Nutritional and Metabolic Diseases 1 & 2 Flashcards
-Know risk factors associated with nutritional disorders (signalment, underlying disease etc) -List and recognise pathological lesions associated with starvation -Discuss pathogenesis of hepatic steatosis and ketosis -Explain effects of key vitamin/mineral imbalances in domestic and exotic species- vitamin A, B1 (thiamine), C, D, E/selenium, perhaps with an emphasis on thiamine and vitamin E/selenium- good comparative pathology. -Explain different manifestations of metabolic bone disease-
NUTRIENT
A substance that provides nourishment essential for growth and the maintenance of life.
METABOLISM
The process involving a set of chemical reactions that modifies a molecule in to another for storage or immediate use in another reaction, or to a byproduct.
CONSTRUCTIVE METABOLISM- anabolism. Synthesis of proteins, carbohydrates and fats, which form tissues and store energy.
DESTRUCTIVE METABOLISM- catabolism. Breakdown of complex substrates and the consequent production of energy and waste matter.
THE POINT OF NUTRITION?
To provide sufficient energy for daily metabolic requirements, via carbohydrates, fats and proteins.
To provide vitamins and minerals, which act as coenzymes or hormones in vital metabolic pathways.
NUTRITIONAL DISORDERS
Seen when tissue concentrations of a nutrient drop to a CRITICAL LEVEL, resulting in deranged cellular metabolism.
Tissues at particular risk- MYOCARDIUM, SKELETAL MUSCLE, BRAIN.
These tissues are fast metabolising so are prone to damage.
IMMATURE ANIMALS are most susceptible. Consider also species/breed (small breeds)/timeline.
NUTRITIONAL IMBALANCE
More common than a simple deficiency. Involves delicate interrelationships and several factors.
eg. Calcium:Phosphorous ratio, Calcium and Vitamin D interrelationship.
An excess of one dietary component may enhance the deficit of the other.
FACTORS CONTRIBUTING TO NUTRITIONAL DEFICIENCY
Underlying contributions to nutritional deficiencies are often seen:
- Decreased intake eg. anorexia, GI disease, allergy, dental disease.
- Decreased absorption eg. intestinal hypermotility, Johne’s disease.
- Interference with storage eg. liver disease (vitamin A), thyroid disease (iodine), storage diseases (glycogen etc.)
- Increased excretion eg. PU, sweating, endocrine imbalances, lactation.
- Increased requirements eg. pregnancy/lactation, fever, hyperthyroidism.
- Natural inhibitors eg. thiaminases
CALORIE DEFICIENCY- STARVATION
Protein or calorie malnutrition- total quantity or quality is deficient.
There is often underlying disease eg. intestinal malabsorption, diarrhoea, increased nutrient demands (excessive heat/cold/work)
eg. the German Shepherd Dog with exocrine pancreatic insufficiency- increased appetite but poor digestion can lead to starvation.
PATHOLOGY OF CHRONIC STARVATION
- Loss of MUSCULATURE (BCS)
- Loss of body FAT (cf. cancer cachexia- targets muscle, body fat is still seen)
- Serous atrophy of fat- the starving, hypoproteinaemic animal will undergo extended periods of lipolysis, leading to atrophy of fat.
Less common signs- subcutaneous oedema, cardiac muscle degeneration, visceral atrophy (liver, pancreas, small intestine- villous shortening)
STARVATION- GROSS LESIONS
-Serous atrophy of fat- CARDIAC fat and BONE MARROW are most commonly affected.
Fat becomes transparent, shiny, gelatinous/watery as it breaks down. Increased mucopolysaccharides.
Trabecular bone is seen in high quantities in the bone marrow- bone loss.
STARVATION- SPECIES DIFFERENCES
HOMEOTHERMIC ANIMALS- withstand starvation for 2 weeks, unless hibernating.
POIKILOTHERMIC ANIMALS can withstand starvation for several months eg. fish, snakes.
LIVER- CENTRAL ROLE IN METABOLISM
The liver is heavily involved in CARBOHYDRATE and FAT metabolism:
CARBOHYDRATE- removes glucose/fructose from plasma and stores them as glycogen/fatty acids.
If is decreased dietary CHO intake, energy balance will be maintained by glycolysis of stored glycogen (by glucagon) and gluconeogenesis.
FAT- production and degradation of plasma lipids- cholesterol, triglycerides, phospholipids, lipoproteins.
Fat deprivation will increase cortisol levels, to increase lipolysis and liberate fatty acids.
Fatty acids are oxidised in the liver to acetoacetic acid and ketones.
TWO PATHOLOGICAL OUTCOMES- steatosis or keratosis.
HEPATOCELLULAR STEATOSIS (LIPIDOSIS)
NOT a specific disease- is a sequelae to ABNORMAL LIPID METABOLISM.
Triglyceride accumulation exceeds metabolic degradation/release as lipoproteins.
There are many possible mechanisms.
eg. Excessive entry of fatty acids (increased dietary intake), increased mobilisation/demand- in lactation, starvation, endocrine abnormailities.
HEPATOCELLULAR STEATOSIS- CAUSES
- Dietary excess in monogastrics- high fat and/or cholesterol diets.
- Toxic and anoxic causes- sublethal injury.
- Ketosis
- Bovine fatty liver syndrome- during high energy demands, usually precipitated by anorexia.
- Feline fatty liver syndrome- idiopathic/anorexic OBESE cats
- Horses- ponies/miniatures/donkeys- overweight, follows anorexia and negative energy balance. Animal is usually hyperlipaemic.
- Endocrine disorders eg. Diabetes mellitus.
KETOSIS
Negative energy balance leads to fatty acid mobilisation.
fatty acids are esterified in to acyl CoA -> ketones (acetoacetic acid, B-hydroxybutyric acid)
-Seen in cattle during peak lactation
-Seen in sheep during late gestation- pregnancy toxaemia.
-INCREASING CIRCULATING KETONES- used by nervous system as alternative fuel. Decreased gluconeogenesis/protein sparing- ketones are a CRUCIAL adaptive survival mechanism!
OBESITY
Obese animals are more likely to develop diabetes mellitus, arthritis, and endocrine diseases.
VITAMIN A
Sources- meat provides preformed vitamin A, plants provide carotene or provitamin A.
ACTIVE FORM- RETINOL.
Important for development (bone growth), vision, immune system.
Stored in the LIVER in stellate cells.
VITAMIN A DEFICIENCY
- Skin lesions- hyperkeratosis etc. Impaired wound healing.
- Multiple species affected- dogs, horses, birds, reptiles, cattle.
- Vitamin A responsive dermatoses- abnormal cornification in adult Cocker Spaniels, Labrador Retrievers, Miniature Schnauzers. Can’t confirm a definitive deficiency, but can confirm that the condition responds to vitamin A.
- SQUAMOUS METAPLASIA- DEFINITIVE VITAMIN A DEFICIENCY. Seen in transitional epithelium of urinary tract, lining of salivary ducts (cattle), oesophageal mucous glands (birds)
- VISION- night blindness in cattle, optic nerve abnormalities.
- BIRDS- blunted choanal papillae are classical lesions of vitamin A deficiency. Also see rhinitis, blepharitis (eyelid inflammation), white plaques on oral mucosa.
- REPTILES- periocular oedema (common in chelonians), conjunctivitis, squamous metaplasia, hyperkeratosis of skin/mouth parts, aural abscesses.
VITAMIN B
VITAMIN B1- THIAMINE.
This is a CRITICAL cofactor in carbohydrate metabolism.
Deficiency leads to BRAIN DAMAGE due to- drop in thiamine-dependent enzymes, energy deprivation, oxidation stress (abnormal free radical metabolism in neurones).
THIAMINE DEFICIENCY CAUSES NEUROLOGICAL DISEASE in carnivores, ruminants and humans.
THIAMINE DEFICIENCY IN CARNIVORES
eg. Dog, cat, mink, fox. Carnivores have an ABSOLUTE requirement for dietary thiamine- they CANNOT synthesise their own.
Possible causes of deficiency- straightforward dietary deficiency, vitamin inactivation- by enzymes eg. thiaminases (found in fish), excessive heating (dog/cat food).
Lesions are BILATERALLY SYMMETRIC, often in the brainstem nuclei, and cause neuronal necrosis/degeneration. Most commonly seen in the caudal colliculi.
Clinical signs are variable- anorexia, vomiting, depression, wide-based stance, ataxia, spastic paresis, circling, seizures, muscle weakness, recumbency, opisthotonus (bridging spasm), coma or death
THIAMINE DEFICIENCY IN RUMINANTS- POLIOENCEPHALOMALACIA
Affects grey matter (polio), brain (encephalo), causes malacia- softening -> necrosis.
Pathogenesis- absolute deficiency, enzyme inactivation (thiaminases found in bracken fern, can be found in rumenal microbes)
Clinical signs usually seen in young animals (<18 months)- neurological signs- depression, stupor, ataxai, head pressing, cortical blindness, opisthotonus, convulsions, recumbency.
Grossly, lesions appear as CEREBROCORTICAL NECROSIS- loss of grey matter. Microscopically- laminar cortical necrosis (neuronal necrosis)
Areas of necrosis will fluoresce under a Woods lamp. Histology of the fluorescent areas should be checked- other areas many not have gross lesions.
Neurones and neuropil are lost.
Inflammatory infiltrate can be seen in chronic cases.
LAMINAR CORTICAL NECROSIS
Seen in polioencephalomalacia (thiamine deficiency) in ruminants.
Similar lesions can also be seen in:
-Water deprivation (salt toxicity)
-Lead poisoning
-High sulphur intake (less common)- leads to toxicity.
VITAMIN C
Most species make their own vitamin C, EXCEPT for HUMANS, NON-HUMAN PRIMATES, GUINEA PIGS etc.
Lesions of deficiency covered in pathology of small animals- scurvy in guinea pigs- periarticular haemorrhage of stifle joint etc.
Gingival erosions and ulcers are seen in guinea pigs and primates, and can lead to tooth loss.
VITAMIN D
Major function- maintenance of normal Ca:P plasma ratio. Helps to prevent rickets, osteomalacia, hypocalcaemic tetany (milk fever- low ionised Ca in extracellular fluid -> continuous excitation of muscle -> convulsive state and hypocalcaemic tetany)
CALCIUM HOMEOSTASIS
Involves hormones- PTH and calcitonin.
PTH and vitamin D are involved in increasing circulating Ca levels when they drop.
Gut Ca reabsorption is increased, osteoclast activation promotes bone remodelling, the kidney tubules resorb Ca, more vitamin D is converted to the active form in the kidneys.
NUTRITIONAL BONE DISEASES
- STARVATION- impedes longitudinal bone growth. Results in narrow growth plates, osteoporosis- decreased bone formation, increased bone resorption -> BONE LOSS.
- OVERNUTRITION- increased Ca in young, large breed dogs. Results in osteochondrosis, hip dysplasia- impaired osteoclastic activity means bone remodelling is defective.
METABOLIC BONE DISEASES
Not nutritional!!! OSTEODYSTROPHIES
- OSTEOPOROSIS
- FIBROUS OSTEODYSTROPHY
- OSTEOMALACIA/RICKETS
OSTEOPOROSIS
REDUCED BONE MASS (cortical and trabecular)- porous, thin brittle bones.
Caused by- protein calorie malnutrition, disuse (eg. long term cast), Ca deficient diet, excess glucocorticoids.
Bone quantity is reduced- bone quality is the same.
Resorption exceeds formation.
Remaining bone is structurally normal, but has a low breaking strength.
Young animals can recover if the underlying cause is resolved, but recovery in older animals is less likely- lost bone cannot be replaced.
OSTEOPAENIA
REDUCED BONE MASS, no clinical disease.
Not the same as osteoporosis (osteoporosis is the clinical disease resulting from severe osteopaenia)
eg. due to starvation.
OSTEOMALACIA
Adults- soft bones. Decreased bone mineralisation; osteoid accumulation.
Young animals- Rickets. Decreased bone mineralisation (osteoid accumulation) PLUS THICKENED GROWTH PLATES- endochondral ossification failure.
Gross lesions- Widening of growth plates, ‘flared’ metaphysis (osteoclasts cannot bind to unmineralised matrix), rachitic rosary (costochondral junction).
Caused by VITAMIN D DEFICIENCY, PHOSPHOROUS DEFICIENCY
OSTEOMALACIA/RICKETS- SUSCEPTIBILITY
Vitamin D, Ca and P are required for bone mineralisation.
- HYPOPHOSPHATAEMIC RICKETS- Llama more susceptible than sheep. Rare in cattle, horses- no inherited forms.
- Pigs- nutritional and inherited forms.
- Dogs and cats- rare- P is plentiful in meat diets. However, high P low Ca diets can cause rickets and osteomalacia.
There are several pathways by which bone resorption/endochondral ossification can occur.
RICKETS
Lack of dietary vitamin D -> vitamin D/Ca/P imbalance -> relative hypocalcaemia -> parathyroid gland production of PTH -> bone resorption, abnormalities of growth plates (thickened).
eg. Inherited rickets in Corriedale sheep. Skeletal deformities, enlarged, irregular physis, parathyroid hyperplasia.
PATHOGENESIS OF RACHITIC ROSARY
Seen in CHRONIC rickets. Failure of endochondral ossification at the costochondral junction.
- Inadequate provisional calcification, failure of cartilage cells to mature and disintegrate.
- > overgrowth of epiphyseal cartilage
- > deposition of osteoid matrix on inadequately mineralised cartilaginous remnants
- > disruption of orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of osteochondral junction.
- > deformation of skeleton due to loss of structural rigidity of the developing bones.
FIBROUS OSTEODYSTROPHY
Decreased bone mass due to increased activity of osteoclasts- bone resorption- and replacement by fibrous tissue.
‘Rubbery’ bone- rubber jaw.
Caused by- hyperparathyroidism (primary/paraneoplastic/secondary nutritional/secondary renal)
FIBROUS OSTEODYSTROPHY
Decreased bone mass due to increased activity of osteoclasts- bone resorption- and replacement by fibrous tissue.
‘Rubbery’ bone- rubber jaw.
Caused by- hyperparathyroidism (primary/paraneoplastic/secondary nutritional/secondary renal)
NUTRITIONAL SECONDARY HYPERPARATHYROIDISM
Dietary Ca:P imbalance gives relative hypocalcaemia eg. low Ca or high oxalate diet, high P (with normal or low Ca) diet, occasionally vitamin D deficiency.
INCREASED PTH PRODUCTION from parathyroid glands.
NUTRITIONAL SECONDARY HYPERPARATHYROIDISM
Dietary Ca:P imbalance gives relative hypocalcaemia eg. low Ca or high oxalate diet, high P (with normal or low Ca) diet, occasionally vitamin D deficiency.
INCREASED PTH PRODUCTION from parathyroid glands.
FIBROUS OSTEODYSTROPHY IN REPTILES
Nutritional secondary hyperparathyroidism is common, caused by inappropriate, unbalanced diets:
-High P diets eg. meat
-Low Ca diets eg. fruit and vegetables.
Bones of the skull and limbs thicken and soften- decreased radiographic bone density (diagnosis).
Bone is replaced with fibrous tissue.
Can present clinically as folding fractures.
FIBROUS OSTEODYSTROPHY IN REPTILES
Nutritional secondary hyperparathyroidism is common, caused by inappropriate, unbalanced diets:
-High P diets eg. meat
-Low Ca diets eg. fruit and vegetables.
Bones of the skull and limbs thicken and soften- decreased radiographic bone density (diagnosis).
Bone is replaced with fibrous tissue.
Can present clinically as folding fractures.
VERTEBRAL FRACTURE IN THE YOUNG HORSE
An example of a pathological fracture, most often caused by osteodystrophy.
VERTEBRAL FRACTURE IN THE YOUNG HORSE
An example of a pathological fracture, most often caused by osteodystrophy.
Vertebral fracture in the horse requires considerable force- there is probably underlying disease as well as trauma.
eg. Dietary Ca:P imbalance- should be 1:1.
Ca:P of 1:3 or greater will cause lesions.
Osteodystrophy likely- rickets, fibrous osteodystrophy.
eg. Vitamin D deficiency- young horse kept inside, fed much alfalfa (contains high levels of vitamin A, which antagonises vitamin D action).
See also ‘bran disease’ in horses, ‘bighead disease’ in sheep- massive deposition of fibrous tissue in the maxilla.
VITAMIN D TOXICITY
Sources- rodenticides (cholecalciferol), antipsoriasis medications.
Vitamin D3 analogues will cause hypercalcaemia -> elevated Ca x P product -> soft tissue mineralisation- lungs, gastric mucosa, kidneys and intercostal muscles predisposed. Crispy critters!
VITAMIN E/SELENIUM
Have important ANTIOXIDANT function- free radical protection.
Selenium- glutathione peroxidase system.
Skeletal and cardiac muscles are particularly sensitive to vitamin E/selenium deficiency and consequent oxidative injury.
Nutritional myopathies are most common in cattle, horses, sheep and goats.
Diseases- WHITE MUSCLE DISEASE (ruminants, horses), HEPATOSIS DIETETICA (pigs), MULBERRY HEART DISEASE (pigs)
WHITE MUSCLE DISEASE
Nutritional myopathy caused by vitamin E or selenium (more common) deficiency.
Pale lesions in heart- necrosis. Usually easiest to see on cut surfaces.
Gross appearance is not specific for white muscle disease (ionophore toxicity- monensin- is a good differential).
Oedema, loss of myofibres, necrosis.
HEPATOSIS DIETETICA
PIGS. Pathogenesis is not completely understood.
Combination effect- vitamin E/selenium is just one component- multifactorial.
Free radical production and lack of free radical scavengers leads to oxidative damage.
Lesions- haemorrhagic CENTRILOBULAR to MASSIVE necrosis of liver.
Seen in rapidly growing pigs fed on grain plus poor quality protein supplements, + stress.
Gross- swollen, haemorrhagic liver, fibrin deposition, icteric fat, peritoneal exudate- modified transudate or exudate.
MULBERRY HEART DISEASE
PIGS, Vascular necrosis produces dramatic haemorrhagic lesions in heart.
Dietary microangiopathy- selenium/vitamin E deficiency.
Fibrinoid necrosis and thrombosis of small vessels -> microhaemorrhages.
Different presentations can be seen- haemorrhagic (acute), chronic/ongoing- much fibrin deposition.
TOXINS
Cause massive necrosis in the canine liver (centrilobular necrosis in mild cases).
eg. XYLITOL- sugar alcohol
BLUE-GREEN ALGAE- microcystin-LR
AMANITA spp. mushrooms- amatoxin
AFLATOXINS- acute toxicity.
-Chronic aflatoxicosis is more common. Seen in multiple species- horses, dogs, pigs, cattle. Causes steatosis and biliary hyperplasia with fibrosis.
PARACETAMOL- liver injury in most species. Also causes METHAEMOGLOBINAEMIA in CATS. Present with ‘muddy’ mucous membranes.
COPPER TOXICITY
DOGS- breed associated genetic mutation (Bedlington terriers- COMMD1 gene mutation).
Leads to excessive copper storage in liver, can result in liver failure.
Breed predisposition, but any dog can be affected.
Special stain used to visualise copper histologically.
Seen in the livers of every dog with chronic liver disease as a secondary finding.
SHEEP- high copper vs low molybdenum.
Stress -> haemolytic crisis -> haemoglobinuria with abundant pigment in renal tubules -> gunmetal blue kidneys and yellow internal organs.
COPPER DEFICIENCY
Swayback/enzootic ataxia in lambs/kids.
SWAYBACK- neonatal Cu deficiency.
ENZOOTIC ATAXIA- delayed onset up to 6 months.
Pathogenesis is complex and poorly understood.
Eliminated by Cu supplementing of dam during pregnancy.
Young may be stillborn/weak/may develop ataxia later.
Lesions in cerebrum, brainstem, spinal cord in congenital form.
NO CEREBRAL INVOLVEMENT in later onset cases.
Cu deficiency also affects wool, hair growth, pigmentation, musculoskeletal development, integrity of connective tissue.
MISCELLANEOUS DEFICIENCIES
TAURINE DEFICIENCY- dilated cardiomyopathy. Essential amino acid in cats; now supplemented in food so DCM is uncommon.
ZINC RESPONSIVE DERMATOSES- Syndrome I- Siberian husky, Alaskan malamute (rare in other breeds). Seen aged 1-3 years, even with balanced diet. Caused by inborn error of zinc metabolism/absorption.
Syndrome II- ‘Generic dog food dermatosis’- rare. Seen in rapidly growing, large breed puppies/young adults, fed in unbalanced diets.
TOXINS
Cause massive necrosis in the canine liver (centrilobular necrosis in mild cases).
eg. XYLITOL- sugar alcohol
BLUE-GREEN ALGAE- microcystin-LR
AMANITA spp. mushrooms- amatoxin
AFLATOXINS- acute toxicity.
-Chronic aflatoxicosis is more common. Seen in multiple species- horses, dogs, pigs, cattle. Causes steatosis and biliary hyperplasia with fibrosis.
STORAGE DISORDERS
-Lysosomal and glycogen storage disorders:
LYSOSOMAL- dysfunction of lysosome-mediated degradation of products of normal cellular metabolism- degradation products accumulate and cause cell death.
GLYCOGEN- storage disorder leads to glycogenesis (many types)
Brain and liver are most affected- neurons and hepatocytes.
Some abnormal glycogen metabolism occurs in and affects equine muscle.
