Endocrine System Flashcards
When homeostasis is out of balance, the endocrine system releases hormones into the blood supply to restore balance. What are the three classes of hormone molecules?
Amines/amino acids
- Thyroid hormones that bind to nuclear receptors which regulate gene transcription.
- Adrenaline/noradrenaline bind to GPCR receptors responsible for intracellular signalling.
Peptides/proteins
- Insulin binds to the receptor tyrosine kinase causing an intracellular signal via the P cascade.
Steroids
- Glucocorticoids bind to nuclear receptors - transcription factors.
What are the different glands of the endocrine system?
Parathyroid - PTH stimulated by calcium levels.
Pancreas - insulin and glucagon - stimulated by glucose levels.
Gonads - androgens in males, oestrogena nd progesterone in females.
Adrenals - medulla produces adrenaline and noradrenaline whilst cortex produces cortisol, corticosterone, cortisone, aldosterone and androgens.
Thyroid - thyroxine, triodothyronine and calcitonin.
Pituitary - anterior produces ACTH, TSH, GH, PRL, MSH, FSH and LH, posterior produces ADH and oxytocin.
Hypothalamus - ADH, oxytocin.
Heart - atrial natruiretic peptide.
Kidney - renin, erythropoitin.
Digestive tract - gastrin, CCK, secretin.
Pineal (in the brain) - melatonin - this establishes 24h circadian rhythm.
What are endocrine glands?
Ductless and richly vascularized glands that secrete messengers directly into the circulation. (Exocrine glands excrete substances onto an epithelial surface by a duct.
What are the different cell signalling methods?
Intracrine - release products which regulate something within cell.
Autocrine - release products which act upon itself.
Paracrine - release products which act on neighbouring cells.
Endocrine - release products which act on distant target cells.
Neuroendocrine - neurons release products which act on distant target cells.
What are the 4 broad areas under important regulation of endocrine organs?
Reproduction
Growth and development.
Maintenance of internal environment.
Regulation of energy.
What are hormones?
Chemical messengers released by glands into the circulation that bind to specific high affinity recognition sites/receptors on/in target cells.
- A single hormone may have different tissue-specific effects.
A single function may be regulated by different hormones.
Some hormones directly target target tissue while others trigger the release of additional hormones which work on target cells.
The catecholamines adrenaline and noradrenaline are derived from tyrosine - explain the synthesis of these hormones.
Tyrosine is converted to L_DOPA by tyrosine hydroxylase. Dopa decarboxylase then breaks this down into dopamine. Dopamine B-hydroxylase then converts this to noradrenaline. Adrenaline is then produced from the breakdown of noradrenaline by the enzyme phenylethanolamine N-methyl transferase.
The thyroid hormones thyroxine and triiodothyronine are derived from tyrosine - explain the synthesis of these hormones.
Tyrosine goes to monoiodotyrosine (MIT) which then goes to di-iodotyrosine (DIT).
2 molecules of DIT turns into thyroxine (T4).
One molecule of MIT and one molecule of DIT produce triiodotyrosine (T3)
What are steroid hormones derived from?
Cholesterol to give the tetra planar structure - hence why some fat is required in the diet in order to provide the body with cholesterol for the synthesis of steroid hormones.
What are the steroid hormones derived from cholesterol?
Adrenal hormones (cortisol and aldosterone), sex hormones (testosterone and estradiol) and vitamin D.
How is progesterone and aldosterone derived from cholesterol?
Cholesterol - pregnenalone - progesterone - corticosterone - aldosterone.
How is cortisol derived from cholesterol?
Cholesterol - pregnenalone - 17hydroxyprogesterone - cortisol.
How is adrostenedione derived from cholesterol?
Cholesterol - pregnenalone - dehydroepiandosterone - androstenedione.
What are peptides?
Short amino acid chains e.g. ADH and oxytocin.
Polypeptides e.g. insulin and prolactin.
What hormones are proteins?
TSH, FSH and GH.
How are proteins synthesised?
Proteins are synthesised in the nucleus, rough endoplasmic reticulum and golgi apparatus. They are then released by exocytosis as prohormone or hormone into the bloodstream.
What are hormone receptors?
For a cell to respond to a hormone it must have receptors for that hormone. The number of receptors for a hormone can increase or decrease. Hormone receptors may be cell surface receptors or intracellular receptors.
What are cell surface receptors?
Rcepetors that activate an intracellular signalling cascade - e.g. GPCR (for adrenaline) and RTK (for insulin).
What are intracellular receptors?
Activate gene transcription e.g. carrier proteins in blood activated by corticosteroids.
Whats a negative feedback loop?
Stop the hormone release from the endocrine cell once the target cell has been successfully activated.
Whats a positive feedback loop?
Increase the release of hormone once the target cell is reached.
What are the different endocrine disorders?
Hyposecretive, hypersecretive, hyporesponsive and hyperresponsive.
How can a tumour affect endocrinology?
A tumour is uncontrolled proliferation of cells - an endocrine tumour could therefore lead to hypersecretion.
Blood glucose levels are usually around 4.5 - 5.5. What regulates this?
When glucose levels rise, pancreas releases insulin which stimulates uptake of glucose into the liver, muscle and adipose tissue.
When glucose levels drop, pancrease releases glucagon which stimulates gluconeogenesis and glyogenolysis.
How are glucagon and insulin counterregulatory hormones?
They have opposite effects - glucagon is catabolic whilst insulin is anabolic.
Explain the biology of the pancreas.
The pancreas is located by the duodenum and has a pancreatic duct running through it. It is composed of acinar cells and islet of langerhans - this is a ball of endocrine cells. The vast majority are beta cells which produce insulin but a ring of alpha cells surround these, responsible for producing glucagon.
delta cells produce somatostatin which suppresses GI motility and release of insulin and glucagon.
What transports glucose in the blood ?
Glut 4.
Whats the structure of insulin?
Insulin is composed of 2 biologically active peptides and one active chain - the A chain and B chain are active and joined by two disulfide bonds, the C peptide is inactive.
How is insulin degraded?
By insulinase in the liver and kidneys - it has a half life of 6 minutes.
Whats an insulin receptor?
An insulin receptor is a type of tyrosine kinase in which insulin binds to the extracellular a-subunits.
How is insulin involved in carbohydrate metabolism?
Insulin facilitates the entry of glucose into muscle and adipose tissue and stimulates the liver to store glucose as glycogen - in turn this leads to a decreased concentration of glucose in the blood.
How is insulin involved in lipid metabolism?
Insulin promotes the synthesis of fatty acids in the liver (when glycogen saturated) leading to an increase in lipoproteins in circulation to release fatty acids which are used in triglyceride synthesis in the adipocytes.
Inhibits the breakdown of fat in adipose tissue.
Promotes glycerol synthesis from glucose and increase triglyceride synthesis.
How do we know that insulin is involved in muscle glucose uptake?
If insulin is present, when the extracellular glucose levels increase, so will the intracellular glucose levels hence demonstrating that insulin stimulates the uptake of glucose in muscle.
Explain the process of stimulation of glucose uptake by insulin.
When extracellular glucose levels rise, insulin is released which binds to insulin receptor tyrosine kinase on the cell, this stimulates the storage microsome of the cell to release glucose transporters hence increasing the uptake of glucose into the cell.
What do insulin sensatizing drugs do?
Increase glucose uptake by skeletal muscle and reduce gluconeogenesis in the liver.
Explain the affects of insulin on muscle.
Insulin promotes the uptake of glucose into the muscle - this then gets converted to glucose-6-p which then gets converted to glycogen and stored. The glucose-6-p can also be converted into lactic acid to produce energy - the lactic acid then goes to the liver.
Insulin also promotes the uptake of amino acids by muscle then get converted into structural proteins.
What affect does insulin have on the liver?
Insulin increases the release of glucokinase (an enzyme facilitating the phosphorylation of glucose into glucose-6-phosphate) whilst decreasing levels of glucose-6-phosphatase (an enzyme that hydrolyses glucose-6-phosphate into glucose) hence overall promoting the uptake of glucose into liver cells and converting it into glucose-6-phosphate.
The glucose-6-phosphate can then be converted to glycogen - this is promoted by insulin triggering the release of glycogen synthetase.
The glucose-6-phosphate can also undergo a series of reactionsto produce lipoproteins which then get deposited in adipose tissue. (glucose-6-p - pyruvate - acetylcoa - fatty acids)
The liver cells convert lactic acid to pyruvate, amino acids to acetylcoa and they take up fatty acids. All of these undergo reactions to produce lipoproteins which then get taken up by adipose tissue.
What are the affects of insulin on adipose tissue?
Insulin increases the uptake of glucose and amino acids by adipose tissue which both undergo a series of reactions to finally produce triglycerides.
Alternatively the glucose absorbed can be converted into glycerol phosphate and then triglycerides.
The adipose tissue also takes up lipoproteins from the liver which get converted to fatty acids by the enzyme lipoprotein lipase (stimulated by insulin) and then converted into triglycerides.
What is glucagon?
A peptide hormone released from alpha cells of the islets of LAngerhans in the pancreas when blood glucose falls. It stimulates glucogenolysis, gluconeogenesis and increases the breakdown of fats (into ketones, an alternative energy source).
What is hypoglycaemia?
A condition where blood glucose levels are abnormally low and the uptake of glucose by glucose dependent tissue is not adequate to maintain tissue function. The CNS becomes very sensitive causing slurred speech, impaired vision, confusion, mood change etc.
There is also overactivity of the ANS causing sweats shakiness and hunger.
Whats diabetes mellitus?
Diabetes is characterised by hyperglycaemia.
Type 1 is incurable and insulin dependent.
Type 2 reuires lifestyle changes and medication.
Gestational diabetes can occur in pregnancy.
Whats the musculoskeletal system?
The skeleton, muscles and accessory tissues allowing locomotion and articulation
What are the 2 main types of tissue in the skeleton?
Bone - a compact exterior and a trabecular interior - encased with fibrous peristoneum.
Cartilage:
- hyaline = growth plate, joint surfaces, temporary scaffold.
- fibrocartilage = intervertebral discs, minisci in joint spaces - this is not encased in fibrous peristoneum.
- elastic = external ear, epiglottis larynx.
Whats the function and composition of bones?
Bones provide support, protection, muscle attachment, mineral reservoir, hematopoiesis, lipid storage and endocrine function.
They are composed of 65% minerals, 5% proteoglycans and 30% type 1 collagen.
What are the cell types of bone?
Osteoblasts (bone forming cells), osteocytes (most abundant) and osteoclasts (bone resorbing).
Whats the function and composition of cartilage?
Cartilage is required for none formation, growth of long bones, articulating joint surface.
They are composed of 65% type 2 collagen, 20% proteoglycans, 10% glycosaminoglycans and 5% glycoproteins.
What are the cell types of the cartilage?
Chondroblasts and chondrocytes.
The bones make up 2 skeletons, what are they?
Axial skeleton - bones of skull, vertebral column and ribs.
Appendicular skeleton - bones of limbs pelvis scapula and clavicle.
Bones can be classified by shape, what are these classifications?
Long bones, short bones, flat bones and irregular bones.
Bone is a living metabolically active tissue consisting of a protein (collagen) matrix upon which calcium salts are deposited. Describe the structure of long bone.
The long bone is divided into the epiphyses (ends) and the shaft (diaphysis). The portion between the epiphyses and the shaft is called the metaphysis - this contains the epiphyseal growth plate of actively proliferating cartilage during growth. There is a nutrient artery running through long bone.
Whats the epiphysis?
The epiphysis is the end of the long bone - it has spongy bone and red bone marrow within it.
Whats the diaphysis?
The shaft - its coated in periosteum.
Whats the medullary cavity?
The medullary cavity is the central cavity of the bone marrow shafts where red/yellow bone marrow is stored.
Whats the endosteum?
The endosteum is a thin vascular membrane of connective tissue lining the inner surface of the medullary cavity.
Whats the periosteum?
The periosteum coats bones - it contains an outer fibrous layer and an inner osteogenic layer. There are periosteal veins and arteries along the periosteum which branch into the bone via perforating canals - these blood vessels run through the bone in central canals alongside lymphatic vessels.
Whats the microanatomy of the trabecular (spongy bone)?
A lining of osteoblasts with a few osteoclasts - inclosed is osteocytes bound with lamellae (cells) joined by canaliculi (junctions)
What are the cells of the bone?
Osteogenic cells develop into osteoblasts (which form bone matrix) these then develop into osteocytes (which maintain bone tissue).
Osteoclasts have functions in resorption, the breakdown of bone matrix.
Describe the process of ossification (bone development)
The skeleton develops from embryonic mesenchyme - these are loosely packed unspecialised skells in a gel like matrix, derived fromthe embryonic mesoderm.
The mesenchymal cells migrate and form condensations - these are cellular aggregates that prefigure sites of bone developement.
- The bone can form directly within the condensation - this is intramembraneous ossification.
- A cartilage template can form within the condensation which is subsequently replaced with bone - this is endochondrial ossification.
Describe intramembraneous ossification.
Developement of ossification centre, calcification, formation of trabeculae, development of the periosteum.
Describe endochondrial ossification.
1 - Chondrocytes at the centre of the growing cartilage model enlarge and then die as the matrix calcifies.
2 - Newly derived osteoblasts cover the shaft of the cartilage in a thin layer of new bone.
3 - Blood vessels penetrate the cartilage. New osteoblasts form a primary ossification centre.
4 - The bone of the shaft thickens and the cartilage near each epiphysis is replaced by shafts of bone.
5 - Blood vessels invade the epiphysis and osteoblasts form secondary centres of ossification.
Whats the epiphyseal plate?
The epiphyseal plate is the location in which growth occurs. Chondrocytes in the epiphyseal plate divide and enlarge and calcified cartilage is replaced by bone - the thickness of the epiphyseal plate remains unchanged but bone is added to the diaphysis.
Explain the process in the epiphyseal plate.
1 - New cartilage is produced on the epiphyseal side of the plate as the chondrocytes divide and form stacks of cells.
2 - Chondrocytes mature and enlarge.
3 - Matrix is calcified and chondrocytes die.
4 - The cartilage on the diaphyseal side of the plate is replaced by bone.
Whats apposition?
The post natal growth of width - the outer bone gets pushed wider (bone deposited by osteoblasts) whilst the bone resorbed by osteoclasts moves outwards.
Explain how bone is maintained.
Resting bone surface - preosteoclasts. Resorption - active osteoclasts. Reversal - mononuclear cells, preosteoblasts. Bone formation - osteoblasts. Mineralization - osteocytes.
There is no net change in bone mass, the remodelling process just allows bones to adapt to changes in mechanical loading and retain its structural integrity.
