endocrine 2 Flashcards
Describe the characteristics of thyroid gland
- The longest of the pure endocrine gland
- Located in front of the neck, just below the larynx
- Secretes thyroid hormones (which are stored as the thyroglobulin, a matrix for thyroid hormone synthesis)
- Contains the follicular cells that secretes T3 & T4
- Contains the parafollicular cells that secretes calcitonin (c cells)
Action & transport of thyroid hormones
- Thyroid secretes 90% T4 (thyroxine) but T3 (tri-iodothyronine) is 4 times more potent
- T4 is converted to T3 in the liver & kidney
- Over 99% of thyroid hormones in the blood are bound to plasma proteins thyroxine binding globulin & albumin, which acts as carriers of insoluble thyroid hormones
→ Only 0.3% T3 & 0.03% T4 are free & biologically active
Effect of thyroid as a catabolic hormone (got 3)
- Increases overall basal metabolic rate (BMR)
→ BMR: no. of calories the body needs to accomplish basic life-sustaining functions
→ Stimulates the consumption of glucose & fatty acids & ↑ metabolic heat (non-shivering thermogenesis)
→ Convert glycogen into glucose & stimulate protein degradation ⇒ leads to lean muscle & low protein in body & ↑ blood glucose level - Sympathetic-mimicking effect: mimics endogenous agonist of the sympathetic nervous system
→ ↑ target cell responsiveness to epinephrine & norepinephrine ⇒ ↑ heart rate & stroke volume - Essential for normal growth & promote the maturation of nervous system
Brown fats convert calories to heat energy and contains the most mitochondria as compared to other fat cells. How does the mitochondria generate heat energy in brown fats and contribute to thermogenesis?
Mitochondria in brown fats lack ATP synthase but have Uncoupling Protein 1 (UCP1) instead.
When H+ diffuses from the intermembrane space to the mitochondrial matrix down the concentration gradient through the UCP1 protein channel, heat is generated and hence, contributing to thermogenesis
What stimulates brown fat activity (thermogenesis)?
What is the relation between cold-activated brown fats and body fats?
As follicular cells secrete T3, the T3 stimulates the target cells, Ventral Medial Hypothalamus (VMH), through the inhibition of AMP-activated protein kinase (AMPK) in response to cold exposure, stimulating thermogenesis in brown fats
Cold-activated brown fat tissues are negatively associated with body fats & BMI
↑ body fats = ↓ brown fat activity
What gives brown fats its colour and how is brown fat different from white fat & beige fat?
- Brown fats have small/less fat droplets, produce/express more UCP1, more mitochondria (which gives it its brown colour)
- White fat cells are derived from young white fat cells while brown fat cells are derived from the same precursor as muscle cells
- Beige fat cells are white fat cells converted to beige adipocytes with irisin via circulation
⇒ Beige fat cells have more mitochondria than white fat cells, but less mitochondria than brown fat cells
⇒ ↑ mitochondria ⇒ ↑ UCP1 ⇒ ↑ thermogenesis, ↑ fats burned, ↓ weight, ↑ insulin sensitivity & homeostasis effect
How does energy-induced irisin rescue synaptic plasticity & memory defects in Alzheimer’s model?
- irisin is reduced in Alzheimer’s Disease brains & Cerebrospinal Fluid (CSF) ⇒ impairs synaptic plasticity
- Boosting brain irisin levels rescues synaptic plasticity & memory
⇒ Irisin mediates the protective actions of physical exercise on synaptic plasticity & memory
Cause & effect of hypothyroidism
Causes: primary or secondary
- Inadequate supply of iodine
- Autoimmune disease (self-destruction)
- Deficiency of thyroid-stimulating hormone (TSH), thyroid-releasing hormones (TRH), or both
Effects:
- Goiter (swollen thyroid) develops when thyroid gland is over-stimulated by TSH
- Neonatal (infant) hypothyroidism can lead to Cretinism ⇒ severely impairing physical & mental growth in infant (can be tested & treated in the 1st few days after birth)
Causes of hyperthyroidism (e.g. Graves’ disease)
Causes:
- Excessive iodine
- Growth on thyroid
- Graves’ disease
Graves’ disease is the most common cause
- In Graves’ disease, the body erroneously (by mistake) produces thyroid-stimulating immunoglobulin (TSI) which exerts TSH-like effects on TSH receptors BUT is not subjected to negative feedback (high concentrations of TSI cannot be brought back to original equilibrium/removed)
- Thyroid gland has no means to inhibit the TSI & is over-stimulated to produce more thyroid hormones, leading to hypersecretion
Hormones involved in calcium homeostasis
Parathyroid hormones, calcitonin (c cells), vitamin D
Homeostasis of Extracellular Fluid (ECF) calcium is vital as the ECF calcium is a Na+ channel blocker.
What happens in hypocalcemia and hypercalcemia
Hypocalcemia:
- Increase neuromuscular excitability ⇒ may lead to muscle cramps easily
- Severe hypocalcemia may cause spasms of respiratory muscles, leading to suffocation
- Hypocalcemia makes it harder to generate action potential
Hypercalcemia:
- Reduce neuromuscular excitability
- Cardiac arrhythmia
Function of parathyroid glands
- To increase [blood Ca2+]
- 4 glands embedded in lateral lobes of the thyroid glands
- Secrete parathyroid hormone (PTH, a 84 a.a. polypeptide)
⇒ Stimulated by a decrease in [blood Ca2+] - The most important hormone in control of [blood Ca2+]
⇒ essential for survival → will suffocate & die if don’t have
How does PTH increase blood calcium in bones, kidneys & intestine?
On bones:
- Promotes transfer of [Ca2+] from bone fluid to plasma
- Stimulates dissolution of calcium phosphate crystals in bone matrix to release [Ca2+] & PO4 3- (slow effect)
On kidneys:
- Stimulates [Ca2+] reabsorption
- Promotes PO4 3- elimination
⇒ Prevent re-precipitation of Ca2+ to form Ca3(PO4)2 crystal
⇒ ↓ likelihood to ppt on bone, ↑ likelihood of blocking Na+ channels
On intestine:
- Increase both Ca2+ & PO4 3- absorption via vitamin D activation in kidneys
Abnormalities associated with Parathyroid Hormone
PTH hyposecretion
- PT glands removal mistakenly during thyroidectomy
- Rarely as a result of autoimmune disease & genetic defect of PTH gene
PTH hypersecretion
- Chronic kidney failure
- Parathyroid hypertrophy/malignancy
Vitamin D also plays a role in calcium homeostasis. Where is vitamin D synthesized from and what is Vitamin D converted to?
Vitamin D is synthesized in the skin or obtained from diet.
In the liver, vitamin D is converted to 25-Hydroxyvitamin D
In the kidney, vitamin D is converted to 1,25-Dihydroxyvitamin D (active form)
Function of vitamin D and effect of vitamin D deficiency
- Promotes absorption of Ca2+ and PO4 3- from the intestine
- Increases responsiveness of bones to PTH
Vitamin D deficiency may lead to rickets (soft bones) and/or osteomalacia (epiphyseal plates not fully calcified
Functions of calcitonin (c cells) [function is opposite of PTH]
- Secreted by the parafollicular cells of the thyroid and stimulated by high [blood calcium]
- Acts as a physiological antagonist to PTH
- Inhibits osteoclast activity → ↑ calcification of bones
⇒ treats osteoporosis - Delays calcium absorption from the intestine
- ↑ calcium urinary excretion
- Used to treat osteoporosis
How are estrogen and androgen are also important for bone health?
Both increases bone density
- Aging is associated to increased risk of osteoporosis especially in women due to reduced sex hormones
- Osteoporosis is characterized by porous bone and deterioration of bone tissue with increasing risk of fracture
Adrenal glands are embedded in a capsule of ___ on top each ___ and consists of the ___ ___ and the ___ ___
(copy paste and fill in the blanks)
Adrenal glands are embedded in a capsule of fats on top each kidneys and consists of the adrenal cortex and the adrenal medulla
Effect of aldosterone (got 3)
- Stimulate the kidneys (kidney tubule) to reabsorb Na+ and secrete K+
- The secondary effects are the osmotic retention of water and expansion of extracellular fluid (ECF) volume
⇒ ↑ reabsorption of water → ↑ blood volume and blood pressure - Essential for life
Regulation of aldosterone is mainly by which organ?
Sensed by the kidneys and regulated by the renin-angiotensin system
Abnormalities with aldosterone secretion
Hypersecretion
- Primary: adrenal tumor of aldosterone-secreting cells (Conn’s syndrome)
- Secondary: overactivity of renin-angiotensin system due to reduced blood flow (due to blockage) to the kidneys (that detects low salt levels → ↑ aldosterone secretion
Hyposecretion
- Primary adrenal cortical insufficiency (Addison’s disease) is mainly due to autoimmune disease which attacks the enzymes involved in the production of aldosterone, affecting all layers of adrenal cortex
- Congenital adrenal hyperplasia due to genetic defect of 21-hydroxylase or 11β-hydroxylase (the enzyme)
Glucocorticoid is a terminology used for hormones produced in that layer of cell. What are the functions of cortisol, corticosterone, and glucocorticoid?
Cortisol: primary glucocorticoid for most mammals
corticosterone/cortisone: serves same function in rodents, birds and amphibians
glucocorticoid: used for drugs to mimic the actions of cortisol
What are the metabolic effects of glucocorticoids?
Metabolic effect:
- Glucose:
⇒ Stimulate hepatic gluconeogenesis
⇒ Inhibits glucose uptake and consumption by many tissues except for the brain tissue
- Protein:
⇒ Reduces protein stores in all tissues except the liver by promoting degradation and inhibiting synthesis
- Lipid:
⇒ Increases lipolysis in the limbs and promote fatty acid oxidation
⇒ Increases lipogenesis in the face and torso (more fats around face and stomach)
What is the immunosuppressive effect of glucocorticoids?
Suppresses all aspects of the inflammatory response
- e.g. immune cell proliferation, cytokine secretion, fever production
What is the effect of stress on glucocorticoids?
Adaptation to stress, any stress is a major stimuli for cortisol secretion (permissive role for catecholamines)
Abnormalities with cortisol secretion
Hypersecretion (Cushing’s syndrome)
- Primary cause: adrenal tumor
- Secondary cause: excessive stimulation by CRH & ACTH
Hyposecretion
- Primary cause: adrenal cortical insufficiency (Addison’s disease)
- Congenital adrenal hyperplasia and hyperpigmentation due to hypersecretion of ACTH
⇒ ACTH is cleaved to form corticotropin-like intermediate protein (CLIP) and αMSH which stimulates melanin production and hence increases pigmentation
⇒ ↓ cortisol, ↑ ACTH as negative feedback
Adrenal androgens role, stimulated by.
Dehydroepiandrosterone (DHEA) is the only biologically significant androgen from the androgen cortex (much weaker than testosterone)
- May play a significant role in females by promoting
⇒ growth of pubic and axillary hair
⇒ Pubertal growth spurt
⇒ Female sex drive
- Secretion is stimulated by ACTH
- Negative feedbacks send to GnRH instead of CRH
Effects of hypersecretion and hyposecretion of adrenal androgen
Hypersecretion
- Commonly caused by the deficiency of 21-hydroxylase or 11β-hydroxylase (congenital adrenal hyperplasia)
- Associated with the hyposecretion of aldosterone and cortisol secretion
- Can lead to adrenogenital syndrome
Hyposecretion
- Hyposecretion has no effects/issues in the body
Adrenal medulla characteristics (got 3)
- Consists of modified postganglionic sympathetic neurons (chromaffin cells)
- Innervated by the preganglionic sympathetic neurons
- Sympathetic stimulation of the adrenal medulla is almost solely responsible for epinephrine release
Hormones secreted by adrenal medulla and its receptors
Adrenal medulla produces 80% epinephrine and 20% norepinephrine (collectively known as catecholamines)
- Norepinephrine is more important as a neural transmitter for sympathetic post-ganglionic neurons
Adrenergic receptors: receptors for epinephrine and norepinephrine
- α1-receptors: Bind stimulatory G proteins (Gs) to activate phospholipase C pathway
- α2-receptors: Bind inhibitory G proteins (Gi) to inhibit adenylate cyclase
- β1 and β2: Mainly coupled to Gs and Gi proteins respectively (α1 → β1, α2 → β2)
Functions of epinephrine (got 3 main points)
- Reinforces sympathetic nervous system and exerts additional metabolic effects
- Fight or flight response
⇒ Increases rate and strength of cardiac contractions (using β1 receptors)
⇒ Dilates the blood vessels supplying the heart and skeletal muscles (exclusively through β2 receptors)
⇒ Constrict blood vessels in internal organs (via α1 receptors), increasing total peripheral resistance - Metabolic response (increase energy/heat production)
⇒ Promotes hepatic glucogenesis and glycogenolysis and lipolysis
⇒ Stimulates glucagon and inhibit insulin secretion
What are the pancreatic hormones and where are they synthesized?
β cells in pancreatic islets of Langerhans: secrete insulin
α cells in pancreatic islets of Langerhans: secrete glucagon
Why does insulin and glucagon have opposing functions
insulin: synthesis of glycogen, proteins, triglycerides
- Secreted when the blood glucose, fatty acids, and amino acids increase
Glucagon: breakdown of glycogen, proteins, triglycerides
- Secreted when the blood glucose, fatty acids, and amino acids decrease
Functions of insulin (got 3)
- Acts on insulin receptors, mainly in skeletal muscles, liver, and adipose tissues
- Promotes entry of glucose, amino acids, and fatty acids into cells and increase its anabolic process (glycogenesis, fat storage, protein synthesis)
- Inhibits catabolism (glycogenolysis, lipolysis, and protein degradation)
The effects result in the decrease of blood levels of glucose, fatty acids, and amino acids
Regulation of insulin secretion
Positive regulators:
- High plasma levels of glucose and amino acids
- Glucagon and glucose-dependent insulinotropic polypeptide (gastric inhibitory peptide) (GIP)
Negative receptors:
- Somatostatin
- Sympathetic activation
Insulin resistance is a common characteristic of type II diabetes. Describe what happens in the body that leads to type II diabetes
Type II diabetes is a condition where the body does not respond to insulin
- The decreased expression, increased internalization or immune destruction of insulin receptor are amongst the suggested causes
- There is also a loss of post receptor components in insulin signal transduction pathway, including a defect in GLUT4 translocation: lipid-induced insulin resistance
Lipid-induced defect in insulin signaling contributes to insulin resistance. How does it contribute and what study is done to support the FFA-induced impairment?
- Intra muscle lipid level predicts insulin resistance
- The metabolic products of free fatty acids inhibits GLUT4 translocation to membrane of muscle cells by inhibiting PI-3K signaling
- Fatless mice study supports FFA-induced impairment
⇒ Too little fats ⇒ manifest liver and muscle insulin resistance ⇒ develop diabetes
