Metabolism and metabolic diseases

Question 1

Name two biochemical features that distinguish cachexia from starvation

Answer 1

Cachexia causes marked activation of the inflammatory cascade and an increase in resting energy expenditure

Question 2

Cachexia results in production of inflammatory cytokines. Name 3 of these cytokines

Answer 2

IL-6, IL-1, TNFalpha

Question 3

Inflammatory cytokines stimulate the ubiquitin pathway. What is this pathway?

Answer 3

Central pathway involved in protein turnover. Ubiquitin complexes with cellular proteins and stimulates their metabolism

Question 4

Cachexia results in altered protein, fat, and carb metabolism. What are the clinical consequences of this?

Answer 4

Loss of muscle mass, loss of adipose tissue, insulin resistance

Question 5

Growth hormone originates in the pituitary gland and stimulates production of what other hormone that is important for growth?

Answer 5

IGF-1 - mainly from the liver, but some local production in tissues and bone growth plates

Question 6

Growth hormone deficiency in young animals results in what disease?

Answer 6

Proportionate dwarfism (growth of all tissues is stunted)

Question 7

How does thyroid hormone affect cartilage cells?

Answer 7

Synergies with IGF-1 to promote chondrogenesis

Question 8

How does juvenile hypothyroidism result in disproportionate dwarfism?

Answer 8

Results in delayed epiphyseal growth and reduced long bone growth

Question 9

Name 5 causes of pathologic polyphagia

Answer 9

Diabetes mellitus, hyperadrenocorticism, hyperthyroidism, acromegaly, malabsorption syndromes, EPI, insulinoma

Question 10

What are lysosomal storage diseases?

Answer 10

Diseases characterized by accumulation of metabolic byproducts within lysosomes - caused by key enzyme deficiencies that result in a failure to break down molecules

Question 11

What are common symptoms of mucopolysaccharidoses?

Answer 11

Growth retardation, facial deformity, corneal opacity, bony and connective tissue abnormalities (dystrophic bony malformations of the spine possible), progressive neurologic signs

Question 12

What are commonly some of the first clinical signs of storage diseases?

Answer 12

Cerebellar signs - dysmetria, truncal ataxia, nystagmus often occur first

Question 13

What are mucopolysaccharidoses (MPS)?

Answer 13

• Group of inherited lysosomal storage disorders characterized by a deficit in the lysosomal enzymes needed for the catabolism of glycosaminoglycans
• 7 subtypes

Question 14

What drug may improve clinical signs of mucopolysaccharidoses (MPS)

Answer 14

Pentosan polyphosphate

Question 15

What causes type A lactic acidosis?

Answer 15

• Decreased aerobic glycolysis from tissue hypoxia leads to an accumulation of pyruvate in the cytosol, which is converted to lactate
• Shock, hypovolemia, severe anemia, ischemia

Question 16

What causes type B lactic acidosis?

Answer 16

• Increased aerobic glycolysis => more pyruvate than the mitochondria can handle
• Defects in the ability of the mitochondria to take up pyruvate (thiamine deficiency, etc)
• Decreased consumption of lactate by the tissues (acute liver failure)

Question 17

What specifically causes type B1 lactic acidosis?

Answer 17

Underlying disease: cancer, diabetes (esp DKA), sepsis, excess catecholamines

Question 18

What specifically causes type B2 lactic acidosis?

Answer 18

Drugs that impair mitochondrial function, liver function, or stimulate the adrenergic system
- Acetaminophen, glucocorticoids, beta-2 receptor agonists

Question 19

What specifically causes type B3 lactic acidosis?

Answer 19

Congenital errors of metabolism associated with mitochondrial dysfunction or the glycolytic pathway