SUGER: Week 5 Flashcards
(217 cards)
1
Q
Where are the thyroid glands located
A
Immediately below the larynx and anterior to the trachea
2
Q
What two major hormones do they produce
A
Thyroxine
Triiodothyronine
3
Q
How do these hormones differ from each other
A
They have a similar function but differ in ACTION INTENSITY
4
Q
What pituitary hormone controls secretion of thyroid hormones
A
TSH
5
Q
Where is TSH produced
A
The anterior pituitary glands
6
Q
What are the right and left lobes of the thyroid glands connected by
A
A narrow isthmus
7
Q
What is the thyroid gland composed of
A
Large numbers of closed follicles
8
Q
What cell synthesises colloid
A
cuboidal epithelial cells
9
Q
Where are these cuboidal epithelial cells found
A
Lining the thyroid glands
10
Q
What is colloid?
A
A large glycoprotein made up of ‘thyroglobulin’
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
12
Q
What cell produces calcitonin and where are they found
A
C-cells in the thyroid glands
13
Q
Role of calcitonin
A
Contributes to the regulation of plasma Ca2+ conc
14
Q
What element is needed for the production of thyroxine
A
Iodine
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
16
Q
How does ingested iodine circulate in the blood
A
Bound to albumin
17
Q
What happens to unwanted iodine
A
Excreted by the kidneys
18
Q
Where are Na-I symporters found
A
Basolateral membrane of the thyroid follicular cells
19
Q
Does the pump require ATP?
A
Yes
20
Q
What does an increase in cellular iodide conc. result in?
A
Increased thyroid gland activity
21
Q
What hormone affects the iodide pumping rate
A
TSH
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
23
Q
What organelles produce thyroglobulin in the thyroid cells
A
The golgi apparatus and Endoplasmic Reticulum
24
Q
Where is thyroglobulin secreted
A
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
