Endocrinology Flashcards
1
Q
What are the endocrine glands?
A
- Endocrine glands, are specialised organs that secrete chemical mediators (hormones) into the circulation.
- Hormones (a regulatory substance of cellular activity) act at sites remote from the site of production
- Target tissues/organs dictated by expression of receptors for the hormone
2
Q
Define
- Endocrine
- Autocrine
- Paracrine
A
- Endocrine - Act on remote tissues
- Autocrine - Mediators act on the cell where they are produced
- Paracrine - mediators act on adjacent cells
3
Q
Which processes are controlled by hormones within the body?
A
- Homeostatic mechanisms in the body
- Energy production, utilisation and storage
- Growth and development
- Reproduction
- Many others
4
Q
What are the categories of Hormones?
A
- Peptides (e.g. ACTH, Prolactin, Insulin Oxytocin)
- Glycoproteins (e.g. LH, FSH, TSH)
- Amino-derived (e.g.ThyroidHormones Thyroxine(T4))
- Steroids (e.g. Cortisol, Testosterone, Vitamin D
- Catecholamines (e.g. Adrenaline + Noradrenaline)
- Others (Fatty acid based hormones)
5
Q
Where do hormones act?
A
- Cell Surface Receptors
- Intracellular Nuclear Receptors
6
Q
How do Hormones work through Cell Surface Receptors?
A
- Proteins and amines bind cell surface receptors
- This triggers intracellular secondary messenger systems which propagate the signal into and throughout a cell
- Hormones that do this include Insulin, or Growth Hormone.
7
Q
What are some Intracellular 2nd Messenger Systems?
A
- Phospholipid systems (e.g. Insulin)
- Cyclic AMP
- Intracellular calcium
8
Q
How do hormones work through nuclear receptrors?
A
- Steroid hormones can diffuse directly into cells and bind intracellular receptors.
- The steroid-receptor complex then moves into the nucleus and activates or suppresses specific genes
- Examples of hormones that do this are Testosterone and Cortisol
9
Q
How is speed affect through the 2 different mechanisms of action?
A
Both can elicit powerful effects with very low hormones concentrations
- Protein hormones via a cell surface receptor can act very quickly (30s – 2 mins) but have shorter effects lasting minutes.
- Steroid hormones can take hours to activate a response but by altering gene expression, steroids produce morelong lasting effects.
10
Q
How is the endocrine response modulated?
A
- Sets of endocrine glands are usually organized into hierarchical loops that allow feedforward and feedback to regulate
- Can be short or long loops
- Vast majority of endocrine pathways are self limiting – incorporate some form of negative feedback loop.
11
Q
What are some major pathways in Clinical Biochemistry?
A
- Hypothalamus – Pituitary – Adrenal (HPA) axis
- Hypothalamus – Pituitary – Gonadal axis
- Hypothalamus – Pituitary – Thyroid axis
- Anti Diuretic Hormone (ADH) – water balance
12
Q
What is the hypothalamus and pituitary gland?
A
- Hypothalamus: Area of the brain involved in a wide range of homeostatic & metabolic processes. Exerts many of its effects through stimulation of the Pituitary gland.
- Pituitary Gland is divided into 2 sections/lobes.
13
Q
How does the hypothalamus communicate with the pituitary gland?
A
- Stimulates the Anterior pituitary using peptides hormones carried by capillaries.
- Stimulates the Posterior pituitary using neuronal signals.
14
Q
Which hormones are released by the anterior pituitary?
A
- Adrenocorticotrophic hormone (ACTH)
- Growth hormone (GH)
- Follicle stimulating hormone (FSH)
- Luteinising hormone (LH)
- Prolactin
- Thyroid stimulating hormone (TSH)
15
Q
Which hormones are released by the Posterior Pituitary?
A
- Antidiuretic hormone (ADH) (aka Arginine vasopressin (AVP))
- Oxytocin
16
Q
What is the pathway that leads to cortisol production?
A
- Stress induces CRH release from the HypoT
- This stimulates ACTH from Pituitary gland, and Cortisol from adrenal glands.
- Cortisol induces own negative feedback
17
Q
What is the action of Cortisol in the body?
A
- Cortisol is a key stress response steroid hormone
- Stimulates glucose production and modulates the immune system
18
Q
Describe the HP Gonadal Axis in males?
A
- GnRH from hypothalamus released and triggers LH and FSH release from the Pituitary Glands
- LH leads to release of Testoterone from the Leydig Cells
- FSH leads to Spermatogensesis in Sertoli Cells
19
Q
Describe the HP Gonadal Axis in females
A
- GnRH from hypothalamus released and triggers LH and FSH release from the Pituitary Glands
- LH leads to release of Oestrogen from Ovaries and Progesterone from the Corpus Luteum
- FSH leads to Oestorgen release from the Ovary which leads to ovulation
20
Q
Describe the HP Thyroid Axis?
A
- TRH released from the Hypothalamus stimulates TSH
- TSH then stimulates thyroid hormone synthesis and release from the thyroid gland
- Thyroid Hormones T4 and T3 are key regulators of metabolic rate
- Neg feedback loop from the Thyroid hormone
21
Q
Describe the ADH and Water Balance Axis?
A
- Major axis regulating circulatory volume
- HypoT stimulates ADH release from Posterior Pituitary via the neuronal connection
- ADH stimulates H2O reabsorption in the kidney
- Falling plasma Osmo will decrease ADH release.
- But, pathway can be overridden by other stimuli leading to XS ADH release.
- Parallel thirst pathway
22
Q
What triggers the release of ADH?
A
- Decreasing blood pressure, stress, pain, nausea, drugs
- Increasing plasma osmolality
23
Q
How are hormones measured in Clinical Biochemistry?
A
- Immunoassay: using a labelled antibody designed to specifically recognise a specific region (epitope) present on the target protein or molecule (antigen). Often only feasible if there is a unique antigen epitope.
- Chemical detection approach e.g. HPLC-UV (catecholamines), or Mass Spectrometry (Vit D)
24
Q
What are the measurements considerations to be taken into account when measuring hormones in Clinical Biochemistry?
A
- Are you confident your assay is measuring what you think?
- Steroid homornes exists with very similar chemical structures causing interference/mis-recognition in many commercial assays
- Are you measuring the correct ‘form’ of the hormone?
- many protein exist in a bound and free forms. Typically only the free form is active but is harder to measure.
- Correct sample type?
- On Treatment?
- Some medications use the same or smilar hormones produced endogenously
25
Q
How can the biochemical result be interperated?
A
- End organ failure: Increase in Pituitary Hormone and Decrease in End Organ Hormone
- Pituitary failure: Decrease in Pituitary Hormone and Decrease in End Organ Hormone
- End organ over activity: Decrease in Pituitary Hormone and Increase in End Organ Hormone
- Pituitary over activity: Increase in Pituitary Hormone and Increase in End Organ Hormone
26
Q
What are dynamic function tests?
A
- For Hypofunction → perform a stimulation test
- For Hyperfunction → perform a suppression test
27
Q
Why do we perform Dynamic Fucntion tests?
A
- Low hormone levels not diagnostic.
- “Normal” hormone levels do not exclude disease.
- Pulsatile secretion and diurnal variations confuse interpretation of baseline values
- Can aid in differential diagnosis in hormone excess states. Remember to consider results in the context of the entire axis.
28
Q
Give an example of Stimulation and Suppression Tests?
A
Suppression Test
- Cushing’s: Give Dexamethasone in a Dexamethasone Suppression Test (DST) for investigation of excess Cortisol
Stimulation Test
- Addison’s: Give Synacthen (ACTH) in a Short Synacthen Test (SST) for investigation of low Cortisol
