02- Endocrinology Flashcards
Where is the thyroid gland located?
The anterior surface of the trachea
What types of cells is the thyroid gland made of?
Follicular cells and parafollicular cells
What do follicular cells of the thyroid gland secrete?
Thyroxine
What do parafollicular cells of the thyroid gland secrete?
Calcitonin
What does calcitonin do?
Regulates calcium and phosphate metabolism
Which essential trace element is required for thyroid hormone production?
Iodine
Where are the receptors for thyroid hormones?
In the nucleus
Where are thyroid hormones synthesized?
Follicular epithelial cells in the thyroid gland
What are the eight steps of the synthesis of thyroid hormones?
- Synthesis of thyroglobulin
- Iodide trapping
- Oxidation of iodide
- Iodination of thyrosine
- Coupling reactin
- Endocytosis of thyroglobulin
- Hydrolysis of T3 and T4 from thyroglobulin
- Deiodination
Where does the synthesis of thyroglobulin take place?
Thyroid follicular cells
What happens to thyroglobulin after it is made?
It is released into the follicular lumen
How is iodide transferred into the cells?
Sodium-iodide symporter
What enhances Na-I activity?
Thyroid stimulating hormone
What enzyme is responsible for the oxidation of iodide in the follicular epithelium?
Thyroid peroxidase
What does thyroid peroxidase catalyze the formation of?
Mono- and di- iodothyrosine
What happens to the iodinated thyroglobulin while it waits for a signal?
It is stored in the follicular lumen as colloid
What does thyroid peroxidase catalyze via the process of conjugation?
The formation of tetraiodothyronine
What comes together to form T4?
Two molecules of di-iodiothyrosine
What comes together to form T3?
One molecule of di-iodiothyrosine and one molecule of mono-iodiothyrosine
When does endocytosis of thyroglobulin occur?
When the thyroid gland is stimulated by thyroid stimulating hormone
What does lysosomal protease within the endocytotic vesicle do?
Hydrolyzes the peptide bonds to release T3 and T4 from thyroglobulin
What occurs in deiodination?
Uncoupled monoiodotyrosine and diiodotyrosine are attached to thyroglobulin and deiodinated inside follicular cells via thyroid deiodinase
What can iodine deficiency lead to?
Hypothyroidism and goiter
What can iodine deficiency cause in infants?
Cretinism
How do thyroid hormones impact basal metabolic rate?
They increase it by stimulating ineffective catabolic and anabolic cycles
What do thyroid hormones do in the bones?
Increase osetoblastic and osteoclastic activity
What do thyroid homrones do in the liver?
Increase triglyceride and cholesterol metabolism
What do thyroid hormones do in the brain?
Encourage axon growth and development
What do thyroid hormones do in the heart?
Have inotropic and chronotropic effects, and reduce smooth muscle resistance in vessels
What do thyroid hormones do in adipose tissue?
Increase lipolysis
What do thyroid hormones do in muscle?
Increase protein breakdown
What do thyroid hormones do in the gut?
Increase the rate of carnohydrate absorption
How is reverse T3 made and what is the problem with it?
The iodine is removed from the inner benzyl ring which makes it biologically inactive
What does 5’/3’-deiodinase do?
Removes an iodine from the outer benzene ring of T4 to produce T3
What does 5/3-deiodinase do?
Removes an iodine from the inner benzene ring of T4 to produce rT3
Where is type 1 5’/3’-deiodinase found and what does it do?
Present in the liver, kidneys, and thyroid
Generates most of the T3 that reaches general circulation
Where is type 2 5’/3’-deiodinase and what does it do?
Found in the pituitary, CNS, and placenta
Responsible for producing the T3 that is used in feedback inhibition
What are T3 and T4 usually bound to?
Thyroxine-binding globulin
Which two hormones influence feedback on TSH?
Somatostatin and dopamine
Where is the problem in a primary thyroid disorder?
The thyroid gland
Where is the problem in a secondary thyroid disorder?
The pituitary of hypothalamus
Which disorders are associated with hypothyroidism?
Cretinism, myxedema, iodine-deficient goiter, and graves disease
What makes up pancreatic cells?
Acini
What makes up acini?
Islets of Langerhans
How do islets use humoral communication?
The blood supply of islets courses outward from the center of the islet towards the periphery carrying glucose, humoral products, and other secretagogues
How do islets uses cell-cell communication?
Communicate through gap junctions
How do islets use neural communication?
Islets are innervated by sympathetic and parasympathetic nerves
What kind of adrenergic stimulation causes excitation and which causes inhibition of islets?
Beta causes stimulation and alpha causes inhibition
What do alpha cells secrete?
Glucagon
What does glucagon do?
Causes glycogenolysis to increase blood glucose levels
What causes glucagon secretion?
Reduced blood glucose, exercise, and protein rich meals
What inhibits glucagon secretion?
Somatostatin and insulin
What do beta cells secrete?
Insulin
What does insulin do?
Lowers blood glucose, glycogenesis, and increased lipogenesis and protein synthesis
What causes insulin secretion?
Elevated blood glucose, ACTH, ACh, glucagon, GIP, hCG, hCS, and hPL
What inhibits insulin secretion?
Somatostatin
What do delta cells secrete?
Somatostatin
What does somatostatin do?
Inhibits secretion of hormones and reduces absorption of nutrients
What inhibits somatostatin secretion?
Pancreatic polypeptide
What do F cells secrete?
Pancreatic polypeptide
What does pancreatic polypeptide inhibit?
Pancreatic digestive enzymes, somatostatin, contraction of the gall bladder, and intestinal motility
What does insulin look like?
Two straight chains linked by disulfide bridges
What tissues use GLUT 1?
Red blood cells and endothelial cells
What tissues use GLUT2?
Renal tubular cells, hepatic cells, and pancreatic beta-cells
What tissues use GLUT4?
Adipose tissue, skeletal muscle, and cardiac tissue
What method of glucose administration is the most powerful insulin stimulant and why?
Oral intake causes an interaction with gastric inhibitory peptide hormone which also influences insulin
How much more insulin is needed in a diabetic to get the same response as 5% insulin in a healthy person?
1000x
Which insulin receptor chains are extracellular and which are membrane spanning?
The alpha chains are extracellular and the beta chains are membrane spanning
What impacts the number of insulin receptors present on a cell?
Receptor synthesis, endocytosis of receptors, endocytosis by degradation
Why do cells chronically exposed to insulin have fewer insulin receptors?
Downregulation
What influences the ability of insulin to act on target cells?
The number of receptors, receptor affinity, and the receptor’s ability to transduce a signal
What are insulin-receptor substrates important form?
The insulin signal transduction pathway
Where is IRS-1 active?
Skeletal muscle
Where is IRS-2 active?
The liver
What does insulin do in the liver?
Promotes storage of glucose as glycogen, lipogenesis, and stimulates protein metabolism
What does insulin do in the muscles?
Enhances the conversion of glucose to glycogen, increases glucose breakdown, and promotes the synthesis of proteins in the skeletal muscle
What does insulin do in the adipose tissue?
Stimulates breakdown of glucose, promotes formation of triglycerides, and induces the synthesis of lipoprotein lipase
What can cause an increase in nitric oxide production?
Insulin, C-peptide, and pro-insulin
What does glucagon cause during hypoglycemia?
Glycogenolysis, gluconeogenesis, and ketogenesis
How does human placental lactogen impact a pregnant mother?
Reduces insulin sensitivity, reduces utilization of nutrients, and enhances maternal lipolysis
What are some microvascular complications associated with diabetes?
Retinopathy, nephropathy, and neuropathy
What are some macrovascular complications of diabetes?
Coronary artery disease, stroke, and peripheral arterial disease
What does cortisol do?
Increases plasma glucose levels, is an anti-inflammatory, optimizes the vascular responsiveness to catecholamines, and enhances glomerular filtration
What does aldosterone do?
Promotes salt and water retention
What do chromaffin cells produce?
Epinephrine and norepinephrine from tyrosine
Where is cortisol produced?
The zona faciculata of the adrenal cortex
What is cortisol bound to in the plasma?
Transcortin (corticosteroid-binding globulin)
How does cortisol increase plasma glucose concentrations?
Activating gluconeogenesis, increasing protein catabolism, and increasing lipolysis
How does cortisol act as an anti-inflammatory?
Increases the synthesis of lipocortin, inhibits the release of cytokines and interleukin-2, and reduces the proliferation of T-lymphocytes, inhibits the release of histamine, inhibits bradykinin and seretonin’s inflammatory effects, decreases eosinophil, basophil, and lymphocyte counts, and impairs cell-mediated immunity
What kind of immunity are T-lymphocytes and B-lymphocytes involved in?
T-lymphocytes are involved in cytotoxic cell-mediated adaptive immunity
B-lymphocytes are involved in humoral or antibody driven adaptive immunity
What is cushing syndrome?
Excess cortisol leading to truncal adiposity, hypertension, loss of subcutaneous adipose and connective tissue, loss of bone mineral, muscle weakness, and hyperglycemia
What is Addison’s disease?
Insufficient cortisol causing adrenal insufficiency and hypocortisolism
Where is aldosterone produced?
In the zona glomerulosa of the adrenal cortex
What other elements are impacted due to the salt-water balance of aldosterone?
Potassium and hydrogen
Where are adrenal andorgens produced?
The zona reticularis of the adrenal cortex
What are examples of adrenal androgens?
Dehydroepiandrosterone and androstenedione
What happens to adrenal androgens in males?
They are converted to testosterone in the testes
What happens to adrenal androgens in females?
Converted into 17beta-estradiol by the granulosa cells of the ovarian follicle
Which enzymes degrade catelcholamines?
Catelcholamine-O-methyltransferase and monoamine oxidase
What stimulates the secretion of cortisol?
Corticotropin-releasing hormone from the hypothalamus stimulates the corticotrophs to secrete adrenocorticotropic hormone which stimulates adrenal cortex
