Metabolism Sessions 7-11 Flashcards
(519 cards)
1
Q
What methods of communication can be used in a control system?
A
Action potentials
Endocrine hormones
Paracrine hormones
Autocrine hormones
2
Q
What is the function of a control centre in a control system?
A
Determines set point, analyses input and determines response
3
Q
Which pathway does the receptor of a control system use?
A
Afferent
4
Q
Which pathway does the effector of a control system use?
A
Efferent
5
Q
What happens in a negative feedback loop?
A
Effector opposes stimulus
6
Q
Which feedback regulates most homeostatic systems?
A
Negative
7
Q
What is positive feedback?
A
Stimulus produces response which increases its effects causing rapid catastrophic change which can result in a change in state e.g. blood clotting
8
Q
What does blood cortisol have to be measured at the same time each day?
A
Follows a circadian/diurnal rhythm
9
Q
What controls the biological clock in the body?
A
Suprchiasmatic nucleus (collection of neurones) in the hypothalamus
10
Q
Why is the body clock cycle reset by external stimuli?
A
It is naturally slightly longer the 24 hours
11
Q
What causes jet lag?
A
External stimuli and biological clock indicate different times
12
Q
What is released from the pineal gland as soon as eyes are closed to regulate the light/dark cycle?
A
Melatonin
13
Q
Why does melatonin release need optic nerve input?
A
Pineal gland it is released from is buried right at the centre of the brain
14
Q
Where is the pituitary gland located?
A
Hangs down from hypothalamus
15
Q
How are the parts of the pituitary gland related to its function?
A
Anterior = endocrine supplied by veins Posterior = neuroendocrine supplied by veins and arteries
16
Q
What percentage of body mass is water in makes and females respectively?
A
50-60% males
45-50% females
17
Q
Why do females have a lower percentage mass of water?
A
They have more fat
18
Q
What is osmolality?
A
Solvent expressed per weight of solvent
19
Q
What is measured along with sodium ion concentration by osmoreceptors in the hypothalamus?
A
Osmolality
20
Q
How does the body counteract and increase in blood plasma osmolality?
A
Released ADH from posterior pituitary to increase reabsorption of water from urine in collecting ducts
21
Q
What is the name given to a biologically active signalling chemical?
A
Hormone
22
Q
Which organs make up the endocrine system?
A
Hypothalamus Pituitary gland Parathyroid glands Heart Adrenal glands Kidneys Pineal glands Thyroid glands Stomach Pancreas Intestines Ovaries/testes
23
Q
What type of responses is the endocrine system good for?
A
Coordinated multiple
24
Q
What blood system does the hypothalamus release factors into?
A
Portal
25
What is considered as the 'master gland' of the endocrine system?
Anterior pituitary
26
What does the anterior pituitary gland release on stimulation from the hypothalamus?
Trophic (stimulating) hormones
27
Which axis is the classic stress response?
Hypothalamic-pituitary-adrenal (HPA)
28
What controls the HPA axis?
-ve feedback
29
Which hormones are elevated in the classic stress response?
Corticotrophin releasing hormone (CRH)
Adrenocorticotrophin releasing hormone (ACTH)
Cortisol
30
What is the rate of secretion in the endocrine system usually controlled by?
-ve feedback
31
Why are hormones very difficult to measure in the body?
Circulate in very low concentrations
32
What is the solubility of hormones like?
Some peptide and amine are water soluble
| Steroid and thyroid are lipid soluble
33
How are steroid and thyroid hormones carried in the blood?
Steroid by specific steroid binding globulins
| Thyroid by thyroid binding globulins (TBG)
34
What is there between the biologically inactive bound form and biologically active free form of hormone?
Dynamic equilibrium
35
What is the function of carrier proteins in hormone transport?
Increase solubility in plasma
Increase half-life
Create readily accessible reserve
36
Why is a readily accessible reserve of hormone provided by carrier proteins important for thyroxine?
It is tightly bound
37
What are the four classes of human hormones?
Peptide
Glycoprotein
Steroid
Amine
38
Which is the largest class of human hormones?
Peptide
39
How many known peptide hormones are there?
~20 but often increases due to new gut discoveries
40
What are all steroid hormones derived from?
Cholesterol
41
Which two steroid hormones is there one group difference between?
Testosterone and progesterone
42
Give some examples of steroid hormones.
```
Vitamin D
Corticosteroids
Progestins
Androgens
Oestrogens
```
43
How many major amine hormones are there?
3
44
What is a main precursor of amine hormones?
Tyrosine
45
Give two examples of locally acting amine hormones.
Histamine and serotonin
46
What is the precursor of histamine?
Histidine
47
What is the precursor of serotonin?
Tryptophan
48
What is the structure of glycoprotein hormones?
2 polypeptides and a carbohydrate side chain
49
Where are all glycoprotein hormones released from?
Anterior pituitary gland
50
Give four examples of glycoprotein hormones.
TSH
FSH
LH
hCG
51
What does the magnitude of a hormonal response depend on?
Concentration of active hormone at target tissue
Receptor number
Affinity of receptor for hormone
Degree of signal amplification
52
Which type of hormones can cross the CSM?
Steroid
53
Where do steroid hormones bind to cellular receptors?
In nucleus or in cytosol (heat shock protein) which moves into the nucleus
54
What effects do steroid hormones have in the nucleus?
Alters transcription process - either switches on or off enzyme expression to affect enzyme action of cell
55
What happens upon binding of a hormone that cannot cross the CSM to a receptor on the cell surface?
Activates second messenger whose products affect enzyme action in cell
56
Can steroid hormones bind to CSM receptors and affect enzyme action in a cell?
New research says yes
57
What do control systems in the body require?
Communication
Control centre
Receptor
Effector
58
What controls appetite?
Appetite centre/satiety centre located in the arcuate nucleus in the hypothalamus
59
How many types of neurones are there in the arcuate nucleus?
2
60
What is the function of the primary neurones in the arcuate nucleus?
Sense glucose and FA in the blood
| Respond to hormones
61
What is the function of secondary neurones in the arcuate nucleus?
Synthesise input
Coordinate a response
Signal to higher sensors in the brain
62
Which hormones are excitatory in the control of appetite?
Neuropeptide Y
| Agouti-related peptide
63
Which hormones are inhibitory in the control of appetite?
POMC
Beta-endorphin
Alpha-melanocytes stimulating hormone
64
What is ghrelin?
Peptide hormone released from stomach wall when empty which is the only known hormone to stimulate appetite
65
When is ghrelin inhibited?
When stomach is filled
66
What is cleaved off POMC which suppresses appetite?
Alpha-MSH
67
Which peptide hormone is released from the wall of the small intestine that suppresses appetite?
PYY
68
What is released from adipocytes to signal appetite suppression?
Lepton
69
How does lepton cause excess energy in stores to be dissipated as heat?
Induces uncoupling protein expression
70
Which peptide hormone is secreted by beta cells in the pancreas to suppress appetite?
Amylin
71
Which peptide hormone uses the same mechanism as leptin but is less important in its role of suppressing appetite?
Insulin
72
How does glucagon-like peptide cause weight loss?
Released from gut to enhance insulin release
73
Which gut hormone causes weight loss and 'cures' T2DM?
Oxyntomodulin
74
What does an injection of leptin into deficient patients treat?
Hyperphagia
75
What conditions comprise metabolic syndrome?
Insulin resistance
Dyslipidaemia
Impaired glucose tolerance
Hypertension
76
What three methods of bariatric surgery are available?
Adjustable gastric band
Roux-en-Y gastric bypass
Vertical sleeve gastrectomy
77
Why is Roux-en-Y gastric bypass the most effective type of bariatric surgery?
Reroutes small intestine so gut hormones no longer act
78
What benefits can Roux-en-Y gastric bypass have?
Rapid weight loss
Reversal of T2DM due to signalling changes
Reverses infertility caused by obesity
79
What is gut microbiome composition associated with?
Obesity
T2DM
CVD
Non-alcoholic fatty liver disease
80
What does the strong association between CHD, hypertension, T2DM (adult disease) and low birth and placenta weight suggest?
Foetal programming
81
What is foetal programming?
Foetus adapts to conditions in utero --> biochemical adaptations are 'programmed in' predisposing to adult diseases
82
What genetic mechanism explains foetal programming?
Epigentics
83
What is epigenetics?
Inherited phenotype resulting from change in a chromosome w/out change in the DNA sequence
84
What changes to histones can cause suppression of gene transcription?
DNA methylation changes histone structure
| 'Tails' on histones affected by surroundings which alters DNA
85
What is diabetes mellitus?
Hyperglycaemia which over years leads to damage of small and large blood vessels causing premature death from CVD
86
What is diabetes mellitus characterised by?
Hyperglycaemia but may have other metabolic abnormalities
87
How can the insulin levels be affected in diabetes mellitus?
Beta-cell failure so not produced
| Production is fine but resistance prevents it from working properly
88
How do patients with diabetes present?
```
Polyuria
Polydipsia
Tiredness
Weakness
Blurring of vision
Urinary tract infections
Weight loss
```
89
What is needed to diagnose diabetes?
Either symptoms and 1 abnormal blood test or asymptomatic with 2 abnormal tests
90
What blood tests can be used to diagnose diabetes?
Fasting glucose
Oral glucose tolerance test
HbA1C
91
What is a long term indicator of glycaemic control?
Glycosylated haemoglobin - HbA1C
92
How is a patient in the impaired glucose tolerance range often treated?
Same as if they were in the diabetic range
93
What is type I diabetes?
Autoimmune or non-immune deficiency of insulin
94
How does T2DM differ from T1DM?
Characterised by insulin deficiency and resistance
95
What can cause T2DM?
```
Iron overload
Pancreactectomy
Genetic beta-cell defects
Drug induced - steroid, diuretics, beta-blockers
Hormone disorders e.g. cortisol
Genetic defects of insulin action
```
96
How does type I diabetes mellitus present?
```
Rapid onset
Weight loss
Polyuria
Polydipsia
Late presentation --> vomiting from ketoacidosis
```
97
Why must identified cases of T1DM be urgently referred?
High risk of ketoacidosis and death
98
What diagnostic feature can be used to differentiate between T1 and T2 diabetes?
T1 has ketones present in the urine, T2 does not
99
What are the functions of insulin on fuel metabolism?
Enhance glucose uptake by the liver
Inhibit liver glycogen breakdown
Enhance glucose uptake by muscle and adipose
100
What effects does insulin have in amino acids?
Inhibits catabolism
Inhibits gluconeogenesis in liver
Stimulates active transportation into cells
101
What effect does insulin have on FA?
Promotes their clearance
102
What treatment is given in ketoacidosis?
SC injection of exogenous insulin w/fluids and potassium
103
What causes diabetic ketoacidosis?
Hyperglycaemia and dehydration lead to production of serum acetone
104
How does obesity cause hyperglycaemia?
Increases insulin secretion --> pancreatic exhaustion
105
What occurs in T2DM that can cause beta-cell failure?
Amyloid type deposits
106
What can be considered as a potentially reversible metabolic disorder which is precipitated by chronic intraorgan fat?
T2DM
107
How does bariatric surgery or hypocalorific diet cause reversal of T2DM?
Calorific intake falls --> profound change in [fat metabolites] --> fat mobilised first from liver then other ectopic sites rather than subcutaneous --> pancreatic fat content decreases normalising bet-cell function
108
Which two pathologies must both happen to cause T2DM?
Insulin resistance and relative lack of insulin
109
Is T2DM caused by genetic or environmental factors?
Both
110
How do T2DM patients present?
Variably due to slow rise in blood glucose
Polyuria
Polydipsia
Weight loss
111
Can T2DM patients be asymptomatic?
Yes
112
In what age group is T2DM usually seen?
40+ but increasingly seen in the young
113
Why are no ketones seen in the urine in T2DM?
Beta cells still produce some insulin, just not enough
114
Why do even asymptomatic T2DM patients have to maintain good blood glucose control?
To reduce risk of complications e.g. significant morbidity, mortality
115
How is T2DM treated?
```
Change lifestyle factors
Metformin
Sulphonylureas
GLP1 to suppress appetite
Insulin as a last resort
```
116
What life-long monitoring methods are used in T2DM?
```
Well being
Glucose control - capillary vs urinary glucose testing
HbA1C
Vascular risk factors
Surveillance for chronic complications
```
117
How is the function of the pancreas split?
~1% of tissue is endocrine
| ~99% of tissue is exocrine
118
What are the exocrine secretions of the pancreas?
Digestive enzymes directly into duodenum
| Alkaline secretions through pancreatic duct into duodenum
119
How does the pancreas develop embryologically?
As an outgrowth of the foregut
120
What are the five major cell types and their respective functions in the endocrine pancreas?
```
Alpha - glucagon
Beta - insulin
Delta - somatostatin
F - pancreatic polypeptide
Unnamed - ghrelin
```
121
What is the combined function of insulin and glucagon?
Regulation of metabolism of carbohydrates, proteins and fats
122
What are the target tissues of insulin?
Liver
Adipose
Skeletal muscle
123
What does insulin affect the metabolism of?
Carbohydrates
Lipids
Proteins
124
Is insulin anabolic or catabolic?
Anabolic
125
What are the target tissues of glucagon?
Liver
| Adipose
126
What does glucagon affect the metabolism of?
Carbohydrates
| Lipids
127
What would cause swelling/shrinking of cells in the brain, thus causing detrimental damage?
Changes in blood glucose altering osmolarity
128
What can alter the renal threshold?
Elderly increases
| Pregnancy decreases it
129
How are insulin and glucagon carried in the blood?
Dissolved in plasma
130
What is the half life of insulin and glucagon?
5 minutes
131
What happens when glucagon and insulin reach target cells?
Interact w/cell surface receptors and form a complex which can be internalised
132
Why does insulin have a rigid structure?
Has 2 sulphide bridges
133
How is insulin mRNA translated?
Single chain precursor called preproinsulin
134
What happens to preproinsulin on insertion to the ER?
Pre cleaved off
135
What happens to proinsulin in the ER?
Exposed to specific endopeptidases which excise C peptide
136
What happens to the mature insulin in the Golgi and cytoplasm?
Insulin and free C peptide packaged in Golgi into secretory granules which accumulate in cytoplasm
137
What is the process of margination in insulin secretion?
Storage vesicles --> CSM --> exocytosis
138
Why is rapid turnover of insulin needed?
Short half life
139
How does [glucose] in beta-cells rise?
Enters by facilitated diffusion through GLUT2
140
How does increasing [glucose] in beta-cells cause release of insulin?
Allows more ATP to be formed so ATP sensitive potassium channel can function --> membrane depolarised --> V-G calcium channel opens and calcium influx triggers exocytosis of insulin
141
What effect can metabolic insulin have in GLUT4?
Increases insertion to increase glucose uptake into target cells and increase glycogen synthesis
142
What is the structure of an insulin receptor?
Alpha-chain on exterior of cell membrane
Beta-chain spans cell membrane in single segment
2 units held together by a disulphide bond
Receptor is a dimer
143
What causes the insulin receptor to become active tyrosine kinase?
Alpha-chains move together and fold round insulin which moves beta-chains together
144
What effects does tyrosine kinase activation by insulin have in the cell?
Initiates phosphorylation cascade which results in increased GLUT4 expression so cells can take up more glucose
145
What causes glucagon secretion?
Low glucose levels within alpha-cells
146
How is glucagon synthesised?
In RER and transported to Golgi where it is packaged into granules
147
Why is glucagon more flexible than insulin?
No disulphide bridges
148
How are granules of glucagon secreted?
Move to cell surface by margination and exocytosis
149
What is the only case where glucagon is not antagonistic to insulin?
When it increases gluconeogenesis when a protein rich meal is consumed
150
Is glycolysis and amino acid and glucose uptake into muscle and adipose rapid, intermediate or delayed?
Rapid
151
What are the delayed effects of insulin and glucagon?
Lipogenesis
Lipolysis
Ketogenesis
152
What happens initially in insulin resistance in the young?
Beta-cells compensate by increasing insulin production which maintains normal blood glucose but kills beta-cells off
153
What happens eventually in insulin resistance in the young to cause impaired glucose tolerance?
Beta-cells are unable to maintain increased insulin production
154
What happens finally in insulin resistance in the young causing overt T2DM?
Beta-cell dysfunction leads to relative insulin deficiency
155
What is decreased in the adipose tissue in addition to decreased lipogenesis in chronic hyperglycaemia?
Esterification
156
What are the long-term consequences of chronic hyperglycaemia?
Muscle wasting
Weight loss
Ketosis
Hyperglycaemia
157
What are chronic long-term microvascular consequences of chronic hyperglycaemia?
Neuropathy
Nephropathy
Retinopathy
158
What are acute metabolic consequences of choroid hyperglycaemia?
Glycosuria - exceeds renal threshold
Polydipsia
Poolyuria
159
What are chronic microvascular consequences of chronic hyperglycaemia?
Stroke
Coronary artery disease
Poor peripheral circulation esp. feet
160
How does the development of the anterior and posterior pituitary gland vary?
Anterior derives from primitive gut tissue
| Posterior is brain tissue
161
Why are tumours seen in the gut and pituitary similar?
Derived from same primitive tissue
162
What is the link between the endocrine and nervous system?
Hyothalamo-pituitary axis
163
What is a slower metabolic response than the neurological response to the external environment?
Endocrine response
164
What characteristic symptom does upward tumour growth in the pituitary gland cause?
Tunnel vision due to optic chiasm disruption
165
Why does sideways tumour growth in the pituitary gland cause headaches and vision problems?
Cranial nerves disrupted
166
What hormones does the anterior pituitary gland secrete?
```
ACTH
Prolactin
Growth hormone
TSH
LH
FSH
```
167
Which hormone released by the anterior pituitary gland is the only one under inhibitory control?
Prolactin
168
Which two hormones are secreted by the posterior pituitary gland?
Oxytocin
| ADH
169
What stimulates lactation after birth?
Oxytocin
170
Do correctly managed benign pituitary tumours reduce life expectancy?
No
171
What are the five anterior pituitary axes?
```
Growth hormone
ACTH
LH/FSH
TSH
Prolactin
```
172
Which anterior pituitary axis is abused by athletes/body builders?
Growth hormone
173
Which growth axis that is important for growth and metabolism increases blood glucose like adrenaline but for longer?
Growth hormone
174
Which tissues does GH act on?
All
175
How does the growth hormone axis work?
Via insulin-like growth factor (IGF-1) produced by the liver which on binding to receptor stimulates secondary messenger by dimerisation of receptor
176
What is secreted by the hypothalamus to increase and suppress growth hormone action?
GRH increases
| Somatostatin decreases
177
Why does somatostatin inhibit lots of hormones, especially gut hormones?
Due to their origin
178
When is GH normally released?
Few pulses each day, mostly during sleep
179
What does a high mean GH level cause?
Acromegaly
180
What are the functions of GH?
```
Skeletal growth
Metabolism
Muscle strength
Bone density
Cardiac function
Quality of life
```
181
How do the changes seen in growth hormone differ in adults and children?
Changes more subtle in adults than children
182
Which anterior pituitary axis is the most important to preserve life and why?
Hypothalamo-pituitary-adrenal axis as lack of ACTH is potentially fatal
183
In what rhythm are CRH and ACTH secreted in?
Circadian
184
What gives a positive hypothalamic control in the hypothalamo-pituitary-adrenal axis?
CRH
185
What external factor causes ACTH release?
Stress
186
How do cortisol deficient patients feel all the time?
Sick and groggy
187
What is used to treat cortisol deficient patients?
Hydrocortisone
188
When would you measure cortisol levels in suspected Addison's and why?
Early in the morning when cortisol level is highest
189
When would you measure cortisol levels in suspected Cushing's and why?
Midnight as this is when cortisol levels are at their lowest
190
Which axis is controlled by the action of LH/FSH?
Hypothalamo-pituitary-gonadal axis
191
What stimulates LH/FSH release from the pituitary gland?
GnRH
192
What feedback mechanism do LH/FSH use in men?
Simple -ve feedback
193
What action do LH and FSH have in men?
LH drives testosterone secretion
| FSH drives sperm production
194
When would you measure LH and FSH levels in men and why?
Highest in morning due to circadian rhythm so measure then
195
Which method of feedback do LH and FSH use during their mid-cycle surge?
+ve
196
What does LH cause in the follicular phase in women?
Pulses cause oestrogen release
197
What do LH pulses cause in the mid-late luteal phase in women?
Progesterone release
198
Which type of feedback does the hypothalamo-pituitary-thyroid axis use?
Simple -ve
199
How is production of T3 and T4 stimulated?
TRH stimulates pituitary to secrete TSH which activates follicular cells in thyroid
200
What is the function of prolactin?
Initiate and maintain lactation
201
What is the target of the lactotroph axis?
Peripheral tissues with no target gland
202
What do high levels of prolactin cause?
Lactation and menstrual disturbance - inhibits menstruation
203
What tonically inhibits prolactin?
Dopamine
204
What increases prolactin levels?
Minor positive control by TRH
| Oestrogen
205
What pattern of secretion does prolactin follow?
Pulsatile, slightly higher at night
206
When can you measure prolactin?
Any time of day
207
What are high levels of prolactin caused by?
5Ps: pregnancy, physiological (stress), pharmacological, pituitary, polycystic ovaries
208
What is primary gland failure?
Failure of actual organ
209
What hormone levels are seen in primary gland failure?
End organ hormone low
| Pituitary hormone high
210
What is lost in primary gland failure which results in high pituitary hormone levels?
-ve feedback
211
Which organ fails in secondary gland failure?
Pituitary
212
What hormone levels are seen in secondary gland failure?
End organ hormone low
| Pituitary hormone low
213
Why is the thyroid not stimulated in secondary hypothyroidism?
Loss of TSH
214
What hormone levels are seen in excess hormone production by the primary gland?
End organ hormone high
| Pituitary hormone low
215
What hormone levels are seen in excess hormone production by the pituitary gland?
End organ hormone high
| Pituitary hormone high
216
What controls water retention using osmoreceptors which measure serum osmolality and rising sodium levels before thirst occurs?
Posterior pituitary
217
When a rise in serum osmolality and sodium is detected, what is released?
ADH
218
What happens when blood concentration increases?
ADH released --> water recycled into bloodstream
219
What happens if osmolality decreases?
ADH is switched off --> water is not recycled to the bloodstream
220
What happens in diabetes insipidus?
Water is not reabsorbed by the kidneys which causes an increase in serum osmolality and decrease in urine osmolality
221
Why are the symptoms of diabetes insipidus?
Polyuria
| Polydipsia
222
What can cause diabetes insipidus?
ADH deficiency due to disease of hypothalamus or pituitary stalk
ADH resistance
223
What are the S/S of acromegaly?
```
Large hand and feet
Sweating
Headaches
Coarse features
Hypertension and diabetes
```
224
What are the S/S of Cushing's disease?
```
Central obesity
Striae
Easy bruising
Rounded moon-shaped face
Diabetes and hypertension
Proximal myopathy
```
225
What are prolactinomas?
Prolactin-secreting pituitary tumours
226
What are the S/S of prolactinomas?
Infertility
Menstrual disturbances
Glactorrhea
227
What does a a big tumour squashing the pituitary gland cause?
Decreased hormone levels of all pituitary hormones except prolactin which increases
228
What are the clinical features of hypopituitarism?
Lethargic
Pallor
Loss of body hair
Poor growth in children
229
What are gonadotropinomas?
LH/FSH secreting pituitary tumours
230
What do gonadotropinomas cause?
Increases of sex steroids
| Increased LH/FSH
231
What are basal endocrine tests used in pituitary disease to measure prolactin and testosterone?
Tests carried out at any time of day due to stable hormone levels
232
What are dynamic endocrine tests in pituitary disease?
Tests where the time of day they are conducted is important due to cyclic or pulsatile hormone release
233
Which hormones are measured by dynamic endocrine tests?
LH
FSH
GH
ACTH
234
What do you do to a gland if there is a hormone deficiency or excess in order to identify pituitary disease?
Deficiency - try to stimulate gland into action
| Excess - try to suppress gland
235
What is growth hormone stimulation test used for?
Suspected GH deficiency
236
What does the GH stimulation test investigate?
Pituitary GH reserve to identify growth disorders in children and pituitary tumours in adults
237
What is the best test of GH reserve?
Insulin tolerance test
238
What happens in an insulin tolerance test?
IV insulin --> hypoglycaemia --> somatostatin inhibited so GH is stimulated (testing for deficiency) --> GH doesn't rise --> unpleasant sensation/hot and sweaty/tachycardia/faint
239
Why is medical supervision important when conducting an insulin tolerance test?
Positive results from the test can be prolonged
240
When is the insulin tolerance test not used?
If patient has ischaemic heart disease, epilepsy or unexplained blackouts
241
When is the growth hormone suppression test used?
Suspected GH excess e.g. Acromegaly
242
What happens in the GH suppression test?
75 g of oral glucose --> increases somatostatin which should suppress GH --> no suppression of GH = acromegaly
243
How often are glucose and GH measured in the GH suppression test?
Every 30 mins starting 30 mins prior to oral glucose dose
244
When is the ACTH stimulation test used?
Suspected ACTH deficiency caused by hypopituitarism or another isolated condition
245
Wha can be used to conduct an ACTH stimulation test if the patient does not suffer from IHD, epilepsy or unexplained blackouts?
Insulin tolerance test
246
What happens in an ACTH stimulation test?
Stress --> CRH rises --> ACTH should rise and cause cortisol release to prevent hypoglycaemia --> hypoglycaemia occurs
247
When is a dexamethasone suppression test used?
Suspected excess ACTH e.g. Cushing's
248
What happens in a dexamethasone suppression test?
Dexamethasone should act in hypothalamus to decrease CRH and subsequently decrease cortisol but ACTH remains high so cortisol remains high
249
What treatments are available for pituitary disease?
Controlled removal of tumour by surgery, radiotherapy or medical therapy
Reduce increased hormone secretion
Replace hormone deficiencies
250
What are the advantages of using radiotherapy to treat pituitary tumours?
Prevents tumour and protects vision
| Can damage gland and increase risk of stroke
251
What medical therapies can be used to remove pituitary tumours?
GH receptor antagonists
Dopamine (D2) agonists
Somatostatin analogues
252
What effects do dopamine agonists have in pituitary tumour treatment?
Reduce prolactin
| Shrink pituitary tumour enough to prevent need for surgery
253
Which axis do somatostatin and its analogues act on?
GH
254
What is given as a monthly injection to treat acromegaly?
Somatostatin and its analogues
255
How do GH receptor blockers work I treating acromegaly?
Normalise IGF-1 (not GH) levels
256
What controls are the cortex and medulla of the adrenal gland?
Cortex - endocrine
| Medulla - neurological
257
What is the only source of testosterone in women?
Androgens released from the reticularis of the adrenal cortex
258
What is the most common enzyme deficiency causing absent mineralocortcoids or glucocorticoids?
21-hydroxylase
259
What causes a newborn to have indistinguishable sex?
Build up of androgens due to deficiency of 21-hydroxylase
260
What allows the dramatic change in shape of mediator proteins due to steroid hormone binding?
Alteration of DNA transcription
261
What happens in mineralocortcoid deficiency?
Decreased sodium
Dehydration
Hyperkalaemia
262
What happens in mineralocortcoid excess?
Increased sodium
Hypertension
Hypokalaemia
263
What actions do glucocorticoids have?
Increase glucose production
Breakdown protein
Redistribute fat
264
What does redistribution of fat due to glucocorticoid action depend on?
Enzyme specific concentration in tissues
265
Where is fat usually distributed in glucocorticoid excess?
Centrally
| Dorso-cervical
266
Why happens in glucocorticoid excess?
Decreased glucose
Weight loss
Nausea
Hypotension
267
What happens in glucocorticoid excess?
```
Increased glucose
Weight gain
Increased appetite
Hypertension
Cushingoid
```
268
What is aldosterone controlled by?
Rennin-cycle
269
What gland failure does increased pigment around knuckles, scars and bucchal mucosa indicate?
Primary adrenal
270
What tumour can cause ectopic ACTH secretion?
Small cell lung
271
What does a Cushingoid appearance but low ACTH levels indicate?
Autonomous cortisol secretion
272
What precursor is ACTH secreted as?
POMC
273
What is POMC broken down into?
Amino terminal fragment --> alpha-MSH
ACTH
Beta-lipoproteins --> meta-MSH and met-enkephalin
274
What does ACTH stimulate in the adrenal glands?
Production of steroid hormones
275
What is ACTH broken down into which leads to pigmentation?
Alpha-MSH
| CLIP
276
What can cause corticosteroid excess?
Cushing's disease
Ectopic ACTH
Primary adrenal tumour
Exogenous steroids
277
What must be considered when testing the HPA-axis?
Its circadian rhythm
278
What social factor might alter testing time of the HPA-axis?
Shift work
279
What test is used for primary adrenal failure?
Synacthen
280
What happens in a synacthen test that indicates primary adrenal failure?
Primary adrenal failure or disease of adrenal cortex means there is no cortisol response to synthetic ACTH
281
What test is used in suspected secondary adrenal gland failure?
Insulin tolerance test
282
How long does there have to be absent pituitary stimulation to cause the adrenal gland to atrophy?
~month
283
What are two causes of pseudocushing's?
Alcohol
| Psychiatric disease
284
What tests are used in suspected corticosteroid excess?
24hr urine free cortisol
| Dexamethasone suppression test
285
What is Addison's disease?
Far endocrine disorder due to auto-immune destruction of adrenal cortex causing a deficiency of all hormones
286
Why are lymphocytes seen in the adrenal cortex of Addison's patients?
Causes inflammatory infiltrate in adrenal cortex
287
What do Addison's disease patients often also present with?
Other auto-immune diseases
288
Is Addison's more common in women or men?
Women
289
What are the S/S of Addison's disease?
```
Weight loss
Anorexia
Malaise
Weakness
Fever
Depression
Impotence
Amenorrhea
Low libido
Abdominal pain
Myalgia
Arthralgia
Nausea
```
290
What are the specific clinical features of Addison's disease?
Pigmentation
Postural hypotension
Salt cravings
291
What are the biochemical features of Addison's disease?
Decreased sodium
Increased potassium
Increased urea (due to dehydration)
Decreased glucose
292
What confirmatory tests can be used in Addison's disease?
```
0900 cortisol
Short synacthen test
ACTH
Plasma renin
Adrenal antibodies
```
293
What can cause primary adrenal failure?
```
Adrenal leucodystrophy
Tuberculosis
Surgical removal
Meningitis
Haemorrhage/infarction
```
294
Is acute primary adrenal failure an emergency?
Yes
295
How is glucocorticoid replacement monitored?
Improvement in clinical symptoms
Restoration of normal weight
Cortisol measurements throughout the day
296
How is fludrocortisone replacement monitored?
Restoration of serum electrolytes to normal
Blood pressure response to posture
Suppression of plasma renin to normal
297
How do the S/S of primary and secondary hypoadrenalism compare?
Primary: high ACTH, pigmented, gluco and mineralcorticoids raised
Secondary: low ACTH, pale, glucocorticoids only raised
298
What results is exogenous steroids cause hypo-adrenal crisis?
```
Hypotension
Hypoglycaemia
Hyponatreamia
Hyperkalaemia
Severe dehydration and death if untreated
```
299
Why are long-term steroid use patients at an increased risk of peri-operative hypoadrenal crisis?
Cannot mount an endogenous stress response
300
What is endogenous Cushing's syndrome?
Rare endocrine disorder caused by pituitary disorder, adrenal tumour/hyperplasia, ectopic ACTH secretion or abnormal receptors in adrenal cortical cells
301
What is the main cause of endogenous Cushing's syndrome?
Pituitary source
302
What are the clinical features of endogenous Cushing's syndrome?
```
Central weight gain
Change in appearance
Depression
Insomnia
Menstrual disturbance
Poor libido
Thin skin
Easy bruising
Hair growth
Acne
Muscle weakness
Growth arrest in children
Back pain
Psychosis
```
303
What is found on examination in endogenous Cushing's syndrome?
```
Moon face
Plethora
Buffalo hump
Striae
Central obesity
Thin skin
Bruising
Hypertension
Proximal myopathy
```
304
What confirmatory tests can be used in endogenous Cushing's syndrome?
24 hour urinary free cortisol
Midnight cortisol
Adrenal CT or MRI
305
What happens if endogenous Cushing's syndrome is left untreated?
```
High mortality
Hypertension
MI
Infection
Heart failure
```
306
What is congenital adrenal hyperplasia?
Rare endocrine disorder causing deficiency of an enzyme that causes a block in the cortisol pathway
307
What are the clinical features of congenital adrenal hypertension?
```
Virilisation of female baby
Neonatal salt-losing crisis
Hypotension
Hypoglycaemia
Hyponatraemia
```
308
Why is urgent confirmation of congenital adrenal hypertension needed?
To identify before gender assignment
309
What is tested for in congenital adrenal hyperplasia?
High 17-hydroxyprogesterone
High androstenedione
High testosterone
High ACTH
310
How is congenital adrenal hyperplasia treated?
Emergency with steroids
311
What is the function of the thyroid gland?
Secrete thyroid hormone to maintain energy homeostasis
312
What is the functional anatomy of the thyroid gland?
```
Wraps around trachea at base of neck below cricoid cartilage
2 lobes connected by isthmus
Ductless
Alveolar
~20 g
```
313
What is the structure of a thyroid follicle, the secretory unit of the thyroid gland?
Polarised cell thyroid epithelia around colloid filled centre
314
How are the epithelial cells of the thyroid polarised?
Transporters on side that face colloid are different from the that face interstitium
315
What accounts for 30% of thyroid mass?
Colloid
316
What is thyroglobulin?
Large glycoprotein rich in tyrosine that is important in thyroid hormone synthesis and secretion
317
What type of cells make up the thyroid epithelium?
Cuboidal or columnar
318
Is there a standard size of thyroid follicle?
Nope
319
How is blood supplied to the thyroid gland?
Superior and inferior thyroid arteries
320
How is blood drained from the thyroid?
Superior, middle and inferior thyroid veins
321
How can the lymphatic system of the thyroid be described?
Rich
322
What innervation is abundant in the thyroid?
Sympathetic and parasympathetic
323
What has a minor role in overall regulation of the thyroid gland in comparison to its cascade stimulus?
Sympathetic stimulation
324
What does TRH binding to Gq receptors on the anterior pituitary cause?
Stimulation of PLC which causes an increase in intracellular calcium levels resulting in exocytosis of TSH
325
Where are the receptors for TSH located on the thyroid follicular cell?
Basolateral membrane
326
What does binding of TSH on thyroid receptors cause?
Stimulation of iodine uptake
Acutely: Stimulate synthesis and storage of T3 and T4
Production and release of thyroglobulin
Chronically: hyperplasia and hypertrophy
327
What electrolytes are found in the fluid that bathes the basolateral membrane of epithelial cells in the thyroid?
Sodium
Potassium
Iodine
328
What creates a sodium gradient in iodine uptake in the thyroid?
Active pumping of sodium out of follicle
329
How is iodine moved against its concentration gradient I tot eh third follicles?
Taken with sodium as it moves down its concentration gradient
330
What happens to the iodine transported into a thyroid follicle on the follicular lumen?
Activated into reactive form by oeroxidase enzyme
331
What associates with thyroglobulin in thyroid follicles?
Reactive iodine
332
Why is the storage of thyroglobulin as colloid in the thyroid follicle considered to be an iodide trap?
Follicular cells concentrate iodine to 20-50x the naturally occurring amount
333
Why is it necessary for the colloid in thyroid follicles to act as an iodide trap?
Thyroid hormones contain large amounts of iodine that is not abundant in the diet
334
How is thyroglobulin synthesised?
Synthesised on ribosomes --> glycosylated on ER cisternae --> translocated to Golgi for packaging into secretory vesicles of follicular epithelium cells
335
Are T3 and T4 fat or water soluble?
Fat
336
Which thyroid hormone is more potent, very biologically active and has a shorter half life?
T3
337
How is T3 made ineffective?
Deiodinated to T2
338
What carries T3 and T4 around the circulation?
Thyronine binding globulin
Albumin
Prealbumin
339
How are T3 and T4 degraded?
Deiodination in the liver and kidney
340
Which thyroid hormone is produced in larger volume, has a greater affinity for binding proteins and has a longer half life?
T4
341
Where can T4 be deiodinated?
Liver or peripheral tissues
342
Which thyroid hormone is given in tablet form as a treatment for hypothyroidism?
T4
343
Which thyroid hormone can shrink thyroid tumours but is a possible growth factor for adenoma?
T4
344
How is BMR increased by thyroid hormones?
Increased number and size of mitochondria
Increased oxygen consumption and heat production
Increased nutrient utilisation
345
What metabolic pathways are stimulated by thyroid hormones?
Lipolysis
Glycolysis
Glycogenolysis
Proteolysis
346
How do thyroid hormones promote normal growth and development of tissues?
Increase synthesis of specific proteins
347
What do thyroid hormones increase responsiveness of tissues to?
Sympathetic nervous system
| Various metabolic and reproductive hormones
348
How do thyroid hormones increase functional capacity of the nervous system in adults?
Increased myelination of nerve fibres
Increased development of neurones
Increased speed of reflexes
Increased mental activity - alertness, emotional tone, memory
349
How do thyroid hormones cause an increase in cardiac output?
Direct effect in heart and increased effect of noradrenaline
350
Where is increase in turnover of proteins and glycoproteins seen due to action of thyroid hormones?
Skin and subcutaneous tissues
351
What is seen with hypothyroidism in the neonate?
Irreversible severe mental retardation due to failed CNS development
Coarse features
Protruding tongue
Diminished linear growth due to failure of genetic aging
Delayed sexual development
352
How soon after birth does hypothyroidism have to be treated in order for it to be reversible?
21 days
353
What is conducted on neonates to look for hypothyroidism?
Heel price test to assay for TSH
354
What can hyperthyroidism cause to be early but not elevated in children?
Maturation
355
Why is hyperthyroidism not usually seen in children?
Exceedingly rare and/or symptoms are not noticeable
356
What are the S/S or hyperthyroidism?
```
Heat intolerance, increased perspiration
Clammy hands
Weight loss (lipid and protein)
Tachycardia
Increased bowel movements
Increased appetite
Nervousness, irritability, emotional liability
Hyper-reflexive
Exophthalmos (anterior bulge of eye)
```
357
What is Grave's disease?
Autoimmune disease which produces antibody that stimulates TSH receptor
358
How does carbimazole treat Grave's disease?
Inhibits incorporation of iodine with thyroglobulin
359
What treatments are available for Grave's disease?
Carbimazole
Radioactive iodine
Surgery
360
How does radioactive iodine treat Grave's disease?
Destroys follicular cells
361
Are males or females more commonly affected by Grave's disease?
Females, there is 10/1 ratio
362
What are the S/S of hypothyroidism?
```
Cold intolerance
Deceased perspiration, cold dry hands
Mild weight gain
Bradycardia
Constipation
Mood swings
Poor concentration, memory and initiative
Oedema and myxoedema
Dry skin
Brittle nails
Hair loss
```
363
What is Hashimoto's disease?
Autoimmune disease that destroys thyroid follicles and produces antibody that blocks TSH receptor and inhibits peroxidase enzyme
364
Is Hashiomot's disease more common in men or women?
Women, 10/1 ratio
365
How is Hashimoto's disease treated?
Oral T4
366
How do you know oral T4 treatment of Hashimoto's disease is effective?
Measure TSH to ensure pituitary function is normal and there will be a loss of s/s with no development of hyperthyroid s/s
367
How can an ectopic thyroid at the back of the tongue arise?
If it does not migrate down to its position in the neck from the back of the tongue by week 12 of development
368
Why does an ectopic thyroid gland at the back of the tongue have a reduced function?
Lack of proper blood supply
369
What subunits form TSH?
Alpha and beta
370
Which portion of thyroid hormones has any biological affect?
Free concentration
371
What two features of T3 and T4 form a combined mean which causes the overall activity of the hormones to be slit equally?
Respective half lives and comparative activity
372
How can the comparative activity of T3 and T4 be explained at the cellular level?
T3 can act directly in mitochondria to increase synthesis of enzymes and structural proteins
T4 must bind to cell membrane receptors
373
Where are there receptors for both T3 and T4 present in the cell?
Nucleus
374
What can cause hypothyroid disease?
```
Autoimmune disease
Post-surgery
Radioactive iodine treatment
Anti-thyroid drug treatment
Secondary - due to lack of TSH
Congenital
Iodine deficiency
```
375
What is the most common cause of hypothyroidism in the UK?
Autoimmune disease
376
What is the most common cause of hypothyroidism worldwide?
Iodine deficiency
377
What cause of hypothyroidism always triggers goitre formation?
Iodine deficiency
378
What can cause hyperthyroid disease?
Autoimmune: Grave's, toxic multinodular goitre, solitary toxic adenoma
Excessive T4 therapy
Thyroid carcinoma
Ectopic thyroid tissue
Excess iodine due to treatment with anti-arrhythmic drug amioderone
379
Is thyroid disease more common in men or women?
Women
380
Why are used to diagnose hyper, hypo or euthyroid?
Thyroid function tests
381
Why are free T4 and TSH both looked at in thyroid function tests rather than just one hormone level?
Individual variation is smaller than population variation so what may be in population range may be unusually for an individual
382
What are free T4 and TSH levels like in the thyroid function test of euthyroid?
Both normal
383
What are free T4 and TSH levels like in the thyroid function test of hypothyroid?
Free T4 is low and TSH is elevated
384
What are free T4 and TSH levels like in the thyroid function test of hyperthyroid?
Free T4 is high and TSH is low
385
What is the spectrum of hyperthyroidism from most to least severe?
Thyroid storm
Gross hyperthyroidism
Mild hyperthyroidism
Autonomous thyroid function
386
What is the spectrum of hypothyroidism from least to most severe?
Compensated euthyroidism
Mild hypothyroidism
Gross hypothyroidism
Myxoedema coma
387
What condition on the spectrum of hypothyroid disease may not require treatment but should be continually monitored?
Compensated euthyroidism
388
What exacerbates myxoedema coma?
Biological stress
389
What is sick euthyroid syndrome?
Sick in-patients often have abnormal TFTs despite being euthyroid
390
What do you need to have in order to carry out a TFT in ill in-patients due to the occurrence of sick euthyroid syndrome?
String clinical suspicion of gross thyroid disease
391
Will all thyroid disease patients have obvious disease?
No
392
How is calcium found in the bloodstream?
1.0-1.3 M free and 0.9-1.3 M bound to plasma proteins or complexed w/citrate
393
Where is most of the calcium in the body stored?
Skeleton
394
What is calcium needed for in the body?
```
Signalling
Activity of some enzymes and hormone receptors
Normal kidney function
Blood clotting
AP transmission at NMJ
Regulate heart rhythm
```
395
Where is 99% of calcium found in the adult human?
Hydroxyapatite crystals of bone
396
Why do we need a calcium store in the skeleton if calcium levels can be regulated by uptake in the GI and excretion in the urine?
This regulation cannot be guaranteed
397
What is the rapid modulator of calcium levels?
Parathyroid hormone
398
What is the action of parathyroid hormone?
Stimulate bone resorption and release of calcium into circulation
Stimulate calcium reabsorption in kidney and excretion of phosphate
Stimulate final hydroxylation of vitamin D
399
What is a long-term modulator of calcium levels?
Dietary vitamin D
400
What action does dietary vitamin D have?
Increase intestinal absorption of dietary calcium
Increase renal reabsorption of calcium
Increase bone resorption
401
What is the name of active vitamin D?
Calcitriol
402
Where is calcitonin produced?
Thyroid gland
403
What is the action of calcitonin?
Counteracts effects of PTH but is not particularly effective in humans
404
Typically how many parathyroid glands are there per lobe of the thyroid?
2
405
Where may extra parathyroid glands be located?
Anywhere in the thorax
406
What is the appearance of chief cells in the parathyroid?
Round
Clear cytoplasm
Large nucleus
Lots of mitochondria
407
What is the function of chief cells?
Secrete PTH
408
What are oxyphil/principle cells of the parathyroid?
Assumed old chief cells that are not associated with PTH secretion
409
How does the number of mitochondria present differ between chief cells and oxyphil cells?
Oxyphil have less
410
What cells are found in a parathyroid gland?
Chief
Oxyphil/principle cells of the parathyroid
Adipose
411
Why does PTH stimulate calcium reabsorption but phosphate excretion in the kidney?
Reduce risk of urinary stones forming
412
How does PTH act in the small intestine?
Increases calcium absorption by activating vitamin D
413
What is the structure of PTH?
Straight chain polypeptide
| Pre-pro-hormone
414
What accelerates cleavage of the pre- section of PTH in the liver?
High serum calcium levels
415
Describe the production and storage of PTH.
Continuously produced but not stored
| Broken down immediately if not needed by chief cells
416
How is the mRNA of PTH affected by serum calcium?
Prolongs its survival
417
What is the half life of PTH?
4 mins
418
What effect do low and high serum calcium levels have on PTH synthesis?
Low increases gene transcription
| High downregulates production
419
How is PTH release controlled?
-ve feedback loop - calcium binds to receptor which leads to inhibition of PTH secretion
420
Is there always a degree of basal PTH?
Yes
421
How are basal PTH secretions maintained if calcium is within normal limits?
2 secondary messenger pathways are balanced
422
What is found on cell surface of chief cells, kidney tubule cells and C cells of thyroid gland?
Unique G-protein calcium receptors
423
What happens to the G-protein receptors when there are high calcium levels present?
Phospholipase is activated which inhibits adenylate cyclase leading to reduce cAMP and reduced PTH release
424
What other ion levels regulate PTH release?
High phosphate --> increased PTH secretion
| High magnesium --> low PTH secretion
425
Levels of which molecule other than calcium ions are important in chronic kidney disease?
Phosphate
426
How do osteoclasts cause bone resorption?
Produce acid micro-environment which dissolves hydroxyapatite crystals
427
How is calcium stored in bone?
Calcium phosphate crystals within collagen fibrils
428
How do osteoblasts create new bone?
Produce collagen matrix which is mineralised by hydoxyapatite
429
Which function of bone is its main priority and what is the consequence of this?
Maintaining serum calcium which results in soft bendy bones in order to maintain calcium levels
430
What is the action of PTH on bone?
1-2 hrs stimulates osteolysis
431
How does PTH affect osteoblastic cells?
Induces them to synthesise and secrete cytokines on CSM which stimulate differentiation and activity in osteoclasts and prevent them from undergoing apoptosis
Decreases their activity
432
Which part of the kidneys does PTH affect?
PCT
Loop of Henle
DCT
433
Where does PTH increase calcium reabsorption in the kidney?
Ascending limb
| DCT
434
How does PTH act on the PCT?
Withdraws phosphate transporters from the surface
435
How much dietary intake of calcium is absorbed by para cellular uptake when calcium is not limited due to PTH action on the gut?
30%
436
What significantly increases transcellular uptake of calcium in the gut upon PTH stimulation?
Vitamin D
437
How is calcium absorbed in the gut?
Carriers in the luminal membrane of the duodenum and jejunum move calcium down concentration gradient extruded across basolateral membrane of epithelial cells
438
What effect does having secretions from the gut rich in calcium have on the minimum load that must be taken in to the diet to maintain calcium balance?
Additive
439
What is vitamin D?
Lipid soluble vitamin derived from plants or action of sunlight on cholesterol in skin
440
How is D3 (cholecalciferol) made?
In skin from dairy product intake and using sunlight
441
Where is D2 obtained from in the human body?
Ingestion of yeast and fungi which is often added to margarine as a supplement
442
Do D2 and D3 form calcitriol?
Yes
443
What can be said about the calcitriol forms from D2 and D3?
Equipotent
444
What are the intermediates of calcitriol formation?
7-dehydrocholesterol
Precalciferol
Cholecalciferol
Calcitriol
445
Where does the first hydroxylation reaction of calcitriol take place?
C25 on molecule in the liver
446
How long can the product of the first hydroxylation reaction in vitamin D activation circulate in plasma for?
15-20 days until it is filtered by the kidneys
447
Where does the second hydroxylation reaction occur if PTH is present?
At C1 on molecule in PCT of kidneys
448
What does D3 bind to in the blood?
Transcalciferin
449
How does the first hydroxylation reaction in vitamin D activation affect the half life of the molecule?
Extends it to ~2 weeks
450
What enzyme catalyses conversion of calcitriol in the PCT?
1-alpha-hydroxylase a
451
What is the half life of calcitriol?
0.25 days
452
Why can the pre-vitamin in vitamin D activation be filtered by the glomerulus?
Bound to carrier small enough
453
What regulates C1 hydroxylation in vitamin D activation?
Negative feedback from serum calcium levels
454
What effect does high PTH have on C1 hydroxylation?
Stimulators
455
What action does calcitriol have in the gut?
Active uptake and extrusion of calcium ions
Transcellular transport
Endocytosis and exocytosis of calcium-CaBP complex
456
What action does calcitriol have on bone?
Stimulates osteoclast formation from haemopoietic stem cells
457
What affect does calcitriol have on the kidney?
Stimulates calcium reabsorption
458
What abolished rickets in the UK during WWII?
Adding calcium carbonate to flour and vitamin D to margarine
459
What secretes calcitonin?
Sporadic parafollicular cells or C cells of thyroid gland
460
What is the importance of calcitonin in pregnancy?
May have role in protecting maternal skeleton
461
Does thyroidectomy in humans demonstrate a marked calcium level affect?
Nope
462
What are the S/S of hypocalcaemia?
```
Hyper excitability of NMJ so:
Pins and needles
Tetany
Paralysis
Convulsions
Death
```
463
What is the normal response to hypocalcaemia?
Increase osteoclast activity and increase C1 hydroxylation in vitamin D activation
464
What is rickets?
Filature to mineralise long bones leading to deformity as skeleton is sacrificed to maintain serum calcium
465
What are the S/S of rickets?
```
Head soft spot slow to close
Bony necklace
Curved long bones
Big lumpy joints
Bowed legs
```
466
What happens in accidental surgical removal of the parathyroid?
PTH deficiency causing life threatening hypocalcaemia with rapid onset as PTH is the rapid modulator of serum calcium levels --> convulsions of respiratory system = death
467
What are the S/S of hypercalcaemia?
```
Renal canaliculi
Kidney damage
Constipation
Dehydration
Tiredness
Depression
(Stones, moans and groans)
```
468
What is the normal response to hypercalcaemia?
Decrease osteoclast activity
| Inhibit transcellular absorption of calcium
469
Is calcitonin used in the normal response to hypercalcaemia?
No
470
How is hypercalcaemia treated?
Fluids to restore blood volume
| Remove causative tumour (likely benign)
471
What do you have to do before you can remove a benign tumour of the parathyroid gland?
Find the glands (they can be anywhere in the thorax)
472
What can cause hypercalcaemia?
Over secretion of PTH from primary hyperoarathyroidism
| PTH analogue secreted from various tumours
473
Is phosphate regulated as tightly as calcium?
No
474
What normal activity gives the human body a classic stress response?
Exercise
475
What just the body do in order to adapt to exercise?
Meet acute oxygen append metabolite needs of muscles
Dispose of carbon dioxide and other metabolic waste
Minimise disturbances to other physiological systems
476
What is the metabolic whole body response to exercise?
Mobilise stored fuels at a rate that matches the increased activity whilst preserving blood glucose levels to protect the brain
477
What effects the body's metabolic response to exercise?
Type of exercise - muscles used
Intensity
Duration
Physical condition and nutritional state of individual
478
Why is a muscle store of glycogen needed in a 100 m sprint?
To help spare blood glucose as extra glucose cannot be delivered fast enough
479
How is ATP created once phosphate stores have been used up in a 100m sprint?
Anaerobic glycolysis
480
How is energy supplied in a 1500m race?
40% anaerobic as some oxygen can be delivered but not enough
| Aerobic can use FA and glucose
481
How much energy is needed in total for a 100m sprint, a 1500m race and a marathon respectively?
30 kJ
500 kJ
10,000 kJ
482
How is energy supplied in a marathon?
At least 95% aerobic
| Muscle and liver glycogen and FA
483
Describe the timeline of energy usage during a marathon.
Muscle glycogen deleted in mins
Glucose from liver glycogen peaks after ~1 hour and steadily declines
After 20-30 mins use FA in addition
484
What are the very short term stores of energy for muscle contraction?
```
ATP
Creatine phosphate (using creatine kinase)
```
485
What does muscle glycogen produce without using ATP which can be metabolised anaerobically?
Glucose-6-phosphate
486
Why is muscle glycogen available when blood flow is limited?
Located within muscle fibres so doesn't need to cross CSM
487
What limits the capacity of FA usage in providing energy for exercise?
Albumin levels in blood
| Carnitine shuttle transporting molecules across mitochondrial membrane
488
Describe the aerobic and anaerobic metabolism balance in exercise > 20 mins.
0-30 s = 95% anaerobic
2-4 mins = 40-50% anaerobic
>20 mins = 5% anaerobic
489
Describe the phases of response in the initial sprint, long middle section and finishing sprint of running a race.
Initial sprint: ATP and creatine phosphate
Long middle: glycogen and FA by aerobic metabolism
Finishing sprint: glycogen by anaerobic mechanism
490
What is needed in order to mobilise energy reserves during exercise?
Insulin to increase the number of GLUT4 to move glucose into muscle cells
491
How does glucagon stimulate glycogenolysis in the liver?
Stimulates glycogen phosphorylase phosphorylation
492
Remembering that exercise causes a stress response, what other hormone can stimulate glycogenolysis in the liver by the Salem mechanism as glucagon?
Adrenaline
493
How do hormones change over the course of running a marathon?
Insulin decreases slowly
Glucagon increases
Adrenaline and growth hormone increase rapidly
Cortisol increases slowly
494
What is the action of rapid increase of growth hormone levels when running a marathon?
Increases lipolysis which mobilises FA
495
How does cortisol stimulate gluconeogenesis if exercise is long duration?
Increases PEPCK and fructose-1,6-bishopshate activity
496
What are the benefits of exercise?
```
Improve muscle sensitivity to insulin - improve glucose tolerance
Better balance of lean tissue and fat
Lower blood lipids
Lower blood pressure
Lower HR for given cardiac output
```
497
What are the benefits of exercise to skeletal muscle?
```
More and bigger fibres
Better FA oxidation capacity
Increased glucose transport capacity
More myoglobin for oxygen storage
More capillaries
Increased glycogen
```
498
Why is reorganisation of maternal metabolism in pregnancy necessary?
So there is a higher concentration of energy and raw materials in maternal circulation so they can diffuse passively and via carrier proteins down a concentration gradient to the developing foetus
499
What is the usually weight gain in pregnancy and how much of this is attributed to energy stores?
8-10 kg of which ~3 kg is energy
500
When do maternal energy stores accumulate?
First 20 weeks of pregnancy
501
When are maternal stores at their highest?
Later pregnancy and during lactation
502
What is the development of maternal stores under?
Reproductive hormones mainly from the placenta w/some contribution from the ovaries until the 12th week of pregnancy
503
How does the placenta supersede maternal HPA?
Ability to secrete just about every hormone
504
How is the foetus adapted to take over maternal metabolism to ensure its own survival?
Via the placenta
505
How are stores built in the first 20 weeks of pregnancy?
Stimulus to appetite (also go off harmful foods)
Increased action of insulin in storage tissues
Decreased action of insulin in tissues which use energy
506
Describe the hormone balance in the early half and second half of pregnancy.
Early half = insulin dominant
| Second half = anti-insulin dominant
507
How do the reproductive steroids enable energy store building during pregnancy?
High levels increase sensitivity of beta-cells to blood glucose and increase appetite so more glucose is ingested and there is a specific effect on calorific foods
508
What do the high levels of oestrogens and progesterone sin pregnancy cause in beta-cells?
Hyperplasia
Hypertrophy
Increased basal and stimulated insulin synthesis
509
What affect do oestrogens and human placental lactogen have in muscle due to their anti-insulin properties?
Make it resistant to insulin
510
What is oestriol?
Oestrogen in placenta
511
Where is progesterone secreted from during pregnancy?
Ovary their high quantities by placenta
512
What happens to blood glucose levels in pregnancy despite the higher insulin levels?
They are higher in average, especially after meals
513
What is the advantage of having elevated blood glucose during pregnancy?
Increases glucose gradient so it easier to move across placenta as well as driving into adipose tissue for storage
514
What happens in gestational diabetes?
Beta-cells do not respond regularly to increased insulin secretion and blood glucose is seriously elevated as extra demand for glucose is met but not controlled
515
How common is gestational diabetes?
Affects 3-10% of pregnancies
516
What are the consequences of gestational diabetes?
Maternal effects of hyperglycaemia
Macrosomia (fat baby) w/lots of liver and muscle glycogen
Difficult delivery
517
Why do you always screen a pregnancy after 24 weeks for gestational diabetes?
Takes a while to develop so may present late and could require C-section
518
What is the treatment for gestational diabetes?
Careful short-term insulin
519
What are the possible sequelae of gestational diabetes?
Normally corrects after placental delivery
| Can result in T2DM
