Clinical veterinary medicine- Ettinger Flashcards

Question

Fever of Unknown Origin Fever of unknown origin (FUO) is defined in human medicine as a fever that has lasted ..........weeks and has a cause that has not been determined through laboratory evaluation and radiographs. In veterinary medicine, most clinicians consider any animal with an increased body temperature that does not have any historical or physical finding that would explain this abnormality to be an FUO. Although research involving a large number of patients with FUO has been completed in humans, there is relatively little in the veterinary literature to help explain the most common causes of apparent FUO in dogs or cats. The information given in this chapter is based primarily on clinical experience. Most dogs and cats with FUO probably have an infection or suffer from the byproducts derived from those agents. The prevalence of the causative infectious agent varies depending on the area where the clinician practices and the previous travel history of the pet. Although ..........infections are probably the most common cause of FUO in the dog, in some geographic locations, systemic ........diseases or ................ infections might be more common. Endocarditis, pyelonephritis, prostatitis, closed pyometra, pyothorax, and other deep abscesses should be considered in a dog with FUO. In the cat, viral diseases such as feline leukemia virus (.........), feline infectious peritonitis (....... virus, and feline immunodeficiency virus (..........) are common infectious causes of FUO and may exceed bacterial infections as the leading cause. Another common cause of FUO in the dog and cat are .............. diseases. Neoplasia is not as common as immune-mediated disease in causing fevers but should always be considered, especially in older animals. Another, often overlooked, cause of fever is tissue trauma. Trauma often causes mild fever (103° F to 104° F [39.6° C to 40° C]) 1 or 2 days postsurgery when there has been significant muscle involvement.

Answer 1

Fever of Unknown Origin Fever of unknown origin (FUO) is defined in human medicine as a fever that has lasted 3 weeks and has a cause that has not been determined through laboratory evaluation and radiographs. In veterinary medicine, most clinicians consider any animal with an increased body temperature that does not have any historical or physical finding that would explain this abnormality to be an FUO. Although research involving a large number of patients with FUO has been completed in humans, there is relatively little in the veterinary literature to help explain the most common causes of apparent FUO in dogs or cats. The information given in this chapter is based primarily on clinical experience. Most dogs and cats with FUO probably have an infection or suffer from the byproducts derived from those agents. The prevalence of the causative infectious agent varies depending on the area where the clinician practices and the previous travel history of the pet. Although bacterial infections are probably the most common cause of FUO in the dog, in some geographic locations, systemic fungal diseases or rickettsial infections might be more common. Endocarditis, pyelonephritis, prostatitis, closed pyometra, pyothorax, and other deep abscesses should be considered in a dog with FUO. In the cat, viral diseases such as feline leukemia virus (FeLV), feline infectious peritonitis (FIP) virus, and feline immunodeficiency virus (FIV) are common infectious causes of FUO and may exceed bacterial infections as the leading cause. Another common cause of FUO in the dog and cat are immune-mediated diseases. Most immune-mediated diseases occur in young adult dogs. Immune complexes are a potent stimulator for the release of fever-producing cytokines and frequently lead to temperatures of 105° F (40.5° C) or 106° F (41° C). Neoplasia is not as common as immune-mediated disease in causing fevers but should always be considered, especially in older animals. Another, often overlooked, cause of fever is tissue trauma. Trauma often causes mild fever (103° F to 104° F [39.6° C to 40° C]) 1 or 2 days postsurgery when there has been significant muscle involvement. Most of these animals do not have infections and probably should not be treated with antibiotics without additional evidence of infection. Evaluating for infectious disease, immune-mediated disease, neoplasia, and causes of tissue trauma will usually lead to a final diagnosis, even when no obvious cause for the fever exists.

Answer 2

NONSPECIFIC THERAPY FOR FEBRILE PATIENTS Mild to moderate elevations in body temperature are rarely fatal and may be beneficial to the body. As stated before, hyperthermia may inhibit viral replication, increase leukocyte function, and decrease the uptake of iron by microbes (which is often necessary for growth and replication). If a fever exceeds 107° F, a significant risk of permanent organ damage and disseminated intravascular coagulation exists. The benefits of nonspecific therapy versus its potential negative effects should be considered before initiating such management. Nonspecific therapy for true fever usually involves inhibitors of prostaglandin synthesis. The compounds most commonly used are the nonsteroidal antiinflammatory drugs. These products inhibit the chemical mediators of fever production and allow normal thermoregulation. They do not block the production of endogenous pyrogens. These products are relatively safe, although acetylsalicylic acid is potentially quite toxic to cats and cyclooxygenase-2 (COX-2) inhibitors are relatively safer. Dipyrone, an injectable nonsteroidal antiinflammatory drug sometimes used in cats, may lead to bone marrow suppression, especially when given over a prolonged period.

Answer 3

Total body cooling with water or fans, or both, in a febrile patient will reduce body temperature; however, the thermoregulatory center in the hypothalamus will still be directing the body to increase the body temperature. This may result in a further increase in metabolic rate, oxygen consumption, and subsequent water and caloric requirements. Unless a fever is life threatening, this type of nonspecific therapy is counterproductive.

Answer 4

Glucocorticoids block the acute-phase response, fever, and most other parts of this (adaptive) response. In general, their use should be reserved for those patients in whom the cause of the fever is known to be noninfectious and blocking the rest of the acute-phase response will not be detrimental (and may prove beneficial). The most common indications include some immune-mediated diseases in which the fever plays a significant role and glucocorticoid therapy is often part of the chemotherapeutic protocol (e.g., immune-mediated hemolytic anemia, immune-mediated polyarthritis).

Answer 5

Phenothiazines can be effective in alleviating a true fever by depressing normal thermoregulation and causing peripheral vasodilation. The sedative qualities and potential for hypotension caused by the phenothiazines should be considered before administration to the febrile patient.

Answer 6

MAINTANENCE OF NORMAL BODY TEMPERATURE Mammalian body temperature is maintained closely around a constant set point at which cellular function is optimal. There are a number of complex mechanisms that maintain body temperature within tight control. The anterior hypothalamus maintains overall control of body temperature. It responds to local increases or decreases in temperature and also to neural input from warm and cold receptors in the skin, the abdominal viscera, and the spinal cord.

Answer 7

To maintain constant temperature, heat generated by muscular activity and metabolism is matched to heat loss. Temperature is regulated largely by control of heat loss from the body surface via the classic routes of heat exchange: conduction, convection, evaporation, and radiation (Web Figure 11-1). Heat is also lost from the respiratory tract through evaporation and in urine and feces.

Answer 8

Through peripheral vasoconstriction, which prevents warm blood reaching the body surface. Piloerection insulates the skin by trapping a layer of stationary air. Some additional heat is generated through muscle activity, such as shivering and voluntary movement. Adrenergic chemical thermogenesis may also have a role in maintaining body temperature. Behavioral responses to cold are important in preventing heat loss; for example, moving into shelter and warmth, curling up, and dams protecting the young. Heat is lost by reversal of these processes, such that vasodilation of superficial blood vessels allows warm central blood to reach the skin. Panting increases evaporation from the respiratory tract. In some species, sweating is stimulated to provide the most effective heat loss through evaporation. Dogs and cats do not sweat from the skin, and loss via the respiratory tract through panting is the most significant form of active heat loss.

Answer 9

DEVELOPMENT OF HYPOTHERMIA Hypothermia develops when either the methods of heat production and conservation are overwhelmed by a cold environment or when the mechanisms of heat retention are impaired. Smaller animals, in which the ratio of body surface area to volume is high, are more likely to develop hypothermia. Old, sick, or otherwise debilitated animals are also more likely to become hypothermic as heat generation and temperature control may be impaired. Neonates, with underdeveloped temperature-regulating mechanisms, are particularly susceptible. Hypothermia leads to a progressive failure of bodily functions, ultimately leading to cardiac standstill and death.

Answer 10

In man, a core body temperature of 35° C is regarded as hypothermia. Although animal temperatures are slightly higher than human temperatures, the definitions of degrees of hypothermia applied in human medicine serve well in other species as a guide to the expected degree of malfunction (Figure 11-1). Initially, as core body temperature decreases below 36° C, respiratory rate, pulse rate and arterial blood pressure fall. As temperature decreases below 34° C, muscular control and neural function begin to fail, consciousness is depressed, and metabolism is slowed.

Answer 11

Acidosis and electrolyte imbalance may occur and, below 30° C, even in the absence of any drugs, cardiac dysrhythmias are likely to develop and temperature regulatory mechanisms fail. Hence, animals with a body temperature below 30° C are unlikely to regain normal temperature without treatment. Progressive metabolic and respiratory failure takes place when body temperature is below 28° C, with a high risk of ventricular fibrillation; cardiac standstill occurs at around 20° C

Answer 12

Normal cats and, particularly, dogs withstand cold environments well. For instance, dogs immersed in water at 20° C can maintain heat regulation for 5 hours with less than a 1° C fall in body temperature. By far the most common cause of hypothermia in small animals is the disruption of normal control mechanisms by sedation and anesthesia,[2] which impair hypothalamic function and behavioral responses.

Answer 13

Many anesthetics and sedatives cause some degree of peripheral vasodilation, which itself allows more heat loss. As a consequence, most small animals are likely to lose body heat during anesthesia. Exposure to a cold environment or near drowning is a much less common cause of hypothermia in animals. In these circumstances, normal heat retention mechanisms are simply overwhelmed by the environmental conditions. The consequences of cold-exposure hypothermia and its treatment are essentially the same as for anesthesia-induced hypothermia. Hypothermia is likely to be more severe after cold exposure, but there is the advantage of being uncomplicated by the effects of surgery or drugs.

Answer 14

Anesthetic-associated heat loss and the resultant decrease in body temperature slow drug metabolism and lead to prolonged recovery from anesthesia.[3] If severe, it is possible that cardiac function may be affected sufficiently to cause death. More commonly, postoperative hypothermia causes morbidity or death through the consequences of a slow recovery. A long period of unconsciousness increases the likelihood of unresolved obstructed airways and prolonged hypoxia. Shivering will worsen this effect through increased oxygen and energy demands. Lack of movement in an animal still under the influence of vasodilating anesthetics and sedatives leads to a vicious circle of further heat loss and reduced drug metabolism, prolonging recovery and further increasing the chance of airway obstruction and hypoxia.

Answer 15

PREVENTION AND TREATMENT It is a great deal easier to prevent heat loss during anesthesia than to try to restore the temperature of a cold, unconscious dog or cat at the end of a long surgical procedure. Effort should be made from the start of anesthesia to maintain body temperature between 36° and 38° C. Body temperature needs to be monitored in order to prompt appropriate treatment; this is easily achieved by measuring rectal temperature, which has been shown to correlate well with core temperature.[4] Much can be done to prevent hypothermia by passive methods, largely insulation, although active methods using external heat are usually required where body cavities are exposed. Warming the limbs rather than the trunk has been shown to be particularly effective

Answer 16

Passive Warming A warm operating theatre may reduce heat loss into the surroundings, but working in an environment at body temperature is unpleasant; some heat loss by conduction into air circuits flowing around the animal will still occur unless it is insulated. Insulation between the operating table and the animal is easy to achieve with foam padding and other positioning aids. It is also easy to insulate the whole animal by wrapping any exposed parts with bubble wrapping or aluminium foil (Web Figure 11-2). A compromise between the ultimate asepsis and the best heat retention must be made by clipping the minimal amount of hair and wetting the smallest area compatible with the proposed surgery. At all costs, excess scrub water must be dried up. No animal should lie in a pool of scrub liquid during surgery. It is impossible to prevent evaporation from the exposed surgical site. Intestinal surgery is the worst in this regard because large surface areas of serous membrane may be exposed. Regular flushing with warm (38° to 40° C) saline helps to reduce the amount of evaporation of body fluid and may help to prevent heat loss. Heat is also lost through the respiratory tract. Use of low-flow rebreathing circuits that retain both heat and moisture are advantageous in this respect. Heat and moisture exchangers placed between the endotracheal tube and the breathing circuit help to retain moisture and hence heat, as evaporation is reduced. However, these exchangers increase dead space and may be inappropriate for the cats and small dogs that most need heat retention.

Answer 17

Active Warming Active methods to prevent heat loss are usually required during surgery of the body cavities. Abdominal lavage with saline warmed to around 43° C has been shown to increase body temperature in dogs undergoing celiotomy.[6] External warming can usually be provided by using heated pads, infrared lights, heated gels, and hot-air circulators. Circulating water-heated pads are the safest because they do not become too hot; electrically heated pads or any non–thermostatically controlled system may burn an unconscious dog or cat unable to move away from the heat source.[7] Gel pads that are catalyzed into an exothermic reaction when changing state to a stiff form are useful in cats and small dogs (Web Figure 11-3). By far the most effective of the active-heating systems are the hot-air blankets, in which hot air is blown into a perforated blanket that is placed about the animal under the surgical drapes (Web Figure 11-4). An extremely wet animal will initially be cooled as the result of evaporation, but in all other circumstances this method has proved extremely effective. Treatment of hypothermia depends on its severity and cause. After anesthesia, active warming is required as homeostatic mechanisms are impaired. Where the environment has caused hypothermia, normal heat-generating mechanisms will be more effective, and passive methods such as insulation with warm, dry blankets may be sufficient (see Figure 11-1). Extreme hypothermia (core temperature 30° C) requires internal active warming with intravenous fluids at 40° C and gastric, colonic, or peritoneal lavage with fluids at 40° to 42° C. This is to prevent further core cooling, which occurs when surface warming causes vasodilation, thereby allowing cold, peripheral blood to circulate into the body core.

Answer 18

The activation of specially modified receptors and neural pathways by noxious stimuli results in the peripheral process referred to generically as nociception. In contrast, the experience of pain is the final product of a complex information-processing network that results in perception; perception takes place only at higher levels of the central nervous system (CNS) as a direct result of nociception. Pain is the conscious recognition of discomfort resulting from injury, disease, or emotional distress as evidenced by biologic or behavioral changes or both. It is a subjective and emotional experience that may be accompanied by feelings of fear, anxiety, and panic. .

Answer 19

Pain elicits protective motor actions, results in learned avoidance, and may modify species-specific traits of behavior including social behavior. Acute pain is the result of a traumatic, surgical, or infectious event that is abrupt in onset, does not persist much beyond the inciting insult, and is generally alleviated by commonly administered analgesic drugs.

Answer 20

Chronic pain persists beyond the normal duration of acute disease or injury despite resolution of disease or healing of injury; chronic pain may also result from a persistent pathologic process or nerve injury (neuropathic pain). Chronic pain is seldom sufficiently alleviated by routinely used analgesics and often requires a multimodal approach including, but not limited to, pharmacologic analgesics, tranquilizers or psychotropic drugs, physical therapy, environmental manipulation, acupuncture, and behavioral conditioning

Answer 21

Simply put, acute pain is a symptom of disease or injury with the protective function of warning the organism of impending or actual tissue damage. Clearly then, acute pain is important; indeed congenital or acquired insensitivity to pain leads to heightened risk of injury and premature death.[4,5] In contrast, chronic pain is a disease itself.[6] Chronic pain does not serve a biologic function and is associated with significant morbidity.

Answer 22

A simplified model of pain pathways describes progression from periphery to the CNS via transduction, transmission, modulation, projection, and finally, perception.

Answer 23

Figure 12-1 Schematic pathways in the neuroanatomic description of pain. Noxious stimuli are transduced into electrical stimuli, transmitted to the spinal cord (where peripheral ascending and descending modulation occurs), and finally are relayed to the brainstem and brain for perception. Descending pathways from higher centers also modulate pain signals.

Answer 24

Transduction occurs in the periphery at the terminal ends of sensory primary afferent nerve fibers. Nociceptors are the specialized termini of these fibers, which respond to noxious stimuli. A so-called minimal or adequate stimulus is required to activate nociceptors above their threshold; this results in transduction of noxious stimuli into nerve impulse signals. Known activating stimuli for nociceptors include mechanical, thermal, or chemical stimuli. Nociceptors may be monomodal or polymodal (responding to more than one stimulus type). Distinct from mono- and polymodal nociceptors are the silent nociceptors.[7,8] Under normal stimulating circumstances these nociceptors are insensitive due to a relatively high threshold. An adequate stimulus is only achieved following the release of tissue inflammatory mediators at the site of injury that reduce the threshold for response. As a result, these previously silent nociceptors can be activated by a variety of thermal and mechanical stimuli. This is an example of peripheral sensitization and hypersensitivity.

Answer 25

Transduced signals are propagated along the primary afferent neuron as action potentials in a process called transmission. Primary afferent neurons transmitting noxious signals are of two classes: (1) fast-conducting (5 to 30 m/sec), lightly myelinated Aδ fibers ,which are associated with sharp or superficial pain; and (2) slow-conducting (0.5 to 2 m/sec), unmyelinated C fibers, which are associated with a dull, burning type of pain, so-called second pain or deep pain. (3) A third class of primary afferent neuron, Aβ, constitutes myelinated, fast-conducting fibers transmitting nonnoxious sensory information such as touch, pressure, and proprioception.

Answer 26

Primary afferent neurons synapse in the dorsal horn of the spinal cord on a number of different neurons, including nociceptive-specific second-order neurons, nonnociceptive-specific so-called wide-dynamic range (WDR) neurons, and interneurons. WDR neurons receive information from Aβ, Aδ, and C fibers. Modulation occurs in the dorsal horn of the spinal cord and suprasegmentally resulting in increased or decreased nerve impulse propagation.

Answer 27

Second-order projection neurons constitute ascending, projection pathways, the most important of which, outside the head in nonhuman animals, are the spinocervicothalamic and spinoreticular tracts.

Answer 28

The spinocervicothalamic tract is chiefly concerned with superficial pain and is the primary conscious pain pathway in carnivores. The spinoreticular is primarily associated with transmission of deep and visceral pain Second-order neurons project to cortical (primary somatosensory cortex, anterior cingulate cortex, insular cortex, and forebrain) as well as several subcortical sites including the reticular formation, nucleus raphe magnus of the medulla, periaqueductal grey matter (PAG) of the midbrain, the hypothalamus, the thalamus, and the limbic system. These projections result in physiologic responses to pain beyond conscious perception, including arousal; altered sympathetic tone; ascending and descending modulation of pain due to release of norepinephrine, serotonin, enkephalin, endorphin, and dynorphin; emotional distress; and memory consolidation. Anatomic data show a high degree of connectivity among these areas. Plasticity, redundancy, and resilience among pain pathways exist such that functions usually performed by one region can be taken over by another.

Answer 29

Figure 12-2 Sensory pathways associated with pain signals. VPL, Ventral lateral nucleus.

Answer 30

Once the pain signal has reached the brain cortex, conscious perception is possible. Perception is recognition, integration, and processing of sensory information. The ability of a given stimulus to result in the conscious perception of pain and in physiologic response to pain is dependent on modification in the periphery, within the spinal cord, the brainstem, and in cortical regions of the brain.

Answer 31

Perception of pain requires consciousness; thus an anesthetized patient cannot perceive a painful stimulus. Importantly, such a patient is capable of all nociceptive responses short of perception and upon recovery from anesthesia is subject to all adverse effects of the unmitigated pain process.

Answer 32

Neuromodulation and Response to Pain The Cartesian model of pain imagines the somatosensory system like a simple line of communication directly linking and not altering pain signals as they are transmitted from the body (periphery) to the brain (cortex) for conscious perception. Further, this model suggests that the stimulus in the periphery is predictably and proportionately transmitted. Modern pain science has revealed that pain pathways are in fact highly labile, and modulation in the periphery, the spinal cord, brainstem, and higher centers is the rule not the exception. Peripheral nociception is altered by changes in nociceptive threshold chiefly as a result of nociceptive sensitizers and activators. These are inflammatory mediators and neuropeptides (e.g., substance P, bradykinin, serotonin, histamine, prostaglandin, interleukin-1, tumor necrosis factor-α) released from damaged tissue that directly stimulate nociceptors, increase their sensitivity, and recruit silent nociceptors. The direct result is peripheral sensitization that leads to primary hyperalgesia, a state of increased responsiveness to noxious stimuli, and allodynia, a state in which normally nonnoxious stimuli are capable of activating nociceptors. Modulation of peripheral sensitization is an important target in pain control.

Answer 33

Central nociception is also capricious. Changes in excitability of neurons and glial cells in the spinal cord result in central sensitization, a process whereby nerve fibers are “trained” to respond more vigorously to further stimulation. This occurs due to bombardment of second-order neurons with high-intensity, high-frequency stimuli from the periphery (primarily C-fibers). The result is presynaptic membrane modulation and increased release of excitatory neurotransmitter, glutamate, along with substance P, BDNF (brain-derived neurotrophic factor), and calcitonin gene–related peptide (CGRP).[13] Substance P and BDNF are neuromodulatory neurotransmitters that bind to G protein–coupled receptors. Neurotransmitters act on excitatory (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate [AMPA], kainite, NMDA) and inhibitory (γ-aminobutyric acid [GABA] and glycine) receptors. NMDA receptors on the postsynaptic membrane, normally silent, are activated by increased glutamate. The consequence is increased calcium influx and subsequent upregulation of receptors resulting in increased membrane sensitivity, so-called spinal facilitation of pain or wind-up. In addition to subcellular modification, neuronal change occurs. WDR neurons are among those cells chiefly associated with wind-up. WDR neurons are capable of receiving information from somatic and visceral structures, noxious and non-noxious stimuli. As a result of high-frequency stimulation, previously nonnoxious stimuli are capable of causing pain, individual peripheral sensory neuron receptive fields expand, and stimulation of one tissue can be perceived as originating in a distant tissue (i.e., referred pain). Additionally, tactile, nonnoxious impulses reaching the WDR neurons via Aβ neurons can inhibit transmission of noxious impulse; this is sometimes called the gate control theory, first introduced by Melzack and Wall

Answer 34

And yet it is more complicated than this. Recent data implicate the role of immune and glial cells in the development of pain disorders. It is clear that neurons alone are not responsible for pain in its many manifestations. So-called neuronal support structures such as microglia, astrocytes, oligodendrocytes, fibroblasts, endothelial cells, Schwann cells, and satellite cells compose 80% to 90% of neurologic tissue and are likely involved in a complex network of intercellular communication for pain signaling and processing.[15] It appears that this communication is multidirectional from support cells to neurons and from neurons to support cells, using gap junctions and chemical modulation (e.g., chemokines, cytokines, nitric oxide, neurotransmitters, excitatory amino acids, prostaglandins).

Answer 35

In the basal state astrocytes provide energy and neurotransmitter precursors for neurons. They also provide trophic support. Astrocytes become activated in response to CNS trauma, ischemia, neurodegeneration, and inflammation. Activation is characterized by increased production of proinflammatory substances such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and nitric oxide (NO). For example, NO, produced by activated glia and neurons, potentiates IL-1–induced cyclooxygenase 2 (COX 2), an important enzyme in the synthesis of inflammatory prostaglandins and a target for nonsteroidal antiinflammatory drugs.[18]

Answer 36

Finally, activity in the spinal cord is further modulated by descending antinociceptive systems originating in suprasegmental structures. Midline nuclei of the midbrain and medulla, such as the periaqueductal grey and the nucleus raphe magnus, respond to input both from ascending spinoreticular and spinocervicothalamic tracts and from descending pathways from higher cerebral centers (e.g., limbic and cortical regions). These nuclei release neurotransmitters for antinociceptive systems including serotonin, norepinephrine, epinephrine, and endogenous opiates. Cortical and noncortical structures include forebrain; cingulate, insular, and somatosensory cortices; thalamic nuclei; amygdala; hypothalamus; and basal ganglia structures such as the globus pallid us. It is important to note that the above is a highly simplified, albeit useful, overview of the enormously complex peripheral, dorsal horn, and central sensitization and modification processes.

Answer 37

In general, pain assessments can be categorized as primarily objective or subjective. Physiologic data (e.g., heart rate, respiratory rate, arterial blood pressure, pupil dilation) may be useful in objectively assessing response to a noxious (painful) stimulus in a lightly anesthetized animal. Physiologic responses also occur in conscious patients as a result of acute pain or other stressors, but not with the same degree of reliability as in anesthetized patients. CNS and cardiopulmonary reflexes control cardiovascular and respiratory function to maintain a state of homeostasis; therefore, reflex control mechanisms may dampen physiologic responses to pain. In addition, physiologic parameters are not specific enough to differentiate pain from other stressors such as anxiety, fear, or concurrent metabolic conditions (e.g., anemia). Holton et al found that heart rate and respiratory rate were not useful indicators of pain in hospitalized dogs following surgery.[27] However, pupil dilation was significantly correlated with the pain score (numeric rating scale) in dogs following surgery.

Answer 38

CLINICAL PAIN MANAGEMENT CONCEPTS Pain States Clinically relevant, pathologic, painful states can be somewhat arbitrarily divided into three main categories. Acute pain is defined as pain that follows bodily injury, disappears with healing, and tends to be self-limiting. The current foundation of acute pain therapy is the opiate drug class and recently, the nonsteroidal antiinflammatory drug (NSAID) class as well. Adjunctive therapies include alpha-2 agonists, local anesthetic techniques, NMDA receptor antagonists, acupuncture, low-level laser therapy, and physiotherapy, among others. Increasingly, it is clear that untreated acute pain results in chronic and neuropathic pain, both of which are notoriously unresponsive to opiates. Chronic pain lasts several weeks or more and persists beyond the expected healing time.

Answer 39

Neuropathic pain is pain that originates from injury or involvement of the PNS or CNS with motor, sensory, or autonomic deficits. Chronic and neuropathic pain treatment involves pharmacologic, nonpharmacologic, surgical, interventional, manual, physical, and rehabilitation therapy. Management of the chronic pain patient requires tailoring treatment to the individual as well as frequent reassessment. Other painful states maybe classified within these three general categories and include cancer pain, inflammatory pain, visceral pain, somatic pain, myofascial pain, and breakthrough pain.

Answer 40

Opiates are powerful, broad-spectrum analgesics and remain the cornerstone of acute pain management. Exogenously administered opioids (opiates) such as morphine, hydromorphone, fentanyl, and buprenorphine achieve their analgesic action through mimicking the effect of endogenous opioids. These compounds bind to µ-, κ-, and δ-opioid receptors found in the periphery, spinal cord, and supraspinal centers. These receptors are G protein‐coupled and ultimately decrease release of neurotransmitter through their interaction with voltage-gated calcium channels.

Answer 41

In the past decade research has focused on peripheral opioid mechanisms in an attempt to curtail undesirable effects of exogenously administered systemic opiates and to improve efficacy in chronic and neuropathic pain states. Undesirable systemic side effects include CNS depression, bradycardia, respiratory depression, excitement, decreased gastrointestinal motility, emesis, increased bladder tone with spasm of ureteral smooth muscle, paradoxical pain, and opiate antinociceptive tolerance. Species variability in response has been noted; in particular, cats may be more sensitive to excitatory effects and dogs appear to be prone to emesis. Capitalizing on the peripheral endogenous opioid system (PEOS) is a promising future strategy for achieving effective analgesia while minimizing these side effects.[38,39]

Answer 42

The PEOS includes peripheral opioid receptors (POR) and peripheral leukocyte-derived opioids (PLDO): endomorphins, endorphins, enkephalins, and dynorphins. In order to activate the PEOS, tissue must have sufficient numbers of leukocytes able to secrete PLDO and functional PORs in sufficient numbers. Inflammation due to tissue damage results in accumulation of PLDO-secreting leukocytes at the site of injury. Perhaps the predominant contributors promoting leukocyte accumulation and PLDO secretion are the chemokines, small proteins important in the trafficking of immune cells and in coordinating the immune response.[40,41] Inflammation also increases the number and efficiency of PORs expressed on primary sensory neurons.[42] PORs are synthesized in the dorsal root ganglion and transported distally to peripheral sensory nerve endings.[43,44] PORs are inactive under normal conditions; however, with tissue injury and inflammation the action of bradykinin improves opioid receptor coupling to G protein–signaling systems.

Answer 43

NSAIDs are a diverse group of agents that possess analgesic, antiinflammatory, antipyretic, and opioid-sparing effects. These drugs are typically classified according to their mechanism of action, inhibition of cyclooxygenase (COX) enzymes.

Answer 44

COX enzymes are important in the synthesis of prostaglandins from arachidonic acid. Prostaglandins are ubiquitous and in turn mediate a variety of critical physiologic functions throughout the body including maintenance of renal function, platelet aggregation, secretion of the protective gastric layer (bicarbonate and mucus), as well as inflammation and pain.

Answer 45

The existence of at least two isoforms, COX1 and COX2, is well established, and now a splice variant of COX1, so-called COX3, is under scrutiny.[56,57] The specific roles of these isoforms and their relative degree of inducibility continue to be debated. However, COX1 is widely viewed as primarily constitutive and COX2 is thought to be inducible.

Answer 46

COX1 generates prostaglandins responsible for mucosal defense, platelet aggregation, and renal function. Inasmuch as COX2 can increase up to twentyfold in the presence of tissue injury and is a known mediator of nociception, COX2 selective agents have been considered more desirable and safer than COX1 specific or nonspecific agents in the treatment of pain.[58,59] The hypothesis that COX1 mediates homeostatic physiologic functions and COX2 important pathophysiologic functions has driven the development of COX2-specific NSAIDs such as the veterinary products carprofen, meloxicam, deracoxib, and tolfenamic acid.

Answer 47

Most NSAIDs that inhibit COX result in the diversion of arachidonic acid to the lipoxygenase pathway (5-LOX) resulting in increased synthesis of leukotrienes, potent mediators of inflammation. This suggests that a dual inhibitor of the COX2 and 5-LOX pathways might be an ideal analgesic agent with an improved safety profile. Currently tepoxalin is the only veterinary-approved drug with dual action.

Answer 48

Gastrointestinal toxicity (vomiting, diarrhea, ulceration), Idiosyncratic hepatotoxicosis, Renal dysfunction especially in the face of hypovolemia. Consequently, the use of NSAIDs requires clinical judgment because the constitutive functions of these enzymes must be considered. These agents should not be administered to patients with acute renal insufficiency, hepatic insufficiency, gastrointestinal ulceration, coagulopathy, hypotension, hypovolemia, or dehydration. NSAIDs should not be used concurrently with corticosteroids or other NSAIDs. There appears to be no consistent recommendation for washout period between corticosteroid use or use of other NSAIDs prior to administration of a new NSAID.

Answer 49

Cats are exquisitely sensitive to the adverse effects of NSAIDs presumably by virtue of limited glucuronidation pathways. As such, toxic plasma levels are easily attained with doses considered safe for an equivalently sized dog.

Answer 50

Local anesthetic agents Local anesthetics prevent nerve transmission by inhibiting the generation and propagation of nerve impulses via reversible blockade of sodium channels within the neuronal membrane. The result is the prevention of neuronal depolarization and nerve conduction. With progressive increase in concentration of local anesthetic, autonomic, somatic sensory, and somatic motor blockade is achieved. The interruption of transmission of nociceptive information from the periphery to the spinal cord has the added advantage of decreasing central sensitization and wind-up by preventing the bombardment of WDR neurons in the dorsal horn.

Answer 51

Commonly used local anesthetics in small animal practice include lidocaine, mepivacaine, ropivacaine, and bupivacaine. These agents differ most importantly in their time to onset and duration of action as well as in their relative toxicity. Toxicity occurs as a consequence of systemic absorption resulting in cardiovascular system (CVS) and CNS signs. CNS toxicity can be recognized as tremoring and/or seizures. All local anesthetics have the potential to cause peripheral nerve fiber damage when used in high enough concentration and if injected directly into a nerve fascicle. Careful attention to dose and increased resistance to injection will minimize this risk. CVS toxicity is less likely with lidocaine, but may cause bradycardia and hypotension, whereas intravenous injection of bupivacaine can lead to sudden, CPR-resistant cardiovascular collapse. CVS toxicities have been treated with bretylium, magnesium, and, more recently, 20% intravenous lipid

Answer 52

Epinephrine can prolong the duration of block, increase the intensity of the block, and decrease systemic absorption 10% to 30%. This effect is likely due to vasoconstriction mediated by alpha-1 adrenergic receptor agonism since most local anesthetics except ropivacaine cause vasodilation.

Answer 53

Alpha-2 adrenoreceptor antagonists have been used extensively to provide sedation and analgesia in small animal patients. The analgesic effect of these drugs is mediated by CNS-localized noradrenergic and nonnoradrenergic neurons. Alpha-2 receptors are located both presynaptically and postsynaptically and analgesia appears to be mediated at both sites. CNS sites of action include the dorsal horn of the spinal cord, the brainstem, and the locus ceruleus (LC) of the pons. Noradrenergic neurons of the LC extend to all segments of the spinal cord and modulate noradrenergic input from higher structures such as the PAG of the midbrain. Activation of alpha-2 receptors in the LC ultimately results in decreased release of norepinephrine; this decrease disinhibits activity in adjacent nuclei, which subsequently results in increased release of norepinephrine at their axonal termini in the dorsal horn. The final result is activation of spinal (dorsal horn) presynaptic and postsynaptic alpha-2 receptors to produce analgesia. Medetomidine is the most commonly used alpha-2 adrenoreceptor agonist since its release in the United States along with its antagonist atipamezole in 1996. In early 2008 dexmedetomidine, the pure S-enantiomer of the racemic medetomidine, was introduced into the veterinary market and likely will surpass medetomidine. Although twice as potent as medetomidine, the two are essentially the same drug; similar effects and side effects can be anticipated. Alpha-2 agonists are used as a component of total intravenous anesthesia; as a preanesthetic sedative-analgesic agent; as a constant-rate infusion supplement to inhalant anesthesia and in the postoperative period; in epidural and intrathecal injections; intraarticularly; and as a synergistic supplement to local anesthetics in regional nerve blockade.

Answer 54

The cardiovascular effects.

Answer 55

Alpha-2 agonists bind to postsynaptic alpha-2 receptors to mediate smooth muscle contraction of blood vessels. The resultant vasoconstriction produces hypertension accompanied by a reflexive, baroreceptor-mediated decrease in heart rate. Cardiac output is diminished by as much as 40% to 50%. After the initial phase of hypertension, central alpha-2 adrenoreceptor effects result in decreased sympathetic tone with concomitant reduced blood pressure, heart rate, and cardiac output. Because of these profound CVS effects, careful patient selection is indicated in using this class of drugs for adjunctive analgesia.

Answer 56

NMDA receptor antagonists (methadone, ketamine, dextromethorphan, amantadine) The NMDA receptor is an excitatory amino acid receptor expressed on the central terminals of primary afferent fibers. Activation of these receptors by glutamate results in sensitization of spinal neurons and has been implicated in the development and modulation of prolonged pain states in animal models.

Answer 57

NMDA antagonists may reduce pain, opiate consumption, or both by two non–mutually exclusive mechanisms. First is the more widely recognized reduction in central hypersensitivity, and second is the fact that NMDA antagonists have also been shown to reduce opiate tolerance in many animal and human studies. Opiate tolerance is defined as the decrease in analgesic activity after previous exposure to the same or similar drug; this can occur over a period of hours to weeks.[105,106] Additionally, NMDA receptor–mediated central sensitization/wind-up is associated with opiate-induced abnormal pain (i.e., prolonged opiate administration produces paradoxical pain).[107-109] Laulin et al have reported that a single dose of opiate can induce a lasting increase in basal pain sensitivity leading to hyperalgesia. A number of studies suggest that NMDA receptor antagonists may prevent opiate-induced tolerance and antinociception and may act synergistically with opiates to provide superior analgesia. Clinically, combined treatment with an NMDA antagonist and an opiate may decrease opiate-induced side effects because heightened analgesia may allow a lower overall opiate dose. Clinically relevant NMDA receptor antagonists in veterinary medicine include methadone, ketamine, amantadine, and dextromethorphan. Since methadone, ketamine, and dextromethorphan are not recommended for oral NMDA-receptor antagonism, their use in chronic, at-home therapy is limited.

Answer 58

Other analgesic agents (tramadol, gabapentin, acetaminophen) Tramadol is a centrally acting agent with multimodal analgesic effects. First, it has modest affinity for the µ-opioid receptor (tramadol: 2500-fold to 4000-fold less than morphine; O-desmethyltramadol, the M1 metabolite: 9-fold to 450-fold less than morphine) and no κ or δ affinity.[141] The M1 metabolite appears to be responsible for µ-opioid agonist effect. A second nonopioid mechanism is suggested by the characteristic of only partial naloxone reversibility.

Answer 59

Tramadol inhibits neuronal uptake of the monoamine neurotransmitters, norepinephrine and serotonin, involved in descending inhibitory pathways in the CNS; this action prolongs antinociceptive effects.[143] In comparison to morphine, advantages of tramadol include less sedation, less respiratory depression, improved oral bioavailability, and tramadol is not currently a controlled substance. Side effects include decreased seizure thresholds, serotonin syndrome, nausea/vomiting, and in some animals altered behavior.

Answer 60

Nausea and vomiting are commonly reported in people and often an antiemetic is recommended. Caution is advised with the use of ondansetron as the analgesic effect of tramadol is impaired by this 5-HT3 (serotonin)–receptor antagonist. This drug is contraindicated in patients receiving monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) due to the increased risk of serotonin syndrome

Answer 61

Acetaminophen (paracetamol) possesses low antiinflammatory activity and as such is not considered a classic NSAID. Furthermore, its exact mechanism of action is unclear although recent evidence suggests indirect activation of the cannabinoid CB(1) receptor. The so-called COX3, splice variant of COX1, has been suggested as an additional mechanism for acetaminophen. Acetaminophen is not approved for use in veterinary species, but has been used effectively for the treatment of breakthrough pain in dogs at a dose of 10 to 15 mg/kg BID for up to 5 consecutive days. Additional benefits of acetaminophen include minimal risk of thrombocytopenia, bleeding, and gastrointestinal side effects. Hepatopathy is of concern and routine serum chemistry evaluation is warranted. Acetaminophen should not be used in cats due to inadequate cytochrome P450-dependent hydroxylation (glucuronidation) and subsequent fatal methemoglobinemia.

Answer 62

PATHOGENESIS OF OBESITY-ASSOCIATED DISEASES Secondary disease associations result either from “mechanical” or “endocrine” effects of excessive white adipose tissue (WAT) deposition.

Answer 63

“Mechanical” effects of excess adipose tissue deposition include excessive weight bearing on joints and bones (exacerbating orthopedic diseases), constriction of collapsible structures (exacerbation of upper respiratory tract disorders and urinary incontinence), inability to groom, and reduced heat dissipation due to the insulating effect of fat (exacerbating heat stroke). Disturbance of normal endocrine function of WAT is also recognized as a major pathogenetic mechanism in obesity. WAT is now known to secrete a range of “chemical” factors that can have a regulatory effect on many body systems.[23-25] Of particular note is the range of cytokines, chemokines, and other inflammation-related proteins (collectively termed adipokines) secreted by WAT as tissue mass rises.

Answer 64

Indeed, obesity is characterized by a state of chronic mild inflammation. Increases in the production certain “inflammatory” adipokines (e.g., leptin, tumor necrosis factor-α, interleukin-6, plasminogen activator inhibitor-1, and haptoglobin) have been causally linked to the development of the metabolic syndrome and other disorders linked to the obese state. Inflammatory adipokine gene expression has recently been documented in canine WAT samples. Further, plasma leptin concentrations have been shown to be independently associated with insulin sensitivity in lean and overweight cats,[28] suggesting that similar pathogenetic mechanisms may exist in companion animals.

Answer 65

Orthopedic disease in dogs, Diabetes mellitus in both species.

Answer 66

In humans, tissues become “insulin resistant” with excessive caloric intake, and plasma concentrations of insulin increase in direct proportion to increasing body mass index (BMI) in both men and women. Thus, obesity, particularly abdominal obesity, is a major determinant of insulin resistance and hyperinsulinemia. A percentage of cats with diabetes mellitus have a form of the disease resembling non–insulin dependent type 2 diabetes of humans. Obesity is a major risk factor for diabetes in cats. Further, weight loss can resolve insulin resistance and clinical signs of diabetes in some cats.

Answer 67

An association between obesity and canine diabetes mellitus has been reported. In one study, diabetic dogs were ∼2.5 times more likely to be overweight (at the time of diagnosis) than controls, and almost 4 times as likely to have been overweight throughout life. The exact pathogenetic mechanisms underlying this association are unclear but, given that the most common type of canine diabetes resembles human type 1 (insulin dependent), mechanisms are likely to differ from those in humans and cats. Nonetheless, research does suggest that insulin resistance can develop in overweight dogs. However, given that cases of canine diabetes mellitus usually require lifelong insulin therapy, weight management strategies do not lead to resolution of diabetes mellitus. In humans, metabolic syndrome is a group of risk factors associated with both insulin resistance and cardiovascular disease and thrombosis. Some of these criteria have been applied to dogs, and this species is often used as a model of metabolic syndrome.

Answer 68

Dietary Management It is preferable to use purpose-formulated diets to achieve weight loss. Such diets are restricted in fat and calories while supplemented with protein and micronutrients. The mean energy requirement for weight loss in dogs is 60% of required calories at target weight. Cats should be fed an average of 32 kcal/kg of target body weight during weight loss. With these restrictions, the mean rate of weight loss is 0.8% body weight/week for both species. Close monitoring is required and energy intake must progressively be reduced to ensure continued weight loss. Using a high-protein diet is important since such diets minimize loss of lean tissue, although weight loss is not more rapid. Supplementation of micronutrients ensures that deficiency states do not arise.

Answer 69

Pharmaceutical Therapy and Weight Loss Two pharmaceutical products have recently been licensed for use in dogs, but NOT in cats. Both are MTP inhibitors, which have a local effect at the level of the intestinal epithelial cell, blocking the assembly and release of lipoprotein particles into the bloodstream.

Answer 70

A standard definition for cachexia is difficult to provide. In clinical practice, cachexia is the term used to describe the weight loss, loss of muscle, and anorexia that accompany many chronic disease conditions. However, it is important to recognize that cachexia is not simply caused by inadequate nutrient intake and that cachexia and starvation are not equivalent physiologic processes.

Answer 71

Two biochemical features distinguish malnutrition caused by cachexia from that caused by starvation. First, unlike starvation, inflammation is a consistent feature of cachexia. Second, cachexia is associated with a rise in resting energy expenditure.

Answer 72

Cachexia causes marked activation of the inflammatory cascade, which is characterized by a pronounced acute phase inflammatory response and excessive production of proinflammatory cytokines such as interleukins (IL-1 and IL-6, among others) and tumor necrosis factor-alpha (TNF-α). Cytokines stimulate the ubiquitin pathway, which is a central pathway in protein turnover. Ubiquitin complexes with target cellular proteins and stimulates their metabolism via the proteasome system.

Answer 73

Second, cachexia is associated with a rise in resting energy expenditure, which increases as a consequence of altered protein, fat, and carbohydrate metabolism. Loss of body muscle and adipose tissues is marked and an insulin-resistant state may develop. Despite the similar clinical appearance, activation of the ubiquitin-proteasome system and increased energy expenditure are not features of starvation.

Answer 74

A diagnosis of cachexia should be considered for any dog or cat with marked weight loss, severe muscle loss, and decreased appetite in the setting of a chronic inflammatory response or cancer. By this definition, cachexia is not a specific diagnosis but a state of disordered metabolism that can be caused by a variety of diseases. When evaluating an emaciated dog or cat, it is important to determine, from diagnostic and therapeutic standpoints, whether the condition has developed as a result of inadequate nutrient intake (maldigestion, malabsorption, or underfeeding, for example) or represents true cachexia

Answer 75

PHYSICAL AND LABORATORY FINDINGS Laboratory findings are not specific for cachexia.

Answer 76

Growth is a complex process that results in an increase in size of an individual. In dogs and cats, growth primarily occurs during the first 6 to 24 months of life.

Answer 77

Genetic, hormonal, metabolic, and nutritional factors influence growth. To meet its full genetic potential, an animal must have growth hormone (somatotropin) to stimulate insulin-like growth factor-I (IGF-I) production, which in turn stimulates skeletal growth, protein synthesis, and cell proliferation.

Answer 78

Full IGF-I activity requires the presence of thyroid hormone. The animal must also consume sufficient calories and nutrients; digest, absorb and retain the nutrients; transport the nutrients to the necessary tissues; and be able to use the nutrients for metabolic maintenance and growth. A defect in any of the previously mentioned processes can disrupt, delay, or stop normal growth (Box 29-1;

Answer 79

Genetic Abnormalities of Bone Growth An inherited endochondral ossification defect in chondrodystrophic animals results in angular limb deformities and subnormal height.

Answer 80

Deficient Nutrient Intake Gastrointestinal parasitism, resulting in a “relative” deficiency in nutrition, is the most common cause of retarded growth in puppies and kittens. Growth retardation due to parasitism is potentially reversible with proper therapy.

Answer 81

Oral disease may cause pseudoanorexia. Regurgitation or vomiting because of esophageal or gastric disorders could cause insufficient food to reach the intestines for digestion and absorption. Maldigestion or malabsorption can result in decreased uptake of nutrients. Renal, hepatic, cardiac, inflammatory, and hypoadrenal disease can suppress the appetite. Absorption and transport of nutrients from the intestines to other tissues can also be inadequate with cardiac disease.

Answer 82

Fever can result in excess caloric loss as body heat. In diabetes mellitus, glucose is lost in the urine. However, in diabetes mellitus, it is the inability to utilize calories that leads to failure to grow or weight loss, rather than the loss of calories into the urine. Proteins and salts can also be lost in the urine in animals with glomerular and renal tubular disease, respectively. Several intestinal disorders can result in protein-losing enteropathy. As previously noted, parasitism is the most common cause of “lost” nutrients.

Answer 83

Abnormal Metabolism Carbohydrate metabolism can be altered in inflammatory disease, renal disease, and hepatic disease. Protein production can also be decreased with hepatic disease.

Answer 84

Hypothalamic or pituitary aplasia or neoplasia (e.g., craniopharyngioma) can result in low growth hormone and IGF-I concentrations.

Answer 85

Hypothyroidism can decrease the activity of growth hormone.

Answer 86

Because insulin has a positive effect on IGF-I production, insulin deficiency caused by diabetes mellitus or malnutrition can slow growth.

Answer 87

Cortisol excess, whether endogenous or exogenous in origin, can inhibit the secretion of growth hormone, which in turn causes failure to grow.

Answer 88

An extremely rare form of juvenile hyperparathyroidism in German Shepherd Dogs has also been reported to cause stunted growth.

Answer 89

Diet If the animal is always hungry and internal parasites have been ruled out or treated, underfeeding (because of inadequate owner knowledge of the pet's nutritional needs), a disorder causing a “relative” lack of calories (e.g., exocrine pancreatic insufficiency), or an increased nutrient loss (e.g., diabetes mellitus, renal disease, intestinal disease) should be considered.

Answer 90

Chondrodysplastic animals and many animals with congenital hypothyroidism will also have an abnormal skeletal conformation (e.g., angular limb deformities). Symmetrical truncal alopecia, the prolonged presence of a soft puppy haircoat, or thin, scaly skin suggests thyroid hormone deficiency, growth hormone deficiency, or cortisol excess. Mental dullness can be seen with hypothyroidism or hepatic encephalopathy. Hepatic failure can also result in cortical blindness.

Answer 91

The number and type of joints involved may help the clinician differentiate septic from nonseptic arthritis. Single joint involvement and involvement of proximal joints (hip, shoulder, stifle, and elbow) are usually septic. Multiple, distal joint (carpi, tarsi) involvement is most commonly seen immune-mediated disease. When a septic process is possible, a period of antimicrobial therapy can be recommended, even if no bacteria are observed on joint fluid cytology and joint fluid cultures are pending or negative.

Answer 92

IMMUNE-MEDIATED POLYARTHRITIS Immune-mediated polyarthritis is the most common polyarthritis in companion dogs and cats. The cause of this condition is likely a type III hypersensitivity reaction, in which immune complexes are deposited in the synovial membrane and an inflammatory cascade is initiated. The immune stimulus is frequently unknown, hence the commonly used term idiopathic polyarthritis. Immune-mediated polyarthritis can be categorized both radiographically and histologically into the common nonerosive form and the uncommon erosive condition.

Answer 93

EROSIVE POLYARTHRITIS Erosive polyarthritis in dogs is similar to human rheumatoid arthritis. These similarities include the progressive, severe, deforming course of the disease and the erosive radiographic appearance of affected joints. In humans, specific antibodies, collectively known as rheumatoid factor (RF), are commonly identified. An IgM antibody, considered the canine RF, has been identified in some dogs with erosive arthritis. Although the term rheumatoid arthritis has been used in veterinary medicine, it is preferable to use the descriptive term erosive arthritis in dogs.

Answer 94

Erosive polyarthritis has been reported in cats and has been termed progressive feline polyarthritis. This is a disease that occurs more commonly in male cats between 1.5 and 5 years of age. It may be an immune-mediated hypersensitivity type III reaction to chronic viral immune stimulation, secondary to chronic feline syncytium-forming virus infection. Two forms of the disease exist: (1) the deforming type, a severely erosive condition that is similar to canine erosive arthritis (2) the more common proliferative form. Both forms can be associated with severe systemic signs of disease, including lymphadenopathy, swollen joints, and muscle wasting.

Answer 95

Secondary to: Chronic infectious disease, systemic lupus erythematosus (SLE), lymphocytic plasmacytic synovitis, use of certain drugs, and malignancies. It may also be a component of immune-mediated diseases, such as inflammatory bowel disease or chronic hepatitis.

Answer 96

Clinical signs typically include cyclic fever, lethargy, anorexia, and varying degrees of pain, lameness, and swollen joints. A stiff gait characterized as walking on egg shells is frequently observed, but some affected dogs have a normal gait. The distal joints (carpi and tarsi) are most commonly affected. Pain, redness, and swelling range from severe to absent. Some dogs exhibit pain that is difficult to localize. Others have signs of back or neck pain. This could be a result of inflammation of the vertebral articulations or concurrent meningitis. Lymphadenopathy and muscle wasting can be profound.

Answer 97

Nonerosive polyarthritis can be seen in any breed at any age but most commonly occurs in young dogs (between 1 and 6 years of age). The condition appears to be overrepresented in German Shepherd Dogs, Doberman Pinschers, Collies, Spaniels, Retrievers, Terriers, and Poodles. Specific syndromes involving immune-mediated polyarthritis have been identified in certain breeds of dogs, such as swollen hock syndrome in Shar-Peis and arthritis in Akitas.

Answer 98

Infectious disease can cause a secondary immune-mediated polyarthritis as a result of chronic immune stimulation inducing immune complex deposition in the synovial tissue. Diseases frequently associated with secondary immune-mediated polyarthritis include heartworm disease, canine ehrlichiosis, anaplasmosis (caused by Anaplasma phagocytophilum, previously known as Ehrlichia equi) Rocky Mountain spotted fever, Lyme disease, and others. Chronic bacterial infections such as discospondylitis, pyelonephritis, prostatitis, and endocarditis can also cause a secondary immune-mediated polyarthritis.

Answer 99

immune-mediated hemolytic anemia, thrombocytopenia, glomerulonephritis, or immune-mediated dermatopathies. The value of antinuclear antibody (ANAs) testing is controversial. This syndrome is thought to occur more commonly in females and in German Shepherd Dogs, Collies, Shetland Sheepdogs, Beagles, and Poodles.

Answer 100

Lymphocytic-plasmacytic synovitis has been reported most commonly in German Shepherd Dogs and other large-breed dogs. This condition is thought to be associated with degenerative joint disease, such as arthritis in the stifle joint after rupture of the cranial cruciate ligament. The diagnosis can be confirmed with histologic evaluation of the synovium.

Answer 101

Drug-induced immune-mediated polyarthritis appears to be rare. It has been reported to occur as a result of trimethoprim-sulfadiazine therapy in a group of Doberman Pinschers. Immune-mediated polyarthritis has been suspected in some cases after vaccinations (e.g., vaccinations for Lyme disease). Inflammatory joint disease (septic or immune mediated) should be suspected in the following instances (Figure 30-1):

Answer 102

PATHOPHYSIOLOGY Skin odor is the result of bacterial decomposition of secretions from sebaceous glands, epidermal lipids, and epitrichial and atrichial sweat glands. Epitrichial glands are present on haired skin just below sebaceous glands and open onto the surface via the piliary canal. These glands are largest and most numerous in mucocutaneous junctions, interdigital spaces, and over the dorsal back and lumbosacral areas. Not surprisingly this is often where odor concentrates in pets. Atrichial glands are located only on footpads.

Answer 103

Sweat contains unsaturated fatty acids, ammonia constituents, and their volatile salts.

Answer 104

Sebum and epidermal lipids on the skin surface are degraded by lipases of gram-positive bacteria to glycerol and unsaturated fatty acids, which are further metabolized to odorous compounds. It is these byproducts that give sebum its antibacterial and antifungal properties. Some of the acids produced by the degradation of these lipids, butyric and caproic acids, are quite volatile and emit a cheesy, rancid odor.

Answer 105

Oral odor may be associated with systemic illnesses, such as uremia, diabetes mellitus, or periodontal disease. Malodor associated with periodontal disease is due to the production of volatile sulfur components. Oral odors are most often the result of byproducts of bacterial metabolism resulting from bacteria colonization of plaque, gingival sulci, and the dorsal surface of the posterior tongue. Oral odors may also be the result of something the pet has ingested (e.g., fecal material).

Answer 106

In a dog or cat with generalized lymphadenopathy, the conjunctiva, third eyelid gland, and uveal tract should be closely examined because they also contain lymphoid tissue or cells. Likewise, a thorough general physical examination of the pet with retinal disease may reveal more widespread vascular, neurologic, or hematologic disease.

Answer 107

Eyelid margins represent a clearly visible mucocutaneous junction that could be involved in primary immune-mediated dermatitis such as the pemphigoid diseases or systemic lupus erythematosus (SLE). Altered lid position, with or without altered pupil size or globe deviation, can also represent central, peripheral, or disseminated neurologic disease, specifically dysfunction of cranial nerve (CN) III or VII or decreased sympathetic tone (Horner's syndrome).

Answer 108

Clinical localization of the lesion or lesions is important, particularly for Horner's syndrome—the triad of enophthalmos (with protrusion of the third eyelid), ptosis, and miosis.

Answer 109

Because of the circuitous, three-neuron route by which sympathetic neurons course from the hypothalamus to the eye, Horner's syndrome can result from disease involving the brain, spinal cord, brachial plexus, thorax and mediastinum, neck, temporal bone and tympanic bulla, or orbit. Diagnostic procedures should be directed at each specific area to eliminate definitive causes. However, even with intensive diagnostic testing, approximately 50% of cases of Horner's syndrome are idiopathic and usually resolve within 2 months.

Answer 110

Conjunctival disease is seen alone, with blepharitis or keratitis, or may reflect inflammation of deeper structures such as the sclera, meibomian glands, orbital contents, third eyelid gland, or intraocular tissues. The rich vascularity of conjunctiva and its almost transparent epithelium also make it an excellent site for detection of hematologic (cyanosis, anemia, icterus) or vascular disease.

Answer 111

Feline herpesvirus (FHV-1) and Chlamydophila felis (formerly Chlamydia psittaci) are primary conjunctival pathogens of cats. Although cats undergoing primary FHV-1 exposure generally demonstrate concurrent signs of upper-respiratory infection, cats infected with C. felis and those undergoing a recrudescent FHV-1 episode may demonstrate few or mild nonocular clinical signs. Despite an apparent lack of systemic signs, recent evidence confirms that cats harbor and shed C. felis from nonocular sites. Studies also suggest that systemic therapy is more effective than topical therapy at decreasing clinical signs and shedding of C. felis.

Answer 112

Conjunctivitis in dogs is usually not associated with systemic disease. Ligneous conjunctivitis is an uncommon but important exception. This is a chronic, membranous conjunctivitis in which gross thickening of conjunctiva occurs bilaterally. Younger, female Doberman Pinschers may be predisposed. Other mucous membranes may also be involved, and the majority of affected dogs also have evidence of upper-respiratory or urinary tract disease. Histology reveals a characteristic amorphous, eosinophilic hyaline material throughout the subconjunctiva.

Answer 113

Cornea and Sclera Corneal clarity is important for normal vision. Although altered corneal appearance may represent primary keratitis or intraocular disease (particularly uveitis or glaucoma), corneal opacification that begins at or is most notable at the limbus is often an indicator of systemic disease.

Answer 114

For example, lymphosarcoma (LSA) tends to cause a homogenous, creamy-pink discoloration of the peripheral corneal stroma. Corneal lipidosis is an important differential diagnosis in these cases and may occur secondary to any disease causing systemic hyperlipidemia. Hypothyroidism is one of the most common causes; however, hyperadrenocorticism, diabetes mellitus, and familial hypertriglyceridemia should also be considered. Serum triglycerides and cholesterol should both be assessed in animals with corneal lipidosis. Rarely, corneal opacification in dogs or cats will be caused by mucopolysaccharidosis.

Answer 115

Although hyperadrenocorticism and diabetes mellitus are associated with prolonged corneal wound healing, dogs with diabetes mellitus have also recently been shown to have significantly decreased corneal sensitivity relative to normal dogs. This may represent a manifestation of diabetic neuropathy, making dogs less likely to blink and produce reflex tears to protect their corneas. In addition, multiple growth factors are transferred to the cornea by sensory nerves, and these are likely to be reduced in such dogs. This likely contributes to the poor wound healing observed in these pets. Therefore therapy and monitoring of corneal disease, especially ulceration, should be more intense in diabetic dogs.

Answer 116

Keratoconjunctivitis Sicca Decreased aqueous tear production with subsequent keratoconjunctivitis sicca (KCS) is common in dogs but uncommon in cats. In dogs it is usually caused by idiopathic lymphocytic-plasmacytic dacryoadenitis. Rarely, cats or dogs with KCS have immune-mediated destruction of the salivary glands and associated xerostomia (Sjögren's-like syndrome), sometimes clinically apparent as dysphagia.

Answer 117

KCS in association with xeromycteria (dry nose) should prompt investigation of neurogenic KCS caused by damage to afferent or efferent pathways of lacrimal innervation. Lacrimal stimuli are transmitted by CN V, and efferent (parasympathetic) fibers are carried first by CN VII and peripherally by CN V. Because these same neural pathways are involved in the production of moisture for the nasal mucosa, ipsilateral xeromycteria evidenced by a dry, crusty nostril may be seen. Diagnostic efforts should be directed at disease processes along the paths of CN V and VII, particularly in the region of the tympanic bullae.

Answer 118

KCS may also occur as a result of drug therapy. Drugs incriminated in decreased tear production include systemically or topically administered atropine, systemically administered sulfa drugs, etodolac, and general anesthesia within the preceding 2 days. Dogs with marginal tear production before administration of these drugs, and those weighing less than 12 kg (in the case of trimethoprim sulfa), appear to be at increased risk of developing KCS. Dose and duration of therapy are less relevant. Restoration of tear production and corneoconjunctival health does not always occur upon discontinuation of the offending drug; therefore Schirmer tear test (STT) results should be monitored before and during therapy.

Answer 119

Finally, KCS may occur as a component of systemic disease but may be overlooked unless a STT test is performed. Systemic infection with canine distemper virus (CDV) is associated with usually transient KCS, while cats undergoing primary infection with FHV-1 may experience transient KCS followed by a period of decreased tear mucin production and associated tear film instability for over 1 month following infection. Dysautonomia (Key-Gaskell syndrome) can cause bilateral reduced aqueous tear secretion, nonresponsive dilated pupils, and protrusion of the third eyelids. Associated systemic signs of autonomic dysfunction, including urinary and fecal incontinence, bradycardia, hypotension, dysphagia, and dry nose are usually more noticeable than the ocular signs; however, ocular signs may help to confirm the diagnosis. Although an association between low STT values and hyperadrenocorticism, diabetes mellitus, or hypothyroidism has been shown in dogs, no association between endocrinopathies and KCS has been proven.

Answer 120

UVEAL TRACT Uveal pathology is commonly seen with systemic disease. The uveal tract includes the iris, ciliary body, and choroid and is the major vascular supply for the avascular components of the eye (cornea, lens, outer retina). It is composed of a large network of arterioles, venules, and fine capillaries and therefore is a sensitive indicator of vascular or hematologic conditions such as vasculitis, hypertension, anemia, and hyperviscosity (see Fundus).

Answer 121

Loss of vascular integrity may be apparent in the anterior chamber as breakdown of the blood-aqueous barrier. This appears differently, based on the extent of breakdown and the presence or absence of inflammatory mediators within the anterior chamber and surrounding tissues. With minimal breakdown, albumin and other small serum proteins are detectable in the anterior chamber as aqueous flare. The aqueous humor may be thought of as a directly visible area of interstitial space, and if serum contents are seen within this space, the possibility of similar plasma “leakage” in other, less visible nonocular interstices should also be considered.

Answer 122

Cellular debris (hyphema, dispersed white blood cells [WBCs], or hypopyon) or larger proteins, particularly fibrin in the anterior chamber, suggests more major vascular compromise or potent, cytokine-mediated extravasation of cells. These blood constituents are more likely to settle into the ventral anterior chamber. Depressing the pet's nose so that the eyes are elevated within the orbits will often assist in seeing this region.

Answer 123

Fine uveal capillary beds can act as a biologic “filter” that traps organisms, particularly fungi, or metastatic neoplastic cells. It is frequently involved in systemic infectious disease or as a site of metastatic neoplasia. The uvea also contains the major aggregations of lymphoid cells and is therefore a common site for LSA. It is also frequently involved in specific or nonspecific ocular inflammatory responses (uveitis) that may reflect broader immunopathology such as infectious or neoplastic disease.

Answer 124

Feline infectious peritonitis (FIP), feline immunodeficiency virus (FIV) (principally a retinochoroiditis), feline leukemia virus (FeLV) (principally via LSA), Toxoplasma gondii, mycobacteria, and the systemic mycoses (principally a chorioretinitis) have traditionally been associated with uveitis. More recently, intraocular detection of other organisms such as FHV-1, Bartonella spp., and some Ehrlichia spp. has led to suggestions that these organisms also warrant consideration as causative agents in feline uveitis. Despite this expanding list of differential diagnoses and thorough diagnostic testing (sometimes including enucleation and histopathology), a definitive cause of uveitis is not identified in 50% to 70% of affected cats.

Answer 125

Fungal organisms, Leishmania donovani, Ehrlichia platys or canis, Rickettsia rickettsii, Brucella canis, Toxoplasma gondii, canine adenovirus, and Leptospira spp. In addition, dogs appear to be more susceptible to immune-mediated uveitis than cats.

Answer 126

(Figure 32-1).

Answer 127

Finally, the iris (anterior uvea) forms the pupil and therefore often provides clinical evidence of neurologic disease. Pupillary abnormalities suggestive of systemic disease include feline “spastic pupil syndrome” in which intermittent periods of anisocoria are seen without obvious iridal or afferent neurologic defects. Most cats are FeLV-positive or become so soon after diagnosis but may not have other systemic signs of infection when pupil abnormalities are noted. Virally induced pathology of CN III is suspected.

Answer 128

Pupilomotor abnormalities with normal vision and without ocular inflammation are also seen with dysautonomia (mydriasis) and Horner's syndrome (miosis).

Answer 129

LENS The two most common conditions affecting the lens are cataract and lens dislocation (subluxation or luxation). Lens dislocation usually occurs secondary to severe intraocular disease, particularly uveitis, which may be a sign of systemic disease. Although lens dislocation may also occur as a primary event in predisposed dog breeds such as Terriers, these pets do not have evidence of the generalized connective tissue disorders seen in some humans.

Answer 130

Although the majority of canine cataracts are hereditary in origin, almost all dogs with diabetes mellitus will develop cataracts within 12 months of diagnosis. By contrast, the most common cause of feline cataracts is uveitis. Cats with diabetes rarely develop cataracts. Other systemic causes of cataracts include altered nutrition (especially orphan animals raised on milk replacement products), hypocalcemia with or without hyperphosphatemia (as seen with hypoparathyroidism), electric shock, lightning strike, and senility.

Answer 131

FUNDUS The ocular fundus is not a single structure. Rather, it is a collective term describing all structures in the posterior portion of the globe that can be viewed with the ophthalmoscope. Visible structures will vary but may include retinal pigment epithelium (if pigmented), neurosensory retina, optic nerve head, retinal vasculature, sclera, tapetum, or choroid. The fundic examination therefore provides a unique opportunity to directly visualize a large cranial nerve (optic nerve), sensitive neural tissue (retina), large venules and arterioles (retinal vessels), and a massive capillary bed (choroid). For this reason, a fundic examination should be performed in all animals with systemic disease. The choroid is perhaps the fundic tissue most commonly affected in animals with systemic disease. Because of its position immediately subjacent to the retina and its critical role in retinal nutrition and function, signs of choroidal disease are frequently first noted once they affect the retina. The classic example is retinal detachment, which may be caused by primary retinal disease but frequently reflects choroidal effusion. As a result of these close anatomic and physiologic relationships, the terms chorioretinitis and retinochoroiditis are used to reflect inflammation of these two tissues. The difference between these two terms is subtle, with the intent that the first-mentioned tissue is the one believed to be primarily involved. For example, the systemic mycoses have a predilection for the choroid and so cause a marked chorioretinitis. By contrast, CDV targets neurologic tissue in general and, within the eye, retinal tissue specifically. Insults to the subjacent choroid usually also occur, and the disease is typically referred to as a retinochoroiditis.

Answer 132

Optic Nerve and Retina Although primary dysfunction of the optic nerve or retina occurs, altered appearance of these tissues often represents disease of the adjacent central nervous system (CNS) or subjacent choroid (see Uveal Tract). Optic neuritis and retinitis may therefore reflect more widespread meningoencephalitis or uveitis. Causes include infectious agents (CDV, systemic mycoses, or Toxoplasma gondii), immune-mediated diseases such as granulomatous meningoencephalitis, or neoplasia involving the CNS, meninges, orbit, or choroid. Diagnosis frequently involves cerebrospinal fluid (CSF) analysis and cross-sectional imaging. Optic nerve edema without hemorrhage, exudates, or blindness is termed papilledema and is seen in association with increased intracranial pressure. Therefore fundic examination is recommended in all animals suspected of having CNS disease, especially when a CSF tap is planned.

Answer 133

Taurine deficiency in cats has been associated with retinal degeneration. Affected cats should also be screened for dilated cardiomyopathy. This syndrome is sometimes called feline central retinal degeneration (FCRD) because abnormal dietary or tissue taurine concentration is not always established.

Answer 134

Sudden acquired retinal degeneration (SARD) describes a rapid onset of complete blindness in middle-aged to older dogs with initially normal fundic examination findings. Generalized retinal degeneration becomes clinically evident within 4 to 6 weeks of blindness. Complete and irreversible loss of photoreceptor function takes place without any clinically or histologically detectable inflammation. Female dogs appear overrepresented and many are moderately overweight. Many have a history suggestive of hyperadrenocorticism and some may have clinical signs, blood work, or both that support the diagnosis. The cause of the apparent hyperadrenocorticism is unknown, but unlike the vision loss, systemic signs typically resolve without treatment. This disease must be differentiated from blindness as the result of optic nerve or CNS disease (particularly a functional pituitary tumor with blindness secondary to pressure effects at the optic chiasm).

Answer 135

Vascular and Hematologic Disease Direct visualization of retinal (and sometimes choroidal) blood vessels permits assessment of many hematologic abnormalities, including anemia (where obvious attenuation or paleness of vessels exists), hyperlipidemia (where retinal vessels take on a creamy orange hue), and hyperviscosity (where increased vessel tortuosity sometimes is noted).

Answer 136

Anemia, hyperviscosity, and systemic hypertension also alter tissue perfusion and vessel wall viability and can be associated with segmental vascular constriction and sacculations of retinal vessels (so-called box-carring), “sludging,” and extravasation of blood or plasma into the choroid, retina, and subretinal space. This is clinically apparent as intraretinal or subretinal edema or hemorrhage or as retinal detachment. Some hypertensive cats also have iridal aneurysms and hyphema.

Answer 137

A recent retrospective study of hypertensive cats established that concurrent chronic renal failure, hyperthyroidism, diabetes mellitus, hyperaldosteronism, and cardiac or neurologic abnormalities were common; however, the majority of cats with systemic hypertension are brought to veterinarians after owners observe apparent vision loss.

Answer 138

Vision loss is seldom truly acute; more commonly it is a sudden recognition of blindness in the patient as perceived by the owner.

Answer 139

Characterization of blindness will assist in lesion localization. For example, a patient with night blindness (nyctalopia) but good day vision would indicate retinal atrophy, or a patient with poor day vision (hemeralopia) but good night vision may indicate that the patient has cataracts. Amaurosis defines blindness with no cause. Mechanical blindness (exophthalmia, facial nerve paralysis, elevated third eyelid [Horner's syndrome]) will give the examiner an area of focus when deciphering the clinical findings.

Answer 140

Evaluation of motion detection in animals is done by tossing an object (cotton balls) across the animal's field of view and monitoring the response. Creating an obstacle course in an exam room allows the examiner to determine if the patient can navigate an unknown environment.

Answer 141

The normal response to a menace response test is avoidance such as moving the head away from the object or blinking the eyes. This response is a learned behavior and is therefore typically absent in puppies and kittens under 12 weeks of age. A palpebral reflex (intact facial nerve CN VII) and eyelid function should be elicited and present prior to evaluating a menace response. Severe buphthalmia, exophthalmia, or blepharospasm will prevent blinking and obtaining a menace response.

Answer 142

An intact menace response requires an intact visual cortex, whereas a dazzle reflex and corneal reflex are strictly subcortical responses. Dazzle reflex is mediated by reflex centers in the rostral colliculi and can evaluate optic nerve function while not stimulating the trigeminal nerve.

Answer 143

Visual Placing and Postural Reactions This test is performed by holding the animal cradled in a horizontal position with its front legs free to move and then moving the patient toward the edge of the tabletop. A visual patient will respond by lifting the legs before touching the table. A blind patient will move the legs after the legs touch the tabletop. Stairs can be used to perform this test on dogs too large to hold.

Answer 144

Pupillary Light Reflexes Pupillary light reflexes (PLR) do not provide a test of vision but rather offer a starting point in lesion localization. Brachycephalic breeds such as Boston Terriers and Chinese Pugs can sometimes be more difficult to examine because of their lateral globe position.

Answer 145

Nervous patients may require a few minutes for the .................. nervous system response to lessen. Stimulation of the sympathetic nervous system causes mydriasis (pupil dilation), giving the examiner the illusion of absent or diminished PLR.

Answer 146

Prior to PLR testing always ensure the pupils are of equal size in both bright and dim light. Unequal pupil size (anisocoria) is commonly pathologic in small animal.

Answer 147

The PLR pathway requires normal optic nerve function, optic chiasm, optic tracts, pretectal and accessory oculomotor nuclei (Edinger-Westphal), oculomotor nerves (parasympathetic portion), and functional iridal muscles. The retinas too are required for the PLR pathway. Marked retinal pathology may be present while still maintaining a diminished to normal PLR. Iris atrophy and opacification of the cornea, anterior chamber, or lens are additional complications that can diminish the PLR or prevent observation of the pupil. In this situation the lesion may or may not be localized to the globe.

Answer 148

Tissue, fluid, gas, feces, or abdominal musculature weakness (Table 34-1 and Figure 34-1).[1]

Answer 149

Ascites is defined as an accumulation of serous fluid in the peritoneal cavity and is usually reserved for a transudate that is associated with liver or right heart failure.

Answer 150

Pure transudates, modified transudates, nonseptic exudate, septic exudate, hemorrhagic effusion, bilious effusion, chylous effusion, pseudochylous effusion

Answer 151

Pure transudates are defined as having <1.017.

Answer 152

Decreases in oncotic pressure. 1. Hypoalbuminemia (from protein-losing nephropathy, Protein-losing enteropathy, Liver failure, burn wounds, or from repeated removal of peritoneal or pleural fluid) 2. Increased hydrostatic pressure (portal hypertension, Budd-Chiari syndrome, or right heart failure) 3. Increased permeability of the vasculature (vasculitis). (Rare cases)

Answer 153

Modified transudates are defined as having >1000 but 1.017 and <1.025. Modified transudates is a catchall between pure transudates and exudates and therefore has a multitude of different cells that can be present.

Answer 154

1. Increases in hydrostatic pressure and vasculitis as previously described with pure transudates, 2. neoplasia, granulomas, 3. postsurgery or postlaparoscopy, 4. splenic or intestinal torsions 5. infarctions.

Answer 155

Exudates are defined as having >5000 cells, >3.0 total solids and >1.025 specific gravity. The cellular component of exudates is chiefly made up of neutrophils and macrophages.

Answer 156

1. Perforation of bowel, 2. neoplasia, 3. pancreatitis, 4. recent surgery, 5. bile duct or gallbladder rupture, urinary tract rupture (bladder, urethral or ureteral), 6. Feline infectious peritonitis

Answer 157

Hemorrhagic effusions are defined as having >1000 cells, >3.0 total solids and >1.025 specific gravity. The effusion should closely resemble the peripheral blood with red blood cells and some white blood cells such as neutrophils and lymphocytes. The only exception is platelets, which are usually not present unless the bleed occurred in the hour previous to diagnosis. The samples rarely are able to coagulate due to the lack of platelets.

Answer 158

1. Coagulopathies, 2. fracture of the liver or spleen, 3. neoplasia, 4. avulsion of renal arteries, 5. iatrogenic such as in postoperative patients.

Answer 159

Chylous abdominal effusions have variable cell counts, >2.5 total solids, and >1.018 specific gravity. The predominant cell early on is the lymphocyte but can become the neutrophil secondary to inflammation as the effusion becomes more chronic. The effusion triglyceride level is usually 2 to 3 times greater than the serum triglyceride with the effusion cholesterol being less than the serum cholesterol.

Answer 160

1. Lymphangiectasia, 2. Strangulation or rupture of the lymph vessels by neoplasia, right heart failure, or lymphoproliferative diseases including the mesenteric lymph nodes.

Answer 161

Pseudochylous effusion is rare and usually has high cholesterol and low triglyceride concentrations as compared with serum.

Answer 162

Bilious effusions are similar to exudates but contain bilirubin crystals. Bilirubin concentrations in the effusion are higher than in serum. The principle cell involved is the neutrophil, which may contain some bile pigments.

Answer 163

Rupture of the bile duct or gallbladder. This happens secondary to trauma, cholelithiasis, pancreatitis, or necrotizing cholecystitis.

Answer 164

Malignant effusions are often a subtype of modified transudates or exudates that contain neoplastic cells. Care should be taken in interpreting malignancy on cytology due to normal mesothelial cells displaying criteria that could be mistaken for neoplasia. Review by pathologist is essential.

Answer 165

Eosinophilic effusions present as modified transudates or exudates with greater than 10% eosinophils. These effusions are often caused by lymphoma, systemic mast cell tumors, aberrant larval migrans, fungal disease, or disseminated eosinophilic granulomatosis.

Answer 166

Peritonitis is defined as inflammation of the peritoneum. Primary peritonitis is inflammation of the peritoneum without any preexisting abdominal pathology (e.g., feline infectious peritonitis). Secondary peritonitis is the predominant form and occurs in conjunction with abdominal pathology (e.g., perforation of gastrointestinal tract).

Answer 167

Secondary peritonitis can be further divided into septic and nonseptic. This determination is most easily made by culture of the peritoneal effusion (most often an exudate). A positive culture is the definitive diagnosis for septic exudate and should be performed in all cases of exudates.

Answer 168

A glucose level can be taken of the effusion by way of a handheld glucometer and compared to blood glucose. If the blood glucose is 20 mg/dL higher than the peritoneal effusion, sepsis is highly likely. This is because the bacteria metabolize glucose present in the effusion. Some malignant effusions can also have a similar decrease in glucose because malignant cells utilize the glucose. Another method for determination of septic effusions is to compare the blood/effusion levels of lactate. If peritoneal effusion is >2.5 mmol/L and higher than the blood lactate, a septic effusion is likely in the dog. This measurement of the lactate is not useful in cats.

Answer 169

In early cases of peritonitis peritoneal effusion may not be present. In these cases a diagnostic peritoneal lavage may be needed. This is rarely the case: within 2 to 3 hours after contamination of the abdomen with gastrointestinal, chylous, bilious, hemorrhagic, pancreatic, or urinary leakage, there is a significant amount of fluid and leukocytes present.

Answer 170

Care should be taken to not drain the abdomen too often or without cause as electrolyte disturbances, hypoalbuminemia, infection and bleeding are just some of the complications that can ensue.

Answer 171

As impaired organ function secondary to increased intraabdominal pressure.

Answer 172

Intraabdominal pressure should be monitored by way of a urinary Foley catheter and monometer centered at the umbilicus of the recumbent patient. The bladder should be drained and 0.5 to 1 mL/kg of 0.9% sodium chloride should be infused prior to application of the manometer. Pressures should be monitored in the case of progressive abdominal distension, azotemia, elevated central venous pressures, evidence of increased intracranial pressure, tachypnea, and tachycardia in patients with recent abdominal surgery or peritoneal effusions. Normal pressures in the dog are 0 to 5 cm water. Pressures after surgery are 35, decompression of the abdomen is required.

Answer 173

Weakness is a common owner concern. In veterinary medicine, the terms fatigue and lethargy are often used synonymously with weakness. Fatigue is the inability to continue performing a task after multiple repetitions, whereas weakness means an inability to initially perform the task. Lethargy refers to a lower level of consciousness, drowsiness, stupor, or inactivity. The term asthenia defines a state of exhaustion in the absence of muscle weakness that can accompany many disease conditions including cardiovascular and metabolic disorders. In dogs and cats, it is usually impossible to distinguish between these states. For the purposes of this chapter the term weakness will be used interchangeably to include fatigue, lethargy, and asthenia.

Answer 174

Metabolic diseases are among the most common causes of weakness. Major organ dysfunction can result in weakness through many pathways, such as accumulation of metabolic products, cytokine production, electrolyte imbalances, acid-base disorders, anemia of chronic disease, and nutritional disturbances. Renal and hepatic failure are two examples of metabolic diseases that cause weakness by multiple mechanisms. Biochemical evaluation is essential in the diagnosis of metabolic disorders.

Answer 175

1. Excessive loss (gastrointestinal, urinary) or be 2. Iatrogenic in nature (fluid diuresis, diuretics).

Answer 176

Hypoadrenocorticism, Congestive heart failure, Liver diseases, Losses through the gastrointestinal system and third space.

Answer 177

Hyperaldosteronism, Salt poisoning Free-water loss.

Answer 178

Hypocalcemia produces excessive excitability of the nervous system, manifested as tetany and possibly seizures. Between bouts of tetany, dogs and cats typically appear weak.

Answer 179

Hypoparathyroidism, Renal disease Ethylene glycol toxicity Eclampsia.

Answer 180

Neoplasia, especially lymphoma Primary hyperparathyroidism Renal failure or toxicities (less common)

Answer 181

Hypomagnesemia, prevalent in critically ill pets because of renal and gastrointestinal losses coupled with decreased intake, may also result in weakness. Hypomagnesemia may be seen in conjunction with hypokalemia and/or hypocalcemia.

Answer 182

Disturbances in blood pH can accompany many metabolic conditions and can be seen with pulmonary disease. Drugs and toxins may also lead to acidosis or alkalosis. Weakness can be seen with either disorder. Significant alterations in bicarbonate on serum chemistry should raise suspicion for an acid-base disorder and may indicate additional diagnostic testing.

Answer 183

Inflammatory Conditions Inflammation accompanies many disease processes such as pancreatitis, hepatitis, neoplasia, infectious disease, and immune-mediated conditions. Systemic inflammation can result in pyrexia, negative energy balance, cytokine production, anemia, and acid-base disorders, all exacerbating signs of weakness. Many of these changes are mediated by increased cytokine production in response to the inflammatory stimuli. Certain cytokines, such as interleukin (IL)-1, IL-6, and interferon (IFN)-α, directly cause fatigue via central pathways. Cachexins, such as IL-1, IL-6, IFN-α, and tumor necrosis factor (TNF)-α suppress hunger, promote muscle wasting, and contributes to weakness. At high concentrations, TNF-α decreases myocardial contractility and vascular smooth muscle tone, resulting in systemic hypotension. Cytokine inhibition of erythropoiesis, resulting in anemia, indirectly contributes to weakness.

Answer 184

Infectious Diseases The infecting agent may produce toxins that cause weakness.

Answer 185

Immune-mediated diseases may lead to anemia, joint or muscle disease with resultant pain, hepatic or renal dysfunction, inflammation, and chronic wasting.

Answer 186

.....even if the magnitude of the anemia is greater in the chronic case. With chronic disease, the pet has time to adapt to the anemia, and clinical signs may be subtle.

Answer 187

Many endocrinopathies, such as hypoadrenocorticism, hypoparathyroidism, and hyperparathyroidism, and diabetes mellitus can produce weakness as the result of electrolyte abnormalities. Endocrinopathies may cause muscle atrophy, which develops secondary to alterations in protein and carbohydrate metabolism. Neuropathies and myopathies resulting in weakness may be seen with diabetes mellitus and hypoglycemia, as well as hyperadrenocorticism and hypothyroidism. Endocrinopathies can also cause pertubations in blood pressure.

Answer 188

Poor cardiac output leading to diminished oxygen delivery to the tissues Cardiac cachexia Arrhythmias Associated septicemia with bacterial endocarditis

Answer 189

Blood Pressure Alterations in blood pressure can produce weakness, often episodically. Hypotension can result from cardiac dysfunction, hypovolemia, or decreased vascular tone. Hypotension creates poor perfusion and oxygen delivery.

Answer 190

Systemic hypertension damages many organs, including the heart, brain, kidneys, and eyes. Systemic hypertension is usually a secondary problem in dogs and cats with underlying diseases including heart disease, renal disease, hyperthyroidism, hyperadrenocorticism, and diabetes mellitus. Caution must be exercised when treating hypertension to not create hypotension.

Answer 191

Respiratory diseases that result in exercise intolerance are commonly infectious or inflammatory in nature. Pulmonary hypertension can also lead to weakness. Pulmonary hypertension may occur secondary to heartworm disease or chronic pulmonary disease and carries a guarded prognosis.

Answer 192

Any disorder affecting the brain can cause weakness. The neurologic exam will localize the problem as being central in origin. Encephalitis caused by infectious agents, inflammatory conditions, or immune-mediated disease; cerebral vascular accidents (embolism or hemorrhage); space-occupying lesions (neoplasia, granulomas, or hydrocephalus); vestibular disease (central or peripheral); and idiopathic epilepsy can cause chronic or intermittent weakness. Additionally, many medications that act on the central nervous system (CNS) result in lethargy or exercise intolerance.

Answer 193

Spinal Cord Disease Lesions affecting the spinal cord between C1 to T2 can result in quadriparesis. More caudal lesions may cause paraparesis.

Answer 194

Causes of spinal cord disease include trauma, degenerative disk disease, vascular accidents, neoplasia, infectious diseases, and inflammatory conditions. Chronic, progressive conditions are more likely to result in the vague signs of weakness compared with the more recognizable problem of acute paraparesis.

Answer 195

Neuropathies Disorders affecting peripheral nerves can result in generalized weakness. The neurologic examination of affected dogs and cats typically reflect lower motor neuron dysfunction with reduced or absent reflexes.

Answer 196

polyradiculoneuritis; paraneoplastic disorders; endocrine diseases including diabetes mellitus, hyperadrenocorticism, and hypothyroidism; drugs and toxins (vincristine, lead); infectious agents (Toxoplasma, Neospora); and developmental disorders.

Answer 197

Weakness may also result from disruption of neuromuscular transmission. Myasthenia gravis can be either acquired or congenital. Severe exercise intolerance is often a hallmark of this disorder. Other neuromuscular disorders include tick paralysis and botulism. Specialized testing such as electromyography, nerve and muscle biopsy, and serology for antibodies to the acetylcholine receptor are often necessary to establish the diagnosis

Answer 198

Myopathies Disorders of muscle may cause weakness. Generalized myopathies may result from infectious, inflammatory, congenital, paraneoplastic, or immune-mediated diseases. In humans, significant age-related muscle weakening is seen. This weakening is seen due to a loss in muscle mass as well as changes in muscle fiber type. It is likely the same changes occur in animals and may explain some weakness seen in geriatric patients

Answer 199

Neoplasia Neoplasia can lead to weakness through many different pathways. Associated inflammation may result in the release of a variety of cytokines that can cause fatigue, cachexia, and anemia. Tumors may specifically release substances such as insulin, steroids, thyroid and parathyroid hormones, catecholamines, and estrogen that cause or exacerbate weakness. Some tumors such as hemangiosarcoma can cause severe, acute blood loss. Cancers can also result in anemia via disseminated intravascular coagulopathy (DIC). Neoplastic invasion or embolization can instigate organ failure. Finally, cancer can produce weakness from pain.

Answer 200

Physical and Psychologic Stress Psychologic causes of lethargy are much harder to evaluate in animals, but should not be completely discounted. Stress of any nature can activate the hypothalamic-pituitary-adrenal axis, with resultant increased levels of corticotropin-releasing hormone (CRH) and cortisol. Hyperactivity of this axis can lead to depression and weakness. CRH may play a specific role in the development of fatigue. It has also been suggested that primary hypothalamic dysfunction may be important in the cause of generalized weakness.

Answer 201

Changes or reduction in protein synthesis, altered glucose homeostasis, or dyslipoproteinemias may all result in weakness. Liver, pancreatic, kidney, and gastrointestinal disease may all cause weakness via nutritional deficits. Lipid disorders can arise from endocrinopathies such as diabetes mellitus, hypothyroidism, and hyperadrenocorticism; renal disease; liver disease; pancreatitis; diet; or familial causes. Any chronic condition can lead to cachexia

Answer 202

PHYSIOLOGY OF WATER METABOLISM Water consumption and urine production are controlled by complex interactions between plasma osmolality, fluid volume in the vascular compartment, the thirst center, the kidneys, the pituitary gland, and the hypothalamus. Dysfunction in any of these can result in apparent incontinence or polyuria (PU). Polyuria typically results in polydipsia (PD).

Answer 203

Vasopressin (antidiuretic hormone [ADH]) plays a key role in the control of renal water resorption, urine production, urine concentration, and water balance. In the presence of ADH and dehydration, the average healthy dog or cat has the capacity to produce urine with an osmolality well above 2000 mOsm/kg. If a dog or cat is chronically deficient in ADH or is chronically unable to respond to ADH at the renal tubular level, the urine may be as dilute as 20 mOsm/kg.

Answer 204

Plasma osmolality and its principal determinant, the plasma sodium concentration, normally are maintained within remarkably narrow ranges. Stability is achieved through adjustment of total body water concentrations to maintain balance with the plasma sodium concentration.

Answer 205

Water balance is controlled by an integrated system that involves precise regulation of water intake via thirst mechanisms and control of renal water loss via ADH secretion and action. Water is continuously lost through the urine, respiratory tract, and feces. Lost water is replaced by that consumed. The urine-concentrating capacity can reduce but not eliminate water loss

Answer 206

ADH, a nonapeptide, is synthesized in the hypothalamus and secreted from the posterior pituitary gland. The primary sites of ADH activity are epithelial cells in the renal distal tubules and collecting ducts. Here, ADH acts to increase the hydro-osmotic permeability of these cells.

Answer 207

The fluid in the tubular lumen normally is dilute, and the fluid in the interstitial space, through which the tubules traverse, is concentrated. Therefore, if water is allowed to diffuse passively along concentration gradients, it flows from the lumen of the nephron, in which the fluid is dilute, into the hypertonic milieu that normally exists in the interstitial space of the renal medulla. If ADH is present, the volume of fluid in the nephron decreases, the osmolality of that fluid increases, and water is conserved.

Answer 208

Thus the “normal” animal has the capacity to secrete ADH in response to appropriate stimuli such as increasing plasma osmolality or decreasing plasma volume, both of which follow dehydration. Secretion of ADH and the ability to respond to ADH at the level of the renal tubules and collecting ducts allow the body to conserve water.

Answer 209

In the absence of ADH (central diabetes insipidus) or if renal tubular cells are resistant to the action of ADH (nephrogenic diabetes insipidus), the cells lining this portion of the nephron are resistant to diffusion of both water and solutes. Hence, the hypotonic filtrate formed in the more proximal portion of the nephron passes unmodified through the distal tubule and collecting duct. This water diuresis is associated with large volumes of urine that has a low osmolality.

Answer 210

It should be noted that 85% to 90% of the fluid filtered by the glomerulus is reabsorbed isosmotically with sodium and glucose in the proximal portion of the nephron. Sodium then is selectively reabsorbed from the remaining fluid, making the fluid in the distal nephron hypotonic. However, if a poorly reabsorbed solute, such as urea or glucose, is present in excess in the glomerular filtrate, fluid resorption from the proximal tubule is impaired. Because of this physiologic process, an abnormally increased volume of fluid reaches the distal nephron and can overwhelm its capacity to reabsorb water. Consequently, urine volume increases despite the presence of ADH. This type of polyuria is called solute diuresis.

Answer 211

When the owner arrives at the veterinary hospital, the urine they collected can be evaluated prior to the pet being examined. The urine specific gravity should be noted and a “dip stick” test completed. Urine is usually considered normally “concentrated” if the specific gravity is >1.025. Since the owner has collected the urine sample from the pet while that animal was in its home environment, problems in interpretation associated with water being withheld prior to an automobile trip or a pet not consuming typical amounts of water due to nervousness or fear are not encountered. The truly polyuric dog or cat will almost always have dilute urine (specific gravity 1.012 but

Answer 212

If the urine bought to the hospital by the owners is concentrated (specific gravity >1.025) and it has no glucose, it is likely that the animal has a lower urinary tract condition. In this situation the veterinarian must consider the possibility of urinary tract infection, bladder calculi, bladder mass, anatomic abnormality, neurologic problems, or behavior issues that may explain the owner's observations.

Answer 213

Concentrated Urine with Glucose Most dogs and cats with diabetes mellitus are first examined after an owner has observed polyuria. These animals frequently also have polydipsia, polyphagia, and weight loss. Less commonly, a diabetic dog is brought in for veterinary examination after an owner notes that it has become acutely blind due to cataract formation. A dog or cat also may be brought in for treatment of vomiting, diarrhea, anorexia, listlessness, or other systemic signs secondary to developing diabetic ketoacidosis. Regardless, almost all diabetic dogs and cats have a urine specific gravity of 1.025 to 1.045 and glycosuria.

Answer 214

Rarely, a dog or cat with glycosuria has a blood glucose concentration within reference limits. In this situation, the veterinarian should consider the possibility of renal glycosuria.

Answer 215

Renal glycosuria is rare and is the result of a renal tubular defect. Renal glycosuria can be congenital in Basenji and Norwegian Elkhound breeds, but it can occur in any dog or cat. In cats, stress may cause glycosuria secondary to stress-induced hyperglycemia, although most cats with stress-induced hyperglycemia do not have glycosuria because the blood glucose never exceeds renal threshold. This concern should be minimized by collecting the urine at home.

Answer 216

1,008 to 1,012

Answer 217

The term isosthenuria usually implies that the urine specific gravity or osmolality is the same as that of serum or plasma. Using this criterion, urine with a specific gravity of 1.008 to 1.012 is isosthenuric. However, for clinical purposes, it is important to remember that a dehydrated animal has a plasma osmolality greater than normal due to loss of water and abnormal retention of solutes (e.g., urea). In this setting, a urine specific gravity as high as 1.020 may be “isosthenuric” despite being greater than the classic 1.008 to 1.012. In other words, what happens if a cat or dog is examined and is thought to be 3% to 10% dehydrated? If the animal has a normal hypothalamus, pituitary, and kidneys, it should have responded to this degree of water loss by secreting maximum amounts of ADH (it has been demonstrated repeatedly that a 3% to 5% decrease in body weight due to water loss is associated with this response). The urine of such an animal, therefore, should reflect maximum release of ADH, and the specific gravity should be well in excess of 1.035. If the dog or cat has a urine specific gravity of 1.018, for example, it should not be considered to have responded appropriately to dehydration.

Answer 218

The primary concern a veterinarian should have when an animal has polyuria and a urine specific gravity within the isosthenuric range is renal insufficiency or failure. In chronic renal failure, a compensatory increase in glomerular filtration rate by surviving nephrons occurs, and a commensurate increase in fluid volume is presented to the distal renal tubules.

Answer 219

The increase in the tubular flow rate causes less urea and sodium to be reabsorbed. The result is an osmotic diuresis, which may be exaggerated by a reduction in the renal medullary concentration gradient. A serum chemistry evaluation (BUN and creatinine) should be the first step in determining the presence or absence of renal disease as a cause of polyuria.

Answer 220

Because of the effects of endotoxin from Escherichia coli, the bacteria most commonly associated with pyometra. Because this endotoxin interferes with the action of ADH at the level of the renal tubules, these animals have a reversible form of nephrogenic diabetes insipidus.

Answer 221

Some, but not all, of the conditions associated with hypercalcemia are: lymphosarcoma, chronic renal failure, hypoadrenocorticism, primary hyperparathyroidism, vitamin D toxicosis, granulomatous disease (histoplasmosis, blastomycosis), multiple myeloma, apocrine gland carcinomas of the anal sac and other cancers.

Answer 222

1. Increased serum calcium concentration may interfere with the action of ADH at the renal tubular level, causing a reversible form of acquired nephrogenic diabetes insipidus. 2. Damage to ADH receptors in the renal tubules, 3. Inactivation of adenyl cyclase, 4. Decreased transport of sodium and chloride into the renal medullary interstitium (see Chapter 286).

Answer 223

1. Loss of renal medullary hypertonicity secondary to impaired BUN production. BUN is an important component of the renal medullary concentration gradient. Decreases in this gradient result in polyuria with compensatory polydipsia (see Chapter 274). 2. Another potential contributor to dilute urine is impaired metabolism of cortisol and subsequent cortisol excess (Cushing's syndrome: see below).

Answer 224

These dogs appear to have secondary and reversible ADH deficiency (central diabetes insipidus). Dogs with CCS typically have additional clinical signs, such as polydipsia, polyphagia, panting, muscle weakness, alopecia, pot belly, and thin skin. Routine laboratory abnormalities commonly include increases in serum alkaline phosphatase and alanine amino transferase activities, increased serum cholesterol concentration, and a decreased or low-normal BUN. Confirmation requires appropriate pituitary-adrenocortical function tests

Answer 225

isosthenuria, polyuria, secondary polydipsia and, eventually, renal failure. A dog or cat with bacterial pyelonephritis may have nonspecific signs of lethargy, anorexia, and fever. Neutrophilic leukocytosis may be noted on the CBC. Urinalysis may reveal white blood cells, casts, bacteria, and red cells. Recurrent urinary tract infection may increase suspicion of pyelonephritis. Urine cultures should be performed on cystocentesis samples, but these may or may not be positive for bacteria. Confirmation of this diagnosis usually requires imaging of the kidneys.

Answer 226

Urine Specific Gravity

Answer 227

Urine Specific Gravity s disease are young to middle-aged females. Despite normal kidney function and severe hypovolemia, animals in an Addisonian crisis frequently have a urine specific gravity of less than 1.030 due to the hyponatremia caused by mineralocorticoid deficiency.

Answer 228

Hyponatremia reduces the renal medullary concentration gradient, impairing the ability to produce concentrated urine. Although “relatively” dilute urine is typical of a dog or cat with hypoadrenocorticism, related signs are overshadowed by the more worrisome and obvious signs of weakness, listlessness, vomiting, diarrhea, anorexia, and weight loss. The combination of signalment and findings of hyperkalemia and hyponatremia should raise suspicion of Addison's disease

Answer 229

Urine Specific Gravity

Answer 230

Urine Specific Gravity <1.020: Iatrogenic Several drugs may cause polydipsia and polyuria, including some that are commonly used, such as glucocorticoids, diuretics, and anticonvulsants.

Answer 231

Urine Specific Gravity

Answer 232

CENTRAL DIABETES INSIPIDUS (CDI), NEPHROGENIC DIABETES INSIPIDUS (NDI), AND PSYCHOGENIC (PRIMARY) POLYDIPSIA (PP) It should be emphasized that CDI, NDI, and PP are quite uncommon. Most causes of polydipsia and polyuria can be identified from the signalment, history, physical examination, urinalysis (especially if the urine is caught by the owner before leaving the home environment), CBC, and serum biochemistry profile. Primary nephrogenic diabetes insipidus (NDI) is an extremely rare condition. However, secondary and often reversible NDI accounts for the polyuria in many of the conditions previously discussed. If an animal has dilute urine and does not appear to have any of the previously discussed conditions, it would be fair to assume that the animal does not have primary or secondary NDI. The dog or cat is more likely to have CDI or PP.

Answer 233

The veterinarian then can ask the following question: Does this animal drink a lot because it urinates a lot (CDI), or does it urinate a lot because it drinks a lot (PP)?

Answer 234

If CDI is present, the serum osmolality should be high-normal or increased. If PP is present, the serum osmolality should be low-normal or decreased. Thus the serum osmolality becomes a reasonable, cost-effective, and simple test to run.

Answer 235

Because the veterinarian has reached a point where it is likely that one of these two conditions may exist and because CDI is much more common than PP, trial therapy at home is recommended using oral DDAVP (synthetic ADH, which is commercially available as 0.1- or 0.2-mg tablets). The dose is empirical. The response in dogs or cats with CDI is quick and obvious (certainly less than 7 days). Owners can collect urine on a daily basis during the trial to substantiate their clinical impressions regarding response. If the pet responds, CDI is likely while Cushing's syndrome remains a possibility. The dose of DDAVP can be slowly tapered to determine the minimum required for long-term treatment. The use of synthetic ADH in the form of nasal drops placed in the eyes is more cumbersome than tablet administration. However, some dogs and cats demonstrate a better response to the eye drops than to oral medication.

Answer 236

The author considers a water deprivation test to be far more dangerous than warranted for the information derived. Remember, the first goal in a water deprivation test is to dehydrate a dog or cat to the point of 3% to 5% loss in body weight. If the test is carried out too long, the dehydration can quickly become life threatening. Additionally, since there are no consistent or reliable treatments for NDI or for PP, benign trial therapy can also serve as a diagnostic tool. Animals that do respond to ADH therapy most likely have hyperadrenocorticism or CDI. Those that don't are more likely to have hyperadrenocorticism (some dogs with Cushing's syndrome respond to ADH therapy and some do not), secondary NDI, or PP. At no point is a water deprivation test warranted.

Answer 237

Micturition is a two-stage process involving the passive storage and the active voiding of urine. Conditions that interfere with these stages are termed micturition disorders and are often divided into neurogenic and nonneurogenic based on their underlying causes.

Answer 238

Neurogenic disorders are further categorized as lower motor neuron disorders (atonic bladder with overflow incontinence), upper motor neuron disorders (automatic bladder), detrusor-urethral dyssynergia, and dysautonomia.

Answer 239

Infection, inflammation, calculi, neoplasia.

Answer 240

Urethral sphincter incompetence, An anatomic abnormality in the termination of the urethra, Inability of the bladder to expand in capacity, Spasms of the bladder, Nerve damage.

Answer 241

The body of the bladder is composed of the detrusor smooth muscle. The outlet conduit consists of the trigone and proximal urethra.

Answer 242

The smooth muscle fibers of the detrusor continue into the proximal urethra, forming a functional internal urethral sphincter. The distal urethra is composed of skeletal muscle functioning as an external sphincter. During the storage phase of micturition, the bladder functions as a low-resistance, high-capacity vessel and the urethra as a high-resistance barrier. During the voiding phase, the bladder acts as a muscular pump and the urethra as a low-resistance vessel.

Answer 243

Functional control of the bladder and urethra is attained through a combination of autonomic and somatic interactions. Sympathetic innervation regulates the filling phase of micturition and is supplied via the hypogastric nerve, composed of preganglionic fibers exiting the lumbar spinal cord (L1 to L4 in dogs and L2 to L5 in cats) and synapsing in the caudal mesenteric ganglion. Alpha-adrenergic fibers synapse in smooth muscles in both the trigone and proximal urethra and stimulation results in contraction of these muscles forming a functional internal urethral sphincter.

Answer 244

Beta-adrenergic fibers synapse in the detrusor muscle; stimulation results in bladder relaxation. Sensory receptors embedded in the bladder wall relay stretch information via the pelvic nerve to the spinal cord. The information is relayed to the brainstem, where it is integrated with information from the forebrain. Assuming that it is an appropriate time to void, the impulse to empty the bladder is carried down the spinal cord. Parasympathetic innervation dominates the emptying phase of micturition and is derived from the pelvic nerve (sacral spinal cord segments S1 to S3). Stimulation results in bladder contraction. Somatic innervation, supplied via the pudendal nerve, arises from sacral spinal cord segments S1 to S3 and provides stimulation to the striated urethral musculature.

Answer 245

Neurogenic Causes Lower Motor Neuron Disorder (Detrusor Areflexia with Sphincter Areflexia) Lower motor neuron disorders result from lesions involving the sacral spinal cord segments or pelvic nerve, including intervertebral disk disease, cauda equina syndrome, sacroiliac luxations, sacrococcygeal fracture/separation, and tumors (e.g., spinal lymphoma). The bladder typically is large, distended, easily expressed. The incontinence is continuous (overflow incontinence), and a loss of perineal, bulbospongiosus, and detrusor reflexes is noted. Lower Motor Neuron Bladder Treatment involves manual expression of the bladder three or four times daily. In the absence of a correctable lesion, long-term therapy is often unrewarding. Complications include urine scalding and recurrent urinary tract infections. Bethanechol, a parasympathomimetic, may be administered in an attempt to increase detrusor contractions.

Answer 246

Upper Motor Neuron Disorder (Detrusor Areflexia with Sphincter Hypertonus) Upper motor neuron disorders result from a lesion involving the spinal cord above the sacral spinal cord segments, such as intervertebral disk disease, tumor, or trauma. This disorder causes incomplete reflex detrusor contraction and spasticity of the urethral sphincter, resulting in incomplete bladder emptying. The bladder is large, turgid, and initially extremely difficult to express. The animal has a history of inability to urinate, and concomitant hindquarter paresis or paralysis frequently is seen. Upper Motor Neuron Bladder Voluntary control is lost, and manual expression is difficult if not impossible. In the absence of a correctable lesion, the spinal reflexes resume in days to weeks and involuntary micturition is initiated when the threshold capacity of the bladder is reached (automatic bladder). Initially it is difficult to express the bladder manually. Baclofen, a skeletal muscle relaxant, decreases muscle tone by exerting a depressive effect on the central nervous system. It inhibits medullary interneurons and spinal reflexes, and it decreases spasticity by reducing the activity of gamma efferent neurons. Because of the risk of bladder rupture, the patient should be catheterized aseptically at least three times daily to empty the bladder completely. An indwelling catheter should not be used because of the risk of urinary tract infection. Frequent urinalyses with culture and sensitivity should be performed. Concurrent administration of antibacterial agents may be indicated, especially with long-term intermittent catheterization.

Answer 247

Detrusor-Urethral Dyssynergia In detrusor-urethral dyssynergia, initiation of the detrusor reflex is followed by involuntary contraction of the urethral sphincter. The term detrusor-urethral dyssynergia refers to involuntary contraction of the external urethral sphincter in the distal urethra (detrusor-striated sphincter dyssynergia) or contraction of smooth muscle in the bladder neck and proximal urethra (detrusor-smooth sphincter dyssynergia) during detrusor contraction. The condition is caused by lesions (masses, degeneration) in the reticulospinal tract. Increased sympathetic activity of both the smooth and striated urethral musculatures may arise from a lesion cranial to or involving the caudal mesenteric ganglion. Detrusor-Urethral Dyssynergia Treatment involves decreasing sympathetic tone or the use of muscle relaxants. Alpha-adrenergic blocking agents (e.g., phenoxybenzamine, prazosin, and terazosin) can be used to decrease internal sphincter resistance. In addition to its alpha-1 antagonism in urethral smooth muscle, prazosin can cause a centrally mediated decrease in somatic input to the external urethral sphincter. Skeletal muscle relaxants (e.g., baclofen, diazepam, and dantrolene) can be used to decrease external sphincter resistance.

Answer 248

Dysautonomia Dysautonomia is a result of dysfunction of the autonomous nervous system. The cause is unknown. It is a rare disease seen mostly in cats in Great Britain, but it has been recognized in dogs and cats worldwide. Clinical signs are acute and involve many autonomic abnormalities (mydriasis, prolapsed third eyelids, constipation). Urine dribbling and dysuria often are presenting clinical signs due to an atonic bladder.

Answer 249

Nonneurogenic Causes of Micturition Disorders Nonneurogenic disorders typically involve mechanical obstructions and include such processes as infection, inflammation, calculi, and neoplasia.

Answer 250

This condition results from a mechanical or functional outflow obstruction that causes the tight junctions of the detrusor muscle to separate. Subsequent contractions of the detrusor muscle are weak and ineffectual. Functional outflow obstruction may have a neurogenic component that is usually the result of excessive sympathetic stimulation to the urethra.

Answer 251

Common examples of mechanical obstruction are urethral obstruction (especially in cats from mucoid or crystalline plugs), urethral calculi, neoplasia of the trigone or urethra, severe urethritis, urethral stricture, and prostatic disease. As a result of a functional or mechanical obstruction, urine volume increases until the intravesicular pressure overcomes urethral resistance resulting in urine dribbling. Typically, the animal has a history of urine outflow obstruction followed by urinary incontinence. Abdominal palpation reveals a large, flaccid bladder. Neurologic examination reveals intact perineal and bulbospongiosus reflexes, yet the detrusor reflex is weak or absent. There is a large residual urine volume. Urodynamic studies such as the cystometrogram and urethral pressure profile may aid in diagnosis.

Answer 252

Overflow incontinence Lower motor neuron bladder (detrusor atony) Upper motor neuron bladder (automatic bladder)

Answer 253

Urethral sphincter mechanism incontinence Detrusor hyperspasticity Ectopic ureter(s)

Answer 254

In dogs incontinence is rarely the sole neurologic abnormality (see above, under neurogenic micturition disorders) detected on physical examination. Treatment of the incontinence and prognosis for resolution or clinical control depend primarily on the underlying cause.

Answer 255

1. Aging and relative lack of estrogen, which may affect the collagenous support structures of the urogenital region as well as decrease the availability and/or responsiveness of alpha receptors. 2. Abnormal positioning or morphology of the bladder or urethra can contribute to functional failure (pelvic bladder, urethral dysplasia, overriding urethra). 3. Obesity or vaginal structural abnormalities can contribute to development of clinical signs. Breed predispositions suggest underlying genetic factors. Hormone-responsive incontinence is one of the most frequently diagnosed disorders.

Answer 256

Urethral incompetence is the most common nonhormonal cause of urinary incontinence in small animals. The cause is thought to be urethral smooth muscle incompetence or urethral malposition (Web Figure 38-2).

Answer 257

Alpha-adrenergic agonists are the preferred treatment for USMI. Phenylpropanolamine, a nonselective adrenergic agonist, is commonly used to treat this condition. Total resolution of incontinence can be expected in more than 85% of cases. Side effects include hypertension, restlessness, irritability, tachycardia, increased intraocular pressure, and hepatic glycogenolysis. Use of this drug is contraindicated in pets with hypertension, diabetes mellitus, or glaucoma. Diethylstilbestrol (DES) is a synthetic estrogen that has been successfully used to treat USMI. Potential side effects include bone marrow suspension, alopecia, behavior change, and signs consistent with estrus; however, most dogs tolerate the medication well. Testosterone cypionate or methytestosterone may be used in male dogs. Minimal side effects have been noted except for prostatic enlargement. In some instances, animals develop a tolerance for hormonal replacement. Additional therapy with a sympathetic alpha agonist that increases urethral tone is then indicated.[6] The most successful drugs are the sympathomimetic alpha-adrenergic agonists, which directly increase urethral smooth muscle tone. The drug of choice is phenylpropanolamine; an alternate drug is ephedrine or pseudoephrine

Answer 258

Detrusor hyperspasticity (instability, urge incontinence) Detrusor hyperspasticity is characterized by involuntary bladder contractions resulting in the frequent voiding of small volumes of urine. Hyperspasticity secondary to infection, neoplasia, or uroliths is called urge incontinence while cases in which no underlying cause is determined are referred to as idiopathic detrusor instability.[5] The syndrome is commonly seen in cats with cystitis or “idiopathic feline lower urinary tract disorders.” Urge Incontinence (Detrusor Hyperreflexia) treatment: Direct-acting smooth muscle relaxants such as flavoxate are promising in the treatment of this syndrome.

Answer 259

Ectopic ureter(s) Ectopic ureter (EU) and other congenital urethral malformations are a common cause of urinary incontinence. The abnormal entry of the ureter(s) into the distal urethra or vagina from a congenital malformation results in continuous or intermittent dribbling of urine

Answer 260

NORMAL URINE Normal urine is typically transparent and yellow or amber upon visual inspection. Two pigments are primarily responsible for the yellow coloration: urochrome and urobilin.

Answer 261

Urochrome is a sulfur-containing oxidation product of the colorless urochromogen. Urobilin is a degradation product of hemoglobin. Because the 24-hour urinary excretion of urochrome is relatively constant, highly concentrated urine will be amber in color, whereas dilute urine may be transparent or light yellow in color. The intensity of the color is in part related to the volume of urine collected and in part related to the concentration of urine produced; therefore, it should be interpreted in the context of the urine specific gravity.. Significant disease may exist when urine is normal in color. Abnormal urine color may be caused by presence of several endogenous or exogenous pigments. Although abnormal urine color usually indicates a problem, it provides relatively nonspecific information

Answer 262

DISCOLORED URINE Urine color that is anything other than yellow or amber is abnormal. There are many potential causes of discolored urine (Table 39-1). The most common abnormal urine color in dogs and cats is red, brown, or black, which may be caused by hematuria, hemoglobinuria, myoglobinuria, and bilirubinuria

Answer 263

Pale Yellow Urine Urine that is pale yellow or clear in appearance may be normal or may be indicative of a polyuric state. Urine may be appropriately dilute if it is associated with recent consumption or administration of fluids, consumption of a diet containing low quantities of protein or high quantities of sodium chloride, glucocorticoid excess, or administration of diuretics.

Answer 264

diabetes insipidus, hyperadrenocorticism, hypoadrenocorticism, hypercalcemia, hyperthyroidism, renal failure.

Answer 265

The reader is reminded that dogs and cats with uncomplicated diabetes mellitus, while typically extremely polyuric, usually have urine specific gravities of 1.025 to 1.045. If urine is pale yellow or clear, the urine specific gravity is often less than 1.015. A simple test to determine whether polyuria is persistent is to determine the urine specific gravity of an owner-collected morning sample. Other tests should include serum biochemical analysis and a complete urinalysis. Additional testing may include measurement of serum thyroxine concentration, adrenal function testing

Answer 266

Presence of red, brown, or black urine suggests blood, hemoglobin, myoglobin, or bilirubin (see Figure 39-1). A positive occult blood reaction is obtained when urine contains any of these substances. Discoloration of urine may also result in false-positive reactions on other urine dipstick test pads. Analysis of urine sediment will reveal the presence of red blood cells if the discoloration is due to hematuria. If no red blood cells are present on microscopic examination of urine sediment, hemoglobin, myoglobin, or bilirubin should be suspected.

Answer 267

Examination of plasma color may aid in differentiating these potential explanations. If the discolored urine is due to myoglobin, the plasma will be clear because myoglobin in plasma is not bound significantly to a carrying protein, which results in filtration and excretion of myoglobin. If the plasma is pink, it is suggestive of hemoglobin. If the plasma is yellow, it is suggestive of bilirubin; serum bilirubin concentration should also be increased.

Answer 268

Myoglobinuria is indicative of muscle damage; serum creatine kinase activity is often increased in this setting. Hemoglobinemia is indicative of intravascular hemolysis resulting from immune-mediated, parasite-mediated, or drug-mediated destruction of red blood cells. Hyperbilirubinemia may result from liver disease, posthepatic obstruction, or hemolysis.

Answer 269

Milky White Urine Milky white–colored urine may be due to presence of white blood cells (pyuria), lipid, or crystals. The more concentrated the urine sample is, the more opaque it may appear.

Answer 270

The presence of pyuria secondary to a bacterial urinary tract infection is the most common cause of milky white urine; however, pyuria may occur due to inflammation and not be associated with an infection. Lipiduria may be observed in healthy animals, but is frequently observed in cats affected with hepatic lipidosis. Crystalluria, if heavy and present in a concentrated urine sample, may also result in milky white urine color. Microscopic examination of urine sediment will aid in differentiation of these causes.

Answer 271

Dogs and cats may normally have small amounts of protein in their urine; however, the term proteinuria usually refers to the presence of an abnormal amount of protein in the urine. The term microalbuminuria refers to the presence of albumin in the urine in a concentration of 1 to 30 mg/dL, which is considered abnormal, but is below the detection limit of the urine dipstick.

Answer 272

A persistently high-magnitude proteinuria is usually an indicator of chronic kidney disease (CKD); however it may be a secondary consequence of infectious, inflammatory, metabolic, or neoplastic disorders. Thus proteinuria can serve as a sensitive indicator of both renal and extrarenal diseases, and its presence may prompt a comprehensive diagnostic evaluation even in the absence of clinical signs. Proteinuria may also serve as a prognostic marker. There is growing evidence in both the veterinary and the human literature suggesting that proteinuria is associated with a more rapid progression of CKD

Answer 273

If voided samples are used, proteinuria should be confirmed in a sample obtained by cystocentesis to exclude the genital tract or external genitalia as its origin. The urine dipstick colorimetric test is the most commonly used method to screen for proteinuria. The urine dipstick is more sensitive to albumin compared to other proteins, and its lower detection limit is 30 mg/dL. Interpretation of any result should be done in light of the urine specific gravity.

Answer 274

The UPC ratio has been shown to be highly correlated with 24-hour urine protein loss. Urine protein to creatinine ratio

Answer 275

Proteinuria can be classified as urinary system or extraurinary system in origin. Extraurinary system proteinuria may result from either prerenal or posturinary system conditions.

Answer 276

Prerenal proteinuria results from presence of excessive amounts of normal (e.g., hemoglobin, myoglobin) or abnormal (e.g., Bence Jones) blood proteins, which can be freely filtered through the glomerulus. Thus, prerenal proteinuria can occur with normal kidney structure and function. This form of proteinuria is typically of low magnitude. Extraurinary system proteinuria can also occur with posturinary conditions, such as contamination of urine with protein arising from genital disorders.

Answer 277

Urinary system proteinuria can be classified as renal (functional or pathologic) or postrenal.

Answer 278

Functional renal proteinuria represents a transient change in the permselectivity characteristics of the glomerulus, and may result from conditions such as seizures, fever, excessive exercise and stress. This form of proteinuria is transient, is typically of low magnitude, and does not require intervention.

Answer 279

Pathologic renal proteinuria may result from glomerular (decreased permselectivity), tubular (decreased reabsorption), or interstitial (exudation of proteins to the urinary space) abnormalities.

Answer 280

Glomerular proteinuria is the most common cause of persistent high-magnitude proteinuria. It requires close monitoring, and often warrants diagnostic evaluation and therapeutic intervention. It results from changes in the glomerular permselectivity characteristics, most commonly due to amyloidosis or glomerulonephritis.

Answer 281

Renal proteinuria that originates from the renal tubules represents failure of the proximal tubule to reabsorb small–molecular weight proteins that are freely filtered in the glomerulus. Additional concurrent proximal tubular abnormalities, such as reabsorption of phosphorous, bicarbonate, and glucose (e.g., Fanconi's syndrome) may be present.

Answer 282

Postrenal proteinuria relates to the entry of proteins into the urine from the renal pelvis, ureters, urinary bladder, or urethra, and results from disorders along the urinary excretory system (e.g., infection, urolithiasis, neoplasia).

Answer 283

Once proteinuria has been established, follow-up measurements should be performed to classify the proteinuria as transient or persistent. Persistent proteinuria was defined in the consensus statement of the American College of Veterinary Internal Medicine as ≥ 3 positive results 2 weeks apart. Recommendations of this consensus statement suggest a diagnostic work up for nonazotemic patients when the UPC ratio is ≥ 1.0. However, recent evidence suggests that even proteinuria of lower magnitude may be detrimental; therefore, diagnostic investigation should be considered even with UPC ratio values of 0.5 to 1.0.

Answer 284

Initially postrenal proteinuria is excluded by evaluating the urine sediment for presence of inflammation and hemorrhage. Next, extraurinary system causes should be excluded. Posturinary (genital system) proteinuria is easily excluded by performing urinalysis on urine obtained by cystocentesis, and prerenal proteinuria is ruled out by evaluating the plasma protein concentration and excluding dysproteinemia and presence of specific proteins in the urine (e.g., hemoglobinuria, myoglobinuria, and Bence Jones proteins).

Answer 285

Glomerular proteinuria can be of any magnitude, but is particularly suspected when persistent high-magnitude (UPC ≥ 2) proteinuria is present and after ruling out extrarenal and postrenal causes. Glomerular proteinuria can be diagnosed by obtaining a kidney biopsy, which can additionally differentiate between amyloidosis and glomerulonephritis. Since glomerulonephritis is often a secondary complication of infectious, inflammatory, or neoplastic conditions, a diagnostic workup should be performed to identify any underlying disease.

Answer 286

Tubular proteinuria should be suspected when concurrent tubular abnormalities such as normoglycemic glucosuria, proximal renal tubular acidosis, or abnormal electrolyte excretion are present; nevertheless, their absence does not exclude tubular proteinuria.

Answer 287

It should be recognized that several origins of proteinuria may coexist and their differentiation may be difficult (e.g., low-grade glomerular proteinuria versus tubular proteinuria).

Answer 288

TREATMENT Treatment goals include decreasing the magnitude of proteinuria to the reference range to minimize progressive kidney damage, as well as preventing and treating the secondary consequences of the protein loss (e.g., thromboembolism).

Answer 289

Due to the decreased number of functional nephrons in azotemic patients, the amount of protein passing through each nephron is higher compared to patients with a normal number of functional nephrons for any given UPC ratio. Current guidelines recommend treating nonazotemic patients when UPC ratio is ≥ 2.0, while azotemic dogs and cats are to be treated when UPC = 0.5 and UPC ≥ 0.4, respectively.

Answer 290

Dietary modification and angiotensin-converting enzyme (ACE) inhibition are the mainstays of therapy. Protein restriction is one of the dietary modifications recommended for protein-losing nephropathies. Even though counterintuitive, increasing dietary protein amounts is associated with increased albuminuria and may result in decreased serum albumin concentration, as has been shown in rats, dogs, and humans.

Answer 291

Decreased efferent glomerular arteriolar resistance resulting in decreased glomerular transcapillary hydraulic pressure is considered the primary mechanism. The beneficial effects of ACE inhibitors were demonstrated in both azotemic and nonazotemic patients

Answer 292

Although there is growing evidence that ACE inhibitors have renoprotective properties in proteinuric patients, their administration should be exercised with caution, especially in severely and acutely azotemic dogs and cats. ACE inhibitors uncommonly cause a decreased intraglomerular pressure that results in a decrease in the glomerular filtration rate. Risk of this adverse effect should not be overlooked, particularly in azotemic patients or in animals prone to dehydration. In these animals, a lower daily dose of ACE inhibition should be used initially, with a gradual increase toward the target dose while monitoring kidney function.

Answer 293

Low-dose aspirin (0.5 mg/kg, PO, q12-24h) may also decrease proteinuria in dogs. It has been shown that glomerular damage may be prevented by thromboxane release inhibition, thus preventing platelet aggregation and neutrophil chemotaxis. An additional potential advantage of low-dose aspirin therapy is decreasing the risk of thromboembolism, especially in animals with a hypoantithrombinemia.

Answer 294

– Gastrointestinal

Answer 295

hyporexia Anorexia is important because complications of prolonged inadequate nutritional intake are numerous and, for certain disease processes (e.g., feline hepatic lipidosis) can be more serious than the underlying disorder. Examples of these complications include immune system suppression (decreased cell-mediated immunity, immunoglobulin and complement production, and phagocytic activity) and secondary organ dysfunction (decreased hepatic detoxification ability and intestinal alterations). Figure 41-2 Therapeutic and diagnostic approach for feline and canine anorexia. ACTH, Adrenocorticotropic hormone; CSF, cerebrospinal fluid; FeLV, feline leukemia virus; FIV, feline immunodeficiency virus.

Answer 296

TREATMENT Numerous chemical appetite stimulants have been utilized including benzodiazepines (Valium), cyproheptadine (Periactin), and mirtazapine (Remeron). In the author's practice, the most commonly used stimulant is mirtazapine (feline: 1.875 to 3.75 mg total dose PO every third day; canine: 3.75 to 30 mg PO daily).[3,4] Dietary appetite stimulation broadly involves modification of the environment or the type of food offered. Prior to discussing dietary modifications, it is important to consider learned food aversions. This condition involves the association of food with an adverse event (e.g., vomiting) and can lead to avoidance of potentially beneficial diets in the future. Warming, feeding multiple small meals, and the addition of nonnutritive flavors (e.g., garlic in dogs) may help prevent the development of learned food aversions to a new diet. Offering a new diet(s) should be avoided in nauseous pets until the nausea is resolved.

Answer 297

A guideline on when to initiate assisted feeding has not been established and often is dependent on patient factors. It is generally indicated when nutritional intake is less than resting energy requirements (RER) = 70 × (body weightkg0.75) for 3 to 5 days. Even with identification of a causative disease process, assisted feeding can be needed during the recovery process for patient support

Answer 298

Polyphagia is the consumption of food in excess of normal caloric intake. Hunger, satiety, and consequently, eating behavior are primarily controlled by certain regions in the central nervous system (CNS), but many factors affect the function of these areas. Thus polyphagia can be classified as primary (i.e., a CNS abnormality) or secondary (i.e., a systemic problem affecting the CNS). Secondary polyphagia is by far more common and is usually accompanied by clinical signs of the underlying disease.

Answer 299

PHYSIOLOGY Food intake is controlled by a variety of factors, including gastrointestinal, environmental, and CNS phenomena. Within the CNS, key circuits regulating energy homeostasis and food intake originate in the hypothalamus and brainstem. The hypothalamus receives sensory input from the external environment plus neurologic and hormonal input from the internal environment, integrates the information, and provides output to key regulatory sites such as the pituitary, cerebral cortex, brainstem, and spinal cord.

Answer 300

The lateral hypothalamic nuclei represent the “feeding center”; their stimulation causes an animal to eat, and their destruction results in severe, fatal anorexia. Conversely, the ventromedial nuclei are the “satiety center,” as their stimulation causes a refusal to eat even highly appetizing food, and their ablation leads to polyphagia and obesity. The feeding center is constantly active unless inhibited by the satiety center (e.g., postprandially). The brainstem serves a secondary coordinating role and the nucleus of the solitary tract and area postrema have minor roles.

Answer 301

In the brain, melanocortin peptides, such as α-melanocyte-stimulating hormone (α-MSH), and the melanocortin-4 receptor (MC4-R), for which α-MSH is the agonist, are extremely important in food intake. Mutations in the MC4R gene are the most common monogenic form of obesity, accounting for up to 6% of severe early-onset obesity in some human cohorts. Neurons that express pro-opiomelanocortin or coexpress agouti-related protein and neuropeptide Y are also vital to food intake.

Answer 302

Gastric distention, The rate of gastric emptying, The release of gastric hormones, Absorption of nutrients, such as fatty acids, glucose, and amino acids.

Answer 303

The gut hormones can act locally on the gastrointestinal tract and centrally on the CNS. Secretion of insulin, glucagon, cholecystokinin and PYY, (a peptide related to neuropeptide Y), and pancreatic peptide results in decreased feeding signals from the CNS. Leptin, a polypeptide released from adipose tissue, may also help to create a sense of satiety.

Answer 304

Conversely, serum concentrations of ghrelin, a peptide secreted mainly by the stomach, decrease with meal ingestion. Concentrations of this hormone rebound to baseline before the next meal and increase with an overnight fast. Ghrelin stimulates eating.

Answer 305

Decreased serum concentrations of glucose, amino acids, or lipid metabolites cause hunger by stimulating neural centers so as to reestablish normal levels. Feeding behavior also can be incited by increased nutrient utilization (i.e., an elevated metabolic rate).

Answer 306

Pathologic conditions that affect the CNS can increase feeding behavior even in the presence of normal energy stores (primary polyphagia). Secondary polyphagia exists when feeding behavior is stimulated by nonneural factors and can be caused by an increased metabolic rate or decreased nutrient supply (Box 42-1).

Answer 307

An augmented metabolic rate can be physiologic (e.g., pregnancy) or pathologic (e.g., hyperthyroidism).

Answer 308

Diabetes mellitus causes an unusual condition of decreased nutrient supply. Due to an inability to respond to or a lack of insulin, the body does not recognize glucose, falsely perceiving hypoglycemia.

Answer 309

Certain diseases (e.g., hyperadrenocorticism and liver disease) lead to polyphagia by unknown mechanisms. Secondary polyphagia can also be caused by certain drugs.

Answer 310

Pathologic secondary polyphagia is more commonly associated with weight loss, because the nutrient supply usually does not meet physiologic demands. However, some causes, such as acromegaly, hypoglycemia caused by an insulinoma, sudden acquired retinal degeneration syndrome (SARDS), and hyperadrenocorticism (HAC), lead to weight gain. An animal with HAC or in the early stages of any of these states, however, may show no weight change. Physiologic polyphagia can result in weight gain (e.g., pregnancy, growth) or maintenance of weight (e.g., lactation, cold environment, increased exercise).

Answer 311

Polyphagia is commonly associated with anticonvulsant and glucocorticoid therapy but has been observed with other medications (see Box 42-1). Psychogenic polyphagia has been noted after introduction of a more palatable diet or in response to a stressful event, most commonly introduction of a new pet into the household.

Answer 312

An animal with primary polyphagia caused by destruction of the satiety center may have a history of trauma or clinical signs associated with CNS disease. Depending on the extent of a hypothalamic lesion, upper motor neuron signs may be seen in all four limbs or unilaterally. A midbrain lesion often leads to incessant pacing, circling, and blindness; polyuria/polydipsia (PU/PD) may also be present. Disorders caused by diffuse or multifocal CNS disease will have other clinical signs as well, depending on the areas affected.

Answer 313

Perturbation of hypothalamic control of the pituitary can lead to reproductive, thyroidal, and adrenal hypofunction and associated clinical signs. Hypothyroidism secondary to pituitary dysfunction is clinically identical to primary thyroidal failure.

Answer 314

Historical findings associated with secondary polyphagia can be highly varied. Animals with diabetes mellitus, acromegaly, SARDS, and hyperthyroidism usually have PU/PD. It is valuable to remember that people and cats with HAC do not typically exhibit polyphagia, PU, or PD, features that are extremely common in dogs with HAC.

Answer 315

Feline acromegaly is seen in middle-aged to older males, and naturally occurring canine acromegaly is seen almost exclusively in intact bitches. In dogs of either sex, progestin administration can lead to acromegaly. Owners may note inspiratory stridor or a change in body conformation, such as increased interdental spaces, skin folds, or head size in acromegalic animals. It should also be noted that progestin administration to dogs and cats can increase appetite without causing acromegaly.

Answer 316

A multitude of historical details can be associated with HAC, including abdominal enlargement, persistent panting, failure to regrow hair after clipping, lethargy, and muscle weakness.

Answer 317

Animals with SARDS typically have the presenting complaint of sudden-onset blindness, but PU/PD and polyphagia may precede the blindness.

Answer 318

Hyperthyroidism commonly leads to increased activity but can be associated with depression and lethargy. Gastrointestinal signs (e.g., vomiting and diarrhea) may also be present.

Answer 319

Hypoglycemia has a number of etiologies. Insulinoma is the most likely to lead to polyphagia, but a few other neoplasias and insulin overdose may also lead to increased appetite.

Answer 320

Weakness, trembling, ataxia, disorientation and, possibly, grand mal seizures.

Answer 321

Parasites, pancreatic exocrine insufficiency (PEI), infiltrative bowel disease, lymphangiectasia Malassimilation generally cause large-volume, malodorous, soft stools. PEI is more common in younger dogs (i.e., those less than 2 years of age), and the German Shepherd breed shows a predisposition for this disorder. In older dogs and cats, PEI is rare but, if seen, is most commonly associated with chronic pancreatitis. The category of infiltrative disease encompasses processes such as inflammatory bowel disease, neoplasia, and infections such as histoplasmosis. Historical details vary according to the underlying disease.

Answer 322

Acquired esophageal disease often leads to anorexia. Animals with congenital megaesophagus are often polyphagic, especially if they have the typical history of regurgitation. Although anorexia is more common in animals with a portacaval shunt, polyphagia has been reported in approximately 10% of cases. Depression, vomiting, weight loss, polydipsia/polyuria, and neurologic signs may also be noted. Polyphagia has been reported rarely with hepatoencephalopathy; other clinical findings are the result of hepatic failure and may be similar to those in an animal with a portasystemic shunt.

Answer 323

Periodontal disease is a broad term used to encompass a subset of two distinct conditions, gingivitis and periodontitis. Briefly, gingivitis is inflammation of the gingiva, while periodontitis is inflammation of the periodontium beyond the gingiva. A dog or cat may have periodontal disease but not periodontitis. However, all patients with gingivitis or periodontitis have periodontal disease. The periodontium is composed of gingiva, periodontal ligament, cementum, and the alveolus (Web Figure 43-1). These tissues support the teeth and are the tissues most intimately involved in periodontal disease.

Answer 324

Ptyalism is defined as a pathologic overproduction of saliva that may occur from a number of disease states. Pseudoptyalism refers to drooling caused by an inability or reluctance to swallow a normal amount of saliva. This chapter will cover both forms as they are often interrelated.

Answer 325

ETIOLOGY AND PATHOGENESIS Ptyalism results from an increase in production by one or all of the salivary glands. Pseudoptyalism results from some disruption of the swallowing mechanism that can be voluntary (often pain induced) or involuntary (obstruction). There are numerous causes for hypersalivation, and numerous locations where the inciting cause may originate. Problems can originate from the oral cavity, esophagus or alimentary tract, or within the salivary glands themselves. Furthermore, hypersalivation can occur secondary to neurologic (central or peripheral), metabolic, infectious or immune-mediated disease, or to a toxic/caustic exposure or drug reaction

Answer 326

Gagging is defined as a swallowing-vomiting reflex activity whereby elevation of the soft palate is followed by a reverse peristalsis of the upper digestive tract.

Answer 327

Swallowing is the taking in of a substance through the mouth and the pharynx and into the esophagus. It is a combination of a voluntary act and a series of reflex actions. Once begun, the process operates automatically. The swallowing reflex is a rigidly ordered sequence of events that results in the propulsion of food from the mouth to the stomach while concurrently inhibiting breathing and preventing the entrance of food into the trachea

Answer 328

1. The trigeminal nerve (cranial nerve [CN] V), 2. The hypoglossal (CN XII), 3. The facial (CN VII) 4. The glossopharyngeal (CN IX) nerves.

Answer 329

(1) oral (or voluntary); (2) pharyngeal; and (3) esophageal.

Answer 330

GAGGING Gagging is often associated with retching. Retching is an involuntary and ineffectual attempt at vomiting. The causes for retching are similar to vomiting. Expulsion is induced when hypercapnia and hypoxia develop during retching, or when the oropharyngeal mucosa is irritated (the gag reflex).

Answer 331

Laryngeal paralysis is a frequently recognized disorder that can cause gagging. Two forms of laryngeal paralysis exist, hereditary and acquired. The hereditary form is found in young dogs and transmitted by an autosomal dominant gene. Antibiotic administration in a solid form that is excessively large to allow passage of the esophagus has been shown to create esophageal injury and produce gagging in the cat. Airway neoplasia or trauma can also be a common cause of gagging in cats. Retching is discussed in Chapter 46.

Answer 332

Another physical sign similar to gagging is expectoration, which is the clearing of the airway of mucus and discharges without nausea. For cats this event can be a normal clearing of hair from the airway after grooming (Figure 45-2)

Answer 333

Dysphagia and regurgitation may both be characterized as swallowing disorders. They may exist as separate conditions or in conjunction with each other. Localization of the disease process requires careful attention to history, clinical signs, and physical examination findings

Answer 334

DYSPHAGIA Dysphagia is defined as difficult or painful swallowing. The swallowing process may be divided into the oropharyngeal. esophageal, and gastroesophageal phases. Oral dysphagia occurs when there is difficulty with prehension and bolus formation. Pharyngeal dysphagia occurs when there is impaired initiation of the involuntary passage of food through the oropharynx. Cricopharyngeal dysphagia occurs when there is inadequate relaxation of the cricopharyngeal muscle (achalasia), or failure of synchronization between pharyngeal contraction and cricopharyngeal relaxation (asynchrony) during swallowing. Esophageal dysphagia occurs when there is difficulty passing a bolus through the esophageal body. Gastroesophageal dysphagia occurs when there is difficulty passing a bolus through the caudal esophageal sphincter.

Answer 335

REGURGITATION Regurgitation is defined as the passive expulsion of food or fluid from the esophagus or stomach. It is important to accurately distinguish regurgitation from vomiting, which is a centrally mediated reflex in which ingesta are expelled from the gastrointestinal tract (stomach, duodenum). Unlike regurgitation, vomiting is usually preceded by hypersalivation, retching, and abdominal contractions. The appearance of the expelled material along with the timing of the episode may also aid in distinguishing regurgitation from vomiting.

Answer 336

PATHOPHYSIOLOGY The physical act of vomiting can be divided into three components: nausea, retching, and expulsion of gastric contents. Nausea precedes vomiting and is associated with an episode that defies exact definition. Outward signs of nausea may include depression, shivering, hiding, yawning, and licking of the lips. Increased salivation and swallowing occur, which serve to lubricate the esophagus with bicarbonate-rich saliva that will neutralize gastric acid as stomach contents pass through. Next, there is a reduction in gastric, lower-esophageal sphincter and esophageal motility followed by increased retrograde motility of the proximal small intestine.

Answer 337

Retching, the second phase in the vomiting process, often helps distinguish the episode from regurgitation, gagging, or coughing. Retching is the forceful contraction of the abdominal muscles and diaphragm producing negative intrathoracic pressure and positive abdominal pressure. These pressure changes cause the movement of gastric contents into the esophagus and out the mouth.

Answer 338

The driving force is contraction of the abdominal muscles and diaphragm causing intrathoracic pressure changes from negative during retching to positive during vomiting. As the vomited material passes through the pharynx, respiration is inhibited and the nasopharynx and glottis close to prevent aspiration.

Answer 339

number of nuclei that collectively have been referred to as the emetic center. These nuclei and their complex, integrated nerve pathways are responsible for initiating vomiting. At the present time this area is known to be abundant in serotonergic (5HT3), adrenergic (α2), and neurokinergic (NK1) receptors. Activation of these receptors in the emetic center occurs either indirectly through a humoral pathway by bloodborne substances activating the chemoreceptor trigger zone (CRTZ) or by other various neural pathways leading to the emetic center.

Answer 340

Figure 47-1 Factors that activate the vomiting center

Answer 341

Neural stimulation of the emetic center arises through either 1. afferent vagal, 2. sympathetic, 3. vestibular, 4. cerebrocortical, 5. or the adjacent nucleus tractus solitarius pathways. Activation of specific peripheral receptors found throughout the body initiate these stimuli. Particularly important are receptors located throughout the abdominal viscera.

Answer 342

The duodenum contains the highest concentration of receptors and hence has been referred to as the “organ of nausea.”

Answer 343

5HT3 and NK1 receptors are abundant on vagal afferent neurons, other neurons, and smooth muscle in the gastrointestinal tract. Gastrointestinal disorders directly stimulate vomiting through vagal afferent pathways.

Answer 344

Certain inflammatory or cytotoxic factors cause the release of serotonin or substance P from local enterochromaffin cells that activate 5HT3 and NK1 receptors respectively on afferent vagal nerves.

Answer 345

Receptors in the kidneys, uterus, and urinary bladder send afferent impulses via sympathetic nerves.

Answer 346

Receptors located in the pharynx and tonsillar fossae transmit impulses thorough afferent fibers of the glossopharyngeal nerve.

Answer 347

CNS disease will also directly activate the emetic center through pathways that lead to the emetic center. Adjacent to the emetic center in the medulla is the nucleus tractus solitarii, which is rich in NK1 receptors. This area also plays a role in activating the emetic center.

Answer 348

Vomiting can also be stimulated by humoral factors in the blood. Such substances activate receptors in the CRTZ, located in the area postrema at the base of the fourth ventricle. The CRTZ is devoid of a blood brain barrier, which allows exposure to chemical stimuli found in the circulation: certain drugs, uremic toxins, electrolytes, osmolar and acid-base disorders, as well as a number of metabolic derangements.

Answer 349

Dopaminergic (D2), cholinergic (M1), histaminergic (H1), serotonergic (5HT3), adrenergic (α2), and neurokinergic (NK1) receptors are associated with the CRTZ and act as excitatory transmitters of neurons leading to the emetic center. Enkephalinergic (ENK) receptors are also thought to occur in the CRTZ, but their exact role is poorly understood.

Answer 350

Cats have poorly developed D2 and H1 receptors while their α2 receptors are more important in vomiting but less important in the dog. Cats usually do not respond to the emetic effects of apomorphine and histamine, but xylazine, a α2 agonist, is a potent emetic in the cat.

Answer 351

Vestibular stimulation passes through the CRTZ before activating the emetic center. Motion sickness, inflammation of the labyrinth, or lesions in the cerebellum result in vomiting via this pathway. Cholinergic (M1), histaminergic (H1,) and possibly neurokinergic (NK1) receptors are associated with vestibular pathways that pass through the CRTZ on the way to the emetic center.

Answer 352

CAUSES Vomiting has a vast number of etiologies. Box 47-1 presents some of the more common causes of vomiting in small animals.

Answer 353

CRTZ, emetic center

Answer 354

-Dolasetron; CRTZ, emetic center, vagal afferents -Ondansetron CRTZ, emetic center, vagal afferents -Metoclopramide (high dose): CRTZ

Answer 355

CRTZ, emetic center, vagal afferents, (vestibular)

Answer 356

Chlorpromazine: CRTZ Prochlorperizine: CRTZ Scopalamine: CRTZ, vestibular

Answer 357

Chlorpromazine; CRTZ Prochlorperizine; CRTZ Diphenhydramine; CRTZ, vestibular

Answer 358

Common side effects: se table 47-1

Answer 359

Alla verkar på CRTZ. Lära vilka som verkar andra ställen

Answer 360

Diarrhea is caused by excess fecal water that may result from decreased intestinal absorption and/or increased intestinal secretion.

Answer 361

Small intestinal disease causes diarrhea only if the material exiting the ileum exceeds the absorptive capacity of the colon or causes colonic secretion of water. Thus, diarrhea means there is intestinal disease, but a lack of diarrhea does not eliminate significant small intestinal disease.

Answer 362

Acute pancreatitis, hepatic insufficiency, renal failure, and hypoadrenocorticism. Hyperthyroidism is an important non-GI cause of feline diarrhea.

Answer 363

The next decision in patients with chronic small intestinal disease is whether maldigestion (e.g., exocrine pancreatic insufficiency [EPI]) or malabsorption exists. Rare in cats, EPI is an important consideration in dogs. Serum trypsin–like immunoreactivity (TLI) is the most sensitive and specific test for EPI. Once EPI is eliminated, malabsorptive disease is diagnosed by exclusion.

Answer 364

Malabsorptive disease is divided into protein-losing enteropathy (PLE) and non-PLE. This distinction is important because severe hypoalbuminemia is associated with a poor prognosis, and PLE is usually an indication for an aggressive diagnostic approach.

Answer 365

Protein-losing enteropathy is typically only considered in hypoalbuminemic patients, but PLE is a concern whenever serum albumin concentrations progressively decrease. One must measure serum albumin; serum total protein is inadequate. Panhypoproteinemia is neither sensitive nor specific for PLE, especially where hyperglobulinemia is common. Serum albumin concentrations

Answer 366

Fecal alpha-1 protease inhibitor concentrations can be helpful when PLE is suspected but cannot be diagnosed by exclusion. Most PLE and hepatic insufficiency patients are hypocholesterolemic while many protein-losing nephropathy patients are hypercholesterolemic. Imaging, endoscopy, and biopsy are usually desirable in PLE patients, but therapeutic trials (e.g., ultra–low-fat diet for lymphangiectasia) are done if anesthetic risk is too great or client constraints dictate otherwise.

Answer 367

Any GI disease may cause PLE, but the most common causes in adult dogs are probably lymphangiectasia, lymphoma, fungal infections (regional), and inflammatory bowel disease (IBD). Lymphangiectasia can be difficult to diagnose unless one is aware of its subtleties. Occult parasitism and chronic intussusception are important in younger dogs. In cats, IBD and lymphoma are the main causes. Other causes include ulcers/erosions, antibiotic-responsive disease, and intestinal crypt lesions.

Answer 368

The major causes of non-PLE malabsorptive disease in dogs are dietary-responsive disease, antibiotic-responsive disease, and parasites. IBD is often listed as an important cause.

Answer 369

A full discussion is beyond the scope of this chapter, but there is concern that IBD has been overdiagnosed in the past because IBD is not simply a histologic diagnosis. One must find inflammation and eliminate known causes (e.g., diet, parasites, bacteria). In cats, dietary-responsive disease, lymphoma, and IBD appear to be the most common causes, but hyperthyroidism closely mimics primary GI disease.

Answer 370

TREATMENT Chronic canine large bowel disease tends to be dietary-responsive, fiber-responsive, “clostridial” colitis (i.e., tylosin-responsive), and parasitic. Histoplasmosis and pythiosis are regionally important. Cats tend to have dietary-responsive, clostridial, parasitic (e.g., Tritrichomonas), and IBD colitis. Measuring serum cobalamin and folate concentrations can be helpful in select dogs and cats. Hypocobalaminemia is relatively specific for small intestinal disease; however, sensitivity is questionable.

Answer 371

Cobalamin and folate determinations are insensitive and nonspecific for canine antibiotic-responsive (i.e., small intestinal bacterial overgrowth) disease. Hypocobalaminemia in an animal with weight loss, but without diarrhea, is strong evidence of small intestinal disease; however, normal values are not helpful. Cobalamin supplementation can benefit hypocobalaminemic cats, and hypocobalaminemia may be prognostic in dogs.

Answer 372

Melena is defined as a black, tarry stool created by the digestion of blood in the proximal gastrointestinal tract. The breakdown products of hemoglobin produce the black color.

Answer 373

Sources of blood to consider are the respiratory tract, where blood may be coughed up (hemoptysis) and swallowed, and the proximal gastrointestinal tract including the oral cavity, stomach, and duodenum. A black stool color may also be produced by antidiarrheal medications containing bismuth and salicylate as well as by diets containing raw meat, leading to a spurious diagnosis of melena. The majority of these conditions result in gastrointestinal hemorrhage and melena by directly or indirectly disrupting mucosal barriers to injury.

Answer 374

Defense mechanisms utilized by the gastrointestinal mucosa include: a hydrophobic mucus layer and hydrophobic nature of mucosal cells, mucosal secretion of bicarbonate, epidermal growth factor and epithelial restitution, a high rate of mucosal blood flow, and prostaglandins.

Answer 375

DIAGNOSIS Assessing a patient who presents with melena is aided first by determining the source of digested blood: respiratory or gastrointestinal. Determine immediately if the owner administered bismuth subsalicylate, or if the patient has ingested raw red meat (especially liver), spleen, or beets. By first ruling out causes for black stool other than respiratory or gastrointestinal hemorrhage, the focus can shift toward diagnosing significant pathology (see Figure 49-1). Question the owners about the presence of clinical signs other than melena. Exercise intolerance, coughing, tachypnea, or dyspnea raise suspicion for disease of the respiratory tract, while anorexia, regurgitation, vomiting, and abdominal tenderness signify a gastrointestinal origin of disease. Ask specifically about administration of corticosteroids and nonsteroidal antiinflammatory drugs (NSAIDs). Both will reduce the production of protective prostaglandins by inhibiting either cyclooxygenase (NSAIDs) or phospholipase A2 (corticosteroids), thus leading to gastric mucosal injury through a variety of mechanisms. NSAIDs also cause direct damage to gastric cells and their protective mucus layer. The concurrent use of NSAIDs and corticosteroids appears to confer the greatest risk for gastric ulceration and erosion (GUE). Determine whether the patient had any opportunity (observed or intimated) to ingest anticoagulant rodenticides, corrosive compounds, trash containing raw or decaying meat, or foreign bodies.

Answer 376

Anemia is the most common finding on the CBC of a patient with melena. The anemia can be mild to severe, and a regenerative response may be evident if sufficient time has elapsed. Chronic low-grade hemorrhage will result in a nonregenerative anemia. Thrombocytopenia may be present as a primary cause for melena, or as a secondary disorder due to consumption. Leukocytes may be decreased, within normal range, or increased as a result of the underlying disease. Common abnormalities on the serum biochemistry include elevated blood urea nitrogen (BUN), and hypoalbuminemia or panhypoproteinemia owing to whole blood loss and/or protein-losing enteropathy (PLE). Elevated hepatic enzymes and azotemia should raise suspicions for liver or renal disease as the primary cause for gastrointestinal hemorrhage. Hyponatremia is often a finding in cases of hemorrhage, as well as in cases of hypoadrenocorticism in conjunction with hyperkalemia. Prolonged coagulation times will aid in diagnosing cases of rodenticide toxicity and disseminated intravascular coagulation (DIC). A variety of gastrointestinal parasites, enterotoxigenic bacteria, and other organisms can create melena.

Answer 377

Stool containing fresh, undigested blood originating from the colon, rectum, or anus. Some overlap exists between the potential causes of melena and hematochezia; however, differentiating the two clinical signs is important in order to formulate the most appropriate diagnostic and therapeutic plans. DIAGNOSIS Similar to the approach to melena described above, thorough history taking and physical exam are paramount to successfully diagnosing hematochezia and its underlying cause

Answer 378

Constipation is defined as infrequent or difficult evacuation of dry, hard feces. Obstipation is a severe form of constipation where the feces are so dry and hard, or the constipation is so longstanding, that the animal is no longer able to defecate. Obstipation requires medical intervention.

Answer 379

Tenesmus is ineffectual and painful straining at defecation or urination. Dyschezia is difficult or painful evacuation of feces from the rectum.

Answer 380

In contrast to tenesmus, dyschezia is a result of disease of the anal and perianal tissues, whereas tenesmus is a result of disease of the large intestine or lower urinary tract.

Answer 381

Fecal incontinence is defined as defecation without conscious control.

Answer 382

PHYSIOLOGY OF THE LARGE INTESTINE The large intestine or colon serves two main functions in the dog and cat: absorption of water and electrolytes and storage of feces.

Answer 383

Absorption of water and electrolytes occurs primarily in the ascending and transverse colon, whereas the descending colon is mostly the site of storage of feces.

Answer 384

At rest, considerable mixing of colonic contents occurs as a result of segmental contractions of the colon. These contractions, called haustral contractions, are coordinated contractions of the circular and longitudinal smooth muscles of the colon that result in accumulation of colonic contents in unstimulated segments. This mixing of colonic contents increases exposure of contents to colonic mucosa for maximum water and electrolyte absorption, while slowly propelling the ingesta down the length of the colon.

Answer 385

In addition to haustral contractions, there are periods of intense propulsive activity down the entire length of the colon. These are called mass movements, and they serve to propel fecal matter toward the anus in preparation for defecation. These mass movements occur only a few times daily in contrast to the continuous haustral contractions. Mass movements are most common following a meal and are stimulated by the autonomic nervous system.

Answer 386

The anal sphincter is composed of two layers: an internal anal sphincter composed of smooth muscle, which is a direct extension of the circular smooth muscle of the rectum, and an external anal sphincter composed of striated muscle.

Answer 387

The internal anal sphincter remains contracted most of the time and is the layer most responsible for fecal continence.

Answer 388

The internal sphincter receives its parasympathetic nervous supply from the sacral spinal segments via the pelvic nerve. Its sympathetic innervation is from the lumbar spinal segments via the hypogastric nerve.

Answer 389

Sympathetic stimulation results in contraction of the internal anal sphincter, whereas parasympathetic stimulation results in relaxation. As mass movements propel feces into the rectum, the internal anal sphincter is stimulated to relax. This usually results in defecation.

Answer 390

Diets low in fiber or high in indigestible material such as hair or bones may contribute to constipation. Lack of exercise and weakness can also be contributing factors to constipation. Good hydration status is essential for normal defecation. Animals who have had restricted access to water or who otherwise experience decreased water intake (e.g., anorexia) commonly experience constipation. Similarly, increased water loss due to polyuria or vomiting can also lead to constipation if there is insufficient water intake to replace lost body water. Colonic or rectal obstruction, either intraluminal (masses or foreign bodies) or extraluminal (mass compressing colon, pelvic fractures, perineal hernia, pseudocoprostasis), can likewise inhibit or prevent defecation and result in constipation. Neurologic abnormalities such as idiopathic megacolon or dysautonomia may likewise result in constipation due to impaired colonic motility (Figure 50-2).

Answer 391

It is important to localize the cause of straining to diseases of either the lower urinary tract or the lower gastrointestinal (GI) tract. Inflammatory and infectious diseases of the lower GI tract, such as inflammatory bowel disease, dietary indiscretion, intestinal parasitism, idiopathic colitis, pythiosis, and bacterial or fungal colitis, can cause irritation and straining at defecation. Obstructions, both intraluminal (colonic neoplasia, foreign bodies, and strictures) and extraluminal (pelvic fractures, extraluminal masses, or organomegaly), can make defecation difficult and result in tenesmus. Dyschezia results from diseases of the anus and perianal region including anal sacculitis, perianal fistulas, perineal hernia, anal/rectal neoplasia, and pseudocoprostasis Urination must be evaluated carefully to rule out lower urinary tract disease as a cause of tenesmus.

Answer 392

FECAL INCONTINENCE Fecal incontinence can be due to damage to the anal sphincter (nonneurogenic sphincter incompetence), disruption of the nervous supply to the anal sphincter (neurogenic incompetence), or reduced capacity or compliance of the rectum (reservoir incontinence).

Answer 393

With reservoir incontinence, the animal is aware of the urge to defecate, but conscious control of defecation is overwhelmed by the presence of colorectal disease causing irritation, decreased storage capacity of the rectum, or overwhelming fecal volume. Diseases that can damage the anal sphincter and cause nonneurogenic sphincter incompetence include anal trauma or surgery, anal neoplasia, and damage to the levator ani and coccygeus muscles. Conditions that can result in neurogenic sphincter incompetence include cauda equina syndrome; damage to the pudendal nerve; sacral spinal cord trauma, neoplasia, compressive lesions, and degenerative myelopathy.

Answer 394

The term flatulence refers to excessive accumulation of gas in the gastrointestinal tract. It may be associated with eructation, borborygmus, or flatus. Eructation is the expulsion of gas from the stomach. Borborygmus is a rumbling noise caused by the propulsion of gas through the gastrointestinal tract. Flatus is the anal passage of intestinal gas.

Answer 395

PATHOPHYSIOLOGY The major gastrointestinal gases are nitrogen and oxygen, which are derived from swallowed air and diffusion from blood, and hydrogen, carbon dioxide, and methane, which are primarily products of bacterial metabolism and fermentation and nonbacterial reactions (e.g., pancreatic bicarbonate interacting with acid to produce carbon dioxide) that occur in the bowel lumen. In human beings, and probably in dogs and cats, as much as 99% of flatus is composed of these odorless gases. The remaining 1% is composed of odoriferous gases, including hydrogen sulfide, methanethiol, dimethylsulfide, ammonia, skatole, mercaptans, volatile amines, and short chain fatty acids. These odoriferous gases also result from bacterial metabolism and fermentation. Sulfur-containing gases, particularly hydrogen sulfide, have been shown to be a major determinant of the malodor of canine flatus.

Answer 396

Most of the gas that enters the digestive tract is thought to come from swallowed air. Aerophagia mainly occurs during the ingestion of liquids and solids and can be exacerbated by rapid or competitive eating situations. Most swallowed air is subsequently eliminated by eructation from the stomach and esophagus. If not eructated, the nitrogen contained in swallowed air travels through the gastrointestinal tract with minimal absorption and subsequently is passed. It is noteworthy that the transit time for gas is considerably shorter than that for liquids or solids. Air entering the intestinal tract can be passed out the rectum rapidly (within minutes). Gases can also be removed by diffusion into blood or consumption by bacteria

Answer 397

The composition and volume of flatus are affected by the quantity and variety of nutrients eaten, as well as by the type and abundance of bacterial flora. A significant amount of gas is formed from the bacterial fermentation of both dietary (e.g., fiber and poorly digestible carbohydrates and proteins) and endogenous substrates (e.g., mucin, bile acids). Foods such as legumes (soybeans, beans, peas) that contain large amounts of indigestible oligosaccharides are apt to produce large amounts of intestinal gas.

Answer 398

The oligosaccharides are fermented to hydrogen and carbon dioxide by Clostridium organisms and other bacteria. Maldigestion due to exocrine pancreatic insufficiency or malabsorption resulting from small intestinal disease often leads to excessive intestinal gas caused by the fermentation of malassimilated substrates. Lactose intolerance also can cause flatulence.

Answer 399

The management of flatulence begins with changing the diet (Figure 51-1). Feeding a highly digestible diet reduces the food residues available for bacterial fermentation. The diet should not contain excessive amounts of rapidly fermentable fiber. Vegetarian-based diets should be avoided because these products often have sulfur-containing vegetables and legumes. Optimally, the diet should be lactose deficient. Changing sources or amounts of dietary protein, carbohydrate, and fat may benefit individual animals. Diets containing rice as the primary carbohydrate source may produce less intestinal gas than diets containing other sources of carbohydrate. Suitable commercial foods are available from most major pet food manufacturers. Dietary trials may be necessary to find a food that reduces flatulence or objectionable flatus. Vitamin-mineral supplements may increase intestinal bacterial activity and probably should be avoided.

Answer 400

Pharmacologic management involves reducing or controlling the amount of flatulence and/or the objectionable odor of flatus. Substances that can be used include simethicone, activated charcoal, bismuth subsalicylate, zinc acetate, Yucca schidigera preparations, alpha-galactosidase, pancreatic enzyme supplements, probiotics, and homeopathic remedies. These substances are preferentially used in conjunction with dietary changes

Answer 401

– Neurologic

Answer 402

The cerebral cortex and the peripheral nervous system are the parts of the nervous system most susceptible to systemic disease. However, white matter changes, brainstem signs, and cerebellar signs have also been documented secondary to systemic conditions.

Answer 403

DISEASES CAUSING CNS SIGNS Diseases causing central nervous system (CNS) signs are presented in Table 52-1.

Answer 404

Hypoxia from Systemic Disease Hypoxic encephalopathy is the result of reduction of cerebral oxygen supply, either from decreased arterial oxygen tension or reduced cerebral blood flow. Hypoxia can occur secondary to an anesthetic accident, hematologic disorders (especially anemia), or cardiovascular and respiratory failure.

Answer 405

Autoregulatory mechanisms provide a relatively constant cerebral blood flow despite changes in systemic arterial pressure. These mechanisms fail when blood pressure decreases below 50 mm Hg. Anesthetic accidents can result in hypotension, cardiac arrhythmia, extensive blood loss, hypercapnia, and hypoxemia. Some areas of the brain are more susceptible to energy deprivation or may contain a higher concentration of N-methyl-d-aspartate (NMDA) membrane receptors.

Answer 406

Increased release of the excitatory neurotransmitter glutamate in cell injury leads to increased cellular influx of calcium and neuronal death.

Answer 407

Changes in blood flow to the brain may occur secondary to 1. hyperviscosity from polycythemia (relative or absolute), 2. hypercholesterolemia/hyperlipidemia (familial hyperlipidemia, hyperadrenocorticism, hypothyroidism), 3. immune-mediated disease, 4. sepsis, 5. coagulopathies 6. hyperglobulinemia.

Answer 408

Visual lost being a common neurologic sign in cats after anesthetic accidents. White matter can be detected on magnetic resonance imaging (MRI) images Steroids are contraindicated and may cause further brain damage. Recovery is slow, taking weeks to months, and residual neurologic signs may be present in severe injuries.

Answer 409

Hypertension A rapid and sustained rise in blood pressure causes the autoregulatory mechanism for maintaining blood flow to fail and results in hypertensive encephalopathy. Neurologic signs occur at a lower blood pressure (170 mm Hg) if hypertension develops rapidly.[5] Common neurologic signs are seizures, ataxia, stupor, and blindness. Postmortem findings may include cerebral edema, caudal displacement of the vermis of the cerebellum, arteriolar hyalinosis, hyperplastic arteriosclerosis, ischemia, and necrosis (the latter two abnormalities are rare). Multiple petechial hemorrhages in the brain have been reported on both autopsy and MRI of persons with longstanding hypertension.[6] Cats may show neurologic signs due to hypertension after renal transplantation. Controlling the hypertension in these patients reduces the prevalence of seizures and neurologic complication–related deaths.[7] Dogs with chronic renal failure are more likely to develop uremic crisis if they have systemic hypertension.[8]

Answer 410

1. portosystemic shunt (PSS), 2. microvascular dysplasia, 3. idiopathic noncirrhotic portal hypertension, 4. other causes of liver failure.

Answer 411

Neurologic manifestations occur in 95% of dogs with PSS. The clinical signs may be more obvious after a meal and tend to be waxing-waning. The neurologic signs are typical of diffuse cerebral disease and vary from mild—an inability to learn new things and behavioral changes—to more severe—head pressing, blindness, mentation changes and seizures. Brainstem and cerebellar signs have also been described.

Answer 412

Various endogenous toxins (amino acids, ammonia, mercaptans, γ-aminobutyric acid [GABA], false neurotransmitters) normally cleared by the liver contribute to CNS signs

Answer 413

glutamine, quinolinic acid, tryptophan, and tryptophan metabolites

Answer 414

Activation of GABA receptors by increased levels of endogenous benzodiazepines may contribute to the clinical signs of HE, and a withdrawal effect may cause postsurgical seizures.

Answer 415

Hepatic encephalopathic signs have successfully been treated with flumazenil, a benzodiazepine-receptor antagonist. Studies in people and rats have demonstrated improvement in neurologic signs after treatment with flumazenil or a benzodiazepine-receptor partial inverse agonist; these data also support a role of increased GABAergic tone in the pathogenesis of HE.

Answer 416

Medical therapy is aimed at decreasing the production and absorption of toxins generated by bacteria in the gastrointestinal tract. These therapies include feeding low-protein diets and administration of antibiotics and/or lactulose.

Answer 417

Potassium bromide at a dose of 40 to 60 mg/kg PO, once daily, or gabapentin 20 to 60 mg/kg/day, divided TID, may aid in controlling seizures. Sodium bromide, IV, can rapidly increase serum levels. Phenobarbital should be used with caution since it is protein bound and metabolized by the liver. However, 3 to 5 mg/kg BID may effectively control seizures. Benzodiazepine (0.5 mg/kg) may prevent postsurgical withdrawal seizures.

Answer 418

Renal Encephalopathy Toxic substances not excreted due to renal failure can cause encephalopathic signs similar to those typical of HE. Increased concentrations of parathyroid hormone (PTH) and subsequent hypercalcemia may have a major role in renal encephalopathy. Treatment can be directed at lowering PTH levels using calcitriol (although not without risk of causing hypercalcemia and hyperphosphatemia) and minimizing uptake of phosphorus through phosphate binders and low-phosphate diets. Treating high blood pressure can lower the risk for hypertension encephalopathy.

Answer 419

Hypothyroidism Acute or chronic progressive central vestibular signs may be the sole clinical sign in dogs with hypothyroidism. Since thyroid hormone affects virtually every cell and organ, neurologic signs as the only evidence of hypothyroidism should be considered rare.

Answer 420

Hypercholesterol-induced or hypertriglyceride-induced microthrombi may result in infarcts detectable with MRI. Intermittent vestibular signs may be seen with transient microthrombi, which result in transient ischemic attacks. In these cases no changes are detected on MRI or on histology of the brain. Cerebrospinal fluid analysis may reveal an increase in protein content.

Answer 421

Pathogenesis of hypothyroidism-associated abnormalities are likely multifactorial, and include atherosclerosis-causing infarcts or transient ischemic attacks, segmental demyelination, dysfunction of metabolic pathways within the brain, and metabolic derangement of neuronal or glial cell populations.[35,36] Treatment with thyroxin usually resolves neurologic signs.

Answer 422

Myxedema coma is a rare but life-threatening manifestation of hypothyroidism. Clinical signs include mentation changes, hypothermia without shivering, nonpitting skin edema, and bradycardia. Brain edema occurs.

Answer 423

Hyponatremia and hypoventilatory hypoxia can worsen neurologic status. Treatment consists of adequate ventilation, 0.9% sodium chloride IV, passive correction of hypothermia, and levothyroxine, 5 µg/kg, IV, q12h followed by maintenance thyroid supplementation orally. Mortality is high with this condition and clinical improvement, if it is to occur, is usually seen within 24 hours.

Answer 424

Congenital hypothyroidism has been described in numerous dog breeds as well as in cats. Clinical signs include disproportionate dwarfism, abnormal hair coat, lethargy, a stiff/stilted gait and abnormal mentation. Histologically, hypomyelination can be seen in the corpus callosum, corona radiata, pons, pyramids, and the lateral funiculi of the spinal cord.

Answer 425

Hyperthyroidism Cats with hyperthyroidism may show mild CNS signs that can include hyperactivity, change in sleep/wake cycle, aggression, or obtundation. The neurologic signs improve and may completely resolve with treatment.

Answer 426

Hyperadrenocorticism Direct compression from a pituitary macroadenoma can cause mild to severe neurologic signs. Inappetence, mild obtundation, pacing, and disorientation. These clinical signs are typically associated with tumors that are >8 mm in greatest diameter but less than 1.5 mm. More worrisome signs are associated with masses >1.5 cm in greatest diameter that include obtundation, circling, tetraparesis, ataxia, and seizures. Blindness is more common in humans with macrotumors than in dogs or cats. Hyperlipidemia may result in infarcts.

Answer 427

Since it cannot synthesize glucose It is estimated that the brain requires ∼100 g of glucose per day. Persistent hypoglycemia not only impairs cellular function directly, it can also cause vascular constriction, which reduces oxygen delivery to the brain.

Answer 428

Simple poor nutrition (puppy hypoglycemia, for example), insulinoma, liver failure, hypoadrenocorticism, nonislet cell tumors producing insulin-like growth factors, large metabolically active tumors (leiomyosarcoma), severe polycythemia, sepsis Hypoglycemia can also be associated with exogenous insulin overdose or as a paraneoplastic syndrome.

Answer 429

Waxing and waning signs with episodes of obtundation and weakness, disorientation, tremors, partial or generalized seizures, blindness, and coma are seen. There is no correlation between the severity or frequency of clinical signs, degree of hypoglycemia, and survival time posttreatment. A low fasting blood glucose helps in the diagnosis.

Answer 430

Symptomatic treatment with IV glucose (2 to 4 mL/kg of 50% glucose diluted to 25% concentration) usually reverses the neurologic signs quickly. Hypoglycemia resolves if the underlying cause is removed. Medical management with prednisone to stimulate gluconeogenesis and glycogenolysis together with frequent feeding of a high-protein, high-fat, and high–complex carbohydrate diet can be used as adjuncts to surgical treatment or as a sole treatment.

Answer 431

Inhibits insulin secretion, stimulates production of glucose by the liver, inhibits glucose uptake by the cell. It has been successfully used in dogs but not in cats with insulin-producing tumors.

Answer 432

Permanent brain damage from neuronal death may cause persistent neurologic signs despite normalization of blood glucose and insulin levels with treatment.

Answer 433

For decarboxylation of pyruvic acid and other α-keto acids.

Answer 434

1. Decreased utilization of pyruvic acid and some amino acids, 2. Increased utilization of fats, 3. Aciduria.

Answer 435

Thiamine deficiency occurs in cats and dogs fed meat preserved with sulfur dioxide, food low in thiamine due to processing, or thiaminase-containing fish.

Answer 436

Polioencephalomalacia with bilateral symmetrical spongiosis, necrosis, and hemorrhage in the medial vestibular nuclei, caudal colliculi, cerebellar nodulus, and the subcortical grey matter. Experimental thiamine deficiency in cats led to learning deficits likely caused by lesions in the hippocampal formation. Neurologic signs of thiamine deficiency reflect lesions in the cerebrum and vestibular nuclei. Hyperintense lesions can be detected with MRI on T2-weighted and FLAIR images, and the lesions contrast-enhance postgadolinium. Oral supplementation with thiamine at 25 to 50 mg BID results in resolution of clinical signs after weeks to months.

Answer 437

Hypercalcemia due to primary hyperparathyroidism or secondary to malignant neoplasm rarely has been related to seizures. The mechanism for seizures due to hypercalcemia is poorly understood. Coagulopathies in hypercalcemic dogs have been documented.[55]

Answer 438

Hypocalcemia due to renal failure, primary hypoparathyroidism, or lactation (eclampsia) causes increased membrane excitability in both CNS and muscle. Hypocalcemia can result in generalized weakness, tetany, and seizures. Treatment consists of 0.5 to 1.5 mL/kg 10% calcium gluconate IV over 10 to 20 minutes while monitoring the heart rate and treatment of the underlying cause to prevent recurrence (see

Answer 439

Hypernatremia/Hyponatremia Severe hyponatremia can cause cerebral edema and life-threatening, diffuse encephalopathy. Overaggressive correction of hyponatremia in dogs may cause CNS signs due to cerebral edema with central pontine myelinolysis and loss of oligodendroglial cells 48 hours to several days after treatment. MRI shows bilateral symmetrical hyperintense areas on T2-weighted images in the central thalamic nuclei.

Answer 440

Correction of hyponatremia should not exceed 10 mEq/L during a 24-hour period to prevent these lesions. Aggressive IV saline treatment in symptomatic patients with hyponatremia of less than 24-hour duration may be successful without causing neurologic signs.

Answer 441

With hypernatremia, osmotic movement of water out of the brain cells results in reduction of brain volume, which may cause rupture of cerebral vessels and focal hemorrhage.

Answer 442

Severity of neurologic signs is related to the rapidity of onset of the hypernatremia rather than the magnitude of hypernatremia. In chronic hypernatremia the brain adapts to the hypertonicity by the production of idiogenic osmoles, which prevent cellular dehydration.

Answer 443

Rapid correction of hypernatremia results in movement of water into the cells and development of cerebral edema.

Answer 444

Mild hypernatremia can be corrected by offering water in animals that are drinking. More severe hypernatremia can be treated with IV hypotonic saline or 5% dextrose in water.

Answer 445

Free water deficit = 0,6 x body weight (kg) x( (plasma Na/148)-1)upphöjt i 61

Answer 446

from direct invasion or metastasis, or secondary to ischemic and hemorrhagic infarcts as well as transient ischemic attacks. Diagnosis is made by MRI and cerebrospinal fluid (CSF) analysis as well as by identifying the primary neoplasia. Paraneoplastic syndromes such as hypoglycemia induced by an insulin-producing tumor and hypercalcemia secondary to lymphoma, thymoma, and apocrine adenocarcinoma directly affect the CNS.

Answer 447

hepatocellular degeneration, disseminated intravascular coagulation, respiratory alkalosis reduction in mean arterial pressure. Mentation changes, loss of pupillary light reflex and oculocephalic reflex, as well as tetraparesis can be seen.

Answer 448

DISEASES CAUSING PNS SIGNS Diseases causing peripheral nervous system (PNS) signs are listed in Table 52-1.

Answer 449

cardiac disease, hyperadrenocorticism, neoplasia, disseminated intravascular coagulation, sepsis, renal disease, atherosclerosis from a condition like hypothyroidism, or autoimmune hemolytic anemia.

Answer 450

Chronic exercise intolerance with pelvic limb weakness, or more acute symmetric or asymmetric pelvic limb ataxia, paresis, or plegia. Such neurologic signs are due to an ischemic myopathy, neuropathy, or myelopathy. Cats usually have peracute signs that include tachypnea, hypothermia, paraparesis, or plegia. Underlying causes are cardiomyopathy, hyperthyroidism, and neoplasia

Answer 451

Thyroxine (T4) stimulates mitochondrial respiratory activity, thus facilitating production of adenosine triphosphate (ATP).

Answer 452

In hypothyroidism, ATP deficiency impairs the Na+/K+ pump activity, reducing axonal transport. This results in axonal degeneration and demyelination. Myopathy has also been described secondary to hypothyroidism. In rare circumstances, neurologic signs may be the only manifestation of hypothyroidism. Neurologic signs include generalized weakness and muscle atrophy, focal signs such as laryngeal paralysis, megaesophagus, facial paralysis, and peripheral vestibular signs.

Answer 453

Hyperthyroidism Hyperthyroidism in cats can cause neuromuscular weakness with ventroflexion of the neck, a plantigrade stance, and exercise intolerance. The clinical signs are reversible with treatment of the hyperthyroidism

Answer 454

Hyperadrenocorticism Hyperadrenocorticism is usually associated with muscle weakness. In rare cases, dogs have fibrotic myopathy or polyneuropathy. Clinical signs in fibrotic myopathy may include a stiff, stilted gait; generalized muscle atrophy; and difficulty flexing the limbs. The clinical signs with the polyneuropathy include a general weakness and muscle atrophy.

Answer 455

Hypoadrenocorticism results in episodes of lethargy, weakness, tremors, and collapse. Painful episodes of muscle cramps are extremely rare.[77] Secondary hypoglycemia contributes to the generalized weakness. Treatment with physiologic doses of glucocorticoids (0.1 mg/kg) results in full clinical recovery.[78,79]

Answer 456

Diabetes Mellitus The peripheral nerves are dependent on glucose for their metabolism. A sensorimotor polyneuropathy is a late complication of diabetes mellitus (DM). The two major theories about the pathogenesis are metabolic derangement and vascular changes. Clinical signs are most prominent in the pelvic limbs with a plantigrade stance, difficulty jumping, postural reaction deficits, decreased tendon reflexes, and muscle atrophy. Neuropathic signs are much more common in cats than in dogs. Horner's syndrome has been reported secondary to DM. Abnormalities on nerve conduction studies and EMG are found in both thoracic and pelvic limbs. Histopathologic findings are demyelination, splitting, and ballooning of the myelin sheath, and axonal injury.

Answer 457

Dogs and cats with chronic renal failure may have weakness associated with renal secondary hyperparathyroidism, which causes a peripheral neuropathy and myopathy.

Answer 458

Inositol phosphates, protein kinase C, and cyclic adenosine monophosphate (AMP), among other regulatory enzymes and signal-transducing systems in muscle cells, are affected by calcitriol directly. The parathyroid hormone-mediated uremic myopathy may be reversible when treated with calcitriol.

Answer 459

Excess PTH also partially affects the motor nerve conduction velocity. Nerve excitability is modulated by calcitriol, which also affects the synthesis of nerve growth factors. Changes can be found on electromyography and nerve conduction studies.

Answer 460

1. reduced intake, 2. loss associated with renal failure, 3. and, in extremely rare situations, secondary to an adrenal tumor causing excess synthesis of aldosterone (primary hyperaldosteronism)— 4. or, even more rare, due to adrenal-dependent hyperadrenocorticism.

Answer 461

Hypokalemia alters the muscle cell resting membrane potential resulting in muscular weakness. The neurologic signs with ventroflexion of the neck and generalized weakness are similar to any generalized neuromuscular disorder and not pathognomic for this condition.

Answer 462

Supplementation via potassium IV initially, followed by oral administration. Administration of fluids with potassium IV may result in worsening of hypokalemia due to expansion of the vascular volume and increased renal loss.

Answer 463

Oral administration of 5 to 10 mEq of KCl per day is a safe treatment. Dopamine causes a shift of potassium from the intracellular to the extracellular fluid.

Answer 464

coagulopathy, vascular disorder, infection, and metabolic and nutritional

Answer 465

insulinoma, adenocarcinoma, cholangiocellular carcinoma, lymphoma, melanoma, myeloma, and thymoma.

Answer 466

Thymoma is a common cause of myasthenia gravis in humans and cats and less common in dogs. Neurologic signs can be focal (megaesophagus) or generalized. The myasthenia gravis may improve with removal of the mass; however, megaesophagus signals a poor prognosis.[89,90]

Answer 467

Spasticity is an increase in muscle tone due to hyperexcitable muscle stretch (myotatic) reflexes.

Answer 468

Muscle tone is the velocity-dependent resistance of muscle to passive stretch and is maintained by intrinsic muscle stiffness and the myotatic reflex mediated by the lower motor neurons. Descending upper motor neuron pathways normally attenuate the myotatic reflex. Lesions of the upper motor neuron pathway cause changes in the excitability of motor neurons, interneuronal connections, and local reflex pathways that over time lead to hyperexcitable myotatic reflexes and spasticity. The interval between injury and the appearance of spasticity varies from days to months.

Answer 469

paresis and ataxia

Answer 470

Treatment of spasticity is directed at the underlying lesion, most commonly a chronic spinal cord disease.

Answer 471

MYOTONIA Myotonia is prolonged contraction or delayed relaxation of a muscle after voluntary or stimulated contraction. Congenital myotonia is well characterized in the Chow Chow and Miniature Schnauzer and occurs sporadically in other breeds of dog and domestic cats.

Answer 472

Acquired myotonia is an uncommon complication of iatrogenic hyperadrenocorticism. Affected dogs show a stilted gait with decreased limb flexion, increased muscle tone, enlarged proximal limb muscles, percussion myotonia, and EMG evidence of myotonia.

Answer 473

TETANY Tetany is sustained muscle contraction that is worsened by stimulation and lessens with relaxation. It occurs with strychnine poisoning, which blocks the inhibitory neurotransmitter glycine.

Answer 474

EPISODIC FALLING IN CAVALIER KING CHARLES SPANIELS Episodic falling in Cavalier King Charles Spaniels, also called hypertonicity syndrome, is characterized by paroxysmal tetany or increased muscle tone usually starting around 3 to 4 months of age.

Answer 475

SCOTTIE CRAMP Scottie cramp is inherited as an autosomal recessive trait in Scottish Terriers. Clinical signs become apparent by 6 weeks to 18 months of age. Excitement or exercise induces progressive increase in muscle tone causing lumbar kyphosis and decreased flexion of the pelvic limbs, in some cases so severe that the dog falls. There is some evidence that the disease is caused by alteration in the function of the neurotransmitter serotonin

Answer 476

CONTINUOUS MUSCLE FIBER ACTIVITY Continuous muscle fiber activity occurs most commonly in Jack Russell Terriers but has also been reported in a Yorkshire Terrier, Border Collie, and a mixed breed dog and cat. The precise nature of this disorder is not yet clarified, so several names for the disease are used including rippling muscle disease and myokymia. There is increased muscle tone and visible undulating muscle contractions more obvious in proximal limb muscles. Dogs are often anxious, restless, and panting during attacks and hyperthermia is common. Episodes last from 10 minutes to several hours, but severe attacks can be fatal.

Answer 477

TETANUS Tetanus is sustained muscle contraction without relaxation. The most common cause is infection with Clostridium tetani. Under anaerobic conditions, the organism produces a toxin, tetanospasmin, that interferes with the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric acid.

Answer 478

Patients with focal tetanus present with sustained contractions in muscles close to the wound, usually the head or a limb. In generalized tetanus, patients suffer generalized muscle rigidity, trismus secondary to masticatory muscle contraction, dysphagia due to pharyngeal muscle involvement, and risus sardonicus resulting from facial muscle involvement (Figure 53-1).

Answer 479

MYOCLONUS Myoclonus is a brief, shocklike contraction of skeletal muscle. Physiological myoclonus occurs in healthy animals and typically causes no disability. Epileptic myoclonus is a rare seizure disorder in which the seizures consist of focal or generalized myoclonic jerks. Drug- and toxin-induced myoclonus occur due to several agents including intrathecal morphine, chlorambucil, and lead. The myoclonus usually resolves on withdrawal of the offending drug or treatment of the intoxication.

Answer 480

ENCEPHALOMYELITIS Encephalomyelitis caused by canine distemper virus is the most common cause of myoclonus in dogs. Affected dogs often have other neurologic signs of distemper such as ataxia or weakness, but myoclonus can be the only sign. The muscle contractions are most obvious at rest and can persist during sleep or even general anesthesia, usually occurring rhythmically every 1 to 3 seconds. Distemper myoclonus is often refractory to treatment although focal myoclonus is usually not terribly disabling. Procainamide (10 to 20 mg/kg orally every 8 hours) is effective in some cases. Other inflammatory diseases of the nervous system can also cause myoclonus in dogs, including granulomatous meningoencephalomyelitis, bacterial encephalitis, protozoal encephalitis, and steroid-responsive meningitis-arteritis.[11]

Answer 481

DYSKINESIA Dyskinesia is a general term for various forms of abnormal movement. The clinical manifestations are variable, entailing several different movements: (1) dystonia: sustained muscle contractions resulting in twisting and abnormal posture of the face, trunk, or limbs, (2) athetosis: slow, writhing movements that tend to flow into one another, and (3) chorea: rapid, arrhythmic, brief movements of the face, trunk, or limbs. Drug-induced dyskinesia should be considered in patients that develop movement disorders while taking medication. Signs typically resolve with withdrawal of the offending drug.

Answer 482

DANCING DOBERMAN Dancing Doberman disease is characterized by flexion of one pelvic limb when standing, then within several months the other pelvic limb becomes affected such that the dog alternately flexes and extends each pelvic limb in a dancing motion and prefers to sit rather than stand. This may be a type of peripheral neuropathy

Answer 483

OTHER ABNORMAL MOVEMENTS Muscle spasms caused by pain, especially intervertebral disk extrusion, can be confused with movement disorders such as myoclonus. Affected animals often suffer intermittent, painful contractions of paraspinal muscles and may flex one limb. Movement often precipitates an attack. Palpation and manipulation of the spine usually identifies the painful region. Tremor is a rhythmic oscillation of the body or body part due to alternating contractions of antagonistic muscles. It occurs with a number of disorders. Seizures can result in variety of abnormal movements and are usually recognized by their stereotypic pattern and spontaneous onset. Seizures are often accompanied by some alteration in consciousness and there may be autonomic signs, such as urination or salivation, and postictal dysfunction such as abnormal behavior and ataxia. Normal and abnormal movements can occur during sleep. Important features are that the movements only occur during sleep and the patient can be awakened normally during an episode with no postictal signs.

Answer 484

DEFINITIONS Tremor is a common presentation in dogs and cats. The terms tremble, shake, quiver, and shiver are used interchangeably to describe this involuntary, rhythmic, and oscillatory movement. Tremor results from simultaneous or alternating contractions of agonist and antagonist muscle groups. Clinically, tremor syndromes present with continuous, rapid, back-and-forth movements of the head, hind legs, or whole body; these movements cease with sleep.

Answer 485

Tremor must be distinguished from myoclonus, fasciculations, tetany, dyskinesia, and seizures. Myoclonus is defined as a sudden, short, jerky, shocklike, involuntary movement caused by an abrupt muscular contraction. Myoclonic jerks arise from electrical discharge of the central nervous system and can involve the head, limbs, or trunk. Fasciculations are arrhythmic, involuntary, visible contractions of groups of muscle fibers that indicate pathologic discharge of spinal motor neurons. Tetany is characterized by skeletal muscle rigidity and spasm. Dyskinesias are rare disorders of the central nervous system that result in involuntary, ticlike, repetitive, and episodic movements of individual muscle groups.

Answer 486

PHYSIOLOGIC TREMOR Physiologic tremors are difficult to see in normal animals, but they are present at low-amplitude movements, at rest, or with posture. Shivering is a normal response to hypothermia, and a fast-rising body temperature in the course of a febrile process may lead to trembling. In both cases, the caudal hypothalamus plays an important role in the induction of muscle oscillations. Fear, stress, joy, anger, and pain are the manifestations of a complex response processed in the limbic system, prefrontal cortex, and hypothalamus. These emotional conditions produce a complex pattern of reactions, including increased muscle tone, adrenergic stimulation, and physiologic muscle tremor. Trembling may also be seen after heavy exercise, hunger, or cold as a result of metabolic exhaustion and weakness.

Answer 487

Tremor is considered pathologic when it impairs the patient's normal function. Abnormal tremor has a more synchronous activation and larger amplitude and is more easily visualized. No classification system has been devised for pathologic tremor in animals, and little information is available on the etiology and pathogenesis of this condition.

Answer 488

Type A kinetic tremor with voluntary movements, commonly called an intention tremor, is evident when the patient performs a voluntary movement, and it is most obvious when the movement is goal oriented. Intention tremor usually presents with slow, high-amplitude, to-and-fro movements. Resting tremor is most visible in a relaxed condition and diminishes with voluntary movement; the amplitude of these oscillations is much lower, and the frequency is midrange. A fine, fast action tremor occurs when parts of the body are activated in certain positions; this type of tremor may occur when the animal is attempting greater precision of movement. Static tremor is manifested when antigravity muscles are activated.

Answer 489

Distribution Involuntary movements can be restricted to the head, and intention tremor is the most common presentation. Head bobbing in either a vertical or horizontal direction also is possible. Localized tremor may be confined to the lumbosacral area and hind legs. Generalized whole body tremors seem to be more common than focal tremors.

Answer 490

In addition to other signs, head or whole body tremors may be present in renal disease, hypoglycemia, hypocalcemia, and hypoadrenocorticism.

Answer 491

Intracranial Diseases A large number of brain diseases may cause tremors, most often with cerebellar involvement. Head tremors, intention tremors and, less frequently, whole body tremors may be part of the syndrome. Other signs often are more obvious than the tremors, such as broad-based stance, ataxia, hypermetria, central vestibular dysfunction and, less frequently, paraparesis or tetraparesis, delayed proprioceptive responses, cranial nerve deficits, abnormal behavior, and seizure like activity.

Answer 492

1. Corticoid-Responsive Tremor Syndrome 2. Orthostatic Tremor 3. Hypomyelination (An inherited genetic defect results in hypomyelination or dysmyelination in the central nervous system but normal peripheral nerves. In shaking pup syndrome, for example) 4. Spongy Degeneration

Answer 493

Numerous toxins are reported to cause generalized tremor.

Answer 494

Ataxia, paresis, and paralysis are clinical signs commonly seen in various diseases of the brain, spine, and peripheral nerves. The main difference between ataxia and paresis is that ataxia affects coordination without affecting strength, while paresis affects only strength.

Answer 495

ATAXIA Ataxia means incoordination. Ataxia is an inability for the patient to coordinate the position of its head, trunk, and limbs into space. Ataxia is a sensory, not motor, dysfunction that can only be identified when the patient moves. The type of the ataxia is characterized through a complete neurologic examination.

Answer 496

Proprioceptive, cerebellar, and vestibular.

Answer 497

A head tilt. Usually the side of the head tilt indicates the side of the lesion. Other common signs of vestibular ataxia are leaning, falling, rolling, occasionally circling, strabismus, and nystagmus.

Answer 498

The severity of vestibular signs depends on a number of factors, but it is usually worse in the acute phase of the disease, while the patient still has spontaneous nystagmus. It is important to differentiate between central and peripheral central vestibular disease because the differential diagnoses and prognoses differ greatly. Patients with central vestibular disease have changes in mental status (most commonly somnolence) and deficits in proprioceptive positioning and/or hopping. Nonambulatory tetraparesis is also commonly associated with central disease. Vertical nystagmus or positional nystagmus (one that changes direction when altering the head position) may also be seen. The proprioceptive positioning deficits are ipsilateral to the head tilt, except in cases of paradoxical vestibular syndrome, where proprioceptive deficits are contralateral to the head tilt.

Answer 499

Central vestibular signs are associated with rostral medullary lesions (brainstem) or with lesions in the flocculonodular lobe of the cerebellum and are commonly caused by encephalitis or tumors.

Answer 500

In peripheral vestibular disease, as the lesion involves the inner ear receptors located outside of the brain (petrosal part of temporal bone), the patient does not display changes in mental status or proprioceptive positioning deficits. The nystagmus is always in the same direction, either horizontal or rotatory, but not vertical.

Answer 501

Both central (brainstem) and peripheral (inner ear) vestibular disease are common. It is important to emphasize that idiopathic vestibular disease is always peripheral. If the patient has signs suggestive of central or paradoxical vestibular disease, further specific neurodiagnostic tests to investigate the brain are warranted. The most frequent causes of vestibular, cerebellar, and proprioceptive ataxias are presented in Box 55-1.

Answer 502

Cerebellar ataxia is characterized by dysmetria (inability to control the rate and range of stepping movements), which is usually manifested by hypermetria (exaggerated step). Other signs characteristic of cerebellar ataxia are head and whole body tremors, intentional tremors, and wide pelvic limb stance and gait. Patients with pure cerebellar ataxia do not display weakness (paresis) or proprioceptive positioning deficits, as they have no involvement of the upper motor neurons or conscious proprioceptive tracts respectively. This can be very useful in distinguishing cerebellar from proprioceptive ataxia.

Answer 503

Due to the close anatomic and functional relationships, occasionally patients present with a combination of vestibular and cerebellar ataxia, which indicates a central lesion.

Answer 504

Proprioceptive ataxia is the type primarily related to spinal cord diseases. This ataxia can be differentiated from vestibular and cerebellar ataxias by the absence of head involvement (tremor or tilt) (Figure 55-1).

Answer 505

Proprioceptive ataxia may be seen with brain lesions (brainstem, thalamus, basal nuclei, or cortex) but is much milder, and other brain signs are usually more obvious than the ataxia (somnolence, behavior changes, cranial nerve involvement, circling, seizures). When evaluating an animal with proprioceptive ataxia, it is important to rule out the influence of any drug (e.g., sedatives) or metabolic disorder (e.g., severe anemia) that may be causing ataxia.

Answer 506

As proprioceptive ataxia is commonly associated with spinal cord diseases, this discussion will focus on this aspect. Proprioceptive ataxia is a phenomenon of the spinal cord's white matter, reflecting a dysfunction of the sensory tracts carrying unconscious proprioception (dorsal, ventral, and cranial spinocerebellar tracts, as well as the cuneocerebellar tract. Proprioceptive ataxia is the very first sign observed with spinal cord compression, and may or may not be accompanied by proprioceptive positioning deficits (conscious proprioception [CP] deficits or knuckling).

Answer 507

Paresis means partial loss of motor function, which is usually manifested as weakness. Paralysis (plegia) refers to the complete loss of motor function.

Answer 508

The terms plegia or paresis can be used in association with a prefix to specify which limb(s) are involved. Tetra-, para-, hemi-, or mono-paresis/-plegia refers to involvement of all four limbs, pelvic limbs, ipsilateral limbs, or a single limb, respectively.

Answer 509

Paresis and proprioceptive ataxia are common signs in patients with spinal cord diseases. The more severe the spinal cord involvement, the weaker the patient becomes, until the point of paralysis.

Answer 510

Paresis can be seen with cortical or thalamic lesions, but it is usually mild and always contralateral to the lesion. More severe paresis can be seen with lesions caudal to the midbrain, and in these cases the involvement is ipsilateral.

Answer 511

Paresis or paralysis can also be seen with involvement of the peripheral nerves, neuromuscular junction, and muscle.

Answer 512

It is important to establish whether the patient has paresis with or without ataxia. Paresis without ataxia indicates that the lesion is located outside of the central nervous system and therefore not affecting the spinal cord. Clinical examples of this presentation are polyneuropathies and polymyopathies, where the patient shows variable degrees of weakness in all four limbs (tetraparesis) but does not have ataxia. In a tetraparetic patient, if the reflexes are decreased or absent, a neuropathy or neuritis (e.g., Coonhound paralysis) is likely. Myopathies cause only mild decrease in spinal reflexes.

Answer 513

If the patient is paralyzed, the lesion is within the spinal cord or somewhere along the peripheral nervous system. It is important to localize the spinal lesion as closely as possible to concentrate diagnostic efforts on the affected region.

Answer 514

The principles of upper motor neuron (UMN) and lower motor neuron (LMN) are used to localize lesions within the spinal cord. Upper motor neuron is a term used to designate a group of motor tracts originating from the brain and terminating within the spinal cord. The most important tracts forming the UMN are the corticospinal, rubrospinal, reticulospinal, and vestibulospinal tracts.

Answer 515

Basically, the combined function of the UMN is to facilitate gait in animals, inhibiting extensor muscles of the limbs while facilitating flexor muscles. As such, when the animal has an UMN spinal cord lesion, there is paresis or paralysis with increased extensor tone of the limbs (due to the lack of UMN inhibition).

Answer 516

The hallmark of UMN signs are then paralysis or paresis with increased extensor tone (spasticity or hypertonus), normal to increased spinal reflexes (hyperreflexia), and slowly progressive muscle atrophy from disuse.

Answer 517

On the other hand, LMN is formed by a group of neurons that originate in the ventral grey horn of the spinal cord or in a nuclei of the brainstem, to give origin to peripheral or cranial nerves that then innervate the target muscle(s).

Answer 518

Lower motor neuron is also known as the final common pathway because any motor activity to be displayed has to go through the LMN.

Answer 519

When the patient has a lesion somewhere along the LMN pathway, such as in the spinal cord enlargement (ventral grey horn), nerve roots, spinal nerve, peripheral nerve, or neuromuscular junction, LMN dysfunction occurs.

Answer 520

Clinical signs of LMN dysfunction are basically the opposite as those seen with UMN lesions: paresis or paralysis with absent to decreased extensor tone (flaccidity or hypotonus), decreased or absent spinal reflexes (hyporeflexia or areflexia, respectively), and rapid and severe (neurogenic) muscle atrophy.

Answer 521

The presence of UMN or LMN signs dictates the location of the lesion within the spinal cord.

Answer 522

cervical (C1-C5), cervicothoracic (C6-T2), thoracolumbar (T3-L3), and lumbosacral (L4-S3).

Answer 523

Involvement of all four limbs suggests a lesion at either C1-C5 or C6-T2.

Answer 524

Involvement of all four limbs suggests a lesion at either C1-C5 or C6-T2. Assuming increased tone and reflexes in the pelvic limbs, normal to increased tone and reflexes (UMN signs) in the thoracic limbs indicate a lesion at C1-5, while decreased to absent tone and reflexes (LMN signs) suggest a lesion at C6-T2

Answer 525

Figure 55-2!

Answer 526

Stupor and coma are pathologic abnormalities caused by an interruption in the structural, metabolic, and/or physiologic integrity of the brainstem or cerebral cortex.

Answer 527

Stupor is characterized by a state in which the animal appears to be asleep or unconscious but can be aroused by a noxious stimulus. Once the stimulus is withdrawn, however, the animal may lapse back into the sleeplike state. Coma is characterized by a state of unconsciousness in which the animal cannot be aroused even by a noxious stimulus. A strong toe pinch, for example, may elicit a flexion reflex or increased extensor tone but does not cause a behavioral response, such as crying or biting. In either case, prompt action is required to attempt to reverse these signs and correct the underlying cause.

Answer 528

PATHOPHYSIOLOGY Consciousness is maintained by sensory stimuli that act through the ascending reticular activating system (ARAS) on the cerebral cortex.

Answer 529

Decreasing levels of consciousness indicate abnormal cerebrocortical function or interference with cortical activation by the ARAS.

Answer 530

The cerebral cortex controls the content of consciousness, whereas the brainstem controls the level of consciousness. In a sense, the cerebrum is the light bulb, and the brainstem is the rheostat that regulates its brightness.

Answer 531

All sensory pathways have collateral input to the ARAS in the pons and the midbrain, and this information is projected diffusely to the cerebral cortex, where cholinergic synapses communicate constantly with cortical neurons.

Answer 532

Balance is maintained between the ARAS and the adrenergic (sleep) system, which projects from the midbrain and diencephalon (thalamus). Signs ranging from hyperexcitability to coma can be observed if imbalance exists between the two systems.

Answer 533

(1) increased intracranial pressure, (2) cerebral edema, (3) herniation of brain tissue.

Answer 534

Increased intracranial pressure can occur secondary to an increase in the volume of tissue or fluid (e.g., cerebrospinal fluid, edema, or blood) within the cranial vault; even small shifts in these volumes can have dramatic consequences. Causes of increased intracranial pressure include: 1. encephalitis, 2. meningitis, 3. mass lesions (e.g., neoplasia, granulomas, or abscesses), 4. vascular events, 5. traumatic injury, 6. underlying metabolic disturbances, such as hypertension.

Answer 535

(1) vasogenic, which is most commonly associated with brain masses and is due to a breakdown in blood-brain barrier integrity; (2) cytotoxic, which is most commonly associated with metabolic disturbances, such as hypoxia and neuroglycopenia, that cause cell or neuronal death; (3) interstitial, which is most likely associated with hydrocephalus.

Answer 536

There are four different types of herniation, two of which can induce stupor or coma: (1) caudal transtentorial herniation, in which portions of the temporal lobe shift ventral to the tentorium cerebelli and cause midbrain compression; and (2) foramen magnum herniation, the most common form, which occurs when the caudal cerebellar vermis moves through the foramen magnum, causing a compression of the displaced cerebellum and the medulla oblongata. In these cases, injury to the respiratory center, descending motor pathway tracts, and cardiovascular centers in the caudal brainstem can lead to irreversible midbrain and cerebral hypoxia and coma.

Answer 537

Mental Status and Level of Consciousness Consciousness is maintained by the midbrain ARAS, which acts as a rheostat, projecting diffusely to the cerebral cortex. Consequently, diffuse cerebral disease or midbrain disease can result in stupor, coma, or other alterations in consciousness, such as dementia. Differentiation between stupor and coma can be achieved with the application of a noxious stimulus, such as a hemostat or needle.

Answer 538

Pupil size and reactivity to light can be normal in the comatose patient; alterations in these parameters can aid in neurolocalization and prognostication. Integrity of the retinae, optic nerves, and chiasm and of the rostral brainstem is consistent with pupils that are equal in size and that respond well to light and darkness. In general, lesions of the cerebral cortex and thalamus result in normal or constricted pupils that respond to both darkness and light.

Answer 539

Lesions in the brainstem can result in unilateral or bilateral pupillary constriction (pons) or dilatation (midbrain), depending on the location. Peripheral lesions involving cranial nerve (CN) III usually result in dilated pupils with normal vision. Pupils that are bilaterally dilated (fixed) and unresponsive to light imply a guarded to grave prognosis.

Answer 540

The pathways that mediate ocular movements lie adjacent to the brainstem regions responsible for consciousness, making it clinically useful to evaluate ocular movements in the stuporous or comatose patient.

Answer 541

1. CN VIII (vestibulocochlear nerve), 2. the brainstem (vestibular nuclei, medial longitudinal fasciculus), 3. the cerebellum (flocculonodular lobe), 4. the nuclei of CN III, IV, and VI. Any disruption in this pathway results in pathologic nystagmus (rotary, horizontal, or vertical downbeat).

Answer 542

Ocular movements are evaluated by moving the head in a slow or rapid fashion from side to side while it is held in a fixed position. In the normal animal, this movement results in several beats of horizontal nystagmus (with the fast component toward the direction of the head movement) that stop once the head movement stops. If the nystagmus continues after the movement stops, if it occurs spontaneously, or if it changes with position, a lesion in the vestibular system is likely to exist.

Answer 543

If there is absence of ocular movements in the comatose patient, severe brainstem injury should be suspected, and the prognosis for return to function is guarded to grave.

Answer 544

Cheyne-Stokes respiration is characterized by hyperpnea alternating with apnea and can be an indication of a bilateral cerebral hemisphere or diencephalic lesion.

Answer 545

Central neurogenic breathing or hyperventilation is associated with lesions in the midbrain pneumotaxic center, whereas lower pontine and medullary lesions result in apneustic or ataxic (gasping) respirations, respectively. When a change in breathing patterns is noted, aggressive therapy may need to be instituted to counteract herniation.

Answer 546

TREATMENT GOALS Most dogs and cats with stupor or coma have life-threatening injuries that require immediate attention. Establishing a patent airway and maintaining respirations and cardiovascular status (in particular, blood pressure) are critical to stabilization, regardless of the underlying cause of the insult. Blood work should be evaluated, and intravenous administration of fluids, anticonvulsants, osmotic diuretics, and, in some cases, corticosteroids can be instituted to aid patient stabilization. Elevation of the head may help reduce excessive cerebral blood flow, and body temperature should be continuously monitored, especially in the case of seizures.

Answer 547

Cerebral edema can be treated using injectable corticosteroids (once the blood pressure has stabilized), osmotic and loop diuretics (mannitol and furosemide, respectively), and hyperventilation.

Answer 548

Seizures can be controlled using injectable anticonvulsants such as diazepam, phenobarbital, and pentobarbital. These treatments are discussed in more detail in the chapters on specific brain diseases. Intensive nursing care is paramount. Frequent turning (to avoid hypostatic lung congestion), bladder evacuation, ocular lubrication, optimal nutrition, and proper bedding are imperative

Answer 549

Sick brain

Answer 550

1. The prodrome is the time period prior to the onset of seizure activity; 2. The aura is the initial manifestation of a seizure. During this time period, animals can exhibit stereotypic sensory or motor behavior (e.g., pacing, licking), autonomic patterns (e.g., salivating, vomiting), or even unusual psychic events; 3. The ictal period is the actual seizure event manifested by involuntary muscle tone or movement and/or abnormal behavior lasting usually from seconds to minutes; and 4. The postictal period occurs upon completion of the seizure and can last from minutes to hours.

Answer 551

1. self-limiting (isolated) or 2. clustered (2 or more within 24 hours) and/or 3. continuous (status epilepticus).

Answer 552

Within each category, seizures are divided into being either focal or generalized. Focal seizures may be associated with a higher incidence of focal intracranial pathology[3] and are commonly seen as facial muscle twitching or with more complex behavior patterns with impaired consciousness and/or bizarre behavioral activity (termed complex partial, psychomotor, or automotor seizures).

Answer 553

Generalized seizures are subdivided into tonic-clonic, clonic, myoclonic, atonic, or absence types. Tonic-clonic seizures are the most common generalized seizure type described. Myoclonic epileptic seizures consist of rhythmic limb and/or head jerk–like movements, often with preservation of consciousness.

Answer 554

1. idiopathic (most likely inherited), 2. symptomatic (underlying brain pathology), 3. probably symptomatic (underlying unidentified brain disease that is not suspected to be of genetic origin), 4. reactive (normal brain reacting to metabolic stresses).

Answer 555

The differential diagnoses in terms of disease prevalence differ according the age of onset of the seizure. In general, dogs that are less than 1 or greater than 7 years of age have an initial interictal interval less than 4 weeks, and/or have initial focal seizures that should carry a higher suspicion for symptomatic epilepsy with appropriate diagnostic tests done, to include MRI scanning of the brain.[3] All cats without a metabolic cause for seizures should undergo MRI scanning of the brain and possible cerebrospinal fluid analysis.[5]

Answer 556

Epileptic seizures are a sign of the disease and not the cause. Always direct specific therapy to the underlying disease, as long-term antiepileptic drug (AED) treatment of seizures may not be necessary.

Answer 557

(1) identification of a structural lesion; (2) status epilepticus has occurred; (3) more than three generalized seizures occurred within a 24-hour period; (4) two or more cluster seizure events occur within an 1-year period; (5) two or more isolated seizure events occur within a 6-month period; (6) first seizure was within 1 month of head trauma; (7) prolonged ictal events (> 10 minutes), regardless of frequency; and (8) prolonged, severe, or unusual postictal periods occur.

Answer 558

Phenobarbital and bromide are the most widely used initial AEDs (Table 57-1).

Answer 559

inflammatory, infectious, neoplastic, and idiopathic.

Answer 560

Fortunately, most of the common peripheral cranial neuropathies are idiopathic and self-limiting. Idiopathic mononeuropathies affect the cranial nerves more commonly than any other peripheral nerves. A thorough neurologic examination helps to localize the lesion either to the peripheral or central nervous system. Differentiating the two is crucial for determining treatment and prognosis.

Answer 561

Multiple cranial nerve deficits most often imply that the problem is within the central nervous system even though specific exceptions are recognized. For instance, the combination of a head tilt, facial nerve paralysis, and a Horner's syndrome strongly suggests a lesion in the middle ear.

Answer 562

CN II—OPTIC NEURITIS Optic neuritis is characterized by acute vision loss and is usually bilateral. Pupils are usually dilated and unresponsive to light stimulation. There are frequently changes on the optic disk such as swollen optic disk margins and hemorrhage. Possible causes include infectious and inflammatory (and other immune-mediated disorders). Most of the time, no underlying cause is identified and the disease is presumed to be immune-mediated. Optic neuritis usually responds to immunosuppressive doses of glucocorticoids. Treatment should be started as early as possible to improve prognosis for vision. Prognosis is fair

Answer 563

Sudden acquired retinal degeneration (SARD) is a common cause of acute blindness in dogs and must be considered as a differential diagnosis. With SARD the fundic exam can be normal initially but the electroretinogram (ERG) will be abnormal (i.e., extinguished).

Answer 564

HORNER'S SYNDROME A lesion in the sympathetic innervation of the head causes a Horner's syndrome. Clinical signs include miosis, prolapsed nictitans, entophthalmia, and ptosis. All components are not necessarily present (i.e., partial Horner's), but miosis must at least be noted for diagnosis. Lesion localization varies from the midbrain through the spinal cord down to T1-T3 spinal segments, up the vagosympathetic trunk, and the cranial cervical ganglion next to the tympanic bulla (middle ear). A lesion at any level can cause a Horner's syndrome. Lesions are classified as first, second, or third order depending on which level is affected. Pharmacologic testing with topical phenylephrine can help to localize the lesion. The faster the response to topical phenylephrine (pupillary dilation), the closer the lesion is to the iris. Most cases are of third order and are recognized as idiopathic Horner's syndrome. Treatment is rarely necessary and is mainly aesthetic as vision is not impaired unless the problem is bilateral. Prognosis for vision is good.

Answer 565

CN V—TRIGEMINAL NEUROPATHY The ophthalmic, maxillary, and mandibular nerves.

Answer 566

Sensory deficits include reduced to absent palpebral and corneal reflexes as well as deficits in nasal sensation. Loss of corneal sensation can result in neurogenic keratopathy. The mandibular branch also provides motor innervation to the masticatory muscles (i.e., masseter, temporalis, pterygoid, and digastric). A dropped jaw results from a bilateral deficit in the motor function of the trigeminal nerves.

Answer 567

A lesion affecting both trigeminal nerves implies a peripheral lesion since a lesion in the brainstem affecting both trigeminal nerves would be too extensive to be compatible with life; the trigeminal motor nucleus is located in the pons at the level of the reticular formation.

Answer 568

It is essential to rule out other conditions that can cause inability or unwillingness to close the mouth such as temporomandibular joint disease, masticatory muscle myositis, or a retrobulbar lesion. Differential diagnoses for a dropped jaw include infectious (e.g., Neospora, Toxoplasma, Cryptococcus, rabies), inflammatory (immune-mediated), neoplasia (e.g., nerve sheath tumor, lymphosarcoma), and idiopathic. Idiopathic trigeminal neuritis (ITN) is the most common neurologic cause of dropped jaw in dogs. ITN mainly impairs motor function, with a variable degree of sensory loss. Treatment includes supportive care with assisted feeding. Animals usually recover within 3 weeks. Nerve sheath tumors (NST) affecting CN V alone are also relatively common.

Answer 569

CN VII—FACIAL PARALYSIS Facial neuropathy is the most common cranial neuropathy. Clinical signs associated with facial nerve deficits are acute; they include lack of palpebral closure, droopy ear, lip, and/or cheek. This condition is often associated with ptyalism. Vestibular signs are commonly seen with facial nerve deficits due to the close relationship of these nerves in two anatomic areas within the skull (i.e., brainstem and petrosal bone).

Answer 570

Peripheral facial paralysis can be secondary to otitis media/interna, trauma/iatrogenic, neoplasia of the middle ear, metabolic (e.g., hypothyroidism, other), sulfonamide neuromuscular diseases (e.g., neuropathy, myasthenia gravis [MG]), or idiopathic. The most common etiology of facial paralysis is reported to be idiopathic in about 75% of dogs and 25% of cats.

Answer 571

CN VIII—PERIPHERAL VESTIBULAR DISEASE The vestibulocochlear nerve has two branches: vestibular (balance) and cochlear (hearing).

Answer 572

Cochlear degeneration is the most common cause of hearing loss associated with aging in dogs. Acute loss of balance is a common presentation in dogs but is also seen in cats. Classic clinical signs include head tilt, ataxia, and nystagmus.

Answer 573

Once the lesion has been attributed to the vestibular system, one must differentiate between peripheral and central vestibular disease. Signs associated with a central lesion include proprioceptive deficits, changes in mentation, multiple cranial nerve deficits (other than CN VII and Horner's syndrome), cerebellar signs, and nystagmus that is either vertical or changing in directions.

Answer 574

Differential diagnoses for peripheral vestibular disease include otitis media/interna, hypothyroidism, neoplasia of the middle/inner ear, trauma/iatrogenic, ototoxic drugs, nasopharyngeal polyps, and idiopathic. Most acute vestibular disorders are idiopathic, historically called old dog vestibular disease as it affects mainly, but not exclusively, older dogs. Cats of all ages can also be affected. Idiopathic vestibular disease is a diagnosis of exclusion. No treatment is recommended except supportive care and medication for motion sickness. Prognosis is good and clinical improvement is usually seen within 2 to 4 weeks.

Answer 575

CN IX, X, XI—DYSPHAGIA, MEGAESOPHAGUS, AND LARYNGEAL PARALYSIS CN IX (glossopharyngeal), X (vagus), and XI (accessory) are important for function of the pharynx, larynx, and esophagus. When presented with possible dysphagia, it is important to differentiate between a prehension problem that would imply the lips (CN VII), the jaw (CN V), and/or the tongue (CN XII) versus a deglutition problem.

Answer 576

Primary muscle or nerve diseases, Neuromuscular disorders (e.g., MG, botulism), Brainstem lesions (e.g., neoplasia, encephalitis, other).

Answer 577

The canine esophagus contains striated muscle and is innervated by the vagus nerve throughout its length. Megaesophagus is mainly seen in dogs, and most cases are classified as idiopathic. Regurgitation is the primary clinical sign seen. Secondary aspiration pneumonia is also common. The diagnosis of idiopathic megaesophagus is a diagnosis of exclusion. Polyneuropathy, polymyopathy, MG, endocrine disorders (e.g., hypoadrenocorticism, hypothyroidism), toxicity (e.g., lead, organophosphate, thallium), esophagitis, systemic lupus erythematosus, and other causes must be ruled out to make a diagnostic of idiopathic megaesophagus.

Answer 578

The larynx is innervated by branches of the vagus, and, more importantly, the recurrent laryngeal nerve innervates the abductor muscles of the larynx. Lesions affecting the recurrent laryngeal nerve can result in dysphonia and inspiratory stridor.

Answer 579

Congenital laryngeal paralysis has been described in specific breeds. Acquired laryngeal paralysis has been associated with polyneuropathy, hypothyroidism, trauma to the recurrent laryngeal nerve, neoplasia close to the nerve (especially thyroid carcinoma), toxicity (e.g., lead, organophosphate), brainstem disease (e.g., neoplasia, encephalitis), and idiopathic.

Answer 580

Awake, Slow-wave sleep (or non-REM sleep), Rapid eye movement (REM) sleep

Answer 581

Sleep disorders are either primary or secondary. Secondary sleep disorders may result from encephalitis, intracranial masses, trauma, drug administration, or other disease processes..

Answer 582

In normal REM sleep central inhibition of the motor neurons causes atonia, with only some random twitching of distal and facial muscle groups. In REM sleep behavior disorder (RBD), there is no atonia, and coordinated movement occurs.

Answer 583

SLEEP-DISORDERED BREATHING OR SLEEP APNEA The English Bulldog has been proposed as a natural model of SDB. Bulldogs demonstrated marked oxygen desaturation in REM sleep, paradoxical breathing patterns (unsynchronized thoracic and abdominal movements), and awakening from events of apnea. These dogs also fell asleep faster than control dogs, suggesting hypersomnolence.

Answer 584

GERIATRIC CHANGES IN CIRCADIAN RHYTHM Changes in sleep-wake patterns in geriatric dogs (16 to 17 years old) have been documented, with aged dogs sleeping less at night, spending more time in SWS in the daytime, and having less REM sleep overall, compared to young adult dogs. The aged dog is proposed as a model for the similar problem in humans.

Answer 585

NARCOLEPSY (NARCOLEPSY-CATAPLEXY) Narcolepsy is a rare neurologic disorder affecting the brain and normal awake/sleep patterns. It occurs in animals (dogs, horses, cats, cows) as well as in humans, and has both sporadic and genetic forms. An abnormality in normal CNS control mechanisms of awake and sleep states appears to underlie this syndrome in affected animals. Clinically, canine narcolepsy is characterized primarily by cataplexy, the sudden involuntary loss of muscle tone, thought to be pathologically equivalent to the lack of muscle tone seen in REM sleep.

Answer 586

Pathophysiology of Narcolepsy-Cataplexy Normal sleep consists of two major stages: non-REM, light, or slow-wave sleep; and REM, deep, or fast-wave sleep. When normal animals first enter sleep, slow-wave sleep occurs initially. Thirty to 90 minutes later, fast-wave sleep occurs and alternates with slow-wave sleep throughout the normal sleep period. Sleep centers in the brainstem direct the sleep cycle by their effects on the reticular activating system (RAS), which in turn influences activity in the thalamus and cerebral cortex. Hypocretins 1 and 2, also know as orexins A and B, are neuropeptides produced in the hypothalamus. Hypocretin-producing neurons project to motor nuclei and other areas in the brain and spinal cord, including the monoaminergic and cholinergic components of the RAS. They function in promoting a wakeful state and in the control and coordination of normal sleep patterns. The hypocretin/orexin system is also involved in other hypothalamic functions including regulation of motor function (locomotion, muscle tone), energy expenditure, and autonomic functions. Clinical signs of narcolepsy-cataplexy reflect the lack of hypocretin-mediated excitation of the pathways normally responsible for inhibiting REM sleep. Excessive sleepiness, also associated with narcolepsy, reflects the lack of hypocretin excitatory influence on the RAS, which normally promotes a mentally alert state. “Primary” narcolepsy is caused by a loss of production of hypocretin peptides (due to absence or destruction of hypocretin-producing cells in the hypothalamus) or by the absence of hypocretin receptors on target cells. Forms of Primary Narcolepsy A familial form of narcolepsy caused by mutations in the hypocretin-receptor-2 gene occurs in Dobermans, Labrador Retrievers, and Dachshunds. CLINICAL SIGNS OF NARCOLEPSY The onset of clinical signs in dogs is usually before 6 months of age and often as early as 4 weeks of age with the familial form. While signs may come on very early in acquired cases, usually dogs are older than 6 months of age with 2.4 years reported as the mean age of onset. Narcoleptic dogs may show excessive sleepiness or reduced daytime activity than normal age and breed-matched dogs. . Following cataplectic episodes, dogs may get up and resume normal activities as if nothing has happened or may go into normal sleep. A diagnosis of narcolepsy is most often based on EEG recordings obtained during cataplexy showing a pattern consistent with normal awake state or REM sleep.

Answer 587

Cognitive Dysfunction in Aged Dogs. Cognitive dysfunction is not an inevitable consequence of aging in dogs and striking individual differences are more likely the rule than the exception. Some aged animals show little or mild behavioral decline. However, a subset of aged dogs develops severe cognitive deficits that may disrupt normal function to a level prompting euthanasia. Cognitive dysfunction syndrome (CDS). The clinical signs have been described using a simplified acronym DISHA—which refers to Disorientation, Interaction changes with owners or other pets, Sleep-wake cycle alterations, House soiling, and Activity changes (which might be increased, stereotypic, or reduced). Additional signs such as increasing agitation and anxiety, altered responsiveness to stimuli (which might be heightened or reduced), altered interest in food (which might be increased or reduced), and decreased ability to perform learned tasks (which might be most obvious in working dogs) may also be seen. Cognitive dysfunction that is not attributable to other systemic or central disease may reflect underlying age-associated neuropathology. There are a number of morphologic features of aging in the canine brain. For example, cortical atrophy and ventricular widening occur with age in dogs. One form of pathology, the accumulation of diffuse plaques, contains a number of proteins, of which the primary constituent is the β-amyloid peptide (Aβ). Further, Aβ can accumulate on the membranes of neurons and on the cerebrovasculature.

Answer 588

Currently there is one pharmaceutical in North America that is approved for the treatment of cognitive dysfunction in aged dogs. Selegiline (Anipryl, Pfizer Animal Health) is a monoamine oxidase B inhibitor that can improve cognitive signs in aged dogs. Its mode of action appears to be able to enhance catecholamine transmission, as well as to decrease the production and increase the clearance of toxic free radicals. Alternatively, a specially formulated senior canine food is also available, Prescription Diet Canine b/d, that contains antioxidants, mitochondrial cofactors that significantly improve cognition in both laboratory and clinical studies.

Answer 589

Cognitive Dysfunction Syndrome Physical changes in the CDS brain include ventricular dilation, vascular changes, decreased cell number, meningeal fibrosis, cerebral and cerebellar white matter degeneration, and diffuse β-amyloid plaques (β-amyloid is neurotoxic). These plaques occur mostly in the cerebral cortex and hippocampus, i.e., brain structures involved in cognition and memory. Changes in neurotransmitter levels, especially a depletion of dopamine and norepinephrine, have been implicated as well. Increase in MAO-B, an enzyme that breaks down dopamine, has been suspected to play a role in CDS. Toxic free radicals are a consequence of MAO-B activity in many species and cause cell damage and neuronal death.

Answer 590

A cough is a sudden, forceful expiration against a closed glottis. Sudden opening of the glottis and turbulent airflow create the noise identified as a cough. Coughing may occur as a conscious action or as a reflex. The coughing reflex is stimulated by mechanical or chemical irritation of the pharynx, larynx, trachea, bronchi, and smaller airways. Less commonly, disease processes involving the pleura, pericardium, diaphragm, nose, nasal sinuses, and mediastinum may also stimulate the coughing reflex. The causes of coughing in small animals may be divided into the following categories (Box 63-1): inflammatory, neoplastic, cardiovascular, allergic, traumatic and physical factors, parasitic, and fungal.

Answer 591

Dyspnea is defined as difficult or labored breathing. Dyspnea is caused by insufficient oxygenation in the blood or hypercapnia, which is sensed in the peripheral and central chemoreceptors, respectively.

Answer 592

Tachypnea is defined as an increased rate of respiration. Panting is often a normal thermoregulatory response in dogs but is almost always abnormal in cats. Inappropriate or persistent panting in dogs may be an indication of pathology including fever, anxiety, pain, metabolic disease, cardiovascular disease, endocrine disease, and hypertension. Orthopnea is defined as difficulty breathing unless in an upright position.

Answer 593

Serosanguineous fluid evident in the endotracheal tube suggests pulmonary edema (cardiogenic or noncardiogenic), fluid and food particles aspiration pneumonia, and frank blood indicates pulmonary hemorrhage.

Answer 594

Upper Airway The upper airway consists of the nasal passages, pharynx, larynx, and trachea. Patients with upper airway disease have inspiratory dyspnea only unless complicated by another condition. Stertor refers to a snoring sound that is generally due to partial obstruction of the nasal passage and/or nasopharynx. Stenotic nares, nasal foreign bodies, neoplasia, or rhinitis are all possible causes. Stridor is defined as a harsh, shrill sound that results from an upper airway obstruction, generally laryngeal in nature, but that can be due to pharyngeal, cervical tracheal, or nasal disease.

Answer 595

Laryngeal paralysis, neoplasia, polyps, brachycephalic syndrome, foreign bodies, inflammation, and tracheal collapse are the more common causes of upper airway dyspnea. These patients can become acutely dyspneic and decompensate within a matter of minutes. Sedation and active cooling procedures (if hyperthermic) may be enough to make the patient more comfortable.

Answer 596

Small Airway Small airways refer to the bronchi and bronchioles. Respiratory patterns of small airway disease are usually a quick/shortened inspiratory period and prolonged expiration, occasionally with an expiratory push. There can be an increase in abdominal effort. Auscultation may reveal very harsh bronchovesicular sounds including rhonchi (wheezes) and rales (crackles) on inspiration or expiration. These sounds are the result of partial lower airway obstruction, either secondary to bronchoconstriction and/or secretions.

Answer 597

Feline asthma is one of the more common small airways conditions encountered. Other diseases include bronchitis (allergic or chronic), smoke inhalation, bronchopneumonia, and chronic obstructive pulmonary disease. Another description of these sounds is sibilant or whistling rales that mimic a high frequency whistling sound on deep inspiration or during the expiratory wheeze.

Answer 598

Pleural Space Respiration with pleural space disease is often referred to as a restrictive pattern of breathing. Due to the pleural pathology, the respiratory rate is increased while the depth of inspiration is decreased due to the lungs inability to expand. There may be increased intercostal contraction resulting in cranial motion of the diaphragm and inward motion of the abdomen. This is referred to as paradoxical abdominal motion.

Answer 599

Auscultation findings depend upon the degree and type of pleural pathology. Types of pleural disease include pneumothorax, mass effects, idiopathic chylothorax, pyothorax, hemothorax, neoplastic and cardiogenic effusions, and diaphragmatic hernia. Effusions can result in muffled heart and lung sounds, or the lung sounds may only be heard in the dorsal fields due to displacement by fluid. Percussion of the thorax reveals dull sounds in the ventral lung fields. Pneumothorax also results in decreased lung sounds but increased resonance on percussion.

Answer 600

Cats usually have compressible chest walls, so patients with cranial thoracic masses may have decreased compliance. In any patient presenting with decreased lung sounds, a restrictive breathing pattern, and suspicion of air or fluid in the pleural space, a diagnostic pleural tap is indicated. When considered safe, a radiograph of the thorax is recommended first to ascertain tap position and other abnormalities.

Answer 601

Lung Parenchyma Dyspnea due to lung parenchymal disease tends to have a mixed (inspiratory and expiratory) component. Oftentimes there are increased bronchovesicular lung sounds and/or crackles. Changes in these sounds can be very useful for monitoring progression or improvement of an individual; however their presence does not indicate the underlying pathology. There are numerous causes of parenchymal disease including both cardiac and noncardiac pulmonary edema. Noncardiogenic pulmonary edema may be caused by upper airway obstruction or strangulation, head trauma, seizures, and electrocution. Presence of a loud heart murmur or gallop rhythm should increase suspicion of cardiogenic pulmonary edema. Pneumonia (bacterial, viral, fungal) is another common cause of parenchymal disease. In any patient with a history of vomiting, regurgitation, or recent anesthesia, aspiration pneumonia should be suspected. Other causes include hemorrhage or contusions (trauma or coagulopathy), metastatic or primary neoplasia, parasitic, or pulmonary thromboembolism (heartworm disease, Cushing's, PLN/PLE, other).

Answer 602

Innocent Heart Murmurs: Innocent heart murmurs are sounds made by the blood circulating through a structurally normal heart's chambers or valves, or through normal blood vessels near the heart.

Answer 603

GENESIS OF INNOCENT HEART MURMURS Heart murmurs are the audible expression of turbulent blood flow. The factors that determine whether flow is laminar or turbulent are described by a dimensionless quantity known as the Reynolds number; Re= V x D x ρ/η where V = mean linear average flow velocity (cm/s), D = tube diameter (cm), ρ = fluid density (no units), η = fluid viscosity (unit: poise). The higher the Reynolds number, the greater the likelihood of turbulence. In the normal circulation, the Reynolds number may rise above 200 to 400, causing small amounts of turbulence at vessel bifurcations, for example, and a Reynolds number >2000 is almost invariably associated with turbulence.

Answer 604

A blood flow velocity increases, Blood viscosity decreases, The area of the vessel increases abruptly.

Answer 605

The first and most common innocent heart murmur, Still's murmur, is a short, buzzing or musical, pure, and medium-frequency sound that is typically heard between the lower left sternal edge and apex. Carotid pulse tracings, echocardiography, and intracardiac phonocardiography indicate that it originates from the left heart. Specifically, it has been associated with high-velocity aortic flow caused by a larger left ventricular stroke volume, with or without a relatively smaller aortic valve and ascending aorta; intraluminal left ventricular bands; fibrous bands in the aortic arch; ventricular false tendons; relative bradycardia; and intraventricular periodic vibrations. The result on auscultation can be a characteristic twanging sound, analogous to the sound made by twanging a piece of string

Answer 606

Web Figure 65-1 Characteristics and examples of heart murmurs relative to their timing within the cardiac cycle. S1, First heart sound; S2, second heart sound. Murmur characteristics are listed on the left, and phonographic characteristics are displayed in blue and orange. Examples of cardiac disorders causing each murmur are listed on the right. Numbers on the far right denote audio files of heart sounds from patients (audio files available electronically). The reader may note that electrical systole (QRS complex) normally requires a brief moment to translate into mechanical systoles (S1 to S2), corresponding to electrical propagation through the ventricles and excitation-contraction coupling.

Answer 607

The second type of innocent heart murmur represents an exaggeration of normal ejection vibrations within the pulmonary trunk. It occurs in the first part of systole, when the velocity of systolic ejection is maximal. This normal pulmonary systolic murmur is short, relatively impure, or coarse. Innocent heart murmurs are better heard in pediatric patients than in adults due to a thin chest wall in youth, more angulated great vessels, and more dynamic circulation.

Answer 608

In the dog, it has been hypothesized that young animals have a larger stroke volume compared to the size of the great vessels than do older animals. This can result in an increase in flow velocity to the point of producing turbulence, either in the aorta or in the pulmonary artery, and a resultant innocent heart murmur. The increase in the velocity and associated turbulence is usually mild, so the heart murmur is soft (i.e., grade I/VI to III/VI). The innocent heart murmur generally disappears before 4 to 6 months of age, when the great vessels enlarge in diameter with growth. A notable exception is the Boxer breed, where a smaller left ventricular outflow tract is associated with systolic murmurs in otherwise normal adults.

Answer 609

A systolic whoop is a loud, high-pitched vibration resembling the call of a seagull and is thought to represent periodic vibrations of the mitral valve leaflets or other structures. A systolic whoop is striking due to its loudness but does not necessarily indicate a cardiac lesion; it occurs rarely in puppies and virtually never in cats.

Answer 610

Innocent murmurs often have a vibrating or musical quality that novice auscultators describe as surprising or “funny-sounding.” Since they are ejection-type murmurs, they are usually crescendo-decrescendo in nature, and they are best heard along the left sternal border and do not radiate to the rest of the thorax. Overall, the sound of innocent murmurs may give the impression of a “puff” (low or medium frequency) or a wheeze or “cooing” (high frequency, “musical”) that occupies part—but not all—of systole. The bell of the stethoscope is particularly useful to identify the lower “twanging” vibratory frequencies that may be present in some innocent heart murmurs. Vagal maneuvers usually decrease the intensity of an innocent (or a pathologic) heart murmur. Increases in heart rate, such as those induced by exercise, invariably increase the intensity of murmurs associated with congenital heart malformations, but increases in heart rate may increase or decrease the intensity of innocent heart murmurs in dogs. In other words, a soft-grade systolic heart murmur that decreases in intensity immediately after exercising the puppy is most likely innocent, but a murmur that increases in intensity with exercise may be innocent or pathologic.

Answer 611

In general all murmurs that are diastolic, holosystolic (pansystolic), late systolic, or continuous, or are loud (grade >III/VI), are considered pathologic and should prompt further diagnostic procedures (Figure 65-4). Indications for proceeding to diagnostic testing include any of the following: the clinician's suspicion of a pathologic murmur on initial examination, the persistence of a murmur previously thought to be physiologic and which has not disappeared several weeks after initial detection and/or by age ≥6 months, the clinician's uncertainty regarding the nature of a murmur, client/owner anxiety or wishes, and the presence of signs of decompensation such as manifestations of congestive heart failure.

Answer 612

Cardiovascular sounds of short duration are referred to as transient heart sounds and include the normally heard first heart sound (S1) and second heart sound (S2). A good orientation is palpation of the precordial impulse (left apex beat) that occurs just after S1, and the arterial pulse that is felt between S1 and S2.

Answer 613

TRANSIENT HEART SOUNDS The First (S1) and Second (S2) Heart Sounds The first heart sound is associated with closure and tensing of the atrioventricular valves (mitral and tricuspid) at the onset of systole coinciding with the QRS complex on the electrocardiogram. S1 is longer, louder, and lower pitched than the second heart sound. Causes of increased intensity of S1 include thin chest wall, tachycardia, high sympathetic tone, systemic arterial hypertension, and anemia. Diminished intensity of S1 may be auscultated in animals with obesity, pleural or pericardial effusion, diaphragmatic hernia, dilated cardiomyopathy, hypovolemia, emphysema, or a prolonged P-R interval. Splitting of S1 is occasionally auscultated at the cardiac apex in healthy, large-breed dogs or may result from electrical disturbances (ectopic beats, bundle branch blocks, cardiac pacing) or mechanical factors (tricuspid or mitral stenosis).

Answer 614

The second heart sound is associated with closure of the semilunar valves (aortic and pulmonic) at the end of systole following the T wave on the electrocardiogram. In dogs and cats, pulmonic valve (P2) closure follows aortic valve (A2) closure by a very short interval, which causes S2 to be heard as a single sound. On occasion an audible split-second heart sound may be seen in healthy, large-breed dogs during inspiration due to a longer right ventricular ejection period. Pathologic splitting of S2 occurs with heartworm disease and right-to-left patent ductus arteriosus. Delayed closure of P2 also occurs with left-to-right intracardiac shunts (atrial septal defects), pulmonic stenosis, right bundle branch block, ectopic beats, and ventricular pacing. Premature A2 closure can on occasion be noted with mitral insufficiency and mitral stenosis. Paradoxic splitting of S2 results from delayed closure of the aortic valve and is sometimes audible in dogs with aortic stenosis, left bundle branch block, ectopic beats, and systemic hypertension.

Answer 615

The Third (S3) and Fourth (S4) Heart Sounds The third and fourth heart sounds occur during diastole and are not audible in normal dogs and cats. S3 and S4 heart sounds are of lower frequency than S1 and S2 and are usually best heard with the bell of the stethoscope. When heard, S3 and S4 may sound like the triple cadence of a galloping horse. The term gallop rhythm should probably be avoided because the presence of an audible S3 or S4 has nothing to do with the heart's underlying electrical rhythm.

Answer 616

Rapid ventricular filling generates the S3 sound, also known as S3 gallop, protodiastolic gallop, or ventricular gallop. An audible S3 is most commonly heard with diastolic volume overloading as in dilated cardiomyopathy, patent ductus arteriosus, and mitral insufficiency. In dogs with mitral insufficiency, the S3 gallop may be mistaken for the second heart sound if a loud pansystolic murmur extends through the second heart sound. Protodiastolic gallop sounds in cats are most commonly associated with dilated cardiomyopathy, anemia, and hyperthyroidism.

Answer 617

The presystolic gallop, also called S4 gallop or atrial gallop, is heard just before S1 and occurs just after the P wave on the electrocardiogram. This low-frequency sound is generated by blood flow into the ventricles during atrial contraction; hence the absence of S4 gallops with atrial fibrillation.

Answer 618

An audible S4 in the cat and dog is usually associated with increased ventricular hypertrophy and stiffness and is sometimes audible in animals with third-degree atrioventricular block. At fast heart rates, rapid ventricular filling and atrial systole transpire very close together, which makes differentiation between S3 and S4 impossible. The resulting single accentuated sound is referred to as a summation gallop.

Answer 619

Ejection Sounds, Systolic Clicks, Opening Snaps, and Pericardial Knocks Ejection sounds are left basilar high-frequency sounds generated by opening of the semilunar valves or dilatation of the great vessels during early systole. These sounds are occasionally noted in pulmonic stenosis, aortic stenosis, tetralogy of Fallot, and heartworm disease.

Answer 620

Systolic clicks are mid to late high-frequency sounds usually heard best over the mitral valve area. Systolic clicks are occasionally associated with degenerative valvular disease, mitral valve prolapse, and mitral dysplasia. The genesis of the sound in dogs is uncertain but is likely caused by the sudden tensing of redundant valve leaflets or elongated chordae tendineae as they buckle into the left atrium. A systolic click should be differentiated from a split or gallop heart sound.

Answer 621

Pericardial knocks are uncommon early diastolic sounds caused by restrictive pericardial disease. Timing of the sound is similar to S3 and appears to be generated by abrupt restriction to ventricular filling by a diseased pericardium.

Answer 622

(See Figure 66-1 for timing of transient heart sounds and description of murmurs.) Figure 66-1 Murmur shapes and descriptions with some common examples. Also depicted are normal and abnormal transient heart sounds and their location within the cardiac cycle. Proto, Early; meso, mid; tele, late; A2, aortic valve closure; P2, pulmonic valve closure; S1, first heart sound; S2, second heart sound; S3, third heart sound; S4, fourth heart sound.

Answer 623

High-velocity flow, Flow from narrow restricted area into a larger area, Low blood viscosity.

Answer 624

The relationship of cardiac murmurs with flow velocity, vessel size, and blood viscosity is defined by the Reynold's number. When the number reaches a critical high level, blood flow becomes turbulent. Murmurs can be characterized and described by their timing within the cardiac cycle (systolic, diastolic, portions thereof), location (point of maximal intensity), radiation, intensity (loudness), shape, and frequency (pitch).

Answer 625

(Radius) x (Velocity)x(Density)/Viscosity

Answer 626

Timing Systolic murmurs may start immediately at the first (S1) heart sound and last through the second (S2) heart sound (pansystolic murmur), may start immediately after S1 and last until S2 (holosystolic), or may occur in early (protosystolic), mid (mesosystolic), or late (telesystolic) systole. Diastolic murmurs most commonly occur in early diastole (protodiastolic), throughout diastole (holodiastolic), or can occasionally be audible only at the end of diastole (presystolic).

Answer 627

Location and Radiation The location of a murmur refers to the valve area at which the murmur is heard best (point of maximal intensity). Alternatively, location can be described simply by the terms apex or base (e.g., left apex or mitral valve area). Some murmurs may also radiate to other areas, yielding important clues as to the source of the murmur. For example, the murmur of subvalvular aortic stenosis (PMI at left heart base) may radiate to the ventral neck area due to turbulence in the carotid arteries and may also be heard on the right cranial thorax.

Answer 628

The intensity of the murmur at its origin is determined by blood flow velocity and the rate of flow (velocity × flow = force). The intensity of the murmur at the body surface is affected by direction of the turbulent jet, character of tissue between auscultation area and the turbulent jet, and the frequency of the murmur.

Answer 629

Pitch (Frequency) A murmur's quality and pitch relate to its frequency components, which may be high, medium, low, or of mixed frequency. Most murmurs consist of midrange mixed-frequency sounds. On occasion high-frequency musical tones or low-frequency “honks” are auscultated. Musical murmurs are most commonly identified in dogs with modest mitral valve disease.

Answer 630

Shape Heart murmurs are often described by their frequency profile within the cardiac cycle in relation to their shape on a phonocardiogram. Terms that are commonly used include plateau- or band-shaped murmurs for those murmurs of equal intensity throughout their duration; decrescendo for murmurs that gradually taper off from an initial peak; and crescendo decrescendo (diamond-shaped, ejection murmur) for murmurs that build up to a peak intensity and then taper in intensity.

Answer 631

SYSTOLIC HEART MURMURS Mitral Insufficiency The murmur of mitral insufficiency is best heard at the left apex (mitral valve area) and commonly radiates dorsally and to the right thorax making reliable diagnosis of tricuspid regurgitation difficult. The characteristic murmur is plateau (band-shaped) and holosystolic; however, in its early stages the murmur may be protosystolic and with mitral valve prolapse the murmur may develop in mid- to late-systole. Mitral insufficiency murmur is typically of mixed frequency and harsh sounding, but it may be high-pitched or musical (whooping) in quality. Mitral insufficiency can be caused by chronic degenerative valvular disease (endocardiosis), endocarditis, hypertrophic obstructive cardiomyopathy, congenital malformations, and diseases that cause left heart enlargement and dilation of the mitral annulus (e.g., patent ductus arteriosus, dilated cardiomyopathy).

Answer 632

Tricuspid Insufficiency The murmur of tricuspid insufficiency sounds similar to that of mitral insufficiency but is loudest over the right apex (tricuspid valve area). It is often difficult to distinguish tricuspid insufficiency from a radiating murmur of mitral insufficiency. Tricuspid murmurs might be a different pitch compared with a radiating mitral murmur and can be accompanied by jugular pulsations. Tricuspid insufficiency can result from congenital malformations of the valve, chronic degenerative valve disease, or any disorders that cause marked right heart enlargement and valve annulus distention, such as pulmonary hypertension and arrhythmogenic right ventricular cardiomyopathy. Tricuspid valve endocarditis is extremely rare in dogs and cats.

Answer 633

Aortic Stenosis Valvular and subvalvular aortic stenosis (SAS) produce a systolic ejection (crescendo-decrescendo) murmur that is usually best heard at the left heart base. The murmur is usually of mixed frequency and harsh, and it sometimes radiates towards the right cranial thorax and up the neck along the carotid arteries. Mild obstructions cause soft murmurs that are difficult to distinguish from innocent or functional murmurs. Murmurs that vary dramatically in intensity with exercise or excitement should prompt consideration of a dynamic left ventricular outflow tract obstruction. Dynamic outflow tract obstruction is the most common type of ejection murmurs in cats with hypertrophic cardiomyopathy and its onset and duration coincide with systolic anterior motion of the mitral valve. Dynamic left ventricular outflow tract obstruction occurs uncommonly in dogs as an isolated abnormality or in association with mitral valve dysplasia or hypertrophy of interventricular septum.

Answer 634

Pulmonic Stenosis Pulmonic stenosis murmur is typically a high-frequency crescendo-decrescendo (ejection) holosystolic murmur, best heard at the left heart base over the pulmonic valve. The murmur can be very similar to aortic stenosis murmur described above but should not radiate along the carotid arteries. As the pressure gradient between the right ventricle and pulmonary artery increases, the murmur intensity becomes louder and peaks later in systole.

Answer 635

Ventricular Septal Defect Ventricular septal defects (VSDs) produce murmurs that vary tremendously in shape and quality. Most often the murmur is a harsh, mid- to high-frequency holosystolic murmur best heard on the right cranial thorax. Murmur intensity may be reduced when the VSD is large and as pulmonary hypertension develops. With severe pulmonary hypertension, the murmur may be entirely absent and splitting of the second heart sound is noted.

Answer 636

Atrial Septal Defect Heart murmurs in dogs and cats with an atrial septal defect (ASD) result from increased flow across the pulmonic valve as a result of the left to right shunting. This murmur resembles that of mild pulmonic stenosis but is often accompanied by a fixed splitting of the second heart sound. Flow across the atrial septal defect is usually not audible.

Answer 637

Physiologic and Innocent Murmurs Functional (physiologic) murmurs are usually caused by decreased blood viscosity or increased cardiac output. Physiologic murmurs are most often noted in animals with anemia, fever, pregnancy, hyperthyroidism, and increased sympathetic tone. These murmurs usually are proto- to mesosystolic, soft to moderate intensity (grade 1/6 to 3/6), and loudest at the left heart base. They tend not to radiate extensively. Innocent murmurs should disappear as the dog matures and appear to be the result of larger stroke volumes in puppies for the size of their great vessels in comparison with adult dogs. In some cats, turbulent blood flow can be noted in the region of the right ventricular outflow tract, often causing a soft systolic apical sternal murmur ranging in grades from 1 to 3/6, with no evidence of structural heart disease and little clinical consequence.

Answer 638

DIASTOLIC HEART MURMURS Aortic Insufficiency The murmur of isolated aortic insufficiency is typically a decrescendo murmur starting at the time of S2 and extending variably into diastole. In young dogs, aortic insufficiency can occur as an isolated defect or in combination with subaortic stenosis or a ventricular septal defect. Detection of aortic insufficiency in an adult dog or cat should prompt consideration of bacterial endocarditis. When the regurgitant volume is large, the diastolic murmur is often accompanied by a soft mesosystolic ejection murmur, creating a distinct “to-and-fro” murmur. The systolic ejection component tapers off in late systole and allows recognition of S2 and differentiation from a continuous murmur. Other causes of “to-and-fro” murmurs include ventricular septal defects that cause loss of aortic root support and pulmonic valve stenosis and significant pulmonic insufficiency (rare). Occasionally massive aortic regurgitation causes premature closure of the mitral valve producing functional mitral stenosis and a diastolic murmur referred to as an Austin Flint murmur.

Answer 639

Pulmonic Insufficiency The murmur of pulmonic insufficiency is similar to that of aortic insufficiency; however, clinically significant pulmonic insufficiency is uncommon. It is sometimes detected in animals with pulmonary hypertension, pulmonic valve dysplasia, or idiopathic dilation of the pulmonary artery

Answer 640

Mitral Stenosis The diastolic murmur of mitral stenosis is difficult to recognize in dogs and cats. This low-frequency murmur begins in mesodiastole and has presystolic accentuation due to atrial contraction. Mitral stenosis might be accompanied by other cardiac malformations, which cause murmurs such as valvular or subvalvular aortic stenosis. In dogs, mitral stenosis may be more common in breeds that are prone to congenital mitral valve malformations such as the Bull Terrier breed, in which it is often associated with aortic stenosis.

Answer 641

.CONTINUOUS MURMURS The most common cause of a continuous murmur at the left heart base is patent ductus arteriosus (PDA). This classic “machinery-like” murmur of a PDA is usually audible throughout the cardiac cycle with peak intensity near S2. The intensity of the murmur is diminished in late diastole in dogs with very slow heart rates and the diastolic component can also disappear with the development of pulmonary hypertension. Less common causes of continuous murmurs include aorticopulmonary windows, ruptured aneurysms of sinus of Valsalva, and coronary arteriovenous fistulas.

Answer 642

Figure 66-2 Algorithm for differentiating causes of abnormal heart sounds and murmurs

Answer 643

Figure 67-1 Algorithm for arterial pulse evaluation.

Answer 644

The intensity of the arterial pulse, termed the pulse pressure, depends on the difference between the systolic and diastolic blood pressure, which may be assessed by digital palpation of artery. However, body condition affects the perceived strength of the arterial pulse, as it is usually more prominent in lean animals as opposed to obese animals.

Answer 645

(1) heart rate, (2) stroke volume, (3) peripheral vascular resistance.

Answer 646

Because the decreased duration of diastole may increase the diastolic pressure, which will decrease the pulse pressure.

Answer 647

Bradycardia lead to excessive run-off during diastole as well as a greater strength of contraction due to greater diastolic filling, causing a strong pulse.

Answer 648

A decrease in stroke volume, as found in patients with left-sided heart failure, hypovolemia, or cardiac tamponade, will produce a hypokinetic pulse (i.e., decreased pulse pressure). However, due to compensatory increase in arterial resistance, a hypokinetic pulse will only be found when the stroke volume becomes markedly reduced.

Answer 649

If peripheral vascular resistance is decreased, or if arterial compliance is increased, pulse pressure may also decrease.

Answer 650

Hyperkinetic pulses may be caused by increased systolic blood pressure and/or decreased diastolic blood pressure, and are most prominent in aortic insufficiency and in left-to-right shunting PDA, leading to a bounding pulse. .. Bounding pulses can also be found in animals with fever, anemia, hyperthyroidism, severe bradycardia, and arteriovenous fistulas.

Answer 651

Pulsus paradoxus denotes an exaggerated decrease in systolic, mean, and pulse pressure on inspiration, and an exaggerated increase on expiration. This phenomenon is strongly suggestive of cardiac tamponade.

Answer 652

Pulsus alternans refers to alternating strong and weak pulses that may occur when the left ventricle is severely dysfunctional, such as in dilated cardiomyopathy.

Answer 653

Pulse deficit occurs in tachyarrhythmias where diastole is not long enough to allow adequate filling of the left ventricle to result in ejection of enough blood.

Answer 654

Systemic thromboembolism secondary to feline cardiomyopathy or hypercoagulable states may result in a complete loss of arterial peripheral pulsations. Altered pulse conformation may also occur.

Answer 655

Dogs with severe aortic stenosis may have a weak pulse or may have a pulse pressure that has a later-than-normal peak in systole due to prolonged ejection time (pulsus parvus et tardus).

Answer 656

.........a shorter ejection time.

Answer 657

VENOUS PULSES Jugular venous distension occurs when right atrial pressure is increased, as jugular venous pressures correlate with right atrial and ventricular pressures.

Answer 658

Distended jugular veins indicate increased systemic venous pressure or occlusion of the venous system between the jugular veins and the right atrium.

Answer 659

An increase in systemic venous pressure is most commonly observed secondary to an increase in right ventricular diastolic pressure. Animals with right-sided heart failure of any cause may have distended jugular veins (Figure 67-2).

Answer 660

Figure 67-2 Algorithm for venous pulse evaluation.

Answer 661

When jugular waveforms are analyzed, the following components can be detected: The A wave, corresponding to right atrial contraction, is the most prominent wave. During right atrial relaxation there is a slight dip in pressure, the Z point. The following C wave, corresponding to right ventricular isovolumetric contraction, is produced by bulging of the tricuspid valve into the right atrium. During right ventricular ejection, the downward displacement of the tricuspid valve produces a prominent negative deflection, the X decent. A third positive deflection, the V wave, occurs late in systole and is caused by increased blood volume and pressure in the right atrium. A second prominent dip in jugular venous pressure, the Y decent, occurs when the right atrium empties as a result of right ventricular relaxation.

Answer 662

Jugular venous pulsations occur when tricuspid regurgitation is present. In normal animals, the jugular pulsations should not extend more than one third the distance up the neck from the thoracic inlet. Pulsations in the underlying carotid arteries may mimic jugular venous pulsations. Occlusion of the jugular vein by manual compression will help differentiate venous pulsations from arterial pulsations.

Answer 663

Performing the hepatojugular or abdominojugular reflux test, by applying abdominal pressure for 30 to 60 seconds, may enhance jugular venous distention, as increased venous return in the presence of right-sided heart disease may elevate right atrial pressure and thus impede jugular venous return.

Answer 664

Jugular vein pulsations may be caused by exaggerated A waves, “cannon A waves,” or prominent V waves.

Answer 665

Exaggerated A waves may occur secondary to severely decreased right ventricular compliance, as may be present in right ventricular hypertrophy, restrictive right ventricular disease, and constrictive pericarditis, resulting in increased right ventricular diastolic pressure.

Answer 666

“Cannon A waves” may also occur in third-degree A-V block and other forms of A-V dissociation, when the atria contract against closed tricuspid valves. Prominent V waves may occur secondary to tricuspid regurgitation as the right atrial volume is increased.

Answer 667

DEFINITION The pleura surround the lung lobes (visceral pleura) and line the thoracic cavity (parietal pleura). Normally, the pleural space contains 3 to 5 mL of a low-protein fluid that lubricates the pulmonary tissue to allow for respiratory motion. The fluid is essentially an ultrafiltrate of blood, and is continually being added to and removed from the pleural cavity.

Answer 668

1. Increased capillary hydrostatic pressure 2. Increased capillary permeability 3. Decreased intravascular oncotic pressure, 4. Impaired lymphatic drainage.

Answer 669

Bilateral. Pleural effusion is typically a secondary phenomenon; therefore recognition of pleural effusion is not analogous to diagnosis of a dog or cat's underlying condition. A thorough investigation should reveal the primary disease (Figure 68-1).

Answer 670

Figure 68-1 Algorithm of differential diagnosis of pleural effusion.

Answer 671

The respiratory pattern caused by pleural effusion results from the interference of normal lung expansion. This observed pattern of ventilation is often called a restrictive pattern of respiration. The respiratory pattern is characterized by a pronounced inspiratory phase and a rapid expiratory phase, often with a prominent abdominal component.

Answer 672

The increased inspiratory effort associated with pleural effusion can be difficult to differentiate from the inspiratory effort of airway disease by observation alone. As a general rule, dogs and cats with pleural effusion have significant tachypnea compared to animals with uncomplicated airway disease and often manifest decreased lung sounds ventrally on thoracic auscultation. The presence of a fluid line may be determined by auscultation of a definitive point on the chest wall, where respiratory sounds shift from muffled to normal or slightly increased. By contrast, dogs and cats with airway disease often have abnormal inspiratory airway sounds such as crackles and wheezes. Most animals with significant pleural effusion are tachypneic as a compensatory measure because total lung expansion capacity is reduced. Coughing is occasionally noted with pleural effusion. Depending upon the underlying cause, systemic signs of disease may also be present.

Answer 673

DIAGNOSTIC EVALUATION A thorough physical examination often provides clues to the underlying cause of pleural effusion. For example, the presence of uveitis may alert the clinician to possible systemic inflammatory conditions such as viral disease (e.g., feline infectious peritonitis), rickettsial disease, fungal infection, or sepsis or systemic neoplasia (e.g., lymphosarcoma). Lymphadenopathy may suggest systemic inflammatory process or lymphosarcoma. Jugular distension and pulsation suggests increased right heart filling pressures that may be associated with cardiomyopathy, pericardial effusion, tricuspid regurgitation, pulmonic stenosis, or any of the many causes of pulmonary hypertension (e.g., heartworm disease, thromboembolic disease, parenchymal lung disease). Jugular distension without pulsation is more likely to be associated with occlusion of right heart inflow, due to mediastinal masses or severely increased intrapericardial pressures. Many cats with large mediastinal masses will have decreased compressibility of the cranial (anterior) thorax. A thorough palpation of the skeleton and the abdomen may uncover masses or painful regions associated with inflammatory disease. Abdominal effusion may be present with cardiac disease, hepatic disease, neoplasia, or hypoalbuminemia.

Answer 674

Fifty to 100 mL of fluid must be present for pleural effusion to be recognized radiographically. A minute amount of effusion may be detected as pleural fissure lines on the radiograph. These radio-opaque lines arc from the periphery toward the hilar region and outline individual lung margins. As effusions progress, lung lobes retract from the chest wall and lung borders become rounded. With large volumes of effusion, the lungs appear to float on the fluid line and the trachea is displaced dorsally on the lateral radiograph, which mimics cardiomegaly or cranial mediastinal mass. The cardiac silhouette is not visualized at all on the dorsoventral radiograph in significant pleural effusion. A ventrodorsal radiograph may provide a better view of the cardiac silhouette in these cases. Lung lobes may appear abnormally dense due to incomplete expansion, collapse, or lung lobe torsion. Pockets of fluid accumulation or unilateral effusions should alert the clinician to the possibility of inflammatory lesions and pleural adhesions.

Answer 675

Transudates and modified transudates; septic and nonseptic exudates; or chylous, hemorrhagic, or neoplastic effusions.

Answer 676

TRANSUDATES AND MODIFIED TRANSUDATES Pure transudates are fluids characterized by low protein concentration (less than 2.5 g/dL) and low nucleated cell counts (less than 1000/µL). Macrophages, lymphocytes, and mesothelial cells are the primary cell types. Pure transudates are classically transparent,

Answer 677

Modified transudates have slightly higher protein concentration of up to 3.5 g/dL and cell counts of up to 5000/µL. In addition to the above cell types, neutrophils are a common finding. Modified transudates may have very slight turbidity.

Answer 678

The most common cause of a pure transudate is decreased oncotic pressure from hypoalbuminemia. The finding of a pure transudate should alert the clinician to assess serum albumin concentration and to screen for underlying causes of hypoalbuminemia (impaired hepatic production, or albumin loss via gastrointestinal or renal lesions). Occasionally, pleural effusions of hypoalbuminemia will be modified transudates in long-standing cases.

Answer 679

The most common cause of modified transudates is increased hydrostatic pressure of the vascular system or lymphatics.

Answer 680

Pleural effusion due to increased intravascular hydrostatic pressure is typically referred to as right-sided congestive heart failure. Cardiomyopathy (dilated and hypertrophic), severe tricuspid regurgitation, pulmonary hypertension, and pericardial effusion or restriction are some common examples of diseases that may result in right heart failure. Pleural effusion from lymphatic obstruction can be caused by neoplasia, lymphangitis, or strangulation of intrathoracic tissue such as with diaphragmatic hernia or lung lobe torsion.

Answer 681

Inflammation and increased vascular permeability.

Answer 682

Exudates have a higher protein content and cell count than transudates. Protein concentrations are classically greater than 3 g/dL and cell counts are greater than 5000/µL. These fluids appear turbid as a result of the higher cellular content. The cell types are similar for septic and nonseptic exudates (neutrophils, macrophages, eosinophils, lymphocytes), but septic processes usually have extremely high nucleated cell counts, that is, greater than 50,000/µL.

Answer 683

In septic exudates, degenerate neutrophils predominate and bacteria can also be observed within the neutrophils or free fluid. However, the absence of bacteria does not rule out an infectious process and all exudative fluids should be submitted for Gram stain and aerobic/anaerobic culture. Prior antibiotic therapy can alter the cellular concentration of the pleural fluid and diminish bacterial numbers; therefore cytology (and culture) should ideally be performed prior to initiation of treatment. In some cases the septic exudates will have a foul odor. Septic pleural effusions are also called pyothorax. Penetrating chest wounds, penetrating esophageal or airway lesions, migrating foreign material such as grass awns, and extension of bacterial pneumonia are relatively common causes of pyothorax in the dog and cat.

Answer 684

Nonseptic exudates may be difficult to differentiate from septic processes. The cell count is usually lower for nonseptic effusions. Although macrophages and lymphocytes may appear activated, neutrophils are typically nondegenerate. As stated earlier, the absence of obvious bacteria in fluid does not guarantee a nonseptic process. Culture and sensitivity testing should be performed. Differential diagnoses for patients with nonseptic exudates include neoplasia, resolving sepsis, chronic diaphragmatic hernia and lung lobe torsion, fungal infection, feline infectious peritonitis, and long-standing chylothorax.

Answer 685

HEMORRHAGIC EFFUSIONS Hemorrhagic effusions are grossly red with red blood cells and may appear similar to frank blood. A packed cell volume (PCV) should be determined on the fluid and compared with a peripheral blood sample. PCV of similar values suggest active bleeding into the chest cavity, whereas effusions with lower PCV than the peripheral blood suggest other factors are responsible for the bloody effusion. Hemorrhagic effusions due to active inflammatory causes often have increased numbers of neutrophils and macrophages compared with the peripheral blood sample, and erythrophagocytosis is commonly present.

Answer 686

Hemorrhagic effusions may result from trauma, neoplasia, lung lobe torsion, and systemic coagulopathies such as rodenticide ingestion.

Answer 687

CHYLOUS EFFUSIONS Chylous pleural effusion (chylothorax) results from leakage of material from the thoracic duct. These effusions may occur from increased lymphatic hydrostatic pressure or obstruction.

Answer 688

Cardiac disease, pericardial disease, dirofilariasis pulmonary hypertension, lung lobe torsion, diaphragmatic hernia, neoplasia, trauma. Idiopathic cases of chylothorax are suspected to be secondary congenital or acquired defects of the thoracic duct.

Answer 689

Chylous effusion is usually milky white due to the presence of chylomicrons, but it may be clear if the animal has fasted. Occasionally, the effusions are blood tinged and resemble tomato soup. These fluids must be differentiated from exudative processes, as protein concentration and cell counts are similar. The predominant cell type in chylous effusion is the mature lymphocyte. With chronic effusions, increasing numbers of nondegenerate neutrophils and macrophages may be seen.

Answer 690

A definitive diagnosis of chylothorax may also be made by comparing the triglyceride content of the effusion to that of serum. The triglyceride content of chyle is classically greater. Occasionally, this test may need to be repeated if an animal has been anorectic. Fibrosing pleuritis can be a complication of chronic chylothorax.

Answer 691

NEOPLASTIC EFFUSION Thoracic neoplasia can cause any type of pleural effusion with the possible exception of pure transudates. Neoplastic cells may or may not exfoliate into the effusion for cytologic identification. Most commonly seen are lymphosarcoma, mast cell tumor, carcinoma, and mesothelioma. Differentiating carcinoma from mesothelioma and reactive mesothelial cells from neoplasia can be extremely difficult cytologically. Repeat thoracic radiography after thoracocentesis (particularly with mediastinal neoplasia), thoracic ultrasonography, or computed tomography may uncover masses, but definitive diagnosis requires fine needle aspiration or biopsy.

Answer 692

Sneezing and Nasal Discharge: Sneezing refers to the explosive release of air from the lungs through the nasal cavity and mouth. It is a protective reflex designed to rapidly remove both chemical and physical irritants from the nasal epithelial surface. Disorders characterized by sneezing are frequently accompanied by nasal discharge. These clinical signs generally result from diseases of the nose, sinuses, and nasopharynx, but may be secondary to diseases of the lower airways. They may also reflect a systemic disease or process

Answer 693

Stertor This term refers to a coarse snoring/snorting respiratory sound and generally indicates an obstruction to airflow at the level of the nasopharynx. It is classically heard in brachycephalic breeds with elongated soft palates, excessive nasopharyngeal tissue, and airway stenoses. It also occurs with nasopharyngeal swellings or mass lesions that cause airway narrowing.

Answer 694

Reverse Sneezing This is a loud inspiratory noise that generally occurs in paroxysms and is usually initiated by nasopharyngeal irritation. The purpose is to move secretions and foreign material to the oropharynx where they can be swallowed. Causes include excitement, foreign bodies, the nasal mite (Pneumonyssus caninum), viral infections, and epiglottic entrapment of the soft palate. Reverse sneezing is usually idiopathic, nonprogressive, and commonly recognized in small dogs.

Answer 695

Brachycephalic breeds commonly have conformational causes of upper airway disease and less commonly nasal neoplasia. This may be related to more pulmonary exposure to pollutants because of less effective nasal air filtration. Brachycephalic cats have been found to be at an increased risk of fungal rhinitis (Aspergillus/Penicillium). Dolichocephalic breeds in general are overrepresented with respect to nasal disease, which may be related to their greater mucous membrane surface area and increased exposure to inhaled irritants and allergens. They have a higher incidence of fungal rhinitis and are about 2.5 times more likely to develop nasal tumors. Outdoor/hunting breeds have a greater opportunity to inhale foreign material and sustain head trauma compared to indoor dogs.

Answer 696

Syncope, from the Greek syn (“with”) and koptein (“to interrupt”), is a transient loss of consciousness and muscle tone caused by inadequate cerebral oxygenation or perfusion to the reticular activating system of the brainstem

Answer 697

Onset and recovery are generally rapid and spontaneous, without the long duration and preictal and postictal period of seizures. While unconscious, the syncopal animal may urinate, have a short duration of myoclonus, or even have tonic spasms that may be confused with seizure activity.

Answer 698

(1) cardiac arrhythmias, (2) structural cardiac and pulmonary causes, (3) reflex-mediated syncope, (4) orthostatic hypotensive syncope, and (5) cerebrovascular disorders. Of these, the first four are described in the veterinary literature; cardiac arrhythmias are the most common cause of syncope in dogs and cats. A sixth reported class is severe and abrupt hypoxemia, described in dogs with laryngeal paralysis or other severe upper respiratory obstruction

Answer 699

Syncope must be differentiated from other conditions such as seizures, narcolepsy, cataplexy, vestibular disease, hypoglycemia, prolonged muscle weakness, and drug intoxication. Differentiation between syncope and these other conditions can be difficult to impossible. Sometimes the cause for syncope remains elusive. In humans, up to 30% of syncopal cases remain undiagnosed.[9]

Answer 700

Figure 70-1 Differential diagnosis for syncope in dogs and cats (neurologic and metabolic causes for diseases that mimic syncope have been ruled out). AV, Atrioventricular.

Answer 701

Cardiac Arrhythmias Bradyarrhythmias or tachyarrhythmias cause syncope by markedly decreasing cardiac output for greater than 6 to 8 seconds. Bradyarrhythmias achieve this by pausing electrical activity, while tachyarrhythmias produce syncope by increasing heart rate to approximately 300+ beats/min, causing inadequate ventricular filling in diastole.[10] These arrhythmias include high-grade (advanced Mobitz type II) second-degree AV block, third-degree AV block, sick sinus syndrome (bradycardia-tachycardia syndrome), severe sinus bradycardia, ventricular preexcitation,[11] supraventricular tachyarrhythmias, atrial fibrillation, and ventricular tachyarrhythmias.

Answer 702

Sudden death is common in high-grade (advanced Mobitz type II) second-degree AV block and third-degree AV block; it is uncommon in sick sinus syndrome. Ventricular tachyarrhythmias are more likely to result in sudden death compared with supraventricular tachyarrhythmias. Therefore, diagnosis of the arrhythmia and underlying disorder with appropriate treatment is vital. Diseases associated with arrhythmias are sinus nodal disease, atrioventricular nodal disease, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, chronic degenerative valvular disease, cardiac neoplasia, abdominal neoplasia, systemic or metabolic disorders (e.g., electrolyte disturbances), sepsis, coagulopathies causing myocardial changes, myocarditis, or drug-induced (e.g., digitalis intoxication). Infectious diseases reported in the veterinary literature causing myocarditis or other conduction disturbances include Blastomyces dermatitidis, Trichinella spiralis, Citrobacter koseri,15 Bartonella spp., and Borrelia burgdorferi.

Answer 703

Stokes-Adams syndrome, originally described in children with heart block, is described in humans where the syncopal episode is accompanied by brief tonic/clonic activity that occurs after 10 to 20 seconds of asystole. These episodes can be mistaken for seizures, but are cardiac in origin. These are seen commonly in syncopal dogs and cats.

Answer 704

Structural Cardiac and Pulmonary Causes Structural cardiac or cardiopulmonary diseases cause syncope when the circulatory demands of the body outweigh the heart's ability to increase cardiac output. Diseases associated with this class include aortic stenosis, pulmonic stenosis,[17] tetralogy of Fallot, atrial septal defect,[18] hypertrophic obstructive cardiomyopathy, cardiac neoplasia causing obstruction to blood flow,[19-21] pericardial effusion/tamponade causing decreased venous return, pulmonary embolism, and pulmonary hypertension with or without Dirofilaria immitis or Angiostrongylus vasorum infestation.

Answer 705

Heart failure by itself is not a cause of syncope; by definition, syncope is transient and self-limiting. The weakness and collapse seen with heart failure is not transient nor self-limiting since it can only be alleviated with medical intervention. Inte enig!

Answer 706

Reflex-Mediated Syncope (Neurally Mediated, Vasovagal, Vasodepressor, Neurocardiogenic Syncope) Reflex syncope is a response that, when triggered, results in reflex vasodilation with or without bradycardia; this leads to hypotension and subsequent transient loss of consciousness. It is characterized by sudden autonomic nervous system failure: withdrawal of sympathetic tone with abrupt increase in vagal tone.

Answer 707

The exact mechanisms underlying neurally mediated syncope remain controversial. The triggering events are variable and determined by which afferent nerve or receptor is stimulated. Types of reflex syncope include 1. carotid sinus syncope—triggered when the carotid sinus is manipulated or during carotid sinus massage in patients with an exaggerated baroreceptor-mediated reflex; 2. situational syncope—triggered when vagal neurons are stimulated by coughing, vomiting, sneezing, micturition, defecating, swallowing, or visceral pain, and; 3. glossopharyngeal neuralgia—where pain associated with the ninth cranial nerve causes activation of a vagal reflex in the neighboring tenth cranial nerve that mimics carotid sinus baroreceptor activation.

Answer 708

Of these reflex triggers, only cough syncope is well recognized though ill defined. It is seen in geriatric small-breed dogs with chronic degenerative valvular disease or chronic pulmonary disease.

Answer 709

There are a few other proposed mechanisms to cough syncope in addition to reflex-mediated causes. One mechanism involves increased intrathoracic and intraabdominal pressures from coughing that cause increased venous pressure with resultant increase in intracranial pressure. A reflex transient decrease in cerebral perfusion results causing syncope.

Answer 710

Animals with aortic stenosis or hypertrophic obstructive cardiomyopathy can also be syncopal for neurally mediated reasons. The Bezold-Jarisch reflex is the primary mechanism for neurally mediated syncope in these patients. This reflex originates in cardiac sensory receptors with nonmyelinated vagal afferent C fibers in the left ventricle. When the receptors are stimulated by increased left ventricular pressure due to outflow obstruction, the increased pressure is perceived as hypertension; reflex vasodilation, bradycardia, and syncope result. Interestingly, this reflex is also triggered in animals suffering rapid, severe hemorrhage. With vigorous contraction of the left ventricle around an almost empty ventricular chamber, an abrupt paradoxical increase in firing of these receptors results in reflex bradycardia and vasodilation.

Answer 711

Orthostatic Hypotensive Syncope This type of syncope, rarely reported in animals, is also caused by a failure of the autonomic nervous system to maintain blood pressure in an upright, bipedal posture. This type of syncope encompasses syncope in these patients that is exacerbated by major volume depletion, decreased circulating blood volume, and drug-induced causes. It has been described anecdotally in one dog, and in dogs with canine dysautonomia

Answer 712

Cerebrovascular Disorders This type of syncope, known as vascular steal syndrome, is not documented in animals and is rare in humans. It involves diversion of blood supply from the brain to another organ. The most common example is the subclavian steal syndrome in patients where the subclavian artery delivers a disproportionate amount of perfusion to the arm at the expense of the brain during exercise of that limb.

Answer 713

Severe, Acute Hypoxemia This is rare, and has been described in dogs with severe laryngeal paralysis or upper airway obstruction. Transient, abrupt hypoxemia results in syncope.

Answer 714

TREATMENT Treatment of syncope is dependent on the underlying cause of syncope: Sick sinus syndrome and third-degree AV block: Pacemaker implantation. Other bradyarrhythmias, including those that are responsive to an atropine response test as well as reflex-mediated bradyarrhythmias: Vagolytic agents (e.g., atropine 0.04 mg/kg PO q8-12h diluted 1 : 10 in corn syrup), beta agonists (e.g., terbutaline), or pacemaker implantation. Dogs that do not respond to medical treatment should be treated with pacemaker implantation. However, reflex-mediated syncope can still occur after pacemaker implantation if the syncope is due to vasodilation and not bradycardia, which is often the case.[33] Atrial tachyarrhythmias: Appropriate antiarrhythmic therapy (e.g., digoxin, beta blockers, calcium channel blockers). Ventricular tachyarrhythmias: Appropriate antiarrhythmic therapy (e.g., mexiletine, amiodarone, sotalol). Cough syncope: Treat the underlying disease that is causing the cough; if ineffective, then use cough suppressants (e.g., hydrocodone, butorphanol). Outflow obstruction due to aortic stenosis (Holter monitor should be evaluated to confirm that syncope is not due to arrhythmia): Beta blockers to prevent the initial increase in sympathetic tone, thus decreasing the reflex increase in contractility, theoretically preventing or alleviating the reflex trigger (e.g., atenolol).

Answer 715

Tissue or mucous membrane color is determined by the amount of oxygenated hemoglobin in the blood, the degree of tissue blood flow (or perfusion), and by the presence of other serum pigments such as bilirubin or myoglobin.

Answer 716

1. Disorders that cause anemia (low red blood cell count) 2. Disorders that cause decreased tissue perfusion (“shock” or severe pain); oftentimes, both mechanisms are responsible for pallor in an individual.

Answer 717

During physical examination, pallor is usually identified on examination of the oral mucous membranes. In some dogs and cats, pallor can also be identified on examination of nonpigmented lips, nose, nares, skin, or urogenital mucous membranes.

Answer 718

Normal CRT is 1.0 to 2.0 seconds; prolonged CRT is >2.0 seconds and is diagnostic for poor tissue perfusion

Answer 719

Hypovolemia, hypotension, and vasoconstriction, it is always important to evaluate a patient's hydration status.

Answer 720

An increased heart rate is commonly seen with pallor regardless of its cause. Severe anemia may increase heart rate to compensate for poor oxygen-carrying capacity of the blood, while almost all causes for poor tissue perfusion increase heart rate.

Answer 721

An abnormal brady- or tachyarrhythmia can be either the sole cause or a contributing cause for pallor by causing poor tissue perfusion. Femoral pulses are palpable on the medial aspect of the proximal hind limbs and are evaluated for symmetry, rate, strength, and synchronicity with the ausculted heart rate. Pulse strength will be reduced in animals that are dehydrated, that have a tachyarrhythmia, or that are hypovolemic. These are all causes for poor tissue perfusion.

Answer 722

In addition to the physical examination, packed cell volume (PCV) or hematocrit (HCT) measurement helps to further determine the basic cause for pallor. If all of the above physical exam parameters are normal and the PCV is low, then anemia is likely the sole mechanism for pallor. If any of the above physical exam parameters are abnormal, then abnormal tissue perfusion may be the sole or a contributing cause. (Figure 71-1).

Answer 723

Baseline diagnostic tests for dogs and cats with pallor should include thorough history, complete physical examination, CBC, chemistry panel, and urinalysis. In an emergency, these tests may not be immediately available. Therefore, in an emergency PCV, total solids (TS), blood glucose, BUN, electrolytes, and blood smear evaluation along with a thorough history and physical examination are indicated. Additional baseline tests that may be indicated based on history and physical examination findings include: electrocardiogram (EKG), blood pressure, pulse oximetry, blood gases, lactate, saline slide-agglutination, coagulation tests (PT/PTT/PIVKA), thoracic or abdominal radiographs, abdominal/cardiac ultrasounds, and fecal occult blood. Additional tests that may ultimately be indicated to determine a definitive diagnosis may include: serum iron assays, bone marrow aspiration cytology/biopsy, direct Coombs' test, ACTH stimulation test, blood or urine cultures, serum insulin level, tissue biopsy and others.

Answer 724

Polycythemia and Erythrocytosis DEFINITIONS In contrast to anemia, polycythemia is a relatively rare clinical presentation. Polycythemia, denoting literally many cells in blood, describes an increase in the total volume of red blood cells or red cell mass without referring to blood leukocytes and platelets. However, an increase in the concentration of erythrocytes, whether measured as number of red blood cells (RBCs), hemoglobin (Hb), or packed cell volume (PCV), is best termed erythrocytosis.

Answer 725

Indeed, erythrocytosis may result either from a reduced blood volume, so-called relative erythrocytosis, or from a true expansion of the red cell mass, known as absolute polycythemia or erythrocytosis. Nevertheless, the terms erythrocytosis and polycythemia are often applied interchangeably, and clinically polycythemia is more frequently used in veterinary medicine.

Answer 726

Figure 72-1 Algorithm showing the diagnostic approach and classification of polycythemia. 2,3-BPG, 2,3-Biphosphoglyceride; EPO, erythropoietin; Hb, hemoglobin; P. vera, polycythemia vera.

Answer 727

Diminished fluid intake and/or rapid severe loss of body fluids reduce the plasma volume and produce a relative erythrocytosis (spurious polycythemia). Hemoconcentration may result from water deprivation, severe diarrhea or vomiting, postoperative complications, shifts of vascular fluid into the interstitial space, heat stroke, and burns. Clinical manifestations of severe dehydration are generally readily evident aside the history of a site of fluid losses and/or a lack of fluid intake.

Answer 728

In contrast, absolute polycythemia reflects an increased red cell volume, and as the red cell mass rises, the total blood volume also expands.

Answer 729

Absolute polycythemia reflects an increased erythropoiesis, while the erythrocyte survival in polycythemic states is generally normal.

Answer 730

Absolute (or true) polycythemia is divided into primary and secondary polycythemias based upon “independent” and “erythropoietin (EPO)-driven” erythropoiesis, respectively. Much has recently been learned about the molecular mechanisms of erythropoiesis that now explains the different forms of polycythemia.

Answer 731

Erythropoiesis involves the staggering production of a few billion erythrocytes per kilogram body weight and day, which is primarily regulated by renal oxygenation and the hormone EPO. Indeed, EPO production and secretion is tightly controlled by a classic feedback loop mechanism.

Answer 732

Renal hypoxia, and not the actual red cell count or mass, stimulates EPO synthesis in the interstitial renal cells in the inner cortex lying in immediate proximity to the proximal tubules. Factors affecting the delivery of oxygen to the kidney such as: 1. anemia, 2. low atmospheric oxygen tension, 3. cardiopulmonary dysfunction, and 4. impeded renal blood flow can stimulate EPO production and erythropoiesis.

Answer 733

Conversely, any adequate or excessive supply of oxygen to the kidneys diminishes EPO production. Normally, plasma EPO concentrations show an inverse relationship with the blood's oxygen-carrying capacity. A rise in plasma EPO level is dependent on de novo synthesis rather than the release of preformed stores, and EPO has a plasma half-life of ~10 hours.

Answer 734

Renal oxygen sensing involves complex regulatory mechanisms. Primary polycythemia is associated with low serum EPO concentrations and may be congenital or acquired. Polycythemia vera (P. vera) is an acquired myeloproliferative disorder leading to clonal expansion of a single hematopoietic stem cell and is characterized by EPO-independent hematopoietic colony formation, proliferation and complete differentiation into the three bone marrow cell lines, and maturation into blood cells. Hence, human patients with P. vera may exhibit not only erythrocytosis but also thrombocytosis and leukocytosis. Moreover, their disease can progress to leukemia and myelofibrosis. Dogs and cats with erythrocytosis are often presumed to have P. vera, but their clonality, EPO-independent proliferation, and molecular basis have never been conclusively studied.

Answer 735

Primary congenital polycythemia (erythrocytosis) in humans may be caused by several dominant mutations in the EPO receptor and more recently in JAK2 that lead to EPO receptor hypersensitivity and downstream signaling pathway activation, respectively. Some of these were previously placed into the idiopathic polycythemia group. These patients neither have a completely EPO-independent nor clonal disorder. Companion animals with isolated persistent erythrocytosis documented in early adulthood that have never been shown to develop thrombocytosis and/or leukocytosis, and never progressed to myelofibrosis and/or leukemia even after years, may well have had EPO receptor or JAK2 mutations rather than P. vera.

Answer 736

Secondary polycythemias may also be associated with congenital or acquired conditions that result in increased EPO production and secretion. Further classification into appropriate and inappropriate secondary polycythemia is based upon whether or not there is chronic systemic hypoxia present that drives EPO production.

Answer 737

The most common causes of secondary appropriate polycythemia are congenital heart defects with right-to-left shunting of blood such as reversed patent ductus arteriosus (rPDA), ventricular septal defects, and tetralogy of Fallot, while acquired heart failure very rarely results in a marked erythrocytosis. Chronic pulmonary diseases (e.g., pulmonary infiltrates with eosinophils) and upper airway obstruction (as seen in Bulldogs with sleep apnea) may cause hypoxia due to abnormal ventilation or ventilation-perfusion mismatch, but are rarely a cause of severe erythrocytosis. (The author followed a young polycythemic mildly tachypneic cat with eosinophilic bronchitis secondary to dirofilariasis that resolved after a couple of years.) Hypoxemia due to high altitude can mildly increase the hematocrit in animals but does not cause clinical signs of erythrocytosis, at least at the elevations we practice at.

Answer 738

However, chronic or recurrent exposure to carbon monoxide may lead to severe erythrocytosis as the author observed in a cat living near a defective furnace and exhaust system. Similarly, defects affecting the oxygen-carrying capacity of Hb can rarely cause polycythemia in cats and in dogs. Methemoglobin reductase deficiency has been documented in several canine breeds and also Domestic Shorthair cats, and due to the inability of methemoglobin to bind oxygen, these animals can develop a moderate erythrocytosis. Hemoglobin mutations resulting in M-Hb, which is unable to bind oxygen, or high-affinity Hb, as well as defects in the generation of 2,3-biphosphoglyceride (2,3-BPG) in erythrocytes affecting the Hb-oxygen dissociation curve, have not been described in dogs and cats.

Answer 739

It should be noted that feline Hb's oxygen release is not 2,3-BPG dependent and has no BPG. And although phosphofructokinase-deficient dogs have low erythrocytic 2,3-BPG concentrations, they do not become polycythemic because of their chronic and alkaline-induced hemolytic disease

Answer 740

Secondary inappropriate polycythemia refers to conditions leading to elevated serum EPO levels without systemic hypoxia. Renal disorders such as renal neoplasia (e.g., carcinoma, nephroblastoma, lymphoma) may cause local hypoxia and thereby trigger EPO production (rather than EPO being produced by tumor cells). Similarly, renal amyloidosis, infection, and inflammation may induce renal hypoxia and erythrocytosis. One cat exhibiting inappropriately high EPO levels following renal transplantation has been reported, which represents a known complication in human patients. Moreover, EPO production may be part of a paraneoplastic syndrome of other extrarenal malignancies which has been documented in dogs with cecal leiomyosarcoma and hepatoma.

Answer 741

Regardless of the cause of absolute polycythemia, the consequence of an increased PCV is an increase in blood viscosity. The rise in viscosity becomes much more pronounced at a PCV >60%, and viscosity is twice normal at a PCV of 70% (for dogs). Furthermore, because it is known that the smaller the RBC size the higher the blood viscosity, companion animals may be exposed to significantly higher viscosity in polycythemia than humans due to the normally very small feline RBCs and microcytic RBCs produced in iron-deficient canine patients.

Answer 742

Depending on the degree of viscosity and local or systemic vascular hindrance, capillary blood flow diminishes leading to local hypoxia, sludging of blood cells, vessel injury, and thrombosis. Impaired microcirculation and arterial thrombosis of the brain is considered a leading cause for the neurologic signs—a common presentation in polycythemic animals.

Answer 743

The manifestations of relative polycythemia are usually obvious and depend on the severity of dehydration and the underlying disease process. As the treatment of relative erythrocytosis (polycythemia) is so different from that of absolute polycythemia, every effort has to be made to detect signs of dehydration based upon prolonged capillary refill time, decreased skin turgor, tachycardia, and hypotension. Moreover, a history of diarrhea or vomiting as well as signs of heat stroke or burns may be noted.

Answer 744

The clinical features of absolute erythrocytosis are related in part to the underlying disorder in addition to manifestations associated with the increased blood volume and increased blood viscosity, which affect blood flow and oxygen delivery. While absolute polycythemia develops slowly and some patients are incidentally discovered to be polycythemic by routine complete blood cell count screening, clinical signs often occur acutely when a certain PCV and degree of hyperviscosity have been reached.

Answer 745

In patients with absolute primary polycythemia, signs are mainly related to hyperviscosity with the conjunctival blood vessels injected and torturous. Mucous membranes appear hyperemic, like red brick, although on occasion they may be a little ruddy due to impaired blood flow. More than half of the cases with primary polycythemia are presented for neurologic complications such as seizures, ataxia, blindness, tremor, or behavior changes. Due to the hyperviscosity, hemorrhage may occur such as epistaxis, hyphema, or gastrointestinal bleeding. Thrombotic events have also been reported in humans. Splenomegaly may also be present.

Answer 746

The clinical hyperviscosity features of absolute secondary polycythemia are similar to cases of primary polycythemias, but they may also have signs referable to the underlying disease process. Clinically helpful, they can be divided into patients with hyperemic versus cyanotic mucous membranes.

Answer 747

Polycythemic animals with cyanosis may have congenital heart disease due right-to-left cardiac shunting and very rarely pulmonary diseases or methemoglobinemia, which is often referred to as chocolate-brown discoloration.

Answer 748

Noteworthy, animals with a rPDA have differential cyanosis of the caudal body parts (anus and prepuce or vulva) and no murmur, while other cardiac right-to-left shunting (typically with a heart murmur) and pulmonary diseases cause generalized cyanosis. All other secondary polycythemias have red and injected mucous membranes. In fact animals with carbon monoxide poisoning have cherry red mucous membranes. Other clinical signs may relate to a specific cause of secondary polycythemia such as a heart murmur (none with a rPDA), respiratory distress, and renal or other masses.

Answer 749

DIAGNOSTIC TESTS Both polycythemia and erythrocytosis depict conditions in which the PCV, Hb concentration, and/or RBC count exceed the upper limit of normal. All of these values refer to concentrations and are therefore dependent on plasma volume as well as circulating red cell mass. It is important to recognize that normal upper values of these erythrocyte parameters for dogs are different from those for cats. Upper limits for dogs versus cats are PCV of 55% versus 48%, RBC count of 8.5 × 106/µL versus 10 × 106/µL, and Hb concentration of 18 versus 15 g/dL. Certain breeds such as Greyhounds and some other sight hounds as well as some Dachshunds have higher PCV values (sometimes slightly exceeding 60%) than other breeds. Splenic contraction can lead to a temporary increase of circulating RBCs in dogs (but not in cats), which is generally slight (except in case of splenomegaly) and never exceeds 60%. Canine hyperadenocorticism and feline hyperthyroidism can also result in slightly increased PCV.

Answer 750

With relative polycythemia the PCV is generally mildly increased (i.e., in dogs 56% to 65% and 49% to 60% in cats) and returns to normal with fluid therapy. Depending on the amount of fluid versus concomitant protein loss (due to diarrhea, vomiting, or burns) or extravascular shift, the plasma protein concentration will be often high but can sometimes be in the normal to low range. In the case of acute hemorrhagic gastroenteritis, dogs may not only be severely hypoproteinemic but also become anemic after fluid administration.

Answer 751

Among absolute polycythemias P. vera is a diagnosis by exclusion in animals; therefore all diagnostic steps are used to identify a secondary cause of polycythemia (see Figure 72-1) before a diagnosis of P. vera is reached and at this time P. vera cannot be differentiated from congenital polycythemias in animals. When presented with an animal with absolute polycythemia a complete blood cell count, reticulocyte count, chest and abdominal radiographs, abdominal ultrasound, echocardiography, blood gases, blood methemoglobin and serum EPO determinations are often indicated, albeit one or the other finding may sway and simplify the diagnostic approach (e.g., discovering met- or deoxyhemoglobin).

Answer 752

While a PCV or complete blood cell count may provide the first evidence of polycythemia, a reticulocyte count, a chemistry panel, and urinalysis belong to the minimal data base as for any sick animal. This generally enables the clinician to further distinguish absolute from relative polycythemia, to assess the degree of polycythemia, and to determine the effects of therapeutic interventions.

Answer 753

In clinical practice it is rarely necessary or feasible to determine total red cell mass. On the other a hand, a reticulocyte count is an inexpensive method to gauge the degree of erythropoietic activity in absolute polycythemia. The absolute reticulocyte count is generally mildly to moderately increased (50 to 250,000/µL) and if only relative reticulocyte counts are determined they need to be corrected upwards for polycythemic animals rather than downward as typically done for anemic animals.

Answer 754

In cyanotic patients it is prudent to first differentiate deoxy- from methemoglobin. This can be quickly accomplished by exposing venous blood to air by gently rotating an aerated EDTA blood tube or placing a drop of blood on a filter paper.

Answer 755

Deoxyhemoglobin rapidly turns bright red on exposure to air, while methemoglobin remains dark brown. In the latter case methemoglobin can be quantified by some veterinary reference laboratories (10% to 55%; >65% fatal; normal <1%), but determination of blood carbon monoxide levels are restricted to human hospital or special toxicology laboratories.

Answer 756

Although an arterial blood gas value should detect systemic hypoxia, the high viscosity can hamper sampling and interpretation. Hence it is recommended to stabilize the patient first and repeat measurements when initially low after phlebotomy. Normal values are expected in all but appropriate polycythemia with cardiopulmonary disease (theoretical exception: hemoglobinopathies where pO2 is normal). If hypoxia is the cause of polycythemia, the changes are usually marked and venous blood gases parallel these changes. Pulse oximetry can be used if arterial blood gas determination is not available. A low saturation (

Answer 757

Abdominal ultrasound is used to detect renal disease, abdominal neoplasia, or both. Unspecific signs such as hyperechoic kidneys may be found in primary polycythemia possibly secondary to hyperviscosity. Thoracic radiographs and echocardiogram (with Doppler) examinations are directed toward identifying pulmonary and cardiac abnormalities and have mostly replaced angiographic radiology.

Answer 758

Mild changes such as myocardial hypertrophy or bronchointerstitial changes can be found in primary and secondary noncardiogenic polycythemia, again resulting from hyperviscosity.

Answer 759

Contrary to the general belief, examination of routine bone marrow aspirate or core biopsy cannot distinguish P. vera from other primary and secondary polycythemia and hence is generally not helpful. In either case erythroid hyperplasia with complete maturation is observed. The subtle differences in bone marrow cell morphology and colony formation noted by experts in humans with P. vera have not been reported in animals.

Answer 760

However, it appears that only an increased EPO value is clinically helpful. And although an increased serum EPO level is diagnostic for secondary polycythemia and values up to fiftyfold elevation have been found in secondary polycythemia, a low or normal serum EPO value can also be found in animals with secondary polycythemia.

Answer 761

THERAPEUTIC AND PROGNOSTIC CONSIDERATIONS Treatment of a polycythemic animal is very much dependent on the cause; most importantly relative polycythemias have to be differentiated from absolute polycythemias as their treatments are opposite. Relative polycythemia is treated with rapid intravenous fluid administration, while absolute polycythemia is initially treated with phlebotomy.

Answer 762

In the case of absolute polycythemia serial phlebotomies are performed and 10 to 20 mL/kg blood is withdrawn until clinical signs have resolved or the target hematocrit is reached. In primary polycythemia the target hematocrit is below 55% for dogs and below 50% for cats. In cases of secondary appropriate polycythemia the aim of treatment is resolving clinical signs of polycythemia and a higher hematocrit (60% to 70%) can be acceptable. A slightly higher than normal hematocrit might provide higher oxygen-carrying capacity without causing hyperviscosity complications.

Answer 763

Alternatively repeated bloodletting may be accomplished by leeching (each leech may suck 5 to 10 mL). Care should be given to maintaining the blood volume as rapid and large blood withdrawal or massive fluid administration can further compromise these patients. Moreover, anticonvulsive drugs are not effective in controlling seizures in polycythemic animals without correction of the erythrocytosis and maintenance of blood volume.

Answer 764

Most treated polycythemic animals will continue to have a lifelong tendency to become polycythemic. This may be readily accomplished by serial phlebotomies every 4 to 8 weeks with regular monitoring of PCV and total protein. Myelosuppressive drug therapy with hydroxyurea should only be used in cases where the underlying cause cannot be corrected and repeated phlebotomies are not well tolerated or are required too frequently. Multiple-dose regimens have been suggested in the literature, but none have been well established. It is advisable to first reduce the PCV by phlebotomy to the target value before initiating treatment with hydroxyurea. Some regimens use a loading dose starting with 30 to 50 mg/kg orally once a day; after 1 week the dose is reduced to 15 mg/kg/day, then titrated to effect. Other regimens propose using a maintenance dose such as 50 mg/kg every other day and titrating to effect. Side effects are reversible and include myelosuppression (thrombocytopenia and granuocytopenia), hair loss, and gastrointestinal upsets. Hence patient's clinical course and complete blood cell count need to be monitored.

Answer 765

The prognosis for primary polycythemia is guarded, but some have remained asymptomatic for years and survival for more than 6 years has been achieved in treated animals. The prognosis for secondary polycythemia depends on the underlying cause. In cases of congenital heart defects, survival of up to 5 years has been reported. Animals with hereditary methemoglobin reductase deficiency generally do not require any specific treatment and have a good life expectancy as long as they are not exposed to oxidative agents.

Answer 766

Cyanosis is blue discoloration of the mucous membranes and/or skin (cyan = blue, Greek); it is the visible result of increased amounts of deoxygenated (reduced) hemoglobin in the blood. This is a subjective property, and depends on lighting, pigmentation of mucous membranes or skin, and the observer. Cyanosis is a clinical sign observed in many different disease processes, and is typically categorized as central or peripheral.

Answer 767

Central cyanosis is caused by a global deoxygenation of arterial blood, most commonly due to cardiovascular, pulmonary, or other diseases resulting in ventilation-perfusion abnormalities. It is generally indicative of a severe and potentially life-threatening condition. Less common causes include methemoglobinemia and polycythemia.

Answer 768

Peripheral cyanosis is caused by a local reduction in oxygenated hemoglobin; it can be secondary to obstructive causes (e.g., thromboembolism), vasoconstriction (e.g., shock, hypothermia), or any of the causes of central cyanosis; peripheral cyanosis may indicate a severe underlying condition, but is not itself life-threatening.

Answer 769

Central cyanosis is generally most evident in the oral mucous membranes (the tongue may be the earliest and most visible indicator), whereas peripheral cyanosis is most evident at the foot pads and nail beds of the affected limb(s).

Answer 770

PHYSIOLOGY AND PATHOPHYSIOLOGY Partial pressure of a gas is the molecular pressure of that gas in a mixed gas environment (alveoli) or in fluid (blood). Normal partial pressure of oxygen in the alveolus (PAO2) at room air (~20% oxygen) averages 104 mm Hg. Normal partial pressure in the arterial blood (PaO2) is also ~100 mm Hg, due to nearly complete oxygen exchange by normal pulmonary tissue. Approximately 97% of oxygen is carried by hemoglobin of red blood cells, with the remaining oxygen dissolved in water.

Answer 771

Cyanosis is generally observed when deoxygenated hemoglobin exceeds 5 g per 100 mL blood within capillary beds. In animals with normal hemoglobin levels (approximately 10 to 20 g/dL), oxygen saturation must decrease to levels below 80% to produce consistently visible cyanosis. As a result, it is an insensitive indicator of blood oxygen content.

Answer 772

Polycythemia is a condition characterized by an elevated red blood cell (RBC) count; in small animal medicine, it is most commonly due to conditions resulting in chronic hypoxia. Polycythemic animals have higher total hemoglobin levels, making it easier for reduced hemoglobin to accumulate. For example, in an animal with a PCV of 65%, 5 g/dL of deoxygenated hemoglobin may be present if oxygen saturation (SaO2) drops below 89%.

Answer 773

Conversely, in anemic animals, cyanosis is rarely present; an absolute reduction in hemoglobin means that SaO2 must decrease to levels incompatible with life to produce cyanosis.

Answer 774

Central cyanosis is most commonly due to cardiovascular or pulmonary diseases that result in arterial deoxygenation (hypoxemia). A decrease in PaO2 results in a decrease in SaO2 according to the oxygen-hemoglobin dissociation curve (Figure 73-1).

Answer 775

Ventilation-perfusion mismatch is probably the most common cause of hypoxemia encountered in clinical practice. In diseases causing pulmonary infiltration (e.g., edema, pneumonia) alveolar ventilation and oxygen exchange are impaired, so that blood flowing to those areas is inadequately oxygenated. This creates a “physiologic shunt,” as the deoxygenated blood mixes with the oxygenated blood returning from better-ventilated areas of lung.

Answer 776

Hypoventilation is another potential cause of decreased PaO2; in these cases, alveoli are not ventilated due to elevated pleural pressure (pleural effusion or pneumothorax), depressed respiratory drive (neurologic disease, drug overdose), or respiratory muscle failure.

Answer 777

Obstructive causes of hypoxemia, such as laryngeal paralysis or tracheal foreign body, result in decreased oxygen availability. Venous-to-arterial shunts (“right-to-left” congenital cardiac or extracardiac shunts) cause deoxygenated venous blood to mix with oxygenated arterial blood, which can result in hypoxemia and cyanosis.

Answer 778

If cyanosis is present in a young animal, congenital heart disease must be suspected. A right-to-left patent ductus arteriosus (PDA) results in differential cyanosis due to the location of the shunt. Deoxygenated blood from the pulmonary artery is shunted through the PDA to the aorta distal to the brachiocephalic and subclavian arteries; this produces cyanosis of the caudal portion of the body without cranial cyanosis. Other cyanotic congenital heart defects (e.g., tetralogy of Fallot) result in central cyanosis, as the shunt occurs at the cardiac level.

Answer 779

Peripheral cyanosis is due to a local reduction of oxygenated blood. Any cause of slowed capillary blood flow will result in increased oxygen extraction by tissues, resulting in deoxygenated hemoglobin. Clinically, this is most commonly due to arterial thromboembolism (saddle thrombus) and/or shock; other causes include occlusion to venous drainage (such as a tourniquet) and hypothermia

Answer 780

SaO2 (ROOM AIR): ↓↓ PaO2 (ROOM AIR): ↓↓ PaCO2: normal PaO2 RESPONSE TO 100% O2: ---

Answer 781

SaO2 (ROOM AIR): ↓↓ PaO2 (ROOM AIR): ↓↓ PaCO2: ↑ PaO2 RESPONSE TO 100% O2:↑

Answer 782

SaO2 (ROOM AIR): ↓ PaO2 (ROOM AIR): ↓ PaCO2: ↑↑↑ PaO2 RESPONSE TO 100% O2: ↑

Answer 783

SaO2 (ROOM AIR): ↓ PaO2 (ROOM AIR): ↓ PaCO2: Normal/↑ PaO2 RESPONSE TO 100% O2: ↑

Answer 784

SaO2 (ROOM AIR): ↓ PaO2 (ROOM AIR): ↓ PaCO2: Normal/↓ PaO2 RESPONSE TO 100% O2: ↑

Answer 785

SaO2 (ROOM AIR): ↓ PaO2 (ROOM AIR): Normal PaCO2: normal PaO2 RESPONSE TO 100% O2: ---

Answer 786

Methemoglobin is a normal product of hemoglobin oxidation, which is maintained at low levels (~1%) by the red blood cell enzyme methemoglobin reductase. When this enzyme is overwhelmed, or congenitally absent (rare), methemoglobin levels can rise to clinically significant levels. As methemoglobin is incapable of carrying oxygen, hypoxia may occur.

Answer 787

Common oxidants resulting in methemoglobinemia include acetaminophen (Tylenol), benzocaine, and nitrites; when levels of methemoglobin exceed 10%, a brown discoloration to blood is grossly visible.

Answer 788

INITIAL EVALUATION/CLINICAL SIGNS A brief assessment of the patient's respiratory pattern (tachypnea, dyspnea, orthopnea) should be made, as well as assessment of airway patency. Stridor, if noted, is usually indicative of upper airway obstruction, which may necessitate emergency tracheostomy or endotracheal intubation. Auscultation is essential; noting the presence or absence of abnormal heart sounds (murmur, gallop, arrhythmia) or lung sounds (crackles, wheezes) is important to determine the most appropriate diagnostic and therapeutic approach to the cyanotic patient. History is often helpful in determining the cause of central cyanosis. Exposure to toxicants (such as acetaminophen or sedatives) may be determined.

Answer 789

The duration of clinical signs is important in identifying chronic pulmonary or cardiac conditions. Peripheral cyanosis may present with signs of acute lameness. Physical examination of these patients may reveal signs of thromboembolism (pain, pulselessness, pallor, and paresis), a mass or foreign body (i.e., rubber band) causing venous occlusion, or generalized peripheral cyanosis due to vasoconstriction that may respond to warming or massage of the extremities.

Answer 790

Cyanotic patients are frequently presented in critical condition. In those cases, most diagnostics should be delayed until the animal is more stable. A working diagnosis can usually be obtained from physical examination, history, and signalment. For example, older dogs are more prone to chronic cardiopulmonary disease, whereas younger animals with cyanosis are more likely to have a congenital cardiac defect or airway obstruction.

Answer 791

Blood work can be helpful if the patient is stable enough for venipuncture. Polycythemia may indicate congenital heart disease or chronic hypoxia; a presumptive diagnosis is usually based on signs and signalment. Gross inspection of the blood may reveal a brownish color, indicating methemoglobinemia. Thoracocentesis can be both diagnostic and therapeutic for pleural effusion and pneumothorax; if a strong index of suspicion exists for either condition, thoracocentesis should be performed prior to other diagnostic tests. Radiographs can be essential to differentiate the many causes of cyanosis, such as pulmonary edema, pneumonia, pleural effusion, pneumothorax, or bronchial disease. Unfortunately, due to stress and limited resources, this can also be a lethal diagnostic test, so the necessity of radiography must be weighed against patient stability. Echocardiography may be extremely helpful in identifying cardiac disease, pulmonary hypertension, and pleural or pericardial effusion. Bubble studies can help determine if right to left shunting lesions are present. Arterial blood gas (ABG) analysis may be helpful in determining the etiology of central cyanosis (see Table 73-1).

Answer 792

ABG should be evaluated on room air and 100% inspired oxygen; unfortunately, this typically requires anesthesia, which is problematic in many patients with cyanosis. Pulse oximetry, which approximates SaO2, can be performed in most clinics, and may correlate with ABG; its use in conscious animals can be poorly tolerated, and must be used judiciously in patients with respiratory distress (Figure 73-2).

Answer 793

TREATMENT Treatment greatly depends on the underlying etiology of cyanosis. In all cases, oxygen therapy should be initiated while basic stabilization and evaluation are performed, as most causes of central cyanosis will improve with oxygen therapy.

Answer 794

Hypoxemia and cyanosis due to hypoventilation, diffusion impairment, and ventilation-perfusion mismatch (unless severe) will show the greatest improvement, although increasing alveolar oxygen concentration should benefit most patients with cyanosis. Animals with alveolar hypoventilation due to obstruction or neuromuscular disease require correction of the obstruction and/or intubation/ventilation to benefit from oxygen supplementation. If pleural effusion or pneumothorax are present, thoracocentesis should be performed.

Answer 795

Other, more specific, therapy will be based on the diagnosis obtained with preliminary workup (e.g., N-acetylcysteine for severe methemoglobinemia, diuretics for cardiogenic pulmonary edema). Treatment of peripheral cyanosis is directed at the underlying cause.

Answer 796

Icterus, jaundice, and hyperbilirubinemia are essentially synonymous terms to describe a single objective clinical finding (hyperbilirubinemia). The terms icterus and jaundice tend to be used when this elevation is clinically evidenced in the tissues (most notably the sclera, mucous membranes, and skin) of the presented patient. However, these are just degrees of severity. Although severity of hyperbilirubinemia may lead one to suspect or prioritize different disease processes, the approach to this clinical finding should be the same whether the patient has a bilirubin of 1.0 or 15.0.

Answer 797

An overview and understanding of hemoglobin metabolism allows the veterinarian to categorize hyperbilirubinemia. This permits prioritizing diagnostics and differentials, eventually leading to the approach to the hyperbilirubinemic patient.

Answer 798

Bilirubin is a byproduct of hemoglobin metabolism. Under normal circumstances, red blood cell senescence and destruction leads to the formation of free hemoglobin. When this occurs intravascularly it is normally removed from the blood stream by the mononuclear phagocytic system (primarily via the liver, but also in the spleen and bone marrow). Extravascular hemolysis is the destruction of red blood cells (RBCs) by the mononuclear phagocytic system; this primarily occurs in the spleen, but may also occur in the liver and bone marrow.

Answer 799

In the mononuclear cells, heme is separated from globin, and some of these components are recycled. Heme, the iron moiety, is then further metabolized to bilirubin (in mammals). Bilirubin is then packaged and released into the blood stream to be reabsorbed and processed in the liver. The liver is the primary site of further bilirubin metabolism and excretion.

Answer 800

Bilirubin is converted to bile by hepatocytes and excreted into the bile canaliculi. Bile is either then further processed and excreted with feces, or reabsorbed as urobilinogen via the ileum and reprocessed by the liver as part of enterohepatic circulation.

Answer 801

Conjugated bilirubin can be excreted via the kidneys. Bilirubinuria can occur in canines under circumstances of high urine concentration and in geriatric patients. However, in feline patients, any confirmed bilirubinuria should always be investigated and is generally an indication of pathology.

Answer 802

1. Prehepatic (increased/inappropriate red cell destruction, overaction of the mononuclear phagocytic system) 2. Hepatic (inability to process and excrete bilirubin) 3. Posthepatic (infection and/or inflammation of the gall bladder, or inability to excrete bile and bile products)

Answer 803

In theory, severe hepatic disease should be associated with a greater ratio of unconjugated bilirubin. Unfortunately, this is not a consistent clinical finding in the veterinary patient, even in those patients with severe hepatocellular dysfunction.

Answer 804

A complete history and physical exam are essential, and will often give the astute clinician a strong indication of which of the three categories are most likely responsible for the hyperbilirubinemia even prior to leaving the exam room. Jaundice or icterus are subjective physical exam findings. However, low-grade hyperbilirubinemia (2.0 to 4.0 mg/dL) may be difficult to see in acute disease, a poorly lit exam room, or by a colorblind clinician. The approach to the problem of hyperbilirubinemia should be consistent to allow a thorough understanding of the disease process. The same approach will be beneficial when hyperbilirubinemia is found unexpectedly on a chemistry panel, in a patient that is found to have jaundice when presenting for nonspecific clinical signs, or when a patient is presented specifically for jaundice.

Answer 805

DIAGNOSTICS CBC: Moderate or severe regenerative anemias are most consistent with prehepatic hyperbilirubinemia. Changes in erythrocyte morphology consistent with increased RBC destruction (spherocytes, acanthocytes, etc.) are also indications of prehepatic disease.

Answer 806

Mild nonregenerative anemias and normal erythrocyte parameters are more consistent with hepatic and posthepatic diseases. An inflammatory leukogram is often present and is nonspecific. A microscopic evaluation of fresh blood smears by a clinical pathologist is often incredibly valuable and may identify the primary etiology in the case of several infectious diseases.

Answer 807

Chemistry: Severely elevated ALT and decreases in other liver “function tests” (albumin, BUN, cholesterol, and glucose) may give indication of primary liver disease. Although this differentiation can be challenging as both prehepatic and posthepatic disease processes can cause secondary hepatocellular damage.

Answer 808

Severity, or quantification of the hyperbilirubinemia, may be used by some to prioritize differentials. This should be used with caution, and in this author's opinion should not cause any etiology to be completely ruled out. High-normal cholesterols and hypercholesterolemia are suggestive of posthepatic biliary obstruction. However, this is not always seen in cases of posthepatic disease.

Answer 809

The following differential algorithms (Figures 74-1 and 74-2) should provide an overview of hyperbilirubinemia. Figure 74-1 Overview of canine hyperbilirubinemia. DIC, Disseminated intravascular coagulation Figure 74-2 Overview of feline hyperbilirubinemia. DIC, Disseminated intravascular coagulation; FeLV, feline leukemia virus; IMHA, immune-mediated hemolytic anemia.

Answer 810

TREATMENT Treatment of hyperbilirubinemia is dependent upon identifying the underlying etiology and correcting or mitigating this process.

Answer 811

Prehepatic Hyperbilirubinemia In cases of autoimmune processes (primary or secondary) leading to hemolytic anemia (IMHA), immunosuppressive doses of glucocorticoids are the mainstay of therapy. They are fast acting, effective, and inexpensive. Some additional immunosuppressive therapy (cyclosporine, azathioprine, etc.) is often instituted in these disease processes. These drugs tend to have significantly longer onsets of action. They are important in the long-term management of these diseases by maintaining immunosuppression and allowing for more rapid steroid reductions. This limits the adverse side effects of ongoing immune suppressive doses of steroids. These medications are significantly more costly than steroids, but are not typically cost prohibitive. RBC destruction regardless of the etiology often causes secondary systemic inflammation and antiinflammatory doses of glucocorticoids are often beneficial in short-term management. These should be used with caution, or avoided in cases suspected of having a primary infectious etiology. Infectious causes of hemolytic anemia and secondary hyperbilirubinemia should be treated by appropriate antimicrobial therapy.

Answer 812

Hepatic Hyperbilirubinemia Treatments for hepatic causes of hyperbilirubinemia are dictated by the underlying etiology. Infectious etiologies should be treated with appropriate antimicrobials. Intoxicants should be treated with appropriate antidotes (if and when available). Autoimmune etiologies should be treated with appropriate immunosuppressive therapies (as above). Congenital etiologies should be addressed as best possible. Regardless of the etiology, hepatocellular inflammation often leads to increased oxygen free radicals and inflammatory cytokines. A variety of antioxidants/hepatobiliary supportive medications including ursodiol, adenosyl, vitamin E, and silymarin are available to help treat the side effects of these diseases. Although these medications are nonspecific, they are often used as “liver support” in both hepatic and posthepatic diseases. Generally, side effects are manageable and most commonly related to gastrointestinal upset. They typically have excellent safety margins. Vomiting caused by ongoing primary disease versus the administration of antioxidant neutraceuticals may be difficult to differentiate.

Answer 813

Posthepatic Hyperbilirubinemia Several reports and texts have documented and advocated medical management of biliary diseases. Partial gallbladder obstruction can resolve over time without surgical intervention. Spontaneous resolution, or resolution with medical management, is more likely to occur with particular etiologies (pancreatitis) than with others (cholelithiasis, neoplastic disease, and mucocele).

Answer 814

The potential choleretic properties of ursodiol may be beneficial in partial gallbladder obstructions, but are theoretically contraindicated in complete obstructions. Differentiating between partial and complete gallbladder obstructions is often challenging and this can lead to frustration and incomplete response to medical management.

Answer 815

Cholecystitis can also be treated medically, but poor perfusion of an inflamed gallbladder will often inhibit antibiotic penetrance and may cause poor response to medical management. There are a variety of surgical procedures (cholecystectomy, cholecystoduodenostomy, cholecystojejunostomy, and biliary stents and tube placements) to address the variety of problems that may result in partial and complete biliary obstructions.

Answer 816

Primary Treatment of Hyperbilirubinemia Extracorporeal hemoperfusion has been documented in dogs. Plasma diafiltration has been documented to primarily remove bilirubin from human blood. These procedures may be theoretically beneficial in cases of severe hyperbilirubinemia although it does not correct the underlying etiology and is not readily available to most clinicians. There is a clinical syndrome of icterus or jaundice without hyperbilirubinemia. Chronic and/or severe hyperbilirubinemia will lead to bilirubin irreversibly bound to albumin and body tissues. This “dyeing” effect may cause clinical jaundice, long after resolving the hyperbilirubinemia. This tissue dyeing effect may be prolonged, but is not clinically significant.

Answer 817

Figure 75-1 Algorithm for epistaxis. Epistaxis is defined as hemorrhage originating from the nose. The following areas should be emphasized when evaluating a dog or cat with epistaxis: Figure 75-1 Algorithm for epistaxis.

Answer 818

SIGNALMENT Pets allowed to roam are susceptible to trauma, parasitic, rickettsial, and fungal infections, rodenticide toxicity, intranasal transmissible veneral tumor (TVT), and foreign body (FB) inhalation. Purebred dogs are more commonly affected with immune-mediated diseases, von Willebrand disease (vWD), or congential coagulation factor deficiencies. Nasal tumors are more common in older animals, although nasal lymphoma occurs in younger cats. Nasopharyngeal polyps occur more often in young cats, while brachycephalic felines are more susceptible to chronic viral respiratory infections.

Answer 819

The owner should be questioned about the pet's history of travel to areas endemic for fungal and rickettsial organisms, leishmaniasis, and hepatozoonosis. Drug and vaccine administration may result in sequelae such as inhibition of platelet function (nonsteroidal antiinflammatory drugs [NSAIDs]), immune-mediated platelet destruction (drugs, vaccines), and thrombocytopenia (estrogen, phenylbutazone, chemotherapy drugs), which may be an underlying cause of epistaxis.

Answer 820

Although bilateral epistaxis may indicate “extranasal” causes such as coagulopathies, hypertension, thrombocytopenia, and thrombocytopathia (a defect in platelet function), such systemic abnormalities can also cause unilateral epistaxis.

Answer 821

Ulceration and depigmentation of the nasal planum may be seen with aspergillosis, immune-mediated disease, lymphoma, or squamous cell carcinoma (4). Polypoid masses extending from the nares are seen with rhinosporidiosis and cryptococcosis. Cats with nasal cryptococcosis often have a characteristic convexity of the nose (“Roman nose”). The mouth should be examined for palate deformity, masses, oronasal fistulas, or loose teeth. Nasal tumors often cause facial or hard palate deformity, inability to retropulse the globe, or epiphora. A fundic examination may reveal chorioretinitis or signs of hypertensive retinopathy or hyperviscosity. Regional lymph nodes should be aspirated and examined for infectious organisms, inflammation (i.e., reactive lymph nodes), or metastatic neoplasia.

Answer 822

Animals with petechia, mucosal bleeding, melena, or fundic hemorrhages are likely to have a defect of primary hemostasis (platelets), whereas those with hemarthrosis, hematomas, or bleeding into body cavities are likely to have a defect of secondary hemostasis (coagulation factors).

Answer 823

Melena and hematemesis may occur when blood from the nasopharynx is swallowed. Central nervous system (CNS) dysfunction may occur with hyperviscosity syndromes or nasal tumors invading the brain. The external genetalia should be examined for masses since intranasal TVT is a rare cause of epistaxis.

Answer 824

DIFFERENTIAL DIAGNOSIS The differential diagnosis for epistaxis can be divided into systemic and local causes (Box 75-1). Local diseases may progress and develop systemic complications that can exacerbate bleeding.

Answer 825

Systemic Conditions Causing Epistaxis (“Extranasal” Causes) Mechanisms of epistaxis include hemostatic defects or increased capillary fragility. Primary hemostatic defects (platelet plug formation) include thrombocytopenia or thrombocytopathia. Mechanisms of thrombocytopenia include decreased production, increased destruction, sequestration, and increased consumption.

Answer 826

Spontaneous bleeding is uncommon unless the platelet count is less than or equal to 50,000/µL, and usually is associated with counts <30,000/µL.

Answer 827

Decreased production of platelets can occur secondary to infections (viral, rickettsial, protozoal, parasitic, or bacterial), neoplasia (resulting in myelophthisis), drug administration, or immune-mediated phenomena. Increased destruction of platelets may be immune mediated or related to microangiopathy (seen with hemangiosarcoma). Sequestration of platelets in the spleen, liver, or large vascular tumors results in peripheral thrombocytopenia. Increased platelet consumption is seen with disseminated intravascular coagulopathy (DIC), vasculitis, and hemorrhage.

Answer 828

Thrombocytopathia may be primary (vWD), or secondary to uremia, dysproteinemias (secondary to ehrlichiosis, multiple myeloma, etc.), or drugs such as NSAIDs.

Answer 829

Coagulation factor defects such as hemophilia A and B are uncommon congenital abnormalities that vary in severity. Acquired coagulopathies include anticoagulant rodenticide toxicity and decreased coagulation factor production secondary to hepatic failure.

Answer 830

Increased capillary fragility and rupture can result from hypertension, neoplasia invading blood vessels, hyperviscosity syndromes, hyperlipidemia, and thromboembolic disease.

Answer 831

Localized Conditions Causing Epistaxis (“Intranasal” Causes) Local processes are the most common cause of epistaxis. Bacterial rhinitis is almost always secondary to inflammation or damage to the nasal mucosa, although Bordetella, Pasteurella, and Mycoplasma spp. may be primary pathogens. Aspergillosis is more common in dogs, and nasal cryptococcosis is seen more frequently in cats. Animals with oronasal fistulas may have nasal discharge or epistaxis. Nasal parasites are highly irritating and can cause severe epistaxis and intractable head rubbing and itching. Viral diseases rarely result in epistaxis in dogs, and cats with upper respiratory infections uncommonly develop chronic nasal discharge and sneezing that results in intermittent epistaxis. Allergic (eosinophilic) and lymphoplasmacytic rhinitis are uncommon immune-mediated phenomena that are often steroid responsive. Arteriovenous malformations can rupture, causing sudden-onset epistaxis. Nasal tumors are the most common cause of epistaxis in older pets.

Answer 832

DIAGNOSTIC PLAN Complete Blood Count Including Platelet Count Regenerative anemia indicates a bone marrow response to blood loss, but with chronic epistaxis, iron deficiency and a nonregenerative anemia may occur. Schistocytes are observed with microangiopathies that occur with hemangiosarcoma and DIC. Leukocytosis is anticipated with chronic inflammation or infection, and leukopenia suggests chronic ehrlichiosis, cytotoxic drug administration, or sepsis. Thrombocytopenia is the result of increased destruction or consumption, sequestration, or decreased production of platelets.

Answer 833

Evaluation of a blood smear may be useful while awaiting laboratory results: normal dogs and cats have 8 to 29 platelets/100× oil immersion field. If the platelet count is 20,000/µL, approximately one platelet per oil immersion field is present. Macroplatelets suggest ............................these platelets may be more functional than normal, explaining why dogs with platelet counts less than 20,000/µL often do not spontaneously bleed.

Answer 834

Chemistry Profile Panhypoproteinemia may develop with chronic blood loss. Hyperglobulinemia is associated with neoplasia or chronic infections, and serum protein electrophoresis can distinguish between monoclonal or polyclonal gammopathy. Monoclonal gammopathies occur with multiple myeloma, chronic ehrlichiosis, lymphoma, leukemias, and macroglobulinemia. Renal, hepatic, or endocrine disease can secondarily cause epistaxis.

Answer 835

Urinalysis The presence of hematuria or glomerulonephropathy support a diagnosis of systemic disease as a cause of epistaxis.

Answer 836

Hemostatic Studies Buccal mucosal bleeding time (BMBT) is a useful in-hospital test of platelet function and is reliable if the platelet count is >100,000/µL. If this test is abnormal, searching for a cause of thrombocytopathia is indicated, including a von Willebrand's titer and evaluation for secondary causes of platelet function defects.

Answer 837

Coagulation studies such as partial thromboplastin time (PTT), prothrombin time (PT), and activated clotting time (ACT) should be performed in cases of epistaxis in which thrombocytopathia and severe thrombocytopenia (

Answer 838

A coagulogram should also include fibrinogen, fibrin degredation products (FDPs), and an antithrombin III level to examine for evidence of DIC.

Answer 839

Cryptococcus can be identified on cytology of nasal discharge with use of India ink

Answer 840

HEMOPTYSIS Hemoptysis (from Greek hamia, “blood” + ptysis, “spitting”) is defined as expectoration of blood or bloody mucus from the respiratory tract at or below the larynx. Detection and confirmation of hemoptysis may be difficult in dogs and cats because they do not expectorate after coughing. To direct the diagnostic and therapeutic process, it must be determined that the coughed up material is actually blood, the blood was coughed up and not regurgitated or vomited, and the blood originated from the lower respiratory tract. Hemoptysis is generally a serious condition that requires aggressive management. The following areas should be emphasized when evaluating a patient with hemoptysis. Figure 75-2 Algorithm for hemoptysis.

Answer 841

SIGNALMENT Animals that roam are susceptible to trauma, rodenticide toxicity, parasitic, rickettsial or fungal infections, or FB inhalation. Older pets are more likely to suffer from primary lung and metastatic neoplasia. Certain fungal diseases and heartworm disease are endemic in limited regions.

Answer 842

Animals that swallow blood from the upper gastrointestinal or respiratory tracts may experience hematemesis, which can be mistaken for hemoptysis. Prior bleeding episodes suggest a primary or secondary coagulopathy. Animals with a history of cough prior to onset of hemoptysis may have chronic diseases such as bronchitis, neoplasia, heartworm disease, or left-sided heart failure.

Answer 843

Nature of the Expectorated Material If the blood is mixed with sputum, suppurative lesions such as bronchopneumonia are likely; pulmonary edema often appears as blood mixed with pink, frothy material; and bright red blood is likely from an artery.

Answer 844

DIFFERENTIAL DIAGNOSIS Coagulopathies and platelet defects uncommonly result in airway mucosal bleeding. Cardiogenic pulmonary edema (secondary to left heart failure) can result in expectoration of blood and pink froth. Pulmonary thromboembolism (PTE) (secondary to cardiac, endocrine, immune-mediated, gastrointestinal, and neoplastic disease) and pulmonary hypertension (secondary to congenital or acquired cardiac malformations that result in abnormal shunting of blood) uncommonly cause hemoptysis. Heartworm disease can cause hemoptysis in dogs and cats (Box 75-2).

Answer 845

In dogs, exercise after adulticide therapy may result in worm embolization, inciting inflammatory lesions in the pulmonary vasculature and parenchyma and resulting in hemoptysis. Parasites including Capillaria, Aelurostrongylus, and Paragonimus spp. cause cavitated pulmonary lesions that rupture and bleed into airways. Chronic inflammatory conditions of the lung including heartworm disease, chronic bronchitis, bronchiectasis, and pulmonary infiltrate with eosinophils (PIE) can result in inflamed and edematous mucosa that bleeds easily during coughing. Bacterial and fungal (Blastomyces, Histoplasma, Coccidioides spp.) pneumonia and lung abscesses may result in hemoptysis. Hemorrhage is a reported complication of transtracheal wash, lung biopsy, and bronchoscopy, and animals should be appropriately monitored after these procedures. Primary or metastatic neoplasia can result in erosion of pulmonary vessels with subsequent hemoptysis. Blunt trauma or FB inhalation into the trachea or airways can result in hemoptysis. Rarely, ruptured arteriovenous malformations, bacterial endocarditis, and lung lobe torsions cause hemoptysis.

Answer 846

Superficial bleeding into the skin or mucous membranes is referred to as purpura.

Answer 847

Petechiae are small, pinpoint hemorrhages (<3 mm) resulting from extravasation of blood from capillaries, Whereas ecchymoses are larger areas of hemorrhage resulting from leakage of blood from small arterioles and venules.

Answer 848

Petechiae and ecchymoses are observed in primary hemostatic defects, i.e., platelet-vessel abnormalities. They represent a mild form of surface bleeding without external blood loss, but may be associated with more serious hemorrhage. Both are commonly seen in dogs but rarely in cats.

Answer 849

PATHOPHYSIOLOGY The vasculature is lined by a layer of endothelial cells that are linked by continuous and well-organized tight junctions varying in width from 0 to 4 nm. This provides a selectively impermeable membrane that prevents the passive transfer of blood into the extravascular space. The subendothelial matrix and additional layers of the vessels (media and adventitia) also act as barriers against extravasation of blood. Vascular integrity is influenced by many factors, one of which is platelets. Ultrastructural and functional changes develop in the vascular endothelium of thrombocytopenic animals, and these abnormalities are promptly reversed by a rise in the platelet count. However, the molecular basis for the observed changes remains unclear.

Answer 850

Thrombocytopenia (reduced platelet numbers), either as a sole hemostatic defect or as part of a combined hemostatic disorder, is the most common cause of petechiae and ecchymoses in dogs and cats. However, thrombopathias and vascular disorders may also cause capillary bleeding.

Answer 851

Decreased platelet production by the bone marrow or increased platelet destruction, consumption, or sequestration. Frequently more than one mechanism is involved. For example, bone marrow suppression, consumption of platelets secondary to vasculitis, splenic sequestration, increased destruction of platelets by both immune-mediated and non–immune-mediated mechanisms, virus-associated myelodysplasia, and myeloproliferative disorders may contribute to thrombocytopenia in dogs and cats with infectious diseases (e.g., ehrlichiosis, babesiosis, Rocky Mountain spotted fever, feline leukemia virus [FeLV], feline immunodeficiency virus [FIV]). In addition to infectious diseases, common underlying causes for thrombocytopenia include neoplasia, drug reactions, and immune-mediated disorders.

Answer 852

The most common cause of petechiae and ecchymoses in the dog is increased platelet destruction associated with immune-mediated thrombocytopenia (IMT), a disorder in which antibody bound to the surface of the platelet results in premature removal by the reticuloendothelial system. The bone marrow typically has normal to increased numbers of megakaryocytes. However, antibodies may also be directed against the megakaryocytes, resulting in decreased platelet production.

Answer 853

Hemolytic anemia, proteinuria, and polyarthritis IMT occurs rarely in cats.

Answer 854

Increased sequestration of platelets resulting in thrombocytopenia has been observed in dogs with splenomegaly, hepatomegaly, and endotoxemia, as well as in experimental hypothermia. However, petechiae and ecchymoses are not typically observed as a result of sequestration of platelets.

Answer 855

Thrombopathia Thrombopathias may be classified as inherited or acquired defects. Inherited disorders of platelet function have been identified in several breeds of dogs, and a few cats. Spontaneous formation of petechiae and ecchymoses, mucosal surface bleeding, and excessive bleeding following surgery or trauma are common features of these disorders, and fatal hemorrhage has been observed in some affected dogs.

Answer 856

Platelet function, as assessed by the bleeding-time test and various in vitro tests, may be affected by various systemic and hematologic disorders (e.g., uremia, liver disease, dysproteinemias) and by a large number of drugs. Although drugs of nearly every classification have been associated with acquired platelet dysfunction in humans, fewer drugs have been evaluated for adverse effects on platelet function in dogs and cats.

Answer 857

Platelet dysfunction induced by aspirin,[5] carprofen,[5,6] cephalothin,[7] and hydroxyethyl starch[8] has been documented in vitro in the dog, but the in vivo effects of these drugs on platelet function are less clear. Nevertheless, it would seem prudent to avoid use of such drugs in dogs with known bleeding disorders.

Answer 858

Von Willebrand Disease Von Willebrand disease (vWD), the most common inherited bleeding disorder in the dog, results from a reduction in the amount of functional plasma von Willebrand factor, leading to impaired platelet-vessel adhesion.

Answer 859

vWD rarely causes petechiae, although ecchymoses may be observed in some dogs with vWD following trauma and surgical procedures.

Answer 860

Bleeding from mucosal surfaces (e.g., epistaxis, melena, hematuria) and excessive bleeding following surgery or trauma.

Answer 861

Vascular Disorders In the absence of a quantitative or qualitative platelet abnormality, the presence of purpura suggests a vascular disorder. Vasculitis, secondary to infectious, inflammatory, immune-mediated, or neoplastic diseases or drug reactions, is the most common cause of vascular purpura. Some dogs with Cushing's disease also are prone to develop ecchymoses following minor trauma (e.g., cystocentesis), possibly as a result of increased protein catabolism leading to dermal and connective tissue atrophy and thus altered dermal vascular support.

Answer 862

Figure 76-1 Algorithm for diagnostic approach to petechiae and ecchymoses. PCR, Polymerase

Answer 863

Spontaneous bleeding is not typically noted unless the platelet count is <30,000/µL, and platelet counts are often less than 10,000/µL in dogs with IM

Answer 864

If the dog or cat is thrombocytopenic, evaluation of the complete blood cell count (CBC) to determine if other cytopenias are present will aid in formulation of a list of differential diagnoses and a focused diagnostic plan. Pancytopenia is most suggestive of bone marrow disease, whereas concurrent anemia and thrombocytopenia may be the result of blood loss anemia due to thrombocytopenia, immune-mediated destruction of both RBC and platelets, or bone marrow disease.

Answer 865

Newly synthesized or reticulated platelets can be identified using the ribonucleic acid (RNA)–binding fluorescent dye thiazole orange and flow cytometry. Reticulated platelets lose RNA within 24 hours after entering the peripheral circulation. The percentage of reticulated platelets is typically increased in dogs with IMT. However, the absolute numbers may be within reference range because of the low total number of platelets

Answer 866

Assessment of coagulation is indicated in the evaluation of a thrombocytopenic patient to rule out a combined hemostatic disorder (e.g., disseminated intravascular coagulation).

Answer 867

Normal ACT in the dog is 60 to 110 seconds and in the cat is 50 to 75 seconds. In dogs and cats with severe thrombocytopenia (

Answer 868

A bone marrow aspirate or biopsy is indicated in dogs and cats with pancytopenia, nonregenerative anemia and thrombocytopenia, persistent thrombocytopenia despite therapy, or atypical cells noted in the peripheral blood.

Answer 869

The buccal mucosal bleeding time (BMBT) evaluates only primary hemostasis or the platelet-vessel interaction. A BMBT is indicated in animals presenting with petechiae and ecchymoses that are not thrombocytopenic.

Answer 870

Altered rheological properties of the blood and a reduced source of adenosine diphosphate (ADP) (RBCs release ADP) to activate platelets are mechanisms proposed for the prolongation of bleeding time in severely anemic patients.

Answer 871

. A prolongation of the BMBT in an animal with a normal platelet count and HCT suggests a thrombopathia, vWD, or a vascular disorder. Because vWD is much more common in the dog than intrinsic platelet function defects or vascular disorders, measurement of plasma von Willebrand factor concentration is recommended before platelet function testing, particularly in dogs being evaluated for development of ecchymoses following surgery rather than spontaneous formation of petechiae.

Answer 872

TREATMENT Medical management of patients with petechiae and ecchymoses varies widely. Treatment is aimed at the underlying disorder (e.g., rickettsial infections, neoplasia, immune-mediated diseases). Because IMT is the most common cause of severe thrombocytopenia in dogs with resultant formation of petechiae and ecchymoses, most thrombocytopenic dogs should be initially treated with doxycycline and prednisone pending results of diagnostic tests. In some cases, discontinuation of medications (e.g., methimazole, sulfonamides) may be all that is necessary to resolve the primary hemostatic disorder.

Answer 873

Dogs and cats presenting with petechiae and ecchymoses as the sole form of bleeding rarely require blood transfusion support. However, if concurrent mucosal surface bleeding exists, particularly into the gastrointestinal tract, leading to anemia, transfusion of packed RBCs may be indicated to provide additional oxygen-carrying support. Platelet transfusions in the form of fresh whole blood, platelet-rich plasma, or platelet concentrate are indicated in life-threatening or uncontrolled bleeding. A small amount of bleeding into the brain, myocardium, lungs, or oropharynx could have devastating consequences without resulting in anemia.

Answer 874

Because the transfused platelets have a short life span (typically destroyed within minutes to hours).

Answer 875

TERMINOLOGY AND NORMAL PHYSIOLOGY Total body water represents about 60 percent of body weight and is about Two thirds intracellular and One third extracellular.

Answer 876

The interstitial fluid (¾ of the ECF), The blood plasma or intravascular fluid (¼ of the ECF) The transcellular fluid (e.g., synovial fluid).

Answer 877

The ECF volume is directly dependent on body sodium content. A disruption in water balance results in hypernatremia or hyponatremia.

Answer 878

Osmolality refers to the concentration of osmotically active particles in a solution.

Answer 879

Tonicity refers to the ability of a solution to initiate movement of water and can be thought of as effective osmolality

Answer 880

Normal plasma osmolality ranges from 290 to 310 mOsm/kg in dogs and 290 to 330 mOsm/kg in cats.

Answer 881

Hypernatremia is defined as a rise in the plasma sodium concentration to a value exceeding reference limits, usually approximately 155 mEq/L (in dogs) or 162 mEq/L (in cats).

Answer 882

Hypernatremia may result from water loss or an excessive sodium intake (Box 77-1, Figure 77-1).

Answer 883

Figure 77-1 Algorithm for the clinical approach to the diagnosis and treatment of hypernatremia. ECF, Extracellular fluid; FENa+, Fractional excretion of sodium = (Urine sodium/Plasma sodium) × (Plasma creatinine/Urine creatinine) × 100; LRS, lactated Ringer's solution.

Answer 884

1. Diabetes insipidus (central or nephrogenic), 2.Inadequate water intake (primary hypodipsia, essential hypernatremia), 3. Increased insensible fluid losses. Hypernatremia due to pure water loss rarely occurs in a conscious animal with normal thirst mechanism and access to water. Loss of hypotonic fluids (common) can result from extrarenal or renal causes.

Answer 885

1. Excessive salt ingestion, 2. Sea water ingestion, 3. Administration of hyperosmolar solutions (hypertonic saline, sodium bicarbonate, sodium phosphate–containing enemas), 4. primary hyperaldosteronism 5. hyperadrenocorticism

Answer 886

The brain is the organ most obviously affected by hypernatremia.

Answer 887

Hypernatremia and hyperosmolality cause water to move out of the brain cells into the extracellular space causing a rapid decrease of brain volume (neuronal dehydration). This can result in rupture of cerebral vessels causing focal intracerebral hemorrhage.

Answer 888

Severity of neurologic signs may be related more to the rapidity of the rise in sodium than to the magnitude of hypernatremia.

Answer 889

When hypernatremia is gradual and develops slowly, the brain cells can produce osmotically active solutes (called idiogenic osmoles) to adapt to hypertonicity, which, in turn, minimizes dehydration of the brain.

Answer 890

Clinical signs of hypernatremia are usually observed when the sodium concentration exceeds 170 mEq/L (plasma osmolality > 350 mOsm/kg). These include lethargy, disorientation, muscle weakness and fasciculations, behavior changes, ataxia, seizures, coma, and death in severe cases.*

Answer 891

If hypernatremia is due to hypotonic losses, clinical signs of hypovolemia can be noted on physical exam. If hypernatremia is due to sodium excess, clinical signs of hypervolemia may be noted.

Answer 892

TREATMENT The first goal in treating a hypernatremic dog or cat is to restore the ECF volume toward normal slowly to avoid neurologic complications. Correction of the serum sodium concentration at a rate of less than 0.5 mEq/L/hr, minimizes the fluid shift from the ECF to the ICF, reducing the risk of brain cell swelling, cerebral edema, and increased intracranial pressure.[35]

Answer 893

Oral water administration is preferable for correcting water deficits. Fluid administered intravenously is necessary when oral administration is not possible.

Answer 894

If a patient's neurologic status deteriorates after initiating treatment to correct hypernatremia, cerebral edema should be suspected and the rate of fluid administration should be reduced. The use of mannitol and/or furosemide may be warranted for their osmotic and diuretic effects, respectively.

Answer 895

If a dog or cat is hypovolemic due to hypotonic losses, isotonic replacement fluid should be used first to restore ECF volume and correct hypovolemia. If poor perfusion persists despite crystalloid therapy, a colloid can be administered.

Answer 896

Once the ECF volume has been expanded, hypotonic fluids can be administered to provide maintenance fluid needs. Free water deficit can be replaced by giving 5% dextrose in water (D5W) intravenously. Typically, glucose is metabolized once it enters cells. Therefore, giving D5W is equivalent to administration of water.

Answer 897

L = 0,6 x lean body weight (kg) x (plasma Na/140)-1)

Answer 898

Serial monitoring of the patient's serum sodium concentration is essential. Dogs and cats with sodium overload are difficult to treat because hypernatremia needs to be corrected without further increasing the ECF volume and causing pulmonary congestion and edema. Administration of a loop diuretic can promote natriuresis and minimize the risk of pulmonary and cerebral edema.

Answer 899

Hyponatremia is defined as a decrease in the plasma sodium concentration to a value below reference limits (usually less than 137 mEq/L). Hyponatremia may result from increased water gain, or an excessive sodium loss, or both.

Answer 900

Lethargy, anorexia, vomiting, weakness, incoordination, disorientation, seizures, and coma.

Answer 901

These CNS signs are due to cerebral edema developing as changes in plasma osmolality cause fluid to shift from the extracellular to the intracellular space.

Answer 902

The onset and severity of clinical signs vary and depend on the rate of decrease of the sodium, but also on the degree of hyponatremia. Clinical signs are usually observed when the sodium concentration falls below 125 mEq/L. With mild or chronic hyponatremia, signs are often absent. With acute hyponatremia, the decrease in plasma osmolality is more rapid then the brain's ability to compensate for the shift of water into the neurons and so clinical signs are noted.

Answer 903

TREATMENT The diagnosis and management of the underlying cause should be a priority. Use of crystalloid solutions is recommended as a fluid replacement for the dehydrated, hypovolemic patient. To avoid neurologic complications such as myelinolysis, hyponatremia correction should not exceed 12 mEq/L during the first 24 hours.

Answer 904

0,6 x body weight (kg) x (normal serum Na+ - patient serum Na+) Na+ mäts i mEq/L

Answer 905

Serial monitoring of serum sodium concentration is necessary. Water intake should be carefully restricted to a volume less than urine output in normovolemic patients with hyponatremia. A loop diuretic and dietary sodium restriction can be considered in overhydrated patients.

Answer 906

Dogs and cats have approximately 50 mEq of potassium per kilogram of body weight within their systems. About 98% of this potassium is intracellular and a small amount is extracellular.

Answer 907

In health, serum potassium concentrations are exquisitely maintained at about 3.6 to 5.6 mEq/L. The large concentration gradient between intracellular and extracellular potassium favors transfer from cells, opposite to that which exists for sodium.

Answer 908

Maintenance of high intracellular potassium and high extracellular sodium concentrations is accomplished with sodium-potassium “pumps” located in cell membranes. This is vital for normal health. .

Answer 909

Cell volume; acid-base status; electrophysiologic properties of cells; and synthesis of RNA, protein, and glycogen.

Answer 910

Too much or too little potassium in the vascular space is worrisome and, if severe and untreated, will result in death. Direct assay of serum electrolyte concentrations is specific and sensitive for diagnosing hyperkalemia or hypokalemia

Answer 911

If P waves are not seen on an electrocardiogram taken on an ill pet, and the heart rate is slow, severe hyperkalemia should be suspected. Invariably, the serum potassium concentration in a dog or cat without P waves is >7.5 mEq/L.

Answer 912

DIFFERENTIAL DIAGNOSIS (Figure 78-1) Dogs and cats with nonadrenal causes of hyperkalemia must be distinguished from those with hypoadrenocorticism (Addison's disease). However, the acute management of hyperkalemia is similar regardless of cause, except that an animal with urinary obstruction or anuria must have either of those specific problems relieved. Clinicians must be certain before diagnosing hypoadrenocorticism and pursuing lifelong therapy. Figure 78-1 Algorithm for the differential diagnosis of hyperkalemia and for determining its cause

Answer 913

Hypoadrenocorticism (Addison's Disease) The classic electrolyte alterations in Addison's disease are hyponatremia, hypochloremia, and hyperkalemia. These abnormalities are due primarily to aldosterone deficiency, causing failure of the kidneys to conserve sodium and excrete potassium.

Answer 914

Deficiency in adrenocortical hormones allows greater amounts of sodium to pass into the intracellular compartment as intracellular potassium concentrations decrease. Hyperkalemia results from a shift of potassium from intracellular to extracellular compartments and from a decrease in renal excretion. The former condition results from a loss of aldosterone effects on the sodium-potassium pump. In addition to the aldosterone deficiency, acidosis also enhances shift of potassium from the intracellular to the extracellular space.

Answer 915

Decreased potassium exchange for sodium in the distal renal tubule leads to decreased urinary potassium excretion and increased sodium excretion.

Answer 916

he shift in electrolytes between body compartments may be partly corrected by the administration of cortisol, but aldosterone, or another mineralocorticoid, must be given to prevent renal loss of sodium and retention of potassium.

Answer 917

Serum potassium concentrations in dogs at the time hypoadrenocorticism is diagnosed vary from normal to extremely increased values that induce clinically obvious cardiac rhythm disturbances. More than 90% of hypoadrenal dogs have serum potassium concentrations greater than 5.5 mEq/L at the time of diagnosis.

Answer 918

Dogs with ACTH deficiency should not have hyperkalemia.

Answer 919

The sodium-to-potassium ratio has frequently been used as a diagnostic tool to aid in gaining a suspicion or in specific identification of dogs with adrenal insufficiency. The normal ratio varies between 27 : 1 and 40 : 1. Values are often below 27 : 1 and may be below 20 : 1 in dogs with primary hypoadrenocorticism. Ratios are nonspecific and are not recommended for confirming a diagnosis. However, determination of serum electrolyte concentrations from dogs or cats that are extremely ill and/or suspected of having adrenal insufficiency is of paramount importance.

Answer 920

Renal failure, urethral obstruction, rupture of the bladder, or avulsion of a ureter These problems prevent excretion of potassium.

Answer 921

Hyperkalemia is not common in chronic renal failure unless the dog or cat is severely dehydrated, anuric, or oliguric. After rupture or avulsion of any component within the urinary system, urine leakage into the peritoneal cavity or into the sublumbar space prevents potassium and urea excretion, two parameters that quickly become severely increased.

Answer 922

Intestinal parasitism (trichuriasis, ancylostomiasis), Intestinal infection (salmonellosis), Perforated duodenal ulcers, and Gastric torsion. Similar serum electrolyte abnormalities have been encountered in some puppies with parvovirus infection or canine distemper. Severe malabsorption syndromes occasionally cause hyperkalemia or hyponatremia or both.

Answer 923

Rapid cellular release of potassium and resultant hyperkalemia may occur as a result of severe acidosis or tissue destruction after surgery, crush injury, or extensive infection. Although not commonly associated with hyperkalemia, examples of disorders that can cause this disturbance are: 1. Pancreatitis, 2. Diabetic ketoacidosis (although total body concentrations are usually decreased), 3. Aortic thrombosis in cats, 4. Rhabdomyolysis secondary to heat stroke or prolonged exercise in dogs or cats. These conditions may also be associated with impaired renal excretion of potassium.

Answer 924

Pleural Effusions Hyperkalemia and hyponatremia have been identified in some dogs with chylous pleural effusion after repeated pleural drainage procedures. The incidence of this complication in dogs with pleural effusion appears to be low because only 2 of 17 dogs with experimentally induced chylothorax had hyperkalemia and hyponatremia. Hyperkalemia and hyponatremia may result from the failure of renal tubular sodium to enter cells in the distal nephron, thereby diminishing sodium resorption and subsequently decreasing potassium excretion into the renal tubule.

Answer 925

Miscellaneous Disorders Low sodium : potassium ratios have been described in dogs with pyometra, perhaps as a result of acidosis, gastrointestinal disturbance, and/or severe dehydration. Hyperkalemia and hyponatremia have also been described in a few near-term pregnant Greyhounds, in several dogs with disseminated neoplasia, rarely in dogs with congestive heart failure, and in one dog with mushroom toxicity. Liver failure could cause similar electrolyte abnormalities, perhaps secondary to interference with the renin-angiotensin-aldosterone system, because angiotensin I is synthesized in the liver.

Answer 926

Iatrogenic and/or Nonadrenal Drug Therapy Excess potassium intake is an uncommon cause of hyperkalemia except in dogs or cats with renal insufficiency. Hyperkalemia can develop with overzealous potassium supplementation in IV fluids, using salt substitutes, or giving parenteral feeding solutions high in potassium. Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, and nonsteroidal antiinflammatory drugs also have the potential to cause mild hyperkalemia.

Answer 927

Adrenocortical Destruction Secondary to Mitotane (o,p′-DDD) or Trilostane Therapy Dogs with hyperadrenocorticism (Cushing's syndrome) overdosed with o,p′-DDD or trilostane can develop hypocortisolemia. This may be the most common cause of hypocortisolemia in veterinary practice. Clinical signs include depression, anorexia, vomiting, and diarrhea. Serum electrolyte concentrations are usually (but not always) within reference ranges. The zones of the adrenal cortex (zonae fasciculata and reticularis), which produce cortisol, are more sensitive to the cytotoxic effects of o,p′-DDD than is the zona glomerulosa, which is responsible for producing aldosterone. Classic “Addison's disease” (including hyperkalemia) secondary to destruction of all three adrenocortical zones can develop from o,p′-DDD or trilostane overdose.

Answer 928

Artifact (non-Akita) Severe hypernatremia may falsely increase potassium measurements performed with dry-reagent analysis. Hypertonicity has been suggested as a cause for hyperkalemia. Extreme leukocytosis (>100,000 mm3) or thrombocytosis (>1,000,000 mm3) may allow sufficient amounts of potassium to be released into the serum during clotting to falsely elevate the serum potassium concentration. In the latter situation, potassium increases in the serum as blood is clotting, an in vitro phenomenon.

Answer 929

Artifact (the Akita) The Akita breed appears to have unusually high red blood cell concentrations of potassium. In one study, six of eight Akitas had high erythrocyte potassium concentrations and plasma from these dogs displayed pseudohyperkalemia after being refrigerated in contact with red cells for longer than 4 hours. The rise in serum potassium concentration (pseudohyperkalemia) correlated with duration of red cell contact and was accompanied by a decrease in serum sodium concentration.

Answer 930

TREATMENT Specific Therapy for Hypoadrenocorticism Therapy need not be overzealous when serum potassium concentrations are less than 6.5 mEq/L, whereas intensive therapy may be vital in dogs and cats with serum potassium concentrations greater than 7.5 mEq/L. Intravenous 0.9% normal saline is a reliable treatment for attempting to lower the serum potassium concentrations rapidly. IV saline rapidly corrects the life-threatening complications of hypoadrenocorticism (e.g., hyponatremia, hypochloremia, hypovolemia, hypotension, hyperkalemia, and azotemia). The serum potassium concentration decreases, in part, because of the dilutional effect provided by saline (which contains no potassium) and by improved renal perfusion. Increased renal blood flow allows further excretion of potassium into the urine. If sodium bicarbonate therapy is used, it will increase the serum sodium concentration and help shift potassium ions into the intracellular space. The other therapeutic mainstay for this condition is mineralocorticoid. For this, desoxycorticosterone pivalate (DOCP) is given at a dose of 2.2 mg/kg IM or SQ. Neither insulin nor calcium therapy has been employed for dogs or cats in hypoadrenal crisis, but may be of value in treating severe, acute hyperkalemia of urinary obstruction and some other conditions.

Answer 931

Nonspecific Methods for Decreasing Serum Potassium Concentrations Hyperkalemia may be treated by antagonizing the effects of excess potassium on cell membranes. Such measures are most often employed in dogs and cats with severe hyperkalemia secondary to urinary obstruction. Calcium gluconate drives potassium into cells. One can administer 2 to 10 mL of a 10% solution IV, slowly. This begins to have effect within minutes and lasts less than an hour. The electrocardiogram must be monitored for arrhythmias induced by overzealous therapy.

Answer 932

Hyperkalemia decreases cellular electrical resting potential. Calcium decreases the threshold potential, thus normalizing the difference between the two potentials. This may transiently protect against cardiac disturbances associated with hyperkalemia. Both glucose and bicarbonate also have the potential to drive potassium from the extracellular to the intracellular space. Administered glucose stimulates insulin secretion. Insulin, in turn, drives glucose into cells. Potassium follows glucose into cells, decreasing its extracellular concentration. The effect of administering 5%, 10%, or even 50% dextrose begins within an hour and may last several hours. Some have recommended administering insulin to cats with severe hyperkalemia secondary to urethral obstruction (0.5 to 1.0 U/kg, IM, regular insulin plus 2 g dextrose per unit of insulin, IV) to ensure potassium lowering. Administration of insulin certainly is more dangerous than that of glucose alone, since iatrogenic hypoglycemia can follow. This is not a concern if only glucose is given. Sodium bicarbonate (1 to 2 mEq/kg, IV) works by driving potassium ions into cells as hydrogen ions leave cells to titrate administered bicarbonate. Bicarbonate begins to work within an hour and lasts several hours.

Answer 933

Atropine has been given to increase the pace of the sinoatrial node if a slow sinoventricular rhythm is present and due to hyperkalemia.

Answer 934

HYPOKALEMIA Hypokalemia, defined as a serum potassium concentration of less than 3.6 mEq/L, may occur with an increased, normal, or decreased total body potassium.

Answer 935

DIFFERENTIAL DIAGNOSIS AND EVALUATION Anorexia, vomiting, and diarrhea cause depletion of body potassium and account for many cases of hypokalemia in dogs and cats. Decreased intake of potassium is unlikely to be the sole cause for this disturbance in any dog or cat. Polyuric disorders (e.g., diabetes mellitus, chronic renal insufficiency) may cause hypokalemia. Long-term therapy for chronic renal failure is commonly associated with hypokalemia in cats, more so than dogs. Serious hypokalemia may occur in dogs or cats being treated for diabetic ketoacidosis (DKA). In treating a dog or cat for DKA, IV fluids, glucose, insulin, and bicarbonate can each cause hypokalemia. Together, these therapies can cause life-threatening hypokalemia.

Answer 936

Hypokalemia has been documented in hypothermic animals and after rattlesnake envenomation. Some forms of renal tubular acidosis are associated with hypokalemia. Pituitary- or adrenal-tumor—dependent hyperadrenocorticism is not typically a cause of hypokalemia. Hypokalemia commonly occurs, if not treated, during diuresis after relief of urinary obstruction in dogs, but even more often in cats. A history of diuretic administration (loop, osmotic, or volume) may be noted in hypokalemic pets.

Answer 937

As previously mentioned, acid-base status may affect extracellular potassium concentrations. Measurement of blood gases and pH, or plasma total CO2, may help in the interpretation of hypokalemia. Alkalosis causes reduction of serum potassium and acidosis the opposite.

Answer 938

Severe potassium depletion usually causes muscular weakness. It may also cause ileus. Polydipsia-polyuria may occur due to a defect in renal concentrating ability. Laboratory evaluation of a hypokalemic pet usually depends on the cause of the disorder. A hemogram, serum biochemical profile, and urinalysis are indicated.

Answer 939

TREATMENT Correction of hypokalemia depends on whether body potassium is decreased or normal (redistribution of potassium). Since 98% of body potassium is located intracellularly and is not practically available for measurement, determining whether or not a “whole-body potassium deficit” is present is difficult. However, it is the extracellular potassium concentration that is vital. Although mild cellular potassium depletion can occur with a normal serum potassium concentration, especially in acidotic animals, most dogs and cats with significant body potassium depletion will become hypokalemic.

Answer 940

Hypokalemia usually indicates cellular potassium depletion but can also be caused by redistribution of potassium from extracellular to intracellular fluid (as seen in alkalosis and insulin therapy).

Answer 941

The rate and route of potassium replacement will depend on the severity of clinical signs and cause of potassium loss. Remember that IV saline and dextrose in water (D5W) solutions contain no potassium while the 4 mEq/L of potassium found in lactated Ringer's solution is virtually the same as that found in saline and D5W.

Answer 942

Maintenance fluid therapy should contain 20 to 30 mEq/L of potassium. Before administering potassium, one should make certain that urine production is adequate. It may be safer to rehydrate a pet with low potassium fluids and establish the presence of urine production prior to administering potassium-enriched solutions.

Answer 943

Life-threatening hypokalemia is rare; therefore, aggressive IV potassium replacement is usually not necessary and is potentially dangerous (it can lead to hyperkalemic cardiotoxicity). Potassium given IV should be administered at a rate not exceeding about 0.5 mEq potassium/kg/hr. However, aggressive IV potassium therapy is warranted in conditions such as diabetics being treated for ketoacidosis (Table 78-1). This challenge presents an example for managing severe and life-threatening hypokalemia

Answer 944

Oral potassium replacement is preferred whenever vomiting is not a problem. Most commercial dog and cat foods contain sufficient potassium to correct mild potassium deficiencies. For moderate and severe potassium depletion (such as the cat with chronic renal failure), potassium-containing tablets and liquids for oral use are commercially available. Liquids are preferred over tablets because of more dependable absorption. Subcutaneous administration of polyionic, isotonic fluids, such as Ringer's or lactated Ringer's solutions enriched with 30 mEq of potassium chloride per liter, is another safe method of potassium replacement. Total daily potassium dosage is estimated based upon suspected severity of potassium depletion. Acid-base disturbances should be corrected, and the primary disorder should be treated appropriately. Hypokalemia due to redistribution of potassium may be corrected by appropriate treatment of the cause (e.g., correction of alkalosis or reduction of insulin dosage).

Answer 945

Calcium in serum or plasma exists in three fractions: ionized (free), complexed (to phosphate, bicarbonate, sulfate, citrate, and lactate), and protein-bound. In normal dogs, protein-bound, complexed, and ionized calcium accounts for 34%, 10%, and 56% of total serum concentration, and these fractions show a similar distribution in cats (40%, 8%, and 52%, respectively). Ionized calcium (iCa) is the biologically active fraction of calcium, and is important for many physiologic functions.

Answer 946

Calcium ions directly bind to iCa-specific cell membrane receptors, and the iCa concentration is maintained within a narrow range by interactions among iCa, phosphorus, parathyroid hormone (PTH), vitamin D metabolites, and calcitonin. The intestine, kidney, and bone are the major target organs involved in calcium regulation.

Answer 947

The skeleton provides a major source of calcium when intestinal absorption and renal reabsorption are inadequate to maintain normal iCa concentration. Parathyroid hormone is secreted by the parathyroid glands in response to a decrease in iCa concentration.

Answer 948

PTH acts to increase the tubular reabsorption of calcium (by decreasing loss of calcium in the urine), to increase bone resorption, and to increase the formation of 1,25-dihydroxyvitamin D (calcitriol) by the kidney.

Answer 949

The net effects of increased PTH are to increase iCa and decrease serum phosphorus concentration.

Answer 950

Calcitonin is synthesized within the thyroid gland and is secreted in response to hypercalcemia; its role in calcium homeostasis is minor.

Answer 951

25-Hydroxyvitamin D and calcitriol are the most important vitamin D metabolites involved in calcium homeostasis.

Answer 952

Dogs and cats are dependent on vitamin D in their diet; hydroxylation of vitamin D occurs in the liver to produce 25-hydroxyvitamin D. The 25-hydroxyvitamin D is then again hydroxylated, to calcitriol, in the proximal tubules of the kidney.

Answer 953

Calcitriol is the only active metabolite of vitamin D, and acts to increase serum iCa and phosphorus concentrations by: 1. Stimulating the resorption of bone; 2. Increasing calcium, phosphorus, and magnesium absorption from the intestine; 3. Increasing renal tubular resorption of calcium and phosphorus by the kidney.

Answer 954

Assessing Ionized Calcium Concentrations The calcium status of any dog or cat is usually based on assessment of serum total calcium (tCa) concentration. Reliance on tCa has been based on the assumption that tCa is directly proportional to the iCa concentration. Use of tCa alone can lead to erroneous interpretation of calcium status in some clinical conditions, with the most important exception being the high percentage of disagreement between tCa and iCa in both dogs and cats with renal disease.

Answer 955

Adjustment formulas perform poorly because they only take into account the protein binding of calcium and ignore the complexed calcium fraction, which can vary, especially in pets with renal disease. The use of adjustment formulas to predict iCa status is not recommended. Accurate measurement of any dog or cat's calcium status should be determined by specifically assaying iCa directly.

Answer 956

Accurate determination of iCa concentration requires that samples be collected and processed correctly. Silicone separator tubes are not recommended, as serum iCa concentration may increase due to release of calcium from the silicone gel. Protein binding of calcium is influenced by pH. For example, an alkaline pH develops with the loss of CO2. This, in turn, favors calcium binding to protein and decreases the amount of calcium that would be ionized. Similarly, mixing serum with air results in an increased pH and a decrease in iCa concentration. Anaerobic collection of serum is technically difficult; therefore, accurate aerobic methods for iCa measurement have been developed. Species-specific correction formulas have been developed by laboratories to correct the measured iCa concentration of aerobically handled samples to a pH of 7.4, with excellent correlation to iCa measured in anaerobically handled samples.

Answer 957

Typically serum is used for iCa measurement, though heparinized plasma or whole blood can also be used. The amount and type of heparin used can impact iCa measurement; therefore it is imperative that when using portable clinical analyzers that utilize heparinized whole blood, a rigid protocol for collection be established. Results using heparinized whole blood cannot be directly compared to serum results, as iCa concentrations are typically lower in heparinized whole blood.

Answer 958

Disorders of Hypercalcemia Approximately 60% of dogs and cats evaluated for calcium disorders are hypercalcemic.[14,15] In hypercalcemia, the interaction of calcium with phosphorus is important. Whenever the product of the tCa (mg/dL) multiplied by the phosphorus concentration exceeds ~70, tissue mineralization is likely. This is critical since the tissues that most often mineralize are nephrons. Mineralized nephrons die, reducing the ability of that individual to excrete phosphorus which, in turn, further increases the Ca × Phosphorus product.

Answer 959

Clinical signs of hypercalcemia are usually present if tCa concentration is >15 mg/dL or if iCa is >1.8 mmol/L; the patient is typically critically ill if tCa is >18 mg/dL or iCa is >2.2 mmol/L. About 60% of dogs with primary hyperparathyroidism (PHPTH) that have a tCa >12 mg/dL have clinical signs. About 40% of PHPTH dogs do not have signs, as observed by owners. Dogs with this condition only rarely become critically ill, regardless of their serum calcium concentration. Hypercalcemic dogs that are critically ill typically have a serious underlying illness (e.g., malignancy, hypoadrenocorticism) and do not have primary hyperparathyroidism.

Answer 960

Polyuria, polydipsia, weakness, and decrease in appetite are the most common clinical signs of hypercalcemia in dogs; vomiting, depression, and constipation can occur. Cats most often exhibit anorexia, and do not exhibit polyuria, polydipsia, or vomiting as often as dogs.

Answer 961

1. Neoplasia (e.g., lymphosarcoma, apocrine carcinoma of the anal sac, multiple myeloma) is the most common cause of hypercalcemia in dogs. 2. Hypoadrenocorticism, 3. Primary hyperparathyroidism 4. Renal failure. Renal failure is characterized by an elevation of tCa but not usually iCa (Box 79-1).

Answer 962

Idiopathic or secondary to neoplasia.

Answer 963

Anticipated changes in calcemic hormones and serum biochemistry results associated with disorders of hypercalcemia are summarized in Table 79-1.

Answer 964

Volume expansion, diuretic administration, glucocorticoid therapy, and bisphosphonate therapy can improve or normalize hypercalcemia. Definitive therapy involves treatment of the underlying disorder.

Answer 965

Muscle tremors, fasciculations, facial rubbing, muscle cramping, stiff gait, seizures, restlessness, aggression, hypersensitivity, and disorientation. Other clinical signs may include panting, pyrexia, lethargy, depression, anorexia, tachycardia, prolapse of the third eyelids (in cats), polyuria, polydipsia, hypotension, respiratory arrest, and death.

Answer 966

Clinical signs are usually present when the serum tCa is <4.5 mg/dL is often life-threatening.

Answer 967

Chronic or acute renal failure and eclampsia.

Answer 968

Acute pancreatitis, hypoparathyroidism, rhabdomyolysis, ethylene glycol intoxication, intestinal malabsorption, and hypovitaminosis D (Box 79-2).

Answer 969

Treatment of hypocalcemia involves a combination of parenteral and oral calcium, with vitamin D supplementation, depending on the underlying condition (Table 79-4).

Answer 970

In patients with renal disease, iCa concentration should always be evaluated. In one study, the serum tCa was increased in 22% of 490 dogs with chronic renal failure, yet iCa was increased in only 9%.[5] This discrepancy in tCa versus iCa can be explained by an increase in complexed calcium in dogs with chronic renal failure. With renal disease, even if serum tCa and/or iCa concentrations are within reference limits, derangements in calcium homeostasis can be occurring and should be evaluated.

Answer 971

Secondary hyperparathyroidism (characterized by normal to low iCa and increased serum PTH concentrations) occurs as the number of functional renal proximal tubules decrease and calcitriol synthesis is impaired. Excess PTH is secreted in the attempt to maintain iCa concentration within a normal range.[1]

Answer 972

PHOSPHORUS Phosphorus Metabolism Phosphorus is important in maintaining the structure of bones and teeth, maintenance of cell membranes, and in the supply of energy.

Answer 973

Most inorganic phosphorus is within bone. Less than 1% is in serum. The majority of phosphorus is in the organic form within phospholipids.

Answer 974

Phosphorus is absorbed in the small intestine and excreted by the kidneys. Phosphorus absorption and excretion is regulated with calcium; calcitriol increases phosphorus absorption, and PTH decreases phosphorus reabsorption in the kidney.

Answer 975

The kidney is the most important regulator of phosphorus, as 80% to 90% of filtered phosphorus is typically reabsorbed by the proximal tubules.

Answer 976

Hyperphosphatemia Phosphorus concentrations are typically higher in young, growing dogs. Increased serum phosphorus concentrations can be caused by: 1. enhanced gastrointestinal (GI) absorption, 2. decreased excretion of phosphorus, 3. transcellular shifts.

Answer 977

An increase in GI absorption is typically the result of an increase in calcitriol or calcitriol-analogue (calcipotriene) concentration (vitamin D toxicity).

Answer 978

Hyperphosphatemia is dangerous in this instance since serum calcium is also elevated, increasing the risk of soft tissue mineralization as previously discussed.

Answer 979

Renal disease, uroabdomen, urinary tract obstruction, hypoadrenocorticism, hypoparathyroidism, acromegaly, and hyperthyroidism.

Answer 980

Transcellular shifts can be seen with tumor cell lysis, rhabdomyolysis, or hemolysis. Hyperphosphatemia may also be seen in hyperlipidemic samples, or with hyperproteinemia.

Answer 981

Hyperphosphatemia does not usually cause clinical signs. However, hyperphosphatemia can induce hypocalcemia (mass law effect) with clinical signs.

Answer 982

1. decreased intestinal absorption, 2. increased renal excretion, 3. from transcellular shifts.

Answer 983

Vitamin D deficiency, malabsorption, vomiting and diarrhea with phosphate binders.

Answer 984

Diabetes mellitus, primary hyperparathyroidism, renal tubular defects, diuretic administration, hyperadrenocorticism, eclampsia, hyperaldosteronism.

Answer 985

Insulin, bicarbonate, or parenteral glucose administration, hypothermia, refeeding syndrome, Respiratory alkalosis.

Answer 986

hemolysis, respiratory failure, seizures, and death.

Answer 987

MAGNESIUM Magnesium Metabolism Magnesium is an important cofactor in many enzymatic reactions. Like calcium, magnesium exists in three fractions: ionized, protein-bound, and complexed. Ionized magnesium (iMg) accounts for approximately 65% of the serum total magnesium concentration in healthy dogs and cats. The ionized fraction is biologically active, and cannot be predicted from the total magnesium concentration, especially in disease states. As with calcium, iMg should be directly measured to provide an assessment of magnesium status.

Answer 988

GI malabsorption, renal loss, concurrent electrolyte disorders, drug administration (gentamicin, carbenicillin, ticarcillin, cyclosporin, cisplatin).

Answer 989

GI disorders resulting in hypomagnesemia include reduced intake, chronic diarrhea, malabsorption, short bowel syndrome, and colonic neoplasia.

Answer 990

Renal loss occurs with diabetes mellitus, diuretic administration, osmotic agents, postobstructive renal diuresis, hyperaldosteronism, hyperthyroidism, and renal tubular acidosis.

Answer 991

1. Primary hypoparathyroidism Depletion of magnesium impairs PTH secretion, impairs calcitriol synthesis, and increases organ resistance to PTH. With low serum iMg concentrations, cell membrane receptors also have reduced sensitivity to iCa. The association of hypomagnesemia and hypoparathyroidism is important, as some patients with hypoparathyroidism may be refractory to calcium and vitamin D therapy if they are also hypomagnesemic. Ionized magnesium concentration should be evaluated in any dog or cat that appears refractory to therapy, and magnesium supplementation (oral magnesium sulfate 1 to 2 mEq/kg/day) should be considered in those with low iMg. 2. Other causes of hypomagnesemia include excessive loss from lactation, acute myocardial infarction, acute pancreatitis, insulin administration, or catecholamine excess.

Answer 992

Hypomagnesemia enhances renal loss of potassium and the potential for secondary hypokalemia. 1. Neuromuscular signs (hyperexcitability, tremors, ataxia, tetany) 2. cardiac arrhythmias.

Answer 993

Chronic renal failure Approximately 20% of dogs (n=2112)[14] and 9% of cats (n=1491)[15] with secondary hyperparathyroidism due to chronic renal failure exhibited elevated iMg.

Answer 994

Paresis, paralysis, cardiovascular depression, hypotension, nausea, and vomiting. Therapy involves treatment of the underlying condition.

Clinical veterinary medicine- Ettinger Flashcards

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