Endocrinology- pancreas, adrenals and thyroid

Question 1

What percentage of cells in the pancreas are small clusters of glandular epithelial cells called acini? What % are Islet of Langerhans cells? What do they do?

Answer 1

98-99%
1-2%
Make and release several peptide hormones into the portal vein

Question 2

3 pancreas cell types and what do they produce? Proximity to each other?

Answer 2

Delta cells- somatostatin, alpha cells- glucagon, Beta cells- insulin
Are close to allow for cell-to-cell communication

Question 3

What is insulin? What does insulin do?

Answer 3

A 51 amino acid PP
It reduces glucose output by the liver, increases storage of glucose, fatty acids and amino acids and stops the breakdown of fat and muscle

Question 4

What is glucagon? What does it do? What is somatostatin?

Answer 4

29 amino acid peptide
Mobilises glucose, fatty acids and amino acids from stores, stimulates breakdown of fat and muscle
An inhibitor

Question 5

What is the precursor of insulin? What does it contain? What links the A and B chains? What occurs when insulin is being produced?

Answer 5

Proinsulin
The A and B chains of insulin joined by the C peptide
Disulphide bridges
Proinsulin is cleaved from its C peptide and then used to make insulin which is then packaged into insulin secretory granules

Question 6

Does synthetic insulin contain C peptide? What can this be used for? What do Beta cells on their cell surface membrane?

Answer 6

No
To determine whether insulin release is natural or synthetic- if high C peptide in blood, then is natural
GLUT2 glucose transporters

Question 7

What type of receptor is GLUT2? What happens when glucose levels are high?

Answer 7

A low affinity receptor- only binds when there is a high conc of glucose
GLUT2 activates, allowing glucose into the beta cell

Question 8

Once inside the beta cell, hexokinase breaks down glucose into what? This process uses what and releases what? The ATP reformed then binds to what?

Answer 8

Glucose-6-phosphate
Uses an ATP and releases an ADP–> back into ATP
A K+ ATP channel on the cell membrane of the beta cell and closes the channel

Question 9

What happens to the beta cell membrane if the K+ ions cannot leave? This results in the opening of what? What do they bind to?

Answer 9

It depolarises
Voltage-gated Ca2+ channels so Ca2+ ions can diffuse into the cells via diffusion
The insulin secretory granules–> moves to cell membrane and fuses, to release contents via exocytosis

Question 10

What happens when insulin binds to insulin receptors on cell membranes of muscle and fat cells?

Answer 10

Intracellular signalling cascade–> mobilisation of intracellular GLUT4 vesicles to cell membrane–> more glucose diffusion into cells

Question 11

What is the first phase response to rising glucose levels? When would the second phase be initiated?

Answer 11

Rapid release of stored insulin

If glucose levels remain high- takes longer than first phase due to more insulin needing to be synthesised

Question 12

What is conversion of glucose–> glycogen called? What does the liver make in the long term?

Answer 12

Glycogenesis

Lipogenesis- make triglyceride

Question 13

Where are primary glucose sensors found? Where are glucose sensors also found? Where are inputs from? What sensory cells in the gut also stimulate insulin release from pancreas?

Answer 13

Pancreatic Islets of Langerhans
In the medulla, hypothalamus and carotid bodies
Eyes, nose, taste buds and gut, all involved in regulating food
Incretins

Question 14

What are incretins secreted by? What are the 2 major incretins?

Answer 14

Endothelial cells in the GI tract in response to eating- amplifies the insulin response to glucose
Glucagon- like peptide 1(GLP-1)
Glucose- dependent insulinotropic peptide (GIP)

Question 15

Postpandial glucose levels are regulated by what 2 main mechanisms, of which they are enhanced by incretins?

Answer 15

1. Rising plasma glucose stimulates B-cells to secrete insulin
2. Plasma glucose inhibits glucagon secretion by pancreatic A-cells

Question 16

In the fasting state, where does the glucose come from? Where is it delivered to? Levels of what are low? Muscles use what for fuel therefore?

Answer 16

All glucose comes from the liver from glycogenolysis–> gluconeogenesis from 3 carbon precursors e.g. lactate, alanine and glycerol
Insulin independent tissues such as brain and red blood cells
Insulin levels- use free fatty acids for fuel

Question 17

Rising glucose levels after feeding stimulates what? What % of ingested glucose goes to the liver and the periphery (mostly muscle) This helps to do what? Excess glucose covered to what? High insulin levels suppress what?

Answer 17

5-10 fold increases in insulin secretion and suppression of glucagon
40%–> liver and 60%–> periphery
Replenish glycogen stores in liver and muscle
Fats
Lipolysis, resulting in levels in non-esterified fatty acids to fall

Question 18

Insulin acts on various cells to do what?

Answer 18

Accelerate facility diffusion of glucose into cells, speed up conversion of glucose into glycogen, increase amino acid uptake and protein synthesis, speed up fatty acid synthesis, slow glycogenolysis and slow gluconeogenesis

Question 19

What 5 hormones does the adrenal cortex secrete? 3 layers of the cortex?

Answer 19

Aldosterone, cortisol, corticosterone, dehydroepiandrosterone (DHEA) and androstenedione
Zona glomerulus- mineralocorticoids, zona fasciculata- glucocorticoids i.e. cortisol and small amounts of androgens and zone reticularis- androgens (sex hormones) and small amounts of cortisol

Question 20

Mnemonic for hormones secreted by adrenal cortex layers? All three zones produced different types of steroids under what steroid band? Negative feedback is important for what steroid types?

Answer 20

GFR- Makes Good Sex
Corticosteroids
Glucocorticoids and mineralocorticoids

Question 21

2 hormones secrete by adrenal medulla belonging to catecholamine family? Causes the cortex to do what? How do they respond to stress? Under what control?

Answer 21

Adrenaline and noradrenaline- to secrete further hormones
Dilates the pupils, increase glycogenolysis, increases lipolysis, increase sweating, increases HR and inhibits insulin release
Sympathetic control

Question 22

Cholesterol is the precursor for what steroid group? 4 features of corticosteroids?

Answer 22

All corticosteroids
Lipid soluble, bind to specific intracellular receptors, alter gene expression directly/ indirectly and exact action depends on the structure

Question 23

Role of mineralocorticoids? Most predominant produced? Important for what? Only issues with what will affect aldosterone release?

Answer 23

To regulate body electrolytes (minerals)
Aldosterone- salt balance and for blood pressure in renin-angiotensin aldosterone system
The kidneys- not hypothalamus/ pituitary

Question 24

Most predominant glucocorticoid made in zona fasiculata and zona reticularis? Facilates bodies responses to what? Examples of threat triggering increase in cortisol?

Answer 24

Cortisol
Stress and regulation of the immune system
Physical trauma, prolonged exposure to cold, prolonged heavy, exercise, infection, shock, decreased oxygen supply, sleep deprivation, pain and emotional stress

Question 25

Stress is detected and transmitted neurally to what? This stimulates the release of what hormone? This hormone is carried by what to where? This stimulates release of what?

Answer 25

Hypothalamus
Corticotropin-releasing hormone (CRH)
Hypothalami-hypophyseal portal vessels to anterior pituitary
Adrenocorticotropic hormone (ACTH)

Question 26

ACTH circulates in the blood and travels where to stimulate release of what? Stimulation of ACTH stimulated by what also?

Answer 26

Adrenal cortex to stimulate cortisol

Vasopressin- increases in response to stress too–> anterior pituitary to stimulate ACTH release

Question 27

How is cortisol distributed in circulation?

Answer 27

90% bound to corticosteroid-binding globulin (CBG), 5% bound to albumin, 5% free- only free cortisol is bioavailable

Question 28

Actions by cortisol in non stress situations?

Answer 28

Permissive reactivity to adrenaline and noradrenaline on smooth muscle around blood vessels, maintain cellular concentrations of enzymes in metabolic homeostasis- increase hepatic glucose production preventing decrease below normal

Question 29

Further actions by cortisol in non-stress situations?

Answer 29

Inhibits production of leukotriene and prostaglandins- involved in inflammations, stabilises lysosomal membranes in damaged cells- prevent release of proteolytic contents, reduces capillary permeability in injured areas- surpasses growth and function of immune cells e.g. lymphocytes

Question 30

Immune system made do what when cortisol is absent? 2 actions during fetal and neonatal life?

Answer 30

Over-react to minor infections
Proper differentiation of numerous tissues and glands e.g. brain, adrenal medulla, intestines and lungs, production of surfactant

Question 31

In stressful situation what does cortisol do?

Answer 31

Increases ability of vascular smooth muscle to contact i.e. vasoconstriction in response to adrenaline, improving cardio performance
Reduces inflammatory response to injury/ infection- increased cortisol during stress dampens immune responses, inhibits non essentials too e.g. reproduction and growth

Question 32

Chronic stress can lead to what?

Answer 32

Decreases in bone density, immune function and reproductive fertility due to increased catabolism than is elicited from increase cortisol

Question 33

Main androgens produced in zona reticularis? Most abundant adrenal steroid? Type of strength? Production of androgens regulated by actions of what?

Answer 33

DHEA and androstenedione- latter major source of androgens in women
DHEA
Androstenedione little stronger, 1/10th strength of testosterone- can be converted in peripheral tissues e.g. testes
ACTH secreted by anterior pituitary

Question 34

Adrenal medulla is part of what nervous system? % of production and secretion noradrenaline/ adrenaline? Normal catecholamine synthesis dependent on what?

Answer 34

Autonomic nervous system
20% noradrenaline and 80% adrenaline
High local cortisol levels- permissive effect

Question 35

Effects during fight/ flight response?

Answer 35

Gluconeogenesis, lipolysis in adipose tissues, tachycardia and cardiac contractility, redistribution of circulating volume, more adrenaline (vasoconstriction) and less noradrenaline released

Question 36

Alpha receptors have higher affinity for what? Beta receptors have higher affinity for what?

Answer 36

Noradrenaline

Adrenaline

Question 37

Thyroid glands located in anterior neck between what vertebrae? Behind what muscles? Wraps around what? Inferior to what?

Answer 37

C5-T1 vertebrae
Sternohyoid and sternothyroid muscles
Cricoid cartilage and superior tracheal rings
Thyroid cartilage of the larynx

Question 38

Thyroid gland innervated by what? Hormone release controlled by what? 2 iodine- containing molecules produced by gland?

Answer 38

Branches from sympathetic trunk
Pituitary gland
Thyroxine- T4(contains 4 iodines) and triiodothyronine- T3 (contain 3 iodines)

Question 39

T4 is converted into T3 by what enzymes where? Levels of both in the blood?

Answer 39

Deiodinases in target cells

T4 higher in blood but T3 is major thyroid hormone

Question 40

In the thyroid gland are numerous what? What occurs during iodide trapping? Colloid contains large amounts of protein called what?

Answer 40

Follicles- enclosed sphere of follicular cells surrounding core of protein-rich colloid
Circulating iodide is actively cotransported with Na+ ions across basolateral membrane of follicular cells, Na+ is then pumped back out of the cells via Na+/K+-ATPases
Thyroglobulin

Question 41

What happens to the iodide once inside the colloid? Under the action of what enzyme? Tyrosine binding to 1 iodine molecule called what? Binding to 2 iodine molecules?

Answer 41

It is rapidly oxidised to iodine which bind to tyrosine residues on the thyroglobulin molecules
Thyroid peroxidase
Monoiodotyrosine (T1)
Diiodotyrosine (T2)

Question 42

What happens when the thyroid is stimulated to produce thyroid hormone? For thyroid hormone to be secreted into the blood what needs to happen?

Answer 42

The T1 and T2 molecules are cleaved from their tyrosine backbone (still attached to thyroglobulin) and join to create T3 or T4
Extensions of the colloid-facing membranes of the follicular cells engulf portions of the colloid(with iodinated thyroglobulin) by endocytosis

Question 43

The iodated thyroglobulin is brought into contact with what? What happens to the thyroglobulin to release the T3 and T4? How much iodinated thyroglobulin within follicles?

Answer 43

Lysosomes in the cell interior
Proteolysis- T3 and T4 then diffuse out of follicular cells into interstitial fluid and from there into blood
Enough to provide thyroid hormone for several weeks even in absence of dietary iodine- unique to endocrine glands

Question 44

Actions of follicular epithelial cells stimulated by what? TSH is stimulated by what? Control mechanism of TSH production?

Answer 44

TSH from anterior pituitary
TRH released by the hypothalamus
Negative feedback action T3 and T4 on anterior pituitary

Question 45

What more than stimulating T3 and T4 does TSH do? What occurs to thyroid cells if greater TSH than normal? Enlarged thyroid gland called what?

Answer 45

Increases protein synthesis in follicular cells, increases DNA replication and cell division and increases amount of RER and other cell machinery needed by follicular cells for protein synthesis
Hypertrophy
Goiter

Question 46

Receptors for thyroid hormone found where? Acts by doing what? Overall actions?

Answer 46

In nuclei of most cells in body- actions of T3 are widespread and affect many organs and tissues
By inducing gene transcription and protein synthesis
Increases metabolic rate and important in brain maturation

Question 47

What does T3 stimulate in the body (metabolically)? Energy created used for what?

Answer 47

Carbohydrate absorption from SI and fatty acid release from adipocytes–> energy for high metabolic rate
To support activity of Na+/K+-ATPases- enzymes stimulated by T3

Question 48

Increased activity of Na+/K+-ATPases due to T3 increases what also? T3 up-regulates what receptors in the body? Symptoms of overactive thyroid?

Answer 48

Heat- essential for body temp homeostasis
Beta-adrenergic receptors for adrenaline in many tissues e.g. heart and nervous system
High HR, anxiety, nervousness

Question 49

T3 is needed for production of what hormone? Also helps in development of what during fetal life? Also needed for what?

Answer 49

Growth hormone from anterior pituitary
Axon terminals, synapses, dendrites and dendritic extensions and myelin
Proper nerve and muscle reflexes and normal cognition in adults