Basic Principles of Neurotransmission

Basic Principles of Neurotransmission

When the nerve impulse arrives at the terminal, it triggers a calcium - dependent fusion of neurotransmitter packets or vesicles with the nerve terminal plasma membrane, followed by release of the neurotransmitter into the gap, or synapse, between the nerve cells. The neurotransmitters and neuromodulators bind to specific plasma membrane receptors, which transmit the information that the neurotransmitter has brought to the receiving cell by means of other membrane proteins and intracellular ‘second messengers’.

The neurotransmitters are inactivated by enzymes or taken up into the nerve that released them and metabolized. The release of the neurotransmitter may be modulated and limited by: (i) autoreceptors on the nerve terminal from which it was released, so that further release of the neurotransmitter is inhibited; and (ii) by presynaptic inhibition, when another neurone synapses with the nerve terminal.

Hormone Transport In Blood

Hormone Transport In Blood

When hormones are secreted into the blood, many are immediately bound to plasma proteins.

The proteins may recognize the hormone specifically and bind it with high affinity and specificity, for example the binding of sex hormones by sex hormone - binding globulin (SHBG). Other proteins, such as albumin, also bind many hormones, including thyroid hormone and the sex hormones, with much lower affinity. Equilibrium is set up between the free and bound hormone, so that a fixed proportion of the hormone travels free and unbound, while most is carried bound. It is currently believed that only the free fraction of the hormone is physiologically active and available to the tissues and for metabolism. When a hormone is bound to plasma proteins it is physiologically inactive and is also protected from metabolic enzymes in organs such as the liver. Some drugs, such as aspirin, can displace other substances such as anticoagulants from their binding sites, which in the case of anticoagulants may cause haemorrhage.

Chemical Transport Inside Human Body

Chemical Transport Inside Human Body

The movement of chemicals between cells and organs is usually tightly controlled.

Diffusion is the movement of molecules in a fluid phase, in random thermal (Brownian) motion. If two solutions containing the same chemical, one concentrated and the other relatively dilute, are separated by a membrane which is completely permeable and passive, the concentrations of the chemical on either side of the membrane will eventually end up being the same through simple diffusion of solutes. This is because there are many molecules of the chemical on the concentrated side, and therefore a statistically greater probability of movement from the more concentrated side to the more dilute side of the membrane. Eventually, when the concentrations are equal on both sides, the net change on either side becomes zero. Lipophilic molecules such as ethyl alcohol and the steroids, for example estradiol, appear to diffuse freely across all biological membranes.

Facilitated transport is the transport of chemicals across membranes by carrier proteins. The process does not require energy and cannot, therefore, transport chemicals against a concentration gradient. The numbers of transporter proteins may be under hormonal control. Glucose is carried into the cell by transporter proteins  whose numbers are increased by insulin.

Active transport uses energy in the form of adenosine triphosphate (ATP) or other metabolic fuels. Therefore chemicals can be transported across the membrane against a concentration gradient, and the transport process can be interrupted by metabolic poisons.

Ion channels mediate active transport, and consist of proteins containing charged amino acids that may form activation and inactivation ‘gates’. Ion channels may be activated by receptors, or by voltage changes through the cell membrane. Channels of the ion Ca2+ can be activated by these two methods.

Osmosis is the passive movement of water through a semipermeable membrane, from a compartment of low solute concentration to one which has a greater concentration of the solute. (‘Solute’ refers to the chemical which is dissolved in the ‘solvent’, usually water in biological tissues.) Cells will shrink or swell depending on the concentrations of the solutes on either side of the membrane.

Phagocytosis and pinocytosis are both examples of endocytosis. Substances can enter the cell without having to pass through the cell membrane. Phagocytosis is the ingestion or ‘swallowing’ of a solid particle by a cell, while pinocytosis is the ingestion of fluid. Receptor - mediated endocytosis is the ingestion of specifically recognized substances by coated pits. These are parts of the membrane which are coated with specific membrane proteins, for example clathrin.

Exocytosis is the movement of substances, such as hormones, out of the cell. Chemicals which are stored in the small vesicles or packets are secreted or released from the cell in which they are stored by exocytosis, when the vesicle fuses with the membrane.

Classification of Endocrine Hormones

Classification of Endocrine Hormones

Hormones are chemical messengers. They may be classified several ways (see Figure):

1. Autocrine: acting on the cells that synthesized them; for example insulin - like growth factor (IGF - 1) which stimulates cell division in the cell which produced it.

2. Paracrine: acting on neighbouring cells. An example is insulin, secreted by pancreatic b cells and affecting secretion of glucagon by pancreatic a cells.

3. Endocrine: acting on cells or organs to which they are carried in the bloodstream or through another aqueous ducting system, such as lymph. Examples include insulin, estradiol and cortisol.

4. Neuroendocrine: this is really paracrine or endocrine, except that the hormones are synthesized in a nerve cell (neurone) which releases the hormone adjacent to the target cell (paracrine), or releases it into the bloodstream, which carries it to the target cell, for example from the hypothalamus to the anterior pituitary gland through the portal system.

5. Neural: this is neurotransmission, when a chemical is released by one neurone and acts on an adjacent neurone. These chemicals are termed neurotransmitters. Neurotransmitters produce virtually instantaneous effects, for example acetylcholine, whereas some chemicals have a slower onset but longer lasting effect on the target organ, and are termed neuromodulators, for example certain opioids.

6. Pheromonal transmission is the release of volatile hormones, called pheromones, into the atmosphere, where they are transmitted to another individual and are recognized as an olfactory signal.

Functions of Blood Vessel

Functions of Blood Vessel

Each vessel type has important functions in addition to being a conduit for blood.

The branching system of elastic and muscular arteries progressively reduces the pulsations in blood pressure and flow imposed by the intermittent ventricular contractions.

The smallest arteries and arterioles have a crucial role in regulating the amount of blood flowing to the tissues by dilating or constricting. This function is regulated by the sympathetic nervous system, and factors generated locally in tissues. These vessels are referred to as resistance arteries, because their constriction resists the flow of blood.

Capillaries and small venules are the exchange vessels. Through their walls, gases, fluids and molecules are transferred between blood and tissues. White blood cells can also pass through the venule walls to fight infection in the tissues.

Venules can constrict to offer resistance to the blood flow, and the ratio of arteriolar and venular resistance exerts an important influence on the movement of fluid between capillaries and tissues, thereby affecting blood volume.

The veins are thin walled and very distensible, and therefore contain about 70% of all blood in the cardiovascular system. The arteries contain just 17% of total blood volume. Veins and venules thus serve as volume reservoirs, which can shift blood from the peripheral circulation into the heart and arteries by constricting. In doing so, they can help to increase the cardiac output (volume of blood pumped by the heart per unit time), and they are also able to maintain the blood pressure and tissue perfusion in essential organs if haemorrhage (blood loss) occurs.

Overview of The Cardiovascular System

Overview of The Cardiovascular System

The cardiovascular system is composed of the heart, blood vessels and blood. In simple terms, its main functions are:

1. distribution of O2 and nutrients (e.g. glucose, amino acids) to all body tissues

2. transportation of CO2 and metabolic waste products (e.g. urea) from the tissues to the lungs and excretory organs

3. distribution of water, electrolytes and hormones throughout the body

4. contributing to the infrastructure of the immune system

5. thermoregulation.

Blood is composed of plasma, an aqueous solution containing electrolytes, proteins and other molecules, in which cells are suspended. The cells comprise 40–45% of blood volume and are mainly erythrocytes, but also white blood cells and platelets. Blood volume is about 5.5L in an ‘average’ 70-kg man. The figure up there illustrates the ‘plumbing’ of the cardiovascular system.

Blood is driven through the cardiovascular system by the heart, a muscular pump divided into left and right sides. Each side contains two chambers, an atrium and a ventricle, composed mainly of cardiac muscle cells. The thin-walled atria serve to fill or ‘prime’ the thick-walled ventricles, which when full constrict forcefully, creating a pressure head that drives the blood out into the body. Blood enters and leaves each chamber of the heart through separate one-way valves, which open and close reciprocally (i.e. one closes before the other opens) to ensure that flow is unidirectional.

Consider the flow of blood, starting with its exit from the left ventricle. When the ventricles contract, the left ventricular internal pressure rises from 0 to 120mmHg (atmospheric pressure = 0). As the pressure rises, the aortic valve opens and blood is expelled into the aorta, the first and largest artery of the systemic circulation. This period of ventricular contraction is termed systole. The maximal pressure during systole is called the systolic pressure, and it serves both to drive blood through the aorta and to distend the aorta, which is quite elastic.

The aortic valve then closes, and the left ventricle relaxes so that it can be refilled with blood from the left atrium via the mitral valve. The period of relaxation is called diastole. During diastole aortic blood flow and pressure diminish but do not fall to zero, because elastic recoil of the aorta continues to exert a diastolic pressure on the blood, which gradually falls to a minimum level of about 80 mmHg.

The difference between systolic and diastolic pressures is termed the pulse pressure. Mean arterial blood pressure (MABP) is pressure averaged over the entire cardiac cycle. Because the heart spends approximately 60% of the cardiac cycle in diastole, the MABP is approximately equal to the diastolic pressure + one-third of the pulse pressure, rather than to the arithmetic average of the systolic and diastolic pressures.

The blood flows from the aorta into the major arteries, each of which supplies blood to an organ or body region. These arteries divide and subdivide into smaller muscular arteries, which eventually give rise to the arterioles – arteries with diameters of <100µm. Blood enters the arterioles at a mean pressure of about 60–70mmHg.

The walls of the arteries and arterioles have circumferentially arranged layers of smooth muscle cells. The lumen of the entire vascular system is lined by a monolayer of endothelial cells. These cells secrete vasoactive substances and serve as a barrier, restricting and controlling the movement of fluid, molecules and cells into and out of the vasculature.

The arterioles lead to the smallest vessels, the capillaries, which form a dense network within all body tissues. The capillary wall is a layer of overlapping endothelial cells, with no smooth muscle cells. The pressure in the capillaries ranges from about 25mmHg on the arterial side to 15mmHg at the venous end. The capillaries converge into small venules, which also have thin walls of mainly endothelial cells. The venules merge into larger venules, with an increasing content of smooth muscle cells as they widen. These then converge to become veins, which progressively join to give rise to the superior and inferior venae cavae, through which blood returns to the right side of the heart. Veins have a larger diameter than arteries, and thus offer relatively little resistance to flow. The small pressure gradient between venules (15 mmHg) and the venae cavae (0 mmHg) is therefore sufficient to drive blood back to the heart.

Blood from the venae cavae enters the right atrium, and then the right ventricle through the tricuspid valve. Contraction of the right ventricle, simultaneous with that of the left ventricle, forces blood through the pulmonary valve into the pulmonary artery, which progressively subdivides to form the arteries, arterioles and capillaries of the pulmonary circulation. The pulmonary circulation is shorter and has a much lower pressure than the systemic circulation, with systolic and diastolic pressures of about 25 and 10mmHg, respectively. The pulmonary capillary network within the lungs surrounds the alveoli of the lungs, allowing exchange of CO2 for O2. Oxygenated blood enters pulmonary venules and veins, and then the left atrium, which pumps it into the left ventricle for the next systemic cycle.

The output of the right ventricle is slightly lower than that of the left ventricle. This is because 1–2% of the systemic blood flow never reaches the right atrium, but is shunted to the left side of the heart via the bronchial circulation (see Figure) and a small fraction of coronary blood flow drains into the thebesian veins.