Endocrinology Flashcards
(379 cards)
1
Q
Which pathway comes first efferent or afferent
A
Afferent->efferent
2
Q
What is the biological rhythm set by?
A
Cicardiam rhythm
3
Q
Where are the collection of neurones responsible for the cicardian rhythm
A
Suprachiasmatic nucleus
4
Q
What hormone is involve in setting the biological clock?
A
Melatonin
5
Q
Where is melatonin released from to control the biological clock?
A
Pineal gland
6
Q
What type of feedback is the most common?
A
Negative
7
Q
When would we want positive feedback?
A
When we want a rapid response, blood clotting, ovulation
8
Q
What is body osmotic pressure monitored by?
A
Osmoreceptors in the hypothalamus
9
Q
What happens if osmolality is low (hypotonic)
A
Osmoreceptors send signal to posterior pituatry to secrete less ADH
10
Q
Is less ADH is secreted due to low osmolality what is the result?
A
Decreased reabsorbtion of H20 in collecting ducts leading to large amount of dilute urine
11
Q
If osmolality is detected and it is high, what signals do the osmoreceptors send?
A
- Stimulate thirst
2. Signal to post pituatry to secrete more ADH- increasing H20 reabsorbtion in collecting ducts of kidney
12
Q
What does insulin stimulate?
A
Uptake of glucose and glycogenesis to decrease plasma glucose levels
13
Q
What does glucagon stimulate?
A
Glycogenolysis to increase plasma glucose levels
14
Q
What are the 4 hormone classifications
A
Peptide
Amino acid derivative
Glycoproteins
Steroids
15
Q
Are peptide hormones water soluble?
A
Yes
16
Q
Are amino acid derivatives water soluble?
A
Adrenal medulla hormones are
Thyroid hormones are lipid soluble
17
Q
Are glycoproteins hormones water soluble?
A
Yes
18
Q
Are steroid hormones water soluble?
A
No, lipid soluble
19
Q
Name some peptide hormones
A
Insulin,
Glucagon
Growth hormone
20
Q
What types of amino acids are amino acid derivative hormones synthesised from?
A
Aromatic
21
Q
Name some amino acid derivative hormones and there precursor
A
Adrenaline, noradrenaline, thyroid hormones (tyrosine), melatonin (tryptophan)
22
Q
Are glycoprotein hormones small or large generally?
A
Large made of sub units
23
Q
What are some examples of glycoproteins hormones?
A
TSH, FSH
24
Q
What are steroid hormones derived from?
A
Cholesterol
25
What are some examples of steroid hormones?
Cortisol, aldosterone, testosterone
26
The fact that many hormones need carrier proteins gives what kind of equilibrium? Why?
Dynamic because the hormones bound are inactive
27
What effect do carrier proteins have on hormones?
Increase solubility, increase half life, create a readily available reserve
28
What 3 main factors determine the level a hormone will be in the blood?
Rate of production (synth and secreion)
Rate of delivery (blood flow to organ)
Rate of degradation
29
Hormones circulate at what kind of concentration?
Picomolar
30
What kind of receptors do water soluble hormones need? Why?
G coupled or tyrosine kinase because they cant cross the plasma membrane
31
Binding of adrenaline to a G protein receptor does what?
```
Causes dissociated of alpha sub unit
Activates adenyl cyclase
CAMP activated
Activate protein kinase
Phosphorylate target
```
32
What happens when something like insulin binds to a tyrosine kinase receptor ?
Initial dimerisation
Autophosphorlyation of specific tyrosines
Recruitment of adapter proteins and protein kinase
Phosphorylation of target proteins
33
How does a type 1 lipid soluble hormones work?
Bind to a cytoplasmic receptor making a complex that enters the nucleus binding to dna
34
How does a type 2 lipid soluble hormone work?
Enters the nucleus ad binds to a pre bound receptor on the dna
35
What produces a slower response a water soluble hormone or lipid soluble
Lipid- has to await the transcription and translation of its target gene
36
What nucleus plays a key role in apeitite/satiety control?
Arcuate nucleus
37
What two types of neurones are in the arcuate nucleus?
Stimulators (of apetite)
| Inhibitors promote satiety
38
What to the stimulators in the arcuate nucleus contain?
Neuropeptide Y (NPY)
Agouti-related peptide (AgRP)
Promote hunger
39
What do the inhibitory neurones in the Arcuate nucleus contain?
Pro-opiomelanocortin (POMC)- with alpha MSH and beta-Endorphin neurotransmitters
Promote satiety
40
What's ghrelin? When is it released? What does it stimulate?
Peptide hormone
Stomach empty
The arcuate nucleus promoting hunger
41
What does leptin tell the brain?
Fat store levels
42
What kind of hormone is leptin? Where is it release from? What does it stimulate? What other hormone can do this?
It's a peptide hormone
Released by adipocytes
Stimulates POMC in accurate to suppress apetite
Insulin
43
What is amylin? What does it do?
Peptide hormone from pancreas
| Suppresses apetite
44
What do some obese people (very rare) have?
Loss of functioning leptin gene
45
Where is the thyroid gland located?
Below thyroid cartilage (Adams apple)
46
How many lobes does the thyroid gland have? What's it joined by?
2
| Isthmus
47
Where is the isthmus?
From the 2-3rd ring of trachea
48
What is the first endocrine to develop? When does this occur?
Thyroid gland
| 3-4 weeks gestation
49
What does the thyroid gland appear as in development?
Epithelial proliferation in floor of pharynx at the base of the tongue, migrating after several weeks
50
The thyroid gland migrates in development but remains connected to the tongue, how?
Via thyroglossal duct
51
Histilogically what can be seen in the thyroid?
Follicular cells in spheres called thyroid follicles
52
What are thyroid follicles filled with? What is it?
Colloid
| A deposit of thyroglobulin
53
Despite being in the cell, what is colloid?
Extracellular
54
How does the parathyroid differ histilogically from the thyroid?
Smaller follicles
55
What do thyroid parafollicular cells produce?
Calcitonin
56
What cells of the parathyroid produce parathyroid hormone?
Chief cells
57
The parathyroid hormone is key in what
Calcium control
58
What's the difference between T3 and T4 thyroid hormone
An extra iodine
59
What is T3 formed from
Monoiodotyrosine and diiodotyrosine
60
How many aromatic rings does t3/t4 have?
2
61
What is t4 formed form?
X2 diiodotyrosine
62
What is thyroglobulin?
The scaffold that thyroid hormone forms on
63
Thyroglobulin (134 tyrosines) - what happens to its residues?
They become iodinated
64
What happens to iodinated residues of thyroglobulin?
They undergo coupling reactions to make t3/t4, these stay attached until they need to be released
65
What 3 reactions does the enzyme thyroid peroxidase regulate?
Oxidation- idodide to iodine (needs H2O2)
Addition of iodine- to the tyrosine receptor residues of thyroglobulin
Coupling- MIT or DIT-> t3/4
66
Dietary iodine needs what to happen to be absorbed?
Reduced to iodide in small intestine
67
What are the only molecules in the body that contain iodine
Thyroid hormones and its precursors
68
Where is 95% of the bodies iodine
Thyroid gland
69
How does the thyroid get all the iodine?
Epithelial cells have sodium iodide symporter (iodide trap)
70
What is more active in the body t3 or t4
T3 4x more likely
71
What happens to 90% of t4?
Converted to t3 in the liver and kidneys
72
What is 80% of t3 derived from?
T4
73
How do t3 and t4 travel?
Bound to thyroxine binding globulin
74
What is the pathway of t3/4 secretion
Hypothalamus-> TRH-> ant pit-> TSH-> thyroid gland-> T3/4
75
What are the 2 main principal effects of thyroid hormones?
Metabolic pathway effects
| Cellular differentiation and development
76
What type of hormone is TSH? What's it composed of?
Glycoproteins
| 2 non covalently bonded subunits
77
What is the alpha subunit of TSH? What is the beta?
Alpha-FSH and LH
| Beta-unique
78
How does TSH hormone cause T3/4 release?
```
Stimulates:
Iodide uptake
Iodide oxidation
Thyroglobulin synthesis
Thyroglobulin iodisation
Colloid Pinocytosis
Proteolysis of thyroglobulin
Cell growth
```
79
How does TSH have such a wide range of effect?
Can couple Gs and Gq inducing cAMP and DAG/IP3
80
Thyroid hormones increase basal metabolic rate and heat production everywhere except?
Brain
Spleen
Testis
81
How does thyroid hormone increase base metabolic rate
By increasing mitochondria size and stimulating synthesis of enzymes in resp chain
82
What metabolic pathways does thyroid hormone predominantly stimulate
Catabolic-
Lipolysis + beta oxidation
Gluconeogenesis
Glycogenolysis
83
What is the so called sympathomimetics effect of thyroid hormone?
Increases target cells response to catecholamines by increasing number of receptors
84
What is the CVS specific effect of thyroid hormone
Increase cardiac output
| Increase peripheral vasodilation
85
What is the nervous system specific effect of thyroid hormones
Increase myelination of nerves and development of neurons
86
Where are thyroid hormone receptors?
Nucleus
87
What modulates the gene expression that thyroid hormone has? What happens in the abscence of thyroid hormone
Transcription factors on specific genes (conformation change)
In abscence there is transcription repression
88
What's goitre
Enlargement of thyroid gland
89
When does goitre occur?
When thyroid gland is overstimulated, this can be hypo or hyper thryroid is
90
What are some causes of hypothyroidism
```
autoimmune (hashimotos)
Inadequate dietary iodine
TSH/TRH defficent
Surgical removal
Anti-thyroid drugs
```
91
How do you treat hypothyroidism
Oral thyroid hormone
92
What are symptoms of hypothyroidism
```
Obesity
Lethargy
Cold intolerance
Bradycardia
Dry skin
Slowed reflexes
Constipation
Menorhagia
```
93
What would serum levels show in hypothyroidism
Low t3/4, high tsh
94
What are some causes of hyperthyroidism?
Autoimmune (graves)
Toxic multinodular thyroid
Excessive t4 therapy
Thyroid carcinoma
95
What are some symtoms of hyperthyroidism
```
Weight loss
Irritable
Heat intolerance
Tachy
Fatigue
Increased bowel movements
Hyper-reflexia
Loss of libido
Breathless
```
96
What's an anti-thyroid drug, what does it do?
Carbimazole
Blocks formation of thyroid hormone by preventing thyroid peroxidase
Pro drug
97
What is used in thyroid scans looking at uptake
Technetium 99
| Short half life
98
What's myxedema?
Thick puffy skin, slow speech, muscle weakness, mental deterioration seen in hypothyroid
99
What can hypothyroid cause in infant?
Cretinism
100
When can you feel a normal thyroid gland?
You can't, if its felt its pathological
101
Why does the thyroid move with swallow?
Attached to tranches and larynx by pre teaches fascia
102
How can the thyroid be imagined?
US
| Uptake scan
103
Where does thyroid development start in development
Foramen caecum
104
What's a thyroglobulin duct cyst?
Remantents of the epithelium from development
| Swelling on the midline within body of hyoid
105
Why is TSH a good screening tool for thyroid issues?
98% of metabolic thyroid disease is thyroid primary
Pituatry adenoma could produce excess TSH rare
Pituatry failure with just TSH change very very rare
106
What is the TSH level an indicator of?
What the brain thinks the thyroid function is like
107
What's normal TSH range
0.505ml IU/L
108
What does the endocrine system seem to be particulary succeptible to ?
Autoimmune diseases
109
How can goitres be described?
Diffuse
Single nodule
Multinodular
110
When can normal thyroid function with goitre occur?
Pregnancy, menopause, menarche (1st menstruation)
111
What's the most common GLOBAL form of goitre?
| What's the most common in the uk?
Iodine defficency globally
| Multinodular in uk (thyroid function ok unless toxic)
112
What are symptoms of cretinism
Mental retardation, deaf retardation, deaf mute, short, goitre, hypothyroidism
113
What can multinodular goitres do to the trachea?
Enlarge inferiorly compressing trachea
114
What symptom doesn't really fit with hypotyroidims?
Mennorhagia
115
What symptom doesn't really fit with hyperthyroidism
Amernorhagia
116
What's thyrotoxicosis?
Overproduction of thyroxine leading to anxiety, heat intolerance, shaking, palpitation, bounding pulse, lid lag and staring eyes
117
Why do you get lid lag in thyrotoxicosis
10% of lid control is smooth muscle,
| Increase thyroxine and you get sympathomimetics
118
What's can a toxic adenoma of the thyroid do?
Produce thyroxine autonomously
119
If you have a thyroid nodule but no metabolic disturbance, what should be investigated?
Thyroid cancer
120
The hypothalamic pituatry axis is the major linn between what 2 systems?
Endocrine and nervous
121
Where is the pituatry gland?
Beneath the hypothalamus in socket called sella turcica
122
What are some of the key functions covered by the hypothalamic pituatry axis?
```
Body growth
Thyroid function
Adrenal gland function
Water homeostasis
Lactation
Reproduction
```
123
What hormones does the posterior pituatry synthesise?
It doesnt synthesise any hormones
124
Where does the ant pituatry arise from embryologically
Oral ectoderm (primary gut tissue)
125
Where does the post pituatry originate from embryologically
Neuroectoderm (primitive brain tissue)
126
Which part of the pituatry is connected to the hypothalamus?what connects them?
Post
| Infundibulum
127
Where are the hormones of the posterior pituatry synthesised?
Oxytocin and ADH are produced in the supraoptic and paraventricular nuclei of the hypothalamus
128
Hormones from the hypothalamus to the anterior pituatry go where before being released into the hypophyseal portal system?
Down axons and stored in median eminence
129
The hormones secreted from the ant pituatry exert effects in what way?
Endocrine
Autocrine
Paracrine
130
The hypophyseal portal system affects the endocrine cells of where?
Ant pituatry
131
The pathway between the hypothalamus and post pituatry is considered what?
Direct
132
The hypo-post pituatry system has what hormones, with what effects?
oxytocin- uterus contraction and milk
| ADH/Vasopressin- regulate body water volume
133
What are tropic hormones
Hormones that affect the release of other hormones
134
What are the hormones released by the hypothalamus to the ant pit
```
TRH
PRH
PIH
CRH
GnRH
GHRH
GHIH
```
135
What's TRH what does it modulate?
Thyrotropin releasing hormone
| Modulates release of TSH
136
What's PRH what does it regulate?
Prolactin releasing hormone
| Positive control of prolactin release
137
What's PIH what does it modulate? What else is it called
Prolactin release inhibition hormone.
Negative control of prolactin
Dopamine
138
What's CRH, what does it regulate
Corticotropin releasing hormone
| Regulates release of ACTH
139
What GnRH, what does it regulate
Gonadotropin releasing hormone
| Regulates leutanising hormone and follicle stimulating hormone
140
What GHRH
Growth hormone releasing hormone
141
What's GHIH
Growth hormone inhibiting hormone
142
What hormones are produced in the anterior pituatry?
```
TSH
ACTH
LH
FSH
Prolactin
Growth hormone
```
143
What does TSH stand for?
Thyroid stimulating hormone
144
What does ACTH stand for?
Adrenocorticotropic hormone
145
What does LH stand for
Leutinising hormone
146
What is the affect of ACTH release?
Secretion of hormones from adrenal cortex
147
What does LH release stimulate
Ovulation and secretion of sex hormones
148
What does FSH stimulate
Egg and sperm developement
149
What does prolactin stimulate
Mammary gland development and milk secretion
150
What does growth hormone stimulate
Growth and energy metabolism and IGFs
151
What must happen for proper folding of growth hormone
Signal peptide cleavage
152
What is secreted from where in response to GH
Insulin like growth factors from liver and skeletal muscle
153
What does growth hormone stimulate in childhood?
Long bone growth (length and pre-epiphyseal closure)
| Cartilage growth
154
In adults what does GH do?
Maintains muscle and bone mass and promotes healing and repair
155
How is growth hormone mainly controlled?
Growth hormone releasing hormone and somatostatin (GHIH)
156
What can alter the release of GHRH/somatostatin explaining why we get variations in levels
```
CNS regulation
Surge with deep sleep
Decrease with R.E.M. Sleep
Increase with stress
Increase with exercise
Low glucose or fatty acids increase it
High glucose or fatty acids decrease it
```
157
How is GHRH regulated?
IGFs inhibit release of GHRH and stimulate soomatostatin
| GH itself stimulates somatostatin release
158
What does low GH in childhood result in
Dwarfism (proportionate)
159
Growth hormone excess in children results in what?
Gigantism
160
Growth hormone excess In adults results in what?
Acromegaly
161
At a cellular level what does GH cartilage to stimulate IGF production?
Janus Kinases
162
What's the major growth factor in adults?
IGF1
163
What's the major growth factor in fetal growth
IGF2
164
What do IGF receptors modulate?
Hypertrophy, hyperplasia, protein synthesis rate, lipolysis rate
165
What happens with GH and hybrid receptors?
Cross over receptors respond to insulin and IGf1
| Result in mitogenic and metabolic effects
166
What other hormones, asides from GH influence growth
'
```
Insulin
Throid hormones
Androgens
Estrogens
Glucocorticosteroids
```
167
What hormones influence somatic growth?
Insulin increases
| Estrogen and glucocorticosteroids inhibit
168
How do thyroid hormones influence growth
Enhance GH secretion
169
What effect do androgens have on growth?
Accelerate pubertal growth
Close epiphyseal plates
Increase muscle mass
170
How do pituatry tumours present as a result of...
Mass effect or
| Abnormal pituatry function
171
What important structures surround the pituatry gland?
Optic chiasm
Occulomotor nerve
Trochlear nerve
Internal carotid artery
172
A pituatry tumour with superior growth would impede on what? What would this cause?
Optic chiasm
| Bitempora hemianopia
173
A pituatry tumour exerting lateral mass effect will cause what?
Pressure on trochlear and occulomotor nerve causing double vision
174
Hypopituatrism results in down regulation of what and up regulation of what?
Down regulation of those under positive control
| (GH, LF/FSH, TSH, ACTH) up regulation of negative controlled prolactin
175
An early pituatry tumour is likely to manifest in what?
```
Ganadotropin defficeny
(GH, FSH, LH)
```
176
A early pituatry tumour has what characteristic features?
Loss of secondary sexual characteristic, loss of periods in women
177
An early pituatry hormone affects GH, LH, FSH, what would the next likely deficit be as the tumour develops?
TSH deficency
178
What would the blood serum look like in someone with TSH defficency due to a pituatry tumour?
Low TSH, low T3/4
179
What is a dangerous complication of a pituatry tumour?
If it progresses to ACTH deficency- low cortisol- life threatening
180
Tumours that cause hyperpituatry functions- what are common manifestations?
High prolactin, Gh or ACTH
181
What are rare elevations due to hyperpituatry functions/
TSH, LH/FSH
182
When testing the pituatry axis, when are basal blood tests sufficient?
When lookin at the thyroid axis, gonadal acids and prolactin axis
183
When are dynamic blood tests needed in the pituatry axis tests
Adrenal axis and GH axis
184
How do you look for a defficency in the adrenal or GH axis?
You stimulate the release of the hormone and measure response
185
How do you test for the excess of hormone from adrenal axis or Gh axis?
You suppress them and see the outcome
186
How do you test for adrenal deficency ?
Either by ACTH stimulation or a hypoglycaemic stress test, both should induce adrenal work
187
How do you test for excess adrenal stimulation?
You suppress them with steroids. If there axis is normal they will feel rotten
188
How do you test for a deficency in GH
Insulin stress test
189
How do you test for GH axis excess
Suppress GH axis with glucose, test levels
190
Why do you get bitemporal heminopia?
Chiasmal lesion affecting the right and left TEMPORAl fields only
191
How do you treat a prolactinoma?
Dopamine agonist (dopamine inhibits prolactin)
192
Who presents late with a prolactinoma?
Men as they have no menstrual disturbance
193
What are some symptoms of prolactinoma
Menstrual disturbance
Fertility issues
Galactorhoeas
194
If the prolactin is over 5000 what is it very likely to be
Prolactinoma
195
If the prolactin is less than 5000, what might it be instead of prolactinoma
Stalk effect
196
What is stalk effect in relation to raised prolactin
Prolactin is under tonic inhibitory control by dopamine
| If you block the stalk prolactin will raise
197
What can cause high prolactin that isn't a prolactinoma and isn't stalk effect/
```
Pregnancy
Dopamine agonists (anti psychotics)
```
198
How does a non functioning pituatry adenoma present?
Symptoms of mass effect or low pituatry hormones (other than prolactin)
199
What does a GH secreting pituatry tumour cause?
Acromegaly
200
What are some long term complications of a GH secreting pituatry tumour?
CV death, colonic tumours, disfiguring body changes, HTN, diabetes
201
How would you test for a GH secreting pituatry tumour?
Oral glucose tolerance test
| GH day curve
202
What's the treatment for a GH secreting tumour?
Surgical removal
Dopamine agonist (decrease GH secretion)
Somatostatin analogues
GH receptor blockers
203
Cushing disease (not syndrome) is a result of what
ACTH secreting pituatry tumour
204
What symptoms come wth Cushing disease
```
Round pink face
Round abdomen
Skinny weak arms
Thin skin
Striae of abdomen
HTN
Diabetes
Osteoporosis
```
205
What can Cushing syndrome be a result of?
Adrenal tumour, actopic ACTH, steroids
206
What's diabetes insipidus
Large quantities of pale urine and extreme thirst.
| Inhibition of ADH
207
Pituatry disease resulting in defficency of vasopressin is termed what
Cranial diabetes insipidus
208
Vasopressin resistance due to kidney disease is termed what?
Nephrogenic diabetes insipidus
209
What does untreated diabetes insipidus result in?
Very high sodium levels, severe dehydration, coma, death
210
What is a pituatry apoplexy
Acute stroke/vascular event in pituatry tumour
211
What symptoms come with pituatry apoplexy?
Headache, double vision, visual field loss, cranial nerve palsy
Hypopituatrism with cortisol deficency being the main danger
212
In the peripheral nervous system where do afferent branches go?
Towards the brain
213
In the peripheral nervous system where do efferent branches go?
Away from the brain
214
Where is the hypothalamus located?
Diencephalon
215
Where is the medulla oblongata located?
Brain stem
216
What are regions of the medulla involved in controlling?
Ventilation and cardiovascular system
217
What is 'hunting behaviour' in relation to negative feedback?
The tendency to overshoot the normal value, indicative of a dynamic equilibrium
218
How is ovulation an example of positive feedback
Build up of FSH causes release of oocyte from follicle in ovary
219
What should always be noted when testing cortisol levels?
The time
220
How long is a humansdiurnal cycle?
24 hours 11 minutes
221
What are zetigebers
Environmental ques that keep us on a 24 h cycle
222
What happens if there is a mismatch between zeitgebers and the diurnal cycle
Jet lag
223
What % of lean body weight is
Intracellular fluid
Extracellular fluid
Blood plasma
35%
12%
5%
224
What hormones are normally stored within the cell?
Polypetide
| Catecholamines
225
Steroid hormones arent stored in cells that produce them, but what is?
Cholesterol
226
What hormone concentration matters?
Free hormone
227
What do trophic hormones do?
Stimulate growth in target tissue
228
How are steroid hormones excreted?
Small chemical structure change making them water soluble-excreted in urine and bile
229
How are protein hormones excreted?
Undergo extensive chemical changes and are degraded to amino acids that are reused for protein synthesis
230
What POMC
Pro-opiomelanocortin
231
What is POMC cleaved into?
Beta endorphin
ACTH
Alpha melanocytes stimulating hormone
232
What does alpha melanocytes stimulating hormone (from POMC) do?
Acts on mealocortin 4 receptors to suppress apetite
233
What is beta endorphins action?
Prince euphoric, tired feeling after a meal
234
What does stretch of the stomach wall inhibit?
Ghrelin release
235
How does leptin produce heat?
Induces expression of uncoupling proteins in mitochondria
236
What two nerves are in close proximity to the thyroid gland?
Recurrent laryngeal
| External branch of superior laryngeal
237
What cells are present in the thyroid gland?
Follicular and parafollicular
238
When are higher levels of TSH released?
Night
239
What trophic effects does TSH have
Increase vascularity, size and number of follicle cells
240
In hashimotos disease what is happening?
Destruction of thyroid follicles or production of antibody that blocks TSH receptors
241
In Graves' disease what is happening?
Antibodies produced that stimulate TSH receptors on follicle cells
242
What is the hypothalamus-> post pituatry a classic example of?
Neurocrine signalling
243
What is the release of hormone from post pituatry into systemic circulation regulated by?
Neuronal inputs into hypothalamus
244
What does ADH induce to allow more reabsorbtion of water?
Translocation of aquaporin channels in the duct cells
245
What hormone is particulary important in resorting BP in hypoboelemic shock?
ADH
246
What cells produce growth hormone?
Somatotrope cells
247
What loops does GH secretion have to control its release?
Long and short
248
What is the long loop in growth hormones release?
IGF mediated inhibition of GHRH release and stimulated release of somatostatin.
249
What is the short loop of GH release?
GH itself stimulating somatostatin
250
What's the most common cause of pituatry malfunction?
Benign tumour (adenoma)
251
What are the anatomical divisions of the adrenal gland?
1. Capsule
2. Cortex- GFS, glomerulosa, fasciculata, reticularis
3. Medulla- chromaffin cells
252
What hormones are produced by the adrenal gland and from where?
```
Salt, sugar, sex, excitement (deeper=better)
G- mineralcorticoids (aldosterone)
F- glucocorticoids (cortisol)
R- androgens
Medulla- Arenaline and noradrenaline
```
253
Describe the structure of steroid hormones?
Cholesterol basis. Lipid soluble
254
How do steroid hormones affect target tissue?
Modulate gene transcription via nuclear receptors
255
How do glucocorticoids affect target tissue
1. Bind to receptor causing dissociation of chaperones
2. translocate into nucleus
3. Bind to glucocorticoid response element (GRE) or transcription factors
256
How is cortisol secretion controlled?
Hypothalamus-> CRH-> ant pit-> ACTH-> adrenal cortex-> cortisol (negative feedback on CRH and ACTH)
257
How does increased ACTH lead to hyperpigmentation?
Low cortisol causes increased production of ACTH
ACTH is made from POMC peptide. Other fragment of peptide is MSH (melanin stimulating hormone) also high ACTH directly stimulates melanin synthesis
258
What are the main physiological actions of cortisol?
```
Proteolysis
Increased gluconeogensis
Increased lipolysis
Inhibition of glut 4 receptors
Increase sensitivity to vasoconstrictors
Anti Inflam (inhibit macrophage and mast cell degranulation)
Immune suppression
```
259
What is the structure and function of adrenaline
It's a dopamine based structure involved in fight or flight responses
260
What is made in the zone reticularis
Androgens
Androstenedione- becomes oestrogen and testosterone
Dehydropiandrosteone
261
What is made in the zona fasculata
Glucocorticoids
| Cortisol, corticosterone, cortisone
262
What is made in the zona glomerulosa?
Aldosterone
263
What are glucocorticoids, mineralcorticoids, androgens, oestrogen, progestin?
Steroids
264
How is alodesterone transported in the blood?
Bound to albumin and to a lesser extent transcortin (mainly takes cortisol)
265
What does aldosterone do?
Promotes expression of Na/K pump in distal tubule and collecting duct of nephron
266
What is the cause of high aldosterone with low renin?
Primary- bilateral idiopathic adrenal hyperplasia or conns syndrome ( adrenal adenoma)
267
What's the cause of high aldosterone with high renin?
Secondary- renal artery stenosis or a renin producing tumour
268
How can you differentiate between primary and secondary hyperaldosterone?
Renin levels. Low if it's primary. High in secondary
269
What are signs of hyperaldosterone?
```
High bp
LVH
High Na
Low K
Stroke
```
270
What is the treatment for hyperaldosterone?
Adenoma surgery if that is the cause
| Sprironalactone- mineralcorticoids antagonist
271
How does cortisol travel in the blood?
Bound to transcortin
272
Why are corticosteroids useful as medication?
1. Anti-inflam- inhibit macrophages and mast cell degranulation
2. Immune suppression
273
Chronic high levels of cortisol has what effect on fat?
Redistribution to stomach, buffalo hump and moon face
274
What is Cushing? What are the overarching sources/causes?
Chronic high cortisol
| External (glucocorticoid) endogenous
275
What are some endogenous causes of Cushing?
Cushing disease- pituatry tumour secreting ACTH
Adrenal Cushing- adrenal adenoma secreting cortisol
Ectopic- somewhere else making cortisol like lung SMC
276
What's the most common cause of Cushing?
Corticosteroid use
277
What is Addison's disease? What is the most common cause?
Chronic adrenal insufficency
| Autoimmune
278
What are some symptoms of Addison's disease?
Lethargy, anorexia, weight loss skin pigmentation, hypoglycaemia, hypotension
279
What is an Addison's crisis? Why does it happen? What are symptoms?
Life threatening adrenal insufficency-
Extremely low cortisol and high acth. Could be due to Addison's or coming off steroids quickly (adrenal suppressed)
Vomiting, hypotension, nausea, pyrexia
280
What is the timeline of adrenaline synthesis?
Tyrosine-> LDOPA-> Dopamine-> noradrenaline-> adrenaline
281
What enzyme converts noradrenaline to adrenaline?
N methyl transferase
282
What does an alpha 1 GPCR do?
Activate phospholipsae C
Cleave pip to ip3 and dag
Activating PKC and calcium via Ip3
283
What do beta 1 and beta 2 receptors do?
Positive effect on adenyl cyclase-> Camp-> PKA
284
What does an alpha 2 GPCR do
Negative effect on adenyl cyclase
285
What receptors in lung and heart
We have 1 heart and 2 lungs
Beta 1 heart
Beta 2 lungs
286
What receptors are on skin and gut? What happens when noradrenaline stim?
Alpha 1- vasoconstriction
287
What receptors for adrenaline on skeletal muscle vessels?
Beta 2- dilation
288
How does adrenaline increase HR
```
Stimulates beta 1 receptor
Increase ardenyl cyclase therfore activate cAMP and PKA
CAMP- HCN activation
PKA- HCN and L type calcium channel
Speeds up funny current
```
289
What's a pheochromocytoma
Chromaffin tumour secreting adrenaline
290
What are symptoms of pheochromocytoma
Extreme HTN, Palpitation, headache, anxiety, sweating
291
Secretions from islets of langerhann enter what blood vessel?
What is the pancreas anterior to?
What is the pancreas superior to?
Portal vein for endocrine excretion
Aorta
Duodenum
292
What are the 2 functions of the pancreas?
Exocrine- digestive enzymes to duodenum
| Endocrine from islets of langerhann (1% of tissue)
293
The endocrine hormones are what type of hormone??
| What are the 7 and there corresponding cells?
Polypeptide hormones
1. Insulin- beta cells
2. Glucagon- Alpha cells
3. somatostatin- delta cells
4. Pancreatic polypeptides- PP cells
5. Ghrelin- E cells
6. Gastrin- G cells
7. Vasoactive intestinal peptide-VIP cells
294
In apetite control what do AgRP and NPY do?
| What does alpha MSH do? Where is it from
AgRP and NPY promote hunger
| Alpha MSH promotes satiety (from POMC)
295
What hormones in particular affect hunger? What are they?
Insulin and leptin inhibit hunger
| Ghrelin and PYY (SI) promote hunger
296
What tissues does insulin target?
| What about glucagon
Insulin- liver, skeletal muscle and adipose
| Glucagon- liver and adipose
297
```
What are plasma glucose levels?
What are they after a meal?
What's the renal threshold?
What fasting level is indicative of DM?
What random level is indicative of DM/
```
```
3-3.6 normal level
Up to 7-8 after a meal
10 is the renal threshold
Fasting above 7
Random above 11.1
```
298
What are some key features of both insulin and glucagon?
Water soluble
Half lives of 5 mins
Cell surface receptors
Receptors become internalised cone activated
299
What properties does insulin have?
| What is its structure?
It's anti lipolytic and anti ketogenic
| A chain and B chain with 2 disulphide bonds and a 3rd within the A chain
300
How is insulin synthesised?
Preproinsulin enters the ER, leaves as proinsulin where it goes to the Golgi, cleaved into proinsulin and c peptide, in vesicles near cell surface membrane
301
How is insulin secreted?
Glucose enters cell via glut 2, ATP rises which inhibits the potassium channel (keeping cell hyperpolarised), cell depolarises, calcium influx leading to vesicle release
302
Describe the insulin receptor?what action does it have?
Dimer of 2 sub-units made of alpha and beta
When activated it caused insertion of glut 4 receptor to cell. Glycogenesis stim, fatty acid synthesis and affects pyruvate
303
What's the effect of insulin in the liver, muscle and adipose?
Liver- increase glycogen, inhibit AA breakdown
Muscle- increase uptake of AA for protein synthesis
Adipose- increase storage of triglycerides
304
What are the effects of glucogen?
| What cells
Alpha cells
| Glyconeolytic, glucogenic, lipolytic and ketogenic
305
What are the rapid effects of GLu/Ins?
Glucose uptake and glycolyis
306
What are the intermediate effects of INS/GLU?
Glucogenesis, glycogenesis, glycogenolysis
307
What are the slow effects of INS/GLU
Lipogenesis, lipolysis, ketogenesis
308
Increased insulin results in what?
Decreased insulin results in what?
Increase glucagon?
Decrease glucagon?
Increase INS hypoglycaemia, decrease INS- hyperglycaemia
| Increase GLU worsens DM decrease GLU Hypoglycaemia
309
T1DM is usually due to what? When can you get relative B cell destruction?
Autoimmune destruction of B cell
| Relative due to abnormal K pump
310
What is the issue in T2DM
Normal insulin but a decrease in sensitivity peripherally, or an excessive release of glucagon
311
What are some common complications of DM
```
Kidney disease
Amputation
CVD-stroke, CAD
Retinopathy
Neuropathy
Nephropathy
```
312
What is metabolic syndrome?
```
Cluster of increased waist size + 2 or more:
Increase triglycerides
Decreased HDL
Increased BP
Increased fasting glucose/ diabetes
```
313
What are symptoms of hyperglycaemia?
Polyuria
Polydipsia
Blurring of vision
UTI
314
What are some symptoms of inadequate energy utilisation seen in T1DM
Tiredness, weakness, lethargy, weight loss
315
HBA1c test for what?
DM
| 6.5% and above
316
Type 1 onset is characterised by what?
Rapid onset
Weight loss, polyuria, polydipsia
If doesnt present then could be vomiting due to ketoacidosis
Patient is usually young with raised plasma glucose and ketones
317
Type2 DM onset is characteristed by what?
90% overweight
Often asymptomatic and picked up on general health check
May have symptoms of polyuria, polydipsia and weight loss
No urinary ketones but raised plasma glucose
318
How do the management of type 1 and 2 DM differ?
Type 1- insulin injection
| Type 2- begin with exercise and diet change, progress to metformin tablets, progress to insulin
319
Hyperglycaemia results in what for T1DM and what for T2DM
T1- ketoacidosis
| T2- hyperosmolar non ketotic syndrome
320
Hypoglycaemia results in what?
Coma
321
What are 4 key components of a control system?
Communication
Control centre
Receptor
Effector
322
What hormones are lipophillic and require specialist transport proteins
Steroid and thyroid
323
How does a hydrophilic hormone elicit a repsonse
Via a 2nd messenger from cell surface receptors
324
What hormones are hydrophilic?
Proteins and catecholamines
325
What is cytoplasmic NADPH production used for?
Biosynthesis
Detoxification
Recycling of oxidised glutathione
C5 production for nucleotides
326
What does an enzyme activity of 1.3 U/g haemoglobin mean?
1 unit of enzyme activity is the amount of enzyme that will catalyse the transformation of 1 µmol of substrate per min at optimal conditions
So for haemoglobin it means that for every gram of haemoglobin there will be enough G6PDH to catalyse the oxidative decarboxylation of 1.3µmol of glucose 6 phosphate per min
327
```
e normal activities of glucose 6-phosphate dehydrogenase in
different tissues (U/g) are:
Red blood cells 13
Liver 1
Adipose tissue 1.5
Skeletal muscle 0.01
Brain 0.2
How do you account for these differences?
```
Red blood cells - maintenance of protein –SH groups. Liver - lipid synthesis and detoxification reactions. Adipose tissue – lipid synthesis. Brain – synthesis of lipids. Skeletal muscle - no major requirement
328
What drugs can have a serious effect on individuals with G6PDH defficency? Why?
Primaquine, aspirin, sulphonamides
They oxidise celllular glutathione which under normal conditions would be recycled back by glutathione reductase, which requires NADPH from PPP
329
Why does GSPDH cause Heinz bodies
Haemoglobin and other proteins become cross linked by disulphide bonds resulting in insoluble aggregates.
Disulphide bonds due to oxidative damage as glutathione not reduced by NADPH and glutathione reductase
330
Other than red blood cells where else is likely to get damaged in G6PDH defficency?
Lens of eye as requires adequate NADPH to protect against oxidative damage. This can cause damage to the lens (cataracts) caused by denatured crystalline protein
331
What stimulates increased t3.4 release?
Stress and fall in temp
332
TSH affects what cells?
Follicular cells of thyroid
333
How is TSH released?(pattern)
Low amplitude pulses following diurnal rhythm
| Higher levels durin night and low in early hours
334
What effect does TSH have to cause goitre
Trophic
335
What does t3/4 travel bound to?
Thyroxine binding globulin, pre albumin and albumin
336
How do thyroid hormones increase heat?
The increased rate of protein synthesis stimulates oxidative energy metabolism in the target cells to provide the extra energy required for protein synthesis. In addition, protein synthesis produces increased amounts of specific functional proteins leading to increased cell activity and an increased demand for energy.
337
How do t3 and 4 increase metabolic rate?
T3 and T4 increase the metabolic rate of most tissues, stimulate glucose uptake and metabolism, stimulate mobilisation and oxidation of fatty acids and stimulate protein metabolism. Their metabolic effects are generally catabolic and lead to an increase in BMR, heat production and increased oxygen consumption.
338
What specific effects does t3/4 have on
Bone
Heart muscle
CNS
Bone- directly affect bone mineralisation
Heart- increase protein synthesis of heart muscle protein
CNS- development of cellular processes of nerve cells, hyperplasia of cortical neurone and myelination of fibres
339
Hypothyroidism symptoms? And why
Weight gain due to reduced BMR.
Cold intolerance due to reduced BMR.
Lethargy/tiredness due to reduced uptake of nutrients by
muscle.
Bradycardia – slow heart rate due to reduced responsiveness
to catecholamines and reduced heart muscle protein
synthesis.
Dry skin and hair loss due to reduced synthesis of proteins.
Slow reflexes and clumsiness due to reduced sensitivity to
catecholamines.
Constipation due to reduced responsiveness of GI tract
Hoarse voice.
340
Symptoms of hyperthyroidism?
```
Weight loss
Heat intolerance
Irritability
Tachy
Fatigue
Increased bowel movement
Menstrual disturbance
Hyper reflexive
Possible tremor
```
341
```
Weight loss
Heat intolerance
Irritability
Tachy
Fatigue
Increased bowel movement
Menstrual disturbance
Hyper reflexive
Possible tremor
Why do these occur in hyperthyroidism
```
Catabolic effects of T3 on tissue metabolism increasing metabolic rate
Effect of catecholamine sensitivity
Bone and nervous system specific effects
342
What does somatostatin inhibit
Release of GH
343
When is CRH secreteed?
Response to physical (temp and pain)
Chemcical (hypo)
Emotional stressors
344
Why can cortisol have androgen like effects at high concentrations?
Binding domains have 60% sequence homology- therefore can bind to have limited activation
345
What is steroid diabetes?
Due to the increased proteolysis and gluconeogensis in high coricosteroid doses hyperglycaemia can develop
346
Why do you get purple striae in Cushing
Reflects the catabolic nature- catabolic effect on protein structure
347
Why do you get HTN in Cushing
Mineralcorticoids effects may produce sodium retention
348
Why do you get postural hypotension in Addison's?
Fluid depletion due to lack of aldosterone
349
What is the onset of addisons normally like?
Insidious non specific symptoms of tiredness, muscle weakness, anorexia, weight loss, dizziness
350
How would an addisonian diseased person react to stress?
May not be appropriate as adrenal steroids likely not working properly
May lead to addisonian crisis
351
What's the treatment of addisonian crisis
Fluid replacement 5% dectose in saline
| Cortisol
352
Signs and symptoms of type 1 diabetes
```
Hyperglycaemia
Glycosuria
Polyuria
Polydipsia
Weight loss
Ketoacidosis
```
353
What does ketoacidosis occur in T1DM
Increase rate of lipolysis therefore large amounts of fatty acids
Activation of ketogenic enzymes
354
What are some of the long term consequences of persistent hyperglycaemia
Macrovascular: increased risk of stroke and mi, poor circulation
```
Microvascular:
Eye disease-glaucoma, retinopathy, cataracts
Nephropathy
PVD
Diabetic foot
```
355
How much calcium in the body roughly? How much in bone? As what?
1000g, 99% in bone as hydroxyapatite
356
What's our dietary intake, how much is lost in the GI, how much is entreated in the day through urine
1000mg, 825 lost in the GI 175 lost in urine
357
What 3 hormones control calcium regulation?
Add a + if they increase plasma levels
And a - if they decrease plasma levels
PTH +
Calcitrol +
Calcitonin -
358
What is PTH action?
Releases calcium into circulation (encourage osteoclast activity)
Increases calcium reabsorbtion in the kidney
Causes hydroxylation of D3 to calcitrol
359
What does calcitrol do? What stimulates it
Increases intestinal absorbtion and renal reabsorbtion, stimulated by PTH
360
What's calcitonins action? Where is it produced
```
Counteracts PTH (pretty minimal)
Made in C cells/ parafollicular cells of the THYMUS
```
361
Where is PTH secreted form?
How does it travel in the blood?
What is its half life?
Chief cells of parathryroid
No serum binding protein
4.5 minutes
362
How is PTH regulation controlled?
Controlled by calcium levels. Low levels increase gene transcription and prolong the survival of the mRNA
High levels- Calcium binds to GPCR and Q subunit caused IP3 to increase intracellular calcium that inhibits PTH secretion
363
Where does PTH exert its effects? What does it do at each site?
Bone- increases resorption
Gut- activated vit D to increase GI uptake
Kidney- decreases loss of calcium
364
What are the 2 functions of bone?
Structure and maintaining calcium concentration in the plasma
365
How does PTH increase plasma calcium in regards to bone?>
Stimulates osteolysis
| Induces cytokine release from osteoclasts
366
What is a key effect the PTH hormone has on the kidney? Both to increase calcium levels but decrease risk of kidney stones
Increase calcium reabsorbtion and inhibit phosphate reabsorbtion
367
How do we get calcitrol?
Conversion of cholesterol with sunlight
Diet d3 (yeast and dairy)
Diet D4 (fungi)
Conversion via PTH
368
How doe calcitrol travle in the blood, whats its half life?
Bound to CBP
| .25 days
369
What symptoms are assocaited with hypocalcaemia? What is a key principle to do with low calcium
Decreased calcium brings nerve tissue closer to threshold
| Pins and needles, tettany, paralysis, convulsions
370
What is hyperthyroidism associated with
Stones, moans and groans
371
In the blood, what is calciums role?
Clotting factor IV
372
What is used in blood for blood transfusions to stop the blood clotting? What's the relevance of that?
Citrate
| If a patient recieves many blood transfusions they also need calcium
373
What are some key clinical causes of hypercalcaemia
Malignant osteolytic bone met
Multiple myeloma
Adenoma
374
What are 5 cancers that mainly cause bone mets?
| Which are osteolytic and which are osteoblastic
```
Prostate- blastic
Breast- lytic
Lungs
Renal
Thyroid
```
375
Where are the main site of bone mets?
Femur, vertabrae, pelvis, humerus, skill
376
What's a primary hyperparathyroidism? What would the serum show?
Primary adenoma of the parathyroid
Raised serum calcium (pth action)
Low serum phosphate (pth action)
High alkaline phosphotase (osteolytic
377
What's secondary hyperparathyoidism? What's the cause? What would serology show
Low vitamin D
Low serum calcium
High PTH
Bone pain due to osteolysis ++
378
What are 2 signs of hypocalcaemia? Tests
Carpopedal spasm
| Chvostek Sign
379
What's the difference between osteomalacia and osteoporosis
Porosis the proportion of mineral to matrix is normal, there's just less of it and therefore brittle
Malaria, there is not enough mineral , and therefore bendy
