Endocrinology and cell signalling Flashcards Preview

Block 1 > Endocrinology and cell signalling > Flashcards

Flashcards in Endocrinology and cell signalling Deck (62):
0

What disease will someone with Hypoadrenalism suffer from?

Addisons

1

What is Cushsings syndrome?

Excess glucocorticoids - cortisol

2

Name 4 hormones which are synthesised in the Anterior Pituitary gland

Growth hormone
Follicle stimulating hormone
Leutinising hormone
Thyroid stimulating hormone
Adrenocorticotrophic hormone
Prolactin

3

Give 5 functions of cortisol

Maintain muscle function
Decrease bone function
Decrease connective tissue
Inhibit inflammatory and immune response
Maintain cardiac output
Facilitate maturation of foetus
Increase glomerular filtration
Modulate emotional tone

4

List 3 things which could cause excess hormone production

Neoplasm in endocrine gland
Ectopic production
Hyperplasia of endocrine tissue

5

List 4 things which could cause a deficit in hormone production

Trauma
Disease
Autoimmune attack of gland
Under development of gland

6

Give 2 examples of peptide hormones

Parathyroid
ACTH

7

How are steroid hormones synthesised?

Hydrolysis of esters or uptake of cholesterol
Cholesterol converted to pregnenalone by C P450 in mitochondria
Pregnenalone is processed in smooth ER
Then diffuses out of the cell

8

Which cells generally have autocrine signalling as a common feature?

Tumour cells
Production of growth hormones perpetuates proliferation

9

What 3 effector mechanisms can be used to change cell behaviour?

Alter gene transcription
Alter ion balance across membrane
Alter level of enzyme activity

10

Which residues does phosphorylation mostly occur on?

Serine and threonine

11

Describe the phototransduction pathway?

Photon binds to rhodopsin receptor
Transducin mediator
cGMP phosphodiesterase converts cGMP to GMP
Closes Na channels and changes membrane potential

12

In order for a molecule to diffuse across a membrane, what must occur?

Solute must dissolve in the hyrophobic core of the membrane

13

What are GLUT transporters?

Passive transporter
Glucose transported into cell and then converted to glucose 6 phosphate in order to maintain concentration gradient

14

What is an endocrine gland?

Gland which secretes hormones directly into the blood stream

15

What is an exocrine gland?

Gland which secretes chemicals via a duct

16

What tissues have endocrine function?

Heart
Gut
Adipocytes
Placenta

17

What are 3 types of hormones?

Polypeptides
Steroids
Modified amino acids

18

Describe steroid hormone synthesis

Hydrolysis of esters and cholesterol uptake
Conversion of cholesterol to pregnenalone in mitochondria
Processing of pregnenalone in smooth ER
Diffusion from the cell

19

Describe protein and peptide hormone synthesis

Gene transcription
Translation on rough ER
Post translational modification in Golgi
Packaging into secretory vesicles which are stored and ready for release when signalled

20

How is parathyroid hormone synthesised?

Peptide hormone
Pre-pro-PTH with signal, pro, biologically active and c terminal fragments
Cleaved twice to form active PTH

21

How is ACTH formed?

Peptide hormone
Formed as propriomelanocortin which is cleaved into ACTH, amino terminal fragment and B-lipotropin

22

Give an example of a tyrosine kinase receptor system

Insulin

23

What is the only example of a positive feedback loop in endocrinology?

LH surge in menstruation caused by oestrogen levels

24

Describe the anatomy of the thyroid gland

2 lateral lobes and an isthmus
In front of trachea
Large: 5cm long, 2-3cm deep, 3-4cm wide, 15-20g

25

What hormones does the thyroid gland make?

Basal metabolic rate: thyroxine (T4), tri-iodothyronine (T3)
Calcium homeostasis: calcitonin

26

What are T3 and T4 derived from?

Tyrosine
4 iodine molecules in T4
3 iodine molecules in T3

27

Describe the thyroid gland microstructure

Made of follicles: follicular cells containing colloid, parafollicular cells (c cells)
Follicular cells produce T3 and T4
Parafollicular cells produce calcitonin

28

What are the steps of thyroid hormone synthesis?

Thyroglobulin synthesis (from tyrosine) - colloid
Uptake and concentration of iodide (I-)
Oxidation of iodide to iodine (Thyroid peroxidase, luminal membrane of follicular cell)
Iodination of thyroglobulin to MIT and DIT mono-, di-iodotyrosine
Conjugation of 2 iodinated tyrosine molecules to form T4 or T3
Secretion

29

What does the thyroid gland do to iodide?

Concentrates it
Follicles actively accumulate iodine (iodide) from blood and secrete it into colloid

30

Describe iodide trapping by the thyroid gland

Iodide enters cell by a Na/iodide symporter located on basolateral side of follicle cell

31

What are dietary sources of iodide?

Seawater so sea food
Sea salt
Fruit and vegetables (depends on soil/imports)
Supplemented foods (salt, chocolate)

32

What is the most important nutritional deficiency? What is done to combat this in the UK?

Iodide
Most salt supplemented with iodine

33

What regulates thryoid hormone secretion?

Hypothalamic, pituitary, thryoid axis
Hypothalamus releases thyroid releasing hormone
Which stimulates anterior pituitary to release thyroid stimulating hormone
This stimulates the thyroid to release T3 and T4. Release of each factor has a negative feedback effect on release of those downstream

34

What is TSH (thyroid stimulating hormone)?

Released from anterior pituitary
Glycoprotein which stimulates follicles
Similar to FSH, LH (follicle stimulating hormone,luteinising hormone) FSH, LH and TSH: All have alpha and beta chains
Made independently

35

How does TSH increase thyroid hormone synthesis and secretion?

Receptor -> cAMP -> activates protein kinases -> phosphorylations at multiple sites to stimulate follicles to release thyroid hormones

36

Describe thyroid hormones in the circulation

Lipophilic so can’t readily dissolve in blood
Associated with proteins – 70% -thyroxin (thyroid) binding globulin (TBG), 30% bound to albumin
TBG has a higher affinity for T4
Only free T3/T4 can enter cell
Free hormones physiologically active

37

Which thyroid hormone can activate the thyroid receptor?

T4 has to be converted to T3 to bind to the T3R and have effect
Deiodinases interconvert T3/T4/rT3

38

Describe the types of Thyroid Hormone deiodinases

Peripheral tissue regulate T3 levels by increased or decreased deiodinases
Type 1 – cell surface of most cells, increase local T3
Type 2 – Intracellular raises T3 in CNS and pituitary
Type 3 - Removes iodine from T4 to make reverse T3(rT3). Especially placenta and CNS

39

What type of receptor is the thyroid hormone receptor?

Nuclear receptor
Leads to transcription and protein synthesis

40

What are the physiological actions of thyroid hormones?

Metabolism: all metabolic pathways, anabolic and catabolic, affects basal metabolic rate
Maturation and differentiation: bone/lungs/brain, CNS development
Neurological functions: synapse formation, myelinogenesis, neuronal outgrowth
Growth: Regulated by GH, but T3/T4 needed, skeletal

41

At what point of gestation does the thyroid gland start producing thyroid hormone?

12 weeks

42

What is Cretinism? And what test can be done for it?

Impaired physical and neurological development due to iodine deficiency during foetal or postnatal development
After 1st 2 years of life effects can’t be reversed screen in USA and UK
TSH in heel prick test

43

What are the effects of activation of the thyroid receptor?

Activity of cell membrane NaKATPase, mitochondrial enzymes
Leads to increased oxygen consumption and increased metabolic rate

44

In order to match increased oxygen consumption caused by T3, what needs to happen?

Increase ventilation (so increase respiration)
Deliver O2 - increase heart rate, increase blood flow, increase myocardial activity so increase cardiac output
O2 use needs substrates for oxidation: proteins/lipids/carbohydrate metabolism so increase food intake or mobilisation of stores

45

What will result from the increased metabolic rate seen with thyroid hormone receptor activation?

Increased CO2, ventilation
Increased urea
Increased renal function
Decreased muscle mass
Decreased adipose tissue
Increased thermogenesis
Leading to sweating, increased ventilation, surface blood flow

46

What symptoms might be seen in hyperthyroidism?

Palpatations, lose weight, increased respiration, anxiety, diarrhoea, heat tolerance, sweating, weight and muscle loss, increased appetite, nervous irritability, goitre

47

What symptoms might be seen in hypothyroidism?

Weight gain, decreased metabolic rate, lethargic/ slow, alopecia, goitre

48

What problems can be see with thyroid gland function?

Gland formation/function
Iodine supply (deficiency)
Signalling pathways (TSH, TRH)
Congenital or acquired
Thyroid hormone resistance (T3R defect)

49

What are the symptoms of hyperthyroidism called?

Thyrotoxicosis

50

What is Graves' disease?

Auto-antibody (TSI) binds to TSH receptor. Causes hyperthyroidism

51

How can hyperthyroidism be diagnosed?

Measure serum TSH, free T3, free T4
Increased T3/T4
Increased TSH – fault in or above pituitary gland
Decreased TSH – thyroid gland problem (tumour/graves)

52

What is an obvious sign of Graves disease?

Protruding eyes - exophthalmos

53

What are symptoms of hypothyroidism called?

Myxoedema

54

What can cause hypothyroidism?

Hasimotos thyroiditis (auto-immune destruction)
Iodine deficiency

55

How can hypothyroidism be diagnosed?

Measure Serum TSH, free T3, free T4
Decreased T3/T4
Increased TSH – usually

56

What is goitre?

Enlarged thyroid gland

57

What can cause goitre?

Iodine deficiency (low levels of T4): induces TSH secretion
Graves disease (high levels of T4): autoimmune disease that produces thyroid stimulating immunoglobulin - acts as TSH
Tumours (benign or cancer)

58

How do both low and high T4 induce a goitre?

Iodine deficiency leads to increased TSH stimulation and therefore gland growth
Graves' disease results in thyroid stimulating immunoglobulin activating the gland and so leads to growth

59

What are treatments for thyroid problems?

Drugs (inhibit production/replace hormone)
Radioactive iodine (131I) (destroy gland)
Surgery

60

What are potential risks with thyroid surgery?

General surgery issues
Vocal cord nerve damage
Bleeding
Parathyroid gland damage

61

List five characteristics of membrane transporters

Integral membrane proteins
Channels or carriers
Specific (or selective)
Regulated
Passive or active