Physiology Flashcards
What does the endocrine system consist of?
Ductless endocrine glands at numerous locations
How is specificity of hormone signalling achieved?
Chemically distinct hormones, specific receptors for each hormone, distinct distribution of receptors across target cells
What are the major endocrine glands?
Pineal, hypothalamus, pituitar, parathyroid, thyroid, adrenal, pancreas, ovaries in female, placenta in pregnant female, testes in male
What are the overall functions of endocrine system?
Regulation of nutrient metabolism, H20/electrolyte balance, RBC production, enabling change to stress, promoting growth +dev, controlling reproduction, controlling and integrating activities of CV and GI system
What is autocrine signalling?
Cell secretes hormone or messenger that binds to autocrine receptors on same cell
What is paracrine signalling?
Cell secretes hormone or messenger that binds to receptors on nearby cells
What is endocrine signalling?
Cells secrete hormone or messenger that travel to target distant cells through bloodstream usually
What are the 3 main classes of hormones?
Glycoproteins and peptides, steroids, tyrosine and tryptophan derivatives
Describe glycoproteins and peptide hormones
Amino acid chains of varied length. May be simple, can contain disulphide bonds, can be multiple. E.g. oxytocin, insulin
Describe steroid hormones
Derived from cholesterol e.g. cortisol, testosterone
What are some tyrosine and tryptophan derivative hormones?
Adrenaline, thyroid hormones, melatonin
Describe amine synthesis, storage, release and transport
Pre-synthesised, vesicle storage, released in response to stimuli by Ca2+ dependent exocytosis
Are amines hydrophilic or hydrophobic?
Hydrophilic
How are amines transported in plasma?
Mainly ‘free’
Describe peptides and proteins synthesis, storage, release and transport
Pre-synthesised from longer precursor, vesicle storage, released in respose to stimuli by Ca2+ dependent exocytosis
Are peptides hydrophilic or hydrophobic?
Hydrophilic
How are peptides transported in plasma?
Mainly ‘free’
Describe steroid synthesis, storage, release and transport
Synthesised and secreted upon demand. Stimuli increase based on: cellular uptake and availability of cholesterol, rate of conversion of cholesterol to pregnenolone
Are steroids hydrophilic or phobic?
Hydrophobic
Are steroids transported in plasma as free or bound molecules?
Mainly bound (~90%) to plasma proteins. Only free if biologically active
Are steroids and thyroxine soluble or insoluble in plasma?
Relatively insoluble
What do hormone carrier proteins do in terms of blood, and kidney filtration?
Increase amount transported in blood, and prevent rapid excretion by preventing filtration at kidney
What does albumin do as a carrier protein?
Binds many steroids and thyroxine
What does transthyretin do as a carrier protein?
Binds thyroxine and some steroids
Are proteins and peptides soluble or insoluble in plasma?
Soluble
What do carrier proteins act as in terms of hormone concentration?
A buffer and reservoir helping to maintain constant concentrations of free lipophilic hormone in blood
Are free and bound hormones at equilibrium in the blood?
Yes
What hormones can cross the capillary wall to activate receptors in target tissues?
Only free hormones
What is the primary determinant of plasma concentration of hormones?
Rate of secretion
What does negative feedback do in terms of hormone concentration?
Maintains plasma concentration at set level
What does tropic mean?
Refers to hormone that acts upon another endocrine gland to regulate its secretion of hormone
What is neuroendocrine control in terms of hormonal levels?
Elicits a sudden burst in secretion to meet a specific stimulus
What is diurnal rhythm control in terms of hormonal levels?
Secretion rates fluctuate as a function of time- entrained to external cues such as day/night
What are the most important routes of hormonal elimination?
Metabolism by liver, excretion by kidney
What is the approximate half life of amines?
Seconds
What is the approximate half life of proteins and peptides?
Minutes
What is the approximate half life of steroids and thyroid hormones?
Hours to days due to binding
What are the cell surface receptors?
GPCR, receptor kinases
What activates GPCR?
Amines and some proteins/peptides
What activates receptor kinases?
Some proteins/peptides
What are the intracellular receptors?
Nuclear receptors
The ligands of intracellular receptors are lipophilic, what does this allow?
Diffusion across the plasma membrane
What activates class 1 nuclear receptors?
Steroid hormones
What activates class 2 nuclear receptors?
Mostly by lipids
What activates the hybrid class of nuclear receptors?
Thyroid hormone (T3) and other substances (similar in function to class 1)
Where are class 1 nuclear receptors located?
In absence of activating ligand mainly located in cytoplasm bound to inhibitory HSP- move to nucleus when activated
Where are class 2 nuclear receptors located?
Present in nucleus
What does binding of insulin to receptor kinases cause?
Autophosphorylation of intracellular tyrosine residues, and recruitment of multiple adapter proteins, notably IRS1, which are also tyrosine phosphorylated- causes cellular effects
What kind of transcription factors are nuclear receptors?
Ligand-gated
Are steroid hormones lipophilic or phobic?
Lipophilic
What happens to the receptor steroid complex after combining the intracellular receptor with steroid hormones?
Moves to nucleus, forms a dimer and binds to hormone response elements in DNA. Transcription of specific genes is switched on/off to: alter mRNA levels and the rate of synthesis of mediator proteins
Describe insulin secretion in pancreatic B cell
Blood glucose elevation> increased diffusion of glutamate into B cell by GLUT2>phosphorylation of glucose by glucokinase>glycolysis of g6p in mito yielding ATP> increased ATP/DP ratio within cells closes ATP-sensitive K+channels causing depolarisation> opening of channels increases intra Ca2+ that triggers insulin secretion
What does ATP binding to each of the Kir6.2 subunits in the Katp channel do?
Closes the channel causing depolarisation of the B cell and insulin release (when extracellular glucose high)
What does ADP-Mg2+ binding to the SUR1 subunits of the Katp channel do?
Opens the channel maintaining the resting potential of the B cell and inhibits insulin secretion (when extracellular glucose is low)
Ingestion of food stimulates the release of what from enteroendocrine cells in the SI?
Glucagon Like Peptide 1 (GLP-1) and Glucose Dependent Insulinotropic Peptide (GIP)
From what enteroendocrine cells is GLP-1 released from?
L cells in the ileum
From what enteroendocrine cells is GIP released from?
K cells in the jejunum/duodenum
What do GLP-1 and GIP enhance from pancreatic B cells?
Increment insulin release (and delay gastric emptying), leading to enhanced glucose uptake/utilisation and decreased blood glucose
What does GLP-1 decrease from pancreatic alpha cells?
Glucagon releae, leading to decreased glucose production and decreased blood glucose
What are the main nutritional considerations in a T1DM patient?
Consistency and timing of meals and CHO, timing of insulin, monitoring blood glucose regularly
What are the main nutritional considerations in a T2DM patient?
Wt loss, smaller meals and snacks, physical activity, monitoring blood glucose and medication (if on insulin)
What can be the risks of alcohol in DM patients?
Hypoglycaemia, confusing hypo symptoms, increased risk of some cancers, HT, liver disease. Hidden calories may not be thought about
What are the similar features of GPCR’s?
7 transmembrane domain, associated G-protein compelx
What are some cytokine receptors?
Prolactin receptor, GH receptor
What does the ability to accurately measure hormone levels depend on?
Secretion pattern, presence of carrier proteins, interfering agents, stability of hormone (t1/2), absolute concentrations
What does a raised TSH indicate about thyroid status?
Hypothyroid
What does a suppressed TSH indicate about thyroid status?
Hyperthyroid
When might TSH not be a reliable marker of thyroid status?
Pituitary dysfunction (secondary hypothyroidism or TSHoma)
What does formal assessment of HPA axis require?
Dynamic testing
At what time of day may a cortisol measurement indicate HPA axis function?
9am
What does formal assessment of GH axis require?
Dynamic testing
What can an IGF-1 measurement indicate?
GH hypersecretion
Where is PRL secreted from?
Lactotroph cells of anterior pituitary
Under what inhibition is PRL secreted under?
Tonic inhibition by hypothalamic dopamine
What are the effects of PRL mediated by?
Prolactin Receptor
What are some physiological causes of hyperprolactinaemia?
Pregnancy, lactation, nipple stimulation
What are some pathological causes of hyperprolactinaemia?
Prolactinomas/mixed secreting adenomas. hypothalamic and pituitary stalk disorders, medication-dopamine antagonists, others (antidepressants, oestrogens etc), chronic renal failure, ectopic PRL production
What is aldosterone regulated by?
RAAS and plasma potassium
When is the RAAS system activated?
In response to a decrease in bp
What happens when the RAAS system is activated?
Production of AT2 which causes vasoconstriction and aldosterone production to increase bp
What is calcium homeostasis based on?
Diet, gut absorption, PTH, vit D
What happens when decreased calcium occurs in the body?
Sensed by parathyroid gland, increase in PTH. Acts on kidneys to cause reabsorption of calcium, on bone for resorption and GI system for increased absorption by activating vitD to increase serum calcium levels
What is the primary action of 1,25-(OH)2 D3?
To promote gut absorption of calcium by stimulating formation of calcium-binding protein within the intestinal epithelial cells
