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Monday, April 5, 2021

Blood

Blood


Blood
The primary function of blood is to deliver O2 and energy to the tissues, and remove CO2 and waste products. It is also important for the defence and immune systems, regulation of temperature, and trans- port of hormones and signalling molecules between tissues. Blood consists of plasma (Chapter 2) and blood cells. Red blood cells contain haemoglobin and transport respiratory gases (Chapter 28), whereas white cells form part of the defence system (Chapter 10). In adults, all blood cells are produced in the red bone marrow. Normal values for cell counts, haemoglobin and proportion of blood volume due to red cells (haematocrit or packed cell volume; estimated by centrifuging a blood sample) are shown in Figure 8a. Platelets are discussed in Chapter 9.


Blood

Plasma proteins
Plasma contains several important proteins (Fig. 8b), with a total concentration of 65–83 g/L. Most, other than γ-globulins (see below), are synthesized in the liver. Proteins can ionize as either acids or bases because of the presence of both NH2 and COOH groups. At pH 7.4 they are mostly in the anionic (acidic) form. Their ability to accept or donate H+ means they can act as buffers (Chapter 36). Plasma proteins have important transport functions, as they bind many hormones (e.g. cortisol and thyroxine) and metals (e.g. iron). They are classified into albumin, globulin and fibrinogen fractions. Globulins are further classified as α-, β- and γ-globulins. Examples and their major functions are shown in Figure 8b.
Conduction Of Action Potentials

Conduction Of Action Potentials


Conduction Of Action Potentials
The action potential described in Chapter 5 is a local event that can occur in all excitable cells. This local event is an all-or-nothing response, leading to abolishion and then reversal of the polarity from negative (−70 mV) to positive (+40 mV) on the inside of the cell with respect to the outside for a short time during the course of the action potential.
Local currents are set up around the action potential because the positive charges from the membrane ahead of the action potential are drawn towards the area of negativity surrounding the action potential (current sink). This decreases the polarity of the membrane ahead of the action potential.
This electronic depolarization initiates a local response that causes the opening of the voltage-gated ion channels (Na+ followed by K+); when the threshold for firing of the action potential is reached, it propagates the action potential and this, in turn, leads to the local depolarization of the next area, and so on. Once initiated, an action potential does not depolarize the area behind it sufficiently to initiate another action potential because the area is refractory (Chapter 5).
This successive depolarization moves along each segment of an unmyelinated nerve until it reaches the end. It is all-or-nothing and does not decrease in size (Fig. 6a).

Conduction Of Action Potentials

Saltatory conduction
Conduction in myelinated axons depends on a similar pattern of current flows. However, because myelin is an insulator and because the membrane below it cannot be depolarized, the only areas of the myelinated axon that can be depolarized are those that are devoid of any myelin, i.e. at the nodes of Ranvier. The depolarization jumps from one node to another and is called saltatory, from the Latin saltare (to jump) (Fig. 6b). Saltatory conduction is rapid and can be up to 50 times faster than in the fastest unmyelinated fibres.
Neuromuscular Junction And Whole Muscle Contraction

Neuromuscular Junction And Whole Muscle Contraction


Neuromuscular Junction And Whole Muscle Contraction
Neuromuscular junction
For skeletal (voluntary) muscle to contract, there must be neuronal activation to the muscle fibres themselves from either higher centres in the brain or via reflex pathways involving either the spinal cord or the brain stem. The neurones that innervate skeletal muscles are called α-motor neurones. Each motor axon splits into a number of branches that make contact with the surface of individual muscle fibres in the form of bulb-shaped endings. These endings make connections with a specialized structure on the surface of the muscle fibre, called the motor end plate, and together form the neuromuscular junction (NMJ) (Fig. 13a).
The role of the NMJ is the one-to-one transmission of excitatory impulses from the α-motor neurone to the muscle fibres it innervates. It allows a reliable transmission of the impulses from nerve to muscle and produces a predictable response in the muscle. In other words, an action potential in the motor neurone must produce an action potential in the muscle fibres it innervates; this, in turn, must produce a contraction of the muscle fibres. The process by which the NMJ produces this one-to-one response is shown in Figures 13a and b.

The motor neurone axon terminal has a large number of vesicles containing the transmitter substance acetylcholine (ACh). At rest, when not stimulated, a small number of these vesicles release their contents, by a process called exocytosis, into the synaptic cleft between the neurones and the muscle fibres. ACh diffuses across the cleft and reacts with specific ACh receptor proteins in the postsynaptic mem- brane (motor end plate). These receptors contain an integral ion channel, which opens and allows the movement inwards (influx) of small cations, mainly Na+. There are more than 107 receptors on each end plate (postjunctional membrane); each of these can open for about 1 ms and allow small positively charged ions to enter the cell. This movement of positively charged ions generates an end plate potential (EPP). This is a depolarization of the cell with a rise-time of approximately 1–2 ms and may vary in amplitude (unlike the all- or-nothing response seen in the action potential; Chapter 6). The random release of ACh from the vesicles at rest gives rise to small, 0–4-mV depolarizations of the end plate, called miniature end plate potentials (MEPP) (Fig. 13c).

However, when an action potential reaches the prejunctional nerve terminal, there is an enhanced permeability of the membrane to Ca2+ ions due to opening of voltage-gated Ca2+ channels. This causes an increase in the exocytotic release of ACh from several hundred vesicles at the same time. This sudden volume of ACh diffuses across the cleft and stimulates a large number of receptors on the postsynaptic membrane, and thus produces an EPP that is above the threshold for triggering an action potential in the muscle fibre. It triggers a self- propagating muscle action potential. The depolarizing current (the generator potential) generated by the numbers of quanta of ACh is more than sufficient to cause the initiation of an action potential in the muscle membrane surrounding the postsynaptic junction. The typical summed EPP is usually four times the potential necessary to trigger an action potential in the muscle fibre, and so there is a large inherent safety factor.
The effect of ACh is rapidly abolished by the activity of the enzyme acetylcholinesterase (AChE). ACh is hydrolysed to choline and acetic acid. About one-half of the choline is recaptured by the presynaptic nerve terminal and used to make more ACh. Some ACh diffuses out of the cleft, but the enzyme destroys most of it. The number of vesicles available in the nerve ending is said to be sufficient for only about 2000 nerve–muscle impulses, and therefore the vesicles reform very rapidly within about 30 s (Fig. 13b).

Neuromuscular Junction And Whole Muscle Contraction

Whole muscle contraction
As the action potential spreads over the muscle fibre, it invades the T-tubules and releases Ca2+ from the sarcoplasmic reticulum into the sarcoplasm, and the muscle fibres that are excited contract. This contraction will be maintained as long as the levels of Ca2+ are high. The single contraction of a muscle due to a single action potential is called a muscle twitch. Fibres are divided into fast and slow twitch fibres depending on the time course of their twitch contraction. This is determined by the type of myosin in the muscles and the amount of sarcoplasmic reticulum. Different muscles are made up of different proportions of these two types of fibre, leading to a huge variation in overall muscle contraction times (Fig. 3d).
The Cytoplasm and Its Organelles

The Cytoplasm and Its Organelles


The Cytoplasm and Its Organelles
The cytoplasm surrounds the nucleus, and it is in the cytoplasm that the work of the cell takes place. Cytoplasm is essentially a colloidal solution that contains water, electrolytes, suspended proteins, neutral fats, and glycogen molecules. Although not contributing to the cell’s function, pigments may also accumulate in the cytoplasm. Some pigments, such as melanin, which gives skin its color, are normal constituents of the cell. Bilirubin is a normal major pigment of bile; its excess accumulation in cells is evidenced clinically by a yellowish discoloration of the skin and sclera, a condition called jaundice.
Embedded in the cytoplasm are various organelles, which function as the organs of the cell. These organelles include the ribosomes, ER, Golgi complex, mitochondria, and lysosomes.

Ribosomes
The ribosomes serve as sites of protein synthesis in the cell. They are small particles of nucleoproteins (rRNA and proteins) that are held together by a strand of mRNA to form polyribosomes (also called polysomes). Polyribosomes exist as isolated clusters of free ribosomes within the cytoplasm (Fig. 4.2) or attached to the membrane of the ER. Whereas free ribosomes are involved in the synthesis of proteins, mainly enzymes that aid in the control of cell function, those attached to the ER translate mRNAs that code for proteins secreted from the cell or stored within the cell (e.g., granules in white blood cells).
Endoplasmic reticulum and ribosomes

Endoplasmic Reticulum
The ER is an extensive system of paired membranes and flat vesicles that connect various parts of the inner cell (see Fig. 4.2). Between the paired ER membranes is a fluid-filled space called the matrix. The matrix connects the space between the two membranes of the nuclear envelope, the cell membrane, and various cytoplasmic organelles. It functions as a tubular communication system for transporting various substances from one part of the cell to another. A large surface area and multiple enzyme systems attached to the ER membranes also provide the machinery for a major share of the cell’s metabolic functions.

Saturday, April 3, 2021

Motor Control And The Cerebellum

Motor Control And The Cerebellum

Motor Control And The Cerebellum
Motor control
Motor control is defined as the control of movements by the body. These movements can be both influenced and guided by the many sensory inputs that are received, or can be triggered by sensory events. They can also be triggered by the need to move using internal mechanisms. The major division of the body into sensory and motor functions is artificial, because almost all motor areas in the central nervous system (CNS) receive sensory inputs.
The organization and physiology of motor systems have been represented as a number of hierarchical structures, but these must be viewed with caution, as they are again artificial and, by necessity, oversimplified.
Motor Control And The Cerebellum
        Figure 59a shows the major ascending sensory inputs and descending motor outputs, and Figure 59b shows the main looped pathways within the CNS.
Fertilization, Pregnancy And Parturition

Fertilization, Pregnancy And Parturition


Fertilization, Pregnancy And Parturition
Fertilization
The unfertilized ovum can survive for up to 24 h after ovulation, and sperm remain viable in the uterus for up to 5 days after ejaculation. The environment of the female tract triggers the capacitation of sperm. This is a prerequisite for fertilization that involves remodelling of the lipids and glycoproteins of the sperm plasma membrane, coupled with increased metabolism and motility. The ovum is surrounded by the zona pellucida, an acellular membrane bearing the glycoprotein ZP3 that acts as a sperm receptor. Fertilization occurs in the oviduct, when a single capacitated sperm binds to ZP3 and under-goes the acrosome reaction. The acrosome is a body containing proteolytic enzymes that is attached to the sperm head (Fig. 52a). When a sperm binds to ZP3, the acrosomal enzymes are released to digest a pathway for the sperm to penetrate the ovum, within which the contents of the sperm head, including its genetic material, are deposited. This event leads to a chain of reactions that denies access to further sperm penetration. The ovum first undergoes electrical depolarization and then discharges granules that impair further sperm binding at the zona pellucida (the cortical reaction). In this way, fertilization is normally restricted to one sperm per ovum. Some 2–3 h after penetrating the ovum, the sperm head forms the male pronucleus which joins with the female pronucleus from the ovum (Fig. 52a). Fusion of the pronuclei combines the parental genetic material from the gametes to form the zygote.

Fertilization, Pregnancy And Parturition

Pregnancy
The zygote is propelled by cilia and muscular contractions of the Fal-lopian tube into the uterus, where it implants in the endometrium. During this journey, the zygote undergoes a number of cell divisions to form the morula, a solid ball of 16 cells that ‘hatches’ from the zona pellucida and develops into the blastocyst, in which embryonic cells are surrounded by trophoblasts (Fig. 52a). The trophoblasts are responsible for implantation, digesting away the uterine endometrial wall to form a space for the embryo, opening up a pathway to the maternal circulation (via the spiral arteries of the uterus) and forming the fetal portion of the placenta. The tissue engineering activities of trophoblasts are mediated by epidermal growth factor (EGF) (Chapter 46) and interleukin-1β. Implantation is complete within 7–10 days of fertilization, at which time the embryo and early placenta begin to secrete human chorionic gonadotrophin (hCG). The appearance of hCG in the plasma and urine is one of the earliest signs of successful conception, and its detection forms the basis of pregnancy testing kits. hCG is a glycoprotein similar to LH that stimulates progesterone secretion from the corpus luteum. Progesterone levels rise steadily throughout pregnancy and fall sharply at term (Fig. 52b). This steroid ensures that the smooth muscle of the uterus remains quiescent during gestation (essential for a successful pregnancy), stimulates mammary gland development and prepares the maternal brain for motherhood. The  placenta  also  secretes  chorionic  somatomammotrophin,  a growth hormone-like protein that mobilizes metabolic fuels (Chapter 43) and promotes mammary gland growth, and oestrogen (mainly oestriol) that stimulates uterine expansion to accommodate the growing fetus. Fetal development occurs within a fluid-filled sac, known as the amniotic membrane, which provides a protective buffer against physical trauma. Pregnancy makes many physiological demands on the mother. The ventilation rate, cardiac output and plasma volume increase to supply fetal–maternal oxygen and water demands; the gastrointestinal absorption of minerals is enhanced; and the renal glomerular filtration rate (Chapter 32) rises to cope with fetal waste production.
Endocrine Control Of Reproduction

Endocrine Control Of Reproduction


Endocrine Control Of Reproduction
Reproductive function in males and females is controlled by common hormonal systems based on the hypothalamic control of the pituitary gonadotrophins, individually known as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These glycoproteins are released from the gonadotrophs of the anterior pituitary gland under the influence of gonadotrophin-releasing hormone (GnRH; Chapter
44) (Fig. 50a,b). Failure of GnRH release is one cause of infertility. It is released in pulses at intervals of 1–3 h in both males and females, a pattern that is accurately reflected in plasma levels of LH. The pulsatile pattern of GnRH secretion is essential for normal reproductive activity, as continuous exposure of gonadotrophs to the hormone leads to a rapid desensitization of the gonadotrophs and a reduction in the release of gonadotrophins. The releasing hormone acts through receptors coupled to Gq (Chapter 3) to stimulate the release and manufacture of the gonadotrophins.

Endocrine Control Of Reproduction

Actions of gonadotrophins
The gonadotrophins produce their effects via interactions with guanosine triphosphate-binding protein (G-protein)-coupled receptors that activate the intracellular production of cyclic adenosine monophosphate (cAMP) (Chapter 3). In the male, LH acts on the Leydig cells of the testes to stimulate the production of the steroid testosterone, which acts in concert with FSH on Sertoli cells of the seminiferous tubules to support spermatogenesis (Fig. 50a). Sperm are generated in a two-stage meiosis from spermatocytes via spermatids. Spermatogenesis proceeds most efficiently at a temperature of 34 °C, which is why the testes are located outside the body cavity. A normal adult male produces some 2 × 108 sperm per day, a process that carries on from puberty until the end of life. Sertoli cells also produce inhibin, a peptide feedback signal that specifically inhibits the release of FSH from the anterior pituitary.
The Adrenal Glands And Stress

The Adrenal Glands And Stress


The Adrenal Glands And Stress
The adrenal glands are located just above each kidney (hence the name; Fig. 49a) and consist of two endocrine tissues of distinct developmental origins. The inner core (the adrenal medulla) releases the catecholamine hormones adrenaline (epinephrine) and noradrenaline (norepinephrine). It develops from neuronal tissue and is functionally part of the sympathetic nervous system (Chapter 7). The outer layers of the gland (the adrenal cortex) originate from mesodermal tissue and secrete steroid hormones, primarily under the control of the anterior pituitary gland (Chapter 44). Removal of the adrenal glands in animals results in death within a few days, which is thought to result from the loss of the ability to cope with stress.

The Adrenal Glands And Stress

The adrenal medulla
The chromaffin cells of the adrenal medulla manufacture and secrete noradrenaline (20%) and adrenaline (80%). These catecholamine hormones are derived from tyrosine by a series of steps catalysed by specific enzymes (Fig. 49b). The production of the rate-limiting enzyme, phenylethanolamine-N-methyl transferase, is stimulated by cortisol, providing a direct link between the functioning of the medulla and cortex. The secretion of catecholamines is stimulated by sympathetic preganglionic neurones located in the spinal cord (Chapter 7), so that the adrenal medulla functions in concert with the sympathetic nervous system, of which noradrenaline is the main neurotransmitter. Catecholamine release contributes to normal physiological functions, but is enhanced by stress (see below). Adrenaline and noradrenaline act through guanosine triphosphate-binding protein (G-protein)-coupled adrenoceptors. These are classified as α1, α2 and β1–β3. The hormones have the same effects in tissues as the stimulation of sympathetic nerves, with important stress-related responses being vasoconstriction (α1), increased cardiac output (β1) and increased glycolysis and lipolysis (β2, β3). These actions support increased physical activity. Noradrenaline has equal potency at all adrenoceptors, but adrenaline, at normal plasma concentrations, will only activate β-receptors (NB: higher levels do stimulate α-receptors). Phaeochromocytoma is a tumour of the adrenal medulla that leads to the excess production of catecholamines, with high blood pressure as the most immediately threatening symptom. It is treated by α-adrenoceptor antagonists and/or surgery.

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