Hepatic, Pancreatic, and Metabolic Disorders

Hepatic, Pancreatic, and Metabolic Disorders

Basic Camelid Energy Metabolism

Fats, sugars, and proteins all can be catabolized to provide energy for cellular functions. These substrates come from the diet or body stores. Fats and sugars are, by far, the more common energy sources in fed domestic animals, with the contribution of fats versus sugars heavily dependent on the type of diet, or in the case of herbivores, the products of microbial fermentation. Insulin is the major regulator of glucose use versus fat use: High concentrations of blood glucose stimulate insulin production and release, increase glucose storage and utilization, and decrease fat mobilization. Low glucose concentrations downregulate insulin release and promote mobilization of body energy stores.

Regardless of this, most or all cells have some obligate glucose requirement. This is higher in certain tissues, including the fetus, mammary gland, brain, and erythrocytes, but relatively universal. Glucose to supply this need may come from the diet, glycogen stores, or hepatic gluconeogenesis. Common substrates for gluconeogenesis include propionate, some amino acids, and glycerol.

Ruminants and camelids absorb very little dietary carbohydrate once their forestomachs have matured and become populated with microbes. These microbes break down complex plant carbohydrates such as cellulose and hemicellulose to simple sugars and also rapidly ferment simple sugars to short-chain or volatile fatty acids (VFAs). Some lipid and protein is also digested in this fashion. The most plentiful VFAs are acetate, propionate, and butyrate. These supply most of the ruminant’s or camelid’s energy in the fed state by supplying substrate for direct oxidation in tissues, conversion in the liver to other lipids for use by other body tissues, or, in the case of propionate only, for hepatic gluconeogenesis.

Gluconeogenesis is an energy-losing process. Ruminants have adapted to the paradox of a high glucose requirement, especially during lactation or pregnancy, and a poor or an expensive supply by enforcing economy. They maintain blood glucose concentrations lower than nonruminant mammals, which limits the activity of insulin. Camelids are very different; they maintain blood glucose concentrations approximately at a level double those of ruminants, higher than many monogastrics, and even within the diabetic range for some animals. Although this feature of camelids is easy to detect and was one of their earliest known physiologic peculiarities, it appears to be just one aspect of a relatively unique system of energy metabolism.

In addition to higher resting blood glucose concentrations, camelids clear exogenous glucose more slowly (Figure 41-1), have lower blood concentrations of fasting and stimulated insulin, and have considerably greater insulin resistance than cattle.16 The combination of high blood glucose and low blood insulin suggests a diabetes-like state. The source of the glucose is still being debated. Considering the unlikelihood of gastrointestinal (GI) absorption, exuberant hepatic gluconeogenesis appears the most likely source and fits with the low insulin environment. This is supported by evidence for a predominance of gluconeogenic enzymes over glycolytic enzymes in the camelid liver.7

Glucose clearance is achieved primarily through tissue uptake. At higher concentrations (>180 milligrams per deciliter [mg/dL; or 10 millimoles per liter [mmol/L], approximately), renal excretion contributes. Cellular uptake occurs either through the sodium–glucose linked transporter (SGLT) or a family of glucose transporters referred to as the GLUTs (glucose transporters). The SGLT has not been investigated in camelids. In other species, it is responsible mainly for the absorption of glucose across epithelial surfaces from ingesta or urine and thus has the role of introducing glucose into blood from one of these sources. Activity of the SGLT is unlikely to be responsible for camelids’ high blood glucose concentrations, although renal reabsorption may contribute to glucose intolerance.

The more interesting transporters affecting blood glucose in camelids are the GLUTs. Of this family, four major representatives principally transport glucose between the intracellular and extracellular spaces. All move glucose down the concentration gradient. GLUT1 is widespread and probably serves to ensure each cell gets its basal glucose supply. GLUT2 is bidirectional and regulates glucose movement in and out of hepatocytes, depending on the relative supply on each side, and regulates glucose uptake, and thereby insulin production, by the pancreas. GLUT3 is mainly found on the neuronal plasma membrane and thus has a role in maintaining glucose supply for the central nervous system (CNS). GLUT4 is found mainly in adipose tissue and striated muscle and is responsible for insulin-mediated glucose uptake. Thus, activation of the GLUT4 system enhances glucose catabolism in most species during times of abundance but appears to be less functional in camelids.

Activation of GLUT4 starts with the insulin response. Glucose is internalized into pancreatic β-islet cells using GLUT2. It is subsequently phosphorylated by glucokinase and subjected to glycolysis. The generation of adenosine triphosphate (ATP) leads to the closing of potassium channels, opening of calcium channels, and activation of protein kinases. Preformed insulin is released by exocytosis, and further insulin production is stimulated. Circulating insulin binds the cell surface insulin receptor, which leads to migration of intracellular GLUT4 to the surface following the action of protein kinases.

Immunohistochemical examination has revealed what appear to be substantial populations of GLUT1, GLUT2, and GLUT3 in the appropriate places in New World camelids.8 GLUT4 was not found, but whether that was caused by the absence of the transporter or lack of cross-reactivity with the test antibody was not determined. GLUT4 was recently found by using the Western Blot test in camels, mainly in the diaphragm and masseter, and the authors suggested some deficiency in its migration to the cell surface.9 Insulin receptors have also been identified in camels and appear to be similar in form and function to those of other mammals.10

The relative lack of GLUT4 activity in camelids is most likely responsible for their partial insulin resistance. However, this insulin resistance may be reversed by using long-acting insulin or insulin continuous rate infusion (CRI), suggesting that adult camelids have the mechanism for a GLUT-4 response but that it is somewhat dormant due to chronic understimulation.11 This further suggests that underproduction of insulin is the primary disorder and peripheral resistance is secondary.

The blood insulin concentrations of fasted adult camelids are roughly one half to a third of those of a variety of other mammals.1,2 Interestingly, neonatal crias have blood insulin concentrations, glucose tolerance, and insulin sensitivity more in line with those other mammals, which suggests that a major change occurs during or after weaning.12 The most obvious changes are in the diet and forestomach digestion. Most dietary carbohydrate in adults is fermented to VFAs, and forestomach bypass ceases with the end of nursing. It is possible that camelids, with their longer gastric retention times and highly efficient fermentative digestion, prevent even more carbohydrate from reaching the intestine compared with ruminants. Carbohydrate in the intestines triggers incretin release, which potentiates the subsequent insulin response to hyperglycemia. The best known incretins are gastric inhibitory polypeptide (GIP, also known as the glucose-dependent insulinotropic peptide) and glucagon-like peptide 1 (GLP1), released by the duodenum and the ileum, respectively. Adult camelids treated with exogenous GLP1 have glucose tolerance and circulating insulin concentrations resembling those of crias or monogastrics, which suggests that lack of incretins is, indeed, the cause of camelids’ poor insulin production and therefore central to their exuberant gluconeogenesis, poor glucose tolerance, low insulin production, and partial insulin resistance.13 Further unpublished work supports this.

The consequences of impeded insulin production on glucose metabolism in the healthy camelid are several. Gluconeogenesis appears to occur unimpeded, increasing camelids’ needs for propionate or amino acid precursors. Stimulation for glycogen storage is less, possibly giving camelids smaller glycogen reserves compared with ruminants.14 Most importantly, or at least most dramatically on blood evaluation, camelids have little ability to counteract hyperglycemia, which leaves them prone to high and prolonged glucose peaks. These consequences may become even more significant in the sick camelid.

Lipid metabolism has historically received less attention than glucose metabolism, chiefly because glucose measurement is easier and more widely accessible. Blood lipids that may be measured include nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BOHB), and triglycerides. NEFAs mainly represent lipid mobilized from adipose reserves, with NEFAs from circulating triglyceride potentially making a small contribution. Thus, NEFAs mainly represent the degree of fat mobilization from adipose tissue and should be low in the fed state. BOHB is a ketone body that represents hepatic lipid, mainly from internalized NEFAs, which is partially oxidized to a water-soluble form and released into blood. This indirectly estimates NEFAs but also reflects a hormonal environment that directs hepatic fat toward incomplete oxidation as opposed to complete oxidation or reesterification to triglyceride. BOHB production is also usually minimal in the fed state. Triglyceride represents fat within lipoproteins. In herbivores with minimal dietary triglyceride and hence few chylomicra, lipoproteins mainly represent lipid exported by the liver and not removed by tissues. Cholesterol is another estimator of lipoprotein fat but is less useful clinically than triglyceride in camelids. The protein fractions of lipoproteins may be assessed as well to differentiate types of lipoprotein, but little work has been done with this in camelids.

Camelids’ low levels of insulin production affect fat metabolism as well. The fed camelid supplies most of its body energy needs through the short-chain fatty acid products of gastric fermentation. These are made in roughly the same proportion as in ruminants on similar diets; the difference is that the camelid gastric wall does not appear to convert butyrate to its ketone form (i.e., BOHB). Short-chain fatty acids may be oxidized for energy by most tissues.

The feed-deprived camelid begins to mobilize NEFAs from peripheral adipose stores within 8 hours. As far as we know, this intracellular lipolysis occurs under similar hormonal conditions as in other species; that is, catecholamines and possibly other hormones stimulate lipolysis, whereas insulin inhibits it.14 Glucocorticoids appear to have little effect.15 Insulin inhibits lipolysis at lower concentrations than it controls hyperglycemia, so healthy camelids are able to regulate fat mobilization better than blood glucose concentrations but are perhaps more vulnerable to disease induced by slight reductions in insulin production compared with ruminants.

The free fatty acids (FFAs) liberated from adipose tissue circulate bound to albumin. The consequences of hypoalbuminemia, a common finding in sick camelids, on this transport are unknown. FFAs are taken up by cells in proportion to their blood concentrations and may be oxidized by most tissues for energy. However, metabolically active cells may not meet their energy needs through NEFAs alone.

The liver plays a central role in modifying NEFAs for use by other tissues. Several types of conversion are possible, the most important of which are modification to water-soluble ketone bodies or reesterification to triglyceride. Ketone bodies are transported from the liver and may be used by the kidneys, skeletal muscle, and, after a period of adaptation, the brain as an energy substrate. However, high concentrations of BOHB inhibit phosphorylation of protein kinases B, a critical step in insulin signaling, thus further impairing insulin-dependent glucose uptake.

Triglycerides are stored in the endoplasmic reticulum or bundled for export as very–low-density lipoproteins (VLDL). Camelids appear to be either more capable of exporting liver triglyceride as lipoprotein compared with cattle, or they have greater problems with end utilization because hypertriglyceridemia is far more common and severe in camelids than in cattle. Lipoproteins circulate in blood. Tissues expressing surface lipoprotein lipase may liberate FFAs from lipoprotein triglyceride (intravascular lipolysis) and use them for energy. Insulin, insulin-like growth factors, and thyroid hormone stimulate lipoprotein lipase activity, whereas some inflammatory mediators and catecholamines inhibit it.

In summary, adult camelids produce little insulin compared with ruminants or monogastrics. This may be a side effect of their highly efficient gastric fermentation but the consequences are that it allows hepatic gluconeogenesis to progress at a higher rate than necessary to meet basic glucose demand, leaves the animal poorly responsive to hyperglycemia, and only precariously inhibits fat mobilization. Small reductions in insulin secretion or increases in insulin antagonism or hormones that counteract insulin may lead to serious medical complications.

Disorders of Carbohydrate Metabolism

Stress Hyperglycemia

Stress hyperglycemia is a well-known phenomenon in camelids. Ruminants and horses rarely develop hyperglycemia of greater than 300 mg/dL, and stressed camelids occasionally have blood glucose concentrations of 500 mg/dL (27.5 mmol/L) or more. Forty-two percent of camelid patients at our clinic have hyperglycemia on initial evaluation, with about 7% having greater than 300 mg/dL (16.5 mmol/L). The frequency and severity of stress hyperglycemia most likely relates to the poor mechanisms for glucose clearance and inability to counteract glucogenic stimuli. Sources of increased blood glucose include absorption from the diet (suckling animals only), administration of exogenous glucose, accelerated gluconeogenesis, and glycogenolysis. Epinephrine and cortisol both appear to mobilize glycogen stores in camelids, as in other species. Epinephrine leads to near-instantaneous increases in blood glucose.14 Cortisol takes longer (90 to 120 minutes) but leads to longer-lasting, higher peaks.15 Both hormones may also induce gluconeogenesis. Although the glycogen stores in camelids appear to be relatively small, epinephrine, cortisol, and other glucogenic factors are likely to increase blood glucose to a greater degree or for a longer duration in camelids than in other species because of the lack of effective countering by insulin.

This condition is not usually associated with any adverse signs. The greatest risk comes from dehydration; once the blood glucose concentration surpasses the renal threshold, urinary glucose and water loss increase. Frequent urination may be noted in the early stages. If the camelid is unable to voluntarily rehydrate itself, signs of obtundation and dehydration may develop. Diagnosis of stress hyperglycemia is usually made after blood evaluation, with consideration for history of stressful events or administration of glucogenic agents. Unless physical or laboratory evidence of dehydration is present, no treatment is necessary beyond trying to remove the cause of stress.

Diabetes Mellitus

Diabetes mellitus has been described empirically but has been reported scientifically in only one camelid.16 That camelid was reported to have type I diabetes mellitus, even though it had a blood insulin concentration within reference ranges for camelids.

The usual basis for diagnosis of diabetes mellitus in camelids is persistent hyperglycemia with or without confirmation of slow glucose clearance or glycosuria. This must be differentiated from repeated bouts of simple hyperglycemia, for example, in a camelid that requires stress-causing handling to obtain a blood sample. In rare cases, diabetic complications such as cataracts, polyuria and polydipsia, weight loss, hypertriglyceridemia, or lipogranulomatous or ulcerative foot lesions develop. These complications suggest a fundamental derangement in insulin activity and provide significant support to the argument for true diabetes mellitus.

We have examined a small number of camelids with persistent hyperglycemia and found no difference in insulin concentrations, glucose clearance, or pancreatic architecture from normal camelids. They also show no evidence of decreased function of tissues that take up glucose in an insulin-independent fashion. Thus, overproduction of glucogenic factors (cortisol, epinephrine, others) appears more likely to cause persistent hyperglycemia in most camelids, rather than pancreatic insufficiency, pancreatic exhaustion, or somatic insulin resistance.

Acute complications are treated according to the general guidelines outlined below. For longer-term glycemic and lipemic control, start with low doses of long-acting insulin (Insulin glargine, 0.1 units per kilogram [units/kg], subcutaneously [SQ], q24h), and increase the dosage in 0.05 units/kg increments until control is achieved or the treatment appears to be effective.

Hyperosmolar Disorder

Hyperosmolar disorder is one consequence of persistent or severe hyperglycemia, usually in conjunction with restricted fluid intake.17 This disorder is most severe in young crias, especially orphans or other bottle-fed crias, but occurs to some degree in camelids of all ages. Factors such as endogenous or exogenous catecholamines or glucocorticoids, pancreatic insufficiency, or exogenous glucose, which increase exogenous glucose, are poorly countered by endogenous insulin, allowing hyperglycemia to develop. In neonates, feeding cow or goat milk or a milk replacer instead of camelid milk may also increase the risk, as camelid milk appears to have an insulin-like effect.

Under normal conditions, glucose is a minor component of blood osmolality, 5 to 10 milliosmoles per liter (mOsm/L) out of a total of around 320 mOsm/L. Its contribution may be estimated by using the following equation:


Even with increases of several hundred milligrams per deciliter, the direct effects of glucose on blood osmolality are minor. However, camelids have limited means of increasing cellular glucose uptake, leaving glycuresis as the major mechanism of reducing blood glucose once the renal threshold is surpassed. This leads to water loss. If this water is not replaced, as occurs in camelids unable or unwilling to drink, hyperglycemia often persists or worsens, leading to progressive shifting of fluid out of the intracellular space into the vascular space and eventually out in urine. In the initial stages, blood sodium is reduced by dilution. In the later stages, it is increased by concentration and then acts as an additional draw for the movement of water out of the intracellular space. With hypovolemia, the mechanisms of sodium retention are activated and lead to further exacerbation of hypernatremia.

If hyperosmolar disorder is mild (blood sodium <170 milliequivalents per liter [mEq/L]), clinical signs include frequent urination, lethargy, anorexia, and obtundation and may be difficult to separate from signs of whatever condition led to the original stress or lack of water intake. As the disorder progresses, affected camelids develop a fine head tremor worsening to a coarse, whole body tremor, a base-wide stance, ataxia, opisthotonus, recumbency, seizures, coma, and death.

Diagnosis is based on history and blood and cerebrospinal fluid (CSF) biochemical evaluation. Blood abnormalities include moderate to severe hyperglycemia (>400 mg/dL), but hyperglycemia alone is not enough to cause most of the signs. In the early fluid redistribution stage, blood sodium may be low. As fluid is lost, sodium climbs above 170 mEq/L, and hyperalbuminemia, azotemia, and lactic acidosis develop. Increases in CSF sodium are also diagnostic. Hematologic changes reflect stress or the underlying infectious disease.

Hyperadrenocorticism or Glucocorticoid Administration

Exogenous glucocorticoids have an exaggerated effect on blood glucose in camelids because of camelids’ inherent slow glucose clearance. Thus, glycuresis and hyperosmolar syndrome may ensue in dehydrated camelids treated with glucocorticoids. Mineralocorticoid activity of glucocorticoids may worsen hypernatremia by promoting renal resorption.

Endogenous glucocorticoids are harder to assess. They have long been blamed for stress hyperglycemia, but because of their delayed onset of efficacy, they are likely only contributing to hyperglycemia in camelids stressed for 2 hours or more.15 Some abnormality of the pituitary–adrenal axis may be responsible for persistent hyperglycemia and diabetes-like signs in certain camelids, although this has not been investigated sufficiently.

Both endogenous and exogenous glucocorticoids have been blamed for unsuccessful outcomes in sick camelids. Mechanisms that might affect that negative outcome include immunosuppression and the induction of hyperosmolar syndrome. The glucose-related aspects may be minimized by ensuring adequate hydration and vascular pressures in patients before and after glucocorticoid administration.

Pancreatic Necrosis

Pancreatic necrosis with damage to islet cells could be another possible cause of hyperglycemia.18 Both acute and chronic forms have been reported but not any effects on glucose homeostasis. Acute pancreatic necrosis appears to cause colic signs, and both forms appear to affect peripancreatic and intrapancreatic fat more than they affect the pancreatic parenchymal cells.

Chronic pancreatic atrophy with islet reduction has also been described and possibly associated with a picorna virus similar to equine rhinovirus.19 Diabetes-like clinicopathologic changes and glucose responses have been described. However, recent work suggests that these assessments of pancreatic form and function were normal for camelids.


Hypoglycemia is an uncommon finding in camelids, even in sick neonates and older camelids with longstanding anorexia. Poor glucose clearance limits its rate of use, even in camelids lacking other forms of energy, and exuberant gluconeogenesis continues in spite of negative energy balance.20,21 Hypoglycemia usually reflects abnormal consumption or impaired gluconeogenesis. Examples of the first are septic camelids or those with Mycoplasma haemolamae infection, in which hypoglycemia may develop from bacterial consumption. With these disorders, bacterial consumption continues in blood samples, so delayed laboratory analysis may yield misleading results with low levels, and the prevalence of hypoglycemia even in these populations is lower than expected. Iatrogenic hypoglycemia following insulin administration also is the result of increased consumption. This occurs most commonly in neonates or any camelid administered a long-acting form of insulin without simultaneous glucose administration. Lactating or pregnant camelids may also be at higher risk because of greater insulin-independent glucose uptake.

Decreased gluconeogenesis is usually the result of severe liver disease. Lymphoma, toxic hepatopathy, and severe hepatic lipidosis all occasionally result in hypoglycemia that continually recurs in spite of supplemental glucose.

Mild hypoglycemia is clinically inapparent. Camelids may show some evidence of weakness and lethargy, but it may be difficult to separate these signs from the primary illness. When hypoglycemia becomes severe (<50 mg/kg [2.75 mmol/L]), the risk of neurologic signs increases. These include profound obtundation and seizures.

Hypoglycemia is best treated by intravenous glucose administration. A bolus of 0.25 grams per kilogram (g/kg) of dextrose should increase blood glucose concentration by 50 to 100 mg/dL (up to 5.5 mmol/L). Slow infusions are also effective. Because of the infrequency of this disorder and the potential for aggravating hyperglycemia, confirmation of hypoglycemia before treatment is advisable.

Treatment of Disorders of Carbohydrate Metabolism

As glucose itself appears to be marginally useful to camelids and the chance of deficiency in low, most efforts are directed at avoiding the complications of hyperosmolality. Transient, severe hyperglycemia may be left to resolve on its own, as long as the camelid remains adequately hydrated. If glucose remains high or the rise in blood sodium concentration is becoming a concern, insulin may be administered to reduce blood glucose. Regular insulin (0.2 units/kg) given intravenously (IV) has a near-instant effect that lasts about 1 hour.5 Regular insulin also may be give as a constant rate infusion (0.02 units/kg/h [0.009 units/lb/hr]).22 Long-acting preparations given subcutaneously (0.4 units/kg) have effects lasting up to 24 hours.11 Newer forms such as insulin glargine appear to be more potent than older preparations and hence may be effective at lower doses (0.2 units/kg, q24h). Both porcine and human recombinant forms appear to be effective. Glucose should be monitored over the period of insulin efficacy to prevent hypoglycemia. Potassium supplementation may be necessary because insulin treatment tends to reduce extracellular potassium.

With hyperosmolar disorder, the severe disorder usually develops acutely, and signs are usually noted quickly. Thus, production of idiogenic osmoles in the brain is less of a concern than with hypernatremia syndromes in other species. However, slow correction of hyperosmolar disorder is rarely contraindicated and decreases the risk for rebound cerebral edema.

Treatment involves addressing hyperglycemia and fluid administration. Oral fluids are preferable to parenteral fluids, if the digestive system is functional, because the slower rate of absorption decreases the chance for rapid shifts in body water. Up to 3% of body weight may be administered orally or by tube at one time. This may be repeated up to three times a day. Free-choice oral water is also an option and rarely leads to complications. Milk or a diluted milk replacer may be used in lieu of water in suckling crias. If used, IV fluids should be administered at near-maintenance rates. Initial crystalloid fluid boluses of 2% to 5% of body weight may be tolerated and may restore renal output. Blood sodium should be measured periodically to avoid worsening of hypernatremia or too rapid correction. Decreasing blood sodium up to 0.5 mEq/L/hr appears to be safe. If hypernatremia is worsening, diluting isotonic salt solutions with 5% dextrose or adding low-sodium oral fluids to the treatment regimen may help. If correction is too rapid, signs of cerebral edema may appear. Administration of diluted fluids should stop until the edema is addressed and antiseizure medications may be necessary (see Chapter 38). Antibiotics, antiinflammatory medications, plasma, or other treatments may be indicated for the primary disease. Because of the role of steroids in stimulating hyperglycemia and retaining sodium, their use should be avoided in the treatment of hyperosmolar disorder.

Hypoglycemia may be treated with exogenous IV glucose. Other glucogenic agents are not recommended because of potential complications. Repeated dosing may be necessary if the inciting cause cannot be eliminated.

Disorders of Lipid Metabolism

Exuberant Lipid Mobilization (Ketosis, Ketonemia, Acetonemia)

Exuberant lipid mobilization (ketosis, ketonemia, acetonemia) is a catch-all term referring to camelids with high NEFA or BOHB levels which have not developed hepatic lipidosis. It is generally believed that this state precedes and may progress to lipidosis.20 It is characterized by general malaise and inappetence, occasionally with weight loss and often with some more obvious disease. It is essentially a laboratory diagnosis, defined by abnormal blood NEFA or BOHB values. Approximately two thirds of all sick camelids have increases in one or both of these determinants, with increases in NEFA values being slightly more common than increases in BOHB values. This is separated from dietary insufficiency because a decrease in feed intake usually occurs and also because it is believed that the hormonal milieu (high catecholamine, low insulin) stimulates lipolysis and ketogenesis beyond that which is normal for fasted camelids. This disorder is treated by using the general strategy outlined below, and it is usually thought that treating at this stage may prevent the camelid from developing hepatic lipidosis.

Hepatic Lipidosis

Hepatic lipidosis appears to represent a progression of exuberant lipid mobilization or possibly hyperlipemia. Specifically, it refers to microscopic fat deposition within hepatocytes (Figure 41-2) although lipid accumulates in renal tubular cells and other tissues as well. Lipidosis is thought to be caused either by increased fat (NEFA) delivery to tissues, or by inhibition of hepatic fat oxidation or export. Unlike with related disorders in cattle or sheep, lipidosis is reasonably common even in nonpregnant, nonlactating camelids and has been seen in both genders and in crias as young as 2 days old.23 In ruminants, negative energy balance and carbohydrate insufficiency are thought to be important in the pathogenesis, but camelids with all fat mobilization syndromes have a high prevalence of hyperglycemia and often have no extraordinary energy demand. Therefore, it is presumed that some factor beyond dietary insufficiency contributes to the condition. In rare cases, lipidosis in newborns may be a physiologic result of their high-fat milk diet, but that is unlikely to be a factor in sick crias.

Most affected camelids show increases in blood NEFA and BOHB values, reflective of peripheral fat mobilization and oversupply to the liver. Some also have hyperlipemia. Blood glucose is rarely low, except in pregnant or lactating females, and is frequently even high. This suggests that pregnant or lactating females may develop hepatic lipidosis when their blood glucose supply does not match demand, a similar situation to ketosis in cattle or sheep.

In addition to simple starvation or competition for food, various stressors may promote lipolysis. These include transport, extreme temperatures, hypoproteinemia, and illness. Concurrent or previous liver disease may compromise its function in energy metabolism. Hormonal mechanisms may also play a role, especially suppression of insulin production or increase in catecholamines. Epinephrine in particular has been shown to be a potent stimulator of adipose mobilization and antagonizes the actions of insulin as well.14

Protein deficiency appears to play a greater role in camelids than in cattle. Hypoalbuminemic hypoproteinemia is common in sick camelids, including those with lipidosis. Healthy camelids seek out high-protein plants in their environment and appear to tolerate intermittent starvation well. It is our belief that they tolerate caloric malnutrition (marasmus) much better than they tolerate protein-calorie malnutrition (kwashiorkor). The reasons for this are unknown but may include the following: as in cows, vital amino acid deficiencies may prevent lipoprotein formation and result in hepatic lipidosis; amino acid deficiencies may inhibit the production of vital protein hormones such as insulin; and the enzymatic pathways that direct glucose and pyruvate away from the citric acid cycle may increase need for other components (amino acids) to enter that cycle to replenish oxaloacetate and to produce energy. Amino acid deficiencies may be exacerbated by camelids’ apparently high rate of gluconeogenesis, which relies on protein substrate during periods of anorexia.

In addition to factors that promote fat delivery to the liver, hepatic injury or dysfunction may play a role in liver fat deposition. Hypoxia and toxic damage caused by compounds such as copper or plant toxins are implicated. Cobalt deficiency may also decrease hepatic lipolytic capacity. The presence of vague histologic changes such as periportal fibrosis and bile duct proliferation in some cases support the contributions of toxins or injury.


Hyperlipemia and hypertriglyceridemia are found in approximately one third of the camelids that have other evidence of a lipid disorder and are seen only rarely (<5%) as the sole abnormality. Thus, triglyceride measurement, which is more widely available than NEFA or BOHB measurements, is relatively insensitive for lipid disorders as a whole. Why hypertriglyceridemia happens in that subset of camelids with high NEFA concentrations is unknown; increases in triglyceride may take sustained increases in fat mobilization, whereas some increases in NEFAs may be labile and transient, or potentially increases in triglycerides occur in animals with inhibition of peripheral uptake as well as fat mobilization.

Based on the Fredrickson classification of hyperlipemia, the disorder in camelids is most likely to be type IIb, with increases in both low-density lipoproteins (LDLs) and VLDLs. In humans, type IIB hyperlipemia may be familial or a component of metabolic syndrome (CHAOS [Coronary artery disease, Hypertension, Adult onset diabetes, Obesity, and Stroke] in Australia). It is associated with increasing age, genetic factors, sedentary lifestyle, and high caloric intake. In camelids, it usually arises in conjunction with another disorder such as endoparasitism, heat stress, hepatic lipidosis, CNS disorders, sepsis, or colic.2427 As such, it is frequently viewed as a complication, usually near-terminal, of those disorders. Other factors associated with metabolic syndrome in humans include high blood pressure, central obesity, fasting hyperglycemia, insulin resistance, poor glucose tolerance, and possible microalbuminuria. Several of these characteristics are normal in camelids, and it may be that the preceding illness exacerbates the metabolic state by reducing blood proteins, by stimulating catecholamine release, or by decreasing or antagonizing insulin activity. As with lipidosis, all ages, signalments, and body conditions of camelid are affected by hyperlipemia.24

Few specific clinical signs are associated with hyperlipemia. As with other disorders of fat metabolism, anorexia, obtundation, weakness, progressing to recumbency and eventually neurologic signs and death are common findings. A small number of camelids with chronic hyperlipemia may develop lipogranulomatous ulcerative skin lesions, particularly of distal extremities. Hyperlipemia may also occasionally be recognized by cloudiness of the plasma or serum. In its milder form, this is difficult to recognize, but as the hyperlipemia worsens, the serum takes on a milky appearance. As a word of caution, hyperlipemia may falsely increase protein readings on the refractometer, causing hypoproteinemia to be missed.

Recent findings suggest mild hyperlipemia tends to worsen unless specifically treated, even if any underlying disorders are appropriately addressed.24 Thus, even mild hyperlipemia may represent the beginning of a serious, progressive metabolic derangement.

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Mar 27, 2017 | Posted by in GENERAL | Comments Off on Hepatic, Pancreatic, and Metabolic Disorders

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