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Phase 1 > SUGER: Week 5 > Flashcards

SUGER: Week 5 Flashcards

1
Q

Where are the thyroid glands located

A

Immediately below the larynx and anterior to the trachea

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2
Q

What two major hormones do they produce

A

Thyroxine

Triiodothyronine

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3
Q

How do these hormones differ from each other

A

They have a similar function but differ in ACTION INTENSITY

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4
Q

What pituitary hormone controls secretion of thyroid hormones

A

TSH

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5
Q

Where is TSH produced

A

The anterior pituitary glands

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6
Q

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

A

A narrow isthmus

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7
Q

What is the thyroid gland composed of

A

Large numbers of closed follicles

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8
Q

What cell synthesises colloid

A

cuboidal epithelial cells

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9
Q

Where are these cuboidal epithelial cells found

A

Lining the thyroid glands

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10
Q

What is colloid?

A

A large glycoprotein made up of ‘thyroglobulin’

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11
Q

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

A

Move from follicles into follicular epithelium and then into the blood

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12
Q

What cell produces calcitonin and where are they found

A

C-cells in the thyroid glands

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13
Q

Role of calcitonin

A

Contributes to the regulation of plasma Ca2+ conc

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14
Q

What element is needed for the production of thyroxine

A

Iodine

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15
Q

What is the first stage of thyroxine synthesis

A

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

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16
Q

How does ingested iodine circulate in the blood

A

Bound to albumin

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17
Q

What happens to unwanted iodine

A

Excreted by the kidneys

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18
Q

Where are Na-I symporters found

A

Basolateral membrane of the thyroid follicular cells

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19
Q

Does the pump require ATP?

A

Yes

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20
Q

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

A

Increased thyroid gland activity

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21
Q

What hormone affects the iodide pumping rate

A

TSH

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22
Q

What happens to this iodide after entering the cell

A

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

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23
Q

What organelles produce thyroglobulin in the thyroid cells

A

The golgi apparatus and Endoplasmic Reticulum

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24
Q

Where is thyroglobulin secreted

A

Into follicles

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25
Q

How many amino acids does each thyroglobulin consist of

A

70

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26
Q

What amino acids are these

A

Tyrosine

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27
Q

How do these thyroglobulin molecules form thyroid hormones

A

By binding to iodide ions

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28
Q

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

A

They need to be oxidised

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29
Q

What two substances catalyse this oxidation reaction

A

Peroxidase and H2O2

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30
Q

What follows ioidide oxidation

A

Organification

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31
Q

What is organification

A

The adding of successive iodine to the tyrosine amino acids

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

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32
Q

What is thyroxine also known as and why?

A

T4 - Has four iodide ions attached

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33
Q

When does storage of thyroglobulin occur

A

After synthesis of thyroid hormones stop

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34
Q

What do these thyroglobulins store

A

Thyroxine and triiodothyronine

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35
Q

Is thyroglobulin secreted into the blood

A

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

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36
Q

What enzyme breaks down the thyroglobulin

A

Proteases

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37
Q

What is the role of colloids

A

Acts as a ‘reserve; of thyroid hormones

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38
Q

How do colloids enter the thyroid cells

A

Endocytosis by binding to megalin receptors

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39
Q

What happens to these colloids when needed

A

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

NOTE: Megalin remains bound to colloid the entire time

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40
Q

What happens to the monoiodotyrosine and diiodotyrosine

A

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

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41
Q

What is the main effect of thyroid hormones

A

They activate nuclear transcription of a large number of genes

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42
Q

Does thyroxine bind to intracellular receptors in its current form?

A

No, it loses one iodide to form triiodothyronine

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43
Q

Why is thyroxine converted to triiodothyronine

A

Because the intracellular thyroid receptors have a HIGHER AFFINITY for triiodothyronine

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44
Q

What does triiodothyronine bind to

A

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

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45
Q

What occurs following binding to this promotor site

A

Transcription

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46
Q

What are deiodinases

A

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

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47
Q

What types of deiodinases are responsible for converting thyroxine to triiodotyronine

A

D1, D2, D3

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48
Q

What two compounds join together to give T4

A

DIT + DIT

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49
Q

What two compounds join together to give T3

A

MIT + DIT

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50
Q

Name a few roles of the thyroid hormones

A 
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
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51
Q

Describe the negative feedback process of thyroxine and triiodothyronine

A

Look in book

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52
Q

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

A

Hypo:
Increased TSH
Decreased T4 and T3

Hyper:
Decreased TSH
Increased T4 and T3

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53
Q

Where are parathyroid glands found

A

Within the thyroid gland

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54
Q

Role of parathyroid glands

A

Regulate Ca2+ and PO43- ion levels

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55
Q

When do they start secreting PTH

A

Low ca2+ levels

High Po4 levels

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56
Q

How does PTH cause an increase in Ca2+

A

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

Decreased PO4 reabsorption

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57
Q

Describe the calcium ion negative feedback loop

A

Check book

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58
Q

What is FGF23e

A

Fibroblast growth factor 23

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

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59
Q

How many AA are found in PTH

A

84

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60
Q

How many of these are biologically active

A

34

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61
Q

What happens to PTH

A

Cleaved

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62
Q

What does PTH bind to

A

G coupled receptors in kidneys and osteoblasts

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63
Q

Affect of PTH at kidneys

A

Increased Ca reabsorption

Decreased PO4 reabsorption

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

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64
Q

Role of 1,25 (OH)2D

A

Inhibits transcription of PTH into RNA

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65
Q

What inhibits translation of PTH mRNA

A

High calcium ion levels

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66
Q

What is the first step in insulin production

A

Translation of insulin RNA to form PREPROINSULIN

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67
Q

Where is this cleaved to Proinsulin

A

At the RER

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68
Q

What peptides does proinsulin consist of

A

A, B and C peptides

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69
Q

Where is proinsulin cleaved to insulin at?

A

The golgi apparatus

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70
Q

What are the products of cleavage of proinsulin

A

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

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71
Q

What are the A and B peptide chains attached by

A

Disulfide Bridges

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72
Q

Label the stages of insulin secretion by the beta cells

A
  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
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73
Q

What enzyme catalyse glycolysis in beta cells

A

Hexokinase

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74
Q

Normal resting potential of beta cells

A

-70mV

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75
Q

What does insulin release being ‘biphasic’ mean

A

First phase - Rapid release of stored insulin into th eblood

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

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76
Q

Describe insulin action in muscles and fat cells

A
  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
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77
Q

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

A

liver glycogenesis

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78
Q

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

A

Lipogenesis (production of triglycerides)

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79
Q

Where are primary glucose sensors found

A

Islets of Langerhans

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80
Q

Where are sensors to glucose also found

A

Medulla, hypothalamus and carotid bodies

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81
Q

Where do glucose sensors receive inputs from

A

Eyes, nose, taste buds and gut

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82
Q

What are incretins

A

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

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83
Q

Where are incretins found?

A

In the gut

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84
Q

Do incretins respond to glucose plasma conc?

A

No, they monitor glucose levels in the gut tract

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85
Q

Name two examples of incretins

A

GIP and GLP-1

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86
Q

How many amino acids are present in GLP-1

A

30

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87
Q

What cells secrete GLP-1

A

Enteroendocrine L-Cells

88
Q

How does insulin affect fats in the body

A

Causes unrestrained fat breakdown

89
Q

How does the pancreas develop embryologically

A

At junction of the foregut and midgut

We get a dorsal and ventral bud

Combine to form the pancreas

90
Q

When does the exocrine function start to function

A

After birth

91
Q

When does the endocrine system start to function

A

Before birth

92
Q

Is the pancreas intra or retroperitoneal

A

Retroperitoneal

93
Q

What two structures does the pancreas contain

A

Islets of langerhans

Acini

94
Q

Most common cell in the islets of langerhans

A

Beta cells

95
Q

Where do islet of langerhans cells secrete their hormones

A

Portal vein

96
Q

What do alpha cells secrete

Beta cells secrete

D cells

(3)

A

Glucagon

Insulin

Somatostatin

97
Q

How many amino acids are in Insulin

A

51

98
Q

How many amino acids are in glucagon

A

29

99
Q

Role of insulin

A

Decreased glucose output by liver

Increased storage of glucose, AA and fatty acids

Suppression of glycogenolysis

100
Q

What does the posterior pituitary gland contain

A

Neuronal projections

101
Q

Where do axonal projections in the posterior pituitary gland come from

A

Hypothalamus

102
Q

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

A

Storage and release of hormones into the systemic circulation

103
Q

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

A

Pars Nervosa

104
Q

What structure connects the hypothalamus to the posterior pituitary glands

A

The pituitary stalk

105
Q

What two nuclei does the posterior pituitary gland recieve inputs from

A

Supraoptic (mostly Vasopressin)

Paraventricular (mostly oxytocin)

106
Q

Is oxytocin solely produced in the paraventricular nuclei

A

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

(Vice versa for vasopressin)

107
Q

What are pituicytes

A

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

108
Q

Where is vasopressin produced

A

By magnocellular neurosecretory neurons in the supraoptic AND paraventricular nuclei

109
Q

Where can granules of vasopressin be found

A

At the Hering Body

110
Q

Where is the Hering Body found

A

On axon terminals

111
Q

Are AVP and ADH the same thing?

A

Yes

112
Q

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

A

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
Q

What two receptors detect the release of ADH

A

Baroreceptors - emergency only

Osmoreceptors

114
Q

Does size of particle affect osmolality?

A

No, only the number of particles

115
Q

Is oxytocin found only in females?

A

No

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

116
Q

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

A

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

117
Q

Name the four layers of the adrenal gland

A

Out to in:
Zona glomerulosa
Zona Fasiculata
Zone Reticularis

118
Q

What are the three major hormones produced in the adrenal cortex

A

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

119
Q

What hormone do adrenal androgens have a similar effect to

A

Testosterone

120
Q

Role of mineralcorticoids

A

Affect electrolytes of ECF

121
Q

Role of glucocorticoids

A

Increase blood glucose concentration

Affect fat and lipid metabolism

122
Q

Where is aldosterone secreted

A

Zona glomerulosa - It’s a mineralcorticoid

123
Q

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

A

Aldosterone Synthase

124
Q

What two stimuli cause secretion of aldosterone

A

K+ and Angiotensin II in the ECF

125
Q

What is the widest zone of the adrenal cortex

A

Zona Fasciculata

126
Q

Name two hormones secreted by the zona fasciculata

A

Cortisol and corticosterone

127
Q

Are adrenal androgens produced in the zona fasciculata

A

Yes

128
Q

What is secretion in the zona fasciculata controlled by

A

Hypothalamic- Pituitary axis via ACTH

129
Q

What is secreted in the zona reticulata

A

Mainly adrenal androgens

Some glucocorticoids

130
Q

What hormone controls secretions in the zona reticularis

A

ACTH

131
Q

What are all adrenocortical hormones derived from

A

Cholesterol

132
Q

What is the chemical structure of a typical adrenocortical hormone

A

Three cyclohexane rings

One cyclopentane ring

133
Q

Two properties of corticosteroids

A

Lipid soluble

Bind to intracellular receptors

134
Q

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

A

21

Pregnane

135
Q

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

A

19

Androstane

136
Q

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

A

18

Estrane

137
Q

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

A

Endoplasmic Reticulum

Mitochondria

138
Q

Describe the chemical stages that take place to produce aldosterone

A

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

139
Q

Describe the chemical stages that take place to produce cortisol

A

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

140
Q

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

A

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

141
Q

How do adrenal hormones circulate in the blood

A

Bound to plasma proteins

142
Q

Where are adrenocortical hormones excreted

A

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

143
Q

What two zones are affected by ATCH

A

Zona fasciculata

Zona Reticulata

144
Q

Describe the action of ACTH

A
  1. ACTH binds to ACTH receptors in the adrenal cortex
  2. Activates Adenyl Cyclase
  3. Increased cAMP
  4. Activation of Protein Kinase C
145
Q

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

A
  • Stimulates delivery of cholesterol to mitochondria
  • Cholesterol cleaved by P450ssc enzyme
  • Stimulates LDL uptake into cortical cells of the adrenal cortex
146
Q

Where is Pregnenolone converted to 17-hydroxypregnenelone

A

SER

147
Q

Where is cholesterol converted to pregnenolone

A

Mitochondria

148
Q

Where is Cortisol produced from 11-deoxycortisol

A

Mitochondria

149
Q

Where is 17-hydroxyprenenolone converted to 11-deoxycortisol

A

SER

150
Q

What does increased ACTH do to the adrenal glands

A

Cause them to increase in size

151
Q

Effect of glucocorticoids in the Brain

A

Depression

Psychosis

152
Q

Effect of glucocorticoids in the endocrine system

A

Decreased LH and FSH release

Decreased TSH release

153
Q

Effect of glucocorticoids in carb and lipid metabolism

A

Hepatic glycogen deposition

Peripheral insulin release

154
Q

Effect of glucocorticoids in the GI tract

A

Peptic ulcers

155
Q

Effect of glucocorticoids in skin/muscle and connective tissues

A

Protein catabolism

COllagen breakdown

156
Q

Effect of glucocorticoids in bones

A

Decreased bone formation and decreased bone mass

157
Q

Effect of glucocorticoids on growth

A

Linear Growth

158
Q

Effect of glucocorticoids on the immune system

A

Anti-inflammatory action

Immunosuppresion

159
Q

Role of glucocorticoids during stress in glucose levels

A

Increased gluconeogenesis
Increased enzymes to convert AA to glucose
Increase lipolysis

160
Q

Effect of glucocorticoids in circulation

A

Increased vascular tone

Na+ and H20 balance

161
Q

Three ways glucocorticoids are transported in the blood

A

Bound to CBG (90%)
Albumin
Free

162
Q

Which four factors affect glucocorticoids synthesis

A

ACTH
Diurnal rhythm
Stress
Illness

163
Q

What receptors does ACTH bind to

A

MC2R

164
Q

What hormone causes release of ACTH

A

CRH

165
Q

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

A

Increased cortisol secretion

Stimulates corticosteroid synthesis

166
Q

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

A

Check book

167
Q

When are cortisol levels highest during the day (diurnal)

A

Between 7 and 9 in the morning

168
Q

When are cortisol levels lowest during the day (diurnal)

A

Between 11pm and 3am

169
Q

What is the effect of stress on cortisol levels

A

Increases cortisol level blood plasma

170
Q

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

A

They stimulate more CRH and ACTH to be released

171
Q

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

A

Increases as less CBG binding takes place

172
Q

Where are mineralcorticoids synthesised

A

Zona glomerulosa

173
Q

Two main hormones secreted in the zona glomerulosa

A

Aldosterone

DOC

174
Q

Which is more active, DOC or Aldosterone

A

ALDOSTERONE

175
Q

Role of mineralcorticoids

A 
Maintains Na+ water balance in:
Kidneys
Salivary Glands
Sweat Glands
Pancreas
Colon
176
Q

Which has higher activity, aldosterone or cortisol

A

Aldosterone

177
Q

What cells do aldosterone effect in the kidneys

A

Principal cells in collecting tubules

178
Q

What does aldosterone cause in the collecting tubules

A

Increased secretion of K+ and absorption of Na+

179
Q

How does Dopamine affect the RAAS system

A

Inhibits secretion of renin

180
Q

What proteins present in the blood stimulates dopamine release

A

Angiotensin II

181
Q

How does aldosterone affect Na conc in ECC

A

Very little increase in conc

182
Q

Why does aldosterone have very little impact of Na in ECF

A

Because increased Na in ECF causes increased water reabsorption

183
Q

What other compound can also bind to mineralcorticoid receptors

A

Cortisol

184
Q

How is cortisol prevented from activating mineralcorticoid receptors

A

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

Convert cortisol to cortisone

185
Q

What is the most common adrenal androgen

A

DHEA

186
Q

How strong is DHEA as an adrogen

A

Very weak

187
Q

Is Androstenione stronger or weaker than DHEA

A

Stronger but weaker than testosterone

188
Q

What are the main source of sex hormones in women

A

Adrenal androgens

189
Q

What do the adrenal glands supply in post-menopausal women

A

Oestrogen precursors

190
Q

What is the adrenal medulla part of

A

The autonomic nervous system

191
Q

What is the adrenal medulla’s nerve supply

A

Sympathetic preganglionic neurons

192
Q

What neurotransmitter is used in the adrenal medulla

A

ACh

193
Q

Where is adrenaline synthesised

A

Adrenal medulla

194
Q

State the relative production of catecholamines

A

80% adrenaline

20% noradrenaline

195
Q

Catecholamines have a permissive effect

What does this mean

A

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

196
Q

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

A

Gluconeogenesis
Lipolysis
Tachycardia
Redistribution of blood

197
Q

What are 6 roles of the skin?

A 
Barrier to infection
Thermoregulation
Protection against trauma
Protection against UV
Vitamin D synthesis
Regulate H20 loss
198
Q

What are the three basic layers of the skin

A

Epidermis
Dermis
Subcutaneous

199
Q

What is the outermost layer of the epidermis called

A

Stratum corner

200
Q

Why does the epidermis have corneo-desomosomes

A

These hold corneocytes together (outer skin cells)

201
Q

What happens to the number of corneodesmosomes in atopic eczema

A

Decreases - leads to a thinning of the stratum corneum

202
Q

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

A

Increased risk of inflammation

203
Q

What is NMF

A

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

204
Q

What produces NMF

A

Filaggrin

205
Q

What form is filaggrin originally synthesised in

A

Inactive precursor form - profilaggrin

206
Q

What is desquamation

A

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

207
Q

What is the pH of the normal skin

A

5.5

208
Q

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

A

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

209
Q

What is the role of lipid lamellae in the epidermis

A
  1. Keeps water inside skin cells

2. Causes irritants and allergens to bounce off skin surface

210
Q

What is the stratum corneum a physical barrier to

A

Water loss

Irritants and allergens

211
Q

Why do we need vitamin D for the skin

A

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

212
Q

How are skin flares ups caused

A

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

These reactions release chemicals

213
Q

What do chemicals released by interaction between lymphocytes and allergens cause

A

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
Q

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

A

Causes the pH to increase

215
Q

How will an increase in pH affect the skin barrier

A

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

216
Q

How is acne caused?

A
  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
Q

How can cosmetics cause acne

A

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

Phase 1 (30 decks)

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