Physiology Flashcards
What are the four types of receptors?
Ligand Gated
G protein coupled
Tyrosine-kinase
Nuclear
What agonists work on ligand gated ion channels/
Neurotransmitter
Hormones
What is the difference between a neurotransmitter and a hormone?
They can be the same substance, neurotransmitters are released across synapse from a nerve.
What occurs after agonist binds to the ion channel?
Conformational change in structure.
Ions allowed to pass through membrane.
How quick is the response in ligand gated ion channels?
Milliseconds
How quick is the response in G protein coupled receptors?
Seconds
In a G protein coupled receptor describe the structure of the G proteins?
Alpha subunit attached to a GDP
Beta and Gamma subunits bound in a dimer
In B2 adrenoreceptor what. type of G protein is present?
Gs alpha
Upon binding of adrenaline to B2 adrenoreceptor what occurs?
Conformational change of the receptor.
GDP is swapped for charged GTP on the alpha subunit.
Alpha subunit breaks away and binds to adenyl cyclase
What does adenyl cyclase do?
Converts ATP to cAMP
What is cAMP?
A cell signalling molecule?
In B2 adrenoreceptors what does an increase intracellular cAMP do?
PKA is activated
Inhibits MLCK activity
Bronchodilation
In G coupled protein receptors why does the reaction stop?
Weak bond between agonist and receptor.
GTP is hydrolysed breaking bond between alpha submit and adenyl cyclase
In A2 adrenoreceptors what is the difference in adenyl cyclase?
Adenyl Cyclase is active before activation
What G protein alpha subunit is present in A2 adrenoreceptors?
Gi (Inhibits)
What occurs after agonistic binding to receptor in A2 adrenoreceptors?
Alpha subunit only
Alpha subunit is activated by GTP.
B
Alpha subunit binds to adenyl cyclase inhibiting it.
What occurs after agonistic binding to receptor in A2 adrenoreceptors?
Beta and Gamma subunits only
The dimer binds to K+ channels
Cell membrane becomes hyperpolarized
What is the resultant action upon A2 adrenoreceptor activation?
Smooth muscle relaxation especially in GI tract
In alpha 1 adrenoreceptors what G subunit is present
Gq
What does the activated alpha subunit do in A1 adrenoreceptors?
Activates phospholipase C
What is the function of phospholipase C in regards to A1 adrenoreceptors?
Converts PIP2 into DAG and IP3
What does an increase in intracellular DAG and IP3 result in?
Increase in intracellular Ca2+
Vasoconstriction
Where are A1 adrenorecpetors commonly present?
Within the vasculature
In regards to G coupled reactions what kind of response do they evoke?
Amplification a large reaction from smaller stimuli
In regards to Tyrosine Kinase what kind of response do they evoke?
Divergent reaction, lots of different responses from the same stimuli.
What are the agonists of tyrosine kinase receptors?
Hormones e.g. insulin
What is the structure of a tyrosine kinase receptor?
They are a dimer
Upon binding of the agonist to the tyrosine kinase receptor what occurs?
It undergoes a conformational change bringing the two pieces together.
Intracellular tyrosine molecules are activated by ATP (phosphorylated)
Relay proteins bind to tyrosine triggering different cellular responses.
What are relay proteins?
These are individual proteins which bind to the tyrosine molecules present on the intracellular extension of the receptor, each one triggers a different response within the cell.
How long is the response in tyrosine kinase receptors?
Up to a few hours
How many folds pass across the membrane in a G protein coupled receptor?
7 times
Autocrine regulation
Self limiting
Chemical released by the cell bind to receptors on the same cell
Example of autocrine regulation
Somatostatin released from D cells
Paracrine regulation
Chemicals released by cell bind to receptors on cells located proximally
Example of paracrine regulation
Somatostatin released by D cells binds to parietal cells to inhibit release of HCL
Both located in stomach
How is endocrine regulation divided?
Negative and positive feedback
Endocrine Regulation
Chemicals released by cells into the circulatory system where they travel and bind to receptors on target cells.
Example of endocrine regulation
Insulin released by B cell in pancreas and target cells in liver.
Negative feedback
Primary Mechanism of maintaining homeostasis by resisting fluctuations away from physiological set point.
Positive feedback
Initial stimuli initiates a response which exaggerates the initial change
Examples of positive feedback
Oxytocin in childbirth
Blood clot cascade
What makes up intrinsic regulation?
Autocrine and Paracrine
What makes up extrinsic regulation?
Nervous system and endocrine
Example of negative feedback ?
Cortisol stress cycle
Cortisol is the final product but high levels of cortisol inhibits ACTH and CRh production all of which are precursors.
What is the function of GLUT2 receptors?
Censorship of blood glucose levels
Allows diffusion of glucose into the B cells in the pancrease.
What enzyme is responsible for monitoring blood glucose and how does it complete its function?
Glucokinase
An enzyme responsible for glycolysis
Increased glucose increases ATP conc
As a result of high ATP levels in the B cells due to high glucose levels what happens?
ATP sensitive K+ channels close
Voltage Gated Ca 2+ channels open
Excretion of insulin via exocytosis
What is the structure of insulin?
Polypeptide dimer held together by disulphide bridges
How is insulin produced then activated
Produced in RER of B cell
Cleaved to form active form
What can be used to monitor inulin production?
C protein
A by product of the cleaving of insulin to form active enzyme
Describe insulin release
Its biphasic
1st phase is dependant on dose larger dose = larger spike
2nd phase smaller as vesicles need to be prepared
What is the 1st phase of insulin release called?
Readily Released Pool
Insulin already packaged in active vesicles so quick response
In type II diabetes what happens to the phases?
They weaken and flatten
Why in type II diabetes does the pattern of release change?
As glucokinase activity is downregulated
Why in type II if enough weight is lost can they symptoms of diabetes disappear?
As B cells still producing insulin however, Blood glucose concentration is higher than the KM of glucokinase so its working at capacity basically.
By loosing weight glucose conc can be brought below KM of glucokinase.
What kind of receptor are the ATP sensitive K+ channels?
Inward rectifier - ion channel
Contain a sulphonylurea receptor - regulatory unit
Octomeric structure - 8 subunits
What is the function of K+ ATP channels and what stimulates them?
They inhibit insulin release by preventing Ca2+ entry
Diazoxide
What are the two main thyroid hormones?
T4 and T3
What is T3
Tri-iodothyronine
What is T4
Thyroxine
What is the basic functional unit of the thyroid?
Follicle
What makes up a follicle?
Colloid surrounded by cuboidal follicular cells
What is dispersed between follicles?
Parafollicular cells or C-cells
Neuroendocrine cells
What do C - cells excrete?
Calcitonin
What is the function of calcitonin?
Reduces blood calcium by opposing the action of parathyroid hormone
What do follicular cells produce?
Thyroglobulin
What is thyroglobulin?
Tyrosine packed full of proteins
What occurs within the follicular cells before formation of MIT and DIT?
Uptake and concentration of Iodide I-
Oxidation of Iodide I- to iodine I
Iodination of Thyroglobulin
What is MIT
Mono-iodotyrosine unit
Tyrosine bound to 1 unit of iodine
What is DIT
Di-iodotyrosine unit
Tyrosine bound to 2 units of iodine
How is T3 formed?
MIT + DIT
Mono + Di
1 iodine units + 2 iodine units = Tri-iodotyronine
How is T4 formed?
DIT + DIT
Di + Di
2 iodine units + 2 iodine units = Thyroxine
When synthesised where are T3 and T4 stored?
They are stored within the colloid thyroglobulin
What percentage of thyroid hormone produced T4?
90%
Which is the most potent thyroid hormone?
T3 is 4x more potent than T4
Where is T4 converted into T3?
Liver and the kidney
What is cycle leading to T3 and T4 secretion?
Hypothalamus stimulates pituitary gland
Anterior pituitary gland secretes Thyroid stimulating hormone
TSH causes stored T3 and T4 to be secreted
What does excess free T3 and T4 trigger?
Negative feedback
Inhibits at the hypothalamus and pituitary
What hormones are secreted by the anterior pituitary?
Growth Hormone GH Thyroid stimulating Hormone TSH Adrenocorticotropic Hormone ACTH Follicle Stimulating Hormone FSH Prolactin PRL Luteinizing Hormone LH
Where do the majority of thyroid hormones find themselves bound to in transport?
Serum proteins
What serum proteins are relevant in thyroid hormone transport?
Thyroxine binding globulin. TBG 70%
Thyroxine binding pre albumin TBPA 20%
Albumin 8%
How else can thyroid hormones be transported?
Free within the blood
In what form can thyroid hormones enter the cells?
Only when free and unbound
What % of T3 is unbound?
0.33%
What percentage of T4 id unbound?
0.015%
Why does T3 have a more rapid onset of action?
As it is less avidly bound by TBG and TBPA than T4
What are some affects of thyroid hormones
Increased Metabolic rate and glucose uptake
Increased Glycogenolysis and Gluconeogenesis
Increased lipolysis
Decreased Gylcogenesis and lipogenesis
Increase breathing, heart rate and force of contraction
What is the metabolic affect of hyperthyroidism?
Increased number and size of mitochondria
Increased oxygen use and ATP hydrolysis
Increased synthesis of respiratory chain enzymes
What percentage of patients with hyperthyroidism have heat intolerance?
30%
What is the affect of hypothyroidism on growth?
Stunted growth
Why does hypothyroidism result in stunted growth?
As thyroid hormones required for growth hormone releasing hormone production and secretion
What are the three types of thyroid hormone degrading enzymes?
D1
D2
D3
Where is D1 found?
Found within the liver and kidneys
Where is D2 found?
Found in : Heart Skeletal Muscle CNS Thyroid Pituitary
Where is D3 found?
Foetal placenta and brain
What is the main function of thyroid hormone degrading enzymes?
Conversion of T4 into the more metabolically active T3
What does the thyroid usually weigh?
15-25g
Where does the thyroid hormone originate from?
Foramen caecum
From what week does the thyroid develop
4th week
Where does the thyroid descend down?
Thyroglossal duct
Descends past the larynx
Where do the c cells originate from?
Originate around area where thyroid descends to
Where should thyroid be found?
C5 level of thyroid cartilage
T1 Fifth tracheal ring
What hormones are produced in the anterior pituitary?
ACTH TSH GH Prolactin FSH LH
What hormones are stored in the posterior pituitary?
ADH
Oxytocin
Where are hormones stored in the posterior pituitary produced?
Hypothalamus
What are the precursor hormones for Cortisol?
CRH (hypothalamus)
ACTH (Pituitary)
Cortisol (Adrenal glands)
What are the precursor hormones for testosterone?
GnRH (Hypothalamus)
LH FSH (Pituitary)
Testosterone (Testes)
What are the precursor hormones for growth hormone?
GHRH (Hypothalamus)
GH (Pituitary)
What is different about Prolactin?
Dopamine inhibits Prolactin
What are the precursor enzymes for thyroxine?
Thyrotropin Releasing Hormone (Hypothalamus)
Thyrotropin TSH (Pituitary)
Thyroxine (Thyroid)
How does the hypothalamus communicate with the anterior pituitary?
Portal system hormones travel within the blood
How does the hypothalamus communicate with the posterior system?
Hormones travel down nerves within axoplasm
What is the paired hormone of ACTH?
Cortisol
What is the paired hormone of TSH?
Thyroxine
What is the paired hormone of LH/FSH?
Testosterone or Estradiol
What is the paired hormone of GH?
IGF-1
Insulin like Growth Factor 1
Which nerves run close to the pituitary that control eye movement?
3
4
6
Which branches of which nerve run close to the pituitary?
5 Facial Nerve
Ophthalmic division
Maxillary division
What nerve makes up the optic chiasm?
2 Optic
What are the two types of dynamic test?
Too much - test suppresses hormone
Too little - test stimulates hormone
In a normal patient how should they react to a dynamic test for too much hormone?
levels of the hormone should drop
In a normal patient how should they react to a dynamic test for too little hormone?
Levels of hormone should rise
Give an example of a too little test used in measuring cortisol level ?
Insulin stress test
IV insulin given to induce a hypoglycaemic event
Cortisol and GH levels should rise
Give an example of a too much test used in measuring cortisol level test?
SynACTHen test
IV synthetic ACTH
Cortisol levels measured at 0, 30, 60 mins
In the synACTHen test how should the cortisol levels change?
Should rise by 150 and reach around 500 in a healthy patient.
Where is the anterior pituitary derived from?
Rathkes pouch
What is the posterior pituitary?
Extension of neuronal tissue formed from modified glial cells and axonal bodies.
What cells secrete GH?
Somatotroph
What cells secrete PRL?
Mammotrophs
What cells secrete ACTH?
Corticotrophs
What cells secrete TSH?
Thyrotrophs
What cells secrete FSH and LSH?
Gonadotrophs
What three zones make up the adrenal cortex?
Glomerulose
Fasciculata
Reticularis
What is produced in the glomerulose layer?
Mineralocrticoids
What is produced in the fasciculata?
Glucocorticoids
What is produced in the Reticularis?
Adrenal androgens
What makes up the medullary zone?
Chromaffin cells
Medullary veins
Splanchnic nerves
What does the medullary zone produce?
Catelcholamines
What is th starting point for all steroid synthesis?
Cholesterol
Under what control is aldosterone under?
Renin-angiotensin system
What is released when a low blood pressure is detected in the kidneys?
Renin
What is the function of renin?
Fist step in the cycle
Converts Angiotensinogen to Angiotensin 1
What enzyme is responsible for the second step in the renin angiotensin system?
ACE
Converts Angiotensin I in II
What is the third and final step in the Renin angiotensin cycle?
Angiotensin II causes aldosterone to be released by the adrenal glands
What is the function of aldosterone ?
Causes Reabsorption of Sodium and water.
Increases blood volume and in turn BP.
As well as acting as a triggering the release of Aldosterone what other affect does Angiotensin II have?
Causes vasoconstriction
Increases systemic resistance
Increasing BP
Where are mineralocorticoid receptors mainly located?
Kidney
Salivary Gland
Gut
Sweat Glands
What is the main role of mineralocorticoids?
Regulates BP extracellular volume and Na+ retention