Endocrine 2 Flashcards
Structure of thyroid gland
- Active follicles
- resting follicles
- parafollicular / C-cells
What does the parafollicular cells secrete? Where these cells located ?
Secretes calcitonin. Located in thyroid gland.
Where’s the thyroid gland located?
In trachea
What does calcitonin do?
Regulates blood Ca+
Structure of follicles in the thyroid gland
Follicles composed of a single layer epithelial or follicular cells. Sender of follicle called colloid
Thyroid hormones
1) synthesizes from tyrosine and iodine
2) Intermediates:
- mono-iodotyrosine (MIT)
- di-iodotyrosine (DIT)
3) Active hormones
- tri-iodotyrosine (T3)
- Tetra-iodotyrosine (T4)
What are thyroid hormones synthesized from
Tyrosine
The “life story of the thyroid hormones
1) uptake of iodide from the blood (active transport)
2) synthesis of thyroglobulin (glycoproteins w tyrosine (TRH))
3) iodination of TRH = MIT and DIT (intermediates)
4) coupling of iodotyrosines = T3 and T4 (active forms)
5) storage in colloid (T4>T3)
6) endocytosis of colloid breakdown by lysosomal enzymes (recycle iodine +AA)
7) secretion of hormones into blood (T4>T3)
8) transport in blood, majority bound/inactive
9) T4 as a prohormone (most T4–>T3 in tissues, T3 is major hormone)
10) thyroid hormone receptors (present in cell nucleus; T3 binds more strongly)
11) half life —> T3=1 day / T4 = 7 days
Where are thyroid hormones stored?
In the colloid regions within the follicle cells
Which thyroid hormone is the major one
T3. T4 converts to become T3 eventually.
In storage, when thyroid hormones is greater in number
T4 > T3
When thyroid hormones are secreted into the blood, which one is greater in number
T4 > T3
Of T3 and T4, which one has a greater % bound/inactive?
T4
Thyroid follicular cell
1) iodine in the blood moved into the follicle via Na+/I- pump
2) iodine moved to luminal side and exits via pendrin transporter channel
3) peroxidase reacts iodine to form the intermediates of MIT and DIT
4) T3/T4 formed in a protein called thyroglobulin. Enter follicle to be stored in the colloid of the follicle
5) once needed, thyroglobulin releases T3, T4, and iodine.
6) T3 and T4 exit follicle out into the blood via endocytosis (active form). Iodine exits back to luminal side
Physiological actions of thyroid hormones
1) act on most tissues —> change translation and transcription
2) increase metabolism
3) necessary for growth and development
Actions of thyroid hormones
(T3 and T4)
1) Metabolism:
1) Metabolism:
- catabolism and anabolism INC
- INC base metabolic rate = INC O2 consumption = inc hear production
- INC carbohydrate absorption
- INC protein breakdown (muscle)
- INC fat breakdown
- INC fat breakdown
- INC cholesterol metabolism
- DEC blood cholesterol
Actions of thyroid hormones
(T3 and T4)
2) Growth and development:
3) other effects:
2) Growth and development:
- act as tissue Growth factors
- INC protein synthesis
- INC GH/IHF production
- CNS maturation in fetus
3) other effects:
- cardiovascular system (INC heart rate)
- potentiation of sympathetic nervous system (INC beta adrenergic receptors)
- reproductive system
Control of thyroid hormone secretion
Hypothalamus = TRH = ant pit = TSH = thyroid gland = Thyroid hormones T3 and T4
What kind of feedback system do thyroid hormones have, and on what
(-) feedback system on BOTH the hypothalamus and ant pit
Cold environments can influence the hypothalamus to increase TSH and TRH, increase thyroid hormone output which increase metabolic process =
increase heat.
Overactivity of thyroid hormones
Graves disorder: autoimmune disorder which stimulated thyroid gland.
- increase in basometabolic rate
- exophthalmos (bulging of eye)
- goitre (neck swelling)
Underactivity of thyroid hormones
Hashimoto’s Thyroidits: Autoimmune disorder which destroys thyroid gland and blocks hormone synthesis.
- Myxedema
- goitre
- cretinism in children
- iodine deficiency
• Goitre =
enlargement of thyroid gland.
• Exophthalmos:
pertution of the eye balls (popping out)
Thyroid hormone mechanism
OVERACTIVTY: Normally follicular cell has receptor for TSH, but now body made antibodies for TSH receptors, these antibodies stimulate the recpetors tho. Causes overstimulation and excessive amount of thyroid hormone and all the effects will be very high.
Thyroid hormone under activity mechanism
UNDERACTIVITY: not producing Normal amount of hormones, so become hypothyroid. When hormone levels goes down, causes less negative feedback = more TRH and TSH that will stimulate the gland, causing goitre.
• Iodine deficiency
most common cause for lack of thyroid hormone, no good source of iodine in diet.
• Cretinism
abnormalities in brain development in children
• Mixedma =
swollen face / skin.
Distribution of Ca+ in the body
Extracellular VS intracellular
Extracellular (0.1%)
- Free Ca+ = 500mg
- Bound Ca+ = 500 mg
(50%:50%)
Intracellular (0.9%)
- Free Ca+ = 0.1mg
- Bound Ca+ = 10g
Importance of Ca+
- structural role
- intracellular messenger
- intracellular messenger
- regulation of excitability
Important of phosphate
- structural role
- metabolism (ATP)
- buffering agent
Target for parathyroid hormone PTH, form parathyroid gland
Bone
Target for active vit D form kidneys
GIT
Target for Calcitonin from thyroid gland
Kidney
Bone structure
Calcified matrix
1) protein framework (osteoid), made of collagen.
2) Ca + Phosphate salts (hydroxyapatite)
Types of Bone cells
1) osteoblasts (bone forming)
2) osteoclasts (bone destroying)
3) osteocytes (long living, response to stress)
Location of parathyroid gland ?
Bottom of the neck
What is the function of PTH?
To increase the level of blood Ca+ and decrease level of blood phosphate
Which cells secrete PTH
Chief cells within the parathyroid
The role of PTH in osteocytic osteolysis
Maintains constant blood Ca+ levels
Which bone cells are on the surface of the bone, and which in inside the matrix ?
- Osteoblasts and osteoclasts are on the surface.
- Osteocytes are inside the matrix, within the inner fluid space.
Osteocytes come from
Osteoblasts
Ca+ in the bone moves from within the
fluid filled inner matrix, out towards the surface
Most of the Ca+ in the bone is present in a
Non readily exchangeable form, but little bit is exchangeable near the surface of the bone.
What is the movement of Ca+ within the bone and bones cells
Ca+ moves from the fluid filled intraceullar matrix of the bone towards outside t the surface, Ca+ is the taken up by the osteocytes, moved through Ca+ channels in osteocytes, transfers Ca+ to the osteoblasts via tight junction, the its pumps out into the blood, under the influence of PTH
Osteoclasts reabsorption
Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood.
Osteoclasts have one or multiple nuclei?
Multiple
Steps for osteolytic reabsorption
1) osteoclasts form attachments to bone surface, and create closed off space.
2) osteocytes secrete H+ and enzymes = eat away at bone = releasing Ca+, collagen, and phosphate into the blood.
3) osteoblasts move inot the eaten away space and secrete osteoid material = fills in hole.
4) osteoid traps the osteocytes, Ca+, phosphate all inside the mixture.
Actions of PTH
- Increases blood Ca+ and decreases blood phosphate.
- Bone is storage site of Ca and phosphate, under PTH, both move into the blood.
- PTH act on small intestine to absorbs into the blood.
- Both Ca and phosphate filtered in kidney, but under PTH, Ca+ is reabsobed, but phosphate is excreted in urine.
Control of PTH secretion
PTH regulated by blood level of Ca+
Is PTH regulated by either hypothamus or ant pit?
NO
What happened to PTH is Ca+ is
- LOW
- HIGH
LOW Ca+ = increase in PTH
HIGH Ca+ = decrease in PTH
How does the chief cell regulate the release of PTH according to blood levels of Ca+??
Chief cells have Ca+ sensor receptors that detect blood Ca levels and producing PTH accordingly.
Ca+ receptor is G protein linked receptor.
- Gi —> inhibitory G protein that decreases release of second messenger cAMP secretion = decrease in PTH
- Gq —> excitatory G protein, increases second dmessneger IP3 and Ca+
= decrease in PTH
So when Ca in blood to high, these both act to decrease PTH release.
How do the G proteins (Gi and Gq) in the chief cell respond to high levels of Ca+ in blood
Gi = Decrease cAMP = decrease PTH
Gq = Increase IP3 and Ca++ = decrease PTH
How do the G proteins (Gi and Gq) in the chief cell respond to low levels of Ca+ in blood
Gi = increase cAMP = increase PTH
Gq = decrease IP3 and Ca++ = increase PTH
A decrease in Ca++ will cause PTH to
Increase
Synthesis of active vit D
From (dehydrocholesterol) in SKIN + diet —> cholecalciferol (vit D3) —> LIVER (25-OH-cholecalciferol) ——> KIDNEY 1,25 (OH)2 cholecalciferol (calcitriol or Vit. D)
What converts 25-OH cholecalciferol into VIT D or calcitriol ?
1 alpha hydroxylase which is increased by PTH in a (+) manner.
What kind of hormon is vit D?
Steroid hormone
In the liver, is vit D active or inactive
Inactive
In the kidneys is vit D active or inactive?
Active
active form of vit D (calcitonin) is produced, in the presence of enzyme
hydroxoxylase
PTH stimulates the conversion of inactive Vit D to
active form, form the liver to the kidneys.
Is pancreas endocrine or exocrine ?
Both .
- Endocrine is ductless gland
- Exocrine is duct cell+ acinar cells
The endocrine part of the pancrease contains what kind of cells ?
islet of langerhans
Pancreatic hormones (5X)
- glucagon
- insulin
- somatostatin (SS)
- pancreatic polypeptide (PP)
- vasoactive intestinal polypeptide
Types of islet of langerhans cells
- Beta cell (make, store, and secrete hormones)
- alpha cells (fewer)
The following are released by what kind of islet of langerhans cell?
- glucagon
- insulin
- somatostatin (SS)
- pancreatic polypeptide (PP)
- vasoactive intestinal polypeptide
- glucagon —-> ALPHA
- insulin —-> BETA
- somatostatin (SS) —-> DELTA
- pancreatic polypeptide (PP)——> F or PP
- vasoactive intestinal polypeptide -> DELTA
• Diabetes mellitus is when your
pancreas doesn’t produce enough insulin to control the amount of glucose, or sugar, in your blood. Large vol of sweet urine (lots of sugar) made.
• Diabetes insipidus:
Has nothing to do with the pancreases or with blood sugar.
It results in diluted fluid/urine produced in the absence of ADH. No ADH = no water reabsorption
Insulin is the _____ hormone
Glucagon is the _______ hormone
Insulin is the feasting hormone
Glucagon is the fasting hormone
Since insulin is the feasting hormone, in term of nutrient movement, it will
- increase uptake of nutrient after large meal
- decrease passage of nutrient into the blood
Since glucagon is the fasting hormone, in term of nutrient movement, it will
- decrease uptake of nutrient after large meal
- increase passage of nutrient into the blood
insulin influences the movement of blood slicker to different sites form the blood, What are the target sites
- Muscle
- adipose
- liver
What does insulin move from the blood to the muscle ?
Moved glucose (+) to become glycogen for storage, and amino acids (+) to become proteins
What does insulin move from the blood to the adipose tissue ?
Moves glucose (+) and FA (+) to form triG (storage form).
What does insulin move from the blood to the liver ?
Moves glucose to become glycogen (storage), Energy, and FA (FA go on to form triG). Also moved AA inot the liver to produce protein
Is the uptake of glucose into the liver by the influence of insulin (+) or (-)?
Neither, Both the brain (hypothalamus) and the liver can take up glucose in the absence of insulin, cuz diff glucose transporters found in diff tissues.
Insulin then effects the end products after having a large meal.
Actions of insulin summary (LIVER)
- INC. glycogenesis (synthesis)
- INC. glycolysis (formed from ATP
- INC. fat synthesis
- DEC. fat breakdown
- INC. proteins synthesis
- DEC. protein breakdown
- DEC. glycogenolysis (breakdown)
- DEC. gluconeogenisis (formed form carbohydrate source)
- DEC. ketogenesis (form ketobodies form broken down fats)
Actions of insulin summary (MUSCLE)
- INC glucose uptake
- INC glycogenesis
- DEC glycogenolysis
- INC amino acid uptake
- INC protein synthesis
- DEC protein breakdown
Actions of insulin summary
ADIPOSE TISSUE
- INC glucose uptake
- INC glycolysis
- INC FA uptake
- INC fat synthesis
- DEC fat breakdown
Mechanism of insulin
Insulin hitting receptor in outer region, causes conformational changes which then cause activation of enzyme (tyrosine kinase) in the inner region of the receptor.
When tyrosine becomes active, causes changes in many molecules inside the cell, which are then glued together to form IRS (insulin receptor substrate).
What does the IRS effect?
- transport systems
- enzyme activity
- gene expression
Transport of glucose mechanisms
1) Secondary Active Transport (uphill)
- SGLT1
- SGLT2
2) Facilitated transport (downhill)
- GLUT1
- GLUT2
Which GLUT transporter is sensitive to insulin?
GLUT 4
SGLT is a
Na+/glucose cotransporter
GLUT is a
Glucose transporter
Action of insulin: glucose uptake
- if there’s no insulin
No action occurs as it uses GLUT 4 transporters, which re insulin dependant and require for it to be present to be activated
Action of insulin: glucose uptake
- if there’s plus insulin (no excercise)
Translocation of vesicle occurs.
- insulin binds to insulin recpetors = forms IRS = takes vesicle with glucose receptors on it to embed to the outside of the cell = all receptors on vesicle are not on the surfaces of the cell = increase the uptake of glucose !
Where does glucose come from?
1) short term?
2) long term?
3) longer still ?
1) short term: glucose readily available after any meal.
2) long term lover glycogen stores are broken down
3) longer still “new” glucose made form non-carbohydrate sources, like amino acids (gluconeogensis)
gluconeogensis
Production of glucose from non carbohydrate sources, like amino acids
Main site of action of glucagon is the
Liver
High insulin leads to
Hypoglycaemia
High glucagon leads to
Hyperglycaemia
Actions of insulin in LIVER
Glycogenesis —> INC Glycogenolysis —> DEC Glycolysis —>INC Glyconeogenesis —>DEC Lipogenesis —> INC Lipolysis —> DEC Ketogenesis —>DEC Protein synthesis —>INC Proteolysis —> DEC
Actions of glucagon on the LIVER
Glycogenesis —> DEC Glycogenolysis —> INC Glycolysis —>DEC Glyconeogenesis —>INC Lipogenesis —> DEC Lipolysis —> INC Ketogenesis —>INC
Other pancreatic hormones
1) amylin
2) somatostatin
3) pancreatic polypeptide
4) vasoactive intestinal polypeptide
Amylin
- secreted w insulin
- decrease food intake
- decrease rate of gastric emptying
- decrease glucagon secretion
Somatostatin
- inhibiting release of insulin and glucagon
Pancreatic polypeptide
- decrease pancreatic enzyme secretion
- inhibit gallbladder contraction
Vasoactive intestinal polypeptide
- increase pancreatic water secretion= diarrhea
Glucose sensing
Glucose enters via GLUT2 ( NOT influenced by insulin) = Metabolized glucose increases the ratio of ADP:ATP = K+ channels close (atp sensitive), = K+ inside the cell increases = depolarization of outer membrane = opening of voltage gated Ca+ Channels = more Ca+ inside the cell = Insulin stored in the granules then is released by Ca+
—> Insulin then lowered blood glucose by taking it into the cell. The opposit effect is true. Low glucose = more insulin goes into the cell.
Why is glucagon secretion increased by amino acids?
1) carbohydrate-rich meal
—> increase blood glucose
Increase blood glucose (effects insulin and glucagon separately) ——>
- Increase insulin = Decrease blood glucose
- Decrease glucagon - Decrease blood glucose
blood glucose levels have been restored back to normal*
Why is glucagon secretion increased by amino acids?
1) protein-rich meal
—-> Increase amino acids in blood
Increase amino acids in blood (effects insulin and glucagon separate) —>
- Increases insulin = Decrease blood glucose
- Increase glucagon = Increase blood glucose
blood glucose remains +/- constant after protein rich meal cuz they cancel each other out
Role of nutrients in blood:
- Increased level of glucose
- Increased levels of some amino acids
Secretion of insulin is:
- Increased level of glucose = Increased
- Increased levels of some amino acids = Increased
Role of nutrients in blood:
- Increased level of glucose
- Increased levels of some amino acids
Secretion of glucagon is:
- Increased level of glucose = Decreased
- Increased levels of some amino acids = Increased
- Role of hormones from GIT:
(“incretins”). eg GLP-1, GIP, CCK, secretin…
Secretion of insulin is
(“incretins”). eg GLP-1, GIP, CCK, secretin… = Increased
- Role of hormones from GIT:
(“incretins”). eg GLP-1, GIP, CCK, secretin…
Secretion of Glucagon is
(“incretins”). eg GLP-1, GIP, CCK, secretin… = depends on which incretin
- Role of local islet hormones:
- Somatostatin
- Insulin
- Glucagon
Secretion of insulin will:
- Somatostatin = decreased
- Insulin = X
- Glucagon = increased
- Role of local islet hormones:
- Somatostatin
- Insulin
- Glucagon
Secretion of glucagon will:
- Somatostatin = decreased
- Insulin = decreased
- Glucagon =. X
- Role of nerves:
- Parasympathetic (ACh)
- Sympathetic
Secretion of insulin will:
- Parasympathetic (ACh) = increased
* Sympathetic. = deadens on type of receptor)
- Role of nerves:
- Parasympathetic (ACh)
- Sympathetic
Secretion of glucagon will:
- Parasympathetic (ACh) = X
* Sympathetic. = increased
Too much insulin causes:
- insulin securing tumour
- insulin overdose
Consequences of too much insulin
- lower blood glucose levels (hypoglycaemia)
- feel hungry
brain requires glucose: - inc sympathetic activity (sweating)
- inc production in glucagon and adrenaline
Diabetes mellitus TYPE 1:
- autoimmune disease
- beta cells destroyed
- insulin deficient
- mainly in young ppl
- 5-10% of all DM cases
Diabetes mellitus TYPE 2:
- increased resistance to insulin
- initial increase in insulin secretion
- relative insulin deficient (linked to obesity)
- more in adults
- 90-95% of all DM cases
Problems with diabetes mellitus
- low blood glucose levels (hyperglycemia)
- tissues are starving
Effect of diabetes mellitus to insulin dependant tissue
Glucose uptake will decrease if insulin is deficient for tissues that are insulin dependant.
Effect of diabetes mellitus to insulin independent tissue
Glucose uptake will increase if insulin is deficient for tissues that are insulin independent (move down conc gradient)
Diabetes mellitus TYPE 1 treatments
Inability to produce insulin
- inject insulin
- pancreatic transplant
- islet cell transplant
- gene therapy
- increase growth of new islet cells
Diabetes mellitus TYPE 2 treatments
Increased resistance to insulin
- dietary control and excersice
- drugs that’s increase insulin secretion and or response to insulin
