functions: transportation, regulation, and protection.

Transportation

Blood transports O₂ and CO₂ between the lungs and the tissues. In addition, blood transports absorbed nutrients from the gastrointestinal tract to the liver and other cells; hormones from endocrine glands to target cells; waste products from cells to excretory sites, including the liver, kidneys, and skin; and heat throughout the body.

Regulation

Blood serves a major role in maintaining homeostasis. Blood helps regulate pH via buffers, and body temperature by either carrying excess heat to the skin for dissipation or by vasoconstricting to conserve heat and osmotic pressure by maintaining blood protein and electrolyte levels.

Protection

Blood plays many roles in immunity. Some blood cells are phagocytic; others produce antibodies. Blood proteins such as complements and interferons are important in immunity. In addition, blood clotting is obviously critical for homeostasis.

Physical Characteristics of Blood

Blood is denser and thicker than water. It contains both cellular and liquid components. The cells (formed elements) and cell fragments are suspended in plasma. Although fibers typically seen in connective tissue are not present, during the clotting process, dissolved proteins combine to form fibrous strands.

When centrifuged, the components of the blood will separate into three distinct compartments (Fig. 13.1). The formed elements move toward the bottom of the tube; the plasma appears near the top. Packed at the bottom of a centrifuged tube will be the erythrocytes or RBCs. Sitting on top of this layer will be a thin, whitish layer called the buffy coat. This layer contains leukocytes, or white blood cells (WBCs), and platelets, which are cell fragments. The top layer is the blood plasma.

The percentage of a blood sample composed of erythrocytes is called the hematocrit. An abnormally high hematocrit is called polycythemia, a reflection that there are too many erythrocytes per milliliter of blood. Such blood can carry elevated amounts of oxygen, but it has a greater viscosity, making it harder for the heart to pump. Polycythemia can occur because of dehydration since decreased fluid volume will also result in a relatively higher number of erythrocytes per ml of blood. Conversely, a low hematocrit reading indicates anemia, meaning that there are not enough erythrocytes, and thus a low level of hemoglobin in the blood. This can result in an increased cardiac output (CO) as the animal attempts to deliver adequate oxygen to the tissues.

A schematic diagram illustrating blood separation by centrifugation, dividing whole blood into plasma and formed elements, then breaking down blood components into proteins, water, electrolytes, and cells, with their respective percentages and functions. — **Fig. 13.1** Blood components. Centrifugation of whole blood containing an anticoagulant results in the separation of red blood cells, a buffy coat containing white blood cells and platelets, and plasma.

In dogs and horses, the spleen stores erythrocytes. In fact, horses can store up to 50% of the erythrocytes in the spleen. Therefore, when the animals exercise, the spleen can release erythrocytes into the circulation, increasing the hematocrit by nearly 25% (Box 13.1).

Box 13.1 Blood doping

In sports, the term doping was first used to describe the illegal drugging of racehorses at the beginning of the 20th century. Today, the term blood doping includes the transfer of autologous or homologous erythrocytes and use of synthetic erythropoietin (EPO) to stimulate an increase in the number of erythrocytes. Synthetic EPO was developed as a treatment for anemia resulting from cancer therapy. Injecting EPO under the skin can increase the hematocrit and, therefore, the oxygen carrying capacity of the blood. Horses that have been doped using drugs designed for Alzheimer’s and Parkinson’s patients may increase blood flow to the brain. In human patients EPO is used to restore function and health, but use of EPO in doping episodes is to increase performance and essentially cheat in athletic events.

In racehorses, using a “milkshake” was a popular practice believed to enhance performance. The practice is thought to have begun in Australia in Standardbreds. The milkshake consisted of dissolving several ounces of sodium bicarbonate in a gallon of water. Sometimes sugar, electrolytes, or other nutrients such as creatine, were added. The thought was that giving the milkshake 4–8 hours before a race would improve performance.

As incredible as it might seem, while gene therapies are rapidly advancing to alleviate the impacts of diseases in humans and animals, these same genetic manipulation tools are also being adapted as means to surreptitiously enhance animal performance, that is, gene doping. Wilkin et al. (2024) describe a set of PCR‐based equine gene doping tests for the Australian horse racing industry. Specifically, they developed tests to detect cDNA‐based transgenes for EPO, follistatin, growth hormone, insulin‐like growth factor‐1, and interleukin‐1 receptor antagonists, all of which are candidates to improve performance while cheating nondoping competitors and the betting public.

Plasma

Plasma consists of about 90% water, but it also contains nutrients, gases, hormones, waste products, electrolytes, and proteins. The nutrients include various components absorbed from the gastrointestinal tract or produced in the liver, including glucose, amino acids, and lipids. Oxygen and CO₂ are transported in the blood as are hormones produced in endocrine glands. Plasma proteins are abundant. These proteins can function as carriers for important nutrients for example iron carried by transferrin, lipoproteins which transport lipids as well as proteins key to blood clotting such as fibrinogen. Most of these proteins are synthesized in the liver.

Formed Elements in Mammals

Formed elements of blood include erythrocytes (RBCs), leukocytes (WBCs), and platelets. RBCs and WBCs are whole cells, whereas platelets are cell fragments. There is only one type of RBC, but there are five types of WBC, neutrophils, lymphocytes, monocytes, eosinophils, and basophils (Table 13.1). WBCs are classified as either granulocytes or agranulocytes, depending on whether they contain obvious membrane‐bound cytoplasmic granules. Granulocytes include neutrophils, eosinophils, and basophils. Agranulocytes include lymphocytes and monocytes. The numbers of various blood cells are shown in Table 13.2.

A closer view of red blood cells, showing their disc-like shape. — **Table 13.1** Summary of formed elements in blood.

A microscopic photograph of a cell containing multiple dark-stained nuclei, likely a white blood cell such as a neutrophil. — **Table 13.1** Summary of formed elements in blood.

Cell Type	Description	Cells (mm³)	Life Span	Function
Erythrocytes
	Biconcave, anucleated discs; 3–7 μm in diameter, depending on species	4–6 million	100–120 d	Transport oxygen and carbon dioxide
Leukocytes (granulocytes)
Neutrophils	Multilobed nucleus; small granules; 10–12 μm in diameter	3000–7000	6 h to a few days	Phagocytize bacteria and some fungi
Eosinophils	Bilobed nucleus; red granules; 10–14 μm in diameter	100–400	8–12 d	Kill parasitic worms; destroy IgE–antigen complexes, inactivate histamine from allergic reactions
Basophils	U‐ or S‐shaped nucleus 8–10 μm	20–50	Few hours to a few days	Release histamine and other inflammatory mediators
Leukocytes (agranulocytes)
Lymphocytes	Rounded nucleus 5–17 μm in diameter	1500–3000	Hours to years	Involved in cell‐ and humoral‐mediated immunity
Monocytes	5–17 μm in diameter	100–700	Months	Phagocytosis; develop into macrophages
Platelets	Granule‐containing cytoplasmic fragments 2–4 μm	150,000–400,000	5–10 d	Blood clotting, seal torn vessels

Table 13.2 Blood cell numbers (cells/μL).^a

Species	Erythrocytes	Total WBC	Neutrophils	Lymphocytes	Monocytes	Eosinophils	Basophils
Dog	6–8 million	6000–17,000	3000–115,000	1000–5000	0–1200	100–1200	0–100
Cat	6–8 million	5500–19,500	2500–12,500	2700–6700	0–800	0–1500	0–100
Horse	7–12 million	5500–12,500	2700–6700	1500–5500	0–800	0–900	0–200
Cow	6–8 million	4000–12,000	600–4000	2500–7000	0–800	0–2400	0–200
Sheep	10–13 million	4000–12,000	700–6000	2000–9000	0–800	0–1000	0–300
Pig	6–8 million	11,000–22,000	3200–10,000	4500–13,000	200–2000	100–2000	0–400
Chicken	2.5–3.5 million	12,000–30,000	Rare	7000–17,500	150–2000	0–1000	Rare

^a From Swenson and Reece (1993) and Thrall et al. (2004).

Types of Blood Cells in Mammals

Erythrocytes

Erythrocytes, or RBCs, are approximately 7–8 μm in diameter and are shaped like biconcave discs. This increases their surface area to volume ratio. They are also flexible and able to deform to move through capillaries. Erythrocytes in mammalian species lack a nucleus and organelles. Avian RBCs, however, are nucleated. Certain glycolipids found on the plasma membrane of RBCs account for the various blood groups. Because RBCs lack organelles, they are unable to reproduce. In addition, they depend on ATP produced anaerobically because they are devoid of mitochondria.

Erythrocytes are filled with hemoglobin (Fig. 13.2). Hemoglobin is a specialized protein critical in oxygen transport. Each hemoglobin molecule consists of four polypeptide chains (two alpha and two beta), each of which contains a nonprotein molecule heme. An iron ion atom (Fe²⁺) resides in the center of each heme molecule and can reversibly bind with one oxygen molecule.

Although most carbon dioxide is transported in the plasma as bicarbonate, about 13% is transported bound to hemoglobin as carbaminohemoglobin. In addition, hemoglobin binds nitric oxide (NO), a gas formed by endothelial cells, which functions as a neurotransmitter that causes vasodilation. As hemoglobin delivers oxygen, it can simultaneously release NO, which dilates the capillaries, allowing even more blood, and therefore more oxygen, to be delivered.

A diagram of hemoglobin showing its protein structure with alpha and beta chains, an iron-containing heme group, and a chemical structure of the heme molecule, alongside an image of erythrocytes (red blood cells). — **Fig. 13.2** Erythrocytes and hemoglobin structure. Erythrocytes (red blood cells) contain hemoglobin. Hemoglobin consists of four polypeptide chains, 2 alpha and 2 beta chains, each having an iron‐containing heme molecule attached.

Erythrocyte Life Cycle

Erythrocytes live for about 120 days (Fig. 13.3). They get damaged as they squeeze through capillaries, and because they lack a nucleus and other organelles, they are unable to replace damaged structures. Figure 4.48 and Figure 4.51 illustrate clusters of RBCs captured in tissue sections. Damaged erythrocytes are removed from circulation by fixed phagocytic macrophages residing in the spleen, bone marrow, and liver. Once destroyed, the following steps occur:

The globin and heme portions are separated.
Globin is hydrolyzed into its component amino acids, which are then available for the synthesis of other proteins.
The iron (Fe²⁺) removed from the heme binds to the plasma protein transferrin and is transported through the bloodstream to muscle fibers, liver cells, and macrophages in the spleen where it is stored attached to ferritin. Because Fe²⁺ and Fe³⁺ can damage molecules in the body, they are transported and stored bound to transferrin and ferritin.
When mobilized, the Fe³⁺–transferrin complex transports iron to bone marrow, where erythrocyte precursor cells internalize it via receptor‐mediated endocytosis and use it to synthesize hemoglobin. Vitamin B₁₂ is needed for hemoglobin synthesis. Thus, explaining the importance of this vitamin.
The noniron portion of heme is converted to biliverdin, a green pigment, and then to bilirubin, a yellow‐orange pigment.
Bilirubin is transported to the liver for secretion into bile.
Bile is released into the small intestine. In the large intestine, bilirubin is converted by bacteria into urobilinogen, which is converted to stercobilin, a brown pigment giving feces their characteristic color.
A small fraction of the urobilinogen is reabsorbed in the large intestine and converted to urobilin, a yellow pigment, which is excreted in the urine.

A diagram depicting the lifecycle of red blood cells, including production in the bone marrow, iron transport and recycling, hemoglobin breakdown, and excretion of waste products via urine and feces. — **Fig. 13.3** Erythrocyte life cycle. Erythropoietin stimulates the production of new erythrocytes in red bone marrow. The erythrocytes circulate in the blood and have a life span of about 120 days. When worn out, they are phagocytized by macrophages in the spleen, liver, or red bone marrow. The iron in the heme molecule is recycled, while the remainder of the heme molecule is metabolized and excreted.

Leukocytes

Leukocytes, also called WBCs, are the only blood cells that are truly complete cells containing nuclei and organelles. They do not contain hemoglobin. They generally account for only 1% of the blood volume, but they are nonetheless critical components of the immune system. Figure 4.56 shows a typical blood smear with abundant RBSs and some leucocytes. Figure 4.57 to Figure 4.60 provide additional examples of the types of leucocytes.

They possess properties that allow them to carry out immune functions. WBCs leave the circulatory system by a process called emigration. Emigration involves several steps:

Near the site of inflammation, the endothelial cells lining the capillaries display cell adhesion molecules called selectins on their surface. Neutrophils express corresponding cell surface adhesion molecules called integrins that recognize selectins. This causes the WBCs to line up along the inner surface of the capillaries near the inflamed site, a process called margination.
WBCs can move out of the capillaries through a process called diapedesis.
After leaving the bloodstream, they migrate via amoeboid action by positive chemotaxis following chemical signals produced by damaged tissue.
Neutrophils and macrophages become phagocytic and act to ingest bacteria and dispose of dead matter.

Granulocytes

Neutrophils

Neutrophils account for 50–70% of WBCs. Twice as large as erythrocytes, their cytoplasm stains a pale lilac with very small granules. The granules stain with both basic and acid dyes. Some granules are considered lysosomes containing hydrolytic enzymes, and others contain antibiotic‐like proteins called defensins. Because the nucleus consists of 3–6 lobes, these cells are often called polymorphonuclear leukocytes (see Fig. 4.60).

Two panels: (A) Histology of tissue with arrowed structures indicating glandular or ductal formations. (B) Closer view of densely packed, dark-stained cells, possibly a tumor or lymphoid tissue. — **Fig. 13.4** A tissue section from a bovine mammary gland showing an influx of lymphocytes (arrows) near developing epithelial structures (panel A). Panel (B) shows an enlargement of the area indicated by the arrow to the lower right.

Courtesy of Dr. Ben Enger, Ohio State University.

Attracted to sites of inflammation via chemotaxis, neutrophils are the first cells to be attracted by chemotaxis to leave the bloodstream. After leaving the capillaries, they are attracted to bacteria and some fungi. Neutrophils phagocytize these foreign cells and then undergo a process called a respiratory burst. Oxygen is converted to free radicals such as bleach (hypochlorite, OCl⁻), superoxide anion (O₂⁻), or hydrogen peroxide. The defensin‐containing granules merge with the phagosomes, and the defensins act like peptide “spears,” producing holes in the walls of the phagocytized cells. The neutrophils then die. Figure 13.4 illustrates a massive migration of neutrophils into the mammary tissue of a cow after an induced infection with Staphylococcus aureus. The initial response to an infection, such as mastitis, is a large infiltration of neutrophils followed by larger numbers of lymphocytes, as illustrated in Figure 13.4.

Eosinophils

Eosinophils account for 2–4% of all leukocytes. They contain large, uniform‐sized granules that stain red orange with acidic dyes. The granules do not obscure the nucleus, which often appears to have two or three lobes connected by strands. The granules contain digestive enzymes, but they lack enzymes that specifically digest bacteria (see Fig. 4.60).

Eosinophils function against parasitic worms that are too large to phagocytize. Such worms are often ingested or invade through the skin and move to the intestinal or respiratory mucosa. Eosinophils surround such worms and release digestive enzymes onto their surface.

Basophils

Accounting for only 0.5–1.0% of leukocytes, these are the rarest WBCs. Slightly smaller than neutrophils, they contain histamine‐filled granules that stain purplish black in the presence of basic dyes. The nucleus stains dark purple and is U‐ or S‐shaped. When bound to immunoglobulin E, these cells release histamine. Histamine is an anti‐inflammatory chemical that causes vasodilation and attracts other WBCs to the site.

Agranulocytes

Lymphocytes

Accounting for 25% of the WBCs, these cells contain a large, dark purple‐staining nucleus. The nucleus is typically spherical, slightly indented, and is surrounded by a pale blue cytoplasm. Lymphocytes are classified as either large (10–14 μm) or small (6–9 μm). The functional significance of the difference in size is unclear. Lymphocytes are further classified based on marker proteins expressed on their cell surfaces. B lymphocytes, when activated, are turned into antibody‐producing plasma cells. These cells have a distinctive nucleus characterized by clumps of chromatin around the periphery, so‐called clock‐face appearance. In addition, plasma cells are often distinctly stained with azure II or toluidine blue. Figure 13.5 shows an example of plasma cells in the bovine mammary gland.

A histological section showing glandular structures with dark-stained nuclei, indicated by arrows, within a light blue stained tissue. — **Fig. 13.5** This tissue section stained with Azure II is from the bovine mammary gland. It illustrates the distinctive staining of plasma cells (arrows).

Photo by R.M. Akers.

Two microscopic photographs of immune cells; (A) shows three cells labeled E, L, and M; (B) shows cells with a black arrow pointing to a cell with multiple nuclei. — **Fig. 13.6** Examples of immune cells isolated from the milk of a cow challenged with *S. aureus*. Panel (A) shows a rare milk eosinophil (E), lymphocyte (L), and macrophage (M). Panel (B) shows two neutrophils. The reason these cells are described as polymorphonuclear (lobed nuclei) is evident. Second, the neutrophil on the lower right has engulfed a cluster of *S. aureus* cells (arrow).

Enger et al. (2018) / Springer Nature.

Monocytes

Monocytes are 12–20 μm in diameter and account for 3–8% of leukocytes. They contain a kidney or horseshoe‐shaped nucleus. They contain very small blue gray‐staining granules that are lysosomes.

After leaving the bloodstream, monocytes turn into macrophages. Some become fixed macrophages, such as alveolar macrophages located in the lungs and Kupffer cells located in the liver. Others become wandering macrophages that move throughout the body and collect at sites of infection and inflammation (see Fig. 4.58). In addition, Figure 13.6 shows an example of immune cells that have migrated into the bovine mammary gland following a challenge with the S. aureus and were captured in a milk smear preparation. Panel (A) shows a rare eosinophil, a lymphocyte, and a macrophage. Panel (B) shows two neutrophils one of which has engulfed a cluster of S. aureus cells (arrow).

Platelets

Platelets, which are fragments of cells, consist of plasma membranes containing numerous vesicles but no nucleus. When there is a tear in a blood vessel, platelets coalesce at the injury site and form a platelet plug. Chemicals released from their granules aid in blood clotting (Box 13.2).

Formation of Blood Cells

The formation of new blood cells is called hemopoiesis or hematopoiesis. Before birth, hemopoiesis begins in the yolk sac and later occurs in the fetal liver, spleen, thymus, and lymph nodes. Postpartum hemopoiesis continues in red bone marrow, which is found between the trabeculae of spongy bone. Spongy bone is found predominately in the axial skeleton, pectoral and pelvic girdles, and proximal epiphyses of the humerus and femur.

Within the red bone marrow are pluripotent stem cells. These can proliferate, or differentiate, into different blood cells, macrophages, reticular cells, mast cells, and adipocytes. Macrophages are part of the innate immune system. Reticular cells form reticular fibers that serve as part of the matrix supporting red bone marrow cells (Fig. 13.7).

Pluripotent stem cells generate two other stem cell populations: myeloid stem cells and lymphoid stem cells. Myeloid stem cells differentiate within the red bone marrow to produce erythrocytes, platelets, monocytes, neutrophils, eosinophils, and basophils. In contrast, lymphoid stem cells begin in the red bone marrow but finish differentiating in lymphatic tissue forming lymphocytes. In addition, lymphocytes produce numerous cytokines, small glycoproteins that act as signals to modify other cells.

Myeloid cells produce progenitor cells. These cells are restricted, meaning that they are committed to becoming selected blood cells and cannot reverse to become stem cells. As shown in Figure 13.7, some of these progenitor cells become colony‐forming units. Colony‐forming units give rise to precursor cells, indicated by names ending in ‐blast.

Box 13.2 Complete blood count (CBC)

When an ill animal is examined, a blood sample is often taken to complete a CBC or hemogram. A CBC includes a hematocrit and descriptions of any abnormalities in blood cell shape, size, color, or appearance. This along with a count of WBCs. A differential count can distinguish the proportions of WBC in each of the classifications and provide clinically relevant information. For example, an overall increase in WBC count is associated with infection or a decrease possibly reflecting the ravages from a prolonged illness. An increase in the number of lymphocytes may indicate a prolonged illness or leukemia. When total neutrophil numbers are increased, this is a typical sign of a bacterial infection or response to a period of prolonged stress. Prolonged stress can also decrease eosinophil numbers. Despite the relative simplicity of a blood smear and blood cell counts, they remain valuable clinical tools.

By the same token, a virtual explosion in the availability of antibodies analogous or cross‐reactive with markers present on the surfaces of human or murine lymphocytes and WBCs generally have made flow cytometry and immunological study of blood cells in pigs, cattle, and pets possible like never before. Hartle et al. (2024) describe efforts to identify immunological reagents sufficiently cross‐reactive for use in the evaluation of WBCs in chickens. Fundamentally, the use of specific antibodies has allowed the identification and in many cases the isolation and collection of multiple subpopulations of lymphocytes with exacting roles in immunological functions. These efforts are most developed in laboratory mice and humans. Nonetheless, these tools have allowed for automated detection of lineages of lymphocytes with specific functions. For example, T and B cells, killer T cells, helper T cells, memory T cells, macrophages, and more. As these tools evolve and reliable markers for farm animals and other domestic animals appear this will offer opportunities for treatment of diseases and physiological understanding not possible before. However, the attendant cost of such advanced diagnostic tools and the equipment necessary may well mean these tools remain limited for typical veterinary care of pets or production animals except for specific research projects.

A diagram showing the developmental pathway of blood cells, from pluripotent hematopoietic stem cells to various blood cell types including erythrocytes, platelets, granulocytes (eosinophil, basophil, neutrophil), and agranulocytes (lymphocytes like T and B cells, monocytes). — **Fig. 13.7** The formation of blood‐formed elements is outlined. Blood cells are produced from pluripotent hematopoietic stem cells.

Tortora and Grabowski (2003) / John Wiley & Sons.

Erythrocyte Formation

Erythropoiesis is the production of erythrocytes in the red bone marrow. Hematopoietic stem cells divide to produce myeloid stem cells, which transform into proerythroblasts (Fig. 13.7). Proerythroblasts give rise to erythroblasts, which synthesize hemoglobin, and then are transformed into normoblasts. When the normoblast contains about 34% hemoglobin, it ejects most of its organelles, becoming a reticulocyte, the precursor of an erythrocyte. The process of hematopoietic stem cell to reticulocyte takes 3–5 days. Reticulocytes are released into the bloodstream where, within 2 days, they release their ribosomes and become erythrocytes.

EPO, a glycoprotein produced mostly in the kidney, stimulates erythropoiesis. Although there is generally a small amount of EPO circulating in the bloodstream, hypoxia causes the kidney to produce more EPO. Hypoxia can be caused by a reduced number of erythrocytes, reduced availability of oxygen such as might occur at increased altitudes, or increased tissue demand for oxygen. This explains the logic of athletes training at higher altitudes, increased oxygen demand, leading to secretion of more EPO, therefore more RBCs and ultimately more oxygen carrying capacity. There are also cases of nonmedical injections of EPO (doping) to gain a performance edge. In contrast, in normal situations, excess erythrocytes or oxygen in the bloodstream reduces normal rates of EPO synthesis.

Leukocyte Formation

Hematopoietic stem cells produce lymphoid stem cells, which produce T and B lymphocytes. Leukopoiesis is the production of WBCs. It is stimulated by various cytokines, generally produced by macrophages and T lymphocytes. Cytokines are glycoproteins, and they include interleukins and colony‐stimulating factors. An abnormally low level of WBCs is termed leukopenia, which can be caused by radiation, shock, or chemotherapeutic agents.

Platelet Formation

Platelet formation is stimulated by the hormone thrombopoietin (TPO). TPO causes myeloid stem cells to develop into megakaryocyte‐colony‐forming cells, which then become megakaryoblasts. Megakaryoblasts are large cells that later rupture into 2000–3000 membrane‐bound fragments producing platelets or thrombocytes.

Formed Elements and Blood Cells in Birds

Although most of the formed elements in birds are like those in mammals, there are some notable differences. Formed elements of blood in birds include erythrocytes, leukocytes, and thrombocytes, the avian equivalent of platelets. Like mammals, the avian leukocytes are divided into granulocytes and agranulocytes. Avian granulocytes include eosinophils, basophils, and heterophils (equivalent to mammalian neutrophils). Avian agranulocytes include lymphocytes and monocytes. The number of various blood cells within the blood is shown in Table 13.2.

Thrombocytes

Thrombocytes are found in birds, reptiles, amphibians, and fish. Unlike platelets, they are nucleated. Thrombocytes are smaller than erythrocytes, and in good preparations, a small eosinophilic vacuole appears as an orange dot located at one end of the nucleus. Whereas mammalian platelets are derived from megakaryocytes, such precursors are lacking in birds. There remains some debate as to whether avian thrombocytes arise from antecedent mononucleated cells or multinucleated cells. Avian thrombocytes have a similar function to mammalian platelets.

Heterophils

Heterophils function similarly to mammalian neutrophils. In some avian species, they are the most common peripheral leukocyte. They are typically round, with colorless cytoplasm and many eosinophilic, rod‐shaped to spherical granules. The granules may partially obscure the nucleus, which usually has two or three lobes and coarsely aggregated purple chromatin. Often in blood smears the heterophil sometimes has a distinct ruby‐colored central granule because the rod‐shaped granules are dissolved, leaving the central one only (Box 13.3).

Hemostasis

Hemostasis is a series of responses that stop bleeding. As blood vessels are damaged or torn, hemostasis quickly controls the bleeding. The hemostasis response is rapid, localized, and well‐controlled so as not to spread throughout the body. Hemostasis entails three mechanisms: (1) vascular spasms, (2) platelet plug formation, and (3) blood clotting (coagulation). If bleeding is not stopped for any reason, an animal will hemorrhage and lose blood (Box 13.4).

Box 13.3 Heterophil/lymphocyte ratio in birds

While in many animals increased plasma corticosteroids are used as an indication of stress, in birds the ratio of heterophils (H) to lymphocytes (L) is also a good indicator of stress. When corticosterone is added to the feed of chickens, the number of blood lymphocytes increases while the number of heterophils decreases. The ratio of H/L is now commonly used as an indicator of prolonged stress in birds. Increased plasma corticosterone concentrations are an indicator of acute short‐term stress in birds, whereas H/L ratios are a better indicator of long‐term stress. The H/L ratio typically does not change until about 12 hours after the stressful event. Jeong et al. (2020) provide an example of such data evaluating the impact of dietary gamma‐ammino butyric acid feeding in broiler chickens.

Box 13.4 Aspirin and gastric bleeding

In some conditions, such as arthritis, aspirin may be prescribed to treat dogs and cats. Aspirin belongs to a class of drugs called nonsteroidal anti‐inflammatory drugs (NSAIDs). Dogs are particularly sensitive to the gastrointestinal effects of NSAIDs, which include pain, bleeding (i.e., gastric hemorrhaging), and ulceration. Coated aspirin may help with the gastrointestinal effects. Aspirin can be given with food, 1–2 times a day.

Because cats cannot break down this drug as quickly as dogs, they are more sensitive to aspirin than dogs. Thus, the time between doses is generally increased with cats. Cats are typically dosed at intervals of 48–72 hours.

Acetaminophen and ibuprofen are generally not recommended for dogs. These drugs can be fatal to cats.

Vascular Spasm

When blood vessels become injured, the vessels constrict. This vascular spasm is triggered by injury to the vascular smooth muscle, chemicals released from endothelial cells and platelets, and reflexes involving local pain receptors.

Platelet Plug Formation

Platelets contain many chemicals, including clotting factors, ADP, ATP, Ca²⁺, serotonin, enzymes that produce thromboxane A2, fibrin‐stabilizing factor, and platelet‐derived growth factor (PDGF). They also contain lysosomes and mitochondria. The platelet‐derived fibrin stabilizing factor helps strengthen blood clots. PDGF induces the proliferation of vascular endothelial cells, increased vascular smooth muscle fibers, and proliferation of fibroblasts, all of which help repair damaged vessels.

A platelet plug forms as follows:

Platelet adhesion: Platelets adhere to the collagen fibers of the connective tissue exposed in a damaged vessel wall.
Platelet release reaction: Adhesion to the vessel wall activates the platelets. They extend processes that allow them to contact and interact with adjacent platelets. They also liberate their vesicular contents so‐called platelet release reaction. Freed ADP and thromboxane A activate neighboring platelets in a cascade of reactions. Serotonin and thromboxane A cause vasoconstriction, thus decreasing blood flow.
Platelet aggregation: Released ADP makes adjacent platelets sticky, causing more and more platelets to adhere at the injured site.
Platelet plug: As more platelets adhere, a plug of platelets helps seal the vessel leak.

Blood Clotting

When blood clots, it forms a straw‐colored liquid called serum and a gel‐like mass called a clot. The clot consists of insoluble protein fibers called fibrin that trap other formed elements of the blood.

Clotting, or coagulation, involves a series of chemical reactions resulting in fibrin thread formation. Clotting factors include calcium ions, inactive enzymes produced in the liver and released into the circulatory system, and chemicals released from platelets and damaged tissue. Clotting factors are generally named by Roman numerals indicating the order of their discovery, not their order in the clotting process.

The formation of a clot in an unbroken blood vessel is called a thrombosis, with the clot being called a thrombus. The movement through the blood of a clot, air bubble, fat from a broken bone, or debris is called an embolus. These often lodge in the lungs producing a pulmonary embolism.

Clotting consists of three stages (Fig. 13.8): (1) two pathways, called the intrinsic and extrinsic pathways, leading to the production of prothrombinase, (2) conversion of prothrombin to thrombin, catalyzed by prothrombinase, and (3) thrombin catalyzing the conversion of fibrinogen into insoluble fibrin.

A diagram illustrating the extrinsic and intrinsic pathways of blood coagulation, showing how damaged tissue and exposed collagen activate clotting factors leading to fibrin formation and blood clot stabilization. — **Fig. 13.8** Blood‐clotting cascade. Both the extrinsic and intrinsic pathways result in the formation of activated factor X then combines with factor V to form the active enzyme prothrombinase.

Extrinsic Pathway

The extrinsic pathway is quicker and has fewer steps than the intrinsic pathway. Damaged tissue releases a tissue protein called tissue factor (TF), or thromboplastin, that initiates the formation of prothrombinase. Because TF comes from outside the blood, this pathway is called the extrinsic pathway. In the presence of Ca²⁺, TF begins a series of reactions resulting in the formation of factor X. Factor X then combines with factor V to form the active enzyme prothrombinase.

Intrinsic Pathway

In the intrinsic pathway, all the factors necessary for blood clotting are present (i.e., an intrinsic part of the blood). The intrinsic pathway relies on the production of PF₃, a phospholipid associated with the external surface of aggregated platelets. Like the extrinsic pathway, the intrinsic pathway results in the production of factor X.

Common Pathway

Both the intrinsic and extrinsic pathways use a common pathway after the activation of factor X. Prothrombin is converted to thrombin by prothrombinase. Thrombin then catalyzes the conversion of fibrinogen to fibrin. Activated factor XIII catalyzes the polymerization of cross‐linked fibrin.

Role of Vitamin K

Although vitamin K is not directly involved in clot formation, it is needed for the synthesis of four clotting factors by hepatocytes. These include factors II (prothrombin), VII, IX, and X. Vitamin K is normally synthesized by bacteria found in the large intestine and is absorbed through the intestinal wall along with other lipids.

Clot Retraction and Repair

Beginning about 30–60 minutes after clot formation, the clot becomes more stable through a process called clot retraction. Platelets contain actin and myosin, and these contractile proteins begin to contract like muscle contraction. This platelet contraction pulls on surrounding fibrin strands, thus squeezing serum from the clot and pulling the ruptured edges of the vessel closer together. The platelets release factor XIII, which helps strengthen the fibrin clot. Simultaneously, PDGF released by degranulating platelets stimulates smooth muscle and fibroblasts to divide and repair the damaged site. The fibroblasts form a connective tissue sheath over the injured area. Vascular endothelial growth factor then causes the endothelial cells to multiply and restore the blood vessel lining.

Fibrinolysis

A clot is not permanent. Following healing, the clot is removed by a process of fibrinolysis. The major clot‐busting enzyme is plasmin, which is produced when the blood protein plasminogen is activated by tissue plasminogen activator secreted by endothelial cells. Plasminogen can also be stimulated by activated factor XII and thrombin released during the clotting process. Plasmin digests the fibrin threads and inactivates fibrinogen, prothrombin, and factors V, VIII, and XII.

Factors Limiting Clot Growth and Formation

Because blood clotting involves a positive feedback system, there must be systems in place to localize clot formation. Clots are prevented from spreading by (1) rapid removal of clotting factors and (2) inhibition of activated clotting factors. Fibrin absorbs thrombin into the clot, thus limiting its site of action. Thrombin that escapes into circulation is inactivated by antithrombin III; an anticoagulant produced in the liver. Endothelial cells and WBCs produce prostacyclin, a prostaglandin that opposes the action of thromboxane A2. Prostacyclin inhibits platelet adhesion.

Heparin, produced by mast cells and basophils, is an anticoagulant that combines with antithrombin increasing its effectiveness. Protein C, also produced in the liver, inactivates factors V and VIII and enhances the activity of plasminogen activators.

Thrombolytic Agents

Thrombolytic agents are chemicals injected to dissolve blood clots. Streptokinase, produced by streptococcal bacteria, was one of the first commercial thrombolytic agents. More recently, a genetically engineered version of tissue plasminogen activator has been used. Aspirin can inhibit vasoconstriction and platelet aggregation. It does so by blocking the synthesis of thromboxane A2.

Blood Groups and Crossmatching

Blood Groups

On the surface of erythrocytes are various glycoproteins and glycolipids that act as antigens. Because of these various markers, blood is categorized into various blood groups or blood types. In humans, the most common blood groups are the ABO blood group and the Rh blood group, whereas animals have a variety of different blood groups.

Cattle have 11 major blood group systems, including A, B, C, F, J, L, M, R, S, T, and Z. The B group has over 60 different antigens. The J antigen is not a true antigen but instead is a lipid found in body fluids that adhere to erythrocytes.

The antigen groups or blood types in dogs are known as the DEA system. They include DEAs 1.1, 1.2, and 3–8. DEAs 1.1 and 1.2 account for 60% of the canine population. Dogs having DEA 1.1 or 1.2 are considered A‐positive; other dogs are considered A‐negative. A‐negative dogs do not have antibodies against A‐positive blood.

Cats have three AB blood groups. Type A is most common, accounting for 95% of short‐ and long‐hair domestic cats. Type B is less frequent, and type AB is rare. Cats with type‐A blood have antibodies against A isoantigens, whereas type‐B cats have alloantibodies (i.e., antibodies found against antigens in some members of the same species) against B isoantigens.

There are seven blood groups in sheep, including A, B, C, D, M, R, and X. The B group is highly polymorphic, and the R system is like the J system in cattle.

Five blood groups have been identified in goats: A, B, C, M, and J, with J being like that of cattle.

Crossmatching

Crossmatching is a procedure to determine whether donor blood is compatible with the recipient’s blood. There are two types of crossmatches. In major crossmatching, the donor erythrocytes are compared to the recipient serum to determine whether either acquired or naturally occurring antibodies are present in the recipient serum against the donor erythrocytes. Minor crossmatching compares donor serum to recipient erythrocytes, checking for preformed antibodies in donor serum that could hemolyze recipient red cells. Minor crossmatching is less important because the donor serum is markedly diluted after transfusion, decreasing the risk of a significant reaction.

The Heart

Anatomy of the Heart

Location and Exterior Landmarks

The heart is an inverted cone‐shaped structure located in the mediastinum, a mass of tissue occupying the medial region of the thoracic cavity extending from the sternum to the vertebral column, and between the lungs. The apex, or “pointed” end of the heart, is directed caudoventrally; the base, or top of the heart, is directed dorsocranially.

The cranial and caudal sides of the heart can be located by other structures. The auricles point left, with the pulmonary trunk located between the two auricles. The aortic arch projects caudally.

The coronary groove partially encircles the heart except at the conus and indicates the separation of the atria and ventricles. The conus is the pyramidal structure that is the right ventricular outflow tract into the pulmonary trunk. The interventricular grooves indicate the divisions between the two ventricles. The two auricles are visible on the left side of the heart, with the pulmonary trunk between them.

Pericardium

The membrane surrounding the heart is the pericardium. It consists of the fibrous pericardium and serous pericardium. The fibrous pericardium is a tough, inelastic, dense irregular connective tissue sac with one end attaching to the diaphragm and the other end fusing with the connective tissue surrounding the blood vessels entering and leaving the heart. The fibrous pericardium anchors the heart within the mediastinum and prevents overfilling of the heart. Inside the fibrous pericardium is the serous pericardium, consisting of a parietal and visceral layer. The parietal layer lines the internal surface of the fibrous pericardium; the visceral layer, also called the epicardium, is an integral part of the heart wall.

Inflammation of the pericardium is called pericarditis. This results in decreased production of serous fluid and a roughened serous membrane. As a result, the beating heart can be heard with a stethoscope rubbing against the serous layer (pericardial friction rubs). In severe cases, inflammation leads to excess fluid production, which compresses the heart and decreases its pumping ability.

Layers of the Heart

The heart wall consists of three layers: epicardium, myocardium, and endocardium. The epicardium is the outermost layer, and it is the visceral layer of the pericardium. It contains a thin, transparent layer of mesothelium and connective tissue. The middle layer, or myocardium, is cardiac muscle and makes up the bulk of the heart. The innermost endocardium is a thin layer of connective tissue providing a smooth lining for the chambers of the heart and valves. The endocardium is continuous with the endothelial lining of the large blood vessels attached to the heart.

Cardiac muscle is also called involuntary, striated muscle. Like skeletal muscle, it contains actin and myosin that are organized into sarcomeres.

Fibrous Skeleton of the Heart

The heart also contains dense connective tissue surrounding the valves, forming a fibrous skeleton (Fig. 13.9). In addition to forming a point of attachment for the valves, the fibrous skeleton serves to electrically insulate the atria from the ventricles (Box 13.5).

Two diagrams: (A) showing major arteries, veins, chambers, and structures such as the aorta, pulmonary arteries and veins, atria, ventricles, and coronary sinus. (B) highlighting heart structures including the atria, ventricles, coronary sinus, aorta, pulmonary trunk, and apex of the heart. — **Fig. 13.9** External structure of the heart. (A) Atrial side of the cat heart. (B) Auricular side of the cat heart.

Reprinted from Constantinescu (2002). Used by permission of the publisher.

Box 13.5 Dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a disease characterized by dilation or enlargement of the heart chambers, resulting in an abnormally large heart. This disease eventually results in heart failure, because the damaged heart muscle is too weak to efficiently pump blood to the rest of the body. DCM is very common in dogs, representing the most common reason for congestive heart failure (CHF). The left ventricle is most always involved. Because the myocardium cannot work effectively to pump blood out of the heart, subsequent backup of blood into the left atrium and ultimately into the lungs occurs commonly. This backup of blood into the lungs results in pulmonary edema and is a sign of congestive heart failure.

The treatment of dogs with DCM varies depending on the severity of the failure and impacts on other organs. Treatment may include oxygen administration, fluid therapy, and administration of drugs to aid breathing (bronchodilators) and drugs that modify heart function, and control arrhythmias. If low doses of antiarrhythmic are effective, the heart can often be stabilized. Serious ventricular arrhythmias that can only be controlled with higher drug doses have a worse prognosis.

Heart Chambers and Vessels

The heart has four chambers. Two atria located superiorly, receive blood and pump it to the ventricles. Two ventricles located posteriorly pump the blood away from the heart (Fig. 13.9). The atria are separated by the interatrial septum; the ventricles are separated by the interventricular septum. There is an oval depression on the interatrial septum called the fossa ovalis (Fig. 13.10), a remnant of the foramen ovale, which is an opening between the atria in the fetus that closes shortly before birth.

A diagram of the human heart, showing internal structures including the right atrium, left atrium, ventricles, vena cava, and valves. — **Fig. 13.10** Internal structure of the heart. The right side of the heart of a large ruminant is opened.

Reprinted from Constantinescu and Constantinescu (2004). Used by permission of the publisher.

Atria

The atria are the receiving chambers of the heart. Protruding from the atria are the auricles, which increase the atrial volume. The auricles are lined with pectinate muscles making them appear as if they were raked with a comb. The atria are relatively small and thin‐walled because they need to pump blood only to the ventricles.

Blood enters the right atrium from three veins: (1) the superior vena cava returns blood from the body regions in front of the diaphragm, (2) the inferior vena cava returns blood from areas posterior of the diaphragm, and (3) the coronary sinus collects blood draining the myocardium (Fig. 13.10). Blood passes from the right atrium into the right ventricle through the tricuspid valve, so named because it consists of three leaflets or cusps.

Blood enters the left atrium via four pulmonary veins. Blood passes from the left atrium to the left ventricle via the bicuspid, or mitral, valve, named because it has two cusps.

Ventricles

The ventricles form the bulk of the heart. The right ventricle wall is thinner than the left because it must pump blood only through the lungs via the pulmonary trunk. The left ventricle pumps blood to the body via the aorta, the largest artery in the body.

Blood leaves the right ventricle via the pulmonary valve. The left ventricle forms the apex of the heart. Blood leaves the left ventricle via the aortic valve. During fetal development when there is no pulmonary respiration, there is a temporary blood vessel called the ductus arteriosus that shunts blood from the pulmonary trunk into the aorta. This vessel closes shortly after birth, leaving a remnant called the ligamentum arteriosum.

Inside the ventricles are muscle bundles called the papillary muscles, which serve as attachments for the chordae tendineae, tendinous cords attaching to the atrioventricular (AV) valves. The papillary muscles and chordae tendineae assist in valve function (Box 13.6).

Pathways of Blood Through the Heart

The heart acts as two side by side pumps. The pulmonary circuit carries blood to and from the lungs, and the systemic circuit transports blood throughout the remainder of the body (Fig. 13.11).

The right side of the heart receives deoxygenated blood from the body. This blood passes into the right atrium, through the tricuspid valve, and into the right ventricle. It is then pumped to the lungs via the pulmonary trunk. In contrast to other major arteries and veins in the body, the pulmonary artery carries oxygen‐poor blood while the pulmonary vein carries oxygen‐rich blood.

The left side of the heart receives freshly oxygenated blood arriving from the lungs via the pulmonary vein. The blood passes from the left atrium to the left ventricle via the bicuspid valve. Blood is then pumped from the left ventricle into the aorta, passing through the aortic valve.

Box 13.6 Feline dilated cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a heart muscle disease (myopathy) in which the muscle walls of the left ventricle thicken. This may be a result that is secondary to other diseases such as systemic hypertension, or hypertrophy may be a primary disease.

HCM is diagnosed when thickening of the left ventricle walls is not caused by another disease. As HCM progresses, it can alter the heart structure and impair function in multiple ways. Some of these include: (1) internal ventricular chamber volume may be reduced, thus limiting its capacity to fill with blood. (2) Ventricular wall stiffness usually increases, which impairs the ability of the ventricle to relax, which also prevents efficient filling. (3) There may be an increase in ventricular pressure during relaxation (diastole), causing the blood to back up into the vessels of the lungs and consequently congestive heart failure. This is typically associated with pulmonary edema and/or pleural effusion (see the section on vascular fluid and movement into the lungs and/or pleural spaces).

Because the left ventricle is unable to fill adequately, less blood is pumped out to the body with each heartbeat. If the blood supply to other vital organs is inadequate, heart rate (HR) is likely to increase as the body tries to compensate. A decrease in blood flow to the kidneys can induce the release of renin, which increases blood volume, leading to even more stress on the heart, further contributing to congestive heart failure.

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Tags: Anatomy and Physiology of Domestic Animals

Mar 15, 2026 | Posted by admin in GENERAL | Comments Off

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