Metabolism/Endocrine Lab

Question 1

What are the functions of the liver?

Answer 1

• Production of cholesterol
  
  • precursor to sex hormones, Vit D
• Storage of Micronutrients:
  
  • Minerals- Cu, Zn, Mg, Fe
  • Vit- A, D, E, K, B12
• Blood Sugar Balance:
  
  • storage of glycogen
• Production of Bile:
  
  • Needed for digestion
  • GI antimicrobial
• Protein Synthesis:
  
  • Blood clotting (prothrombin)
  • Cholesterol transport (lipoproteins)
  • Immune Function (globulins)
  • Oncotic pressure (albumin)
  • Copper Bioavailability (ceruloplasmin)
• Immune System:
  
  • Contains viruses and pathogens
  • Maintenance of the hepatic and portal vein immune system
• Metabolism:
  
  • Conversion of T4 ⇢ T3
  • Detoxification of Fat
• Detoxification:
  
  • Drugs/alcohol
  • Fatty acids
  • Steroid hormones
  • Ammonia ⇢ urea
  • Environmental toxins/allergens

Question 2

How is fat metabolized in hepatocytes?

Answer 2

• 3 outcomes for Free Fatty Acids (FFA) that are synthesized in the liver or taken up from the plasma
  
  • Mitochondrial-oxidation to generate ATP
  • Esterification and storage in the liver as triglycerides
  • Secretions as very low-density lipoproteins (VLDL)
    
    • carry newly synthesized triglycerides from the liver to adipose tissue

Question 3

What are the Key Concepts of Hepatic Lipidosis?

Answer 3

• Result of endogenous, intracellular accumulation of lipid within hepatocytes
  
  • Cytoplasmic vacuoles which peripheralize the nucleus
• Can be due to physiologic causes
  
  • High fat diet
  • Increased periparturient energy
  • Anorexia
• Can be due to pathologic caues
  
  • Hepatotoxins
  • Hypoxia
  • Starvation

Question 4

Case #1 Sunny

OW left home for 2 months in neighbors care. Sunny was lethargic, very thin (down 11lbs) and jaundiced.

Summarize and interpret observations of these photos.

Answer 4

• Sunny hasn’t had adequate access to food and has been stressed by the owners absence
• Her liver is enlarged and pale
• Has an abundance of abdominal Fat
• Morphologic diagnosis: Liver, lipidosis
• Most likely occurred due to excessive mobilization of peripheral fat to maintain energy production

Question 5

What is the Pathogenesis (story) of Hepatic Lipidosis?

Answer 5

1. Anorexia/Decreased caloric intake
2. Increased Mobilization of fat
3. Increased hepatic uptake of lipids
4. Lipid deposition in hepatocytes

Question 6

How does Hepatic Lipidosis affect cats?

Answer 6

• Obesity is a common risk factor
• Disease initiated by anorexia
• Disruption of normal fat metabolism results in excessive deposition of lipid in hepatocytes
• Hepatocyte alterations destabilize plasma membranes and cause cell enlargement
  
  • Elevated liver enzymes (AST, ALT, ALP)
  • Compression of bile canaliculi leading to cholestasis ⇢ Icterus
• Without good, aggressive nutritional/fluid management this can be fatal
  
  • feeding tube almost always needed

Question 7

What can cause anorexia in felines?

Answer 7

• Other disease
• Environmental changes
• Poor ration
• Stressful events

Question 8

How is lipid deposition in hepatocytes characterized?

Answer 8

• By discrete vacuoles which peripheralize the nuclei

Question 9

How does fasting affect cat’s lipid metabolism?

Answer 9

• Fasting promotes lipolysis in adipose tissue and transportation of FFA to the liver
• The hepatic load of FA is also increased by hepatic synthesis of fatty acids
  
  • Acetyl-CoA derived from carbohydrates (or FFA) enters the Krebs cycle to result in production of ketone bodies and additional FFA
• An imbalance between these different aspects of the feline lipid metabolism leads to accumulation of lipids in the liver

Question 10

Case #2 Bob

7 YO intact CS. Hair Loss and thin haircoat in general. Gained 10Lbs. Lethargic, House-soiling, infertile

Summarize and interpret observations (several pictures missing)

Answer 10

• Patchy hair loss and epidermis appears crusty and irregular
  
  • Histologically the epidermis is thin, hyperkeratinized, hair follicles are dilated and filled with keratin, there is a deduction in sebaceous and sweat glands
• Low RBC level and increased cholesterol
• Thyroid gland is extremely small
  
  • few recognizable follicles histologically
• Liver is enlarged and tan-brown
• Pale discolored regions in one of the hepatic vessels
• Cardiac vessels are enlarged and have a whit/mottled appearance
  
  • Histologically these vessels have thin walls thickened by white, foamy material along with excess number of cells.

Question 11

What would the interpretation for Bob’s necropsy be?

Answer 11

• Skin, epidermal atrophy and hyperkeratinization and adnexal atrophy
  
  • “endocrine dermatopathy”
• Anemia
• Hypercholesterolemia
• Thyroid gland, atrophy
• Liver, lipidosis
• Cardiac and hepatic vessels, atherosclerosis

Hypothyroidism

Question 12

Why was this clinical pathology seen in Bob?

Answer 12

• Hematology:
  
  • Mild non-responsive normochromic normocytic anemia will sometimes accompany decreased thyroid hormone levels due to decreased RBC formation
• Cholesterol:
  
  • Hypercholesterolemia reflects decreased utilization of cholesterol due to overall decreased metabolic rates

Question 13

What was the pathogenesis of Hypothyroidism and all other symptoms in Bob?

Answer 13

• Thyroid atrophy⇢ loss of functional cells ⇢ decreased thyroid hormones
• Hepatic lipidosis:
  
  • Decreased thyroid hormone ⇢ reduced metabolic rate ⇢ (increased glycolysis, gluconeogenesis, glucose and protein absorption) increased lipid metabolism ⇢ Increased conversion of cholesterol into bile acids
• Endocrine Dermatopathy:
  
  • Decreased thyroid hormones ⇢ decreased stimulation of anagen phase of hair cycle ⇢ increased telogen (inactive) phase of hair cycle ⇢ Hair loss and increased keratin formation
• Atherosclerosis
  
  • Increased cholesterol ⇢decreased lipid metabolism ⇢increased deposition of cholesterol in vessels

Question 14

What are the potential causes of Thyroid atrophy?

Answer 14

• Immune mediated:
  
  • lymphocytic thyroiditis
  • Autoantibodies produced against thyroglobulin/thyroid components
• Idiopathic:
  
  • unknown pathogenesis, possibly inherited
• Physiologic loss of thyroid hormone:
  
  • Decreased thyroid stimulation by thyrotropin or decreased Thyrotropin releasing hormone levels

Question 15

What are the Key features of Hypothyroidism?

Answer 15

• Idiopathic/Autoimmune-induced atrophy of the thyroid gland leads to decreased thyroid hormones
• Systemic lesions are due to loss of thyroid hormone stimulation of metabolism
• Lipid accumulates in the liver due to altered mobilization from hepatocytes
• High cholesterol levels and hyperlipidemia are present

Question 16

What is Atheromatous plaque formation?

Answer 16

1. Atherogenic risk factors cause endothelial dysfunction
   
   1. lipids deposit in the intima
   2. Leukocyte adhesion molecules are expressed
   3. Leukocytes migrate into vessel wall
2. Macrophages in the vessel internalize lipoproteins to become foam cells
3. Macrophages, T cells and other leukocytes release O₂ radicals pro-inflammatory cytokines, and growth factors
4. Vascular smooth muscle migrates into the intima and differentiates into a proliferating phenotype
   
   1. produce extracellular matrix proteins, including collagen
5. Apoptosis of cells in the plaque leads to formation of a necrotic core
6. Neovascularization and MMP secretion by macrophages destabilizes the plaque, leading to plaque rupture
7. Exposure of plaque contents to blood initiates platelet activation, coagulation, and thrombus formation

Question 17

Case #3 Sara

13 YO TS terrier

Hair loss, PU/PD, lethargy, polyphagia, weakness. High WBC and neutrophils. High AST and Glucose.

Summarize observations (some slides missing)

Answer 17

• Hair loss, and white, multifocal areas in cross sections of the skin
  
  • Histologically, epidermis is thin, there are reduced numbers and size of adnexa, and large, irregular purple areas are present
• Brain and pituitary look normal
• White, nodular mass in the adrenal cortex comprised of large, round foamy cells
• Multifocal groups of myofibers are small
• Liver is enlarged and pale-tan
  
  • hepatocytes are swollen nd have foamy cytoplasm
• Urinary bladder mucosa isred and expanded (“puffy”)

Question 18

What are the interpretations of the findings on Sara?

Answer 18

• Skin, epidermal and adnexal atrophy, with dermal mineralization
• Pituitary gland, normal
• Adrenal gland, cortex, adenoma
• Skeletal muscle, atrophy, multifocal
• Liver, lipidosis and glycogenosis
• Urinary bladder, cystitis, emphysematous

Question 19

What is Canine Hyperadrenocorticism?

Answer 19

• Commonly due to pituitary chromophobe adenoma
• There is excessive and unregulated secretion of corticosteroids
  
  • Corticosteroids are gluconeogenic, lipolytic, protein catabolic, anti-inflammatory and immunosuppressive
• Common multisystemic effects:
  
  • Liver (hepatic glycogenosis)
  • Skin (Endocrine dermatopathy)
  • Skeletal muscle (atrophy)

Question 20

How does Excess glucocorticoids affect Hepatic lipidosis?

Answer 20

1. Increase in appetite and high caloric intake
2. Increased blood glucose levels due to GC-induced gluconeogenesis
3. Stimulation of lipogenesis that is augmented by high glucose and insulin levels, and my GC itself
4. Increased release of FFA from adipose tissue and uptake of these by the liver

Question 21

What is the Pathogenesis of Hyperadrenocorticism?

Answer 21

• Functional Adrenal neoplasia OR ACTH producing pituitary neoplasia OR iatrogenic steroid administration ⇢ Chronically increased cortisol ⇢ systemic effects
  
  • Hepatic gluconeogenesis and hepatomegaly/pendulous abdomen
  • Increased lipolysis and protein catabolism
  • Pu/PD
  • Polyphagia
  • Alopecia
  • Pyoderma
  • Obesity
  • Immune suppression and chronic infections
  • Calcinosis cutis

Question 22

Case #4 Nellie

33 YO mare

Polyphagia PD/PU, reluctant to work, Hyperglycemia, Increased Beta-endorphin, Increased Melanocyte stimulating hormone, increases ACTH

Summarize observations

some pictures missing

Answer 22

• Eats, drinks and urinates a lot
• High glucose and ACTH
• Hairy
• Large pituitary
• Adrenal gland looks okay
• P3 and the hoof wall aren’t parallel
• Hoof laminae are hypercellular

Question 23

Interpret the findings on Nellie

Answer 23

• Polyphagia, polyuria, polydipsia
• Hyperglycemia and high ACTH
• Hypertrichosis
• Pituitary adenoma (pars intermedia)
• Normal adrenal gland
• Hoof, laminitis

Question 24

What is Equine Pituitary Pars Intermedia Dysfunction (PPID)?

Answer 24

• Equine par intermedia contains melanotropes
  
  • Directly innervated by dopaminergic neurons of the periventricular nucleus
  • Dopamine interacts with dopaminergic D2 type receptors on melanotropes to inhibit Proopiomelanocortin (POMC) expression
    
    • POMC is the pituitary precursor of circulating melanocyte stimulating hormone ( α MSH),
      ACTH, and β endorphin.
  • Cortisol exerts negative feedback on ACTH secretion by the pars distalis but not the pars intermedia
• PPID is due to oxidative injury to periventricular neurons
  
  • Loss of inhibitory effect of dopamine results in melanotrope hyperplasia and unregulated production of POMC
  • Predisposes to melanotrope neoplasia within pars intermedia.
  • Hyperplasia/neoplasia compresses neurohypophysis, hypothalamus and optic chiasma

Question 25

What are the Clinical Features of PPID?

Answer 25

• Increased age is the biggest risk factor
• Hirsutism/hypertrichosis
  
  • delayed or absent seasonal molting resulting in long shaggy hair
• PU/PD due to diabetes insipidus
  
  • NOT hyperglycemia
• Hyperhidrosis
• Myopathy with type 2 fiber atrophy
• Weight loss and/or Obesity with excess fat in crest f the neck and supraorbital fossae
  
  • not specific to PPID - may be Equine Metabolic Syndrome
• Laminitis
  
  • Obesity, insulin resistance, hyperinsulinemia and laminitis are correlated in horses
• Rarely blindness
• Clin path is variable
  
  • changes can include hyperglycemia, hyperinsulinemia, increased/decreased or normal cortisol

Question 26

What is the Pathogenesis of PPID?

Answer 26

1. Adenoma of the pars intermedia
2. Physical disruption of the pars nervosa
3. Overproduction of pro-opiomelanocortin and ACTH
4. Chronic laminitis and insulin resistance, PU/PD, Hypertrichosis with wavy coat and failure to shed in the spring, Hyperhidrosis, narcolepsy, reoccurring infections, polyphagia, muscle wasting, pendulous abdomen

Question 27

What is the morphologic diagnosis?

Answer 27

• Pituitary gland, pars distalis adenoma, chromophobe adenoma

Question 28

What is this?

Answer 28

Secondary

Question 29

Is this pheochromocytoma of the adrenal gland?

Answer 29

NO

Question 30

Case #5 Dolly

8 YO FS Dog

Decreased appetite, PD, vomiting, breath smell worse, Painful urination - red and cloudy, High WBC, Neutrophils, Bands, and Monocytes. High Glucose and ALT

What are the observations?

Answer 30

• WBC, Neutrophils, Band cells, monocytes are elevated
• Glucose and ALT are elevated
• There is opacity behind the iris
• There are tan bands of tissue that separate and sometimes distort pancreatic lobules
• Liver is slightly pale, has an accentuated lobular pattern
• Histologically, the hepatocytes contain large vacuoles or have a foamy appearance
• Urinary bladder is red and puffy
• Histologically urinary submucosa is hypercellular an there are large open spaces multifocally i

Question 31

What are the interpretations for Dolly’s results?

Answer 31

• Leukocytosis, neutrophilia, monocytosis
• Hyperglycemia and elevated liver enzymes
• Lens, cataract
• Pancreas, fibrosis, multifocal to coalescing
• Liver, lipidosis and glycogenosis
• Urinary bladder, cystitis, emphysematous

Question 32

What is Canine Diabetes mellitus?

Answer 32

• Pancreas: Pancreatic fibrosis, diffuse, severe
  
  • Chronic damage to pancreas may have started as an acute injury/injuries (pancreatitis)
  • Damage to the Beta cells (insulin secreting cells) of the pancreas
• Liver: Hepatic Lipidosis
  
  • Increased fat mobilization overloads ability of liver to metabolize lipids
  • Glucose is still able to enter hepatocytes (stored as glycogen)
• Eye: Cataract
  
  • Excess glucose enters the lens nd is converted to sorbitol and fructose
  • These substances cannot diffuse out of the lens and osmotically attract water
  • Swelling and degeneration of lens fibers
• Urinary bladder: Cystitis, emphysematous
  
  • High levels of glucose pass through the kidney ad enter the urinary bladder
    
    • Bacteria thrive in high glucose environments
• Clinical Pathology:
  
  • Inflammatory leukogram (response to the bacterial cystitis)
  • Elevated glucose (lack of insulin)
  • Elevated ALT (hepatic lipidosis causes slight hepatocellular damage and leakage of intracellular hepatic enzymes)0
• In Advanced disease rapid breakdown of fats to release FA results in formation of ketoacids
  
  • Diabetic ketoacidosis suggests advanced, uncontrolled disease

Question 33

Case #6 Franklin

Observtations

Answer 33

• PB< BUN and Phosphorus are all elevated, Ca low
• Kidneys, pale, have irregularly contracted surface
  
  • Histologically fibrosis and increased cellularity in the interstitium, fibrosis in the glomeruli, and reduced numbers of tubules
• Parathyroid glands are bilaterally enlarged
• Maxilla is enlarged an lack of boney trabeculae on cut surface
• Stomach contains multifocal red spots
  
  • Contains hemorrhage along with loss of mucosa, decreased gastric glands, or glands that are dilated and contain cellular debris. A gastric vessel contains acellular material in its lumen and appear hypercellular

Question 34

What are the interpretations of Franklins observations

Answer 34

• Hypocalcemia and hyperphosphatemia
• Markers for kidney disease are elevated
• Kidney, glomerulonephritis and interstitial fibrosis
• Parathyroid glands, hyperplasia, bilateral
• Maxilla, fibrous osteodystrophy
• Stomach, gastritis and hemorrhage, ulcerative, multifocal with vasculitis and thrombosis

Question 35

What is Renal secondary hyprparathyroidism?

Answer 35

• Chronic renal failure leads to retention of phosphorus and loss of calcium
• Hypocalcemia leads to parathormone (PTH) secretion to elevate serum calcium
• Persistent hypocalcemia leads to parathyroid hyperplasia and continuous PTH secretion
  
  • Functions of PTH include to enhance renal retention of calcium, increase intestinal absorption of calcium and to mobilize calcium from bone
• Mineralized bone is replaced by collagen (Fibrous osteodystrophy)