CEP Flashcards
1
Q
How can hormones travel in the blood?
A
- In free form
- Bound to a protein (typically lipid hormones)
2
Q
What are the three types of hormones?
A
- Amino acid derivative
- Peptide hormone
- lipid derivative (steroids and thyroid hormones)
3
Q
How do protein and amino acid derived hormones bind to cells to initiate a response?
A
Bind to cell receptors on the plasma membrane.
4
Q
How do steroid and thyroid hormones bind to cells to initiate a response?
A
Pass through the plasma membrane as they are lipid derived and bind to cell receptors in the cytoplasm.
5
Q
What is the hypothalamus responsible for producing?
A
Antidiuretic Hormone and oxytocin
Regulatory hormones
6
Q
What is secreted by the posterior lobe of the pituitary?
A
ADH and oxytocin.
They are produced in the hypothalamus but released by the pituitary.
7
Q
What is secreted from the anterior lobe of the pituitary?
A
ACTH-(Adrenocorticotropic hormone) TSH-(Thyroid stimulating hormone) GH-(growth hormone) PRL-(prolactin) FSH-(follicle stimulating hormone) LH-(lutenising hormone)
8
Q
What regulates secretion of hormones from the anterior pituitary?
A
Regulatory hormones produced by the hypothalamus
9
Q
What does the pineal glad secrete?
A
Melatonin-internal body clock
pineal gland located in brain
10
Q
What is secreted by the thyroid gland?
A
Throxine (T4) (increase metabolic rate)
triiodothyronine (T3) (increase metabolic rate)
Calcitonin
11
Q
What is secreted by the parathyroid gland?
A
PTH-(parathyroid hormone)
12
Q
What is secreted by the adrenal cortex?
A
Mineralcorticoids-Aldosterone
Glucocorticoids-Cortisol
Androgens-testosterone
13
Q
What is secreted by the adrenal medulla?
A
Adrenaline and noradrenaline
14
Q
What saliva is produced by the parotid gland?
A
watery serous saliva
15
Q
What saliva is produced by the submandibular glands?
A
Mixed serous and mucous saliva
16
Q
What saliva as produced by the sublingual glands?
A
Mixed saliva that is thicker
17
Q
Which salivary gland produces the majority of the saliva?
A
The submandibular gland produces 60%
18
Q
Which nerve supplies the parotid gland?
A
parasympathetic motor component of the glossopharngeal nerve
19
Q
What nerve supplies the submandibular gland?
A
supplied by the secretomotor fibres of the chorda tympani branch of facial nerve
20
Q
What nerve supplies the sublingual gland?
A
Supplied by the chorda tympani branch of the facial nerve
21
Q
Because of their relationship to the cavernous sinus which cranial nerves are susceptible to compression or injury from infections?
A
CN III, CN IV, CN V, CN VI
22
Q
How does an integral ion channel work?
A
2 agonists bind to receptor
Breaks down hydrophobic interactions opening the pore
Allows specific ion movement
23
Q
How does an integral tyrosine kinase work?
A
Agonist binds
tyrosine kinase phosphorylates receptor
causes a change in conformation
24
Q
How does a steroid receptor work?
A
Steroid can move through membrane as it is lipid soluble
binds to receptor on nucleus
has effect by promoting or suppressing gene expression
25
How does a G protein coupled receptor work?
Agonist binds to g protein coupled receptor
this interacts with the g protein
this interacts with the effector protein
this starts the signal transduction pathway by producing a second messenger
26
What molecule is bound to the alpha sub-unit of a non activated G-protein?
GDP
27
What happens to a G-protein when a ligand binds to a g-protein coupled receptor?
Causes a conformational change that activates the G-protein
| This causes the alpha sub unit to lose its GDP and pick up GTP
28
What happens to the G-protein when GTP binds to the alpha sub-unit?
It breaks off from the beta and gamma complex and moves to the effector
here it will either activate or inhibit it
29
What happens after an alpha subunit of a G protein has activated or inhibited its effector?
It hydrolyses the GTP back to GDP
| The alpha subunit reattaches to the beta gamma complex
30
What are the three types of GPCRs?
Gs Protein- Stimulates Adenylyl cyclase
Gi Protein- Inhibits Adenylyl cyclase
Gq/G11 protein- activate phospholipase C
31
What is the effector protein in the cell membrane for the Gq/G11 protein?
Phopholipase C
32
What happens when the alpha sub unit attaches to phospholipase C?
It hydrolyses the membrane protein PIP2 to DAG and IP3
33
What do DAG and IP3 do in the cell signalling pathway?
DAG recruits protein kinase C
| IP3 increases intracellular calcium that is essential for DAGs function
34
How does cAMP work as a second messenger?
Activates protein kinase A which phosphorylates specific target proteins
35
What happens in the G1 phase of the cell cycle?
Cell growth
| this prepares the cell for DNA replication
36
What happens in the S phase of the cell cycle?
DNA replication occurs
| Forms two sets of genes that can then be seperated
37
What happens in the G2 phase of the cell cycle?
Organelle replication occurs
| increase in the amount of cytoplasm also occurs
38
What are the stages of mitosis?
Prophase- chromosomes condense
Metaphase- Chromosomes line up on the metaphase plate
Anaphase- chromosomes pulled apart by spindle fibres
Telophase- chromosomes are at poles ready for cell division
39
What is checked at the G1 checkpoint in the cell cycle?
Checks the cell has sufficient nutrients to divide into two daughter cells
40
What is checked at the G1/S checkpoint?
That there is no damage to the dna before it undergoes division
41
What is checked at the G2 checkpoint?
Checks that DNA replication the the S phase has been completed correctly
42
How does regulation at the G1 checkpoint occur?
If the G1 cyclin is present from growth factors then this will activate G1-CDK
This CDK phosphorylates pRB (retinoblastoma protein)
This causes it to release its binding of transcription factor regulators
These activate the genes for cell proliferation.
43
How does regulation at the G1/S checkpoint occur?
DNA damage increases the concentration of p53
This activates the transcription of p21 which is an inhibitor of G1/S CDK
If this CDK is not present prevents continuation into S phase
44
How does a growth factor signalling pathway work?
When a growth factor binds to the receptor it activates a RAS protein
This causes a kinase cascade which affects gene regulatory proteins
these cause cell proliferation
45
What is the Arterial supply to the thyroid gland?
Superior thyroid artery is branch off external carotid artery
supplies superior and anterior aspects
Inferior thyroid arteries branch from the thyrocervical trunk that is a branch of the subclavian artery
supplies the inferio-posterior aspects
46
What is the venous drainage of the Thyroid Gland?
The middle and superior thyroid veins drain into the internal jugular vein
The inferior thyroid vein drains into the brachiocephalic vein
47
What is the arrangement histologically of the thyroid tissue?
circular lobules of follicle cells that produce the thyroid hormones
Blood vessels run between adjacent lobules
48
What is the process by which thyroid hormone is released?
TRH (thyrotropin releasing hormone is released by the hypothalamus)
This stimulates release of TSH from the anterior pituitary
This binds to a GPCR on the thyroid cells which cause an increase in cAMP
This stimulates secretion of T3 and T4
49
How do thyroid follicular cells produce thyroid hormones?
Thyroglobulin precursor is made by the smooth ER which is the packaged by the golgi apparatus and transported into the lumen of the lobule containing the fluid coloid
Iodide ions symported into follicular cells with Na+ then antiported with cl- into lumen
Here Iodide is converted to iodine and combines with thyroglobulin to form T3 and T4 chains
These chains are pinocytosed into follicular cells where lysosomes break them down into individual hormones which are secreted into the blood
50
How do T3 and T4 travel in the bloodstream?
Bound to Thyroid binding proteins because they are lipid soluble
51
Which is more active T3 or T4?
T3 10x more active than T4
However much more T4 secreted
T4 converted to T3 at target cell
52
What hormones control blood calcium levels?
Calcitonin and parathyroid hormone
53
What hormone lowers blood calcium and where is it produced?
Calcitonin lowers blood calcium
| It is produced in the parafollicular cells of the thyroid gland
54
What hormone increases blood calcium and where is it produced?
Parathyroid Hormone
| It is produced in the chief cells of the parathyroid gland
55
What effect does Vitamen D have on blood calcium?
Increases it through increased uptake of calcium from the intestines
56
What effects does Parathyroid hormone have on the body?
Increases blood calcium and lowers phosphate (PO3-)
Kidneys: increases calcium reabsorption and decreases phosphate reabsorption
Bone: increases osteoclast activity and decreases osteoblast activity
GIT:increases calcium and phosphate absorption
57
What effects does Calcitonin have on the body?
Decreases blood calcium and phosphate (PO3-)
Kidneys: decreases calcium and phosphate reabsorption
Bone: Increases osteoblast activity
GIT:no effects
58
What is the bodies hormonal response to low blood pressure?
Kidney release the enzyme renin
This converts angiotensinogen to angiotensin I in the blood
This is then converted to angiotensin II by ACE which increases blood pressure through aldosterone release
59
What would the short and long feedback loops be for Glucocorticoid relase?
The short feedback loop would be ACTH feedback to the hypothalamus
The long feedback loop would be the glucocorticoid feedback to the hypothalamus
60
Where is the pituitary gland located?
In the sella turcica of the sphenoid bone in the middle cranial fossa
61
What is the arterial supply to the pituitary gland?
The superior and inferior hypophyseal arteries that are branches off the internal carotid artery
62
What is the venous drainage of the Pituitary gland?
Vessels from capillary plexi that eventually drain into the hypophyseal veins that are present in the cavernous sinus
63
What does the supraoptic nucleus do?
Connects the hypothalamus and posterior pituitary
| Carries ADH in large vesicles from the hypothalamus to be released by the pituitary
64
What does the praventricular nucleus do?
Connects the hypothalamus and posterior pituitary
| Carries oxytocin in large vesicles from the hypothalamus to be released by the pituitary
65
What are the 6 hypothalamus regulatory hormones for the anterior pituitary?
```
CRH-Corticotropin releasing hormone-ACTH
TRH-Tyrotropin releasing hormone-TSH
GHRH-Growth hormone releasing hormone-GH
Somatostain-Inhibits GH and TSH release
Dopamine-Inhibits prolactin release
GnRH-Gondaotropin releasing hormone-FSH and LH
```
66
What are the 5 cell types in the anterior pituitary?
```
Corticotropic cells- ACTH
Thyrotropic cells - TSH
Somatotropic cells- Somatostatin
Gonadotropic cells- FSH and LH
Mammotropic cells- Prolactin
```
67
What are herring bodies?
neural swellings in the posterior pituitary
| These store ADH and oxytocin for release
68
What is the arterial supply of the Adrenal gland?
Superior suprarenal arteries: come off the phrenic arteries
Middle suprarenal arteries: come off the aorta
Inferior suprarenal arteries: come off the renal arteries
69
What is the venous drainage of the adrenal gland?
On the left the suprarenal vein joins the renal vein
| On the right the suprarenal vein joins directly onto the vena cava
70
What are the layers of the adrenal cortex and what hormones are secreted there?
Zona glomerulosa: mineralocorticoids e.g. aldosterone
Zona Fasticulata: Glucocorticoids e.g. cortisol
Zona reticularis: androgens e.g. DHEA then converted to testosterone
71
What stimulates aldosterone release and what does it do?
Stimulated by Angiotensis II
| To increase BP aldosterone promotes Na+ and water retention and stimulates K+ excretion
72
What stimulates cortisol and what does it do?
Stimulated by ATCH from the anterior pituitary
Cortisol stimulates gluconeogensis and glycogenolysis to increase glucose levels
It also promotes breakdown of fat
73
What does the Adrenal medulla secrete and what causes this?
Chromaffin cells of the medulla are stimulated to secrete adrenaline and noradrenaline by cholinergic nerve endings of sympathetic nerves
74
What is hexamethonium and what does it do?
It is a nicotinic receptor competitive antagonist
As the acetycholine nicotinic receptor is present in both parasympathetic and sympathetic ganglia hexamethnium interferes with transmission
75
What would be the result of hexamethonium on a man?
Reduced Autonomic NS:
All secretions would be reduced including lacrimation, salivation, sweating and even gastric juices
Marked orthostatic hypotension due to reduction in vascular tone
Cardiac output would be reduced
Patient would be tachycardiac
Sexual dysfunctions will be marked such as impotence
76
What is an example of a muscarinic antagonist? what would it be used to treat?
Atropine is a muscarinic antagonist
used to inhibit the effects of the parasympathetic NS
e.g. decrease salivary production during surgery
77
What are the three peripheral muscarinic receptors and where do they act?
MI: Stomach and salivary glands
MII: Cardiac
MIII: Smooth muscle
78
Give an example of two agonists that compete with each other and for which receptor?
Muscarin and acetylcholine compete for the muscarinic receptor
79
What is E(Max) in terms of drug graphs?
The concentration in which the maximum response is provoked
80
What is efficacy?
Efficacy is the likelihood of the channel being openwhen the agonist is bound
81
What is potency?
This is the minimal concentration of an agonist to produce an effect
82
What is a beta blocker? give an example
A beta blocker is a beta adrenoreceptor competitive antagonist
An example of this would be propanalol (used to treat high BP)
83
How would a competitive antagonist affect an typical agonist log concentration vs response curve?
Would shift the sigmoid curve to the right and would be identical
84
How would a non-competitive antagonist affect an typical agonist log concentration vs response curve?
Would cause a fall in the maximum response, hence a lower peak of the sigmoid curve
85
How would a partial agonist affect an typical agonist log concentration vs response curve?
Lower maximum response so lower sigmoid curve
86
What is an example of an allosteric antagonist?
Gallamine acts as an allosteric antagonist at the muscarinic receptors
87
What are the main routes of drug administration?
Enteral routes: This involves the GI tract, with the drug being swallowed and absorbed from the intestine. The drug may be injected into the rectum
Parenteral routes: This includes the IV route, routes through the subcutaneous layer, intra-muscular
Percutaneous: This includes transdermal/topical (via skin), inhalation (membrane of lungs), sublingual (under tongue)
88
In which form is a drug lipid soluable to pass through tissues?
Unionised form
89
What is the therapeutic index?
The therapeutic index is the difference between the effective and toxic concentration
A larger therapeutic index results in a safer drug
90
In terms of what is happening at the receptor what effect does an antagonist have?
Antagonists bind to the receptor but do not produce a response
They prevent the binding of the agonist
Therefore, this blocks/reduces the response to an agonist
They possess affinity but not efficacy
91
What is the embryological origin of the parathyroid glands?
inferior parathyroids originate from the 3rd pharyngeal pouch
superior parathyroids originate from the 4th pharyngeal arch
both endoderm tissue
92
What is the embryological origin of the thyroid gland?
derived from 1st pharyngeal arch along with mucosa of the anterior 2/3 of the tongue
derived from a diverticulum ( a blind tube leading from a cavity or passage) in the developing tongue
93
How does a thyroglossal cyst arise and what problem may it cause?
The thyroid gland embryologically decends from the first pharangeal arch behind the tounge to its location anterolateral to the tongue.
This is due to passage along the thyroglossal duct that usually closes up
If remnants of the epithelium do not disappear they can cause a thyroglossal cyst
This can cause fistulas that can affect breathing or become infected.
94
What is an ectopic thyroid and what problems may it cause?
When the thyroid tissue fails to properly travel down the thyroglossal duct into its final position
ectopic thyroid tissue can be mistaken for cysts and removed, this may cause hypothyroidism
95
What is Goiter?
Enlarged thyroid gland resulting from lack of iodine
| It may compress the oesophagus, trachea and recurrent laryngeal nerves
96
What is likely to be damaged during neck surgery and what is the result?
Likely to damage the recurrent laryngeal glands which unilateral damage will cause hoarseness of the voice
97
Where are foreign bodies likely to get stuck in the laryngopharynx?
In the piriform recess
98
What is graves disease and what are its main symptoms?
Also known as toxic nodule goiter, it causes hyperthyroidism
| Symptoms are Weight loss and eye bulging due to effects on fibroblasts behind the eyes
99
How is graves disease treated?
Antithyroid drugs e.g. carbimazole (often leads to hypothyroidism)
Surgical removal of thyroid
radioiodine therapy (destorys follicular cells)
100
How do thinoamide drugs (e.g. carbimazole) work?
Inhibits enzyme that converts iodide to iodine so cant produce T3 and T4
101
What radioactive isotope is used to treat hyperthyroidism? What is the major radiation form emitted?
Iodine 131 emits beta radiation
102
What is hashimotos thyroiditis?
Autoimmune reaction that causes hypopituitism
103
What are two inhibitors of replication in the cell cycle?
pRB acts as an inhibitor by binding to transcriptional regulators when there are no growth factors bound.
P53 acts as an inhibitor by being produced when DNA is damaged and this stimulates transcription of p21 which stops the cell cycle moving into the S phase
104
What are the three sources for generating acetyl coA?
Pyruvate
Fatty acids (beta-oxidation)
Amino acids
105
What is the fuction of NADH and FADH?
To serve as electron carriers
106
What is the final electron acceptor in the elctron transport chain and what does this form?
Oxygen acts as the final acceptor.
| Along with H+ ions it forms water
107
How is ATP generated by the electron transport chain?
H+ ions are transported across the inner membrane on the mitochondia
They move back down their electrochemical gradient through ATP synthase
108
What are the three enzymes the are control points for the TCA cycle?
citrate synthase
isocitrate dehydrogenase
alpha-ketoglutarate dehyrogenase
109
What is the main enzyme for control of metabolism and how does it work?
Phosphofructokinase
allosterically inhibited by ATP
Also inhibited by glucagon to prevent glycolysis and gluconeogensis happening simultaneously
110
What is a sebaceous gland?
Sebaceous glands are microscopic exocrine glands in the skin that secrete an oily or waxy matter, called sebum, to lubricate and waterproof the skin and hair
111
What does iatrogenic mean?
Caused by surgery
112
What are the three tests for cortisol excess
- 24 hour urinary free cortisol
- Dexamethasone suppression test (should suppress cortisol levels) negative feedback to pituitary wi
- Late night salivary cortisol
113
What are the two most common causes of addisons?
Autoimmune
| Tuberculosis
114
Why do addisons patients feel dizzy and become hyperpigmented?
Dizziness is from low blood pressure from lack of aldosterone
Hyperpigmentation is from excess ACTH binding to melanocytes and causing excess melanin secretion
115
What is the treatment for addisons?
hydrocortisone to replace Cortisol
| Fludrocortisone to replace aldosterone
116
What are the three junctions in metabolism?
--Junction 1-gluose-6-phosphate
can either go through glycolysis or the pentose phosphate pathway
--Junction 2-pyruvate
Junction between carbohydrate and amino acid metabolism
can be converted to acetyl CoA or lactate, amino acids can also input here by being turned into pyruvate
Pyruvate can also be converted back to glucose-6-phosphate
--Junction 3-acetyl CoA
junction between carbohydrate and fat metabolism
acetyl coa can be created from fatty acids
it can form ketone bodies
can also enter TCA cycle
117
What are the two types of control of the junction points in metabolism?
- -intrinsic control (by cell) - substrate concentration via trasporters, enzyme activity via feedback inhibition
- -extrinsic control (by hormones) - substrate concentration e.g. by insulin to control gluscoe uptake, enzyme activity controlled by hormone signalling pathways
118
What is the rate determining step of a metabolic pathway?
The pathway is only as fast as its slowest step (enzymes)
| therefore not all of the enzymes need to be regulated and controlled
119
Where is the rate determining step usually found in a metabolic pathway?
usually at the start of the pathway or at branch points in the pathway i.e. hexokinase for glycolysis
120
What are the 3 ways RDS enzymes are controlled?
- feedback inhibition- product of reaction acts as negative feedback to enzyme producing it
- allosteric enzymes- when bound to the substrate activity curve changes to a sigmoidal shape
- phosphorylation changes the action of many enzymes
121
How do sulphonureas work?
In B cells of islets of langerhans
Bind to the sulphonurea receptor that causes inhibition of the ATP sensitive K+ channel
This causes depolarisation of the cell that opens Ca2+ channels
Increase of intracellular calcium causes insulin vesicles to fuse to membrane and release contents
122
How does the insulin receptor work?
tyrosine kinase receptor
causes phosphorylation of IRS (insulin receptor substrate)
Causes gene transcription which increases expression of glut 4 hence increasing glucose uptake
123
How does metformin work?
Increases glucose uptake into muscle cells
works in conjunction with insulin so unless for type 1 diabetics
decreases gluconeogenesis in liver
124
Thiazolidinediones
Bind to Trans. Factor, increase glucose uptake in muscles, decreased gluconeogenesis. LIPOGENSIS (weight gain!)
125
Acarbose
This causes inhibition of a-glucosidase is an enzyme in the gut, thus preventing carbohydrate breakdown
This reduces glucose absorption
126
- Sitagliptin
Stops incretin breakdown so increases insulin release
127
Which cells secrete adrenaline and noradrenaline?
chromaffin cells of the adrenal medulla
