Physiology Kanani Flashcards
What is meant by the ‘resting membrane potential’ for a cell?
This is the potential difference across the cell membrane. This occurs due to the ionic fluxes of Na, K, and Cl across the membrane, the sizes of which are determined by their electrochemical gradients. It is calculated by the Goldman equation, which takes into account the contribution of the equilibrium potentials of each species of ion that crosses the membrane.
What is the typical value of the resting membrane potential for a neurone?
A typical value is 70 mV. The value is negative because the interior of the cell is negatively charged with respect to the exterior.
What is the importance of the Na/K pump for the equilibrium potential?
This pump, which is ATPase-driven, transports 3 Na out of the cell for 2 K pumped in. It helps to maintain the internal and external ionic environment that pro- gressively alters as ions naturally flow down their elec- trochemical gradients. In doing so, it maintains and sustains the potential difference across the cell (Resting membrane potential).
Briefly describe the ionic basis for the action potential.
The changes in the fluxes of ions that account for depolarisation may be summarised in the following
Once the threshold potential is reached by the stimulus, the voltage-sensitive Na-channels open, causing a rapid influx of Na into the cell. This causes depolarisation, and the membrane potential becomes positive. Once open, the Na-channel closes again within milliseconds
During the initial opening of the Na-channels, a positive feedback loop is initiated; so more channels open up, leading to rapid depolarisation
The cell would remain depolarised if it were not for the rapid closure (inactivation) of the Na-channels
At the same time there is a constant background movement of K out of the cell. This has the effect of placing a limit on the change of membrane potential during the depolarisation phase of the action potential
During repolarisation, there is the opening of the voltage-sensitive K-channels, leading to loss of K from the cell. These react more slowly than the Na-channels, and are open for longer. Thus, repolarisation, with a return to the resting membrane potential is a slower process than depolarisation
After lots of action potentials, when there is the exchange of many ions, the ionic environment is returned to the steady state by the continued and persistent action of the Na/K pumps
What types of nerve fibres are there?
Peripheral nerve fibres may be classified in the follow- ing way:
Group A: These are the largest (up to 20 m):
(Ia and Ib): Motor and proprioception fibres
(II): Touch, pressure and proprioception fibres
(II): Muscle spindle fusimotor fibres
(III): Touch pain and pressure fibres
Group B: Myelinated fibres which are autonomic preganglionic (up to 3 m)
Group C (type IV): Unmyelinated fibres which carry postganglionic fibres, and fibres for touch and pain (up to 2m)
Briefly list some drugs that may alter the conduction along a neurone.
Some agents which can modify the activation and propagation of the action potential include:
Tetrodotoxin: a neurotoxin that is a selective blocker of Na-channels
Tetraethylammonium: a selective K-channel blocker, which prolongs the action potential
Local anaesthetic agents: composed of an amine group connected to an aromatic side chain via an ester or amide bond. They are selective blockers of the voltage-dependent Na-channels
What are the anatomic layers of the adrenal cortex, and which hormones do they produce?
Zona glomerulosa: the superficial layer. Mineralocorticoid production occurs here
Zona fasiculata: the middle layer
Zona reticularis: the deepest layer
The deepest two layers are for the production of glucocorticoids, androgens, and oestrogens. Progestogens are also produced, but they act mainly as precursors in the production of the other hormones
What are the physiological effects of aldosterone?
Sodium balance: stimulation of sodium reabsorption in the distal convoluted tubule (DCT) and collecting duct of the kidney, sweat glands, salivary glands and gut
Potassium balance: through the active exchange with sodium ions at the membrane, leading to the loss of serum potassium
Acid-Base balance: H may also be exchanged with Na, leading to loss of H from the plasma. Therefore, aldosterone excess may lead to a metabolic alkalosis
Water balance: as a consequence of increasing the serum [Na], there is stimulation of pituitary osmoreceptors, leading to increased release of arginine vasopressin (AVP) (also known as antidiuretic hormone (ADH)). This leads to water retention, and so a return of the [Na] back to normal at the expense of increased circulating volume
Describe the principle mechanisms controlling aldosterone release
Aldosterone release is stimulated by
Increased renin secretion: this increases the serum aldosterone through increasing serum angiotensin II. Important stimuli for the release of renin is reduction of renal perfusion and reduced presentation of sodium to the kidney’s macula densa
Decrease of plasma [Na]
Increase of plasma [K]
Aldosterone secretion is reduced by the opposite of the above together with
Increased circulating atrial natriuretic peptide (ANP): this has an inhibitory effect on renin release, and so acts indirectly to inhibit aldosterone release
What are the most common causes of Cushing’s
syndrome of cortisol excess?
In their order of frequency:
Iatrogenic steroid administration
Cushing’s disease: due to an adenoma of the pituitary leading to over secretion of adrenocorticotrophic hormone (ACTH)
Ectopic ACTH secretion: such as a peripheral tumour, often in the lung
Adrenal adenoma: leading to hypersecretion of cortisol. Note that unlike the above two cases, cortisol excess here is autonomous and independent of ACTH
Adrenal carcinoma
What are the principle causes of adrenal insufficiency?
Auto-immune adrenalitis: leading to Addison’s disease
TB: of the adrenal glands
Less commonly due to tumours, amyloid or other bacterial infection of the glands
What is the most common cause of congenital adrenal hyperplasia?
21-hydroxylase deficiency. This leads to ACTH excess following reduced glucocorticoid and mineralocorti- coid synthesis. Can produce congenital hyperkalaemia and an Addisonian crisis with vomiting and dehydra- tion. Since the path of hormone production goes down that of androgen synthesis, leads to developmentally ambiguous genitalia.
How does the embryonic origin of the adrenal cortex differ from that of the medulla?
The adrenal cortex is mesodermal in origin, whereas the medulla is derived from neuroectoderm. This deter- mines the pattern of innervation of the adrenal gland.
How is the adrenal medulla innervated?
Preganglionic sympathetic fibres synapse directly onto the chromaffin cells of the adrenal medulla. As with other preganglionic autonomic synapses, the neuro- transmitter at this point is acetylcholine (ACh).
ACh release from the preganglionic sympathetic fibre stimulates the release of catecholamines by exocytosis, just in the same manner as any other synapse.
Therefore, in effect, the chromaffin cells are specialised postganglionic sympathetic neurones that secrete their transmitter directly into the circulation. The origin of this arrangement arises from the neuroectodermal ori- gin of the adrenal medulla.
What biochemical tests may be performed to make the diagnosis?
A number of tests can be performed to establish the diagnosis, predominantly based on measuring catecholamine metabolites:
24 urinary measurement of vanillyl mandelic acid: the traditional investigation, but misses 30% of cases of phaeochromocytoma
Metadrenaline: more sensitive than the above
Plasma or urinary epinephrine or norepinephrine:
best measured during hypertensive episodes
