Physiology + Pharmacology Flashcards

1
Q

How is specificity of signalling achieved in the endocrine system?

A
  1. Chemically distinct hormones
  2. Specific receptors for each hormone
  3. Receptors are distributed at specific locations in specific tissues
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2
Q

What are the four main types of hormone?

What are the typical durations of action of each?

A
  1. Amine derived hormones (tyrosine derivatives) - quite short duration
  2. Peptides - slightly longer duration of action
  3. Proteins - same as above
  4. Steroids - longest duration of all
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3
Q

Give some examples of each of the four main types of hormone

A
  1. Modified amino acids e.g. adrenaline, thyroid hormones
  2. Peptides e.g. ACTH, ADH
  3. Proteins e.g. insulin
  4. Steroids e.g. cortisol, progesterone, testosterone
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4
Q

Name the main hormones that each of the following secrete:

  • Anterior pituitary
  • Intermediate pituitary
  • Posterior pituitary
  • Pineal
  • Thyroid
  • Parathyroid
  • Pancreas
A
Anterior pituitary
- ACTH
- GH
- FSH
- LH
- Prolactin 
- TSH
Intermediate pituitary - MSH
Posterior pituitary
- ADH
- Oxytocin
Pineal - melatonin
Thyroid
- Thyroxine (T4)
- Tri-iodothyronine (T3) 
- Calcitonin
Parathyroid 
- PTH
Pancreas
- Insulin 
- Glucagon
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5
Q

Name the main hormones that each of the following screte:

  • Adrenal cortex
  • Adrenal medulla
  • Gonads (male)
  • Gonads (female)
  • Placenta
A
Adrenal cortex
- Glucocorticoids (including cortisol)
- Mineralocorticoids (aldosterone)
- Androgens
Adrenal medulla
- Catecholamines e.g. Adrenaline, Noradrenaline 
Gonads (male) - testosterone
Gonads (female)
- Oestradiol
- Progesterone 
Placenta
- Human chorionic gonadotrophin (hCG)
- Progesterone
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6
Q
Define
Endocrine 
Autocrine
Paracrine 
NB - these are not absolute
A

Endocrine – release of either a preformed or newly synthesized chemical substance from a secretory cell into the general circulation – acts at target cells to produce a response in the body.
Autocrine – a substance synthesized and released from a cell feeds back and modulates the activity of the same cell e.g. WBCs secrete interleukins  some act back on the cell
Paracrine – a secretory cell releases a hormone which acts locally upon surrounding

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7
Q

The overall concentration of a particular hormone in the blood is incredibly low.
What does this mean for the affinity and potency?

A

Receptors must have an extremely high affinity; molecule itself must have a very high potency

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8
Q

How does the speed of action of a hormone compare to that of a neurotransmitter?

A

The speed at which hormones act in comparison to neurotransmitters is relatively slow and very variable as discussed previously; however their time frame of action is much longer

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9
Q

Describe the steps of amine synthesis, storage, release and transport

A

Amine hormones are synthesized from amino acids via a series of enzymatic steps to produce the final hormone e.g. adrenaline
Amines are stored within storage vesicles in the endocrine cell
Release is by ligand binding to receptor -> influx of Ca2+ -> vesicle fuses with membrane and releases the amine product into the interstitial fluid -> systemic circulation

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10
Q

Are amine neurotransmitters hypdophilic or lipophilic?

What does this mean about their transport in the blood?

A

Amine neurotransmitters are highly hydrophilic – easily dissolve in the aqueous medium of the blood -> no need for specialised transport process to keep the amines in solution

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11
Q

Describe the steps of peptide + protein hormone synthesis, storage, release and transport

A

synthesized from larger precursor proteins -> enzymatically cleaved so that it gives rise to several different peptide hormones
A particular gene is specific to a precursor protein (occurs at ribosomes on RER) -> as the product progresses through the RER, it eventually becomes modified + snipped into bits to produce the mature hormone -> done collectively by convertases
Packaged into storage granules
When a ligand binds to the receptor, peptide is released

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12
Q

Are protein + peptide neurotransmitters hypdophilic or lipophilic?
What does this mean about their transport in the blood?

A

Protein + peptide neurotransmitters are highly hydrophilic – easily dissolve in the aqueous medium of the blood -> no need for specialised transport process to keep the amines in solution

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13
Q

Describe the steps of steroid hormone synthesis, storage, release and transport

A

Starting point – the import of cholesterol into the endocrine cell
A key initial product is pregnenolone, which is acted up by a variety of enzymes in a specific manor to produce a steroid hormone
There is no vesicle or granule store of the steroid hormone – they are synthesized upon demand; happens when a ligand binds to the receptor
Released by simple diffusion across the cell membrane and into the circulation

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14
Q

Are steroid neurotransmitters hypdophilic or lipophilic?

What does this mean about their transport in the blood?

A

Most steroids are highly lipophilic - need to transport a lipophiic substance along a large distance -> requires transport proteins – pick up the steroid, and allow it to be delivered to appropriate biological target
If the steroid hormone is bound to a carrier protein, is it pharmacologically inert
About 90% of steroid hormones are bound to a transport protein – its only the remaining 10% which can elicit an affect

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15
Q

which hormones are relatively insoluble in plasma?

What are the three main functions of carrier proteins?

A
Steroids 
Thyroxine (T4)
Triiodothyronine (T3)
1. Increase amount transported in blood
2. Provide a reservoir of hormone 
3. Extend half-life of the hormone in the circulation (contributing to long duration of action)
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16
Q

Name two important general carrier proteins

A

Albumin - binds many steroids + thyroxine

Transthyretin - binds thyroxine and some steroids

17
Q

Give one reason why protein + peptide hormones have a shorter duration of action

A

They are soluble in plasma and do not require carrier proteins for transport, so they are more readily excretable by the kidneys

18
Q

Describe the role of carrier proteins in

A

In the plasma, a steroid hormone binds to a transport protein -> generates an equilibrium between steroid which is bound to plasma protein and that which is freely dissolved
Equilibrium is such that the vast majority of steroid is bound to protein
Steroid leaves the plasma by diffusion across the capillary wall -> note that the movement from plasma to the inside of the cell reduces the concentration of the steroid in the plasma -> in response to this reduction, some steroid dissociates from the binding protein, replenishing the amount which is free in the plasma which is able to elicit a biological effect
Acts like a sink, holding steroid ready for release

19
Q

A sudden release of steroid hormone from an endocrine organ will have chat effect on the plasma concentration of the hormone?
Why?

A

Sudden release of steroid from endocrine organ -> plasma concentration of hormone will decrease. This is because steroid binding hormones will mop up any sudden increase or surge in steroid hormone concentration -> held in a reservoir

20
Q

What are the three structurally and functionally distinct types of hormone receptor?
Which types of hormone activate which receptors?
Which receptors are intracellular and which are extracellular?

A
  1. G-protein coupled (GPCR) – activated by amines and some proteins/peptides
  2. Receptor kinases - activated by proteins + peptides
  3. Nuclear receptors - divided into
    - Class 1 - activated by steroid hormones
    - Class 2 - activated by lipids
    - Hybrid class - activated by T3
    1 +2 - cell surface receptors
    3 - intracellular
21
Q

What are the four types of cell found in the pancreas?

A
In islets of Langerhans:
- Alpha cells - secrete glucagon
- Beta cells - secrete insulin
Other:
- Delta cells - secrete somatostatin 
- PP cells (F cells) - secrete pancreatic polypeptide
22
Q

Where in the beta cell is insulin synthesized?
What are the steps of insulin synthesis?
How is insulin formed from this?
What is the basic structure of insulin?
What is the function of the connecting (C) peptide?
What the function of proinsulin?

A

In the rough endoplasmic reticulum
Starts off as a larger single chain prehormone called preproinsulin -> signal peptide is cleaved off, leaving proinsulin -> C peptide is cleaved off, leaving insulin
Insulin contains two polypeptide chains linked by disulfide bonds
C peptide has no known physiologic function
Proinsulin provides a tertiary structure which is recognised by insulin receptors

23
Q

What are the basic steps in secretion of insulin, from glucose entering the cell to the release on insulin?

A
  1. Glucose enters the beta cell through the GLUT2 glucose transporter
  2. Glucose is phosphorylated by glucokinase, creating glucose phosphate
  3. Glucose phosphate is metabolised, leading to the production of ATP
  4. ATP blocks removal of K+ from the cell by inhibiting the ATP-sensitive K+ channel (called KATP)
  5. This causes depolarization of the membrane
  6. Voltage gated Ca2+ channels open
  7. Influx of Ca2+
  8. Causes fusion of secretory vesicles with the cell membrane
  9. Insulin is released
24
Q

What is the pattern of release of insulin?

Why is there this pattern?

A

Release of insulin is biphasic
Only 5 % of insulin granules are immediately available for release i.e. the RRP – readily releasable pool
Reserve pool must undergo preparatory reactions to become mobilised and available for release

25
Q

Mutations in which proteins can lead to diabetes?

A

Kir6.2 and SUR1 - the two types of subunit which make up the ATP sensitive K channel in beta cells

26
Q

Name seven functions of insulin when gene expression is on

A
Amino acid uptake in muscle
DNA synthesis
Protein synthesis
Growth responses
Glucose uptake in muscle and adipose tissue
Lipogenesis in adipose tissue and liver
Glycogen synthesis in liver and muscle
27
Q

Give two functions of insulin when gene expression is turned off?

A

Lipolysis

Gluconeogenesis in liver

28
Q

What are the three basic steps in signalling cascades?

A
  1. Reception – signal molecule binds to the receptor
  2. Transduction – signal transduction pathway how the initial binding triggers a cellular response
  3. Response – activation of cellular responses
29
Q

The insulin receptor is a member of which family?

A

The insulin receptor is a member of the receptor tyrosine kinase family.

30
Q

What are the two enzymes involved in protein phosphorylation?

A

Remember that this is a reversible reaction:

  • Protein kinase phosphorylates the protein to a phosphorylated protein
  • Phosphatase converts the phosphorylated protein back to a protein
31
Q

Leprechaunism-Donohue syndrome
What type of genetic defect?
Where is the mutation and what does this lead to?
Three classic symptoms/signs?

A

Rare autosomal recessive genetic trait.
Mutations in the gene for the insulin receptor, leading to severe insulin resistance.
Developmental abnormalities
- Elfin facial appearance
- Growth retardation
- Absence of subcutaneous fat, decreased muscle mass

32
Q

Rabson Mendenhall syndrome
What type of genetic defect?
What does it cause?
Symptoms/signs?

A

This is a rare autosomal recessive genetic trait.
It causes severe insulin resistance, hyperglycemia and compensatory hyperinsulinemia.
Developmental abnormalities.
Acanthosis nigricans (hyperpigmentation).
Fasting hypoglycaemia (due to hyperinsulinemia).
Diabetic ketoacidosis.