General Noninfectious Disease

Question 1

What are the three most toxic freshwater cyanobacteria?

What toxins do each of them produce?

What are the mechanisms of the follwoing cyanobacterial toxins:

Microcystin

Nodularin

Saxitoxin

Cylindrospermopsins

Lynbyatoxin A

Aplysiatoxin

Answer 1

Fowler 7 Ch 14 - Cyanobacterial Biointoxication in Free-Ranging Wildlife

Auth: Peter E. Buss & Roy G. Bengis

Introduction

Cyanobacteria:

• Blue Green Algae (BGA)
• Aerobic OR Anaerobic
• Eutrophic water = rapid multiplication, intense blooms
• Global warming leading to increased eutrophication of waters and expansion of cyanobacterial geographic ranges
• Most toxic freshwater cyanobacteria = Microcystis, Anabaena, Panktothrix
  
  • Microcystis – produces Microcystins
  • Anabaena – produces Anatoxins, microcystins, saxitoxins
  • Panktothrix – produces Anatoxins, aplysiatoxins, microcystins, saxitoxins

Toxins:

• Microcystin – most commonly produced toxins
  
  • Hepatotoxin – disrupts hepatic cellular structure – sinusoid destruction – intrahepatic bleeding – fatal hemorrhagic shock
• Nodularin – closely related to microcystin – similar hepatic effects
• Anatoxins – Alkaloid toxin
  
  • Depolarizing neuromuscular blocking agents in higher vertebrates
  • Not affected by Acetylcholinesterase – excessive stimulation muscle cells – fatigue paralysis – death d/t resp arrest
  • No antidote;
• Saxitoxins – Alkaloid toxin;
  
  • Inhibit opening of Na gated channels – paralysis and respiratory arrest
• Cylindrospermopsins – Alkaloid toxin
  
  • Irreversible inhibition of protein synthesis
  • Greatest effect on liver, but also affects other organs
• Lyngbyatoxin a – Alkaloid toxin
  
  • Inflammatory toxin
  • Strong tumor promoter through protein kinase C
• Aplysiatoxins
  
  • Dermatotoxins – cause inflammation of the skin
  • Potent tumor promoters
• Cell based toxins, therefore released in high conc w/ BGA cell lysis

Question 2

What factors influence the toxicity of cyanobacterial blooms?

What factors affect the growth of cyanobacterial blooms?

Answer 2

Factors Contributing to Growth and Toxicity of Cyanobacterial Blooms

Toxicity:

• Influenced by:
  
  • Temperature
  • pH
  • Light intensity
  • Organic nutrients
  • Age of algal cells
• Changes in toxicity occur on spatial and temporal scale
• Level of toxicity NOT associated with greatest growth rate

Growth:

• Dependent upon temperature:
  
  • Severely limited growth below 15C
  • Optimal growth 25-32C
  • Maximal toxin production 20C
    
    • Growth not very inhibited above 30, but toxin production markedly decreased
• Ability to grow at higher temps give advantage over other phytoplankton spp
• Global Warming:
  
  • Warmer surface waters – increased vertical stratification/decreased mixing
  • Surface waters warmer longer – increased growing season for BGA
• Increased light intensity = decreased growth
• Eutrophication – higher nitrogen-to-phosphorus ratios
  
  • Increased occurrence with organic nutrients (ex/ human or animal waste, pollution from mining, fertilizers from farming)
  • Results in increased growth and toxin production
• Zn & Fe – influence growth and toxin rates b/c required for nitrogen assimilation, respiration and chlorophyll synthesis

Question 3

Why are aquatic invertebrates potential sources of cyanobacterial toxins?

Why do mass mortalities of fish occur during cyanobacterial blooms? How are juvenile fish versus adult fish affected differently?

What cyanobacterial bloom was responsible for mass flamingo mortalities in East Africa?

How does suceptibility to toxins differ across taxa?

What are the various timelines these toxins can produce disease?

How are these diseases diagnosed?

Answer 3

Toxicity in Animal Species

• Reported mortalities in fish, turtles, birds, mammals
• Invertebrates:
  
  • Bivalves – ingest cyanobacterial toxins by filtering water – may promote or reduce blooms (conflicting reports); May be source of toxin if consumed
  • Crayfish, shrimp – tolerate and grow w/ Microcystis ingestion; toxins accumulate in liver; potential sources of toxin if consumed
  • BUT - Evidence of transfer of microcystins w/in food web & biomagnification is limited
• Fish:
  
  • Mass mortalities reported
  • Contributing factors: low water level, high water temps, high pH, high ammonium, low DO, presence of other toxin producing organistms
  • Juveniles – Microcystins interfere w/ development
    
    • Dose dependent alterations in hatching time, survival and growth rates
    • Poor yolk resorption, small head, curved body and tail, hepatobiliary abnormalities, altered hepatocytes, cardiac problems
  • Adults – Kidney, liver most affected; similar problems to mammals, but also experience gill necrosis
    
    • Gill chloride ion pumps may be disrupted affecting osmotic bal.
  • Species native to eutrophic habitats usually more resistant
  • Hepatotoxins may accumulate in fish tissue – risk to predators?

Flamingo Mass Mortalities

• Lesser flamingos
• East Africa – Lakes in Kenya, Tanzania
• Arthrospira fusiformis
  
  • Important natural food source for these flamingos
  • Presumed cause of morts
  • Produces microcystins and anatoxin a
  • Clinical Signs: Muscle fasciculation, hyperpnea, cyanosis, paralysis, hyperesthesia, opisthotonus, convulsions, resp failure
• Spatial Variation
  
  • Patches of high and low concentration of algal elements
  • Winds push the floating cyanobacteria cells – algae accumulates on leeward side of water bodies
• Consumption – animals do not avoid consuming the algae – some selectively consume it over cleaner water

Clinical Signs and Treatment:

• Variable susceptibility in domestic spp
• Anatoxins – Dogs, pigs most affected; waterfowl susceptible; ruminants relatively resistant
• Peracute to Chronic presentations
  
  • Peracute – death in hours
  • Acute/Subacute – liver failure sign inc. photosensitization, death 1-2 wks
  • Chronic – from ingestion of sublethal doses over time; emaciation, anorexia, photosensitivity, alopecia, occ liver effects

Diagnosis:

• Dx based on hx, i.d. of BGA in water, i.d. & quantification of toxin in water
• Also, wet mount from suspect water body or GI tract of affected animal
• ELISA, protein phosphatase inhibition assay or mouse bioassay – assess degree of liver toxicity
• High performance liquid chromatography and other chromatography methods may be used to i.d. and quantify toxins

Question 4

What species were affected by the major algal blooms in Kruger National Park in 2005 & 2007?

What methods are used to control cyanobacterial blooms?

Answer 4

Kruger National Park: A Case Study

• Major algal blooms 2005, 2007
• Warm autumn and early winter following dry summer
• Low water levels w/ high conc hippos (lots of waste = high nitrogen & Ph + stir up river bed providing organic nutrients)
• White Rhino, zebra, wildebeest over-represented in carcass counts
  
  • Not wading spp – likely drank surface water
  • Often drink from downwind side of water bodies
• Elephants, buffalo, hippos under-represented
  
  • Thought to wade out past scum line or drink from windward side

Control of Cyanobacterial Blooms

• Treatment to kill algae may release large amts of toxin making water undrinkable for 2-3 weeks
• Most commonly used algacides:
  
  • Copper sulfate
  • Diquat
  • Simazine aluminum sulfate (alum) – removes Ph from water; coagulates cyanobacteria resulting in flocculation and less release of toxin
  • Lime – removes Ph from water; coagulates cyanobacteria resulting in flocculation and less release of toxin
  • Decomposing barley straw or hay
  • Bacillus cereus – in floating biodegradable plastic carriers was effective in situ control of Microcystis blooms
    
    • Eliminated 99% floating BGA in 4 days
  • Ph removal w/ alum, ferric salts, ferric aluminum sulphate, clay particles, lime
  • Lanthanum – rare earth element – bound to bentonite to reduce toxicity – decreases Ph w/o affecting pH and nitrate concentration
  • Floating booms, curtains – prevent rafts of BGA from reaching shore

Question 5

What is gout?

How are urates formed?

Describe urate metabolism and excretion. How does it differ with pigs and spiders?

What is the nitrogen metabolism of aquatic turtles, fish, and invertebrates?

What diets are at higher risk of gout formation? Why?

How does kidney damage or decreased perfusion lead to gout?

What is teh difference between primary and secondary gout?

Answer 5

Fowler 8 Ch 67 - Gout in Exotic Animals

• Gout = inflammatory arthritis, in response to deposition of urate crystals in tissues
• Urate = derived from breakdown of purine bases (guanine/adenine)
  
  • originate from nucleic acids of both exogenous and endogenous sources
• In humans, nonhuman primates, birds, terrestrial reptiles, amphibians, insects 🡪 uric acid is formed on purine breakdown.
  
  • Urate salts and uric acid are relatively insoluble
  • Use uricase/urate oxidase to break down urates to allantoin (which is soluble)
• Pigs and spiders excrete guanine directly (weird random fact)
• Aquatic turtles excrete urea or ammonia
• In fish allantoin is further degraded into allantoic acid and urea
• Aquatic invertebrates break down purines to ammonia
• Excretion of ammonia and urea result in the concomitant loss of water
  
  • i.e. the form of excretion generally seen in semi-aquatic and aquatic species
• Fructose phosphorylation in liver requires abundant ATP
  
  • Thus, diets high in fructose increase the risk of gout development
  • Fructose is only carbohydrate that has a direct effect on urate metabolism
• Kidney damage = increased urate retention
• Decreased perfusion = decreased urate clearance (dehydration or renal disease)
• Nephrotoxic drugs (aminoglycosides, sulfonamides) decrease urate excretion by damaging the renal tissue.
• Decrease in GFR in hypertension results in decreased urate excretion and increased gout risk
• Diuretics, alcohol intake, and acute diarrhea reduce hydration and decreases urate excretion
• Liver failure decreases effectiveness of filtering of blood 🡪 increased circulating urate levels
• In humans, gout seen in assoc. with diabetes, insulin resistance, heart dz, hypertension, nephropathy, & diseases with increased cell turnover (i.e., neoplasia)

ETIOLOGY

• Primary gout = overproduction of uric acid as an innate metabolic problem
  
  • Caused by a defect in the renal urate transporters
  • Primary gout is most common form in humans, usually has familial inheritance
• During primate evolution, gene mutations resulted in variable activity of uricase enzyme
• Retention of these gene mutations suggests that loss of uricase confers some advantage
  
  • Urate may act as bloodborne antioxidant, removing free radicals
  • Hyperuricemia appears protective against neurodegenerative dz: Alzheimers, Parkinsons, and amyotrophic lateral sclerosis
  • Uric acid may be important in maintenance of blood pressure with low salt diets
• Secondary gout = develops with loss of balance between uric acid production and excretion
  
  • Results in net under-excretion and eventually hyperuricemia
  • Excess purine intake occurs when purine in diet fed exceeds amount in natural diet for a particular species
  • Common example = herbivorous reptiles fed a meat-rich diet
    
    • Meat, fish, shellfish have higher purines then vegetable-based diets
• Availability of water (hydration) further affects purine levels

Question 6

How does chronic versus acute gout differ?

Describe the radiolucency of urate deposition? How does it change and why?

What may be seen on imaging?

How is gout confirmed cytologically?

How does the immune system respond to urate crystals?

What factors influence the solubility of urate in synovial fluid?

What are the typical pathologic findings of gout?

Answer 6

CLINICAL SIGNS AND DIAGNOSIS OF GOUT

• Chronic gout = deposition of crystals as tophi; form of dz diagnosed in birds/ reptiles
• Acute gout = Identified to occur naturally in humans; induced experimentally in other species
• Physical examination of joints that exhibit swelling and visible deposition of white substance and a history with respect to predisposing factors may lead to a diagnosis of chronic gout
• Monosodium urate stones are radiolucent
  
  • Addition of calcium to crystals causes radio-opacity
• Tophi and renal enlargement may be dx with radiography, US, or renal biopsy
• Biopsy and cytology may be used to confirm a dx of gout in veterinary cases
• Cytologically, under polarized light, crystals have a cross-hatched pattern

PATHOPHYSIOLOGY

• Hyperuricemia occurs w decreased urate/uric acid excretion
• Urate crystals stimulate both humoral and cell-mediated immunities

1. Interact w membrane lipid/proteins & cause histamine release from mast cells
2. Gout crystals cleared by macrophages releasing inflammatory mediators (including IL-1)
3. Complement system is also activated.
4. Synovial lining cells and resident inflammatory cells are stimulated.
5. Neutrophils adhere to endothelial cells through IL-1 and TNF-α.
6. Tophi cause cartilage lysis, metalloproteinases secreted, chondrocytes are activated

• Solubility of urate in synovial fluid influenced by temp, pH, cation conc, articular hydration:
  
  • When urine pH is reduced, increase risk for urate crystal deposition
  • Nucleating agents (collagens, chondroitin sulfate, nonaggregated proteoglycans) may form a nidus for crystal deposition and growth
  • In humans, lesions tend to develop first at the extremities (big toe), thought to be assoc with reduction in temp at the periphery

PATHOLOGIC FINDINGS

• Acute gout in humans characterized as a neutrophilic synovitis
• Tophi seen in chronic disease = urate crystals surrounded by inflammatory cells
• Over time, tophi may cause chondrolysis, metalloproteinase secretion, and bone erosion
• Renal changes are seen in 40% of humans with gout
• In uricotelic species, customary to refer to condition as articular and visceral gout

Question 7

What are some important differentials to consider for gout?

What treatments are available to treat gout? How do they work?

What palliative care is available?

What is the prognosis for animals with severe gout?

How can gout be prevented?

What drugs shoudl be avoided?

What dietary changes can be made to reduce risk?

Answer 7

DIFFERENTIAL DIAGNOSIS (OF GOUT)

• Pseudogout = when a crystal other than monosodium urate is deposited at joints
  
  • Periarticular calcium hydroxyapatite deposition reported in red-bellied, short-necked turtles (Emydura albertisii)
• Fluorosis = May see nodular bone deposits extend from the subperiosteum
• Nutritional fibrous osteodystrophy = May see osteophytes in reptiles w Ca/P imbalances
• Hypervitaminosis D = May see metastatic calcification of soft tissues
• Septic Arthritis = may see joint swelling, can ID via gram stain/culture of joint aspirates

TREATMENT

• Circulating uricemia may be reduced in humans via change to a purine-free diet
  
  • Decreased intake of animal-derived protein, and supportive therapy
  • Optimizing hydration improves urate excretion.
• Main forms of drug treatment are used:

1. Xanthine oxidase inhibitors (allopurinol, febuxostat): Decrease uric acid formation
   
   1. Appear to be relatively ineffective in reptiles and birds.
2. Uricase or urate oxidase: Oxidizes uric acid to allantoin (soluble)
   
   1. Used in the treatment of gout in humans.
   2. Some uricase treatments require IV administration (limiting factor)
   3. Little info available in veterinary literature on use of uricase
3. Uricosuric drugs (probenicid, sulfinpyrazone): Promote urate excretion by the kidneys, thus lowering serum uric acid.
   
   1. Probenicid - promotes urate excretion in the kidney, inhibits tubular reabsorption
4. Supportive care in the form of palliative management
   
   1. Colchicine - decreases inflammatory response within 24 hours)
   2. Corticosteroids
5. Surgical removal and flushing of crystals from joints
   
   1. Some residual changes are frequently seen in the joints
   2. Underlying hyperuricemia has not been addressed

• Severe gout has poor prognosis in animals; humane euthanasia may be considered when management with analgesia, diet, and environment has failed

PREVENTIVE MEDICINE

• Drugs to avoid = diuretics, cyclosporine, tacrolimus, β-blockers, low-dose salicylate
• Avoid nephrotoxic plants and drugs (aminoglycosides, sulfonamides)
• Purine in the diet should be minimized.
• Increased consumption of meat or seafood increases the risk of development of gout
• Increase in dairy proteins is protective (milk proteins increase UA excretion in urine)
• Increased purine-rich vegetable protein in diet has not been shown to increase risk
• Bioavailability of purines varies: more available from (RNA) source compared w (DNA)
• Scientifically prepared diets (low in protein and calcium) commercially available for dogs
  
  • Have been used in reptiles
• Optimal ambient temp. important for metabolism and body functions in reptiles
• Adequate hydration important to maintain renal secretion (use fluid therapy)
• Use of omega-3 fatty acids for chronic arthritis
  
  • In cases with concomitant gout, ensure patient receives a plant-sourced rather than usual fish oil source (higher purine levels)

Question 8

What is iron overload?

What is the difference between hemosiderosis and hemochromatosis?

What are primary and secondary causes of iron overload?

What are the two main forms of dietary iron? What nutritional sources do they come from?

What enhances iron absorption?

How is iron transported?

What is the primary regulatory hormone of iron metabolism? What causes its release?

Answer 8

FOWLER 8 CH 69 UPDATE ON IRON OVERLOAD IN ZOOLOGIC SPECIES

• Iron overload (IO), also called iron storage disease (ISD) or iron over- load disorder, was considered rare in veterinary species until the 1970s and 1980s, after which it became increasingly recognized in many taxa of birds and mammals
• Hemosiderosis = accumulation of stainable iron without morphologic or biochemical evidence of toxicity
• Hemochromatosis = pathologic accumulation of iron
• Iron overload may be primary (implying a constitutional, genetic propensity to accumulate iron, generally as a result of inability to control intestinal absorption, as in human hereditary hemochroma- tosis) or secondary to a variety of causes, including excessive enteral or parenteral (e.g., transfusions) intake, diseases of the erythron, liver disease (including intoxications and infections), systemic inflamma- tory processes (with iron sequestration as an antibacterial defense), stress, chronic renal disease, and malnutrition
• Hepatocytes are the major site of iron storage in overload states

Review of iron absorption and transport and liver handling of iron

• Off-loading is difficult so primary control is at the level of intestinal absorption
• Dietary iron is present in 2 main forms: heme and non heme. Heme iron is highly bioavailable and is the primary source of iron in carnivores, whereas non-heme iron is complexed with organic acids or peptides and is the predominant form of dietary iron available to omnivorous, frugivorous, folivorous, granivorous, and other plant-eating species
• In humans, non-heme iron in the oxidized state is reduced and then taken up by the cellular iron importer divalent metal transporter-1 (DMT-1).
• Gastric acid enhances the solubility and absorption of non-heme iron complexes, and dietary vitamin C increases iron absorption by forming highly bioavailable, soluble iron complexes.
• Within the enterocyte, depending on the metabolic demand, iron is either bound to the iron storage protein, ferritin, in the cytosol or is exported into plasma via ferroportin
• Oxidized iron is taken up by plasma transferrin for distribution throughout the body, and a majority is carried to erythropoeitic cells.
• Hepcidin, the key iron regulatory hormone, expressed primarily in the liver, is induced when tissue and plasma iron levels are high
• Hepcidin production is also induced in inflammatory states and appears to be a key mediator in anemia of chronic disease. Hepcidin is strongly suppressed in states requiring accelerated erythropoiesis.
• In humans, in a majority of cases, hereditary hemochromatosis is associated with a deficiency in hepcidin because of mutations in the hepcidin (HAMP) gene itself or its regulators

Question 9

What are some of the consequences of iron overload?

How is iron overload diagnosed?

What are teh typical clinical signs?

What might be seen on imaging?

What is the gold standard for quantifying iron accumulation? What stain is used?

What analyte is considered the best noninvasive measurement of iron stores?

What does serum iron measure?

What about total iron binding capacity?

Answer 9

Consequences of iron overload

• Unbound iron is cytotoxic and causes peroxidation of membranes and cell death
• Can cause cirrhotic liver failure
• Also increases susceptibility to bacterial and fungal infections through direct effects on immune system function and by providing iron for microbial growth
• May also be connected to development of metabolic syndrome and type 2 diabetes in dolphins and rhinos

Diagnosis

• Early diagnosis of ISD poses a challenge, as clinical signs are not specific and often not apparent until disease is advanced
• Clinical signs typically associated with liver failure, though some species such as cattle and red deer also develop poor bone quality and hair coat and sometimes incisor fractures in young animals and birds can have cardiomegaly, dyspnea, and wheezing
• Rads can be useful in identifying hepatomegaly and cardiomegaly
• Lier biopsy for histologic grading of iron accumulation and liver damage is the gold standard
• Serum iron analytes have been used as a proxy when biopsy is not possible
• Serum ferritin (SF) is considered the best test for noninvasive measurement of body iron status in mammalian species
  
  • Variation in the molecular structure of ferritin requires species-specific radioimmunoassays, only available for humans, dogs, cats, cattle, horses (used for bats), pigs, rhinoceroses (used for tapirs), lemurs (used for callitrichids), dolphins, and fur seals
• Serum iron (SI) levels reflect the total amount of iron in blood, including transferrin-bound and non–transferrin-bound iron. In mammalian species and birds, diurnal and seasonal variations exist in SI.
• Total iron binding capacity (TIBC) and the calculated percentage transferrin saturation (%TS) are also used as indicators of body iron stores, with %TS considered more reliable than SI, TIBC, or both.
• In birds, SI analytes seem to be of little diagnostic value, although relative changes in SI and %TS may be used to monitor treatment
• If accessible, MRI signal intensity has been shown to correspond well with hepatic iron concentrations
• Prussian blue is the stain used on liver samples
• Normal reference ranges for liver iron concentrations (LIC) are lacking for most species and can also be complicated by seasonal variation, reproduction status etc

Question 10

Iron overload in reptiles and amphibians is commonly secondary to what conditions?

What avian species are particularly susceptible to iron overload?

Are there any documented genetic isues in these species?

Answer 10

Iron overload syndromes in zoologic species

• Amphibians and reptiles
  
  • Hepatocellular hemosiderosis, often with hepatic lipidosis, is not uncommon in amphibians and reptiles and is likely secondary to systemic inflammation or inanition, not caused by a primary susceptibility to ISD
• Birds
  
  • Both primary and secondary ISD occur
  • Toucans, birds of paradise, mynahs and starlings are considered to be most susceptible
  • Mynahs have a much higher expression of DMT-1 (divalent metal transporter 1) than other species, such as doves–supports the hypothesis that diets for iron sensitive species are low in bioavailable iron leading to selection for enhance uptake
    
    • Diets in captivity provide too much iron may exacerbate primary ISD, as shown in starlings
  • Psittacines are a diverse order with both generalist and specialized feeders
    
    • Loris (nectivorous) seem to be susceptible to ISD
  • ISD seen in flamingos, may be primary or secondary due to systemic inflammation (pododermatitis)

Question 11

What mammalian species are particularly sensitive to iron overload?

Iron storage disease is common in what chiropteran species? How do these cases present and what are some of the common findings on necropsy?

What perissodactyl species are at risk? Are there any genetics that may play a role?

What artiodacyl species are commonly affected? What are their presenting signs?

What carnivore species are susceptible?

What marine mammals?

What primates are more susceptible? Which are more resistant?

Answer 11

IRON OVERLOAD IN MAMMALS

• Mammals
  
  • Chiroptera
    
    • Hemochromatosis is the leading cause of morbidity and mortality in captive Egyptian fruit bats
    • Clinical signs characteristic of liver failure or generally not apparent until advanced stages of the disease - icterus, weight loss, ascites
    • Elevated iron analytes and bilirubin have been reported
    • Histologically, disruption of hepatic architecture occurs, with extensive periacinar and periportal fibrosis bordering foci of nodular regeneration and areas of hepatocellular necrosis
    • In a retrospective of Egyptian fruit bats, bats with hemochromatosis were significantly more likely to develop hepatocellular carcinoma compared with bats with hemosiderosis
• Perissodactyls
  
  • ISD is well described in black and sumatran rhinos
  • Iron is present in many tissues suggesting a problem in iron mobilization
  • In black rhinos iron levels increase with age and time in captivity
  • Mechanism is unclear
  • Hereditary predisposition has been suggested on the basis of the presence of an S88T polymorphism in the hemochro- matosis gene (HFE) of the black rhinoceros. However, this polymor- phism is also present in the Indian rhinoceros (Rhinoceros unicornis), which only occasionally exhibits ISD.
  • Possibly due to the fact that they are browsing species and captive diets are inadequate/higher in iron than their natural diet
  • Baird, Brazilian, and Malayan tapirs (Tapirus bairdii, T. terrestris, and T. indicus) are also affected by ISD in captivity, as shown by necropsy data
  • Occasionally seen in equids as well
• Artiodactyls
  
  • Clinical signs of IO in artiodactyls are not restricted to those of liver failure and include loss of weight in spite of good appetite, poor hair coat, and osteopenia with incisor loss and fractures in young animals
  • Has been reported in reindeer related to winter foraging on mosses high in iron and low in nutrients
  • Has been reported in captive red deer bucks
  • Hepatocellular hemosiderosis is fairly common in neonatal zoo-housed hoofstock (gazelles, caprines, ovines, and cervids) but is considered physiologic rather than pathologic
• Carnivores
  
  • Carnivores would be expected to efficiently control iron absorption as most of their dietary iron is easily absorbed heme-iron
  • Nonetheless, hepatic hemosiderosis has been reported in several felids (cheetah, Acinonyx jubatus; and snow leopard, Uncia uncia), procyonids (red panda, Ailurus fulgens; and coati mundis, Nasua spp.
• Marine mammals
  
  • Hemosiderosis is common in neonatal pinnipeds dying in rehab facilities, especially pacific harbor seals–may be a normal physiologic finding
  • IO is commonly seen in yearling CSL’s with malnutrition
  • Also common in bottlenose dolphins
• Nonhuman primates
  
  • Hemosiderosis commonly seen in lemurs, new world monkeys, colobines, and apes
  • Old world cheek-pouch monkeys seem to be more resistant
  • Hemochromatosis has been found in zoo house lemurs
    
    • In one study severity of ISD increased with age, and liver necrosis and neoplasia were seen
    • Attributed to diet–esp too much vitamin C and paucity of tannins
    • Hepatic neoplasia is common in prosimians and may be in part due to ISD
  • Hepatocellular IO is often noted in adult captive western lowland gorillas (Gorilla gorilla gorilla [Ggg]) but is infrequent in wild moun- tain gorillas
• Misc other mammalian species
  
  • ISD in hyraxes, pikas, gerbils, and other rodents is discussed in detail elsewhere.
  • Recently reported to be a consistent finding in nake mole rats

Question 12

How is iron storage disease managed and treated?

Answer 12

• Prevention and treatment
  
  • Dietary manipulation
    
    • Decreasing iron, limiting vitamin C
    • Adding tannins
  • Treatment
    
    • Phlebotomy–reduction of hematocrit by as little as 5% is therapeutic
    • Chelation–most commonly used are injectable deferoxamine (DFO) and oral deferiprone
    • The advantages of chelation are better mobilization of iron from tissues such as heart muscle and not having to induce anemia in cases of RBC disease and transfusion- induced ISD; however, these drugs may be toxic.