Endocrinology S1 Flashcards
Homeostasis
A dynamic steady state of maintaining a constant internal environment despite changing conditions
Negative feedback
Initial stimulus occurs and initiates a response that decreases the stimulus. Stabilizing effect
Positive feedback
Stimulus starts a response that further stimulates it. Must be turned off by an outside factor and is reinforcing.
Gap junctions
Local communication. Holes connecting neighbouring cells for free-passage of small ions and molecules
Contact-dependent control
Membrane proteins binding to membrane proteins of another cell. Local communication
Autocrine control
Molecules move through interstitial fluid to communicate with cells a short distance away. Local communication
Long-distance communication
Occurs in the endocrine system or nervous system (neurohormones)
Simple reflexes
Reflexes mediated by either the nervous system or endocrine system
Complex reflexes
Reflexes mediated by both system and go through several integrating system
Differences between neural and endocrine reflexes
Have different specificity, nature of the signal, speed, duration of action, coding for stimulus intensity
Exocrine glands
Secrete chemicals into an external environment
Endocrine glands
Secrete chemicals directly into the bloodstream
Primary endocrine organs
Main function is releasing hormones
Secondary endocrine organs
Have a primary function and release hormones in addition to the primary function
Hydrophilic hormone characteristics
Water-soluble, dissolve in blood, can’t cross the plasma membrane, not lipid-soluble
Hydrophobic hormone characteristics
Not water-soluble, can’t dissolve in plasma (have carrier-protein), lipid-soluble, cross plasma membrane by diffusion
Hydrophilic hormone examples
Peptide hormones, protein hormones, catecholamines
Hydrophobic hormone examples
Steroids and thyroid hormones
Protein/peptide hormones
3+ hydrophilic AAs made in advance and stores in vesicles before release to bind to membrane receptors. Short half-life
Preprohormones
Can contain many copies of the same hormone or more than one type. Cleaving separates them
Steroid hormones
Made from cholesterol and made on demand. Long half life
Amine hormones
Made from tryptophan or tyrosine and behave based on synthesis
Tryptophan derivatives
Behave like peptides or steroids. Ex, melatonin
Tyrsosine derivatives
Catecholamines behave like peptides and thyroid hormones behave like steroids
Hypothalamus function
Sends hormones to the anterior pituitary to secrete its own hormone
Anterior pituitary vs posterior pituitary
Only the anterior pituitary can synthesize and release its own hormones
Synergistic effects
Caused by multiple hormones that act together for greater effect
Permissive effects
One hormone enhances the target organ’s response to a second hormone (both are required)
Agtagonisitic effect
One hormone opposes actions of another
How is hormone secretion regulated?
Endocrine cells send signals to hypothalamus and anterior pituitary which also sends signals to hypothalamus to stop secretion. Negative feedback
Properties of receptors
High affinity, saturable, specific, reversible
Intracellular receptors
Bind lipid soluble hormones and can be in the cytosol or nucleus to alter gene transcription
Hormone response element
Hormone receptor complex binds to response element DNA sequence to elicit response
G Protein-coupled receptors
Large multisubunit-protein membrane-spanning proteins. Use lipids as second messengers to open ion channels and alter enzyme activity in the cytoplasm
Gs mechanism
1) signal molecule binds GPCR to activate Gs
2) G protein activates adenylyl cyclase to convert ATP > cAMP
3) cAMP activates protein kinase A
4) PKA phosphorylates proteins, leading to a cellular response
Gq mechanism
Activates phospholipase C to convert membrane phospholipids into diglyercol so IP3 can diffuse into the cytoplasm and release Ca++
Gi mechanism
Targets adenylyl cyclase and inactivates it
Off switch membrane receptors
Receptors can be endocytosed by a clatherin-coated pit, trapping receptors. Triggered by a ligand
How is Ca+ stored in bone?
In crystals called hydroxyapatite (have calcium and phosphate)
Osteoblasts
Bone forming cells
Osteoclasts
Break down bone, multi-nucleated by fusion of multiple cells
Osteocytes
Previously osteoblasts that are surrounded by bone matrix and maintain bone nearby
Osteoclast mechanism
Secrete HCl and proteases to break down bone and release Ca++ into the blood
How do osteoblasts and osteoclasts interact?
Osteoclast precursors communicate with osteoblasts through RANK receptor on the precursor and RANKL on the osteoblasts. Both coming together creates mature osteoclast
Osteoprotegerin
Osteoblasts secrete OPG to block RANKL/RANK interaction by binding to RANKL which reduces osteoclast activity
Parathyroid hormone
Released by cells on the back of the thyroid gland to increase plasma Ca++ when low
Parathyroid sensing
Have a Gq coupled receptor that inhibits PTH synthesis when calcium is bound
PTH mechanism
1) On bone, it increases cAMP > increases RANKL and decrease OPG > stimulates osteoclast activation
2) In kidneys, PTH increases Ca++ reabsorption at distal tubule, increases calcitriol
Calcitriol (vitamin D3)
Targets intestine, bone, and kidney to increase plasma calcium through reabsorption and mobilization from bone
Calcitriol formation
Skin has precursors that become inactive vitamin D3 when hit by UV > become another precursor in liver > PTH creates active form in kidneys
Calcitriol signalling
Lipophilic hormone that binds vitamin D to form a heterodimer to enter the nucleus and bind vitamin D response element that eventually creates calcium channels
Blood phosphate regulation
1) PTH increases phosphate release from bone and decreases reabsorption in kidney
2) Calcitriol increases phosphate absorption and reabsorptiomn
Calcitriol vs PTH
Calcitriol wants to make bone, PTH wants to increase blood Ca++
Calcitonin
Peptide hormone secreted from C cells of thyroid to reduce osteoclast activity
Nephrons
Excretes waste, regulates blood volume, controls electrolytes, blood pH and vitamin D (via PTH)
Nephron function at sections
Water is reabsorbed in loop of Henle > ions reabsorbed before distal tubule > variable water/solute reabsorption in cortex medulla
Vasopressin
Synthesized in hypothalamus, secreted from posterior pituitary to increase water reabsorption in the kidneys by regulating permeability (increases it)
Vasopressin regulation
If there is high plasma osmolarity, vasopressin (ADH) is released by osmoreceptors. Low blood pressure detected in the heart also stimulates the release
Vasopressin mechanism
Inserts water pores into the distal convoluted tubule and collecting duct of cell membranes in nephrons. Aquaporin water pores inserted into the apical membrane
Aldosterone
Steroid synthesized in the adrenal cortex to regulate sodium through Na+ reabsorption and K+ secretion
Aldosterone regulation
Stimulated by high K+ concentration in plasma and angiotension II via blood pressure. Inhibited by high Na+ in ECF
Aldosteron mechanism
Acts in the distal tubule and collecting duct to initiate the synthesis of protein channels and pumps for increase Na+ reabsorption and K+ secretion
Renal Juxtaglomerular Cells
Secrete renin to go into the liver to cleave angiotensinogen to create angiotension
Angiotension II
Created from cleavage of angiotension I in the lungs and acts on hypothalamus to stimulate aldosterone secretion
Natriuertic peptids
Peptides that act as hormones to stimulate water to be released from the body
ANP
Secreted by atria and neurons to decrease Na+ and water reabsoption and increases K_+reabsorption
BNP
Secreted by ventricles and neurons
CNP
Secreted by brain, pituitary, vessels and kidneys
Adrenal Medulla
Neuroendocrine tissue that produces and secretes catecholamine and is stimulated by the SNS (short-term stress)
Adrenal cortex structure
Surrounds adrenal medulla and is surrounded by a capsule
1) zona glomerulosa secretes aldosterone
2) zona fasciculata secretes glucocorticoids
3) zona reticularis secretes sex hormones
Zona ___ hormone formation
All are synthesized by cholesterol
Androgens (sex hormones) formation
DHEA > androstenedione > testosterone > DHT OR from androstenedione > estrone w/ aromatase enzyme > estradiol OR testosterone > estradiol w/ aromatase
Cortisol
Main gluccorticoid and is secreted following a diurnal rhythm to mediate long-term stress
Cortisol release
CRH released by hypothalamus > corticotropic cells stimulate anterior pituitary > ACTH send to adrenal cortex > cortisol secreted
Cortisol regulation
Excess cortisol sent to hypothalamus and anterior pituitary through negative feedback to turn off ACTH and CRH
Addison’s disease
Excess secretion of adrenal steroids which causes hypotension and hypoglycemia
Cushing’s syndrome
Cortisol excess causing hyperglycemia, muscle protein breakdown, lipolysis, etc
Cortisol roles
1) promotes gluconeogensis
2) breakdown of skeletal muscle protein for AA
3) enhances lipolysis
4) suppresses immune system
Anabolic processes
Occurs in a fed state and promotes glycogenesis, lipogenesis
Catabolic processes
Occurs in a fasted state and promotes glycogenolysis, lipolysis
Gluconeogensis
Creates of glucose from non-carbohydrate substrates. Occurs in a fasted state but is anabolic
Insulin
Anabolic peptide that binds to tyrosine kinase receptor to reduce blood glucose by promoting formation of glycogen, fat and protein
Insulin mechanism
Triggers GLUT4 receptors in the liver to increase glucose in the cell and out of the blood stream
Hexokinase
Activated by insulin to phosphorylate free glucose into glucose 6-phosphate to keep intracellular glucose low
Insulin release
Beta-cells in the pancreas detect glucose in the blood and increase ATP to block K+ channels, preventing K+ from leaving the cell > causing a depolarization > releasing Ca++ to trigger insulin release
Incretin effect
Gastrointestinal hormones cause an increase in insulin when glucose is in the small intestine
Gluagon-like peptide 1
Stimulated by nutrients and parasympathetic activity to increase insulin and decrease glucagon
Gastric inhibitory peptide
Stimulated by glucose and fatty acids to increase insulin
Glucagon
Increases glycogenolysis, gluconeogensis and ketogensis to prevent hypoglycemia by causes GLUT2 to transport glucose into blood
Cortisol and glucagon
Cortisol is catabolic and helps glucagon build up glucose by glycogenolysis
Glucagon mechanism
Alpha cells secrete glucagon in response to low glucose, SNS, amino acids to increase blood glucose
Sulfonylureas
Close K+ channels to treat type 2 diabetes, allowing Ca++ to enter cell, releasing insulin
