Metabolic Disease

Question 1

What are the 3 major causes of metabolic disease?

Answer 1

• Genetic
• Nutritional
• Hormonal

Question 2

What are examples of genetically caused Metabolic Disease?

Answer 2

• Lysomal storage diseases
  
  • Glycogenoses
  • Mucopolysaccharidose
• Hyperlipidemia syndromes
• Certain Endocrine disorders

Question 3

What are examples of nutritionally caused Metabolic Disease?

Answer 3

• Vitamin and mineral deficiency
• Oral neoplasia or inflammation
• Malabsorption syndromes
  
  • Johnes disease

Question 4

What are examples of hormonally caused Metabolic Disease?

Answer 4

• Diabetes mellitus
• Hypothyroidism
• Hyperthyroidism
• Hyperparathyroidism

Question 5

What are Genetic Metabolic Disease?

Answer 5

• Problems due to a problem with a single protein in a metabolic pathway
  
  • single gene defects
• Most of these gene defects are inherited
• Some have congenital morphological defects
• Some are not manifested morphologically or functionally until later in life
  
  • manifestations of the problem occur only upon continued growth and development
• Some inherited metabolic diseases remain subclinical for life
• Most are irreversible
  
  • severity of the anomaly determines the severity and progression of the disease
• Inherited deficiencies of a protein will not improve
  
  • animal may adapt to compensate in some situations

Question 6

What is Lysosomal Storage Disease?

Answer 6

• Characterized by the accumulation of mucopolysaccharides or lipid components within cellular lysosomes
  
  • Lysosomes are the principal site of intracellular degradation of complex molecules
  • Inherited enzyme deficiency inhibits the degradation of these large molecules
  • Intermediate catabolic products can’t be degraded and accumulate within lysosomes

Question 7

What is Alpha Mannosidosis?

Answer 7

• Deficiency of alpha-mannosidase
  
  • Inherited as an autosomal recessive trait
  • Described in humans, cats, and cattle
  • Skeletal and ocular abnormalities may occur
  • Progressive neurologic disease
  • Cytoplasmic inclusions in neurons, mesenchymal and epithelial cells

Question 8

What Is Feline Alpha-Mannosidosis?

Answer 8

• Clinical onset occurs at an early age (8-10 weeks)
  
  • Disease is heterogenous; being less sever in DLH cats
• Progressive neurologic disease
  
  • Tremor, ataxia, dysmetria, weakness, and emaciation
• Cytoplasmic inclusions consist mainly of mannose and N-acetylglucosamine
  
  • Inclusions in neurons, hepatocytes and other cells
  • High concentrations of these products are excreted in the urine
• Affects Persians, DSH and DLH

Question 9

What are Nutritional Metabolic Diseases?

Answer 9

• Most Nutritional problems exert their effect by altering metabolism
• Improper nutrition can result from
  
  • Inadequate nutrient in the diet
  • Inadequate nutrient uptake
  • Inadequate nutrient absorption
• Most are reversible
  
  • Nutrient deficiency in the diet is corrected
    
    • Rickets is reversed by adding Vit D
  • Dramatic excess demands are resolved
    
    • Rapid changes during parturition and lactation
  • Nutrient imbalances are corrected
    
    • Calcium and phosphorus ratios and bone disease

Question 10

What is Liver Lipidosis?

Answer 10

• Liver plays a central role in metabolism
  
  • Synthesis and metabolism of proteins, lipids, and carbs
  • Conjugation and detoxification reactions
  • Waste product excretion
  • Bile secretion
  • Storage of nutrients
• Some degree of lipidosis accompanies many metabolic alterations
  
  • Hyperlipidemia syndromes
  • Endocrine disorders
  • Nutritional problems
  • Physiological changes
• Metabolic Imbalance between protein, fat, or carbs can result in lipidosis
  
  • Increased rate of fat entry to hepatocytes
  • Decreased rate of lipoprotein formation within hepatocytes
  • Decreased energy levels

Question 11

What are Hormonal metabolic diseases?

Answer 11

• Hormones are a major regulator and integrator of metabolism
• Any endocrine dysfunction or disease will have metabolic manifestations
• Examples:
  
  • Fibrous osteodystrophy
  • Pituitary adenoma
  • Diabetes mellitus

Question 12

What are Hormonal metabolic diseases?

Answer 12

• Hormones are a major regulator and integrator of metabolism
• Any endocrine dysfunction or disease will have metabolic manifestations
• Examples:
  
  • Fibrous osteodystrophy
  • Pituitary adenoma
  • Diabetes mellitus

Question 13

What is Fibrous Osteodystrophy?

Answer 13

• Inadequate intake or loss of calcium requires mobilization from tissues
• Excessive and prolonged action of parathormone results in bone demineralization

Question 14

What is a pituitary adenoma?

Answer 14

• Neoplasia of chromophobes results in excessive ACTH production and can compress regions of the hypothalamus
• Adrenal cortical hyperplasia results in excessive adrenocorticosteroid production (hyperadrenocorticism)
• Hypothalamic pressure can interfere with function of regulator centers
  
  • Ie. appetite, thermal regulation (often results in hirsutism)

Question 15

What is Diabetes mellitus?

Answer 15

• Most common in dogs, sometimes in cats
• Problem is inadequate insulin activity
  
  • Type 1 (insulin-dependents)
    
    • due to decreased insulin secretion
  • Type 2 (Non-insulin-dependent)
    
    • Due to inadequate insulin release or target cell response

Question 16

What conditions can cause reduced insulin activity?

Answer 16

• Islet cell hypoplasia
• Destruction of pancreatic islets
  
  • Acute pancreatic necrosis in dogs
  • Islet amyloidosis in cats
• Failure of insulin release from islet cells
• Failure of tissue to respond to insulin
  
  • Antagonism between insulin and other hormones
    
    • Growth hormone and glucocorticosteroids

Question 17

What are the clinical signs of Diabetes Mellitus?

Answer 17

• Emaciation
• PU/PD
• Increased infections
  
  • not as prominent as in humans
• Hyperglycemia
• Glycosuria
• Ketoacidosis and Ketonuria

Question 18

What are the pathological features of Diabetes Mellitus?

Answer 18

• Hepatic lipidosis and glycogenosis*
• Glomerulosclerosis and glycogen nephrosis
• Cataracts
• Vascular lesions and necrosis are not as prominent as in humans
• Other lesions associated with any predisposing factor
  
  • Adrenal cortical hyperplasia or pituitary adenoma

Question 19

What is the Pathogenesis of Irreversible Disease?

Answer 19

• Most Commonly inherited
  
  • Lysosomal storage diseases
• Sometimes hormonal depending on causes
  
  • Neoplasia
  • Chronic organ failure

Question 20

What is the Pathogenesis of Reversible Disease?

Answer 20

• Most commonly nutritional
  
  • Nutritional deficiency
    
    • Starvation
    • Vitamin or mineral deficiency
  • Excessive demand that exceeds supply
    
    • Pregnancy or lactation
  • Nutrient imbalance
    
    • Calcium/phosphorus rations

Question 21

What is the Morphology of Metabolic Diseases?

Answer 21

• Highly variable
  
  • Endocrine disease disrupting homeostasis
    
    • Endocrine organ atrophy or neoplasia
  • Intestinal disease inhibits nutrient absorption
    
    • Granulomatous enteritis
  • Renal Failure and electrolytes
    
    • Chronic glomerulonephritis
  • Multisystemic effects of hepatic disease

Question 22

What are the Central Metabolic Tissues?

Answer 22

• Liver
  
  • Synthesis of plasma proteins
  • Biotransformation and conjugation reactions
  • Lipid, carb, and protein metabolism
  • Storage of nutrients
  • Secretion of bile and waste products
• Kidneys
  
  • Excretion of metabolic waste products
  • Maintain acid-base, electrolyte and water balances
• Endocrine tissues
  
  • Regulate interactions between multiple metabolic processes
  • Maintain overall homeostasis
• Gastrointestinal
  
  • Absorption of nutrients
  • Elimination of waste products
• Bones
  
  • Storage of minerals
  • House hematopoetic tissues

Question 23

What are the manifestations of Metabolic Disease?

Answer 23

• Signs of metabolic disorders are very diverse
  
  • Some are ill-defined and mild
  • Others are severe and life-threatening
• Metabolic problems are often multi-systemic, but system-specific signs often occur
  
  • Neurologic symptoms
  • Musculoskeletal symptoms
  • Endocrine symptoms