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Flashcards in SUGER: Week 5 Deck (217):
1

Where are the thyroid glands located

Immediately below the larynx and anterior to the trachea

2

What two major hormones do they produce

Thyroxine
Triiodothyronine

3

How do these hormones differ from each other

They have a similar function but differ in ACTION INTENSITY

4

What pituitary hormone controls secretion of thyroid hormones

TSH

5

Where is TSH produced

The anterior pituitary glands

6

What are the right and left lobes of the thyroid glands connected by

A narrow isthmus

7

What is the thyroid gland composed of

Large numbers of closed follicles

8

What cell synthesises colloid

cuboidal epithelial cells

9

Where are these cuboidal epithelial cells found

Lining the thyroid glands

10

What is colloid?

A large glycoprotein made up of 'thyroglobulin'

11

Outline the movement of secretions in the thyroid glands to target cells

Move from follicles into follicular epithelium and then into the blood

12

What cell produces calcitonin and where are they found

C-cells in the thyroid glands

13

Role of calcitonin

Contributes to the regulation of plasma Ca2+ conc

14

What element is needed for the production of thyroxine

Iodine

15

What is the first stage of thyroxine synthesis

The movement of one iodide ion and two sodium ions into a cell via a sodium-iodide symporter

16

How does ingested iodine circulate in the blood

Bound to albumin

17

What happens to unwanted iodine

Excreted by the kidneys

18

Where are Na-I symporters found

Basolateral membrane of the thyroid follicular cells

19

Does the pump require ATP?

Yes

20

What does an increase in cellular iodide conc. result in?

Increased thyroid gland activity

21

What hormone affects the iodide pumping rate

TSH

22

What happens to this iodide after entering the cell

It's moved to the opposite side of the cell and is moved out of the cell into the follicle via a pump called Pendrin

23

What organelles produce thyroglobulin in the thyroid cells

The golgi apparatus and Endoplasmic Reticulum

24

Where is thyroglobulin secreted

Into follicles

25

How many amino acids does each thyroglobulin consist of

70

26

What amino acids are these

Tyrosine

27

How do these thyroglobulin molecules form thyroid hormones

By binding to iodide ions

28

What must happen to iodide ions before they can bind to the tyrosine amino acids

They need to be oxidised

29

What two substances catalyse this oxidation reaction

Peroxidase and H2O2

30

What follows ioidide oxidation

Organification

31

What is organification

The adding of successive iodine to the tyrosine amino acids

Tyrosine -> Monoidodotyrosine -> Diiodotyrosine -> triiodotyronine -> Thyroxine

32

What is thyroxine also known as and why?

T4 - Has four iodide ions attached

33

When does storage of thyroglobulin occur

After synthesis of thyroid hormones stop

34

What do these thyroglobulins store

Thyroxine and triiodothyronine

35

Is thyroglobulin secreted into the blood

No, thyroxine and triiodotyronine are cleaved from thyroglobulin and are released

36

What enzyme breaks down the thyroglobulin

Proteases

37

What is the role of colloids

Acts as a 'reserve; of thyroid hormones

38

How do colloids enter the thyroid cells

Endocytosis by binding to megalin receptors

39

What happens to these colloids when needed

They move to the opposite side of the cell and are released into the blood

NOTE: Megalin remains bound to colloid the entire time

40

What happens to the monoiodotyrosine and diiodotyrosine

They are not needed so they are cleaved in order for the iodide to be recycled

41

What is the main effect of thyroid hormones

They activate nuclear transcription of a large number of genes

42

Does thyroxine bind to intracellular receptors in its current form?

No, it loses one iodide to form triiodothyronine

43

Why is thyroxine converted to triiodothyronine

Because the intracellular thyroid receptors have a HIGHER AFFINITY for triiodothyronine

44

What does triiodothyronine bind to

RXR receptors at a specific THYROID HORMONE RESPONSE ELEMENT on the DNA

45

What occurs following binding to this promotor site

Transcription

46

What are deiodinases

These are enzymes that add or release iodide ions from a molecules

47

What types of deiodinases are responsible for converting thyroxine to triiodotyronine

D1, D2, D3

48

What two compounds join together to give T4

DIT + DIT

49

What two compounds join together to give T3

MIT + DIT

50

Name a few roles of the thyroid hormones

Increased mitochondrial activity
Decreased conc of cholesterol, phospholipids and triglycerides in plasma
Increased BMR
Decreased Body Weight
Increased HR
Increased CO
Increased rate of respiration

51

Describe the negative feedback process of thyroxine and triiodothyronine

Look in book

52

How does hyperthyroidism/hypothyroidism affect serum TSH, T4 and T3 levels

Hypo:
Increased TSH
Decreased T4 and T3

Hyper:
Decreased TSH
Increased T4 and T3

53

Where are parathyroid glands found

Within the thyroid gland

54

Role of parathyroid glands

Regulate Ca2+ and PO43- ion levels

55

When do they start secreting PTH

Low ca2+ levels
High Po4 levels

56

How does PTH cause an increase in Ca2+

Increased reabsorption at kidney distal tubules
Increased reabsorption at intestines
Increased release of calcium from the bones

Decreased PO4 reabsorption

57

Describe the calcium ion negative feedback loop

Check book

58

What is FGF23e

Fibroblast growth factor 23

Secreted in response to increased calcitriol levels which act on kidney tubules to reduce reabsorption of phosphate

59

How many AA are found in PTH

84

60

How many of these are biologically active

34

61

What happens to PTH

Cleaved

62

What does PTH bind to

G coupled receptors in kidneys and osteoblasts

63

Affect of PTH at kidneys

Increased Ca reabsorption

Decreased PO4 reabsorption

Production of vitamin D as activated 1,25(OH)2D

64

Role of 1,25 (OH)2D

Inhibits transcription of PTH into RNA

65

What inhibits translation of PTH mRNA

High calcium ion levels

66

What is the first step in insulin production

Translation of insulin RNA to form PREPROINSULIN

67

Where is this cleaved to Proinsulin

At the RER

68

What peptides does proinsulin consist of

A, B and C peptides

69

Where is proinsulin cleaved to insulin at?

The golgi apparatus

70

What are the products of cleavage of proinsulin

Insulin (A and B peptides) and a C-peptide

71

What are the A and B peptide chains attached by

Disulfide Bridges

72

Label the stages of insulin secretion by the beta cells

1. Voltage-Gated Ca2+ channels + ATP-sensitive K+ channels are found in the membrane
2. Ca2+ are closed while K+ are open
3. K+ diffuses out of the cell down a conc gradient making the inside more negative
4. When glucose conc. is high, it enters the cell by FACILITATED DIFFUSION via GLUT2
5. Glucose is used by the cell in GLYCOLYSIS producing glucose-6-phosphate
6. This increases ATP levels
7. Increase in ATP to ADP ratio
8. ATP-sensitive K+ channels close when ratio rises
9. K+ accumulates in the cell causing it to DEPOLARISE
10. Voltage-gated Ca2+ channels open
11. Ca2+ enter the cell and insulin is released via EXOCYTOSIS

73

What enzyme catalyse glycolysis in beta cells

Hexokinase

74

Normal resting potential of beta cells

-70mV

75

What does insulin release being 'biphasic' mean

First phase - Rapid release of stored insulin into th eblood

Second phase - Slower release as this is the release of newly-synthesised hormones

76

Describe insulin action in muscles and fat cells

1. Insulin binds to receptors on the plasma membrane
2. This causes an intracellular cascade by signaling molecules
3. More expression of GLUT4 channels on plasma membrane
4. Glucose enters the cell via GLUT4 channels

77

What acts as a short-term buffer to increased glucose levels

liver glycogenesis

78

What acts as a long-term buffer to increased glucose levels

Lipogenesis (production of triglycerides)

79

Where are primary glucose sensors found

Islets of Langerhans

80

Where are sensors to glucose also found

Medulla, hypothalamus and carotid bodies

81

Where do glucose sensors receive inputs from

Eyes, nose, taste buds and gut

82

What are incretins

Hormones that augment release of insulin by pancreas and further suppress release of glucagon

83

Where are incretins found?

In the gut

84

Do incretins respond to glucose plasma conc?

No, they monitor glucose levels in the gut tract

85

Name two examples of incretins

GIP and GLP-1

86

How many amino acids are present in GLP-1

30

87

What cells secrete GLP-1

Enteroendocrine L-Cells

88

How does insulin affect fats in the body

Causes unrestrained fat breakdown

89

How does the pancreas develop embryologically

At junction of the foregut and midgut

We get a dorsal and ventral bud

Combine to form the pancreas

90

When does the exocrine function start to function

After birth

91

When does the endocrine system start to function

Before birth

92

Is the pancreas intra or retroperitoneal

Retroperitoneal

93

What two structures does the pancreas contain

Islets of langerhans

Acini

94

Most common cell in the islets of langerhans

Beta cells

95

Where do islet of langerhans cells secrete their hormones

Portal vein

96

What do alpha cells secrete

Beta cells secrete

D cells

(3)

Glucagon

Insulin

Somatostatin

97

How many amino acids are in Insulin

51

98

How many amino acids are in glucagon

29

99

Role of insulin

Decreased glucose output by liver

Increased storage of glucose, AA and fatty acids

Suppression of glycogenolysis

100

What does the posterior pituitary gland contain

Neuronal projections

101

Where do axonal projections in the posterior pituitary gland come from

Hypothalamus

102

What are the role of the axons in the posterior pituitary glands

Storage and release of hormones into the systemic circulation

103

What part of the posterior pituitary gland are oxytocin and vasopressin stored

Pars Nervosa

104

What structure connects the hypothalamus to the posterior pituitary glands

The pituitary stalk

105

What two nuclei does the posterior pituitary gland recieve inputs from

Supraoptic (mostly Vasopressin)

Paraventricular (mostly oxytocin)

106

Is oxytocin solely produced in the paraventricular nuclei

No, it’s produced in small quantities at the supraoptic nuclei too

(Vice versa for vasopressin)

107

What are pituicytes

Glial cells in the posterior pituitary glands that assist in the storage and release of hormones

108

Where is vasopressin produced

By magnocellular neurosecretory neurons in the supraoptic AND paraventricular nuclei

109

Where can granules of vasopressin be found

At the Hering Body

110

Where is the Hering Body found

On axon terminals

111

Are AVP and ADH the same thing?

Yes

112

What receptors does vasopressin bind to, what does binding do in each one and where are these receptors found

V1a - vasoconstriction, platelet aggregation, release of factor 8 and von willebrand factor (Liver)

V1b - Hormone secretion in response to stress (Pituitary Glands)

V2 - Insertion of aquaporin-2 (Basolateral membrane of kidneys)

113

What two receptors detect the release of ADH

Baroreceptors - emergency only

Osmoreceptors

114

Does size of particle affect osmolality?

No, only the number of particles

115

Is oxytocin found only in females?

No


Note: Oxytocin increases intracellular Ca2+ to invoke ejection of milk during lactation and uterine contractions)

116

How does decreased absorption of iodide ions affect the size of the thyroid gland

It will increase the size as more TSH will be released from the anterior pituitary gland

117

Name the four layers of the adrenal gland

Out to in:
Zona glomerulosa
Zona Fasiculata
Zone Reticularis

118

What are the three major hormones produced in the adrenal cortex

Zone G - Minercorticoids
Zone F - Glucocorticoids
Zone R - Sex hormones (adrenal Androgens)

119

What hormone do adrenal androgens have a similar effect to

Testosterone

120

Role of mineralcorticoids

Affect electrolytes of ECF

121

Role of glucocorticoids

Increase blood glucose concentration

Affect fat and lipid metabolism

122

Where is aldosterone secreted

Zona glomerulosa - It's a mineralcorticoid

123

What enzyme is present in the zona glomerulosa that aids production of aldosterone

Aldosterone Synthase

124

What two stimuli cause secretion of aldosterone

K+ and Angiotensin II in the ECF

125

What is the widest zone of the adrenal cortex

Zona Fasciculata

126

Name two hormones secreted by the zona fasciculata

Cortisol and corticosterone

127

Are adrenal androgens produced in the zona fasciculata

Yes

128

What is secretion in the zona fasciculata controlled by

Hypothalamic- Pituitary axis via ACTH

129

What is secreted in the zona reticulata

Mainly adrenal androgens

Some glucocorticoids

130

What hormone controls secretions in the zona reticularis

ACTH

131

What are all adrenocortical hormones derived from

Cholesterol

132

What is the chemical structure of a typical adrenocortical hormone

Three cyclohexane rings
One cyclopentane ring

133

Two properties of corticosteroids

Lipid soluble
Bind to intracellular receptors

134

How many carbon atoms are in progesterone corticoid steroids and give an example of one

21

Pregnane

135

How many carbon atoms are in androgen steroids and give and example of one

19

Androstane

136

How many carbon atoms are in oestrogens and give an example of one

18

Estrane

137

What two organelles are involved with the process of adrenal steroid synthesis

Endoplasmic Reticulum
Mitochondria

138

Describe the chemical stages that take place to produce aldosterone

Cholesterol -> Pregnenolone -> Progesterone -> 11-Deoxycorticosterone -> corticosterone -> aldosterone

139

Describe the chemical stages that take place to produce cortisol

CHolesterol->Pregenolone -> 17-hydroxypregnenolone ->17-hydroxyprogesterone -> 11-deoxycortisol -> Cortisol

140

Describe the chemical stages that take place to produce androstenedione and where it is released

Cholesterol -> Pregnenolone -> 17-hydroxypregnenolone -> dehydroepiandrosterone -> androstenedione
Zona reticulata

141

How do adrenal hormones circulate in the blood

Bound to plasma proteins

142

Where are adrenocortical hormones excreted

Metabolised in phase II reactions by being conjugated with glucuronic acid and sulphates in the liver

143

What two zones are affected by ATCH

Zona fasciculata
Zona Reticulata

144

Describe the action of ACTH

1. ACTH binds to ACTH receptors in the adrenal cortex
2. Activates Adenyl Cyclase
3. Increased cAMP
4. Activation of Protein Kinase C

145

What is the effect of ACTH to the process of steroid synthesis

- Stimulates delivery of cholesterol to mitochondria
- Cholesterol cleaved by P450ssc enzyme
- Stimulates LDL uptake into cortical cells of the adrenal cortex

146

Where is Pregnenolone converted to 17-hydroxypregnenelone

SER

147

Where is cholesterol converted to pregnenolone

Mitochondria

148

Where is Cortisol produced from 11-deoxycortisol

Mitochondria

149

Where is 17-hydroxyprenenolone converted to 11-deoxycortisol

SER

150

What does increased ACTH do to the adrenal glands

Cause them to increase in size

151

Effect of glucocorticoids in the Brain

Depression
Psychosis

152

Effect of glucocorticoids in the endocrine system

Decreased LH and FSH release
Decreased TSH release

153

Effect of glucocorticoids in carb and lipid metabolism

Hepatic glycogen deposition
Peripheral insulin release

154

Effect of glucocorticoids in the GI tract

Peptic ulcers

155

Effect of glucocorticoids in skin/muscle and connective tissues

Protein catabolism
COllagen breakdown

156

Effect of glucocorticoids in bones

Decreased bone formation and decreased bone mass

157

Effect of glucocorticoids on growth

Linear Growth

158

Effect of glucocorticoids on the immune system

Anti-inflammatory action
Immunosuppresion

159

Role of glucocorticoids during stress in glucose levels

Increased gluconeogenesis
Increased enzymes to convert AA to glucose
Increase lipolysis

160

Effect of glucocorticoids in circulation

Increased vascular tone
Na+ and H20 balance

161

Three ways glucocorticoids are transported in the blood

Bound to CBG (90%)
Albumin
Free

162

Which four factors affect glucocorticoids synthesis

ACTH
Diurnal rhythm
Stress
Illness

163

What receptors does ACTH bind to

MC2R

164

What hormone causes release of ACTH

CRH

165

What two things does ACTH do when binding to the adrenal glands

Increased cortisol secretion

Stimulates corticosteroid synthesis

166

Describe the hypothalamic-pituitary axis negative feedback with ACTH and CRH

Check book

167

When are cortisol levels highest during the day (diurnal)

Between 7 and 9 in the morning

168

When are cortisol levels lowest during the day (diurnal)

Between 11pm and 3am

169

What is the effect of stress on cortisol levels

Increases cortisol level blood plasma

170

How do stress cytokines affect the pituitary-hypothalamic axis negative feedback mechanism

They stimulate more CRH and ACTH to be released

171

During stress, how is the amount of free floating cortisol in the blood change

Increases as less CBG binding takes place

172

Where are mineralcorticoids synthesised

Zona glomerulosa

173

Two main hormones secreted in the zona glomerulosa

Aldosterone
DOC

174

Which is more active, DOC or Aldosterone

ALDOSTERONE

175

Role of mineralcorticoids

Maintains Na+ water balance in:
Kidneys
Salivary Glands
Sweat Glands
Pancreas
Colon

176

Which has higher activity, aldosterone or cortisol

Aldosterone

177

What cells do aldosterone effect in the kidneys

Principal cells in collecting tubules

178

What does aldosterone cause in the collecting tubules

Increased secretion of K+ and absorption of Na+

179

How does Dopamine affect the RAAS system

Inhibits secretion of renin

180

What proteins present in the blood stimulates dopamine release

Angiotensin II

181

How does aldosterone affect Na conc in ECC

Very little increase in conc

182

Why does aldosterone have very little impact of Na in ECF

Because increased Na in ECF causes increased water reabsorption

183

What other compound can also bind to mineralcorticoid receptors

Cortisol

184

How is cortisol prevented from activating mineralcorticoid receptors

Renal epithelial cells express 11 beta-hydroxysteroid dehydrogenase type II enzymes

Convert cortisol to cortisone

185

What is the most common adrenal androgen

DHEA

186

How strong is DHEA as an adrogen

Very weak

187

Is Androstenione stronger or weaker than DHEA

Stronger but weaker than testosterone

188

What are the main source of sex hormones in women

Adrenal androgens

189

What do the adrenal glands supply in post-menopausal women

Oestrogen precursors

190

What is the adrenal medulla part of

The autonomic nervous system

191

What is the adrenal medulla’s nerve supply

Sympathetic preganglionic neurons

192

What neurotransmitter is used in the adrenal medulla

ACh

193

Where is adrenaline synthesised

Adrenal medulla

194

State the relative production of catecholamines

80% adrenaline
20% noradrenaline

195

Catecholamines have a permissive effect

What does this mean

They are only synthesised and can function in the present of high cortisol levels

196

What is the role of catecholamines in the fight or flight response

Gluconeogenesis
Lipolysis
Tachycardia
Redistribution of blood

197

What are 6 roles of the skin?

Barrier to infection
Thermoregulation
Protection against trauma
Protection against UV
Vitamin D synthesis
Regulate H20 loss

198

What are the three basic layers of the skin

Epidermis
Dermis
Subcutaneous

199

What is the outermost layer of the epidermis called

Stratum corner

200

Why does the epidermis have corneo-desomosomes

These hold corneocytes together (outer skin cells)

201

What happens to the number of corneodesmosomes in atopic eczema

Decreases - leads to a thinning of the stratum corneum

202

What is the significance of a thinning stratum corner in atopic eczema

Increased risk of inflammation

203

What is NMF

A compound that helps maintain skin hydration (prevents evaporation of water from skin surface) + maintains acidic environment in stratum corneum

204

What produces NMF

Filaggrin

205

What form is filaggrin originally synthesised in

Inactive precursor form - profilaggrin

206

What is desquamation

This is skin peeling when keratinocytes shed from the stratum corneum as newly differentiated keratinocytes move up from the stratum basale

207

What is the pH of the normal skin

5.5

208

Why is it important for the skin to be at a pH of 5.5

Allows proteases to remain on the skin which are necessary for desquamination

209

What is the role of lipid lamellae in the epidermis

1. Keeps water inside skin cells

2. Causes irritants and allergens to bounce off skin surface

210

What is the stratum corneum a physical barrier to

Water loss
Irritants and allergens

211

Why do we need vitamin D for the skin

Produces anti-microbial peptides necessary to defend the skin from pathogens

212

How are skin flares ups caused

By allergens which are able to penetrate into the skin and react with lymphocytes.

These reactions release chemicals

213

What do chemicals released by interaction between lymphocytes and allergens cause

Red skin: Dilation of blood vessels due to lymphocytic activity

Itchy skin: Stimulation of nerves

Dry Skin: Skin cells leaking to due lymphocytic activity

214

How would an absence of filaggrin affect the pH of the stratum corneum

Causes the pH to increase

215

How will an increase in pH affect the skin barrier

Damage as it will break down the corneodesmosomes and break down the stratum corneum

216

How is acne caused?

1. hypercornification of the stratum corneum occurs resulting in corneodesmosomes blocking entrance to hair follicles

2. Results in increased production of sebum by sebaceous glands causing skin to feel greasy

3. Increased sebum production means some will become trapped in narrowed hair follicle

4. There is now no oxygen at the pit of the follicle for sebum

5. Anaerobic conditions favour growth of propionic bacteria acnes

6. Bacteria breakdown triglycerides in sebum into free fatty acids resulting in irritation, inflammation and attraction of neutrophils since p.acnes release chemicals that attract them

7. Pus formation as follicles is filled with attracted neutrophils

217

How can cosmetics cause acne

Oily hair gels can plug the hair follicle and initiate the acne process